Page 346 - 2014 Printable Abstract Book
P. 346
model that can serve as a human surrogate of neutron-gamma irradiation to study survival and
biomarkers of radiation induced lung pneumonitis. Unanesthetized female Sprague Dawley rats (120-150
gms) will be exposed to total body irradiation of mixed gamma-neutron (80:20%) over 30 mins (6-12 Gy)
without shielding and then will receive an autologous bone marrow transplant post irradiation to reduce
complications of infection and bone marrow depletion. Kaplan-Meier survival curves will be reported at
sacrifice over 14 weeks, or upon death. Necropsy to collect blood and urine samples, and kidney, lung,
heart, and GI tissues will be analyzed by histopathology for all animals. The precise dosimetry will be
reported for gamma using optically stimulated or alanine dosimeters, and neutron dose track-etch
dosimeters. This new model will be used for the identification of biomarkers and for mitigation and
protection studies for neutron-gamma irradiation (Funding NIHR01 AI101898 and U01AI107297).
(PS6-37) Statistical Analysis and Classification of Non-Human Primate and Human Data Sets for
Radiation Biodosimetry. Robert Balog; David Cooper; Howard Javitz; Shirley Lee; Polly Chang; and Paul
Titterton, SRI International, Menlo Park, CA
Radiation biodosimetry based on a panel of proteomic markers requires use of robust
classification algorithms. We will review and discuss results obtained using several supervised
classification algorithms on both NHP and human data sets. Classification methods to be discussed include
logistic regression, conditional inference tree, and support vector machine approaches with k-fold cross
validation and cross-study validation. The data sets were obtained from acute irradiation studies in non-
human primates, and from human clinical samples obtained from radiotherapy patients undergoing total
body irradiation. Blood plasma samples were analyzed by mass spectrometry and immunoassay. Different
combinations of blood plasma proteins were evaluated for their ability to accurately classify the data sets
and the top performing panels were selected for use in our radiation biodosimeter. This project has been
funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development
Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response, Office of the
Secretary, Department of Health and Human Services, under Contract No. HHSSO10020100007C to SRI
International.
1
(PS6-38) A natural history exploratory study of GI-ARS in the Gottingen minipig. Maria Moroni ; Nicolaas
1
3
1
1
1
2
Deutz ; Jatinder Gulani ; Amory Koch ; Cara H Olsen ; Christine Christensen ; Mark Chappell ; and Mark
1
1
Whitnall , Armed Forces Radiobiology Research Institute, Bethesda, MD ; Center for Translational
2
Research in Aging & Longevity, Texas A&M University, College Station, TX ; and Uniformed Services
In the absence of supportive care, lethality from the hematopoietic syndrome in the Gottingen
minipig is achieved at doses below 2 Gy. Additionally, in the dose range between 2 and 5 Gy, an
accelerated hematopoietic syndrome occurs, characterized by villus blunting and fusion, the beginning of
sepsis, and a mild, transient reduction in plasma citrulline concentration. In levels up to 5 Gy, though, the
classic signs of gastrointestinal (GI) damage, characterized by vomiting, diarrhea, loss of crypts, bacterial
translocation, and a drop in plasma citrulline levels, are absent. Reasonable concern over the feasibility
of inducing classic gastrointestinal acute radiation syndrome (GI-ARS) in the minipig, prior to lethality
related to cardio-vascular and respiratory complications, prompted us to test doses of 5 Gy and above.
Methods: Thirty-two male Gottingen minipigs, approximately 5 months old, weight 9-11 kg, were
344 | P a g e
biomarkers of radiation induced lung pneumonitis. Unanesthetized female Sprague Dawley rats (120-150
gms) will be exposed to total body irradiation of mixed gamma-neutron (80:20%) over 30 mins (6-12 Gy)
without shielding and then will receive an autologous bone marrow transplant post irradiation to reduce
complications of infection and bone marrow depletion. Kaplan-Meier survival curves will be reported at
sacrifice over 14 weeks, or upon death. Necropsy to collect blood and urine samples, and kidney, lung,
heart, and GI tissues will be analyzed by histopathology for all animals. The precise dosimetry will be
reported for gamma using optically stimulated or alanine dosimeters, and neutron dose track-etch
dosimeters. This new model will be used for the identification of biomarkers and for mitigation and
protection studies for neutron-gamma irradiation (Funding NIHR01 AI101898 and U01AI107297).
(PS6-37) Statistical Analysis and Classification of Non-Human Primate and Human Data Sets for
Radiation Biodosimetry. Robert Balog; David Cooper; Howard Javitz; Shirley Lee; Polly Chang; and Paul
Titterton, SRI International, Menlo Park, CA
Radiation biodosimetry based on a panel of proteomic markers requires use of robust
classification algorithms. We will review and discuss results obtained using several supervised
classification algorithms on both NHP and human data sets. Classification methods to be discussed include
logistic regression, conditional inference tree, and support vector machine approaches with k-fold cross
validation and cross-study validation. The data sets were obtained from acute irradiation studies in non-
human primates, and from human clinical samples obtained from radiotherapy patients undergoing total
body irradiation. Blood plasma samples were analyzed by mass spectrometry and immunoassay. Different
combinations of blood plasma proteins were evaluated for their ability to accurately classify the data sets
and the top performing panels were selected for use in our radiation biodosimeter. This project has been
funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development
Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response, Office of the
Secretary, Department of Health and Human Services, under Contract No. HHSSO10020100007C to SRI
International.
1
(PS6-38) A natural history exploratory study of GI-ARS in the Gottingen minipig. Maria Moroni ; Nicolaas
1
3
1
1
1
2
Deutz ; Jatinder Gulani ; Amory Koch ; Cara H Olsen ; Christine Christensen ; Mark Chappell ; and Mark
1
1
Whitnall , Armed Forces Radiobiology Research Institute, Bethesda, MD ; Center for Translational
2
Research in Aging & Longevity, Texas A&M University, College Station, TX ; and Uniformed Services
In the absence of supportive care, lethality from the hematopoietic syndrome in the Gottingen
minipig is achieved at doses below 2 Gy. Additionally, in the dose range between 2 and 5 Gy, an
accelerated hematopoietic syndrome occurs, characterized by villus blunting and fusion, the beginning of
sepsis, and a mild, transient reduction in plasma citrulline concentration. In levels up to 5 Gy, though, the
classic signs of gastrointestinal (GI) damage, characterized by vomiting, diarrhea, loss of crypts, bacterial
translocation, and a drop in plasma citrulline levels, are absent. Reasonable concern over the feasibility
of inducing classic gastrointestinal acute radiation syndrome (GI-ARS) in the minipig, prior to lethality
related to cardio-vascular and respiratory complications, prompted us to test doses of 5 Gy and above.
Methods: Thirty-two male Gottingen minipigs, approximately 5 months old, weight 9-11 kg, were
344 | P a g e
