Monte Carlo Analysis and Physics Characterization of a Novel Nanoparticle Detector for Medical and Micro-dosimetry Applications

The outcomes for both (i) radiation therapy and (ii) preclinical small animal radio- biology studies are dependent on the delivery of a known quantity of radiation to a specific and intentional location. Adverse effects can result from these procedures if the dose to the target is too high or low, and can also result from an incorrect spatial distribution in which nearby normal healthy tissue can be undesirably damaged by poor radiation delivery techniques. Thus, in mice and humans alike, the spatial dose distributions from radiation sources should be well characterized in terms of the absolute dose quantity, and with pin-point accuracy. When dealing with the steep spatial dose gradients consequential to either (i) high dose rate (HDR) brachytherapy or (ii) within the small organs and tissue inhomogeneities of mice, obtaining accurate and highly precise dose results can be very challenging, considering commercially available radiation detection tools, such as ion chambers, are often too large for in-vivo use.

In this dissertation two tools are developed and applied for both clinical and preclinical radiation measurement. The first tool is a novel radiation detector for acquiring physical measurements, fabricated from an inorganic nano-crystalline scintillator that has been fixed on an optical fiber terminus. This dosimeter allows for the measurement of point doses to sub-millimeter resolution, and has the ability to be placed in-vivo in humans and small animals. Real-time data is displayed to the user to provide instant quality assurance and dose-rate information. The second tool utilizes an open source Monte Carlo particle transport code, and was applied for small animal dosimetry studies to calculate organ doses and recommend new techniques of dose prescription in mice, as well as to characterize dose to the murine bone marrow compartment with micron-scale resolution.

Hardware design changes were implemented to reduce the overall fiber diameter to <0.9 mm for the nano-crystalline scintillator based fiber optic detector (NanoFOD) system. Lower limits of device sensitivity were found to be approximately 0.05 cGy/s. Herein, this detector was demonstrated to perform quality assurance of clinical 192Ir HDR brachytherapy procedures, providing comparable dose measurements as thermo-luminescent dosimeters and accuracy within 20% of the treatment planning software (TPS) for 27 treatments conducted, with an inter-quartile range ratio to the TPS dose value of (1.02-0.94=0.08). After removing contaminant signals (Cerenkov and diode background), calibration of the detector enabled accurate dose measurements for vaginal applicator brachytherapy procedures. For 192Ir use, energy response changed by a factor of 2.25 over the SDD values of 3 to 9 cm; however a cap made of 0.2 mm thickness silver reduced energy dependence to a factor of 1.25 over the same SDD range, but had the consequence of reducing overall sensitivity by 33%.

For preclinical measurements, dose accuracy of the NanoFOD was within 1.3% of MOSFET measured dose values in a cylindrical mouse phantom at 225 kV for x-ray irradiation at angles of 0, 90, 180, and 270˝. The NanoFOD exhibited small changes in angular sensitivity, with a coefficient of variation (COV) of 3.6% at 120 kV and 1% at 225 kV. When the NanoFOD was placed alongside a MOSFET in the liver of a sacrificed mouse and treatment was delivered at 225 kV with 0.3 mm Cu filter, the dose difference was only 1.09% with use of the 4x4 cm collimator, and -0.03% with no collimation. Additionally, the NanoFOD utilized a scintillator of 11 µm thickness to measure small x-ray fields for microbeam radiation therapy (MRT) applications, and achieved 2.7% dose accuracy of the microbeam peak in comparison to radiochromic film. Modest differences between the full-width at half maximum measured lateral dimension of the MRT system were observed between the NanoFOD (420 µm) and radiochromic film (320 µm), but these differences have been explained mostly as an artifact due to the geometry used and volumetric effects in the scintillator material. Characterization of the energy dependence for the yttrium-oxide based scintillator material was performed in the range of 40-320 kV (2 mm Al filtration), and the maximum device sensitivity was achieved at 100 kV. Tissue maximum ratio data measurements were carried out on a small animal x-ray irradiator system at 320 kV and demonstrated an average difference of 0.9% as compared to a MOSFET dosimeter in the range of 2.5 to 33 cm depth in tissue equivalent plastic blocks. Irradiation of the NanoFOD fiber and scintillator material on a 137Cs gamma irradiator to 1600 Gy did not produce any measurable change in light output, suggesting that the NanoFOD system may be re-used without the need for replacement or recalibration over its lifetime.

For small animal irradiator systems, researchers can deliver a given dose to a target organ by controlling exposure time. Currently, researchers calculate this exposure time by dividing the total dose that they wish to deliver by a single provided dose rate value. This method is independent of the target organ. Studies conducted here used Monte Carlo particle transport codes to justify a new method of dose prescription in mice, that considers organ specific doses. Monte Carlo simulations were performed in the Geant4 Application for Tomographic Emission (GATE) toolkit using a MOBY mouse whole-body phantom. The non-homogeneous phantom was comprised of 256x256x800 voxels of size 0.145x0.145x0.145 mm3. Differences of up to 20-30% in dose to soft-tissue target organs was demonstrated, and methods for alleviating these errors were suggested during whole body radiation of mice by utilizing organ specific and x-ray tube filter specific dose rates for all irradiations.

Monte Carlo analysis was used on 1 µm resolution CT images of a mouse femur and a mouse vertebra to calculate the dose gradients within the bone marrow (BM) compartment of mice based on different radiation beam qualities relevant to x-ray and isotope type irradiators. Results and findings indicated that soft x-ray beams (160 kV at 0.62 mm Cu HVL and 320 kV at 1 mm Cu HVL) lead to substantially higher dose to BM within close proximity to mineral bone (within about 60 µm) as compared to hard x-ray beams (320 kV at 4 mm Cu HVL) and isotope based gamma irradiators (137Cs). The average dose increases to the BM in the vertebra for these four aforementioned radiation beam qualities were found to be 31%, 17%, 8%, and 1%, respectively. Both in-vitro and in-vivo experimental studies confirmed these simulation results, demonstrating that the 320 kV, 1 mm Cu HVL beam caused statistically significant increased killing to the BM cells at 6 Gy dose levels in comparison to both the 320 kV, 4 mm Cu HVL and the 662 keV, 137Cs beams.

Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.

Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations in cancer patients. A population-based retrospective cohort was identified from 31 Phase 2-3 oncology trials (excluding targeted therapies) conducted from 1985 to 2005 to evaluate background rates of LC elevations in patients (n = 3998) with or without liver metastases. Patients with baseline liver metastases (29% of patients) presented with a 3% prevalence of alanine transaminase (ALT) ≥ 3x upper limits normal (ULN) and 0.2% prevalence of bilirubin ≥ 3xULN. During follow-up, the incidence (per 1000 person-months) of new onset ALT elevations ≥3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2 (95% CI: 0.9, 4.5) in patients without and with liver metastases, respectively. No new incident cases of ALT and bilirubin elevations suggestive of severe liver injury occurred among those with liver metastases; a single case occurred among those without metastasis. Regardless of the presence of liver metastases, LC elevations were rare in cancer patients during oncology trials, which may be due to enrollment criteria. Our study validates uniform thresholds for detection of LC elevations in oncology studies and serves as an empirical referent point for comparing liver enzyme abnormalities in oncology trials of novel targeted therapies. These data support uniform LC stopping criteria in oncology trials.

Absolute line intensities for formic acid and dissociation constant of the dimer

Absolute line intensities in the v6 and v8 interacting bands of trans-HCOOH, observed near 1105.4 and 1033.5 cm -1, respectively, and the dissociation constant of the formic acid dimer (HCOOH)2 have been measured using Fourier transform spectroscopy at a resolution of 0.002 cm-1. Eleven spectra of formic acid, at 296.0(5) K and pressures ranging from 14.28(25) to 314.0(24) Pa, have been recorded between 600 and 1900 cm-1 with an absorption path length of 19.7(2) cm. 437 integrated absorption coefficients have been measured for 72 lines in the v6 band. Analysis of the pressure dependence yielded the dissociation constant of the formic acid dimer, k p=361(45) Pa, and the absolute intensity of the 72 lines of HCOOH. The accuracy of these results was carefully estimated. The absolute intensities of four lines of the weak v8 band were also measured. Using an appropriate theory, the integrated intensity of the v6 and v 8 bands was determined to be 3.47 × 1017 and 4.68 × 10-19 cm-1/(molecule cm-1) respectively, at 296 K. Both the dissociation constant and integrated intensities were compared to earlier measurements. © 2007 American Institute of Physics.

Comportamiento de las formas de fósforo en un Ultisol con diferentes manejos de implantación forestal

En sistemas forestales, la preparación del terreno antes de la implantación de un monte adquiere gran importancia debido al impacto de diferentes sistemas de manejo de residuos sobre el capital de nutrientes. El objetivo de éste trabajo fue estudiar la dinámica de las fracciones de P en una plantación de Pinus taeda (L) con diferentes sistemas de manejo de residuos de la cosecha anterior y evaluar el efecto de estas prácticas sobre la adsorción de P en un Ultisol de la provincia de Misiones. Para ello se realizó un ensayo con un diseño experimental de bloques completos al azar con los siguientes tratamientos: 1) sin residuos: extracción de residuos y mantillo y plantación con Pinus taeda; 2) quema: quema de residuos y rastra y plantación con Pinus taeda; 3) plantación directa: conservación de residuos de la cosecha y plantación con Pinus taeda; 4) capuera: conservación de residuos y desarrollo de la vegetación natural denominada capuera y 5) monte nativo (MN). A los 6 y 9 años de aplicados los tratamientos se muestreó a dos profundidades superficial (0-5 cm) y subsuperficial (5-15 cm), y se realizó el fraccionamiento secuencial de P de Hedley, las curvas de adsorción y el cálculo de los coeficientes e índices derivados de las mismas. También fueron evaluadas las variables químicas COT, Ca, Mg, Na, K, suma de cationes, CIC, porcentaje de saturación de bases, pH en agua y pH en ClK (1M). Como resultado se observó que la extracción total de residuos presentó el mayor impacto negativo sobre el P orgánico, lábil y moderadamente lábil en la capa superficial del suelo de 0 a 5 cm. Con respecto a la quema de residuos, después de transcurridos 9 años, no se presentó ningún efecto sobre las fracciones de P más disponibles del suelo. También se observó que ninguna de las distintas prácticas de manejo aplicadas produjo cambios en el contenido de P total. En relación al efecto de los distintos manejos sobre la capacidad de adsorción del P se observó que donde se eliminaron los residuos, ya sea por extracción manual o por quema, se presentó un mayor efecto de adsorción de este nutriente por parte del suelo. Cuando se estudió el cultivo de pino comparado con monte nativo, se observó que la implantación del bosque produjo una mayor adsorción de P en el suelo. De acuerdo a los resultados obtenidos es de esperar que, en el mediano plazo, el manejo con conservación superficial de los residuos conduzca a un aumento de los niveles de COT y de las formas orgánicas de P más disponibles y por otro lado, a una disminución de la sorción de P por parte del suelo. Por lo tanto, es recomendable la aplicación de dicha práctica para reducir la exportación de nutrientes y sostener los aportes de materia orgánica al suelo como mecanismo de protección y reserva de nutrientes

Aplicación anticipada de fósforo : efectos sobre la disponibilidad del nutriente, eficiencia de uso y rendimiento.

Tradicionalmente el P es colocado en la línea de siembra, aunque las cantidades que pueden agregarse son relativamente bajas por razones operativas y riesgos de fitotoxicidad. Las aplicaciones al voleo podrían presentar una menor eficiencia, pero permiten agregar mayores dosis. Localmente existen experiencias que comparan aplicaciones en línea y anticipadas al voleo con una única dosis, pero no hay estudios que evalúen comparativamente las aplicaciones al voleo a la siembra y antes de la siembra con un rango de dosis. El tiempo prolongado de contacto entre el nutriente y el suelo incrementaría los procesos de fijación, aunque esto podría ser compensado por una mayor incorporación. Los objetivos de este trabajo fueron evaluar cambios del P disponible a inicios del ciclo del cultivo de maíz, las respuestas y eficiencias agronómicas y de recuperación del P para las distintas dosis, momentos y formas de aplicación de fertilizante fosforado. Para responder a los objetivos se realizaron tres ensayos de campo en Hapludoles del Partido de Junín y se evaluaron 9 tratamientos: del 0 a 8 corresponden a un factorial con cuatro dosis (10, 20, 30 y 40 kg P ha -1) aplicados al voleo y dos momentos (anticipado -90 días antes de la siembra del maíz- y al momento de la siembra), un testigo y un tratamiento con P en línea (con la dosis de 20 kg P ha-1). Se midieron: contenido de P disponible, biomasa aérea, contenido de P absorbido y rendimiento de maíz. Con la fertilización anticipada hubo una tendencia a menores contenidos de P de 0-5 cm a inicios del ciclo del cultivo, pero no se observaron diferencias en crecimiento de maíz en ningún estado fenológico. No se detectaron diferencias en rendimiento, sin embargo se observó una tendencia a respuestas superiores con las aplicaciones a la siembra sólo con las dosis más altas. Se registraron efectos de las dosis sobre la producción de biomasa aérea, el rendimiento en grano y el contenido de P disponible. Las eficiencias de recuperación (ERP) y eficiencias agronómicas (AE) no difirieron entre momentos de aplicación, sin embargo las EA fueron un 26 por ciento superiores con las aplicaciones a la siembra. Las ERP medias halladas, por el método de la diferencia, fueron de 6,5 por ciento con el cultivo en sexta hoja (V6) y 3,2 por ciento en madurez fisiológica (MF). No se detectaron diferencias según el método de ubicación del P.

Fertilización y estres salino en plantas ornamentales anuales

p.93-100

Demografía de semillas de Sorghum halepense (L.) Pers. en un suelo cultivado con maíz

p.29-37

Evaluación del efecto de la fertilización con boro para híbridos de girasol en suelos haplustoles énticos de Gral. Pico, Departamento de Maracó, Prov. de La Pampa

p.45-49

Respuesta del cultivo de maíz a la fertilización nitrogenada en la pampa ondulada, campañas 1980-81 - 1983-84 : modelos predictivos y explicativos

p.65-84

Dinámica de la población de semillas de Sorghum halepense (L) Pers. en un suelo arable : I-efecto de la germinación (in situ)

p.1-9

Propiedades físicas de un compost obtenido a partir de residuos de poda

p.95-99

Effect of caffeine ingestion during prolonged exhaustive exercise on salivary immunoglobulin A, alpha-amylase and cortisol

Exercise can have deleterious effects on the secretion of salivary immunoglobulin A (s-IgA), which appears to be related to perturbations in sympatheticoadrenal activation (Teeuw et al., 2004). Caffeine, commonly used for its ergogenic properties is associated with increased sympathetic nervous system activity, and it has been previously shown that caffeine ingestion before intensive cycling enhances s-IgA responses during exercise (Bishop et al., 2006). Therefore, the aim of the present study was to examine the effect of a performance cereal bar, containing caffeine, before and during prolonged exhaustive cycling on exercise performance and the salivary secretion of IgA, alpha-amylase activity and cortisol. Using a randomised cross-over design and following a 10 – 12 hour overnight fast, 12 trained cyclists, mean (SEM) age: 21(1) yr; height: 179(2) cm; body mass: 73.6(2.5) kg; maximal oxygen uptake, VO2max: 57.9(1.2) completed 2.5 h of cycling at 60%VO2max (with regular water ingestion) on a stationary ergometer, which was followed by a ride to exhaustion at 75% VO2max. Immediately before exercise, and after 55 min and 115 min of exercise participants ingested a 0.9 MJ cereal bar containing 45 g carbohydrate, 5 g protein, 3 g fat and 100 mg of caffeine (CAF) or an isocaloric noncaffeine bar (PLA). Unstimulated timed saliva samples were collected immediately before exercise, after 70 min and 130 min of exercise, and immediately after the exhaustive exercise bout. Saliva was analysed for s-IgA, alpha-amylase activity and cortisol concentration. Saliva flow rates were determined to calculate the s-IgA secretion rate. Data were analysed using a 2-way repeated measures ANOVA and post-hoc t-tests with Holm Bonferroni adjustments applied where appropriate. Time to exhaustion was 35% longer in CAF compared with PLA ((2177 (0.2) vs 1615 (0.16) s; P < 0.05)). Saliva flow rate did not change significantly during the exercise protocol. Exercise was associated with elevations in s-IgA concentration (9% increase), s-IgA secretion rate (24% increase) and alpha-amylase activity (224% increase) post-exhaustion (P < 0.01), but there was no effect of CAF on these responses. Salivary cortisol concentration increased by 64% post-exhaustion in the CAF trial only (P < 0.05), indicating an increase in adrenal activity following caffeine ingestion. Values were 35.7 (5.5) and 19.6 (3.4) nmol/L post-exhaustion for CAF and PLA, respectively. These findings show that ingestion of a caffeine containing cereal bar during prolonged exhaustive cycling enhances endurance performance, increases salivary cortisol secretion post-exhaustion, but does not affect the exercise-induced increases in s-IgA or alpha-amylase activity.

Evaluation of the new ESR network software for the retrieval of direct sun products from cimel ce318 and prede pom01 sun-sky radiometers.

The European Skynet Radiometers network (EuroSkyRad or ESR) has been recently established as a research network of European PREDE sun-sky radiometers. Moreover, ESR is federated with SKYNET, an international network of PREDE sun-sky radiometers mostly present in East Asia. In contrast to SKYNET, the European network also integrates users of the CIMEL CE318 sky–sun photometer. Keeping instrumental duality in mind, a set of open source algorithms has been developed consisting of two modules for (1) the retrieval of direct sun products (aerosol optical depth, wavelength exponent and water vapor) from the sun extinction measurements; and (2) the inversion of the sky radiance to derive other aerosol optical properties such as size distribution, single scattering albedo or refractive index. In this study we evaluate the ESR direct sun products in comparison with the AERosol RObotic NETwork (AERONET) products. Specifically, we have applied the ESR algorithm to a CIMEL CE318 and PREDE POM simultaneously for a 4-yr database measured at the Burjassot site (Valencia, Spain), and compared the resultant products with the AERONET direct sun measurements obtained with the same CIMEL CE318 sky–sun photometer. The comparison shows that aerosol optical depth differences are mostly within the nominal uncertainty of 0.003 for a standard calibration instrument, and fall within the nominal AERONET uncertainty of 0.01–0.02 for a field instrument in the spectral range 340 to 1020 nm. In the cases of the Ångström exponent and the columnar water vapor, the differences are lower than 0.02 and 0.15 cm, respectively. Therefore, we present an open source code program that can be used with both CIMEL and PREDE sky radiometers and whose results are equivalent to AERONET and SKYNET retrievals.

Effect of elevated CO2 on the dynamics of particle-attached and free-living bacterioplankton communities in an Arctic fjord

In the frame of the European Project on Ocean Acidification (EPOCA), the response of an Arctic pelagic community (<3 mm) to a gradient of seawater pCO(2) was investigated. For this purpose 9 large-scale in situ mesocosms were deployed in Kongsfjorden, Svalbard (78 degrees 56.2' N, 11 degrees 53.6' E), in 2010. The present study investigates effects on the communities of particle-attached (PA; >3 mu m) and free-living (FL; <3 mu m > 0.2 mu m) bacteria by Automated Ribosomal Intergenic Spacer Analysis (ARISA) in 6 of the mesocosms, ranging from 185 to 1050 mu atm initial pCO(2), and the surrounding fjord. ARISA was able to resolve, on average, 27 bacterial band classes per sample and allowed for a detailed investigation of the explicit richness and diversity. Both, the PA and the FL bacterioplankton community exhibited a strong temporal development, which was driven mainly by temperature and phytoplankton development. In response to the breakdown of a picophytoplankton bloom, numbers of ARISA band classes in the PA community were reduced at low and medium CO2 (similar to 185-685 mu atm) by about 25 %, while they were more or less stable at high CO2 (similar to 820-1050 mu atm). We hypothesise that enhanced viral lysis and enhanced availability of organic substrates at high CO2 resulted in a more diverse PA bacterial community in the post-bloom phase. Despite lower cell numbers and extracellular enzyme activities in the post-bloom phase, bacterial protein production was enhanced in high CO2 mesocosms, suggesting a positive effect of community richness on this function and on carbon cycling by bacteria.

Changes in significant and maximum wave heights in the Norwegian Sea

This paper analyses 10 years of in-situ measurements of significant wave height (Hs) and maximum wave height (Hmax) from the ocean weather ship Polarfront in the Norwegian Sea. The 30-minute Ship-Borne Wave Recorder measurements of Hmax and Hs are shown to be consistent with theoretical wave distributions. The linear regression between Hmax and Hs has a slope of 1.53. Neither Hs nor Hmax show a significant trend in the period 2000–2009. These data are combined with earlier observations. The long-term trend over the period 1980–2009 in annual Hs is 2.72 ± 0.88 cm/year. Mean Hs and Hmax are both correlated with the North Atlantic Oscillation (NAO) index during winter. The correlation with the NAO index is highest for the more frequently encountered (75th percentile) wave heights. The wave field variability associated with the NAO index is reconstructed using a 500-year NAO index record. Hs and H max are found to vary by up to 1.42 m and 3.10 m respectively over the 500-year period. Trends in all 30-year segments of the reconstructed wave field are lower than the trend in the observations during 1980–2009. The NAO index does not change significantly in 21st century projections from CMIP5 climate models under scenario RCP85, and thus no NAO-related changes are expected in the mean and extreme wave fields of the Norwegian Sea.