Integration of New Biological and Physical Retrospective Dosimetry Methods Into EU Emergency Response Plans – Joint RENEB and EURADOS Inter-Laboratory Comparisons

RENEB, \u27Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,\u27 is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation

RENEB – Running the European Network of biological dosimetry and physical retrospective dosimetry

Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. Conclusions: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.European Commission 10.13039/501100000780 [GA 295513

Potential protein activity modifications of amino acid variants in the human transcriptome

Background: The occurrence of widespread RNA and DNA sequence differences in the human transcriptome was reported in 2011. Similar findings were described in a second independent publication on personal omics profiling investigating the occurrence of dynamic molecular and related medical phenotypes. The suggestion that the RNA sequence variation was likely to affect disease susceptibility prompted us to investigate with a range of algorithms the amino acid variants reported to be present in the identified peptides to determine if they might be disease-causing. Results: The predictive qualities of the different algorithms were first evaluated by using nonsynonymous single-base nucleotide polymorphism (nsSNP) datasets, using independently established data on amino acid variants in several proteins as well as data obtained by mutational mapping and modelling of binding sites in the human serotonin transporter protein (hSERT). Validation of the used predictive algorithms was at a 75% level. Using the same algorithms, we found that widespread RNA and DNA sequence differences were predicted to impair the function of the peptides in over 57% of cases. Conclusions: Our findings suggest that a proportion of edited RNAs which serve as templates for protein synthesis is likely to modify protein function, possibly as an adaptive survival mechanism in response to environmental modifications

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, ‘Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,’ is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation-induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.VII Programa Marco de Investigación y Desarrollo (VIIPM) de la Unión Europea. nº 295513European Radiation Dosimetry Group (EURADOS) de la Unión Europea. EURADOS WG1

RENEB - Running the European Network of Biological Dosimetry and Physical Retrospective Dosimetry

Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios

Seeking for Genetic Signature of Radiosensitivity- Methods for Data Analysis

Abstract. The aim of the study was to develop a data analysis strategy capable of discovering the genetic background of radiosensitivity. Radiosensitivity is the relative predisposition of cells, tissues, organs or organisms to the harmful effect of radiation. Effects of radiation include the mutation of DNA . Identification of polymorphisms and genes responsible for an organism's radiosensitivity increases the knowledge about the cell cycle and the mechanism of radiosensitivity, possibly providing the researchers with a better understanding of the process of carcinogenesis. To obtain this information, mathematical modelling and data mining methods were used

DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation

Abstract For many diseases with a foetal origin, the cause for the disease initiation remains unknown. Common childhood acute leukaemia is thought to be caused by two hits, the first in utero and the second in childhood in response to infection. The mechanism for the initial DNA damaging event are unknown. Here we have used in vitro, ex vivo and in vivo models to show that a placental barrier will respond to agents that are suspected of initiating childhood leukaemia by releasing factors that cause DNA damage in cord blood and bone marrow cells, including stem cells. We show that DNA damage caused by in utero exposure can reappear postnatally after an immune challenge. Furthermore, both foetal and postnatal DNA damage are prevented by prenatal exposure of the placenta to a mitochondrially-targeted antioxidant. We conclude that the placenta might contribute to the first hit towards leukaemia initiation by bystander-like signalling to foetal haematopoietic cells

Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity

Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment. A comprehensive analysis of genome-wide single-nucleotide polymorphisms (SNPs) and a transcriptional response to ionising radiation exposure in twins have the potential to identify such an individual. In the present work, we investigated SNP profile and CDKN1A gene expression in blood T lymphocytes from 130 healthy Caucasians with a complex level of individual kinship (unrelated, mono- or dizygotic twins). It was found that genetic variation accounts for 66% (95% CI 37-82%) of CDKN1A transcriptional response to radiation exposure. We developed a novel integrative multi-kinship strategy allowing investigating the role of genome-wide polymorphisms in transcriptomic radiation response, and it revealed that rs205543 (ETV6 gene), rs2287505 and rs1263612 (KLF7 gene) are significantly associated with CDKN1A expression level. The functional analysis revealed that rs6974232 (RPA3 gene), involved in mismatch repair (p value = 9.68e-04) as well as in RNA repair (p value = 1.4e-03) might have an important role in that process. Two missense polymorphisms with possible deleterious effect in humans were identified: rs1133833 (AKIP1 gene) and rs17362588 (CCDC141 gene). In summary, the data presented here support the validity of this novel integrative data analysis strategy to provide insights into the identification of SNPs potentially influencing radiation sensitivity. Further investigations in radiation response research at the genomic level should be therefore continued to confirm these findings.Peer reviewe

Tropical Channel NEMO-OASIS-WRF Coupled Simulations at Very High Resolution

International audienc

Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk

IntroductionVarious definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes.Materials and methodsIn this French multicentre retrospective study, we included 606 patients with ≥moderate-to-severe isolated functional TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm2) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality.ResultsThe relationship between the EROA and TCG was poor (R2 = 0.22), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA <60 mm2 vs. ≥60 mm2 (68 ± 3% vs. 64 ± 5%, p = 0.89). A TCG ≥10 mm was associated with lower four-year survival than a TCG <10 mm (53 ± 7% vs. 69 ± 3%, p < 0.001). After adjustment for covariates, including comorbidity, symptoms, dose of diuretics, and right ventricular dilatation and dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95% CI] = 1.47[1.13–2.21], p = 0.019) and cardiovascular mortality (adjusted HR[95% CI] = 2.12[1.33–3.25], p = 0.001), whereas an EROA ≥60 mm2 was not associated with all-cause or cardiovascular mortality (adjusted HR[95% CI]: 1.16[0.81–1.64], p = 0.416, and adjusted HR[95% CI]: 1.07[0.68–1.68], p = 0.784, respectively)ConclusionThe correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10 mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated significant functional TR