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This thesis combines five published research papers investigating methods of improving the safety and control of oral anticoagulation, with the use of computer assisted dosage and the standardisation of the International Normalised Ratio (INR). The INR is a conventional measurement derived from the time it takes blood of a patient to form a clot and is used to monitor the effects of widely used oral anticoagulants such as warfarin for the prevention of stroke and other related disorders. The first paper investigates whether the use of computer-assisted programs was as safe and effective as medical staff manual dosage in the prevention of bleeding or thrombotic complications during oral anticoagulant treatment. This was an international multi-centre randomised study conducted by the European Action on Anticoagulation (EAA) investigating the clinical benefit of two computer programs, PARMA 5 (Italy) and DAWN AC (UK). Composite clinical events were reduced by 7.6% using computer programs, though not achieving statistical significance (p=0.1), showing computer programs to be not dissimilar to medical staff dosage. The second paper recommends guidelines for screening safety and effectiveness of other marketed computer programs based on the results of the EAA study. A process for a candidate computer program to achieve non-inferiority relative to the medical staff dosage arm from the EAA study is explained. The third paper introduces a modified approach to the 'Direct INR' method for the standardisation of INR termed the 'Prothrombin Time/INR Line' (PT/INR). This was directly compared to the local International Sensitivity Index (ISI) calibration procedure originally approved by the World Health Organisation and later by the United States Food and Drug Administration (FDA). Using manually certified lyophilised plasmas tested by specialist centres, the PT/INR Line using a set of 5 calibrant plasmas to establish a fitted line to estimate local INR was shown to be as effective as the FDA procedure. The fourth paper investigates the PT/INR Line further by using simulated sets of calibrant plasmas across the therapeutic range of 2.0-4.5 INR and determining the PT/INR Line. Local INR of five validation plasmas, certified by 3 centres using the manual PT technique, was determined using the estimated PT/INR Lines and compared with local ISI calibration. Using 4 or 5 calibrant plasmas to determine the PT/INR Line was shown to be as accurate as local ISI calibrations for reliable local INR.The fifth and final paper assessed INR variability and control in oral anticoagulant therapy using a method termed the Variance Growth Rate (VGR), and compared its predictive ability of adverse events with the Time in Target INR range (TIR), the conventional method used in evaluating the quality of oral anticoagulant therapy. The VGR method was shown to be a better predictor of adverse bleeding or thrombotic episodes in the short term period prior to an event (3 and 6 months) compared with TIR.

Advanced-stage nasopharyngeal carcinoma (NPC) presents very difficult scenarios for radiation therapy (RT) planning. The infiltration of tumor to the skull base and beyond means that the tumor is very close to critical normal organs (organs at risk, OARs). Despite the advent of intensity-modulated radiotherapy (IMRT) treatment technique---the state-of-art RT technique, conflicting requirements between organ protection and target dose conformity is still problematic. The objectives of the present research are (1) to investigate the dosimetry properties of IMRT treatment in advanced-stage NPC in respect of its dosimetric limitations and planning problems, (2) to develop new methods and tools to resolve such problems, in particular to improve the quality of treatment plans and efficiency of the dose planning and optimization process. A series of four inter-linked studies were conducted to address these issues. / In conclusion, the solutions to several major problems in IMRT planning for advanced-stage NPC were investigated and established. It has been demonstrated in this research that, by applying these methods and tools, significant improvement in the dosimetry and efficiency of IMRT treatment planning can be accomplished as compared with conventional IMRT planning techniques. It is expected that such would translate into an improvement in treatment throughput, better tumor control and reduction in normal tissues complications. The methods developed have potential to be applied to all stages of NPC and to other tumor sites. / The first study was to improve the efficacy in target coverage and organs sparing using an "organ-splitting" approach. The OARs which overlapped with targets were split into target-overlapping and non-overlapping segments and each segment was assigned with different constraints parameters to increase the degree of flexibility during optimization. As a result, a steep gradient in the dose distribution at the regions of interface between the targets and normal critical organs could be achieved and treatment quality was improved. In the second study, a thorough dosimetric comparison between conventional 2-dimensional (2D) RT and IMRT plans was conducted to determine, with reference to outcome of 2D treatments, the extended tolerance dose limits for the critical organs, especially that of the brainstem and spinal cord, and their planning organ at risk volume. Such data could then serve as reference in IMRT planning when the dose of critical organs need be exceeded in order to allow adequate dose to a very close by target. In the third study, the feasibility of using interpolated contours for segmentation of targets and OARs in IMRT planning was investigated. The result indicated that the use of interpolated contours in IMRT planning could significantly reduce the contouring time by about 50% without degrading the target coverage and OARS sparing. In the final study, an array of dose constraint templates that could accommodate different degrees of overlap between the targets and OARs, together with a template selection program, were developed to improve the efficiency of IMRT planning. By applying the methods and tools developed, IMRT treatment planning of advanced NPC could become more efficient and less dependent on planner's experience. / Chau, Ming Chun. / Adviser: Anthony Chan Tak Cheung. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0948. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 118-128). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

O principal objetivo desta pesquisa foi o acompanhamento clínico-laboratorial do ciclo reprodutivo de jabuti-piranga (Geochelone carbonaria, SPIX, 1824) e jabuti-tinga (Geochelone denticulata, Lineu, 1766) servindo-se de métodos minimamente invasivos como imagens radiográficas, ultrassonográficas e alterações hormonais séricas em fêmeas hígidas em idade reprodutiva. Para tanto, ao longo de 13 meses seguidos, foram utilizadas 7 fêmeas de G. carbonaria e 5 fêmeas de G. denticulata mantidas em recinto comum, hígidas e em idade reprodutiva. As variações médias de umidade do ar, índices pluviométricos, temperatura e fotoperíodo foram acompanhados semanalmente. Todos os animais foram avaliados uma vez ao mês. As imagens radiográficas dorso-ventrais foram feitas com os animais em estação na Fundação Parque Zoológico de São Paulo em aparelho fixo e submetidos a exposições de 300 mA por 1/60 segundo. Cada fêmea radiografada teve seus ovos mensurados com o auxílio de um paquímetro. No acompanhamento ultrassonográfico utilizou-se aparelho com microtransdutor convexo de freqüência dupla 4 e 7,5 mHz, enfatizando-se as estruturas ovarianas (folículos em desenvolvimento e desenvolvidos) e a presença ou não de ovos com casca no oviduto. Esta avaliação foi feita através das janelas acústicas craniais e inguinais por período um pouco maior que 10 minutos. As estruturas ovarianas foram mensuradas seguindo uma escala interna ao aparelho durante o exame e as imagens foram gravadas digitalmente para posterior recuperação. Realizou-se o acompanhamento do ciclo reprodutivo através de colheitas seriadas de sangue para a dosagem de estrógeno, progesterona, testosterona e corticosterona. Para as colheitas de sangue os animais foram fisicamente contidos, permanecendo sustentados por suporte metálico. Estas foram feitas prioritariamente através de punção da veia jugular. As amostras foram dosadas no Laboratório de Dosagens Hormonais do Departamento de Reprodução Animal da Faculdade de Medicina Veterinária da USP, por meio de kits comerciais de radioimunoensaio (RIA) em fase sólida. Onde foi possível se verificar alterações entre as duas espécies no que diz respeito ao ciclo anual. Foi possível verificar um pico de progesterona dois meses antes do pico de folículos em desenvolvimento na G. carbonaria enquanto que na G. denticulata, houve início de desenvolvimento folicular dois meses após uma marcada elevação dos níveis séricos de progesterona, porém o pico de progesterona só se verificou no início do verão. Os níveis séricos de testosterona e corticosterona observados em fêmeas de ambas as espécies não mostraram variações significativas ao longo do ano. Pela ultrassonografia foi possível verificar a vitelogênese nas fêmeas estudadas. A G. carbonaria apresentou pico de estradiol no início do verão enquanto a G. denticulata no final deste, coincidindo coma maior freqüência de observação de folículos desenvolvidos pelo exame ultrassonográfico. As fêmeas de G. carbonaria se mostraram mais eficientes na produção de ovos que as G. denticulata. Ambas as espécies realizaram uma postura anual. / The main objective of this study was to evaluate the reproductive cycle of red-foot (Geochelone carbonaria, SPIX, 1824) and yellow-foot tortoises (Geochelone denticulata, Lineu, 1766) using minimally invasive clinical and laboratory methods, such as radiographic and ultrasound images and hormone dosages. Seven G. carbonaria and 5 G. denticulata healthy females at reproductive age were kept together for 13 consecutive months. Mean variations in air humidity, pluviometric indexes, temperature and photoperiod were recorded weekly. All animals were evaluated once a month. Dorsoventral radiographic images of the animals in a standing position were obtained at the Fundação Parque Zoológico de São Paulo, by means of a fixed x-ray device, using 300 mA for 1/60 second. Eggs of each female that was analyzed by x-ray were measured using a caliper. Ultrasound examination was carried out using a convex micro transducer at two frequencies, 4 and 7.5 mHz. Ovarian structures (developing and developed follicles) were analyzed, as well as the presence or absence of shelled eggs inside the oviduct, using the cranial and inguinal acoustic windows for a little longer than 10 minutes. Ovarian structures were measured during the examination according to an internal scale of the device, and images were digitally recorded to be recovered later. Reproductive cycle was analyzed by means of serial blood collections for estrogen, progesterone, testosterone, and corticosterone dosage. Animals were physically restrained and blood samples were collected, which was preferentially performed by means of a puncture in the jugular vein. Samples were analyzed in the Laboratório de Dosagens Hormonais at the Departamento de Reprodução Animal, Faculdade de Medicina Veterinária at USP, using commercial solid phase radioimmunoassay kits (RIA) in order to assess differences in the annual cycle of the two species. A progesterone peak was observed two months before the peak of developing follicles in G. carbonaria, whereas G. denticulata showed follicular development two months after a marked increase in progesterone serum levels. However, progesterone peak was only observed in the beginning of the summer while in G. denticulata it was observed at the end. Testosterone and corticosterone serum levels observed in females of both species did not show significant variations throughout the year. Ultrasound examination showed vitellogenesis in females studied. An estradiol peak was observed in G. carbonaria in the beginning of the summer, and in G. denticulata in the end of this season, coinciding with a greater rate of developed follicles in ultrasound images. G. carbonaria females were more efficient in egg production than G. denticulata. Both species laid eggs once during the year.

O objetivo do presente estudo foi avaliar os perfis de metabólitos de glicocorticóides fecais através de radioimunoensaio em cachorros-vinagre (Speothos venaticus) mantidos em cativeiro e suas possíveis implicações na função reprodutiva. Duas fêmeas e quatro machos adultos, após período de condicionamento, foram marcados e tiveram suas fezes recolhidas durante 45 dias. Estes animais recebiam diariamente marcadores (corantes e miçangas) para a devida identificação das amostras fecais. O desafio com ACTH foi realizado em uma das fêmeas e mostrou o perfil reativo esperado, validando a técnica do ponto de vista fisiológico. As concentrações de metabólitos de glicocorticóides fecais para o grupo em geral variaram de 2,32 a 65,09 μ/g de fezes secas, com média e desvio-padrão de 18,11±11,33 μ/g de fezes secas, respectivamente. Quatro animais apresentaram um pico cada um, porém aparentemente, sem relação com qualquer evento estressante em particular. Não se verificou diferença significativa nos perfis de glicocorticóides fecais entre machos e fêmeas, nem entre a fêmea dominante e os outros indivíduos. Tais resultados sugerem que os animais estão bem adaptados à condição do cativeiro e provavelmente isentos ou minimamente afetados pelo estresse. A dosagem dos glicocorticóides fecais é uma ferramenta útil no monitoramento não-invasivo para avaliar a condição de estresse do cachorrovinagre, demonstrando se aspectos de manejo e fatores ambientais interferem de modo importante ou não no bem-estar animal e no potencial reprodutivo, sendo de interesse para a manutenção e conservação da espécie. / The aim of this study was to evaluate the fecal glucocorticoid metabolite profiles by radioimmunoassay in captive bush dog (Speothos venaticus) and its possible role in the reproductive function. Six adult animals (two females and four males), after training, were marked and their fecal samples were collected during 45 days. Every day the animals received markers (dye and colored plastic beads) for the appropriate identification of each sample. One female was used to the ACTH challenge and showed the expected classical response, with a significant peak one day after stimulation, therefore confirming the physiological validation. The overall fecal glucocorticoid metabolite concentrations for the whole group, ranged from 2,32 to 65,09 μ/g of dried feces, with an average and standard deviation of 18,11±11,33 μ/g of dried feces, respectively. Four animals revealed one individual peak during the observation period, however they could not be correlated with any stressful event. The fecal glucocorticoid metabolite concentrations did not show significant differences between males and females neither between the dominant female and the other animals in the study. The results suggest that the animals are well adapted to the captive conditions and likely without or minimally affected by stress. The fecal glucocorticoid metabolite dosage is a useful non-invasive tool to evaluate the bush dog stress situation and to monitor local management and environmental factors that could possibly influence the well being and reproductive success, considered both key factors for the specie maintenance and conservation.

O presente trabalho foi desenvolvido com o objetivo de avaliar as condições de pastagens em degradação e a influência do nitrogênio e do enxofre na recuperação de Brachiaria decumbens Stapf. em estado de degradação. O estudo foi realizado em duas etapas. A primeira consistiu no levantamento das condições nutricionais da forrageira em duas áreas contíguas, sendo uma não recentemente adubada e outra recentemente adubada. Foram coletadas folhas diagnósticas e raízes, bem como foram realizadas avaliações do teor de clorofila. Amostras de solo nas camadas de 0 a 10 cm e 10 a 20 cm também foram coletadas para a avaliação de fertilidade do solo. O solo amostrado na área recentemente adubada apresentou teores mais elevados de matéria orgânica, B, Cu, Fe e Zn em ambas camadas, que aquele da área não recentemente adubada. O capim na pastagem da área recentemente adubada apresentou concentrações mais elevadas de N, Cu, Fe e Zn que o capim da área não recentemente adubada. A segunda etapa, constituída de dois experimentos, foi conduzida em casa-de-vegetação com a utilização de 96 cilindros de solo contendo capim-braquiária, coletados nas áreas em estudo e colocados em vasos plásticos. Empregou-se um esquema fatorial 4 x 3 (doses de nitrogênio e de enxofre) perfazendo 12 combinações, as quais foram distribuídas segundo o delineamento experimental de blocos completos ao acaso, com quatro repetições, para cada experimento. Foram utilizadas quatro doses de nitrogênio (0; 50; 100 e 200 mg dm-3) em combinação com três doses de enxofre (0; 30 e 60 mg dm-3), com objetivo de avaliar os efeitos na produção de matéria seca da parte aérea, no perfilhamento, no teor de clorofila, na área foliar e na composição mineral da folha diagnóstica dessa forrageira. O primeiro corte das plantas ocorreu 40 dias após o corte de nivelamento, o segundo corte aos 40 dias após o primeiro corte e o terceiro corte aos 40 dias após o segundo corte. Os resultados evidenciaram que a interação entre nitrogênio e enxofre foi significativa (P<0,01) na produção de matéria seca da parte aérea da Brachiaria decumbens, no primeiro e no segundo crescimentos. Para o terceiro crescimento houve significância (P<0,01) para as doses de nitrogênio para a forrageira procedente da área não recentemente adubada. Na produção de matéria seca da área recentemente adubada houve significância (P<0,01) para as doses de nitrogênio e de enxofre no primeiro e no terceiro crescimentos. No segundo crescimento houve efeito significativo (P<0,01) para doses de nitrogênio. No perfilhamento da forrageira houve significância (P<0,01) para as doses de nitrogênio, nos crescimentos avaliados da forrageira, nos dois experimentos. As doses de nitrogênio tiveram significância (P<0,01) na concentração de nitrogênio na folha diagnóstica dessa forrageira no primeiro crescimento, para ambos os experimentos. A interação entre doses de nitrogênio e de enxofre foi significativa (P<0,01) para a concentração de nitrogênio na folha diagnóstica no segundo crescimento, nos dois experimentos e para a concentração de enxofre no terceiro crescimento, no experimento da área recentemente adubada. Para a produtividade da Brachiaria decumbens na pastagem estudada sugere-se a aplicação conjunta de nitrogênio e enxofre. / The present work was conducted with the objective of evaluating pastures under degradation and the influences of nitrogen and sulfur supply for Brachiaria decumbens recovery. The study was accomplished in two stages. In the first one it was evaluated the nutritional conditions of this grass in two areas, one not recently fertilized and another recently fertilized. Diagnostic leaf laminae and roots were collected and chlorophyll concentration was determined. Soil samples, at 0 to 10 cm and 10 to 20 cm depth, were also collected for soil fertility evaluation. The soil sampled in the recently fertilized area showed higher concentrations of organic matter, B, Cu, Fe and Zn in both soil depth, than in the not recently fertilized area. The grass in the pasture of the recently fertilized area showed higher concentrations of N, Cu, Fe and Zn than in the not recently fertilized area. The second stage of this research was carried out in two experiments in a greenhouse for which 96 soil cores containing signal grass were collected in the studied pastures and put in plastic pots. A 4 x 3 factorial (nitrogen rates and sulfur rates) in a randomized complete block design, with four replications, was used in each experiment. Nitrogen rates were 0; 50; 100 and 200 mg dm-3 whereas sulfur rates were 0; 30 and 60 mg dm-3. Plant tops dry matter yield, plant tillering, chlorophyll concentration, leaf area and plant tissue mineral composition were evaluated. Plants were harvested three times at: 40 days after the leveling cut, 40 days after the first harvest and 40 days after the second harvest. The results showed that the nitrogen x sulfur interaction was significant (P<0.01) for the plant tops forage yield in the first and second harvests of both experiments. For the third harvest, nitrogen application had significant (P<0.01) effect on forage yield in the grass coming from the area not fertilized in the field. Dry matter yield by the grass collected in the fertilized area was significantly (P<0.01) affected by the nitrogen and sulfur rates in the first and third harvests. In the second harvest nitrogen rates had significant (P<0.01) effects on forage yield. For the tiller number nitrogen rates were significant (P<0.01), in the two experiments. Nitrogen rates significantly (P<0.01) influenced nitrogen concentration in the diagnostic leaf laminae from the first harvest, in both experiments. Nitrogen x sulfur interaction was significant (P<0.01) for the nitrogen concentration in diagnostic leaf laminae in the second harvest in the two experiments, and for the sulfur concentration in diagnostic leaf laminae in the experiment with the grass originated in the not recently fertilized area. The joint application of nitrogen and sulfur is suggested for the productivity of Brachiaria decumbens in the studied pastures.

This research demonstrates that a 3D printed bolus can be customized for electron radiation therapy. Both extruder and powder based printers were used, along with, paraffin wax, super stuff, and H20. The plan dose coverage and conformity for the planning target volume (PTV), was such that the distal side of the PTV was covered by the 90% isodose line. The structure is read, and converted into an STL file. The file is sent to a slicer to print. The object was filled with parafin wax, superstuff or water and sealed. Materials Hounsfield units were analyzed, along with the structure stability. This method is evaluated by scanning the 3D printed bolus. The dose conformity is improved compared to that with no bolus. By generating a patient specific 3D printed bolus there is an in improvement in conformity of the prescription isodose surface while sparing immediately adjacent normal tissues. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

The purpose of this study is to verify and validate the dose at various points of interest in accelerated partial breast irradiation (APBI) treated with the Strut Adjusted Volume Implant (SAVI) applicator using Thermoluminescent Dosimeters (TLDs). A set of CT images were selected from a patient’s data who had received APBI using the SAVI applicator. The images were used to make 3D models. TLDs were calibrated for Brachytherapy. Various points of interest were marked out and slots were carved in the 3D models to fit the TLDs. CT scans were taken of the 3D models with expanded SAVI applicator inserted. A plan was made following B-39 protocol. The TLDs were read and the absorbed doses were calculated and compared to the delivered doses. The results of this study show that the overall average reading of the TLDs is within expected value. The TPS shows overestimated dose calculations for brachytherapy. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

Medication related errors are a significant cause of morbidity and mortality. In Brazil, most errors are related to prescribing, preparing, and administering medications. One way to deal with this barrier to safe care is through assessment and education of medication calculation dosage skills. Considering the Brazilian reality, this dissertation is a context and language adaptation of an evidence-based intervention called safeMedicate, a program that reinforces learning synthesis in crucial elements of medication dosage problem solving and provides the foundation for development in remaining levels of the hierarchy of learning. A guideline for medication calculation skills development or improvement based on the seven research-based principles for smart teaching was developed. Teaching approaches are beneficial for multiple methods of learning by addressing cognitive, motivational, and developmental goals. Web-based software would be a strong ally on adopting those approaches by complementing the class practice and providing opportunities for practice learning. The two-phases of adaptation and preliminary evaluation of safeMedicate for use in Brazil were guided by the Participatory and Iterative Process Framework for Language Adaptation (PIPFLA) cross-cultural equivalence model. A triangulation method of face validity survey, journaling, and multiple focus groups was used. The focus groups were (1) language adaptation team, (2) panel of experts, and (3) student panel. In order to analyze focus group data, a systematic coding procedure was performed through an iterative process, solving any differences between coders in order to guarantee internal consistency. The main themes were language, visual, content, programing, and data while discussing necessary adaptations of safeMedicate for use in Brazil.

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