O Instituto de Pesquisas Energéticas e Nucleares, IPEN, pesquisa e produz radiofármacos que são distribuídos para todo o Brasil. Atualmente o radiofármaco com a maior quantidade de embalados expedidos por ano e com a maior atividade total é o gerador de tecnécio-99m. Com o intuito de diminuir as doses individuais dos trabalhadores envolvidos na produção de radiofármacos foi realizado um estudo de otimização da proteção radiológica no processo de expedição do gerador de tecnécio-99m, utilizando as técnicas de análise de custo-benefício diferencial, análise de custo-benefício integral, análise de prioridade com atributos múltiplos e análise com critérios múltiplos excedentes. Com alterações na configuração do embalado para despacho do gerador e com a aquisição de uma esteira transportadora foi possível estabelecer 4 opções de proteção. Os atributos considerados foram o custo da proteção, a dose coletiva, a dose individual e o esforço físico realizado pelo trabalhador para movimentar o embalado na falta da esteira. Para verificar a robustez das soluções analíticas encontradas com as técnicas utilizadas na otimização foi realizado um estudo de sensibilidade e foi constatado que a opção 3 é mais robusta que a opção 1, que deixa de ser a solução analítica com um aumento de R$ 20.000,00 no custo da proteção. / The Instituto de Pesquisas Energéticas e Nucleares, IPEN, radiopharmaceuticals research and produce that are distributed throughout Brazil, currently the radiopharmaceutical with the largest number of packaged shipped per year and with the highest total activity is the 99m technetium generator. To reduce individual doses for workers involved in the production of radiopharmaceuticals was performed a study of radiological protection optimization in the shipment process of technetium generator, using the techniques: diferencial cost-benefit analysis, integral cost-benefit analysis, multi-attribute utility analysis and multi-criteria outranking analysis. With changes in the configuration of packed for generator dispatch and with the acquirement of a mat transporter it was possible establish 4 protection options. The attributes considered were the protection cost, collective dose, individual dose and physical effort by worker to move the package without the mat. To assess the robustness of analytical solutions found with the techniques used in the optimization we performed a sensitivity study and found that option 3 is more robust than option 1, which is no longer the analytical solution with an increase of R$ 20.000,00 the cost of protection.

In collaboration with the United States Environmental Protection Agency (USEPA), the University of South Florida Health Risk Methodology Group has developed dose-time-response models to characterize neurobehavioral response to chemical exposure. The application of dose-time-response models to neurobehavioral screening tests on laboratory animals allows for benchmark dose estimation to establish exposure limits in environmental risk assessment. This thesis has advanced dose-time-response modeling by generalizing a published toxico diffusion model to allow for dose dependent time of peak effects. To accomplish this, a biphasic model was developed which adopted the effect compartment model paradigm used in pharmacokinetics/pharmacodynamics to estimate a distributional rate constant to account for dose related variation in the time of peak effect. The biphasic model was able to describe dose-dependent time of peak effects as observed in the data on acute exposure to parathion and adequately predicted the observed response. However, the experimental design appeared insufficient in statistical power to confirm statistical significance for each parameter of interest. Motivated by the question of what design requirement might be necessary to validate the biphasic model, Monte Carlo simulation was adopted. Simulations were performed to assess the efficacy and efficiency of various experimental designs for detecting and evaluating some critical characteristics of the biphasic model, including the TOPE. The results of simulation suggest that the location of measurement times around the TOPE have important implications for assessing the statistical significance of the parameter that describes dose-dependent TOPE and that the mean squared error of the parameter estimator was improved most when testing times were chosen to bracket the TOPE. While dose dependent time of peak effects has underlying physiological mechanisms such as synergistic or capacity limited kinetics, the biphasic model estimates these physiological properties through a mathematical function which may be physiologically relevant but does not necessarily define physiological mechanisms underlying the response. However, if verified through further testing, the biphasic model may contribute to the USEPA’s aim of developing physiologically relevant dose-response models for assessing risk of neurotoxicity with repeated measurements of response.

External beam radiation therapy for prostate cancer can result in urinary, sexual, and rectal side effects, often impairing quality of life. A polyethylene glycol-based product, SpaceOAR hydrogel (SOH), implanted into the connective tissue between prostate gland and rectum can significantly reduce the dose received by the rectum and hence risk of rectal toxicity. The optimal way to manage the hydrogel and rectal structures for plan optimization is therefore of interest. A retrospective planning study was completed with 13 patients to examine optimal planning and treatment methods. Computerized tomography (CT) scans were taken pre- and post-SOH implant. Six hypofractionated (60 Gy in 20 fractions) treatment plans were produced per patient using either a structure of rectum plus the hydrogel, termed composite rectum wall (CRW), or rectal wall (RW) as the inverse optimization structure and intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) as the treatment technique. Dose-volume histogram metrics were compared between plans to determine which optimization structure and treatment technique offered the maximum rectal dose sparing. RW structures offered a statistically significant decrease in rectal dose over CRW structures, whereas the treatment technique (IMRT vs VMAT) did not significantly affect the rectal dose. However, there was improvement seen in bladder and penile bulb dose when VMAT was used as a treatment technique over IMRT. Overall, treatment plans using the RW optimization structure offered the lowest rectal dose while VMAT treatment technique offered the lowest bladder and penile bulb dose. These treatment techniques and optimization structures have now been implemented at BC Cancer - Victoria based on this retrospective study. SOH implant has been shown not to be equally effective in all patients. Determining a priori patients in which the implant will offer most benefit allows for effective management of SOH resources. Several factors have been shown to be correlated to reduction in rectal dose including distance between rectum and planning treatment volume (PTV), volume of rectum in the PTV and change in rectum volume pre- to post-SOH. Several of these factors along with other pre-SOH CT metrics were found via multiple linear regression models to predict reduction of rectal dose using data from 21 patients who received SOH implant. Two high rectal dose metrics were modeled, change in the relative volume receiving 55 Gy and change in the partial high dose integral, integrating over the dose-volume histogram (DVH) from 55 Gy to 60 Gy. Models were also produced to predict pre-SOH RV55Gy. These models offered R-squared between 0.57 and 0.87 with statistical significance in each model. Applying a 3.5% lower limit on pre-SOH RV55Gy removed one third of patients as implant candidates. This may offer a clinically useful tool in deciding which patients should receive SOH implant given limited resources. Predictive models, nomograms and a workflow diagram were produced for clinical management of SOH implant. / Graduate

<p>Radioiodine has been used in nuclear medicine for the treatment of thyroid diseases such as Thyroid Cancer and Thyrotoxicosis for many years. The treatment renders the patient radioactive. To minimize the dose to the patients’ relatives and the general public, restric-tions are imposed on the behaviour of the patient. This project presents the person dose equivalents actually received by family members of radioiodine patients following such restrictions. The family members wore hospital ID-bands on left and right wrists for up to four weeks. Each ID-band contained two LiF: Mg, Ti Thermo Luminescence Dosimeters (TLD) calibrated to measure air kerma. The TLDs were analysed and a total person dose equivalent received by the relative was calculated from the measured air kerma values. The results were compared to the dose constraints imposed by The Swedish Radiation Protection Authority (SSI FS 2000:3) in order to confirm that the new set of restrictions used at Karolinska University Hospital Huddinge maintains the dose to family members below the applicable limits.</p><p>A total number of 22 relatives were recruited, 8 elderly, 7 adults and 7 children. Of the recruited relatives 4 (2 adults, 2 children) were excluded from the study as they had lost their dosimeter ID-bands or had other reasons not to participate in the study. This leaves the number of relatives used for data analysis at 18 individuals (8 elderly, 5 adults and 5 children) with a min age of 10 years and max age of 80 years.</p><p>The observed average person dose equivalent of 0.43 mSv (max, 1.27; min, 0.12) indi-cates that the new method of individualised restriction used at Karolinska University Hospital Huddinge work as desired in keeping the dose to family members at an accept-able level. The accuracy of the clinical study has been shown to depend greatly on the method by which the dose is investigated but also on the properties of the TLD material used. There is a potential underestimation of air kerma due to fading of up to 30 %. In addition there are contributing uncertainties from both the calibration method and the conversion to person dose equivalent with the combined uncertainty estimated to be 14%.</p>

<p>The International Atomic Energy Agency (IAEA) and the World Health Organisation (WHO) operate the IAEA/WHO TLD postal dose audit programme. The purpose of the programme is to verify the beam calibration in radiotherapy centres in developing countries and to check the Secondary Standards Dosimetry Laboratories (SSDLs). Thermoluminescence dosimeters (TLDs) are used as transfer dosimeters and the evaluation of these are done at the IAEA Dosimetry Laboratory. In the present work the uncertainties in the process of dose determination from TLD readings have been evaluated.</p><p>The analysis comprises the TLD reading reproducibility, uncertainties in the calibration coefficient, and uncertainties in factors correcting for fading of TL signal, influence of TLD holder, energy response and dose response non-linearity. The individual uncertainties were combined to estimate the total uncertainty in the evaluated dose from TLD readings. Experimental data from 2001-2005 were used in the analysis.</p><p>The total uncertainty has been estimated to be 1.2 % for irradiations with 60Co -rays and 1.6 % for irradiations with high-energy X-rays. Results from irradiations by the Bureau International des Poids et Mesures (BIPM), Primary Standard Dosimetry Laboratories (PSDLs), Secondary Standard Dosimetry Laboratories (SSDLs) and reference centres compare favourably with the estimated uncertainties.</p><p>The largest uncertainty components are in the energy correction factor (for high-energy X-rays) with a value of 1.1 % and in the dose response non-linearity correction factor with a value of 0.9 %.</p><p>It has been shown that the acceptance limits of 5 % for TLD results of hospitals and 3.5 % for SSDLs are justified when related to the uncertainties in the dose calculations and the uncertainty in the determination of absorbed dose to water at the centre, as discussed in IAEA TRS-398 (IAEA, 2000), provided that it is followed.</p>

<p>The dose distribution around brachytherapy (BT) sources is characterized by steep dose gradients and an energy spectrum varying rapidly with depth in water around the source. These two properties make experimental verification of the dose distribution difficult, and put high demands on the dosimetry system in use regarding precision, size and energy dependence. The American Association of Physicists in Medicine (AAPM) recommends lithium fluoride (LiF) thermo-luminescence dosimetry (TLD) to be used for verification measurements, as it is the only dosimetry system meeting the requirements, but still the total combined uncertainty in dose-rate determination is as high as 7-9 % (1 σ). Lithium formate is a new dosimetry material that is less energy dependent than LiF, but more sensitive than the most common EPR (electron paramagnetic resonance) dosimetry material, alanine. In order to evaluate lithium formate EPR for BT dosimetry, dosimeters were produced for experimental dose determination around BT source 192Ir. The dosimeters were calibrated against an ionization chamber in a high energy photon beam. Dose to water was determined at 1, 3 and 5 cm radial distance from the source, which was stepped along a straight line in a PMMA phantom. The experiments were performed twice using 4 dosimeters per distance and experiment. Methods to correct for energy dependence were developed and evaluated. The uncertainty in measured dose was estimated. The experimental dose values agreed with the values from the treatment planning system with a maximum deviation of 3.3 %, and an average 1 σ uncertainty of 3 % at 3 and 5 cm and 5 % at 1cm. Uncertainty in radial distance from the source as well as source calibration were the dominating contributions to the total combined uncertainty. Lithium formate EPR has been shown to be a promising alternative to LiF TLD for BT dosimetry.</p>

<p>Dosimetric characteristics of a CVD single crystal diamond detector have been evaluated. Detector stability, linearity, optimal bias, temperature dependence, directional dependence, priming and pre-irradiation behaviour, depth dose curves and dose profiles were investigated.</p><p>The optimal bias was determined to be 50 V. The detector stability measurement showed a too large variation for absolute dosimetry in a day to day measurement, but acceptable variation during one and the same day. The linearity constant, , in the relation between signal and dose rate, (Fowler 1966), was determined to 0.978 and 0.953 for two detectors. The sub-linearity was also observed in the depth dose curves and could be eliminated with a correction method. The diamond detector showed smaller temperature dependence than the EFD silicon diode. The directional dependency was, <1 %, up to at least ± 15˚ and therefore no angular correction is needed. A priming dose of 0.6 Gy was determined, which is considerably smaller than for existing detectors on the market. After pre-irradiation with electrons (8 and 18 MeV) a large and permanent desensitization of up to 31 % / 500 Gy was detected. This is in contradiction to what previous published articles claim. 15 MV photons also reduced the sensitivity of the detector, but no evidence that 5 MV photons do has been found. A 50 Gy dose of 180 MeV protons did not reduce the sensitivity either. The detector dose rate linearity was improved by electron pre-irradiation. The dose profile penumbras of the diamond detector were, for the most part, smaller than the RK ionization chamber, indicating a better spatial resolution.</p>

<p>The county of Dalarna is at present carrying through a process of digitalization where traditional x-ray film is being replaced with digital detectors. Earlier used methods for dose optimization turned out not being sufficient. This report presents a method to harmonize dose levels between x- ray sites equipped with Fujifilm imaging plate systems. An exposure index, S, related to the dose level of the examination is computed to every x-ray image. S turned out to be inversely proportional to the detector dose used at the examination. Detector dose is also the one simulated factor that doubtlessly affects S the most.There are however a lot of parameters, e.g difference between patients, that are not easily simulated even though they still have considerable affect. The method for harmonizing dose levels between x-ray sites are based on statistics of collected S-values for a kind of examination. The average of the collected S-values levels variations and is a more solid measure of the dose level for the examination. By means of this method the dose level of frontal images of the lungs at a site have been reduced by 30 per cent without endanger the diagnostic security.</p>

<p>The county hospital of Dalarna has for the last couple of years carried through a process of digitalization. The result is that within the county it exists image plate systems from two different manufacturers. In an attempt to create a tool for dose optimization and dose surveillance the county of Dalarna would like to investigate if the exposure index from Agfa and Fuji is suitable as a dose indicator. An investigation of the exposure index, S, from Fuji has already been done. This thesis has been continuing the investigation by evaluating the stability of the exposure index, lgM, from Agfa. Simultaneously an observation if there is a simple relation between the exposure indicators from Agfa and Fuji has been performed. The result showed that the average of lgM, for a set of images from the same type of examination, is appropriate as a dose indicator to the image plate for that specific examination type and X-ray equipment. The usefulness is linked to the same tube voltage and Speed Class for a specific examination, and is to a certain degree restricted by the collimating. There is a relation between the exposure index from Agfa and Fuji, and there is in a simple way possible to transform S-values to lgM-values for comparison. The relation turned out to be examination specific.</p>

Tn5 mutagenesis of apdA (for antibiotic production) and deletion of gacA (for global antibiotic and cyanide) resulted in the same pleiotropic phenotype in Pseudomonas fluorescens (i.e. production of an array of secondary metabolites including the antibiotics pyrrolnitrin, pyoluteorin, and 2,4-diacetylphloroglucinol as well as a tryptophan-side-chain oxidase, hydrogen cyanide, and an extracellular protease was abolished). The apdA and gacA loci were identified and cloned from the genome of Pf-5. Nucleotide sequencing of the apdA and gacA loci was used to identify the open reading frames for these genes. The deduced amino acid sequences for apdA and gacA exhibited similarity to sensor kinase (ApdA) and response regulator (GacA) proteins that comprise two-component regulatory systems. The C-terminal domain of GacA containing the putative helix-turn-helix DNA-binding motif was fused to the glutathione S-transferase protein. The glutathione S-transferase GacA C-terminal fusion protein was used in a cycle selection procedure that was designed to identify GacA binding sites from a complex pool of DNA fragments. Although a putative binding site for GacA was identified using the cycle selection procedure, the results were inconclusive due to several inconsistencies in the DNA-binding assay. The upstream region of one gene, which codes for a putative porin, was identified as a putative binding site for GacA by the cycle selection procedure. Studies initiated to determine whether gacA regulates transcription of this putative porin gene have been unsuccessful, so it remains unclear whether this gene is regulated by GacA. Also, asymptotic limits to biological control of Rhizoctonia damping-off of cotton were observed with the biological control agent P. fluorescens Pf-5. / Graduation date: 1999