Double Diffusion Encoding Prevents Degeneracy in Parameter Estimation of Biophysical Models in Diffusion MRI

Purpose: Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, the general Standard Model has recently shown that model parameter estimation from dMRI data is ill-posed unless very strong magnetic gradients are used. We analyse this issue for the Neurite Orientation Dispersion and Density Imaging with Diffusivity Assessment (NODDIDA) model and demonstrate that its extension from Single Diffusion Encoding (SDE) to Double Diffusion Encoding (DDE) solves the ill-posedness and increases the accuracy of the parameter estimation. Methods: We analyse theoretically the cumulant expansion up to fourth order in b of SDE and DDE signals. Additionally, we perform in silico experiments to compare SDE and DDE capabilities under similar noise conditions. Results: We prove analytically that DDE provides invariant information non-accessible from SDE, which makes the NODDIDA parameter estimation injective. The in silico experiments show that DDE reduces the bias and mean square error of the estimation along the whole feasible region of 5D model parameter space. Conclusions: DDE adds additional information for estimating the model parameters, unexplored by SDE, which is enough to solve the degeneracy in the NODDIDA model parameter estimation.Comment: 22 pages, 7 figure

Funcionalismo e causação mental

O que colocou o fundonalismo no centro do debate em tomo do problema mente-cmpo nos últimos trinta anos parece ter sido a sua capacidade de condliar intuições fisicalistas com uma espécie de não-redudonismo: se por um lado postula-se a existência de entes físicos somente, distribuídos em uma ontologia estratificada, por outro não se falha em explicitar uma distinção real entre as propriedades de entes capacitados a sentir e representar. A supemniência mente-corpo aparentam esclarecer essas intuições dos jisica/istas não-redutims. Vários dos trabalhos de Kim em tomo dessa relação, em especial aqueles publicados antes do fim da década de. oitenta, sugeriram a supemniência como uma possível, e promissora, elucidação do estado de coisas em tor no do problema da relação entre a mentalidade e o fisico. Nos últimos anos, contudo, Kim apresentou um dilema, expressando com bastante pungência que a causação mental revela-se ininteligível, valendo ou não valendo a supemniência mente -corpo. Por conseguinte, a superveniência deixa de compor uma possível solução para o problema, passando a constituí-lo. Como tal conceito de sujxrveniênda mente-corpo estende-se naturalmente a uma região de intersecção entre todas ai posturas não -reducionistas minimamentefisicalistas, as preocupações de Kim, se defato justificadas, sugerem algo de bastante grave com o fisicalismo não-redudonista. Defenderemos neste trabalho que, apesar do problema da exclusão causal sergenuíno, ainda é cedo para concluirmos a falsid ade do fisicalismo não-redutivo. ____________________________________________________________________________________________________________ ABSTRACTWhat has placed functionalism in the center o f the debate around the mind-body problem in the last three decades seems to ham been its capacity to conciliate pbysicalist intuitions with non-reductionism: if, on the one hand, the functionalist o f plysicalist persuasion postulates the existence o f physical entities only, distributed in a stratified ontological model, on the other, she does not sly away fm m a realism regarding these entities 's properties, in particular with respect to the ones related to sensing and representing. Mitul-body sttpemnience seems to haiv come along to bring light upon these non-reductionist andpljysicalist intuitions. KJm, notably in the eighties, suggested supervenience to offer a clear sense in which the relation between mentality and the physical could be understood. In the last years, nonetheless, he has become increasingly skeptic about the possibility o f our understanding mental causation through mind-body supervenience. H e sets forth a dilemma, according to which mental causation is unintelligible, etm mere supervenience true. In Kim ’s vie», then, mind-body supervenience turns out to compose the problem, instead o f expressing a solution to it. Moreover, since mind-body supervenience seems to apply to a ll minimally pkysicalist positions on the mind-body problem, K im ’s misgivings suggest something critical with non-reductive pbysicalism in general. We shall argue in this paper that, although Kim's misgivings seem justified, it would be headlong to assume the falsity o f non-reductive pljysicalism

Automobile Usage-Based-Insurance: Improving Risk Assessment measured through telematics

Dissertation presented as the partial requirement for obtaining a Master's degree in Statistics and Information Management, specialization in Risk Analysis and ManagementAccurate risk estimation with proportionate fees is the cornerstone of insurance activity, a billion-dollar service industry. Due to progressive technological development, insurance companies are now able to improve their risk assessment in the underwriting process of automobile insurance. Through the installation of Onboard-diagnostic devices or with an application in the customers’ smartphones, insurance companies may measure behavioral and situational risk factors such as distance covered and driving habits. These new risk factors provide further information that helps the client’s risk evaluation beyond the traditional risk factors of customer and car specific. The objective of this research is to measure the increased prediction capacity of the claim predicting model by including driver behavior variables. A Generalized Linear model was applied, that includes not only the traditional risk factors, but also additional risk factors measured by telematics, and a new model-based ensemble predictor to a dataset with more than 3 million drivers. Results show that the incorporation of driver’s behavior variables increases the overall capacity of the model. By adding these behavioral risk factors, the actuarial accuracy is increased, leading to a more tailored approach of risk assessment and also awarding the clients that have safer conduct on the road and penalizing those with a more hazardous behavior prone to incurring in car accidents

Diffusion MRI for Well-posed and Optimal White Matter Microstructure Characterisation: Beyond Single Diffusion Encoding

The human brain hosts a colossal number of water molecules which are constantly moving due to Brownian motion. Their movement, random by nature, is restricted by the brain tissue walls. Magnetic Resonance Imaging (MRI) provides macroscopic measurements of the diffusion process in a non-invasive manner, i.e. diffusion MRI. Hidden in these measurements lies information about the underlying architecture. The ability to unravel tissue microstructure from the coarse-grained diffusion measurements is extremely valuable since this information is 2-3 orders of magnitude below typical MRI resolution. This makes diffusion MRI sensitive to pathological and developmental processes occurring at the mesoscopic scale, in the order of microns. Accessing this level of detail can lead to clinical biomarkers specific to early stages of neurodegenerative diseases or brain development. Computational models of biophysical tissue properties have been widely used in diffusion MRI research to elucidate the link between microstructural properties and MR signal formation. The potential increase in sensitivity and specificity in detecting brain microstructural changes is their major driving force. However, these models establish complex relationships between biophysical properties and the MR signal, making the inverse problem of recovering model parameters from noisy measurements ill-conditioned with conventional diffusion MRI acquisitions. This thesis explores ways to make diffusion MRI biophysical modelling more robust while maintaining time and hardware requirements that are feasible in clinical conditions. Firstly, we explore theoretically the benefits of incorporating functionally independent measurements, such as double diffusion encoding. Secondly, we propose an optimal experiment design framework that gives us, after exploring the whole multidimensional diffusion MRI measurement space, the acquisition that maximises accuracy and precision in the parameter estimation. Finally, we extract relevant information from histology images that can be used to feed or benchmark diffusion MRI models

Avaliação de Propriedades Biológicas de Cimentos Biocerâmicos em Cultura de Células Osteoblástica Humanas e um Relatório de sua Aplicação Clínica em Perfuração Radicular

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Odontologia, Programa de Pós-Graduação em em Odontologia, 2020.Atualmente o agregado de trióxido mineral (MTA) ainda é considerado o material de escolha para o tratamento reparador de perfuração radicular e cirurgias apicais. Ao longo dos anos esse material vem sendo aperfeiçoado, o que culminou na consolidação dos cimentos biocerâmicos para esse tipo de tratamento. Seu potencial bioativo e resistência a humidade também o credenciam como cimento obturador do sistema de canais radiculares. O objetivo desse estudo foi avaliar as propriedades biológicas dos cimentos biocerâmicos em cultura de células osteoblásticas humanas e relatar um caso clínico de tratamento de perfuração radicular com cimento obturador biocerâmico. O estudo foi dividido em 5 capítulos: No capítulo 1, foi apresentada uma introdução sobre a complexidade do tratamento endodôntico e a necessidade do desenvolvimento de materiais biocompatíveis tanto para obturação de canais radiculares quanto para tratamentos mais complexos como perfurações radiculares, lesões apicais persistentes, tratamentos regenerativos, ápices incompletos dentre outras. Uma revisão da literatura também foi realizada com pesquisas atuais que contribuíram para a execução deste trabalho. No capítulo 2, foi apresentado um estudo sobre a biocompatibilidade e bioatividade de cimentos biocerâmicos em cultura de células do tipo osteoblastos humanos (Saos-2). O objetivo deste trabalho foi avaliar a biocompatibilidade e a bioatividade de dois novos cimentos biocerâmicos reparadores, Bio-C® Repair e PBS HP®, que foram recentemente disponibilizados com a promessa de apresentarem propriedades biológicas superiores aos cimentos convencionais. Foram realizados experimentos para avaliação da viabilidade celular (MTT), proliferação celular (ensaio de Wound Healing) e bioatividade por PCR em tempo real (qPCR) dos genes marcadores de osteogênse (BGLAP, ALPL e BSP). A atividade enzimática (ALP) também foi aferida. O capítulo 3 é o relato retrospectivo de um caso clínico de tratamento de perfuração radicular no terço apical de um molar inferior com o cimento biocerâmico EndoSequence BC Sealer. O paciente foi inicialmente encaminhado para tratamento cirúrgico. Entretanto, diante dos estudos demonstrando excelentes propriedades biológicas dos cimentos biocerâmicos, optou-se por um tratamento conservador com o Endosequence BC sealer. Este relato de caso teve proservação por 3 anos. Condições clínicas como perfurações radiculares apresentam prognóstico desfavorável por afetar significativamente o periodonto e ser de difícil reparo sem uma intervenção cirúrgica. Os cimentos obturadores biocerâmicos surgiram como uma alternativa conservadora para tratamentos de perfuração desde que seja possível a descontaminação e selamento da área afetada. Nos capítulos 4 e 5 foram apresentadas as considerações finais sobre os cimentos biocerâmicos e um press release respectivamente.Currently, the mineral trioxide aggregate (MTA) is still considered the material of choice for the repair of root perforation and apical surgeries. Over the years, this material has been improved, which culminated in the consolidation of bioceramic cements for this type of treatment. Its bioactive potential and resistance to moisture also qualify it as a filling cement for the root canal system. The objective of this study was to evaluate the biological properties of bioceramic cements in human osteoblastic cell culture and to report a clinical case of root perforation treatment with bioceramic sealer. The study was divided into 5 chapters: In chapter 1, an introduction was presented on the complexity of endodontic treatment and the need for the development of biocompatible materials for both root canal filling and for more complex treatments such as root perforations, persistent apical lesions, treatments regenerative, incomplete apexes among others. A literature review was also carried out with current research that contributed to the execution of this work. In chapter 2, a study was presented on the biocompatibility and bioactivity of bioceramic cements in human osteoblast cell culture (Saos-2). The objective of this work was to evaluate the biocompatibility and bioactivity of two new bioceramic repair cements, Bio-C® Repair and PBS HP®, which were recently made available with the promise of presenting superior biological properties than conventional cements. Experiments were carried out to evaluate cell viability (MTT), cell proliferation (Wound Healing assay) and bioactivity by real-time PCR (qPCR) of osteogenesis marker genes (BGLAP, ALPL and BSP). Enzymatic activity (ALP) was also measured. Chapter 3 is a retrospective report of a clinical case of treatment of root perforation in the apical third of a mandibular molar with the bioceramic EndoSequence BC Sealer. The patient was initially referred for surgical treatment. However, in view of studies showing excellent biological properties of bioceramic cements, a conservative treatment with Endosequence BC sealer was chosen. This case report was follow-up for 3 years. Clinical conditions such as root perforations have an unfavorable prognosis because it significantly affects the periodontium and is difficult to repair without surgical intervention. Bioceramic filling cements have emerged as a conservative alternative for drilling treatments as long as decontamination and sealing of the affected area is possible. Chapters 4 and 5 presented the final considerations on bioceramic cements and a press release respectively

Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS)

BACKGROUND: In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients. OBJECTIVE: The aim of the present study is to evaluate the safety and usefulness of patch testing in DRESS. PATIENTS/METHODS: Between January 1998 and December 2008, we studied 56 patients with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in 19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1 patient each (7%). RESULTS: A positive patch test reaction was observed in 18 patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In the antiepileptic group, carbamazepine alone was responsible for 13 of 17 positive reactions (76.5%). Patch tests with allopurinol and its metabolite were negative in all cases attributed to this drug. CONCLUSIONS: In this study, patch testing was a safe and useful method in confirming the culprit drug in DRESS induced by antiepileptic drugs, whereas it had no value in DRESS induced by allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but positive patch tests suggest a drug-dependent delayed hypersensitivity mechanism

Gestão de cinzas produzidas em centrais de cogeração operadas com biomassa

Mestrado em Engenharia do AmbienteA produção de energia térmica e electricidade a partir da combustão de biomassa tem sofrido um aumento em Portugal, onde existe actualmente um importante conjunto de unidades de cogeração e unidades dedicadas à produção de energia eléctrica. Num futuro próximo esse número de unidades será incrementado, logo que entrem em actividade as 17 novas unidades dedicadas à produção de energia eléctrica previstas. À semelhança do que acontece com qualquer outro combustível sólido, a combustão de biomassa origina um resíduo sólido, as cinzas, cuja gestão apropriada é do máximo interesse, não só do ponto de vista económico mas também ambiental. No presente trabalho foram avaliadas as opções de gestão de cinzas produzidas em centrais termoeléctricas, ou de cogeração, operadas a biomassa em Portugal. Realizou-se, numa primeira fase, a identificação e caracterização das centrais existentes, actualmente e num futuro próximo, permitindo estimar a produção de cinzas. Em conjunto com a avaliação do Inventário Florestal Nacional foi também possível estimar a disponibilidade de biomassa, no geral e na proximidade de cada central, avaliando se a biomassa existente é suficiente. Numa segunda fase foi realizado o enquadramento jurídico da gestão de cinzas biomassa, numa perspectiva de gestão de resíduos. Foi seleccionado e estudado o caso de uma central de cogeração de uma indústria de produção de pasta e papel, onde foram recolhidas amostras de cinzas volantes e de fundo, de um sistema de combustão em grelha e um sistema em leito fluidizado. Foi realizada a caracterização das cinzas, sendo posteriormente realizada a avaliação às opções de valorização disponíveis.The thermic and electric energy production from biomass combustion had suffered a huge growth in Portugal, where we can actually find a considerable number of cogeneration units, as well as dedicated centrals for electric energy production. In a near future, that number will be increased, as soon as the 17 new dedicated centrals start working. As it happens with any other solid fuel, biomass combustion originates a solid residue, the ash, which management has the maximum interest, nor only from the economic view but also from the environmental view. In this work it was done an evaluation of ash management options, focusing the ashes produced in thermoelectrics or cogeneration units, working with biomass in Portugal. In a first stage, I’ve done the identification and characterization of the existing units and of the new ones, calculating the ash production. Analyzing the National Forest Inventory, the availability of ashes were predicted, making it possible to predict if the biomass produced near each central is enough for the needs. In a second stage it was done the backgroud for biomass ash. It has been selected and studied the case of a cogeneration central from a pulp and paper industry, where there were collected fly ash and bottom ash from a grate system and from a fluidized bed installation. The ash characterization has been made, and then the option evaluation for as depositing where studied