Otimização de esquemas terapêuticos do carcinoma da próstata envolvendo braquiterapia de baixa taxa de dose e radioterapia externa : abordagens física e radiobiológica

RESUMO: Este trabalho teve como objetivo a determinação de esquemas de tratamento alternativos para o carcinoma da próstata com radioterapia externa (EBRT) e braquiterapia de baixa taxa de dose (LDRBT) com implantes permanentes de Iodo-125, biologicamente equivalentes aos convencionalmente usados na prática clínica, com recurso a modelos teóricos e a métodos de Monte Carlo (MC). Os conceitos de dose biológica efetiva (BED) e de dose uniforme equivalente (EUD) foram utilizados, com o modelo linear-quadrático (LQ), para a determinação de regimes de tratamento equivalentes. Numa primeira abordagem, utilizou-se a BED para determinar: 1) esquemas hipofracionados de EBRT mantendo as complicações retais tardias de regimes convencionais com doses totais de 75,6 Gy, 77,4 Gy, 79,2 Gy e 81,0 Gy; e 2) a relação entre as doses totais de EBRT e LDRBT de modo a manter a BED do regime convencional de 45 Gy de EBRT e 110 Gy de LDRBT. Numa segunda abordagem, recorreu-se ao código de MC MCNPX para a simulação de distribuições de dose de EBRT e LDRBT em dois fantomas de voxel segmentados a partir das imagens de tomografia computorizada de pacientes com carcinoma da próstata. Os resultados das simulações de EBRT e LDRBT foram somados e determinada uma EUD total de forma a obterem-se: 1) esquemas equivalentes ao tratamento convencional de 25 frações de 1,8 Gy de EBRT em combinação com 110 Gy de LDRBT; e 2) esquemas equivalentes a EUD na próstata de 67 Gy, 72 Gy, 80 Gy, 90 Gy, 100 Gy e 110 Gy. Em todos os resultados nota-se um ganho terapêutico teórico na utilização de esquemas hipofracionados de EBRT. Para uma BED no reto equivalente ao esquema convencional, tem-se um aumento de 2% na BED da próstata com menos 5 frações. Este incremento dá-se de forma cada vez mais visível à medida que se reduz o número de frações, sendo da ordem dos 10-11% com menos 20 frações e dos 35-45% com menos 40 frações. Considerando os resultados das simulações de EBRT, obteve-se uma EUD média de 107 Gy para a próstata e de 42 Gy para o reto, com o esquema convencional de 110 Gy de LDRBT, seguidos de 25 frações de 1,8 Gy de EBRT. Em termos de probabilidade de controlo tumoral (igual EUD), é equivalente a este tratamento a administração de EBRT em 66 frações de 1,8 Gy, 56 de 2 Gy, 40 de 2,5 Gy, 31 de 3 Gy, 20 de 4 Gy ou 13 de 5 Gy. Relativamente à administração de 66 frações de 1,8 Gy, a EUD generalizada no reto reduz em 6% com o recurso a frações de 2,5 Gy e em 10% com frações de 4 Gy. Determinou-se uma BED total de 162 Gy para a administração de 25 frações de 1,8 Gy de EBRT em combinação com 110 Gy de LDRBT. Variando-se a dose total de LDRBT (TDLDRBT) em função da dose total de EBRT (TDEBRT), de modo a garantir uma BED de 162 Gy, obteve-se a seguinte relação:.......... Os resultados das simulações mostram que a EUD no reto diminui com o aumento da dose total de LDRBT para dose por fração de EBRT (dEBRT) inferiores a 2, Gy e aumenta para dEBRT a partir dos 3 Gy. Para quantidades de TDLDRBT mais baixas (<50 Gy), o reto beneficia de frações maiores de EBRT. À medida que se aumenta a TDLDRBT, a EUD generalizada no reto torna-se menos dependente da dEBRT. Este trabalho mostra que é possível a utilização de diferentes regimes de tratamento para o carcinoma da próstata com radioterapia que possibilitem um ganho terapêutico, quer seja administrando uma maior dose biológica com efeitos tardios constantes, quer mantendo a dose no tumor e diminuindo a toxicidade retal. A utilização com precaução de esquemas hipofracionados de EBRT, para além do benefício terapêutico, pode trazer vantagens ao nível da conveniência para o paciente e economia de custos. Os resultados das simulações deste estudo e conversão para doses de efeito biológico para o tratamento do carcinoma da próstata apresentam linhas de orientação teórica de interesse para novos ensaios clínicos. --------------------------------------------------ABSTRACT: The purpose of this work was to determine alternative radiotherapy regimens for the treatment of prostate cancer using external beam radiotherapy (EBRT) and low dose-rate brachytherapy (LDRBT) with Iodine-125 permanent implants which are biologically equivalent to conventional clinical treatments, by the use of theoretical models and Monte Carlo techniques. The concepts of biological effective dose (BED) and equivalent uniform dose (EUD), together with the linear-quadratic model (LQ), were used for determining equivalent treatment regimens. In a first approach, the BED concept was used to determine: 1) hypofractionated schemes of EBRT maintaining late rectal complications as with the conventional regimens with total doses of 75.6 Gy, 77.4 Gy, 79.2 Gy and 81.0 Gy; and 2) the relationship between total doses of EBRT and LDRBT in order to keep the BED of the conventional treatment of 45 Gy of EBRT and 110 Gy of LDRBT. In a second approach, the MC code MCNPX was used for simulating dose distributions of EBRT and LDRBT in two voxel phantoms segmented from the computed tomography of patients with prostate cancer. The results of the simulations of EBRT and LDRBT were added up and given an overall EUD in order to obtain: 1) equivalent to conventional treatment regimens of 25 fraction of 1.8 Gy of EBRT in combination with 110Gy of LDRBT; and 2) equivalent schemes of EUD of 67 Gy, 72 Gy, 80 Gy, 90 Gy, 100 Gy, and 110Gy to the prostate. In all the results it is noted a therapeutic gain using hypofractionated EBRT schemes. For a rectal BED equivalent to the conventional regimen, an increment of 2% in the prostate BED was achieved with less 5 fractions. This increase is visibly higher as the number of fractions decrease, amounting 10-11% with less 20 fractions and 35-45% with less 20 fractions. Considering the results of the EBRT simulations an average EUD of 107 Gy was achieved for the prostate and of 42 Gy for the rectum with the conventional scheme of 110 Gy of LDRBT followed by 25 fractions of 1.8 Gy of EBRT. In terms of tumor control probability (same EUD) it is equivalent to this treatment, for example, delivering the EBRT in 66 fractions of 1.8 Gy, 56 fractions of 2 Gy, 40 fractions of 2.5 Gy, 31 fractions of 3 Gy, 20 fractions of 4 Gy or 13 fractions of 5 Gy. Regarding the use of 66 fractions of 1.8 Gy, the rectum EUD is reduced to 6% with 2.5 Gy per fraction and to 10% with 4 Gy. A total BED of 162 Gy was achieved for the delivery of 25 fractions of 1.8 Gy of EBRT in combination with 110 Gy of LDRBT. By varying the total dose of LDRBT (TDLDRBT) with the total dose of EBRT (TDEBRT) so as to ensure a BED of 162 Gy, the following relationship was obtained: ....... The simulation results show that the rectum EUD decreases with the increase of the TDLDRBT, for EBRT dose per fracion (dEBRT) less than 2.5 Gy and increases for dEBRT above 3 Gy. For lower amounts of TDLDRBT (< 50Gy), the rectum benefits of larger EBRT fractions. As the TDLDRBT increases, the rectum gEUD becomes less dependent on the dEBRT. The use of different regimens which enable a therapeutic gain, whether deivering a higher dose with the same late biological effects or maintaining the dose to the tumor and reducing rectal toxicity is possible. The use with precaution of hypofractionated regimens, in addition to the therapeutic benefit, can bring advantages in terms of convenience for the patient and cost savings. The simulation results of this study together with the biological dose conversion for the treatment of prostate cancer serve as guidelines of interest for new clinical trials.

Rendimento e condições de desdobro de 20 espécies de madeiras da Amazônia

Neste trabalho, procedeu-se à avaliação do rendimento e condições de desdobro de espécies de madeiras tropicais provenientes da área de construção da UHE-Balbina e da reserva florestal ZF-2. Utilizou-se o mínimo de 5 toras por espécie para a coleta das informações sobre diâmetro médio das toras, grau de conicidade das toras, grau de dificuldade corte, índice de durabilidade do fio, rendimento e densidade básica. O rendimento médio das espécies estudadas variou entre 41,9 e 61,8%, sendo que 6 espécies (caroXXX, cedrorana, cupiúba, louro aritu, madioqueira e quarubarana), apresentaram rendimento médio acima da faixa normal de 45 a 55%, considerada para madeiras tropicais. Entre as espécies estudadas, as toras de Brasimum rubescens (pau rainha) e as Manilkara huberi (maçarandba), foram as que apresentaram maior grau de dificuldade de corte das toras entre as diferentes espécies. As fórmulas apresentadas neste trabalho permitem estimar o volume de madeira serrada produzido a partir das toras de uma determinada espécie.

Xenogeneic M2-polarization of Macrophages by undifferentiated and differentiated adipose tissue-derived stem cells

Mesenchymal stem cells (MSCs) are considered to be â â immunologically privileged.â â In a previous work when human adipose tissue-derived stem cells (hASCs) subcutaneously implanted in mice we did not identify an adverse host response1. Recently, it was shown that tissue regeneration could benefit from the polarization of M2 macrophages subpopulations 2. In this study we hypothesised that undifferentiated hASCs and derived osteoblasts and chondrocytes are able to switch murine bone marrow-derived macrophages (mBMMÃ s) into M2 phenotype, aiding tissue regeneration. Murine BMMÃ s were plated in direct contact with undifferentiated and osteo or chondro-differentiated hASCs for 4 h, 10 h, 24 h and 72 h. The cytokine profile was analysed by qRT-PCR and the surface markers were detected by flow cytometry. The direct interaction of both cell types was observed by time lapse microscopy. The results showed that mBMMÃ s polarized after contacting tissue culture polystyrene. This M2 phenotype was maintained along the experiment in direct contact with both undifferentiated and osteo or chondro-differentiated hASCs. This was confirmed by the expression of IL-1, IL-10, IL-4, TNF-a and IFN-g (genetic profile) and surface markers (CD206 + + , CD336 + + , MHC II + and CD86 + + ) detection. These data suggest the potential of hASCs in contemporary xenogenic tissue engineering and regenerative medicine strategies, as well as host immune system modulation in autoimmune diseases. 

The influence of low-frequency noise pollution on the quality of life and place in sustainable cities: a case study from northern Portugal

Discussing urban planning requires rethinking sustainability in cities and building healthy environments. Historically, some aspects of advancing the urban way of life have not been considered important in city planning. This is particularly the case where technological advances have led to conflicting land use, as with the installation of power poles and building electrical substations near residential areas. This research aims to discuss and rethink sustainability in cities, focusing on the environmental impact of low-frequency noise and electromagnetic radiation on human health. It presents data from a case study in an urban space in northern Portugal, and focuses on four guiding questions: Can power poles and power lines cause noise? Do power poles and power lines cause discomfort? Do power poles and power lines cause discomfort due to noise? Can power poles and power lines affect human health? To answer these questions, we undertook research between 2014 and 2015 that was comprised of two approaches. The first approach consisted of evaluating the noise of nine points divided into two groups â near the sourceâ (e.g., up to 50 m from power poles) and â away from the sourceâ (e.g., more than 250 m away from the source). In the second approach, noise levels were measured for 72 h in houses located up to 20 m from the source. The groups consist of residents living within the distance range specified for each group. The measurement values were compared with the proposed criteria for assessing low-frequency noise using the DEFRA Guidance (University of Salford). In the first approach, the noise caused discomfort, regardless of the group. In the second approach, the noise had fluctuating characteristics, which led us to conclude that the noise caused discomfort.

Métodos para superação da dormência e biometria de frutos e sementes de Parkia nitida Miquel. (Leguminosae - Mimosoideae)

Foram realizadas avaliações biométricas em frutos e sementes de Parkia nitida e estudado o efeito dos tratamentos escarificação mecânica sem (T2) e com (T3) aplicação do fungicida Benomyl; imersão em Η2Ο a 80°C (T4) e a 100°C (T5); imersão em H2SO4 durante 10 (T6), 20 (T7), 40 (T8) e 80 (T9) minutos, na superação da dormência das sementes. Foram totalizadas as sementes germinadas aos 10, 20, 30 e 40 dias após a semeadura. O ensaio foi instalado com quatro repetições de 50 sementes, semeadas em substrato de vermiculita. O número de frutos/inflorescência variou de um a oito. O comprimento e largura dos frutos e o número de sementes/fruto variaram de 36,0 a 80,0 cm, de 4,6 a 6,5 cm e de 17 a 37 sementes, respectivamente. O comprimento, a largura e a espessura das sementes variaram de 16,1 a 24,0 mm, de 8,1 a 14,0 mm e de 5,1 a 9,0 mm, respectivamente. Houve interação significativa entre métodos para superação da dormência e dias decorridos após a semeadura na germinação das sementes. As análises de regressão mostraram significância para os tratamentos T2, T3, T4, T6 e T8. O T4 proporcionou apenas 10,0% de germinação; entretanto os tratamentos T2 e T3 tiveram efeito satisfatório, com 50,0% e 72,5% de germinação, respectivamente. Os tratamentos com H2SO4 estiveram entre os mais eficientes, com 80,0%, 82,5%, 80,5% e 74,5%, durante 10, 20, 40 e 80 minutos de imersão, respectivamente. As percentagens de germinação para o T1 (testemunha) e T5 foram inferiores a 2,5%. Concluiu-se que sementes de P. nitida apresentam dormência devido à impermeabilidade do tegumento à água; é necessária a escarificação das sementes para se obter elevada percentagem de germinação; tratamentos com H2SO4, por 20 minutos, e escarificação mecânica + fungicida constituem-se métodos eficientes para superação da dormência.

O efeito da salinidade no desenvolvimento larval do caranguejo - uçá, Ucides cordatus (Linnaeus, 1763) (Decapoda: Ocypodidae) no Norte do Brasil

O presente trabalho estudou o efeito da salinidade na sobrevivência e na duração do desenvolvimento larval do caranguejo-uçá, Ucides cordatus (do estuário do Rio Caeté, Norte do Brasil), até a fase de megalopa em sete tratamentos de salinidade (0, 5, 10, 15, 20, 25 e 30). A salinidade afetou significativamente a sobrevivência das larvas zoea, no entanto não afetou a duração do desenvolvimento larval (20,77 ± 1,56 dias). Nas salinidades 0, 5 e 10 houve total mortalidade das larvas zoea. Somente a partir da salinidade 15 observou-se um desenvolvimento completo até a fase de megalopa. A taxa de sobrevivência foi maior em salinidade 30 (72%) e menor em 15 (16%). A reduzida taxa de sobrevivência das larvas zoea de U. cordatus, em salinidades baixas, indica a necessidade de dispersão larval do estuário para as águas costeiras onde as condições de salinidade para o desenvolvimento larval são mais favoráveis. Caso contrário se não houvesse a dispersão, a reduzida salinidade das águas estuarinas no período chuvoso, causaria uma elevada mortalidade, afetando desta forma o recrutamento, a manutenção e o crescimento da população de U. cordatus nos manguezais.

Energy harvesting performance of BaTiO3/poly(vinylidene fluoride-trifluoroethylene) spin coated nanocomposites

The energy harvesting efficiency of poly(vinylidene fluoride-trifluoroethylene) spin coated films and its nanocomposites with piezoelectric BaTiO3 have been investigated as a function of ceramic filler size and content. It is found that the best energy harvesting performance of ~0.28 W is obtained for the nanocomposite samples with 20% filler content of 10 nm size particles and for 5% filler content for the 100 and 500 nm size fillers. For the larger filler average sizes, the power decreases for filler contents above 5% due to increase of the mechanical stiffness of the samples. Due to the similar dielectric characteristics of the samples, the performance is mainly governed by the mechanical response. The obtained power values, easy processing and the low cost and robustness of the polymer, allow the implementation of the material for micro and nanogenerator applications.

Search for new phenomena in the dijet mass distribution using pp collision data at s√=8 TeV with the ATLAS detector

Dijet events produced in LHC proton--proton collisions at a center-of-mass energy s√=8 TeV are studied with the ATLAS detector using the full 2012 data set, with an integrated luminosity of 20.3 fb−1. Dijet masses up to about 4.5 TeV are probed. No resonance-like features are observed in the dijet mass spectrum. Limits on the cross section times acceptance are set at the 95% credibility level for various hypotheses of new phenomena in terms of mass or energy scale, as appropriate. This analysis excludes excited quarks with a mass below 4.09 TeV, color-octet scalars with a mass below 2.72 TeV, heavy W′ bosons with a mass below 2.45 TeV, chiral W∗ bosons with a mass below 1.75 TeV, and quantum black holes with six extra space-time dimensions with threshold mass below 5.82 TeV.

Search for Higgs bosons decaying to aa in the μμττ final state in pp collisions at s√= 8 TeV with the ATLAS experiment

A search for the decay to a pair of new particles of either the 125 GeV Higgs boson (h) or a second CP-even Higgs boson (H) is presented. The dataset correspods to an integrated luminosity of 20.3 fb−1 of pp collisions at s√= 8 TeV recorded by the ATLAS experiment at the LHC in 2012. The search was done in the context of the next-to-minimal supersymmetric standard model, in which the new particles are the lightest neutral pseudoscalar Higgs bosons (a). One of the two a bosons is required to decay to two muons while the other is required to decay to two τ-leptons. No significant excess is observed above the expected backgrounds in the dimuon invariant mass range from 3.7 GeV to 50 GeV. Upper limits are placed on the production of h→aa relative to the Standard Model gg→h production, assuming no coupling of the a boson to quarks. The most stringent limit is placed at 3.5% for ma= 3.75 GeV. Upper limits are also placed on the production cross section of H→aa from 2.33 pb to 0.72 pb, for fixed ma = 5 GeV with mH ranging from 100 GeV to 500 GeV.

Stabilization in early adult-onset myopia with corneal refractive therapy

Purpose: To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Methods: Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between ?1.50 and ?2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ)lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January–December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Results: Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. Conclusions: We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment.

Examining mindfulness and its relation to self-differentiation and alexithymia

Published online first in 10 July 2013

Investigação do potencial antioxidante e anticolinesterásico de 20 espécies da família Lauraceae

Lauraceae é uma das famílias mais importantes na floresta amazônica. Diversas de suas espécies apresentam em sua composição substâncias com pronunciadas atividades biológicas. Nesse trabalho, os extratos obtidos em etanol de galhos e folhas de 20 espécies de Lauraceae foram coletados na Reserva Florestal Ducke e avaliados quant o às atividades antioxidante frente ao radical livre 2,2-difenil-1-picrilhidrazila(DPPH) e inibidora da enzima acetilcolinesterase. O extrato dos galhos de Licaria martinianal apresentou a maior capacidade de sequestro do radical DPPH (6,96 µg.mL-1),mas os extratos de Ocotea iminor foram os mais ativos na inibição da enzima acetilcolinesterase, apresentando também pronunciada atividade antioxidante. O perfil de atividade antioxidante e anticolinesterásico destes extratos está sendo relatado pela primeira vez neste trabalho.

Segmentação do tecido tumoral cerebral em imagens de ressonância magnética

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Eletrónica Médica)

Comparative leaf morphological analysis of 20 species of Chrysobalanaceae

Morphological studies focusing on vegetative traits are useful in identifying species when fertile material is not available. The aim of this study was to assess the application of comparative leaf morphology to identify species of the Chrysobalanaceae family. The morphological observations were made with a stereomicroscope. We used the diaphanization technique for viewing venation details. It is shown the descriptions of the leaf morphology, illustrations and an identification key for 20 species from genera Couepia, Licania and Parinari (Chrysobalanaceae) occurring in the Adolpho Ducke Forest Reserve, Manaus, AM, Brazil. The key was constructed using the DELTA (DEscription Language for TAxonomy) software. Leaf traits such as the presence of intersecondary venation and the type of insertion of secondary veins were recorded for each species. These morphological leaf traits are reliable for identifying species of Chrysobalanaceae