Development of an equipment to detect and quantify muscular spasticity

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Fast screening for diagnostic of heart ischemic episodes

Dissertação para obtenção do Grau de Doutor em Química Sustentável

A nanopore-based stochastic detection method: Single molecule characterisation of nanoparticles using ()- hemolysin

Dissertation presented to obtain the Ph.D degree in Chemistry.

Perfil sociodemográfico e saúde mental em cuidadores informais de idosos no município de São Paulo-Brasil: desafios para as políticas públicas

RESUMO: INTRODUÇÃO: O rápido envelhecimento populacional, o aumento da prevalência de transtornos neuropsiquiátricos, o aumento das taxas de morbilidade clínica e incapacidade entre idosos de países em desenvolvimento têm trazido preocupações sobre a saúde mental e sobrecarga de cuidadores informais. Está bem estabelecida a elevada prevalência de transtornos mentais comuns (TMC) associada à adversidade socioeconômica, baixo nível educacional, estresse e gênero. Idosos e cuidadores vivendo em comunidade compartilham fatores de risco para morbilidade física e psiquiátrica. Adicionalmente, os cuidadores tem uma tripla carga, sendo simultaneamente familiares, trabalhadores leigos em saúde sem suporte dos serviços de saúde e assistência social e um paciente com necessidades não atendidas. O cuidador informal é o principal provedor de cuidado em todos os países. OBJETIVOS: Acessar perfil sociodemográfico, níveis de transtorno mental comum (TMC) e sobrecarga em cuidadores, características do cuidado e prevalência de demência e depressão no idosos, numa área carente da região oeste de São Paulo –Brasil. MÉTODO: Esta pesquisa transversal deriva do São Paulo Ageing and Health Study (SPAH) que incluiu idosos com 65 anos ou mais e seus respectivos cuidadores. Os participantes foram identificados por arrolamento domiciliar e entrevistadas em suas casas com protocolo padronizado de pesquisa. O instrumento utilizado para acessar os transtornos mentais comuns, foi o Self Rating Questionnaire SRQ-20.A sobrecarga foi quantificada pelo Zarit Caregiver Burden Scale. Diagnósticos psicogeriátricos foram mensurados através do SRQ-20 e critérios do CID-10 e do DSM-IV. 8 RESULTADOS: 588 cuidadores e respectivos idosos foram incluídos. Nos idosos, a prevalência de demência foi 15,9%, de depressão pelo CiD-10 9.9% e de TMC 39,25% Nos cuidadores, a prevalência de TMC foi de 55,1% e 32,8% dos cuidadores apresentaram sobrecarga elevada. O perfil do cuidador foi filha,com idade em torno dos 49 anos, casada e com baixo nível educacional.------------------ABSTRACT: BACKGROUND: With the fast population aging, growing prevalence of neuropsychiatric disorders, clinical morbidity and disability among the elderly particularly in low income countries (LAMIC), has brought concerns about informal caregiver Mental Health and Burden. It is well established the high prevalence of Common Mental Disorders (CMD) associated to socioeconomic adversity, low educational attainment, stress and gender. Community-dwelling elders and caregivers share risk factors for physical and psychiatric morbidity. In addition, caregivers have a triple strain, being simultaneously, family members, lay health workers with lack of support from health and social work services and a hidden patient with unmet needs. The world main source of caregiving relies on informal caregiver. AIMS: To assess 1) the sociodemographic profile, levels of CMD and burden among caregivers, and 2) the characteristics of care and prevalence of dementia and depression in elderly in a socioeconomic underprivileged area in western region of Sao Paulo – Brazil. METHOD: The present investigation is a cross-sectional part of Sao Paulo Ageing and Health Study (SPAH) which included participants aged 65 or older and their respective caregivers. Participants were identified by household enrollment and interviewed in their homes using a standardized research protocol. The assessment of common mental disorders was performed with the Self Rating Questionnaire – 20 (SRQ-20), used to establish psychiatric caseness. The assessment of burden was performed with Zarit Caregiver Burden Scale. Dementia and psychogeriatric diagnosis were reached through ICD-10, SRQ-20 and DSM-IV criteria. 10 RESULTS: 588 caregivers and respective elderly relatives were included. Prevalence of dementia was 15.9%, ICD-10 depression 9.9% and CMD 39.3% among the elderlys. Common mental disorder prevalence in caregivers was 55.1% and high burden was reached in 32.8% of the caregiver sample. Most of the caregivers were married and co-resident daughters with a mean age of 49 years (CI 95% - 48.7 to 51).

Optimization of breast tomosynthesis image reconstruction using parallel computing

Breast cancer is the most common cancer among women, being a major public health problem. Worldwide, X-ray mammography is the current gold-standard for medical imaging of breast cancer. However, it has associated some well-known limitations. The false-negative rates, up to 66% in symptomatic women, and the false-positive rates, up to 60%, are a continued source of concern and debate. These drawbacks prompt the development of other imaging techniques for breast cancer detection, in which Digital Breast Tomosynthesis (DBT) is included. DBT is a 3D radiographic technique that reduces the obscuring effect of tissue overlap and appears to address both issues of false-negative and false-positive rates. The 3D images in DBT are only achieved through image reconstruction methods. These methods play an important role in a clinical setting since there is a need to implement a reconstruction process that is both accurate and fast. This dissertation deals with the optimization of iterative algorithms, with parallel computing through an implementation on Graphics Processing Units (GPUs) to make the 3D reconstruction faster using Compute Unified Device Architecture (CUDA). Iterative algorithms have shown to produce the highest quality DBT images, but since they are computationally intensive, their clinical use is currently rejected. These algorithms have the potential to reduce patient dose in DBT scans. A method of integrating CUDA in Interactive Data Language (IDL) is proposed in order to accelerate the DBT image reconstructions. This method has never been attempted before for DBT. In this work the system matrix calculation, the most computationally expensive part of iterative algorithms, is accelerated. A speedup of 1.6 is achieved proving the fact that GPUs can accelerate the IDL implementation.

Dynamic stiffness of the piled foundation of a onshore wind turbine

One of today's biggest concerns is the increase of energetic needs, especially in the developed countries. Among various clean energies, wind energy is one of the technologies that assume greater importance on the sustainable development of humanity. Despite wind turbines had been developed and studied over the years, there are phenomena that haven't been yet fully understood. This work studies the soil-structure interaction that occurs on a wind turbine's foundation composed by a group of piles that is under dynamic loads caused by wind. This problem assumes special importance when the foundation is implemented on locations where safety criteria are very demanding, like the case of a foundation mounted on a dike. To the phenomenon of interaction between two piles and the soil between them it's given the name of pile-soil-pile interaction. It is known that such behavior is frequency dependent, and therefore, on this work evaluation of relevant frequencies for the intended analysis is held. During the development of this thesis, two methods were selected in order to assess pile-soil-pile interaction, being one of analytical nature and the other of numerical origin. The analytical solution was recently developed and its called Generalized pile-soil-pile theory, while for the numerical method the commercial nite element software PLAXIS 3D was used. A study of applicability of the numerical method is also done comparing the given solution by the nite element methods with a rigorous solution widely accepted by the majority of the authors.

Diffusional kurtosis imaging using a fast heuristic constrained linear least squares algorithm: a plugin for OsiriX

Diffusion Kurtosis Imaging (DKI) is a fairly new magnetic resonance imag-ing (MRI) technique that tackles the non-gaussian motion of water in biological tissues by taking into account the restrictions imposed by tissue microstructure, which are not considered in Diffusion Tensor Imaging (DTI), where the water diffusion is considered purely gaussian. As a result DKI provides more accurate information on biological structures and is able to detect important abnormalities which are not visible in standard DTI analysis. This work regards the development of a tool for DKI computation to be implemented as an OsiriX plugin. Thus, as OsiriX runs under Mac OS X, the pro-gram is written in Objective-C and also makes use of Apple’s Cocoa framework. The whole program is developed in the Xcode integrated development environ-ment (IDE). The plugin implements a fast heuristic constrained linear least squares al-gorithm (CLLS-H) for estimating the diffusion and kurtosis tensors, and offers the user the possibility to choose which maps are to be generated for not only standard DTI quantities such as Mean Diffusion (MD), Radial Diffusion (RD), Axial Diffusion (AD) and Fractional Anisotropy (FA), but also DKI metrics, Mean Kurtosis (MK), Radial Kurtosis (RK) and Axial Kurtosis (AK).The plugin was subjected to both a qualitative and a semi-quantitative analysis which yielded convincing results. A more accurate validation pro-cess is still being developed, after which, and with some few minor adjust-ments the plugin shall become a valid option for DKI computation

Botnet cluster identification

Botnets are a group of computers infected with a specific sub-set of a malware family and controlled by one individual, called botmaster. This kind of networks are used not only, but also for virtual extorsion, spam campaigns and identity theft. They implement different types of evasion techniques that make it harder for one to group and detect botnet traffic. This thesis introduces one methodology, called CONDENSER, that outputs clusters through a self-organizing map and that identify domain names generated by an unknown pseudo-random seed that is known by the botnet herder(s). Aditionally DNS Crawler is proposed, this system saves historic DNS data for fast-flux and double fastflux detection, and is used to identify live C&Cs IPs used by real botnets. A program, called CHEWER, was developed to automate the calculation of the SVM parameters and features that better perform against the available domain names associated with DGAs. CONDENSER and DNS Crawler were developed with scalability in mind so the detection of fast-flux and double fast-flux networks become faster. We used a SVM for the DGA classififer, selecting a total of 11 attributes and achieving a Precision of 77,9% and a F-Measure of 83,2%. The feature selection method identified the 3 most significant attributes of the total set of attributes. For clustering, a Self-Organizing Map was used on a total of 81 attributes. The conclusions of this thesis were accepted in Botconf through a submited article. Botconf is known conferênce for research, mitigation and discovery of botnets tailled for the industry, where is presented current work and research. This conference is known for having security and anti-virus companies, law enforcement agencies and researchers.

Zara: Marketing in Fast Fashion: A case-study

Zara was founded in 1975 by Amancio Ortega Gaona, soon becoming the largest and most successful chain of the Galician group Inditex (Industria de Diseño Textil) and a pioneer of the rising fashion category of Fast Fashion. Its innovative vertically-integrated strategies, combined with its emphasis on quality and demand-based offer have shaped the world of fashion and brought forth many questions on its future sustainability and growth. Zara has always relied on its store network for advertising its product offer; allowing its garments to “speak for themselves”. With the continued pressure felt in the industry, management has pressed some concerns about future company growth and creative, innovating solutions must be implemented to guarantee Zara’s future growth. The case-study narrative focuses on these issues and leaves readers with an open question regarding what decision to implement.

Almirante: Evaluating the board game: Board game, startup, discounted cash flow, venture capital method, real options

This thesis evaluates a start-up company (Jogos Almirante Lda) whose single asset is a board game named Almirante. It aims to conclude whether it makes sense to create a company or just earn copyrights. The thesis analyzes the board game’s market, as part of the general toy’s market, from which some data exists: European countries as well as the USA. In this work it is analyzed the several ways to finance a start-up company and then present an overview of the valuation of the Jogos Almirante based on three different methods: Discounted Cash Flow, Venture Capital Method and Real Options.

Gold nanoprobes for assessing expression of critical genes in the infection pathway of MRSA

Staphylococcus aureus is an important opportunistic pathogen that can cause a wide variety of diseases from mild to life-threatening conditions. S. aureus can colonize many parts of the human body but the anterior nares are the primary ecological niche. Its clinical importance is due to its ability to resist almost all classes of antibiotics available together with its large number of virulence factores. MRSA (Methicillin-Resistant S. aureus) strains are particularly important in the hospital settings, being the major cause of nosocomial infections worldwide. MRSA resistance to β-lactam antibiotics involves the acquisition of the exogenous mecA gene, part of the SCCmec cassette. Fast and reliable diagnostic techniques are needed to reduce the mortality and morbidity associated with MRSA infections, through the early identification of MRSA strains. The current identification techniques are time-consuming as they usually involves culturing steps, taking up to five days to determine the antibiotic resistance profile. Several amplification-based techniques have been developed to accelerate the diagnosis. The aim of this project was to develop an even faster methodology that bypasses the DNA amplification step. Gold-nanoprobes were developed and used to detect the presence of mecA gene in S. aureus genome, associated with resistance traits, for colorimetric assays based on non-crosslinking method. Our results showed that the mecA and mecA_V2 gold-nanoprobes were sensitive enough to discriminate the presence of mecA gene in PCR products and genomic DNA (gDNA) samples for target concentrations of 10 ng/μL and 20 ng/μL, respectively. As our main objective was to avoid the amplification step, we concluded that the best strategy for the early identification of MRSA infection relies on colorimetric assays based on non-crosslinking method with gDNA samples that can be extracted directly from blood samples.

Semantic relations extraction from unstructured information for domain ontologies enrichment

Based in internet growth, through semantic web, together with communication speed improvement and fast development of storage device sizes, data and information volume rises considerably every day. Because of this, in the last few years there has been a growing interest in structures for formal representation with suitable characteristics, such as the possibility to organize data and information, as well as the reuse of its contents aimed for the generation of new knowledge. Controlled Vocabulary, specifically Ontologies, present themselves in the lead as one of such structures of representation with high potential. Not only allow for data representation, as well as the reuse of such data for knowledge extraction, coupled with its subsequent storage through not so complex formalisms. However, for the purpose of assuring that ontology knowledge is always up to date, they need maintenance. Ontology Learning is an area which studies the details of update and maintenance of ontologies. It is worth noting that relevant literature already presents first results on automatic maintenance of ontologies, but still in a very early stage. Human-based processes are still the current way to update and maintain an ontology, which turns this into a cumbersome task. The generation of new knowledge aimed for ontology growth can be done based in Data Mining techniques, which is an area that studies techniques for data processing, pattern discovery and knowledge extraction in IT systems. This work aims at proposing a novel semi-automatic method for knowledge extraction from unstructured data sources, using Data Mining techniques, namely through pattern discovery, focused in improving the precision of concept and its semantic relations present in an ontology. In order to verify the applicability of the proposed method, a proof of concept was developed, presenting its results, which were applied in building and construction sector.

Lag-user method: Using laggards to leverage user innovation

Laggards are the last users to adopt a product. Prior literature on user-led innovation ignores laggards’ impact on innovation. In this paper, we develop the Lag-User Method, through which laggards can generate new ideas. Through six studies with 62 teams in three countries, we apply the method to different technologies and services and present our findings to executives to get managerial insights. Findings reveal that laggards who generate new ideas (lag-users) have different perceptions of user-friendly products and different unfulfilled needs. They prefer simple products. We propose that by involving lag-users in NPD, firms can improve the effectiveness of NPD.

Therapeutics bioconjugates: evaluation of iminoboronates as payload delivery system for cancer

The advent of bioconjugation impacted deeply the world of sciences and technology. New biomolecules were found, biological processes were understood, and novel methodologies were formed due to the fast expansion of this area. The possibility of creating new effective therapies for diseases like cancer is one of big applications of this now big area of study. Off target toxicity was always the problem of potent small molecules with high activity towards specific tumour targets. However, chemotherapy is now selective due to powerful linkers that connect targeting molecules with affinity to interesting biological receptors and cytotoxic drugs. This linkers must have very specific properties, such as high stability in plasma, no toxicity, no interference with ligand affinity nor drug potency, and at the same time, be able to lyse once inside the target molecule to release the therapeutic warhead. Bipolar environments between tumour intracellular and extracellular medias are usually exploited by this linkers in order to complete this goal. The work done in this thesis explores a new model for that same task, specific cancer drug delivery. Iminoboronates were studied due to its remarkable selective stability towards a wide pH range and endogenous molecules. A fluorescence probe was design to validate this model by creating an Off/On system and determine the payload release location in situ. A process was optimized to synthetize the probe 8-(1-aminoethyl)-7-hydroxy-coumarin (1) through a reductive amination reaction in a microwave reactor with 61 % yield. A method to conjugate this probe to ABBA was also optimized, obtaining the iminoboronate in good yields in mild conditions. The iminoboronate model was studied regarding its stability in several simulated biological environments and each half-life time was determined, showing the conjugate is stable most of the cases except in tumour intracellular systems. The construction of folate-ABBA-coumarin bioconjugate have been made to complete this evaluation. The ability to be uptaken by a cancer cell through endocytosis process and the conjugation delivery of coumarin fluorescence payload are two features to hope for in this construct.