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Abstract: In the aftermath of a radiological terrorism incident or mass-casualty radiation accident, first responders and receivers require prior guidance and pre-positioned resources for assessment, triage and medical management of affected individuals [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA]. Several recent articles [Dainiak, N., Waselenko, J.K., Armitage, J.O., MacVittie, T.J., Farese, A.M., 2003. The hematologist and radiation casualties. Hematology (Am. Soc. Hematol. Educ. Program) 473–496; Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A.L., Dickerson, W.E., Tsu, H., Confer, D.L., Coleman, C.N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N., Strategic National Stockpile Radiation Working Group, 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140(12), 1037–1051; Blakely, W.F., Salter, C.A., Prasanna, P.G., 2005. Early-response biological dosimetry—recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys. 89(5), 494–504; Goans, R.E., Waselenko, J.K., 2005. Medical management of radiation casualties. Health Phys. 89(5), 505–512; Swartz, H.M., Iwasaki, A., Walczak, T., Demidenko, E., Salikhov, I., Lesniewski, P., Starewicz, P., Schauer, D., Romanyukha, A., 2005. Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. Appl. Radiat. Isot. 62, 293–299; . Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol. Blood Marrow Transplant. 12(6), 672–682], national [. Management of persons accidentally contaminated with radionuclides. NCRP Report No. 65, Bethesda, Maryland, USA; . Management of terrorist events involving radioactive material. NCRP Report No. 138, Bethesda, Maryland, USA; NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA] and international [IAEA, 2005. Generic procedures for medical response during a nuclear or radiological emergency. EPR-Medical 2005, IAEA, Vienna, Austria] agencies have reviewed strategies for acute-phase biodosimetry. Consensus biodosimetric guidelines include: (a) clinical signs and symptoms, including peripheral blood counts, time to onset of nausea and vomiting and presence of impaired cognition and neurological deficits, (b) radioactivity assessment, (c) personal and area dosimetry, (d) cytogenetics, (e) in vivo electron paramagnetic resonance (EPR) and (f) other dosimetry approaches (i.e. blood protein assays, etc.). Emerging biodosimetric technologies may further refine triage and dose assessment strategies. However, guidance is needed regarding which biodosimetry techniques are most useful for different radiological scenarios and consensus protocols must be developed. The Local Organizing Committee for the Second International Conference on Biodosimetry and Seventh International Symposium on EPR Dosimetry and Applications (BiodosEPR-2006 Meeting) convened an Acute Dosimetry Consensus Committee composed of national and international experts to: (a) review the current literature for biodosimetry applications for acute-phase applications in radiological emergencies, (b) describe the strengths and weaknesses of each technique, (c) provide recommendations for the use of biodosimetry assays for selected defined radiation scenarios, and (d) develop protocols to apply these recommended biological dosimetry techniques with currently available supplies and equipment for first responders. The Acute Dosimetry Consensus Committee developed recommendations for use of a prioritized multiple-assay biodosimetric-based strategy, concluding that no single assay is sufficiently robust to address all of the potential radiation scenarios including management of mass casualties and diagnosis for early medical treatment. These recommendations may be used by first responders/first receivers that span time-windows of (i.e. 0–5 days) after the radiological incident for three radiological scenarios including: (a) radiation exposure device (RED), (b) radiological dispersal device (RDD), and (c) an improvised (or otherwise acquired) nuclear device (IND). Consensus protocols for various bioassays (i.e. signs and symptoms recording, bioassay sampling for radioactivity analysis, nail-clipping sampling for EPR analysis and blood collection for hematology, cytogenetics, and blood chemistry analyses) are presented as Appendix materials. As stated in NCRP Commentary No. 19 [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA], multi-parameter triage (i.e. time to vomiting, lymphocyte kinetics, and other biodosimetry indicators) offers the current best strategy for early assessment of absorbed dose. [Copyright &y& Elsevier]

Estetrol (E4) is a natural estrogen with promising therapeutic applications in humans. The European Medicines Agency and the Food and Drug Administration have approved the use of 15 mg E4/3 mg drospirenone for contraceptive indication. Phase III clinical trials with 15-20 mg E4 for the relief of climacteric complaints are currently running. Relevant data from preclinical animal models are needed to characterize the molecular mechanisms and the pharmacological effects of E4 and possibly to reveal new therapeutic applications and to anticipate potential adverse effects. Therefore, it is important to design experimental procedures in rodents that closely mimic or anticipate human E4 exposure. In this study, we compared the effects of E4 exposure after acute or chronic administration in women and mice. Women who received chronic E4 treatment per os at a dose of 15 mg once daily reached a steady state within 6 to 8 days, with a mean plasma concentration of 3.20 ng/mL. Importantly, with subcutaneous, intraperitoneal or oral administration of E4 in mice, a stable concentration over time that would mimic human pharmacokinetics could not be achieved. The use of osmotic minipumps continuously releasing E4 for several weeks provided an exposure profile mimicking chronic oral administration in women. Measurements of the circulating concentration of E4 in mice revealed that the mouse equivalent dose necessary to mimic human treatment does not fit with the allometric prediction. In conclusion, this study highlights the importance of precise definition of the most appropriate dose and route of administration to utilize when developing predictive preclinical animal models to mimic or anticipate specific human treatment.