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.

Should my company use Bitcoin?

This work project analyses the possibility for a company to trade their goods and services for bitcoins, by joining the Bitcoin network. It analyses the technological and business requirements to join the Bitcoin Network by looking at Bitcoin’s potential to act as a mean of exchange for trade, unit of account and store of value. The analysis points to the motives, benefits and risks for investors to use the Bitcoin as a traditional currency and recommends on strategies for addressing those risks and maximizing benefits. Other than companies this report, to a lesser extent, will also analyse the Bitcoin from an investor’s point of view, this is, should an investor buy bitcoins for trade and make savings on a regular and everyday basis? A major finding in this work project is that companies could start using the Bitcoin system as a legit form of payment since the benefits of using this technology outweigh the costs and risks, given the right approach. This form of payment will contribute for the upgrade of a company’s business’ image, attract a new pool of consumers and businesses that already trade in bitcoins and pressure existing financial institutions and electronic payment vendors to upgrade their service levels.

LAY USE OF AMAZONIAN PLANTS FOR THE TREATMENT OF TUBERCULOSIS

The Brazilian State of Amazonas has a high incidence of Tuberculosis, 91.4 in 10,000 habitants (SESAU, 1994) and resistant strains of Mycobacterium tuberculosis are frequently being found in the region (SALEM et.al, 1990). These problems have been associated with side effects caused by the antibiotics used to treat Tuberculosis, which have in rum been associated with treatment non-compliance (PATTISAPU, 1984). To resolve this problem a cost effective alternative treatment for Tuberculosis with few or no side effects, needs to be found. Amazonas has an abundance of plants, many of which are used by the lay population for medicinal purposes. A survey was carried out in five towns of the region, interviewing patients receiving treatment for Tuberculosis, to find out whether and which plants have been used to treat Tuberculosis. Results showed that the majority of patients in the sample had used medicinal plants before or after diagnosis of Tuberculoses. Thirteen different plants were recorded for this purpose. Chenopodium ambrosioides L, popularly known as Mastruz, was the most commonly used, followed by Caesalpinia ferrea Mart. Jucá and Spilanthes acmella DC. Jambu. This study concentrates on Mastruz as it was used more frequently than the other medicinal plants. No significant effects on baciloscopy test results were found when Mastruz was used before diagnosis. ln-vitro laboratory tests have also not shown any tuberculocidal effects for Mastruz. Further tests are being carried out on the other medicinal plants.

Establishing guidelines for obtaining optimal cell sources to use in tendon tissue engineering strategies

Cell-based approaches in tissue engineering (TE) have been barely explored for the treatment of tendon and ligament (T/L) tissues, requiring the establishment of a widely available cell source with tenogenic potential. As T/L cells are scarce, stem cells may provide a good alternative. Understanding how resident cells behave in vitro, might be useful for recapitulating the tenogenic potential of stem cells for tendon TE applications. Therefore, we propose to isolate and characterize human T/L-derived cells (hTDCs and hLDCs) and compare their regenerative potential with stem cells from adipose tissue (hASCs) and amniotic fluid (hAFSCs)(1). T/L cells were isolated using different procedures and stem cells isolated as described elsewhere(1). Moreover, T/L cells were stimu- lated into the three mesenchymal lineages, using standard differentia- tion media. Cells were characterized for the typical stem cell markers as well as T/L related markers, namely tenascin-C, collagen I and III, decorin and scleraxis, using different complementary techniques such as real time RT-PCR, immunocytochemistry and flow cytometry. No differences were observed between T/L in gene expression and protein deposition. T/L cells were mostly positive for stem ness markers (CD73/CD90/CD105), and have the potential to differentiate towards osteogenesis, chondrogenesis and adipogenesis, demonstrated by the positive staining for AlizarinRed, SafraninO, ToluidineBlue and OilRed. hASCs and hAFSCs exhibit positive expression of all tenogenic mark- ers, although at lower levels than hTDCs and hLDCs. Nevertheless, stem cells availability is key factor in TE strategies, despite that it’s still required optimization to direct their tenogenic phenotype.

Exploring the use of HPFRC and GFRP grids for the production of manhole covers

Corrosion of the steel reinforced concrete elements is one of the common pathologies that limits the long-term performance of urban infrastructures. This problem causes the loss of structural serviceability by decreasing the concrete-steel bond strength and reducing the cross section of the reinforcements. The present study introduces a new system for developing free-corrosion resistance prefabricated manhole covers for applications in the aggressive environments, i.e. wastewater collector systems, sewer systems, stormwater systems, etc. Fibre reinforced cement composites were applied in this system in order to suppress the corrodible steel mesh and maintain the structural ductility as well. Application of fibre reinforced polymer (FRP) system is adopted as the additional solution for increasing the load carrying capacity of these elements without concerns about corrosion. The effectiveness of the applied strategy in developing the manhole covers in terms of load carrying capacity and failure mode is evaluated in this research. Furthermore, this paper discusses a FEM-based simulation, aiming to address the possibility of calibrating the constitutive model parameters related to fracture modes I and II.

A systematic approach for externalities in occupational safety through the use of the delphi methodology

Ramos, D., Arezes, P. M., & Afonso, P. (2015). A systematic approach for externalities in occupational safety through the use of the delphi methodology. Paper presented at the Occupational Safety and Hygiene III - Selected Extended and Revised Contributions from the International Symposium on Safety and Hygiene.

Plastic waste use as aggregate and binder modifier in open-graded asphalts

Road pavements are very important infrastructures for the Society, but they can cause serious environmental impacts during construction, operation and rehabilitation phases. Thus, it is essential to develop surface paving solutions that promote not only the durability but also a comfortable and safe use. In fact, this work aims to study the properties of new opengraded mixtures for surface layers produced with plastic wastes. First, HDPE and EVA wastes were used as bitumen modifiers, and then another plastic waste (PEX) replaced part of the aggregates. After studying the modified binders, the open-graded mixtures were designed, and then they were tested concerning their particle loss, rutting resistance, surface texture and damping effect. It was concluded that both ways of using the plastic wastes can improve the mechanical and functional properties of the open-graded mixtures related to the pavement performance.

Local seismic cultures: the use of timber frame structures in the south of Portugal

Given the fact that using timber frame structures has proven to improve the seismic behavior of vernacular architecture, as has been reported in past earthquakes in many countries, its preservation as a traditional earthquake resistant practice is important. This paper firstly intends to evaluate whether the use of timber frames as a traditional seismic resistant technique for vernacular architecture in the South of Portugal, traditionally a seismic region, is still active. Secondly, the city of Vila Real de Santo António was selected as a case study because it also followed a Pombaline development contemporary to the reconstruction of Lisbon. The plan included the provision of timber frame partition walls for some of the buildings and, thus, an overview of the type of constructions originally conceived is provided. Finally, the alterations done in the original constructions and the current state of the city center are described and the effect of these changes on the seismic vulnerability of the city is discussed.

Antibacterial activity of textiles for wound treatment

Major advances in the development and use of antimicrobial textiles to control bacterial proliferation on wound beds continue. However, wound dressings are, in general, not included in standardized regimens for measuring and monitoring their antimicrobial effectiveness. This work adapts these methods to assess the antibacterial activity of textiles designed for wound healing purposes. Environmental conditions representative of those present at the wound site (i.e., moisture levels, infection, and available nutrients) were evaluated. This work shows that moisture levels were the environmental factor that had the greatest influence on the antimicrobial agent activities tested. These results suggest that it is possible to use the more representative environmental conditions present on the wound bed for in vitro screening of textile antimicrobial activity.

Changes in population and land use over time in the Ecuadorian Amazon

This paper draws upon a detailed longitudinal survey of households living on agricultural plots in the northern three provinces of the Ecuadorian Amazon, the principal region of colonization by migrants in Ecuador since the 1970s. Following the discovery of petroleum in 1967 near what has subsequently come to be the provincial capital and largest Amazonian city of Lago Agrio, oil companies built roads to lay pipelines to extract and pump oil across the Andes for export. As a result, for the past 30 years over half of both Ecuador's export earnings and government revenues have come from petroleum extracted from this region. But the roads also facilitated massive spontaneous in-migration of families from origin areas in the Ecuadorian Sierra, characterized by minifundia and rural poverty. This paper is about those migrants and their effects on the Amazonian landscape. We discuss the data collection methodology and summarize key results on settler characteristics and changes in population, land use, land ownership, technology, labor allocation, and living conditions, as well as the relationships between changes in population and changes in land use over time. The population in the study region has been growing rapidly due to both natural population growth (high fertility) and in-migration. This has led to a dramatic process of subdivision and fragmentation of plots in the 1990's, which contrasts with the consolidation of plots that has occurred in most of the mature frontier areas of the Brazilian Amazon. This fragmentation has led to important changes in land tenure and land use, deforestation, cattle raising, labor allocation, and settler welfare.

Contribution of the evaluation strategy and the use of hearing protection for the uncertainty associated with occupational exposure to noise

Doctoral Thesis for PhD degree in Industrial and Systems Engineering

(Un)suitability of the use of pH buffers in biological, biochemical and environmental studies and their interaction with metal ions - a review

The use of buffers to maintain the pH within a desired range is a very common practice in chemical, biochemical and biological studies. Among them, zwitterionic N-substituted aminosulfonic acids, usually known as Good's buffers, although widely used, can complex metals and interact with biological systems. The present work reviews, discusses and updates the metal complexation characteristics of thirty one commercially available buffers. In addition, their impact on biological systems is also presented. The influences of these buffers on the results obtained in biological, biochemical and environmental studies, with special focus on their interaction with metal ions, are highlighted and critically reviewed. Using chemical speciation simulations, based on the current knowledge of the metal-buffer stability constants, a proposal of the most adequate buffer to employ for a given metal ion is presented.

Use of a polyphasic approach including MALDI-TOF MS for identification of Aspergillus section Flavi strains isolated from food commodities in Brazil

Brazil is one the largest producers and exporters of food commodities in the world. The evaluation of fungi capable of spoilage and the production mycotoxins in these commodities is an important issue that can be of help in bioeconomic development. The present work aimed to identify fungi of the genus Aspergillus section Flavi isolated from different food commodities in Brazil. Thirty-five fungal isolates belonging to the section Flavi were identified and characterised. Different classic phenotypic and genotypic methodologies were used, as well as a novel approach based on proteomic profiles produced by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Type or reference strains for each taxonomic group were included in this study. Three isolates that presented discordant identification patterns were further analysed using the internal transcribed spacer (ITS) region and calmodulin gene sequences. The data obtained from the phenotypic and spectral analyses divide the isolates into three groups, corresponding to taxa closely related to Aspergillus flavus, Aspergillus parasiticus, and Aspergillus tamarii. Final polyphasic fungal identification was achieved by joining data from molecular analyses, classical morphology, and biochemical and proteomic profiles generated by MALDI-TOF MS.

A first evaluation on the use of Ardea albus feathers as bioindicators of mercury burden in Amazonian ecosystems

We evaluated in this study the total mercury concentration in feathers of Ardea albus collected in a colony located in the city of Belem-PA, Brazil in a prospective trial for its use as bioindicators of mercury burden in Amazonia ecosystems. An Atomic absorption spectrophotometry with gold amalgamation was used for the metal determination. The total mercury average concentration in body feathers was 2.2 ± 1.5 µg.g-1 and 1.3 ± 0.9 µg.g-1 in wing feathers. No correlation was observed between total mercury concentration and the length of body or wing feathers. Total mercury concentration was above 5 µg.g-1 dry weight in only one body feather sample.

Use of the flooded forest by fish assemblages in lakes of the National Park of Anavilhanas (Amazonas, Brazil)

We evaluated diversity and distribution of fish species in two habitats: flooded forest and open water of lakes of Rio Negro. Each of four lakes within the Anavilhanas Archipelago was sampled three times from 2009-2010. Species diversity generally was higher in flooded forests and at night, according to correspondence analysis. Predators were most active at night, but showed no preference between the flooded forest and open water habitats. Omnivores, filter feeders, and detritivores were most active during the day.