Editorial: Developing novel materials and new techniques of biological and physical retrospective dosimetry for affected individuals in radiological and nuclear emergencies

Retrospective dosimetry estimates radiation doses received by an individual in the past using physical and biological methods. Because of the increasing threat of radiological accidents or terrorist attacks involving radioactive material, the development of this area of research has become extremely important (1, 2). This Research Topic, entitled “Developing Novel Materials and New Techniques of Biological and Physical Retrospective Dosimetry for Affected Individuals in Radiological and Nuclear Emergencies,” provided an opportunity to receive new relevant contributions from various experts who provided new insights and perspectives in the field of retrospective dosimetry. The aim was to connect more scientific fields, researchers and infrastructures from this interdisciplinary research area and to collect studies relevant to human health. The main objective is to improve complementary physical and biological measurement techniques with lower detection limits of received radiation doses, to characterize different appropriate dosimeters, to develop and validate individual dose estimation models, and to propose standardized dosimetry protocols required in the most likely scenarios. It also aims to estimate more accurately radiation dose received by individuals involved in a nuclear accident or radiological emergency using materials on or near the victim and the victim's blood in a relatively short period of time to allow appropriate medical treatment and therapy to increase survival rates

RENEB accident simulation exercise

Purpose: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event. Materials and methods: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants. The exercise was performed over 27 weeks and involved the network consisting of 28 institutes: 21 RENEB members, four candidates and three non-RENEB partners. Results: The duration of a single exercise never exceeded 10 days, while the response from the assisting laboratories never came later than within half a day. During each week of the exercise, around 4500 samples were reported by all service laboratories (SL) to be examined and 54 scenarios were coherently estimated by all laboratories (the standard deviation from the mean of all SL answers for a given scenario category and a set of data was not larger than 3 patient codes). Conclusions: Each participant received training in both the role of a reference laboratory (activating the network) and of a service laboratory (responding to an activation request). The procedures in the case of radiological event were successfully established and tested

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

NATO Science for Peace and Security (SPS) project “BioPhyMeTRE”: “Novel biological and physical methods for triage in radiological and nuclear (R/N) emergencies”

In case of Radiological and Nuclear (R/N) emergencies, the early knowledge on the individual radiation absorbed dose is of paramount importance for sorting out unaffected subjects from those requiring medical intervention. Retrospective dosimetry by using biological and physical methods aims to prioritize the selection of over-exposed individuals for a rapid triage-dose assessment. In this context, the BioPhyMeTRE project focuses on the validation of innovative biological and physical methods allowing a rapid screening/triage of potential victims, by using inexpensive and user-friendly analytical procedures and devices. The biological method combines the two most standardized biodosimetry methods into a single one and the physical technique concerns the use of a low-cost, portable mini photo-luminescence reader for the individual dose assessment by using personal objects that civilians wear or carry every day. Next to the experimental work, the project includes training for the transfer of knowledge and skills among the partners, inter-laboratory exercises for the validation of the analytical procedures and disseminations of the results. The preliminary results of these activities are here reported

SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis

The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis

Autosomal dominant hereditary spastic paraplegia: DHPLC-based mutation analysis of SPG4 reveals eleven novel mutations.

We set up a new denaturing high-performance liquid chromatography (DHPLC)-based protocol to screen patients with autosomal dominant hereditary spastic paraplegia (AD-HSP) for mutations in SPG4. Six patients had a complicated form and 49 a pure HSP phenotype. We also analyzed 19 unrelated patients presenting with an HSP phenotype (pure in 17 and complicated in two subjects) but no clear family history, as such patients may be cases of dominant inheritance with low penetrance. The overall frequency of SPG4 mutations in our study of HSP (in which prior linkage data were unavailable) was 32.4%, rising to 46.9% when only pure AD-HSP patients were considered. This figure falls well within the range reported in different populations. Rather as expected, the clinical data available for the patients did not support an easy genotype-phenotype correlation. Moreover, the clinical picture was not influenced by the length of the predicted residual gene product. As well as identifying novel variants in SPG4, this study constitutes the molecular characterization of the largest cohort of Italian AD-HSP patients studied to date. In addition, it provided an efficient, cost-effective, and reliable detection protocol for mutational screening of SPG4, which might facilitate medical genetic counseling