Appendix C
List of Questions Submitted to Speakers and Panelists1
- How do we add dose rate to radiation risk assessment?
- Is anyone considering psychological effects of low dose radiation with no physiological basis and how this may direct or be affected by biophysical research?
- There are still high dose experts being developed through Rad Onc departments (this is limited). How much do high dose experts help with low dose issues?
- Of the 22,000 estimated deaths per year from radon in BEIR VII, has anyone calculated the true number realized? If so, how does it compare?
- Are there incentives that might be offered to governmental agencies to participate in low dose radiation research efforts?
- Can someone talk about the work that the OSTP is doing for low dose radiation?
- To John Neumann: How was a decision made for OSTP to focus on radiation biology (as opposed to radiation biology and epidemiology)?
- What research is being done or needs to be done on health effects of combined radiation/chemical exposure at DOE cleanup sites?
- While we wait for this research, how do you currently answer the question “how much radiation is safe”?
- When involving private sector participants as funders, how are conflicts of interest mitigated?
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1 This list of questions is unedited other than for spelling mistakes and for consistency.
- To Ted Lazo: How did NEA come to the conclusion that coordination of low dose research nationally and internationally is efficient?
- Ted: Great points about opportunities to increase data networks/sharing. One area we could leverage is radiation oncology patient registries. Comments?
- What is the relationship of the NEA to the IAEA? Might the IAEA be a better synchronizer for international coordination of research and research funding?
- What about the uncertainty of choosing adults, primarily males to look at dose-response versus LIFECYCLE which every species has? And have cumulative impacts?
- I didn’t see a lot of U.S. survey respondents and was wondering if the different NIH Institutes that fund radiation research were invited to participate?
- How does ICRP fit in the OECD/NEA?
- Has anyone considered how to bring industry into the conversation? Maybe through radiation protection?
- Consider knowledge on risk communication in medicine, Image Gently/ Wisely, and for example in the Bonn Call for Action (WHO/IAEA).
- Smoking is not just a confounder of radon exposure, but also is a source of low dose radiation exposure.
- Every adult was in utero. Ignoring exposures pre-birth/childhood, prior to adulthood is UNCERTAINTY for outcomes of adult exposure. Do we have model 4 this?
- Has the NEA LDR resulted in changes in radiation protection policies or programs?
- Tony: How do you translate systems biology based risks from model systems to genetically diverse humans, given the strong impact of genetic background on risk?
- Dr. Brooks: What were the top 2 or 3 contributions of the DOE low dose radiation research program to radiation protection policies or regulations?
- Has there been any work within MELODI on in utero effects?
- Are there any longitudinal studies of cancer, fertility, and birth defects in St. George, Utah?
- How has MELODI avoided conflicts of interest? For example, a small group of scientists creating a research agenda that they will pursue and be awarded?
- Michaela: How rapidly do individual labs cycle in and out of MELODI as priorities are adjusted?
- What is total investment in LDR in Americas, Europe, and Asia?
- Tony: Based on DOE research what in your opinion should be the shape of the low dose curve?
- How does MELODI track translation of research results into medical practice, trading, and policy?
- Michaela: I am encouraged by the response of students. Are there any goals for gender balance in participation or leadership? USA so far behind on these matters.
- Any cataract data from the animal research in Japan by age?
- What was the justification used for financial support for the great facilities at IES?
- What is the cause of death of mice that undergo premature death in low dose exposures?
- How does MELODI translate results into best practice and policy?
- How do reports that help set radiation protection standards (BEIR, UNSCEAR, ICRP, NCRP, other) also help inform your program’s research priorities?
- How well do animal models represent human health outcomes? Do we know enough about this to plan research?
- Dmitri: Is the Canadian low dose exposure faculty available for fee for service research?
- Tony: Do you think the European model of collaborative prioritization and funding of research could work in the U.S.? Comment on challenges (e.g., funding)?
- Michaela: Can you tell us more about the move to include humanities within the European low dose radiation research collaborative framework?
- What is your definition of low dose in quantitative terms? What is your definition of low dose rate?
- For Dmitri: In Canada, what conflict of interest protections are in place when accepting funding from industry?
- Dmitri: Do the CANDU funders have a role in setting priorities and/or have influence on results reporting?
- Are there any efforts to develop an international consortium of low dose work that would allow for interface of Canada, Europe, Japan, U.S., Korea, etc.?
- How well do endpoint driven animal studies capture cumulative or progressive effects? What types of studies are needed to interrogate these phenomena?
- Isaf: How is DOE coordinating with other federal agencies in the low dose arena? Could that be enhanced?
- Dr. Al-Nabulsi: Can you provide examples of the methods your organization is using to integrate low dose radiobiology and epidemiology?
- There are so many agencies and groups that handle radiation issues in the U.S. Is there ever a forum where everyone gets together to discuss issues?
- Can Dr. Al-Nabulsi please comment on the current/future status of the DOE Low Dose Radiation Research Program in OBER, given Congress seems willing to fund?
- Armin: Is risk communication research too delusional to the main issues of radiobiology and risk estimation?
- Given the general need for better information on low dose risk, is there a mechanism where all agencies contribute to a coordinated research effort?
- How much does the atomic veteran program cost DoD?
- For Gilsted: Have we not made significant strides in cancer treatment, cures, screening, and prevention?
- How will artificial intelligence affect LDRR?
- Al-Nabuisi: The DOE had a Memorandum of Understanding with CDC to support public health research. Does the DOE view that as a model of future collaboration?
- What are some immediate, low-cost steps agencies could take to better communicate radiation risk on issues of current public interest?
- I love basic science, but how much of this impacts public health? We can agree that risks are very low at low dose and uncertainty will likely always be high.
- Steve: Are there NASA programs in place to obtain biosamples from astronauts before and during exposure for response assessment?
- For Terry Brock: Has the NRC’s Advisory Committee on Medical Uses of Isotopes (ACMUI) ever taken up the issue of low dose research and radiation protection?
- Terry Brock: How much do you think public perception of radiation affects the decisions that are made by NRC in regulating radiation exposures?
- If you could define the data quality objective for low dose research, what would it be?
- What information do you hope to receive by the end of this symposium as far as the future of the low dose program is concerned?
- How do your agencies differentiate risks of low dose external penetrating ionizing radiation and internal radionuclide exposures?
- How much of low dose research drivers are actually science vs. acceptable legal culpability?
- Should a low dose research be independent rad bio, epidem., dosimetry, risk comm. vs. a consortium research model w/all integrated into larger joint projects?
- Will there be a messaging strategy or plan to address public concerns that will be heightened from watching the popular miniseries Chernobyl?
- Suggestion, not question: make it easier for webcast participants to submit questions. Add link to agenda, webpage, etc.
- Why isn’t there more emphasis on analyzing malignant human tissue for radionuclides, to assess causal linkage between nuclear sites and nearby disease incidence.
- Donald: Is EPRI coordinating with the NIH on any research themes?
- All: As leaders of organizations that promote radiation research, what do you see as the barriers to the development of an integrated low dose research program?
- Note to all: Detecting effect requires knowledge of normal. The NIH Human Biomolecular Atlas Program will provide much of what is needed for many tissues.
- Do any of your organizations coordinate efforts with funding agencies such as DOE or NIH?
- NCRP and ICRP: How is independence of your recommendations for regulators and researchers ensured? Reflected in forming committees, selecting report topics?
- Alan, you cited several non-radiogenic effects of nuclear disasters. What responsibility does the nuclear industry take for the social impacts of its disasters?
- How do you see your organization contributing to a potential low dose program in the U.S.?
- What is the status of the million radiation worker study?
- Much of the science is inaccessible to the public (e.g., NCRP/ICRP docs) due to cost. Are we impeding public understanding because they are inaccessible?
- Kimberly, given your example of the industry outreach, why are there so many concerns about radiation?
- Larry Dauer didn’t answer the question. He spoke of modeling. The question was about tissue analysis.
- Is the RERF biased by many young health men being away in active duty?
- Dr. Ullrich, with the updates to the LSS have the slopes of cancer incidence vs. dose changed (increased or decreased) significantly from earlier LSS studies?
- Bob: What is the status of “use consent” for the RERF biospecimens?
- RERF: Please comment on present or future efforts to generate and analyze Next Generation Sequencing data (DNA-seq and RNA-seq) from the Survivor Cohort?
- Bob: Can you talk about the lung cancer differences for men and women that have been discussed with the A bomb cohort?
- For Bob Ullrich: Have you seen any perturbations in estrogen signaling in your cohort? We have seen some stimulation of estrogen pathway signaling in mice.
- Does the thyroid cancer data in atomic bomb survivors show a longer latency due to the iodine-sufficient diet in the Japanese population as claimed recently?
- David: Are combined cohort data being organized so they are conveniently available to the general scientific community?
- Is LNT likely to be replaced with another curve, or with an algorithm with many inputs?
- David or Bob: Please describe current efforts/results on occupational studies of Fukushima cleanup workers.
- David: Are you aware of the development any consortia similar to MELODI in North America? If not, how do you suggest interested researchers start?
- Dale: Please elaborate why we should over sample the higher dose groups if we are interested in the dose response shape at lower doses.
- Amy, was dose given to pediatric patients randomized?
- Which EPI studies from those discussed by the panel, if any, were supported by DOE’s past low dose program?
- Is there any genetically based confounding in the childhood medical exposure cohorts? Could this population be more genetically susceptible?
- Any: Are their plans to continue to follow the participants in the million children study and if so for how long.
- Any: Are the radiation data and associated metadata in the EMRs now standardized across the U.S.?
- Amy: What are the sex and age distributions for the childhood medical exposure studies you discussed?
- Why are all solid tumors being considered? Doesn’t a person typically have one specific type of tumor instead of multiple site tumors in the same person?
- Comment on Slido poll re: potential epidemiology/radiobiology research contributions to understanding risks @ low doses. What happened to the role of dosimetry?
- Ted Lazo: If sums of multiple small exposures cause statistically significant risks, do many “very small” doses also cause statistically significant risks?
- How are you integrating low dose radiobiological data into your epic studies?
- What types of biological studies help increase the power of the EPI studies at low doses? Where will the best samples come from?
- Gayle: Is the exposure and biological metadata associated with the archived FFPE samples organized and available?
- Gayle: How heavily are the animal archive tissues being used and is the resulting data being added to the dB as it is acquired?
- Gayle, do you know if the old Oak Ridge mega-mouse data were preserved and are they represented in your summary?
- Do you see value in cooperation with chemical toxicology studies and the AOP approach?
- How will the change to poly energetic X-ray beams complicate dosimetry and interpretation of systemic radiobiological effect?
- Al: What is the mechanism proposed to explain the long term maintenance of lesions that attract repair complexes like gh2ax?
- Dr. Fornace: You listed DOE as a stakeholder. Would you please elaborate on what your research means for DOE? You did not include NRC, was that intentional?
- Randy: Did the level of radiation induced methylation differ by cell type?
- For Randy Jirtle: Could you please comment on how the Agouti methylation data would translate to other murine strains?
- Randy, did you follow the mice for any other effects from radiation?
- Are epigenetic changes maintained or diluted down generations?
- Dr. Jirtle: Does your research represent a significant shot across the bow of LNT?
- Can stress from radiological emergency affect your epigenetic state and therefore susceptibility to radiation damage?
- Randy: There are some differences in epigenetic effects from mice to humans. Can mice be used to predict human responses?
- Randy, what do your results suggest regarding what we really know about redox imbalance or “dysfunction” mediated by radiation exposure?
- What efforts have been taken by the radiobiology community to address the concerns about reproducibility and replicability in science?
- A previous poll showed that EPI and radiobiology combined can help better understand risks at low doses. How do you think EPI can support your work?
- How does the agouti transposon result translate to post gestational effects on the epigenome?
- Randy: If hormesis was the right model for radiation dose-response and cancer in humans, what would the public health/radiation protection implications be?
- Can you provide examples of collaboration/coordination with epidemiologists to answer low dose questions?
- What effect does low dose exposure have on adult agouti mice?
- Given the methylation effects could be positive or negative, is a j-shaped curve a better, less charged way to refer to the obs. in Agouti mice?
- Would it be correct to say that in vitro work (such as Dr. Fornace’s) is “blind” to epigenetic effects?
- For Michaela: Could AOP “Key Events” be considered as relevant in the context of identifying biomarkers?
- Given the lack of unity among the organizations involved in low dose research and lack of funding, how can the task of biomarker be undertaken?
- Is there a study that shows RET/PTC1 and RET/PTC3 rearrangements are not radiation specific?
- Have the technologies presented by the OHSU experts been tested/ applied in samples collected by longitudinal studies (radiation/non-radiation related)?
- Chuck: How much heterogeneity do you see when scRMAseq or scDNA seq are applied to cells from patients treated with DNA damaging drugs?
- Chuck: What are the prospects for seeing a Radiation specific genomic signature at the single cell level?
- Why don’t many radiobiologists report confidence intervals for their low dose risk models?
- Joe: For each of the microscopy techniques you discussed, how long does it take to generate the data? What is the resolution of each?
- Single cell DNA assays detect radiogenic outcomes, e.g., deletions and inversions?
- Frank: Please comment on the relative merits of diffeq vs agent based models to predict the behavior of complex systems.
- Eleanor: How do you think the individual variation of the microbiome affects individual radiosensitivity?
- Ellie: Do we understand the mechanisms by which changes in the microbiome alter radiation response?
- Ellie: How do you interpret mouse microbiome data in light of humans since the microbiomes of different species are so different?
- Would ASTRO/ESTRO and the Children’s Oncology Group (COG) be a collaborator in testing radiation biomarkers in humans?
- Ellie: How much of the change in microbiome is caused by stress?
- In the event of a radiological event, at what dose level would you consider evacuating your family?
- What are your suggestions for integrating research in these new directions in a potential low dose program?
- How do go from exposure to disease outcome for single cell omics studies?
- Dan: How was the initial $50m funding level decided?
- What metrics does HEI use to judge success of its research model?
- Dan and Joe: What do you think about the idea of creating a Low Dose Radiation Health Effects Institute using HEI as an example?
- I did not see social sciences experts on the research committee for HEI. Can you please comment on that?
- Dan: Can you provide examples of how HEI work resulted in concrete changes to federal regulations/policy?
- What is HEI’s primary funding source?
- Dan: Is HEIs strategic plan publicly available?
- For Anna Baker: Newer technology we are discussing in radiology and dosimetry is AI/Machine Learning. Please comment for low dose radiation research program.
- To Dr. Barker: You mentioned a number of times that you communicated about TCGA. Who did you communicate to and who did the communication?
- At what level of informed consent were you required to go to use data?
- Anna Barker: Were individual science/discovery studies, beyond sequencing and publishing the sequences, also fully funded by the TCGA project?
- For Ann: For TCGA the infrastructure support could be provided by NCI. Is it possible to do a large-scale project without agency structural support?
- The panel: Is TCGA your legacy?
- Dan, did your field also face disagreement between epidemiology and biology results?
- Could a new low dose research program be leveraged by pairing it’s objectives with better funded cancer research, e.g., in looking for biomarkers?
- Does HEI have a view on nuclear power as it relates to the topic of air pollution?
- Why isn’t there a mandate to the NCI to fund radiation research to a greater extent given that ~50% of all cancer patients are treated with radiation?
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