Wong Wai Lun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 119-125). / Abstract also in Chinese. / Acknowledgments --- p.i / Legend for Figures --- p.ii / Legend for Tables --- p.iv / Abstract --- p.v / Abstract in Chinese --- p.ix / Chapter Chapter I --- Introduction --- p.1 / Objective --- p.5 / Chapter Chapter II --- Literature Review / Chapter II.1. --- Anatomy of the urinary system --- p.6 / Chapter II.2. --- Physiology of the urinary system --- p.10 / Chapter II.3. --- Methods for investigating the urinary system --- p.12 / Chapter II.3.1. --- Plain film radiography --- p.12 / Chapter II.3.2. --- Excretory Urogram --- p.12 / Chapter II.3.3. --- Ultrasound --- p.13 / Chapter II.3.4. --- Computed Tomography --- p.15 / Chapter II.3.5. --- Renal Angiography --- p.16 / Chapter II.3.6. --- Magnetic Resonance Imaging (MRI) --- p.16 / Chapter II.3.7. --- Radionuclide Imaging --- p.17 / Chapter II.4. --- Radiopharmaceuticals for renal parenchyma imaging --- p.17 / Chapter II.4.1. --- Tc-99m GHA --- p.18 / Chapter II.4.1.1. --- Chemistry of Tc-99m GHA --- p.18 / Chapter II.4.1.2. --- Preparation --- p.18 / Chapter II.4.1.3. --- Doses --- p.18 / Chapter II.4.1.4. --- Biological behavior --- p.19 / Chapter II.4.2. --- Tc-99m DMSA / Chapter II.4.2.1. --- Chemistry of Technetium-99m Dimercaptosuccinic Acid (Tc-99m DMSA) --- p.20 / Chapter II.4.2.2. --- Chemical property of Tc-99m DMSA --- p.21 / Chapter II.4.2.3. --- Preparation --- p.22 / Chapter II.4.2.4. --- Radiochemical purity measurement --- p.22 / Chapter II.4.2.5. --- Doses --- p.23 / Chapter II.4.2.6. --- Pharmacokinetic of Tc-99m DMSA --- p.23 / Chapter II.4.2.7. --- Renal handling of injected Tc-99m DMSA --- p.25 / Chapter II.5. --- General consideration for quantitative uptake measurement in organs --- p.26 / Chapter II.5.1. --- Clinical significance of renal Tc-99m DMSA uptake --- p.28 / Chapter II.5.2. --- Special consideration and problems for quantitative renal Tc-99m uptake measurement --- p.29 / Chapter II.5.3. --- Suggestions and solutions for quantitative renal Tc-99m uptake measurement --- p.29 / Chapter II.5.3.1. --- Planar images Vs SPECT images for quantification --- p.29 / Chapter II.5.3.2. --- Background subtraction --- p.31 / Chapter II.5.3.3. --- Choice of location for background ROI --- p.32 / Chapter II.5.3.4. --- Attenuation --- p.35 / Chapter II.5.3.5. --- Principle of the conjugate view method --- p.36 / Chapter II.5.3.6. --- Body thickness and kidney depth measurement --- p.37 / Chapter II.6. --- Glomerular Filtration / Chapter II.6.1. --- Introduction --- p.39 / Chapter II.6.2. --- Gold standard for GFR measurement --- p.40 / Chapter II.6.3. --- Laboratory studies for the measurement of glomerular filtration : Serum Creatinine and Blood Urea Nitrogen (BUN) levels --- p.41 / Chapter II.6.3.1. --- Calculation of Creatinine Clearance Rate --- p.43 / Chapter II.6.3.2. --- Critique for using creatinine clearance as a measurement of renal function --- p.44 / Chapter II.6.3.3. --- Limitation of the serum creatinine concentration used alone as a measurement of renal function --- p.46 / Chapter II.6.4. --- Radionuclide technique for the assessment of the glomerular function --- p.48 / Chapter II.6.4.1. --- Diethylene Triamine Penta Acetic acid (DTPA) --- p.49 / Chapter II.6.4.2. --- Methods / Chapter II.6.4.2.1. --- Measurement of Glomerular Filtration Rate using Tc-99m DTPA with single injection techniques --- p.51 / Chapter II.6.4.2.2. --- Compartment model --- p.52 / Chapter II.6.4.2.2a. --- Two-compartment model --- p.52 / Chapter II.6.4.2.2b. --- Single-compartment model --- p.54 / Chapter II.6.4.2.3. --- Single blood sample technique: a modification of Tauxe's OIH method in which counts in a single plasma sample correlated with a GFR nomogram --- p.56 / Chapter II.6.4.2.4. --- Gamma camera based method --- p.58 / Chapter II.6.4.2.4a. --- Gates-modification of Schlegel's OIH technique --- p.58 / Chapter II.6.4.2.4b. --- Critique for the Gamma camera technique for measuring GFR --- p.62 / Chapter II.7. --- The relationship between the Tc-99m DMSA uptake and GFR --- p.67 / Chapter Chapter III --- Material and Methods --- p.69 / Chapter III.1. --- Subjects and Sampling Methods --- p.69 / Chapter III.2. --- Quantitation of Absolute DMSA uptake --- p.70 / Chapter III.2.1. --- Parameters for Tc-99m DMSA uptake study --- p.70 / Chapter III.2.1.1. --- Materials and methods --- p.70 / Chapter III.2.1.1.1. --- Instrumentation --- p.70 / Chapter III.2.1.1.2. --- Dosage --- p.70 / Chapter III.2.1.1.3. --- Optimum acquisition start time --- p.70 / Chapter III.2.1.1.4. --- Length of acquisition time --- p.71 / Chapter III.2.1.1.5. --- Acquisition parameter --- p.71 / Chapter III.3. --- Calculation of absolute renal DMSA uptake --- p.72 / Chapter III.3.1. --- Attenuation Coefficient factor(μ) --- p.73 / Chapter III.3.2. --- Table attenuation --- p.75 / Chapter III.3.3. --- Body thickness measurement --- p.77 / Chapter III.3.4. --- Decay correction --- p.78 / Chapter III.3.5. --- Calculation of DMSA uptake --- p.78 / Chapter III.3.6. --- Counting dose injected --- p.80 / Chapter III.3.7. --- Calculation of absolute quantitation of Tc-99m DMSA uptake --- p.80 / Chapter III.3.8. --- Dose infiltration --- p.81 / Chapter III.4. --- GFR measurement --- p.82 / Chapter III.4.1. --- Instrumentation --- p.82 / Chapter III.4.2. --- Methods --- p.82 / Chapter III.5. --- Statistical and analytical methods --- p.84 / Chapter Chapter IV --- Results --- p.87 / Chapter IV. 1. --- Characteristics of experimental subjects and their serum creatinine profile --- p.88 / Chapter IV.2. --- Absolute Tc-99m DMSA uptake / Chapter IV.2.1. --- The change of absolute Tc-99m uptake with time --- p.89 / Chapter IV.2.2. --- Absolute Tc-99m DMSA uptake measurement at 6 and 24 hours --- p.90 / Chapter IV.2.3. --- Gender difference in absolute Tc-99m uptake measurement at 6 hour --- p.92 / Chapter IV.3. --- GFR measurement --- p.93 / Chapter IV.3.1. --- GFR measurement by single (3hr) and double (1&3 hrs) plasma sampling --- p.93 / Chapter IV.3.2. --- Gender difference in GFR measurement using single plasma sampling --- p.96 / Chapter IV.4. --- Univariate Correlation --- p.97 / Chapter IV.4.1. --- Correlation between GFR using single plasma sampling and absolute Tc-99m uptake --- p.97 / Chapter IV.4.2. --- Correlation between GFR using single plasma sampling and plasma creatinine levels --- p.98 / Chapter IV.4.3. --- Correlation between anthropometric variables on GFR(3 hr) --- p.99 / Chapter IV.4.4. --- Correlation between anthropometric variables and serum creatinine plasma level on absolute Tc-99m DMSA uptake measurement at 6 hour --- p.101 / Chapter IV.4.5. --- Multiple linear stepwise regression --- p.103 / Chapter Chapter V. --- Discussion / Chapter V. 1 --- . Review of the study --- p.104 / Chapter V.1.1. --- Experimental subjects and their absolute Tc-99m DMSA uptake (%) at 6 hr --- p.104 / Chapter V.1.2. --- Experimental subjects and their GFR(3 hr) --- p.105 / Chapter V.2. --- Discussion on subject --- p.105 / Chapter V.2.1. --- Subject preparation --- p.106 / Chapter V.3. --- Discussion of method --- p.106 / Chapter V.3.1. --- Equipment --- p.106 / Chapter (a) --- Dose calibrator --- p.106 / Chapter (b) --- The sensitivity of the head 1 and 2 of the gamma camera --- p.106 / Chapter (c) --- Validation of quantification of injected activity by gamma camera method--------constancy of performance for gamma camera --- p.110 / Chapter (d) --- LEHR Collimator --- p.112 / Chapter (f) --- Dead time loss --- p.112 / Chapter V.4. --- Discussion on measurement --- p.113 / Chapter (a) --- Length of acquisition time --- p.113 / Chapter (b) --- Attenuation Coefficient factor (\x) --- p.113 / Chapter (c) --- "Body thickness, L, measurement" --- p.113 / Chapter (d) --- Optimum acquisition time for data collection --- p.115 / Chapter v.5. --- Discussion on overall error estimation --- p.115 / Chapter (a) --- Tc-99m DMSA uptake measurement at 6 hr --- p.115 / Chapter (b) --- GFR measurement by single (3 hr) sample --- p.116 / Chapter Chapter VI --- Conclusion --- p.117 / Reference --- p.119 / Appendix I --- p.126 / Appendix II --- p.128 / Appendix III --- p.134

The nuclear waste inventory of the UK comprises large quantities of intermediate level wastes (ILW), which will be immobilised by encapsulation within a cementitious grout in stainless steel containers, followed by disposal in a deep engineered geological disposal facility (GDF) within a suitable geological formation. These wastes contain, in addition to radioactive elements, a heterogeneous mix of organic materials, including plastics, cellulose and rubber. Cellulosic items, such as cloth, tissue, filters, paper and wood, are considered particularly problematic, because they are known to be susceptible to degradation under alkaline conditions, forming small chain organic acids with the ability to complex metals and radionuclides. It is predicted that under alkaline conditions isosaccharinic acid (ISA) will form particularly strong complexes with Ni(II), Am(III), Eu(III), Np(IV), Th(IV), and U(IV). As a result, the presence of ISA could affect the migration behaviour of these elements, by increasing their solubility and reducing sorption, thus enhancing their mobility into the near and far field surrounding a GDF. During site operation and then after closure of a GDF, microbial communities have the potential to colonise the steep biogeochemical gradients, running from highly alkaline in the GDF “near field” to circumneutral pH conditions in the surrounding geosphere. Within these steep pH gradients microbial processes can control the fate of organic compounds, such as ISA, and have therefore been considered as an effective self-attenuating mechanism to remove ISA from the groundwater. This thesis aims to deliver a greater understanding of the microbial processes that can potentially use ISA as a carbon source and electron donor, removing it from solution, and thus having a positive impact on radionuclide mobility under GDF-relevant conditions. A microbial enrichment approach was chosen that approaches GDF-relevant conditions to explore the biodegradation of ISA. Cross-disciplinary analyses of water chemistry (pH, Eh, photospectroscopy, IC, ICP), mineralogy (ESEM, XRD, TEM, XAS) and microbiology (light microscopy, next generation sequencing) have demonstrated the ability of bacteria to degrade ISA over a wide range of biogeochemical conditions. Furthermore, key radionuclides (and their non-active analogues), including Ni(II) and U(VI), were precipitated from the groundwater system during ISA biodegradation. Moreover, in the case of uranium, microbial metabolism led to the reduction of U(VI) to U(IV), which is also less soluble. This study highlights the potential for microbial activity to help remove chelating agents from groundwaters surrounding an ILW GDF, and suggests that safety cases that do not include microbial processes may be overly conservative, over-estimating the impact of ISA on radionuclide transport.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2018-01-17T11:04:30Z No. of bitstreams: 1 kleberrobertosantanna_dissert.pdf: 2567533 bytes, checksum: eae324ad76ed0dfd667eaf47bad5c5ea (MD5) / Made available in DSpace on 2018-01-17T11:04:30Z (GMT). No. of bitstreams: 1 kleberrobertosantanna_dissert.pdf: 2567533 bytes, checksum: eae324ad76ed0dfd667eaf47bad5c5ea (MD5) Previous issue date: 2017-03-08 / Introduction: Lymphedema is a clinical condition in which there is an accumulation of macromolecules in the interstitial space. As a result, it promotes water retention, consequently a failure in the formation or lymph drainage. Objectives: To access the images obtained from Computed Scintigraphy Chamber through a specific protocol of Lymphoscintigraphy and associate them to epidemiological data such as gender, age, educational level, socioeconomic status and prevalence of Lymphedema. Method: Epidemiological data were evaluated in a quantitative cross-sectional study comparing the diagnostic results for Lymphedema of the lower limbs using the Lymphoscintigraphy. They were correlated with gender, age, education level, family income and prevalence among the lower limbs at Hospital de Base in the last 10 years, 2006 to 2016. All patients clinically suspected of Lymphedema of the lower limbs were included and lymphoscintigraphic examinations of the upper limbs were excluded. Descriptive data were considered, and Fisher's exact test was used to correlate these variables considering alpha error of 5%. Results: A total of 430 patients were analyzed, 320(74.42%) were female and 110 (25.58%) male patients. Their age ranged from 10 to 90 years (mean = 48 years). A total 199 (46.27%) were positive findings and 231 (53.73%) negative. Among the images analyzed as positive; female patients were the majority, 183 (91.95%); Fisher's exact test p-value <0.001. When comparing patients with the first grade of high school with patients with complete college education, it was clear that Lymphedema was more prevalent in the first grade of high school, according to Fisher's exact test, p<0.0001. Comparing the second grade of high school with the ones with college education, it was observed that Lymphedema was more prevalent in those with high school; Fisher's exact test, p<0.0001. When comparing the wage gain from one to three minimum wages per month with three to five gains, five to seven and over seven salaries, a higher prevalence of Lymphedema was observed in the group of one to three salaries in relation to the others by Fisher's exact test, p<0.0001 in all evaluations. Comparing the salary range of three to five salaries with the salary range of five to seven and over seven monthly minimum wages, greater prevalence was observed in the range of three to five minimum wages; Fisher's exact test, p<0, 0.001 in both comparisons. The right lower limb presented 65 patients (32.66%), and 87(43.71%) unilateral left limb and 7 patients (23.63%), bilaterally were found. The left side was more prevalent than the right side; Fisher's exact test, p<0.01. Conclusions: Lymphedema is a public health issue that affects mostly women from lower cultural-educational socioeconomic status. One-sided onset can occur in the limb, but bilateral occurrence is frequent and Lymphoscintigraphy is useful in defining the diagnosis in cases of doubt. / Introdução: O Linfedema é uma condição clínica na qual ocorre um acúmulo de macromoléculas no espaço intersticial. Como consequência, promove retenção hídrica tendo como causa uma falha na formação ou na drenagem da linfa. Objetivos: Avaliar as imagens obtidas em Câmara de Cintilação Computadorizada por meio do protocolo de Linfocintilografia específico e relacioná-las com dados epidemiológicos como sexo, idade, grau de escolaridade, nível socioeconômico e prevalência de Linfedema. Método: Foram avaliados em estudo transversal quantitativo, dados epidemiológicos comparando-se os resultados diagnósticos para Linfedema de membros inferiores, utilizando a Linfocintilografia. Foram correlacionados com o sexo, idade, grau de escolaridade, renda familiar e predominância entre os membros inferiores no Hospital de Base nos últimos 10 anos, 2006 a 2016. Foram inclusos todos os pacientes com suspeita clínica de Linfedema de membros inferiores e excluídos os exames Linfocintilográficos de membros superiores. Foram considerados dados descritivos e utilizado o teste exato de Fisher para correlacionar essas variáveis, considerando-se erro alfa de 5%. Resultados: Foram analisados 430 pacientes sendo que 320(74,42%) eram pacientes do sexo feminino e 110(25,58%) pacientes do sexo masculino. A idade dos pacientes variava de 10 a 90 anos (média=48 anos). Os achados positivos somavam 199(46,27%) e negativos 231(53,73%); dentre as imagens analisadas como positivas, predominavam pacientes do sexo feminino; 183(91,95%); no teste exato de Fisher valor p<0,001. Quando se comparou o primeiro grau de escolaridade do ensino médio com o segundo grau do ensino médio, ficou evidenciado que o Linfedema é mais prevalente no primeiro grau do ensino médio, de acordo com o teste exato de Fisher, valor p<0,0001. Comparando-se o primeiro grau do ensino médio com os pacientes que possuíam grau do ensino superior, detectou-se que a prevalência do Linfedema é maior no primeiro ano do ensino médio de escolaridade; teste exato de Fisher, valor p<0,0001. Comparando-se segundo grau do ensino médio de escolaridade com os do ensino superior, detectou-se que o Linfedema é mais prevalente no segundo grau do ensino médio; teste exato de Fisher, valor p<0,0001.Quando se comparou o ganho salarial de um a três salários mínimos por mês com ganhos de três a cinco, cinco a sete e acima de sete salários detectou-se uma maior prevalência do Linfedema no grupo de um a três salários em relação aos demais com teste exato de Fisher, valor p<0,0001 em todas as avaliações. Comparando-se a faixa salarial de três a cinco salários com a faixa salarial de cinco a sete e maior que sete salários mínimos mensais detectou-se maior prevalência na faixa de três a cinco salários mínimos, teste exato de Fisher, valor p<0,0001 nas duas comparações. O membro inferior direito apresentou 65 pacientes (32,66%), e 87(43,71%) achados unilaterais de membro inferior esquerdo e bilateralmente em 47 pacientes (23,63%). O lado esquerdo é mais prevalente que o lado direito; teste exato de Fisher, valor p<0,01. Conclusões: O Linfedema é um problema de saúde pública que acomete na sua maioria, as mulheres de classe socioeconômica cultural e educacional mais baixa. Ocorre uma unilateralização no acometimento do membro, porém a ocorrência bilateral é frequente e a Linfocintilografia é útil na definição do diagnóstico nos casos de dúvida.

O objetivo deste estudo foi avaliar o uso da cintilografia de perfusão miocárdica planar de repouso para o diagnóstico de insuficiência coronariana aguda em pacientes com dor torácica e eletrocardiograma sem alterações sugestivas de isquemia. Foram estudados 71 pacientes com idades entre 34 e 87 (média 58, desvio-padrão 12) anos; 44 (62%) eram do sexo masculino e 27 (38%) do feminino. Os pacientes com dor torácica foram avaliados na unidade de emergência com anamnese, exame físico e eletrocardroqrarna de 12 derivações. Pacientes com dor torácica de duração superior a 20 minutos, em vigência da dor ou sem dor, mas que sofreram dor torácica até seis horas anies do atendimento e com eletrocardioqrarna sem alterações sugestivas de isquemia miocárdica, foram submetidos à cintilografia planar de perfusão miocárdica de repouso quando solicitada pelo médico assistente. O tempo médio entre o início da dor toràcica e a Injeção do radiotraçador foi de três horas e seis minutos. Treze pacientes apresentavam dor torácica no momento da injeção. Foram colhidas amostras sanguineas para dosagens de atividade da creatinoquinase-MB (CK-MB), CK-MB massa, troponina I e mioglobina, seis horas após o início da dor torácica. O diagnóstico de insuficiência coronariana aguda foi feito em pacientes com angina de repouso, infarto agudo do miocárdio, pacientes submetidos à revascularização miocárdica, presença de lesões coronarianas significativas na angiografia (>- 70% estenose em artérias coronárias ou seus ramos ou .- 50% em tronco de artéria coronária esquerda) realizada durante a inernação e morte cardíaca foram considerados eventos cardíacos maiores. As cintilografias com defeito de captação foram consideradas sugestivas de isquemia miocárdica e foram comparadas com o diagnóstico clínico e com a ocorrência de eventos cardíacos maiores até três meses após a alta.Pacientes sem insuficiência coronariana aguda, dispensados da unidade de emergência, foram encaminhados para realização ambulatorial de cintilografia de perfusão miocárdica tomográfica de esforço ou com dipiridamol. Vinte e um pacientes (29,6%) tiveram o diagnóstico de insuficiência coronariana aguda e em 15 (21,1%) ocorreram eventos cardíacos maiores (oito com infarto agudo do miocárdio e sete foram submetidos à revascularização miocárdica). A cintilografia planar de perfusão miocárdica demonstrou defeitos de captação em 21 (29,6%) pacientes, dos quais 16 (76,2%) tiveram o diagnóstico de insuficiência coronariana aguda, 12 (80%) apresentaram eventos cardíacos maiores e 7 (87,5%) infarto agudo do miocárdio. O valor preditivo negativo da cintilografia planar de perfusão miocárdica foi de 90% para o diagnóstico de insuficiência coronariana aguda e de 94% para detecção de eventos cardíacos maiores. Portanto a cintilografia planar de perfusão miocárdica foi eficaz para o diagnóstico de insuficiência coronariana aguda em pacientes com dor torácica e electrocardiograma sem alterações sugestivas de isquemia / The objective of the study was to evaluate the usefulness of rest scintigraphic planar myocardial perfusion imaging in patients with acute chest pain suspected of myocardial ischemia and nondiagnostic ECG in the diagnosis of acute coronary syndromes and to predict adverse cardiac outcomes. Patients within 6 hours of chest pain onset and nondiagnostic ECGs underwent planar myocardial perfusion imaging with Technetium-99m sestamibi and measurements of serum creatine kinase-MB, creatine kinase-MB mass. troponin and myoglobin 6 hours after the onset of symptoms. Studies showing perfusion defects were considered suggestive of acute coronary syndromes and were compared to the diagnosis made by the attending cardiologist. Clinical diagnosis of acute coronary syndromes was made In patients with rest angina admitted to the hospital, acute myocardial Infarction, myocardial revascularization, demonstration of significant coronary artery disease on angiography or cardiac death. Acute myocardial revascularization and cardiac death were considered major cardiac events. Patients discharged without acute coronary syndromes were scheduled for outpatient stress myocardial perfusion imaging. A total of 71 patients underwent planar myocardial perfusion imaging. The mean age was 58 +- 12 years, 44 (62%) were male and 27 (38%) female. The mean time between chest pain onset and radiotracer injection was 3 hours and 6 minutes, thirteen patients had chest pain at the moment of iniection. Twenty-one (29,6%) patients had acute coronary syndromes, 15 (21,1 %) had major cardiac events (8 myocardial infarction and 7 underwent myocardial revascularization). Planar perfusion imaging demonstrated perfusion defects in 21 patients, 16 (76,2%) patients with acute coronary syndromes, 12 (80%) patients who had major cardiac events and in 7 (87,5%) patients with myocardial infarction. The negative predictive value of planar perfusion image was 90% for diagnosis of acute coronary syndromes and 94% for detecting major cardiac events. In conclusion, early planar perfusion imaging allowed for a rapid and accurate risk stratification of emergency departments patients with possible myocardial ischemia and nondiagnostic ECGs

The rapid rate of global warming currently underway highlights the need for a deeper understanding of abrupt climate change. The Younger Dryas is a Late-Glacial climate event of widespread and unusually rapid change whose study can help us address this need for increased understanding. Reconstructions from the glacial record offer important contributions to our understanding of the Younger Dryas due to (among other things) the direct physical response of glaciers to even minor perturbations in climate. Because the glacier equilibrium line altitude (ELA) provides a more explicit comparison of climate than properties such as glacier length or area, ELA methods lend themselves well to paleoclimate applications and allow for more direct comparisons in space and time. Here we present a physically based ELA model for alpine paleoglacier climate reconstructions that accounts for differences in glacier width, glacier shape, bed topography and ice thickness, and includes error estimates using Monte Carlo simulations. We validate the ELA model with published mass balance measurements from 4 modern glaciers in the Swiss Alps. We then use the ELA model, combined with a temperature index model, to estimate the changes in temperature and precipitation between the Younger Dryas (constrained by 10Be surface exposure ages) and the present day for three glacier systems in the Graubünden Alps. Our results indicate an ELA depression in this area of 320 m ±51 m during the Younger Dryas relative to today. This ELA depression represents annual mean temperatures 2.29 °C ±1.32 °C cooler relative to today in the region, which corresponds to a decrease in mean summer temperatures of 1.47 °C ±0.73 °C. Our results indicate relatively small changes in summer temperature dominate over other climate changes for the Younger Dryas paleoglaciers in the Alps. This ELA-based paleoclimate reconstruction offers a simple, fast, and cost-effective alternative to many other paleoclimate reconstruction methods. Continued application of the ELA model to more regions will lead to an improved understanding of the Younger Dryas in the Alps, and by extension, of rapid climate events generally.

Event-based sediment budgets were developed in a small agricultural sub-watershed using radionuclide tracers in conjunction with traditional monitoring techniques. The result of these budgets quantified the flux of material from each sediment source in the sub-watershed. The first step in the study was to quantify the net flux of material through the watershed outlet for runoff events. Results indicated that a pronounced clockwise hysteresis effect occurred during all studied events. The cause of the hysteresis effect was attributed to exhaustion of the upland (i.e., hillslopes and floodplains) sediment source. The hysteresis effect was dampened during an extreme flash flood event that caused overbank flow. This dampening was attributed to an increase in upland sediment mobilization resulting from overbank flow. Results of the event-based monitoring were compared against a previously developed sediment rating curve that assumed a power-law relationship between suspended sediment transport and water flow rates. The results indicate that the power-law relationship grossly under predicted the sediment flux over each runoff event. A tracing technique was utilized to establish the relative contributions from the uplands and the stream channel (i.e., channel banks and bed). This technique used the relationship between the naturally occurring radionuclide tracers 7Be and 210Pbxs to differentiate eroded upland soils from channel-derived sediments in the suspended sediment loads. A simple two end-member unmixing model was used to determine the relative contribution from each source. Results indicate that the upland source was the dominant contributor to the suspended load early in the runoff events, but channel contributions were more prevalent at later stages, reinforcing the conclusion drawn from the hysteresis observation. Further analysis of the results indicated that the uplands contributed the majority of the material to the suspended load because the sediment transport rate during the early stages of the event was much larger than during the later stages. Therefore, watershed managers wishing to minimize non-point source pollution resulting from erosion should first focus their efforts on reducing erosion of upland soils.

Le mélanome cutané est un cancer très invasif, dont l'évolution est rapidement fatale au stade métastatique du fait d'une absence de thérapies réellement efficaces. Face à ce constat, une stratégie de multimodalité a été évaluée au moyen d'un vecteur spécifique des cellules de mélanome et présentant la double potentialité diagnostique (imagerie TEP) et thérapeutique (radiothérapie interne vectorisée (RIV)) en fonction du radioélément introduit. Dans ce but, des analogues iodés et fluorés d'ICF01012, un vecteur ciblant la mélanine surexprimée dans un grand nombre de mélanomes, ont été synthétisés puis radiomarqués (iode-125 d'une part et fluor-18 d'autre part). Les profils pharmacocinétiques des radiotraceurs ont par la suite été étudiés in vivo sur modèle murin de mélanome, par imagerie scintigraphique γ (125I) et par imagerie TEP (18F). A l'issue de ces études, le traceur 4 a été sélectionné comme molécule leader de cette série, en raison d'un tropisme tumoral spécifique, élevé et durable, associé à élimination rapide des tissus non-cibles. Ce composé a ensuite été radiomarqué à l'iode-131 pour une évaluation en RIV sur le même modèle murin. Le traitement avec [131I]4 a induit une inhibition significative de la croissance tumorale et une augmentation significative de la médiane de survie. Au vu des résultats prometteurs obtenus avec le traceur 4, des études de métabolisme sur le même modèle murin ont été effectuées. En conclusion, en termes de chimie, radiochimie, stabilités in vitro et in vivo, TEP et RIV, le traceur 4 a validé notre concept de multimodalité. A terme, ce composé pourrait être transféré pour des études cliniques afin : de sélectionner les patients présentant des lésions de mélanome pigmentées (18F/TEP) et donc susceptibles de répondre au protocole de RIV ; de traiter ces patients (131I/RIV) ; de suivre la réponse au traitement (18F/TEP). En parallèle a été développé le premier groupement prosthétique iodé et fluoré multimodal, le 4-fluoro-3-iodobenzoate de tétrafluorophényle 108, pour le marquage de vecteurs d'intérêt (peptides, protéines, nanoparticules…). Le composé 108 et les précurseurs de radiomarquages correspondants ont été synthétisés en peu d'étapes, avec de bons rendements. Les radiomarquages ont ensuite été mis au point, et ont permis d'obtenir [125I]108 et [18F]108 en des temps relativement courts, avec d'excellents rendements et puretés radiochimiques. Le groupement prosthétique a ensuite été couplé avec succès à un ligand organique et deux peptides. En conclusion, nous avons démontré que le composé multimodal 108 peut être utilisé pour la radiofluoration et la radioiodation de vecteurs d'intérêt, autorisant des applications à la fois diagnostiques (TEP/18F) et thérapeutiques (RIV/131I) pour la prise en charge de nombreux cancers. / Melanoma is the most serious form of skin cancer with a poor prognosis for patients with metastatic disease. Our project deals with a multimodal approach, using a single fluorinated and iodinated melanintargeting compound, and offering both imaging (PET/18F) and therapeutic (targeted radionuclide therapy (TRT)/131I) applications, depending on the radioisotope introduced. Furthermore, using PET imaging, our strategy allows a selection of TRT-responded patients (i.e. bearing pigmented metastases) as well as a monitoring of treatment response. In previous works, the iodinated quinoxaline-carboxamide compound ICF01012 was evaluated in a TRT protocol, using melanoma-bearing mice models. It demonstrated efficacy, with significant inhibition of tumoural growth and improvement of the median survival. Based on these results, iodinated and fluorinated analogs of ICF01012 were synthesized, for multimodality purposes. All new compounds were then radiolabelled with iodine-125 and fluorine-18 (fully automated radiosyntheses), with good radiochemical yields and excellent radiochemical purities. For pharmacokinetic profile studies on melanoma-bearing mice, [125I]radiotracers were evaluated by γ-scintigraphy and [18F]radiotracers by PET. Compound 4 emerged as the lead tracer, with a specific and long-lasting tumoural uptake and a fast clearance from non-specific tissues, leading to highly contrasted images. The tracer 4 was then radiolabelled with iodine-131, with excellent radiochemical yield and purity, to perform a TRT assay on the same melanoma model. Treatment with [131I]4 significantly inhibited tumoural growth and lung metastasis occurrence. Moreover, it significantly improved the median survival. As tracer 4 demonstrated promising results in PET imaging and TRT of melanoma, its metabolism was investigated with [125I]4 and [18F]4: radiotracers were found unchanged in melanin-containing tissues (tumour and eyes), while a fast breakdown was observed in excretion organs and fluids (four metabolites were identified). In conclusion, in terms of chemistry, radiochemistry, in vitro and in vivo stability, PET imaging and TRT, compound 4 validated our multimodality concept. We also developed the first bimodal fluorinated and iodinated prosthetic group, the 2,3,5,6-tetrafluorophenyl 4-fluoro-3-iodobenzoate (108), as a suitable acylating agent for the labelling of a large variety of compounds. In this approach, this new compound allows applications in diagnosis (PET imaging/18F) and therapy (TRT/131I). Compound 108 and its corresponding precursors for radiolabelling were synthesized in very few steps, with good yields. [125I]108 was then prepared in one-step starting from a perfluorostannane precursor, and purified by F-SPE cartridge to avoid time-consuming HPLC. As for [18F]108, it was produced by a fully automated three steps, two-pots radiosynthesis process. [125I]108 and [18F]108 were both obtained in a short time, with excellent radiochemical yields and purities. These prosthetic groups were then successfully used to radiolabel small organic ligand N,N-diethylethylenediamine and peptides NDP-MSH and PEG3[c(RGDyK)]2, in mild conditions, with good yields. In conclusion, we demonstrated that compound 108 could be a promising acylating bimodal prosthetic group for radiofluorination and radioiodination of small organic molecules, peptides, proteins, antibodies as well as nanoparticles.

The objective of this study was to determine the origin of sediment currently collected in Black Lake, an extremely productive salmon fishing environment located along a remote section of the Alaska Peninsula, AK. To meet the goals of this project, soil cores were collected at the site during an extensive field study. The field investigation was based on a prior numerical study, which revealed the most erodible areas and the hydrologic patterns in Black Lake and its tributaries, namely the Alec River. From this study, select locations of the catchment were chosen for coring. These included the Alec River Delta, Black Lake, and four tributaries in the catchment. These samples were analyzed for the radionuclides 137Cs and 210Pb to determine soil deposition rates using Gamma Spectroscopy. To determine the sedimentation rate of each coring location, spikes in the 137Cs activity were connected to the known cesium deposition peak in 1964 and the depth of soil above the peak was divided by the number of years that have passed. This gave a spatially averaged deposition rate within the lake of roughly 0.25 cm/y. This result closely compared to the numerical study of Elhakeem and Papanicolaou (2008) and to a study done in close proximity to Black Lake in the early 1990s (Stihler et al. 1992). The rate of each location was then validated by visually analyzing each core using soil color demarcation lines to determine the soil composition. This analysis resulted in the discovery of a variety of soil types ranging from silts and clays, to coarse sands, to volcanic tephra. It was concluded that the lake flow patterns, the introduction of volcanic material from nearby Mt. Veniaminof, and back water resulting from deposition occurring down stream of Black Lake at the Black River's junction with the West Fork River are some of the main contributors for the deposition in the lake.

Bibliography: leaves 94-106. / v, 106, [33] leaves, [2] leaves of plates : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Assessment of myocardial metabolism with radiolabelled substrates and positron emission tomography provides a potentially sensitive technique to investigate physiological and pathological cardiac states "in vitro". Prior studies have indicated that overall metabolic activity cannot be estimated from rates of utilization of any one particular substrate. It was hypothesized that acetate labelled with carbon-11 would provide an index of oxidative metabolism, based on fundamental biochemical principles. The hypothesis is confirmed in studies using isolated perfused rabbit hearts and closed chest canine studies. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1995

<p>The two purposes of this thesis were to evaluate new diagnostic techniques of lymphnode staging in invasive bladder cancer and to evaluate the results of neoadjuvant chemotherapy in invasive bladder cancer.</p><p>Sentinel node detection was performed in 13 patients in preparation for radical cystectomy. The method showed to be feasible, and the results displayed the occurrence of metastatic nodes outside the traditional area of diagnostic dissection in a majority of patients. Four patients were metastasized, each one with one metastatic node detected with the help of the sentinel node procedure.</p><p>Four randomly selected sentinel nodes from four different unmetastasized patients were compared to the four metastatic sentinel nodes from the first series. After microdissection, p53 genomic structure, immunohistochemical expression and MVD (microvessel density) were assessed in the primary tumors and corresponding sentinel nodes. The results suggested that invasive bladder cancer mainly involved monoclonal proliferation with predominantly homogenous biomarker profile, but there were also signs of clonal evolution.</p><p>The Nordic Cystectomy Trial 2 (NCT2), is a randomized prospective trial investigating the possible benefit of neoadjuvant chemotherapy versus cystectomy only, in 311 eligible patients with urinary bladder cancer T2-T4aNXM0.Evaluation of overall survival did not show any statistically significant benefit in the experimental arm. This probably due to lack of statistical power.</p><p>To increase the statistical power we performed a combined analysis of randomized patients from both the Nordic Cystectomy Trial 1 (NCT1) and NCT2, n = 620. Eligible patients from NCT1 had T1G3, T2-T4a NXM0 urinary bladder cancer. Standard meta-analysis methods were used. The only end-point analysed was overall survival. Neoadjuvant platinum based combination therapy was associated with a 20 % reduction in the relative hazard in probability of death.</p>