Dosimetric and biologic intercomparison between electron and proton FLASH beams.

BACKGROUND AND PURPOSE: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASHvs. pFLASH has yet been performed and constitutes the aim of the present study. MATERIALS AND METHODS: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models. RESULTS: The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was -1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate. CONCLUSION: Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate.

Dosimetric and biologic intercomparison between electron and proton FLASH beams.

Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. Results: Doses measured at Gantry1 were in agreement (± 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. Conclusion: Despite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

Caracterización de la Lámpara Flash-LED: EBNeuro Usada para Adquirir Potenciales Evocados Visuales en Ratas / Characterization of the Flash-LED Lamp: EBNeuro Used to Acquired Visual Evoked Potentials in Rats

Resumen: La señal de la amplitud en análisis de Potenciales Evocados Visuales (PEVs) es una variable que depende del tipo y posición de los electrodos, de la fuente, del estímulo y por consecuente, de la intensidad luminosa por lo que es fundamental reportarla para cada diseño experimental y así, garantizar su reproducibilidad. El objetivo de este trabajo es caracterizar una lámpara con 96 LEDs para la adquisición de PEVs en ratas. Se midió la iluminancia y la intensidad luminosa promedio en un sistema espacial XYZ de 8 cm3 aplicable a un sistema estereotáxico para la fijación de ratas. Se realizaron desplazamientos cada 2 cm en cada plano. Se observó que debido a la distribución geométrica de los LEDs la distribución de la iluminancia no sigue la ley del inverso cuadrado, ya que aumenta conforme la lámpara se aleja. Finalmente, se seleccionó una coordenada para la colocación del ojo de la rata empleando una intensidad luminosa promedio para la adquisición del PEV de 1.043 cd e iluminancia de 128.77 luxes a una distancia ojo-lámpara de 9 cm. Una vez caracterizada la intensidad luminosa y de acuerdo con los PEVs obtenidos, esta lámpara puede utilizarse para estudios PEV en ratas en investigaciones posteriores.

Abstract: Signal amplitude for recordings of Visual Evoked Potentials (VEPs) is a variable dependent on the type and position of the electrodes, the source, the stimulus and consequently the luminous intensity; therefore, it is relevant to report it to assure experimental reproducibility. The objective of this work is to characterize flash lamp with 96 LEDs in order to perform the acquisition of VEPs in rats. We measure the illuminance and mean light intensity on space system XYZ of 8 cm3 corresponding to a stereotaxic frame for rodents. Displacements were performed every 2 cm in each plane. Because of the geometric distribution of the LEDs in the EBNeuro lamp the spatial distribution of illuminance does not follow the law of the inverse square, because the illuminance increases as the lamp goes away. Finally a spatial coordinate was selected for the rat eye positioning were the mean luminous intensity was 1.043 cd and 128.77 luxes of illuminance at an eye-lamp distance of 9 cm. According to the obtained VEPs and spatial characterization this lamp can be used for acquire of recordings PEV in rats for further investigations.

Sensitive high performance liquid chromatographic assay for nitazoxanide metabolite in plasma.

A sensible and specific HPLC analytical method for the determination of tizoxanide (TZO), the active metabolite of nitazoxanide (NTZ) in rat plasma was developed and validated. Samples of 200 microL were efficiently deproteinized with acetonitrile. Assay was performed using a C18 CC with a ternary gradient elution of 50 mmol x L(-1) KH2PO4 : acetonitrile : methanol and UV/Vis detection at 416 nm. The analytical method was linear in a range of 10-1280 ng x mL(-1), precise (RSD % > 2.2), accurate (RE % < 7.8) and with high recovery (% > 95%). Stability studies showed that TZO was stable in plasma for short and long-time period (45 days) and proved to be suitable for pharmacokinetic studies of NTZ in rats. The method was also evaluated using human plasma samples and no statistical differences were found in the response-curve between rat and human samples.

Development and validation of a spatially explicit individual-based mixed crop growth model.

Spatial disposition of plants in intercrops, and differences in sowing time between species, can strongly affect their ecological interactions and, in consequence, the system's viability and performance. Empirical exploration of a wide range of spatial and temporal plant arrangements is costly and time-consuming. Modelling the growth of mixed crops is a tool which, combined with empirical tests, can greatly reduce the time and investment required for this task. Spatially explicit, individual-based dynamic models seem well suited for this purpose; their exploration and experimental validation for the case of simple, two-species, artificial plant communities, can also provide further insight as to how the spatial and temporal scales of a plant's multispecific neighbourhood affect its growth and performance. The aim of this investigation was to further develop a published spatially explicit individual-based mixed crop growth model [Vandermeer, J. H. (1989). The Ecology of Intercropping, Cambridge, U.K.: Cambridge University Press, p. 237], and to validate it experimentally. With this purpose in mind: (1) computer programs to simulate individual plant growth and to perform statistical analysis of both deterministic and stochastic versions of the model were developed; (2) the model was parametrized using a complex experimental diculture with several cohorts and spatial arrangements; (3) the predictive capacity of the model was tested using independent spatio-temporal experimental arrangements; (4) a modified version of the model was written, which abandons the assumption of linearity of the neighbourhood index at the cost of increasing the number of parameters; (5) The performance of stochastic versions of both Vandermeer's and our modified model were compared, employing a non-parametric measure of goodness of fit. We conclude that this approach to modelling plant growth subject to intra and interspecific competition is a remarkably efficient, general, conceptually elegant, heuristic tool whose predictive power can be further improved when nonlinear terms are introduced into the neighbourhood competition index, as done in our modified version of Vandermeer's model.