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.

Methodological improvement of 3D fluoroscopic analysis for the robust quantification of 3D kinematics of human joints

3D video-fluoroscopy is an accurate but cumbersome technique to estimate natural or prosthetic human joint kinematics. This dissertation proposes innovative methodologies to improve the 3D fluoroscopic analysis reliability and usability. Being based on direct radiographic imaging of the joint, and avoiding soft tissue artefact that limits the accuracy of skin marker based techniques, the fluoroscopic analysis has a potential accuracy of the order of mm/deg or better. It can provide fundamental informations for clinical and methodological applications, but, notwithstanding the number of methodological protocols proposed in the literature, time consuming user interaction is exploited to obtain consistent results. The user-dependency prevented a reliable quantification of the actual accuracy and precision of the methods, and, consequently, slowed down the translation to the clinical practice. The objective of the present work was to speed up this process introducing methodological improvements in the analysis. In the thesis, the fluoroscopic analysis was characterized in depth, in order to evaluate its pros and cons, and to provide reliable solutions to overcome its limitations. To this aim, an analytical approach was followed. The major sources of error were isolated with in-silico preliminary studies as: (a) geometric distortion and calibration errors, (b) 2D images and 3D models resolutions, (c) incorrect contour extraction, (d) bone model symmetries, (e) optimization algorithm limitations, (f) user errors. The effect of each criticality was quantified, and verified with an in-vivo preliminary study on the elbow joint. The dominant source of error was identified in the limited extent of the convergence domain for the local optimization algorithms, which forced the user to manually specify the starting pose for the estimating process. To solve this problem, two different approaches were followed: to increase the optimal pose convergence basin, the local approach used sequential alignments of the 6 degrees of freedom in order of sensitivity, or a geometrical feature-based estimation of the initial conditions for the optimization; the global approach used an unsupervised memetic algorithm to optimally explore the search domain. The performances of the technique were evaluated with a series of in-silico studies and validated in-vitro with a phantom based comparison with a radiostereometric gold-standard. The accuracy of the method is joint-dependent, and for the intact knee joint, the new unsupervised algorithm guaranteed a maximum error lower than 0.5 mm for in-plane translations, 10 mm for out-of-plane translation, and of 3 deg for rotations in a mono-planar setup; and lower than 0.5 mm for translations and 1 deg for rotations in a bi-planar setups. The bi-planar setup is best suited when accurate results are needed, such as for methodological research studies. The mono-planar analysis may be enough for clinical application when the analysis time and cost may be an issue. A further reduction of the user interaction was obtained for prosthetic joints kinematics. A mixed region-growing and level-set segmentation method was proposed and halved the analysis time, delegating the computational burden to the machine. In-silico and in-vivo studies demonstrated that the reliability of the new semiautomatic method was comparable to a user defined manual gold-standard. The improved fluoroscopic analysis was finally applied to a first in-vivo methodological study on the foot kinematics. Preliminary evaluations showed that the presented methodology represents a feasible gold-standard for the validation of skin marker based foot kinematics protocols.

Formal planning rationality in public sector professional work: between discourse and practice

Although rational models of formal planning have been seriously criticized by strategy literature, they not only remain a widely used organizational practice in private firms, but they have increasingly been entering public, professional organizations too, as part of public sector managerial reforms. This research addresses this apparent paradox, exploring the meaning of formal planning in public sector professional work. Curiously, this is an issue that remains under-investigated in the literature: the long debate on formal planning in strategy research devoted scant attention to its diffusion in the public sector, and public sector studies have scrutinized the introduction of other management tools in professional work, but very limitedly formal planning itself. In fact, little is known on the actual meaning of formal planning in public, professional services. This research is based upon a case of adoption of formal planning tools in a public hospital. Embracing a discourse analytical lens, it examines which formal planning discourse entered professional work, to what extent, and how professionals interpret it and engage with it in their practice. The analysis uncovers dynamics of social construction of meaning where, eventually, a formal planning discourse both shapes and is shaped by professional practice. In particular, it is found that formal planning rationality largely penetrated professional work, but not to the detriment of professional values. Morevover, formal planning ‘fails’ as a tool for rational decision making, but it takes up a knowledge work and a social value in professional work, as a tool for explicitation of action courses and for dialogue between otherwise more disconnected parts of the organization.

The abuse of intellectual property rights and regulations in China: a law and economic analysis

From the institutional point of view, the legal system of IPR (intellectual property right, hereafter, IPR) is one of incentive institutions of innovation and it plays very important role in the development of economy. According to the law, the owner of the IPR enjoy a kind of exclusive right to use his IP(intellectual property, hereafter, IP), in other words, he enjoys a kind of legal monopoly position in the market. How to well protect the IPR and at the same time to regulate the abuse of IPR is very interested topic in this knowledge-orientated market and it is the basic research question in this dissertation. In this paper, by way of comparing study and by way of law and economic analyses, and based on the Austrian Economics School’s theories, the writer claims that there is no any contradiction between the IPR and competition law. However, in this new economy (high-technology industries), there is really probability of the owner of IPR to abuse his dominant position. And with the characteristics of the new economy, such as, the high rates of innovation, “instant scalability”, network externality and lock-in effects, the IPR “will vest the dominant undertakings with the power not just to monopolize the market but to shift such power from one market to another, to create strong barriers to enter and, in so doing, granting the perpetuation of such dominance for quite a long time.”1 Therefore, in order to keep the order of market, to vitalize the competition and innovation, and to benefit the customer, in EU and US, it is common ways to apply the competition law to regulate the IPR abuse. In Austrian Economic School perspective, especially the Schumpeterian theories, the innovation/competition/monopoly and entrepreneurship are inter-correlated, therefore, we should apply the dynamic antitrust model based on the AES theories to analysis the relationship between the IPR and competition law. China is still a developing country with relative not so high ability of innovation. Therefore, at present, to protect the IPR and to make good use of the incentive mechanism of IPR legal system is the first important task for Chinese government to do. However, according to the investigation reports,2 based on their IPR advantage and capital advantage, some multinational companies really obtained the dominant or monopoly market position in some aspects of some industries, and there are some IPR abuses conducted by such multinational companies. And then, the Chinese government should be paying close attention to regulate any IPR abuse. However, how to effectively regulate the IPR abuse by way of competition law in Chinese situation, from the law and economic theories’ perspective, from the legislation perspective, and from the judicial practice perspective, there is a long way for China to go!

Data Mining in Clinical Practice for the Quantification of Motor Impairment in Parkinson's Disease

Advances in biomedical signal acquisition systems for motion analysis have led to lowcost and ubiquitous wearable sensors which can be used to record movement data in different settings. This implies the potential availability of large amounts of quantitative data. It is then crucial to identify and to extract the information of clinical relevance from the large amount of available data. This quantitative and objective information can be an important aid for clinical decision making. Data mining is the process of discovering such information in databases through data processing, selection of informative data, and identification of relevant patterns. The databases considered in this thesis store motion data from wearable sensors (specifically accelerometers) and clinical information (clinical data, scores, tests). The main goal of this thesis is to develop data mining tools which can provide quantitative information to the clinician in the field of movement disorders. This thesis will focus on motor impairment in Parkinson's disease (PD). Different databases related to Parkinson subjects in different stages of the disease were considered for this thesis. Each database is characterized by the data recorded during a specific motor task performed by different groups of subjects. The data mining techniques that were used in this thesis are feature selection (a technique which was used to find relevant information and to discard useless or redundant data), classification, clustering, and regression. The aims were to identify high risk subjects for PD, characterize the differences between early PD subjects and healthy ones, characterize PD subtypes and automatically assess the severity of symptoms in the home setting.

The Effectiveness of the Clean Development Mechanism – A law and economics analysis

Climate change has been acknowledged as a threat to humanity. Most scholars agree that to avert dangerous climate change and to transform economies into low-carbon societies, deep global emission reductions are required by the year 2050. Under the framework of the Kyoto Protocol, the Clean Development Mechanism (CDM) is the only market-based instrument that encourages industrialised countries to pursue emission reductions in developing countries. The CDM aims to pay the incremental finance necessary to operationalize emission reduction projects which are otherwise not financially viable. According to the objectives of the Kyoto Protocol, the CDM should finance projects that are additional to those which would have happened anyway, contribute to sustainable development in the countries hosting the projects, and be cost-effective. To enable the identification of such projects, an institutional framework has been established by the Kyoto Protocol which lays out responsibilities for public and private actors. This thesis examines whether the CDM has achieved these objectives in practice and can thus be considered an effective tool to reduce emissions. To complete this investigation, the book applies economic theory and analyses the CDM from two perspectives. The first perspective is the supply-dimension which answers the question of how, in practice, the CDM system identified additional, cost-effective, sustainable projects and, generated emission reductions. The main contribution of this book is the second perspective, the compliance-dimension, which answers the question of whether industrialised countries effectively used the CDM for compliance with their Kyoto targets. The application of the CDM in the European Union Emissions Trading Scheme (EU ETS) is used as a case-study. Where the analysis identifies inefficiencies within the supply or the compliance dimension, potential improvements of the legal framework are proposed and discussed.

Il ruolo della Narrative in Medical Ethics, Medical Practice e Medical Education. Elementi di ricerca

La mia tesi di dottorato ha ad oggetto lo studio e l’analisi del ruolo della Narrative all’interno di tre ambiti, quali Medical Ethics, Clinical Practice e Medical Education. La tesi è strutturata in 4 capitoli: i primi tre vanno a comporre la parte teorica mentre nel quarto capitolo viene riportata una ricerca sul campo da me svolta negli Stati Uniti. Nel primo capitolo, analizzo il ruolo della narrative all’interno della Medical Ethics specificando che cosa si intenda con etica narrativa, quali sono le motivazione alla base del suo sviluppo e chi sono i suoi principali esponenti. In questo capitolo, inoltre, esamino i problemi che l’etica narrativa solleva suggerendo un nuovo modo in cui essa si integra alla riflessione bioetica. Il secondo capitolo è dedicato al contributo della narrative nella Medical Practice investigando sia le modalità attraverso le quali il paziente può avvalersi della narrazione per analizzare la sua esperienza di malattia sia la cosiddetta Medicina Narrativa. Il terzo capitolo è dedicato all'analisi delle Medical Humanities, ossia di quelle discipline che all’interno della Medical Education si stanno rivelando strumenti efficaci per una formazione più equilibrata e completa dei professionisti della salute. Il quarto capitolo, invece, è dedicato alla descrizione di una ricerca svolta presso l’University of California – Irvine . Durante questa esperienza ho frequentato i corsi del Program in Medical Humanities and Arts diretto dalla Prof.ssa J. Shapiro, (programma in vigore da 13 anni e implementato allo scopo di migliorare alcune competenze nei futuri medici quali: l'empatia, l’altruismo, la compassione e la predisposizione alla cura verso i pazienti, oltre che per affinare le comunicazione clinica e la capacità di osservazione) e intervistato gli studenti che hanno preso parte a queste lezioni.

Movement Analysis by means of inertial sensors: from bench to bedside

in the everyday clinical practice. Having this in mind, the choice of a simple setup would not be enough because, even if the setup is quick and simple, the instrumental assessment would still be in addition to the daily routine. The will to overcome this limit has led to the idea of instrumenting already existing and widely used functional tests. In this way the sensor based assessment becomes an integral part of the clinical assessment. Reliable and validated signal processing methods have been successfully implemented in Personal Health Systems based on smartphone technology. At the end of this research project there is evidence that such solution can really and easily used in clinical practice in both supervised and unsupervised settings. Smartphone based solution, together or in place of dedicated wearable sensing units, can truly become a pervasive and low-cost means for providing suitable testing solutions for quantitative movement analysis with a clear clinical value, ultimately providing enhanced balance and mobility support to an aging population.

Role of new molecular approaches for the early diagnosis of bladder cancer in clinical practice

There is an urgent need to improve the performance of urine cytology for the diagnosis of bladder cancer. In preliminary studies, telomerase activity evaluated by telomeric repeat amplification protocol (TRAP) assay and chromosomal aneuploidy detected by fluorescence in situ hybridization (FISH) in the diagnosis of bladder cancer have produced important results. Urine cell-free (UCF) DNA has also been proposed as a potential marker for early bladder cancer diagnosis. In the first study the diagnostic performance of TRAP assay and FISH analysis was assessed, while the second study evaluated the potential role of UCF DNA integrity in early bladder cancer diagnosis. In the first cross-sectional study, 289 consecutive patients who presented with urinary symptoms underwent cystoscopy and cytology evaluation. In the second study, UCF DNA was isolated from 51 bladder cancer patients, 46 symptomatic patients, and 32 healthy volunteers. c-Myc, BCAS1 and HER2 gene sequences longer than 250 bp were quantified by real time PCR to verify UCF DNA integrity. In the first study, sensitivity and specificity were 0.39 and 0.83, respectively, for cytology; 0.66 and 0.72 for TRAP; 0.78 and 0.60 for the cytology and TRAP combination; 0.78 and 0.78 for the cytology, TRAP and FISH combination; and 0.65 and 0.93 for the TRAP and FISH combination. In the second study, at the best cutoff of 0.1 ng/µl, UCF DNA integrity analysis showed a sensitivity of 0.73 and a specificity of 0.84 in healthy individuals and 0.83 in symptomatic patients. The preliminary results suggest that these biomarkers could potentially be used for the early diagnosis of bladder cancer, especially in high-risk populations (e.g, symptomatic individuals exposed to occupational risk) who may benefit from the use of noninvasive diagnostic tests in terms of cost-benefit.

Structural patterns for document engineering: from an empirical bottom-up analysis to an ontological theory

This thesis aims at investigating a new approach to document analysis based on the idea of structural patterns in XML vocabularies. My work is founded on the belief that authors do naturally converge to a reasonable use of markup languages and that extreme, yet valid instances are rare and limited. Actual documents, therefore, may be used to derive classes of elements (patterns) persisting across documents and distilling the conceptualization of the documents and their components, and may give ground for automatic tools and services that rely on no background information (such as schemas) at all. The central part of my work consists in introducing from the ground up a formal theory of eight structural patterns (with three sub-patterns) that are able to express the logical organization of any XML document, and verifying their identifiability in a number of different vocabularies. This model is characterized by and validated against three main dimensions: terseness (i.e. the ability to represent the structure of a document with a small number of objects and composition rules), coverage (i.e. the ability to capture any possible situation in any document) and expressiveness (i.e. the ability to make explicit the semantics of structures, relations and dependencies). An algorithm for the automatic recognition of structural patterns is then presented, together with an evaluation of the results of a test performed on a set of more than 1100 documents from eight very different vocabularies. This language-independent analysis confirms the ability of patterns to capture and summarize the guidelines used by the authors in their everyday practice. Finally, I present some systems that work directly on the pattern-based representation of documents. The ability of these tools to cover very different situations and contexts confirms the effectiveness of the model.