Enhancing analytical development in the pharmaceutical industry: A DoE-QSRR model for virtual Method Operable Design Region assessment.

Recently, the pharmaceutical industry has increasingly adopted the Analytical Quality by Design (AQbD) approach for analytical development. To facilitate AQbD approach implementation in the development of chromatographic methods for determining cephalosporin antibiotics, an in silico tool capable of performing virtual DoEs was developed enabling to obtain virtual operable regions of method. To this end, the drugs cephalexin, cefazolin, cefotaxime and ceftriaxone were analyzed using four experimental designs, deriving a DoE-QSRR model and employing Monte Carlo method. The DoE-QSRR model and virtual DoEs were validated using data not used in model's construction, obtaining coefficients of determination of 84.72 % for DoE-QSRR model and over 77 % for virtual DoEs. Virtual MODRs were constructed using data from the virtual DoEs. The virtual MODRs were validated by comparing them with experimental MODRs under various scenarios, with overlap areas reaching values exceeding 84 %. Therefore, the in silico tool was considered suitable for indicating analyte trends under different analytical conditions, being capable of performing virtual DoEs for cephalosporin drugs with sufficient assertiveness to guide analytical development and allow obtaining a MODR capable of providing results of adequate quality.

Optimized Monte Carlo simulations for voxel-based internal dosimetry.

Objective.The scientific community has considered internal dosimetry by the Monte Carlo method the gold standard. However, there is a trade-off between simulation processing time and the statistical quality of the results that makes it a challenge to obtain accurate absorbed dose values in some situations, such as dose estimation in organs affected by cross-irradiation or limited computing power. Variance reduction techniques are used to reduce computational processing time without impairing the statistical quality of the results, such as tracking energy cutoff, secondary particle production threshold, and parallelism of different types of emissions from radionuclides.Approach.In this work, GATE Monte Carlo code and its variance reduction techniques were evaluated to calculateSvalues of organs from the international commission on radiological protection (ICRP) report 110 male phantom for the lutetium-177, iodine-131, yttrium-90, and radium-223 radionuclides. The results are compared with the data from the OpenDose collaboration.Main results.A cutoff of 5 MeV for local electron deposition and 2.0 mm of secondary particle production range resulted in a computational efficiency increase of 7.9 and 1.05 times, respectively. Simulation of ICRP 107 spectra-based source proved to be about 5 times more efficient when compared to a decay simulation usingG4RadioactiveDecay(Geant4-based radioactive decay processes). Track length estimator (TLE) and split exponential track length estimator (seTLE) techniques were used to calculate the absorbed dose of photon emissions, resulting in computational efficiency up to 29.4 and 62.5 times higher when compared to traditional simulations, respectively. In particular, the seTLE technique accelerates the simulation time by up to 1426 times, achieving a statistical uncertainty of 10% in volumes affected by cross-irradiation.Significance.The variance reduction techniques used in this work drastically reduced the simulation time and maintained the statistical quality of the calculated absorbed dose values, proving the feasibility of the use of the Monte Carlo method in internal dosimetry under challenging situations and making it viable for clinical routine or web applications.

ECG Measurement Uncertainty Based on Monte Carlo Approach: An Effective Analysis for a Successful Cardiac Health Monitoring System.

Measurement uncertainty is one of the widespread concepts applied in scientific works, particularly to estimate the accuracy of measurement results and to evaluate the conformity of products and processes. In this work, we propose a methodology to analyze the performance of measurement systems existing in the design phases, based on a probabilistic approach, by applying the Monte Carlo method (MCM). With this approach, it is feasible to identify the dominant contributing factors of imprecision in the evaluated system. In the design phase, this information can be used to identify where the most effective attention is required to improve the performance of equipment. This methodology was applied over a simulated electrocardiogram (ECG), for which a measurement uncertainty of the order of 3.54% of the measured value was estimated, with a confidence level of 95%. For this simulation, the ECG computational model was categorized into two modules: the preamplifier and the final stage. The outcomes of the analysis show that the preamplifier module had a greater influence on the measurement results over the final stage module, which indicates that interventions in the first module would promote more significant performance improvements in the system. Finally, it was identified that the main source of ECG measurement uncertainty is related to the measurand, focused towards the objective of better characterization of the metrological behavior of the measurements in the ECG.

Development and optimization of stability-indicating method of ethinylestradiol, levonorgestrel, and their main impurities using quality by design approach.

The association of Ethinylestradiol 0.03 mg and Levonorgestrel 0.15 mg is a hormonal contraceptive that combines estrogen and progestogen. According to a bibliographic survey, these combined drugs present at least 18 known degradation products, which are required to control the potential impurities harmful to human health. The high number of impurities and the low concentrations of the active pharmaceutical ingredients (APIs) and their respective degradation products increase the complexity of the stability-indicating method development for this medicine. Thus, this work aimed to develop and optimize the stability-indicating method using the quality by design (QbD) approach and in-silico tools for application in samples of oral contraceptives sold in Brazil. The analysis samples were initially subjected to a forced degradation study through 7 days of exposure under acid and alkali hydrolysis, oxidative condition, and oxidation by metal ions. In addition to the chemical exposure, the sample was subjected to physical stress through 10 days of exposure under dry heat, moisture, and photolytic degradation. These exposure samples were analyzed in the development and optimization of chromatographic conditions. As a result, the developed method was able to separate 20 known substances, including the two APIs and their respective 18 degradation products, as well as unknown degradation products obtained by the forced degradation study. Finally, this stability-indicating method was successfully applied for comparative analysis of contraceptive drugs marketed in Brazil, newly purchased and subjected to accelerated stability condition at 40 °C and 75% RH over the 6-month period.

A new approach to assess the degree of contamination and determine sources and risks related to PTEs in an urban environment: the case study of Santiago (Chile).

In 2017, a geochemical survey was carried out across the Commune of Santiago, a local administrative unit located at the center of the namesake capital city of Chile, and the concentration of a number of major and trace elements (53 in total) was determined on 121 topsoil samples. Multifractal IDW (MIDW) interpolation method was applied to raw data to generate geochemical baseline maps of 15 potential toxic elements (PTEs); the concentration-area (C-A) plot was applied to MIDW grids to highlight the fractal distribution of geochemical data. Data of PTEs were elaborated to statistically determine local geochemical baselines and to assess the spatial variation of the degree of soil contamination by means of a new method taking into account both the severity of contamination and its complexity. Afterwards, to discriminate the sources of PTEs in soils, a robust Principal Component Analysis (PCA) was applied to data expressed in isometric log-ratio (ilr) coordinates. Based on PCA results, a Sequential Binary Partition (SBP) was also defined and balances were determined to generate contrasts among those elements considered as proxies of specific contamination sources (Urban traffic, productive settlements, etc.). A risk assessment was finally completed to potentially relate contamination sources to their potential effect on public health in the long term. A probabilistic approach, based on Monte Carlo method, was deemed more appropriate to include uncertainty due to spatial variation of geochemical data across the study area. Results showed how the integrated use of multivariate statistics and compositional data analysis gave the authors the chance to both discriminate between main contamination processes characterizing the soil of Santiago and to observe the existence of secondary phenomena that are normally difficult to constrain. Furthermore, it was demonstrated how a probabilistic approach in risk assessment could offer a more reliable view of the complexity of the process considering uncertainty as an integral part of the results.

Simulación de dosis absorbida en terapia molecular mediante método de Montecarlo utilizando software libre GEANT4: GATE

RESUMEN Fundamento: aún no existe una forma óptima para determinar la dosis absorbida por los tumores; este desconocimiento es la causa de que la dosis final del tratamiento sea impredecible. Por esta causa los pacientes pueden estar recibiendo dosis mayores que las mínimas requeridas para su correcto diagnóstico. Objetivo: crear un código fuente para un proyecto de aplicación del programa GATE en la simulación de la dosis absorbida en radioterapia molecular, por método Montecarlo, para un maniquí de Giap. Métodos: se realizó la simulación por método de Montecarlo a partir de modelar el maniquí de Giap, mediante la plataforma de simulación GATE. Se compararon los resultados obtenidos con la información reflejada en la bibliografía sobre las mejores prácticas estandarizadas. Resultados: se confeccionó un código fuente implementado en GATE para la determinación de la dosis absorbida en radioterapia molecular. Se obtuvo distribución no uniforme de dosis en un medio de actividad uniforme y un 2 % de incertidumbre aproximado (en buena correspondencia con los valores reportados en la literatura), los resultados permiten afirmar que la simulación de dosis por medio de la plataforma GATE es confiable, de poco gasto computacional y altamente recomendable. Conclusiones: es recomendable utilizar la plataforma GATE para la simulación del cálculo de la dosis absorbida por ser rápida, de bajo costo computacional y confiable.

ABSTRACT Background: there is still no optimal way to determine the dose absorbed by tumors; this lack of knowledge is the reason why the final dose of treatment is unpredictable. For this reason, patients may be receiving doses greater than the minimum required for their correct diagnosis. Objective: to create a source code for an application project of the GATE program in the simulation of absorbed dose in molecular radiotherapy, by Monte Carlo method, for a Giap phantom. Methods: the simulation was carried out by the Montecarlo method from modeling the Giap phantom, using the GATE simulation platform. The results obtained were compared with the information reflected in the bibliography on standardized best practices. Results: a source code implemented in GATE was prepared for the determination of the absorbed dose in molecular radiotherapy. Non-uniform distribution of doses was obtained in a medium with uniform activity and an approximate 2% uncertainty (in correspondence with the values reported in the literature), the results allow to affirm that the dose simulation through the GATE platform is reliable, of little computational expense and highly recommended. Conclusions: it is advisable to use the GATE platform for the simulation of the calculation of the absorbed dose because it is fast, of low computational cost and reliable.

Ferramenta in silico para desenvolvimento de métodos cromatográficos - aplicação em misturas de filtros solares / In silico tool for development of chromatographic methods - application in mixtures of sunscreensPalavras-chave em inglês

Planejamento de Experimentos (DoE) permite obter e explorar conhecimentos sobre inúmeros sistemas, facilitando a coleta de informações com reduzido número de experimentos. No entanto, DoE é restrito ao delineamento do desenho experimental. Para superar essa limitação e permitir uma previsão precisa dos tempos de retenção para uma seleção de filtros UV orgânicos sob diversas condições, usamos a Relação Quantitativa entre Estrutura e Retenção combinada com o método de Monte Carlo para desenvolver uma plataforma in silico capaz de prever o perfil cromatográfico de filtros UV orgânicos. Sete analitos foram usados para estabelecer o modelo de predição: benzofenona-3, avobenzona, ethilhexil triazona, octil dimetil PABA, metoxicinamato de octila, tinosorb® S e octocrileno. Os valores residuais obtidos no modelo de análise de regressão múltipla mostraram distribuição normal, homocedasticidade e independência. Os coeficientes de determinação (R2) e predição (R2 pred) foram de 99,82% e 99,71%, respectivamente. A plataforma in silico apresentou grande potencial para predição do perfil cromatográfico de filtros UV orgânicos, da coeluição de analitos, de seus parâmetros cromatográficos, além de permitir, sem experimentação, uma visão geral do comportamento de retenção de compostos sob diversas condições cromatográficas

Design of Experiments (DoE) allows obtaining and explorer knowledge about innumerous systems, facilitating the information collection with reduced number of experiments. However, DoE is restricted to the limited range which experimental design was delineated. In order to overcome this limitation and enable accurate prediction of retention times for a selection of organic UV filters under various conditions, we used the Quantitative Structure-Retention Relationships tool combined with Monte Carlo method to develop an in silico platform capable of predicting chromatographic profile of organic UV filters. Seven analytes were used to established to prediction model: benzophenone-3, butyl methoxydibenzoilmethane, ethylhexyl triazone, ethylhexyl dimetyl PABA, ethylhexyl methoxycinnamate, bisethylhexyloxyphenol methoxyphenyl triazine and octocrylene. Residual values obtained from multiple regression analysis model showed normal distribution, homoscedasticity, and independence. Determination (R2) and prediction (R2 pred) coefficients were found to be 99,82% and 99,71%, respectively. In silico platform presented great potential for predicting chromatographic profile of organic UV filters, analytes coelution, chromatographic parameters and allowing, without experimentation, an overview of retention behavior of compounds under various chromatographic conditions

Financial impact of healthcare-associated infections on intensive care units estimated for fifty Brazilian university hospitals affiliated to the unified health system.

BACKGROUND: Studies show that healthcare-associated infections (HAIs) represent a crucial issue in healthcare and can lead to substantial economic impacts in intensive care units (ICUs). AIM: To estimate direct costs associated with the most significant HAIs in 50 teaching hospitals in Brazil, affiliated to the unified health system (Sistema Único de Saúde: SUS). METHODS: A Monte Carlo simulation model was designed to estimate the direct costs of HAIs; first, epidemiologic and economic parameters were established for each HAI based on a cohort of 949 critical patients (800 without HAI and 149 with); second, simulation based on three Brazilian prevalence scenarios of HAIs in ICU patients (29.1%, 51.2%, and 61.6%) was used; and third, the annual direct costs of HAIs in 50 university hospitals were simulated. FINDINGS: Patients with HAIs had 16 additional days in the ICU, along with an extra direct cost of US$13.892, compared to those without HAIs. In one hypothetical scenario without HAI, the direct annual cost of hospital care for 26,649 inpatients in adult ICUs of 50 hospitals was US$112,924,421. There was an increase of approximately US$56 million in a scenario with 29.1%, and an increase of US$147 million in a scenario with 61.6%. The impact on the direct cost became significant starting at a 10% prevalence of HAIs, where US$2,824,817 is added for each 1% increase in prevalence. CONCLUSION: This analysis provides robust and updated estimates showing that HAI places a significant financial burden on the Brazilian healthcare system and contributes to a longer stay for inpatients.

Determination of the correction factors used in Fricke dosimetry for HDR 192Ir sources employing the Monte Carlo method.

PURPOSE: Fricke dosimetry has shown great potential in the direct measurement of the absolute absorbed dose for 192Ir sources used in HDR brachytherapy. This work describes the determination of the correction factors necessary to convert the absorbed dose in the Fricke solution to the absorbed dose to water. METHODS: The experimental setup for Fricke irradiation using a 192Ir source was simulated. The holder geometry used for the Fricke solution irradiation was modelled for MC simulation, using the PENELOPE. RESULTS: The values of the factors determined for validation purposes demonstrated differences of less than 0.2% when compared to the published values. Four factors were calculated to correct: the differences in the density of the solution (1.0004 ± 0.0004); the perturbations caused by the holder (0.9989 ± 0.0004); the source anisotropy and the water attenuation effects (1.0327 ± 0.0012); and the distance from the center of the detection volume to the source (7.1932 ± 0.0065). CONCLUSION: Calculated corrections in this work show that the largest correction comes from the inverse squared reduction of the dose due to the point of measurement shift from the reference position of 1 cm. This situation also causes the correction due to volume averaging and attenuation in water to be significant. Future versions of the holder will aim to reduce these effects by having a position of measurement closer to the reference point thus requiring smaller corrections.

Estimation of the kidney metabolic heat generation rate.

Thermogenesis results from the cellular metabolism and has a fundamental role for body thermoregulation in endothermic species. The motivation for this work is the analysis of the kidneys' contribution for thermoregulation. An inverse problem is solved for the estimation of the heat generation rate that results from the metabolic activities in the kidney, by using transient temperature measurements of the urine. The Markov chain Monte Carlo (MCMC) method is applied for the solution of the inverse problem, which presents inherent difficulties associated with low sensitivity of the parameters of main interest that represent the transient heat source term and strong correlation of the remaining model parameters. Such difficulties are dealt with in this work by using a version of the Metropolis-Hastings algorithm that samples the parameters in blocks. Simulated temperature measurements are used for the inverse problem solution, and the convergence of the Markov chains is verified with two different techniques.

Measurement uncertainty and risk of false conformity decision in the performance evaluation of liquid chromatography analytical procedures.

Liquid chromatography is one of the main techniques used in pharmaceutical quality control analytical procedures. However, there will always be a measurement uncertainty (MU) associated with them, that can lead to the approval of an out of specification lot (consumer risk) or rejection of a lot within specification (producer risk). Thus, the aim of this study was to evaluate the performance of liquid chromatography analytical procedures based on their measurement uncertainty and to estimate the risk of false conformity decisions. The uncertainties of the analytical procedures were estimated based on the results of validation (trueness and precision). Then, the ratio between overall uncertainty and specification range (U/T%) was calculated. It was noted that in most cases (73%), random errors (precision) contributes more significantly to the overall uncertainty when compared to systematic errors (trueness). Monte Carlo method was used, generating different manufacturing processes scenarios, and analytical results based on the MU of each analytical procedure. Then, consumer's and producer's risks were estimated from the simulated values. Pharmaceutical dosage forms that require more steps in sample preparation had higher measurement uncertainties, often above the recommended target uncertainty. As most of the analytical procedures showed U/T% values above recommended, the majority presented high estimated risk values and did not fit for purpose. Therefore, it is important to considerate the measurement uncertainty as part of analytical procedures validation, since trueness and precision values affect directly the measurement uncertainty and the risk of false conformity decisions.

Improving the theoretical description of charge transport in organic crystals.

Charge hopping based on Marcus theory is often used to predict charge carrier mobilities in organic crystals, although it is known to systematically underestimate the values. Here we show that this deficiency may lie on a fundamental aspect of quantum statistical averages, rather than on the approximation itself. Under adequate Boltzmann weighing procedure used to evaluate electron and hole transfer integrals, a kinetic Monte Carlo model is employed to describe mobilities in an azacene derivative. The values are in good agreement with experimental data suggesting that the evaluation of transfer integrals may be the weak link in hopping transport models.

Monte Carlo simulation of the radiation transport in chromium compensated gallium arsenide detectors / Simulación por Monte Carlo del transporte de las radiaciones en detectores dearseniuro de galio compensado con cromo

Abstract Some results obtained with the use of Monte Carlo mathematical simulation of radiation transport in Timepix hybrid detectors based on chromium compensated gallium arsenide are presented in this contribution. The MCNPX, GEANT4, SRIM and MCCM code systems were used for this purpose. The in-depth profiles of the deposited energy by the incident photons within the sensor active volume, the shapes and dimensions of the generated charge carriers clouds for different incident energies and specific geometrical conditions were obtained and presented. The 22Ne ions ranges in the target material for two different energies and the contributions of each energy loss channel were also determined. Finally, for a selected detector irradiated with photons of different energies, the displacement cross sections for each chemical element in the active material, as well as the number of displacements per atoms produced for each atomic species were calculated.

Resumen En este trabajo se presentan algunos de los resultados obtenidos con el uso de la modelación matemática por Monte Carlo del transporte de radiación en detectores híbridos Timepix basados en el arseniuro de galio compensado con cromo. Se emplearon para este propósito los sistemas de códigos MCNPX, GEANT4, SRIM y MCCM. Fueron obtenidos los perfiles en profundidad de la energía depositada por la radiación incidente dentro del volumen activo del sensor, las formas y dimensiones de las nubes de portadores de cargas generados por fotones incidentes de diferentes energías y condiciones geométricas específicas. También se determinaron los alcances de los iones de 22Ne de dos energías diferentes en el material blanco y las contribuciones de cada canal de pérdida de energía. Finalmente, para un detector seleccionado irradiado con fotones de diferentes energías se calcularon las secciones eficaces de desplazamiento para cada elemento químico en el material activo, así como el número de desplazamientos por átomos producidos para cada especie atómica.

Exploring the possibility of radiography in emission mode at higher energies: Improving the visualization of the internal structure of paintings / Explorando las posibilidades de la radiografía en modo de emisión a altas energías: Cómo optimizar la visualización de la estructura interna en pinturas

Summary We demonstrated in previous investigations that the internal structure of paintings can be visualized with conventional radiography in transmission mode when paintings have the proper stratigraphy. Unfortunately, there are many paintings that do not result in useful images. This problem can be solved by using radiography in emission mode. With this technique, the painting is irradiated with high energetic X-rays originating from an X-ray tube operating at 100 keV - 320 keV while inside the painting low energetic signals such as photoelectrons or characteristic photons are being generated. These signals escape from the top 10 µm of the painting and are able to illuminate the imaging plate. However, this technique has also some disadvantages. One of them is that it is not able to visualize underlying paintings. In this study, we explored the possibility to enhance the information depth by increasing the energy of the photon source from 100 keV up to 1.3325 MeV (i.e., 60Co source). At the same time, we also studied how the contrast between pigments is generated in emission mode. For this, we used mathematical simulation of particle transport in matter to understand the relation between input particle (particle type such as photon, electron or positron and the energy of the particle), the material being irradiated (element from which it is composed, thickness and density) and the output signal (generated particle types and energy). Finally, we will show that it is possible to image paintings using a 192Ir and even a 60Co source.

Resumen En investigaciones previas se ha demostrado que la estructura interna de las pinturas se puede visualizar satisfactoriamente con la radiografía convencional en modo de transmisión, siempre y cuando dichas pinturas tengan la estratigrafía adecuada. Desafortunadamente, hay muchos casos en los que la aplicación de este método no resultan en imágenes útiles. Este problema puede ser resuelto usando la radiografía en modo de emisión. Con esta técnica, la pintura se irradia con rayos X de alta energía originados en un tubo de rayos X trabajando entre 100 keV y 320 keV. Esto genera señales de baja energía (fotoelectrones o fotones característicos) en el interior de la pintura que, al escapar de las 10 μm superiores, pueden iluminar una placa de imágenes. No obstante, su aplicación también implica ciertas desventajas. Una de ellas es la incapacidad de visualizar las pinturas subyacentes. En este estudio, exploramos la posibilidad de incrementar la información obtenida a mayores profundidades aumentando la energía de la fuente de fotones desde 100 keV hasta 1.3325 MeV (fuente de 60Co). También estudiamos el impacto de esta energía en el contraste obtenido entre los pigmentos. Para esto, utilizamos la simulación matemática del transporte de partículas en la materia para comprender la relación entre partículas de entrada (fotones, electrones o positrones y la energía de las partículas), el material que se irradia (elemento del que está compuesto, espesor) y la señal de salida (tipos de partículas generados y energía). Finalmente, mostraremos que es posible crear imágenes de pinturas usando una fuente 60Co.

Reimagining ARUBA: Theoretical Optimization of the Treatment of Unruptured Brain Arteriovenous Malformations.

BACKGROUND AND PURPOSE: The results of the A Randomized Trial of Unruptured Brain Arteriovenous (ARUBA) study, indicating that conservative medical management of unruptured brain arteriovenous malformations (UBAVM) is superior to interventional therapy, have generated debates that have hampered their application into clinical practice. Irrespectively of study conclusions, it seems reasonable to explore how much better interventional therapy would have to be to become competitive with conservative medical management. METHODS: We conducted an exploratory analysis to replicate the original data from ARUBA. The functional form of the replicated ARUBA data, according to their Weibull distribution, allowed estimation of parameters. We carried out Monte Carlo simulations while introducing theoretical reductions of interventional risk, and the results were used to construct theoretical and example Kaplan-Meier curves from simulations. RESULTS: The "ARUBA Replication" analysis showed results nearly identical to those published in the study, with an estimated hazard ratio of 0.27 (95% CI: 0.14-0.55). At 50% interventional risk reduction, the simulations showed an estimated event rate of 14.9%, and the protective effect of conservative medical management was no longer statistically significant. Greater risk reductions hastened the time to benefit for interventional therapy, and an 80% risk reduction demonstrated superiority of interventional therapy at just over 2 years Hazard Ratio (HR: 1.44, 95% CI: 0.55-4.92). CONCLUSIONS: Reduction in risk of interventional therapy by 50%-80% results in more competitive clinical outcomes, equating or surpassing the benefit of conservative medical management of UBAVM. This conjecture should be taken into consideration in the design of future studies of this patient population, particularly because it is supported by recent observational studies.

Financial risk of increasing the follow-up period of breast cancer treatment currently covered by the Social Protection System in Health in México.

BACKGROUND: The objective of this work is to estimate the financial impact of increasing the monitoring period for breast cancer, which is financed by the Sistema de Protección Social en Salud (SPSS-Social Protection System in Health). METHODS: A micro-simulation model was developed to monitor a cohort of patients with breast cancer, and also an estimation was made on the probability of surviving the monitoring period financed by the SPSS. Using the Monte Carlo simulation, the maximum expected cost was estimated to broaden such monitoring. Morbimortality information of the Ministry of Health and cases of breast cancer treated by the SPSS were used. RESULTS: Between 2013 and 2026, the financial resources to provide monitoring during 10 years to women diagnosed with breast cancer would reach up to $3607.40 million pesos on a base scenario, $4151.79 million pesos on the pessimistic scenario and $3414.85 million pesos on an optimistic scenario. In the base scenario, additional expenditure represents an annual increase of 9.1% of resources allocated to treating this disease, and 3.0% of the availability of the resources for the Fondo de Protección contra Gastos Catastróficos (FPGC-Fund for Protection against Catastrophic Expenditure). CONCLUSIONS: Increasing monitoring for patients with breast cancer would not represent a financial risk to the sustainability of the FPGC, and could increase patients survival and life quality.

Evaluación por Monte Carlo de los métodos de corrección de dispersión con empleando colimador pinhole / Monte Carlo evaluation of scattering correction methods in studies using pinhole collimator

La dispersión es un efecto significativo a corregir para la cuantificación de actividad. El objetivo del trabajo fue estimar la influencia de la dispersión en estudios de tiroides con 131I y colimador pinhole (5 mm) empleando el método de Monte Carlo (MC) y evaluar la eficacia de los métodos de corrección de múltiples ventanas en este tipo de estudios. Para simular la geometría de la cámara gamma y el estudio de tiroides se utilizó el código de Monte Carlo GAMOS. Para validar la geometría del cabezal se simuló y verificó experimentalmente un maniquí de tiroides, comparando la sensibilidad estimada con la medida, experimentalmente en agua y aire. Para evaluar la influencia de la dispersión a escala clínica se simularon diferentes tamaños de tiroides y profundidades del tejido, se estimaron y compararon los resultados de los métodos de Triple Ventana, Doble Ventana y Doble Ventana Reducida. Se calcularon las diferencias relativas al valor de referencia obtenido por MC. La geometría modelada fue verificada y validada. La contribución de la dispersión a la imagen fue significativa y se ubicóentre el 27 y 40 % a escala no clínica. Las discrepancias de los resultados de los diferentes métodos de corrección de dispersión a escala clínica fueron significativas (p>95 %) y estuvieron en el rango entre 9 y 86 %. El método de mejores resultados fue el de la Doble Ventana Reducida (15 %) que mostró discrepancias entre 9 y 16 %. Se concluyó que el método de la Doble Ventana Reducida (15 %) fue el más eficiente de los estudiados

Scattering is quite important for image activity quantification. In order to study the scattering factors and the efficacy of 3 multiple window energy scatter correction methods during 131I thyroid studies with a pinhole collimator (5 mm hole) a Monte Carlo simulation (MC) was developed. The GAMOS MC code was used to model the gamma camera and the thyroid source geometry. First, to validate the MC gamma camera pinhole-source model, sensibility in air and water of the simulated and measured thyroid phantom geometries were compared. Next, simulations to investigate scattering and the result of triple energy (TEW), Double energy (DW) and Reduced double (RDW) energy windows correction methods were performed for different thyroid sizes and depth thicknesses. The relative discrepancies to MC real event were evaluated. Results: The accuracy of the GAMOS MC model was verified and validated. The image’s scattering contribution was significant, between 27-40 %. The discrepancies between 3 multiple window energy correction method results were significant (between 9-86 %). The Reduce Double Window methods (15%) provide discrepancies of 9-16 %. Conclusions: For the simulated thyroid geometry with pinhole, the RDW (15 %) was the most effective

Photocatalytic degradation of an emerging pollutant by TiO2-coated glass rings: a kinetic study.

This work presents the photocatalytic degradation of the pharmaceutical drug clofibric acid in a fixed-bed reactor filled with TiO2-coated glass rings. Experiments were carried out under UV radiation. A kinetic model that takes into account radiation absorption by means of the local surface rate of photon absorption (LSRPA) has been developed. The LSRPA was obtained from the results of a radiation model. The Monte Carlo method was employed to solve the radiation model, where the interaction between photons and TiO2-coated rings was considered. Data from experiments carried out with rings with different numbers of catalyst coatings and different irradiation levels were used to estimate the parameters of the kinetic model. A satisfactory agreement was obtained between model simulations and experimental results.

Spatial Association of Canine Rabies Outbreak and Ecological Urban Corridors, Arequipa, Peru.

In the city of Arequipa, Peru, a rabid dog was detected in March 2015, marking the reintroduction of the rabies virus in the area; more rabid dogs have been detected since then. The presence of free-roaming dogs in Arequipa seems to be higher in dry water channels, which are widespread in the city. We created a geographic information system (GIS) with surveillance data on the location of rabid dogs detected during the first year of the outbreak, as well as the water channels. We conducted a spatial analysis using Monte Carlo simulations to determine if detected rabid dogs were closer to the water channels than expected. Thirty rabid dogs were detected during the first year of the outbreak, and they were statistically associated with the water channels (average distance to closest water channel = 334 m; p-value = 0.027). Water channels might play a role in the ecology of free-roaming dog populations, functioning as ecological corridors. Landscape ecology could assist in understanding the impact of these urban structures on control activities and the persistence of transmission.

Determinación de la eficiencia de detección de Descripción: Descripción: D:/Scielo/Nucleus html/n 59/img/e01085916.jpgen tiroides utilizando el método Monte Carlo / Determination of the detection efficiency of Descripción: Descripción: D:/Scielo/Nucleus html/n 59/img/e01085916.jpgin thiroid using Monte Carlo method

El Método Monte Carlo fue la base para la estimación de la eficiencia de detección de , utilizando el detector identiFINDER ultra en geometría “tiroides”. Se discute la idoneidad de la metodología de calibración al comparar los resultados del Método Monte Carlo Directo y Corregido, con los valores de eficiencia calculados experimentalmente. El Método Monte Carlo Corregido fue la metodología adoptada debido a que el porcentaje de error estimado, respecto a los resultados experimentales, fue menor que el 10 %. Para las simulaciones, los parámetros geométricos del detector fueron optimizados, utilizando un estudio de tomografía computarizada. El arreglo detector – fuente puntual- fue simulado para obtener los factores de corrección a las distancias prefijadas, y el arreglo detector – maniquí simulador de tiroides- fue simulado para la obtención de la curva de eficiencia de detección, en función de la distancia de medición. Para validar la metodología propuesta, el Laboratorio de Dosimetría Interna del Centro de Protección e Higiene de las Radiaciones participó en un ejercicio de intercomparación regional de estimación, de actividad medida en tiroides, se utilizó para el cálculo de la misma, tanto la metodología tradicional de cálculo de eficiencia como la metodología basada en la utilización del Método Monte Carlo, y se alcanzaron resultados satisfactorios, en todos los casos. Como resultado final de este trabajo, fue obtenida la curva de eficiencia de detección en función de la distancia de , sin necesidad de utilizar simuladores físicos, supliendo, así, la carencia actual de los mismos.

Monte Carlo Method was the base to estimate the detection efficiency of of the identiFINDER ultra detector in “thyroid” geometry. The suitability of the calibration methodology is discussed using a comparison of the results of the Direct Monte Carlo Method and the Transfer Monte Carlo Method calculations with the values of experimentally calculated efficiency. Transfer Monte Carlo Method was the elected methodology because of the differences with the real detection efficiency stay below 10 %. In the simulations, the geometric parameters of the detector were found using a tomography study. The arrangement detector – point source was simulated to obtain the correction factors for preset distances, and the arrangement detector – thyroid phantom was simulated to obtain the detection efficiency curve in function of the distance for . In order to validate the proposed methodology the Internal Dosimetry Laboratory of the Centre for Radiation Protection and Hygiene participated in a regional intercomparison exercise of measured activity estimation in thyroid, for the estimation were used the traditional calculation methodology as well as the methodology base on Monte Carlo Method, the results were satisfactory in both cases. As a final result, the curves of detection efficiency for the measurement of in the thyroid gland was obtained without using physical phantoms, replacing the current lack of it.