3 results on '"Oskamp, D."'
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2. RENEB Inter-Laboratory Comparison 2021 : The Gene Expression Assay
- Author
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Abend, M., Amundson, S. A., Badie, C., Brzoska, K., Kriehuber, R., Lacombe, J., López-Riego, Milagrosa, Lumniczky, K., Endesfelder, D., O'Brien, G., Doucha-Senf, S., Ghandhi, S. A., Hargitai, R., Kis, E., Lundholm, Lovisa, Oskamp, D., Ostheim, P., Schüle, S., Schwanke, D., Shuryak, I., Siebenwith, C., Unverricht-Yeboah, M., Wojcik, Andrzej, Yang, J., Zenhausern, F., Port, M., Abend, M., Amundson, S. A., Badie, C., Brzoska, K., Kriehuber, R., Lacombe, J., López-Riego, Milagrosa, Lumniczky, K., Endesfelder, D., O'Brien, G., Doucha-Senf, S., Ghandhi, S. A., Hargitai, R., Kis, E., Lundholm, Lovisa, Oskamp, D., Ostheim, P., Schüle, S., Schwanke, D., Shuryak, I., Siebenwith, C., Unverricht-Yeboah, M., Wojcik, Andrzej, Yang, J., Zenhausern, F., and Port, M.
- Abstract
Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and
- Published
- 2023
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3. RENEB inter-laboratory comparison 2021 : inter-assay comparison of eight dosimetry assays
- Author
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Port, M, Barquinero, J-F, Endesfelder, D, Moquet, J, Oestreicher, U, Terzoudi, G, Trompier, F, Vral, Anne, Abe, Y, Ainsbury, L, Alkebsi, L, Amundson, S A, Badie, C, Baeyens, Ans, Balajee, A S, Balazs, K, Barnard, S, Bassinet, C, Beaton-Green, L A, Beinke, C, Bobyk, L, Brochard, P, Brzoska, K, Bucher, M, Ciesielski, B, Cuceu, C, Discher, M, D Oca, M C, Dominguez, I, Doucha-Senf, S, Dumitrescu, A, Duy, P N, Finot, F, Garty, G, Ghandhi, S A, Gregoire, E, Goh, V S T, Guclu, I, Hadjiiska, L, Hargitai, R, Hristova, R, Ishii, K, Kis, E, Juniewicz, M, Kriehuber, R, Lacombe, J, Lee, Y, Lopez Riego, M, Lumniczky, K, Mai, T T, Maltar-Strmecki, N, Marrale, M, Martinez, J S, Marciniak, A, Maznyk, N, McKeever, S W S, Meher, P K, Milanova, M, Miura, T, Monteiro Gil, O, Montoro, A, Moreno Domene, M, Mrozik, A, Nakayama, R, O'Brien, G, Oskamp, D, Ostheim, P, Pajic, J, Pastor, N, Patrono, C, Pujol-Canadell, M, Prieto Rodriguez, M J, Repin, M, Romanyukha, A, RoSSler, U, Sabatier, L, Sakai, A, Scherthan, H, Schule, S, Seong, K M, Sevriukova, O, Sholom, S, Sommer, S, Suto, Y, Sypko, T, Szatmari, T, Takahashi-Sugai, M, Takebayashi, K, Testa, A, Testard, I, Tichy, A, Triantopoulou, S, Tsuyama, N, Unverricht-Yeboah, M, Valente, M, Van Hoey, O, Wilkins, R C, Wojcik, A, Wojewodzka, M, Younghyun, Lee, Zafiropoulos, D, and Abend, M
- Subjects
Medicine and Health Sciences - Abstract
Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses 2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.
- Published
- 2023
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