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The development of new radiotherapy technologies is a long-term process, which requires proving the general concept although clinical requirements with respect to beam quality and controlled dose delivery may not yet be fulfilled. Exemplarily, the necessary radiobiological experiments with laser-accelerated ion beams are challenged by fluctuating beam intensities. Based on tumour-growth data and dose values obtained in an in-vivo trial comparing the biological efficacy of laser-driven and conventional Linac electrons [2], different statistical approaches for analysis were compared. In addition to the classical averaging per dose point, which excludes animals with high dose deviations, multivariable linear regression, Cox regression and a Monte-Carlo-based approach were tested as alternatives that include all animals in statistical analysis. The four methods were compared based on experimental and simulated data. All applied statistical approaches revealed a comparable radiobiological efficacy of laser-driven and conventional Linac electrons, confirming the experimental conclusion. However, in the simulation study, significant differences in dose-response were observed by all methods except for the conventional method. Thereby, these statistical approaches may allow for reducing the total number of required animals in future pre-clinical trials.

Introduction: The development of new radiotherapy technologies is a long time process which requires proving the general concept although clinical requirements with respect to beam quality and controlled dose delivery may not yet be fulfilled. Exemplarily, the necessary radiobiological experiments with laser-accelerated ion beams, which promise to compact ion radiotherapy facilities, are challenged by low particle energy and fluctuating beam intensities delivered by currently available laser systems. The first issue was handled by establishing a small tumour model on mouse ear that allows full penetration by ~25 MeV proton beams [1], whereas the latter, i.e. the subsequent deviations of the delivered from the prescribed dose, should be considered mathematically. Methods: Based on tumour growth data and dose values obtained in a preceding in vivo trial comparing the biological efficacy of laser-driven and conventional LINAC electrons [2], different mathematical approaches to determine corresponding dose-response relationships were compared. During this experiment, the beam intensity fluctuations were not fully gathered by online dosimetry, which results in deviations of more than 10 % from scheduled dose as measured by retrospective absolute film dosimetry. Instead of classical averaging-per-dose point, which excludes animals with high dose deviations, multivariate linear regression, Cox regression and a Monte Carlo based approach were tested as alternatives to include all animals in statistical analysis. Results: The application of different mathematical approaches to the same set of experimental tumour growth data and dose values led to similar results, revealing a comparable radiobiological efficacy of laser-driven and conventional LINAC electrons. Although the inclusion of those animals that were previously excluded because of more than 10% dose deviation did not change the experimental conclusion, the new mathematical approaches allowed for including all animals in the analysis. Comparing the different approaches, multivariate linear regression and Cox regression were considered as most feasible for future analysis, since they were already implemented in commercial statistical software, like SPSS (IBM). Conclusion: The previously established small animal tumour model on mouse ear [1] together with the recently tested regression methods enable the investigation and evaluation of beams at new accelerators relative to their conventional equivalents despite their still limited beam stability, like laser-driven particle beams. The tested mathematical approaches allow for increasing the number of animals in analysis and therewith reduce the total number of animals in experiment with respect to the 3R of animal experimentation. Acknowledgement: The work was supported by the German Government, Federal Ministry of Education and Research, grant nos. 03ZIK445 and 03Z1N511. [1] Beyreuther et al. An optimized small animal tumour model for experimentation with low energy protons. PLOS One,2017; 12: e0177428. [2] Oppelt et al. Comparison study of in vivo dose response to laser-driven versus conventional electron beam. Radiat Environ Biophys, 2015; 54:155-166.

International audience; We present two separate time series of the near-Earth heliospheric magnetic field strength (B) based on geomagnetic data and sunspot number (SSN). The geomagnetic-based B series from 1845 to 2013 is a weighted composite of two series that employ the interdiurnal variability index; this series is highly correlated with in situ spacecraft measurements of B (correlation coefficient, r = 0.94; mean square error, MSE = 0.16 nT2). The SSN-based estimate of B, from 1750 to 2013, is a weighted composite of eight time series derived from two separate reconstruction methods applied to four different SSN time series, allowing determination of the uncertainty from both the underlying sunspot records and the B reconstruction methods. The SSN-based composite is highly correlated with direct spacecraft measurements of B and with the composite geomagnetic B time series from 1845 to 2013 (r = 0.91; MSE = 0.24 nT2), demonstrating that B can accurately reconstructed by both geomagnetic and sunspot-based methods. The composite sunspot and geomagnetic B time series, with uncertainties, are provided as supporting information.

This is Part 2 of a study of the near-Earth heliospheric magnetic field strength, B, since 1750. Part 1 produced composite estimates of B from geomagnetic and sunspot data over the period 1750–2013. Sunspot-based reconstructions can be extended back to 1610, but the paleocosmic ray (PCR) record is the only data set capable of providing a record of solar activity on millennial timescales. The process for converting 10Be concentrations measured in ice cores to B is more complex than with geomagnetic and sunspot data, and the uncertainties in B derived from cosmogenic nuclides (~20% for any individual year) are much larger. Within this level of uncertainty, we find reasonable overall agreement between PCR-based B and the geomagnetic- and sunspot number-based series. This agreement was enhanced by excising low values in PCR-based B attributed to high-energy solar proton events. Other discordant intervals, with as yet unspecified causes remain included in our analysis. Comparison of 3 year averages centered on sunspot minimum yields reasonable agreement between the three estimates, providing a means to investigate the long-term changes in the heliospheric magnetic field into the past even without a means to remove solar proton events from the records.

International audience; This is Part 2 of a study of the near-Earth heliospheric magnetic field strength, B, since 1750. Part 1 produced composite estimates of B from geomagnetic and sunspot data over the period 1750-2013. Sunspot-based reconstructions can be extended back to 1610, but the paleocosmic ray (PCR) record is the only data set capable of providing a record of solar activity on millennial timescales. The process for converting 10Be concentrations measured in ice cores to B is more complex than with geomagnetic and sunspot data, and the uncertainties in B derived from cosmogenic nuclides (~20% for any individual year) are much larger. Within this level of uncertainty, we find reasonable overall agreement between PCR-based B and the geomagnetic- and sunspot number-based series. This agreement was enhanced by excising low values in PCR-based B attributed to high-energy solar proton events. Other discordant intervals, with as yet unspecified causes remain included in our analysis. Comparison of 3 year averages centered on sunspot minimum yields reasonable agreement between the three estimates, providing a means to investigate the long-term changes in the heliospheric magnetic field into the past even without a means to remove solar proton events from the records.

The solar meridional circulation is a "slow", large scale flow that transports magnetic field and plasma throughout the convection zone in the (r, theta) plane and plays a crucial role in controlling the magnetic cycle solutions presented by flux transport dynamo models. Observations indicate that this flow speed varies in anti-phase with the solar cycle at the solar surface. A possible explanation for the source of this variation is based on the fact that inflows into active regions alter the global surface pattern of the meridional circulation. In this work we examine the meridional circulation profile that emerges from a 3D global simulation of the solar convection zone, and its associated dynamics. We find that at the bottom of the convection zone, in the region where the toroidal magnetic field accumulates, the meridional circulation is highly modulated through the action of a magnetic torques and thus provides evidence for a new mechanism to explain the observed cyclic variations.

This article reviews some of the leading results obtained in solar dynamo physics by using temporal oscillator models as a tool to interpret observational data and dynamo model predictions. We discuss how solar observational data such as the sunspot number is used to infer the leading quantities responsible for the solar variability during the last few centuries. Moreover, we discuss the advantages and difficulties of using inversion methods (or backward methods) over forward methods to interpret the solar dynamo data. We argue that this approach could help us to have a better insight about the leading physical processes responsible for solar dynamo, in a similar manner as helioseismology has helped to achieve a better insight on the thermodynamic structure and flow dynamics in the Sun's interior., 28 pages; 16 figures, ISSI Workshop 11-15 November 2013 - The Solar Cycle, http://www.issibern.ch/program/workshops.html

We develop and subsequently explore the solution space of a simple flux transport dynamo model that incorporates a time dependent large scale meridional circulation. Based on recent observations we prescribed an analytical form for the amplitude of this circulation and study its impact in the evolution of the magnetic field. We find that cyclic variations in the amplitude and frequency of the meridional flow affect the strength of the solar cycle. Variations in the amplitude of the fluctuations influence the shape of the solar cycle but are only relevant to the cycle's strength variations when they occur at a frequency different from or out of phase of the solar cycle's., 5 pages, 4 figures. Accepted for publication in MNRAS, February 2012

El scrapie es una enfermedad neurodegenerativa transmisible de ovinos y caprinos. Se caracteriza por la acumulación en el sistema nervioso central de una isoforma anómala de una proteína celular normal (PrPc) codificada por el gen PrP. En el exón 2 del gen se han identificado mutaciones en los codones 136, 154 y 171. La combinación de estos codones muestran diferentes niveles de asociación con la susceptibilidad a la enfermedad, desde muy resistentes (ARR/ ARR) a muy susceptibles (VRQ/VRQ). Los codones 171 y 136 son los mayores determinantes de la susceptibilidad al scrapie, mientras que el codón 154 juega un rol menor. En el presente trabajo se estudió una muestra de ovinos Criollos Uruguayos (N=28) para los codones 136 y 171. Las muestras de ADN genómico se procesaron por PCR-RFLP. Los resultados se obtuvieron por electroforesis en geles de poliacrilamida (10,5%) teñidos con AgNO3. Se analizaron las frecuencias genotípicas para los codones 136 y 171. Cinco genotipos diferentes fueron obtenidos, encontrándose en mayor frecuencia los genotipos de alta susceptibilidad: VQ/AQ= 0,39 y AQ/AQ= 0,29. El análisis de riesgo genético de esta majada según los genotipos obtenidos, reveló un 72% de animales muy susceptibles a la enfermedad en caso de manifestarse las condiciones ambientales propicias. scrapie is a transmissible neurodegenerative disorder of sheeps and goats. It is characterized by the deposition in the central nervous system of an abnormal isoform of a normal cellular protein (PrPc), coded by the PrP gene. Mutations at 136, 154 and 171 codons of exon 2, are described. Combinations of these codons show different levels of association with the susceptibility to this disease; from highly resistants (ARR/ARR) to highly susceptibles (VRQ/VRQ). Codons 171 and 136 are the main determinant of scrapie susceptibility while codon 154 plays a minor role. In the present communication, a sample of Uruguayan Creole sheeps (N=28) was analysed for 136 and 171 codons. Samples of genomic DNA were processed by PCR-RFLP. The results were obtained by electrophoresis in polyacrylamide gel (10.5%) stained with AgNO3. Genotypic frequencies for the 136 and 171 codons were analysed. The results revealed 5 different genotypes. The most frequent genotypes were those associated with more susceptibility to the disease: VQ/AQ= 0.39 y AQ/AQ= 0.29. The analysis of genetic risk revealed a 72% of highly susceptible individuals, in case of proper environmental conditions.

The concentration of Cd, Cu, Hg, Pb and Zn in the liver of the European eel (Anguilla anguilla) was determined to evaluate the contamination burden of this species in Portuguese brackish water systems (Aveiro lagoon, Óbidos lagoon, Tagus estuary, Santo André lagoon and Mira estuary) and relate it to anthropogenic pressures within those ecosystems. The highest levels of most metals were found in eels from the Tagus estuary, in opposition to specimens from Santo André lagoon, which exhibited the lowest values. These results confirmed that eels from the most impacted areas show higher metal concentrations in their liver. Although little variability in metal load was observed within each brackish water system, some heterogeneity in contamination profiles among sampling stations was detected, demonstrating the efficacy of using the European eel as a sentinel species to monitor metals contamination at both large and small spatial scales. published