 Thanks for coming to our session. My name is Terry Brock. I'm a senior health physicist in NRC's research office We're glad we were able to present the results of this study that's been going on for a while When we asked it started out with a interagency agreement between EPA NASA and and NRC with the DOE low-dose program at the time and One of the things NRC asked for let's let's do an epidemiology study Of our radiation workers now after the three years of COVID. I think we're all become epidemiologists So, but that's infectious disease epidemiology. We're talking now about mostly cancer and chronic disease Epidemiology in an occupational setting. So the two cohorts that we're looking at Are the nuclear power worker cohorts and the industrial radiographer cohorts that? That the NRC has regulatory authority over it. So to kick us off on the first presentation Is we're lucky to have dr. Catherine Held. She's the president of the NCRP the National Council on Radiation Protection and Measurements She became president in January 2019 And you've been with the NCRP since looks like 2008 Dr. Held is an associate Radiation Biological biologists in the Department of Radiation Oncology At Massachusetts General Hospital and associate professor of Radiation College oncology at Harvard Medical School Okay, hello Well, thank you all for being here and thank you to the NRC for the support We've had over the years for the million person study and for setting up this session for us today. Thank you, Terry I'm a stand-in for Dr. John Boyce who at the last minute couldn't be here So you've got to kind of have to put up with me because I got the slides in his transcript yesterday And there's 52 slides for 25 minutes. So this is going to be really a challenge So it is Really this talk is going to be an overview of the million person study Which has really been going on For 25 years or more since Dr. Boyce and his colleagues started the early cohorts that are in the in the population and has been going on as Terry just mentioned with support from a lot of different agencies for a number of years So what I'm going to do is a quick overview with some emphasis on the the populations that the NRC has been interested in and then Larry Dower is going to tell you a little more about those populations. So why are we studying a million a million people? We need to evaluate Radiation doses among healthy American workers and veterans the people that are being regulated in terms of radiation doses by the NRC and by by other agencies And at this point most of our risk calculations are based on the underlying Population the main population being used are the Japanese atomic bomb survivors who were exposed very briefly virtually instantaneously to relatively high doses of radiation during during war and so what we need is a population that is more Characteristic to set risks of the populations that we now are worried about Regulating and so we need good science good science is what's needed to lead to informed regulations for the protection of our workers in our environment and So this is what we're going to see dr. Boyce Who I'm substituting for and then Larry and then we'll have a zoom in by dr. Steve Blatnick from NASA So a reference for all of you who are interested in this topic this past April there was a Entire issue of the International Journal of Radiation biology that was devoted to the Million Person Study 24 peer-reviewed articles that talk about the various populations and any of you who are interested in More information can look at these this whole issue of the journal In particular of interest for today are two of those articles the one that talks about the nuclear power workers nuclear nuclear power plant workers that will talk about a little more and then an Overview article about the Million Person Study as shown here So I'm going to start out giving you a little bit of background and then some details on some of the cohorts So I've already sort of addressed this question of why another epidemiology study Well that as I said the Japanese atomic Bomb victims who were the underlying population that has been studied so carefully for so many years By RERF in Japan is not an ideal population by any means for which to base risk for Healthy American workers and so we really need information on Current populations or that's applicable to current populations and that information is going to apply to setting risk standards and dose standards for medicine for Occupation for the environment and so forth and NASA which is why we're going to have it talk about NASA in a few minutes But why a million workers well it boils down to statistics if you don't have large enough populations you can't get statistical significance and By having this large population We're going to be able to look at very low dose radiation effects with good statistics We'll be able to look at rare cancers as well as extending to other kinds of endpoints besides cancer cardiovascular disease cerebrovascular disease and And dementia and cognitive effects effects on the central nervous system The million workers will give us enough Numbers to look for differences between men and women and we'll talk about that some more in these talks today and to be able to look at some effects from high let t radiation That comes from intakes of radionuclides, but those health effects are also applicable to The astronauts being exposed to galactic cosmic rays that include high let t radiation So who are the populations? Here's the summary slide and the two of interest to the NRC are the the nuclear power plant workers and the industrial radio Radiologists that will hear about radiographers that will hear about in more detail But I'm going to touch on a number of these populations in talking about an overview In very important underlying all of these epidemiology studies is good dosimetry You can't have good epidemiology without good dosimetry and the NCRP has really been important in sponsoring and supporting a lot of the Development of the dosimetry. This is just three of our relatively recent publications that talk about specifically how to do organ doses for Million-person study for general organ dose dosimetry as well as specifically for the lung and for the brain a Million people that's a lot of people You got to have the big population to be able to do the studies in get good epidemiology good statistics So let's look at some of this the cohorts that we have looked at one is the DOE a number of cohorts that are DOE Manhattan project workers and one of the unique features of some of these populations is that they have received radiation Exposures from the intakes of radionuclides and so we can look at dose response analyses By using the guidance in the dosimetry that has been worked out for looking at organ specific doses from Radionuclide intakes This just shows you a listing of some of the radionuclides that we're looking at Plutonium tritium polonium amyresium are a radium of interest in looking at particularly doses for the lung Doses for the brain and Another of the important characteristics of our populations is that there's good percentages of women and This becomes particularly important when we start to think about sex dependent Different risk estimates and whether there are difference is in risk for certain organs between Men and women and a number of our populations that are used in the million person study can really get at these studies with women one of the examples of the data that's been used is the girls of the atomic city the Tennessee Eastman Corporation women who worked at Oak Ridge National Lab are one of the populations in the million person study This is just one example of some of the data being looked at In this case the data is for lung cancer induction in these women that inhaled uranium dust and Got doses to the lung from that and you can see that in this particular population at this stage There's no increase in lung cancer and Another one that's really a snazzy one is the radium dial painters that is a study that we have There's been reactivated as part of the the million person study and The interest here even though this is a relatively small cohort. It's a very special cohort Because it's one of the few cohorts where we're now to completion all of these women have died and so we can follow have complete follow-up in this particular population and There's also much better dosimetry that is available from since the last time a study was done in 1980 when the last Epidemiology study of these these young women was done 60% of them are still alive and We have improved the dosimetry For many different cancers Substantially since then this population also presents a really nice population to use for teaching and We have been very interested at NCRP and through the million person study in Trying to encourage the next generation in the workforce And this is a study that is important for radiation professionals for the future So military cohorts the big a big military cohort is the the atomic veterans Where we have over a hundred thousand individuals that were exposed from 1945 through 1958 in above-ground atomic tests and Another example of some of the data that's available on this population. This is looking at Ischemic heart disease and again, you can see that with increasing doses There's no increase in the risk of ischemic heart disease in this population at this point Another of our big populations in the million person study comes from the Navy Navy Submariners are an important characteristic an important population cohort for us, but there are also other Navy personnel including People who have worked at shipyards and in the nuclear in the atomic veterans so this makes up a sizable population and this is a population with Relevance believe it or not to NASA because of the many similarities between Astronauts and Submariners in that submarine you're very isolated. You're very confined You're with the same people for days and days and days And all of this these many stresses that are characteristic from these Exposures are also on top of or underlying or whichever is on top of which radiation exposure and So as an analog population for what might be used to look at effects of radiation and other Stressors in in the NASA population and in a few minutes Steve's going to tell you more about this study And that's just showing that we even go into the submarines. There's Dr. Boyce in a submarine another big population is the medical workers and One of the importance of this population is that it's about half women and so in this population again examples of some of the data that that have been derived looking at Increased hazard ratios in men and women separately in the industrial radiographers nuclear medicine technicians and physicians radiation oncology workers and You can see that in this particular study. There is Both looking at men and women. There is Not a sex-specific difference yet in lung cancer. We're not showing up in lung cancer and an important part of all of these studies now is to start to harmonize these populations and to be able to combine from the 100,000 medical workers with large numbers of nuclear power plant workers and industrial radiographers and other Populations to look at cancer risks. This is some of the data on lung and in a few minutes Larry's going to tell you a little more about these data and harmonizing them For this audience of interest, I hope is the Nuclear Regulatory Commission cohorts And NCRP is interacted with the NRC for many years in work that we've done in a number of different publications LNT doses to the organs and and integrating exposures and understanding exposures One of the advantages of the rears Population that we have through the NRC is that the dosimetry is really fantastic very complete dosimetry in this this population in the database that the NRC has and exceptional follow-up because We have really good information and identifiers on all of these Individuals and can also therefore get career doses when the people went to work somewhere else This population the history behind how we the NRC started developing the rears Database is something that Larry's going to tell you a little bit more about in a couple of minutes because I'm already running out of time So some recent data three three end points that we're going to talk about first leukemia Nuclear power plant workers again something that Larry will tell you about more But this is one example of the kind of data that we have looking at Leukemia in the nuclear power plant workers where there is a significant increase with radiation dose This is a meta-analysis of a number of different populations and looking at leukemia Comparing or combining the nuclear power plant workers with the other populations and you can see a small but Really suggestive increase in leukemia in these populations that have been exposed to very low doses of radiation Another of the end points that's being looked at in the million-person study is ischemic heart disease again and a Combined analysis of the nuclear power plant workers and the industrial radiographers So that we have almost a quarter of a million or a little over a quarter of a million people involved and there's no evidence for a significant increase in ischemic heart disease in these populations this is really an important potentially finding because as ICRP and other organizations are now looking at changing Reconsidering what we should add to the system of radiation protection one of the things that's being thought about is heart disease This data says we probably maybe don't need to include it Here's a meta-analysis that brings in with those two populations some of the other populations being looked at in the million-person study and Again no evidence from these studies for an increase in ischemic heart disease with radiation dose But a surprise has been Parkinson's disease and Although there were animal studies and the animal studies in some NASA funded work go back many years that have suggested that Galactic cosmic ray type radiations can significantly increase damage to the central nervous system and This particular paper from from almost 10 years ago now was really a hallmark in Specifically using an Alzheimer's model and showing high let induced heart disease And it brought up this quote from Ray Bradbury that says it's not good It's not going. It's not going to do any good to land on Mars if we're stupid So what did the data show? Well the interesting thing that really stimulated in humans the studies was a few years ago a Publication that was based on looking at the Mayak workers in Russia And this as you can see here that particular graph showed a very significant increase although it relatively high doses in Parkinson's disease in these Russian Workers and at the time many people in the field said that's a flu that can't possibly been right nobody else has seen that So dr. Boy said well, we better better look at this and he went back and started looking at the million-person study Workers here's the data for the nuclear power plant and the industrial radiographers and Believe it or not there it is so this is consistent with that study from the Mayak workers Suggesting that there is a radiation dose dependent increase in Parkinson's disease a lot more work needs to be done This is really a challenging area, and it's going to be really interesting to see what comes out of this Here's the meta-analysis for several populations again a significant increase in Parkinson's disease induced by ionizing radiation So a quick summary Some of the most conclusion so far from the million-person study and again Emphasizing this is very much a work in progress There's enough work here to go on for many many years But at this point it looks like chronic exposures are important in causing leukemia not not particularly surprising Chronic exposures to radiation do not seem to be causing ischemic heart disease good news Chronic exposures are associated with Parkinson's disease as I've already indicated a real a real surprise and a lot of research needs to be We just have no no biological explanation. I mean there are people throwing out theories but nothing that is is really good at this point and Chronic exposures might be associated with lung cancer, but in the million-person study it's not a very strong association and the Potentially relevant thing here is there doesn't seem to be a difference in so far in the million-person study between men and women and so That's a big difference from what's been seen in the atomic bomb survivors where women were three times more greater risk for Lung cancer induction So there's lots of work still to do in these million-person cohorts and many many questions to follow up I've got to acknowledge all of the funding that Has gone into support for the million-person study into NCRP for that study over the years it's really been a team effort many of the agencies of the federal government involved and that's been really important and Many many people involved and this cast of characters keeps growing Very very much. So we now have many collaborators at at other institutions in the United States I'm known have time to go through them all So where are we going? Lots lots of things. I've been trying to point out the future as I've gone through this We have a lot more studies to do with the DOE workers a lot of Studies to be done to look at the effects on the central nervous system and now putting all of these cohorts together To really get to the advantage of using a million persons The vision Potentially a center a national center for radiation epidemiology and biology And this will be really important for among other things addressing the issue of the linear no threshold Model and its use in radiation protection It's an open question and we need a lot more data For those of you who are interested in learning more about radiation epidemiology the CDC Recorded a number of lectures given by dr. Boyce a few years ago. That's freely available on the CDC website go to those And I'm going to end with an advertisement the NCRP annual meeting is here in Bethesda down at the Hyatt in less than two weeks now and It's very very relevant to the NRC Because the topic is integration of physics biology and epidemiology and radiation risk assessment And I finished on time Thanks, dr. Held I appreciate that we're gonna be Please So the problem I'm running into is it looks like I got a train coming at me, you know with those lights But it's causing my my my pupils to go like this. I'm trying to see in the dark here. So Just bear with me Okay, our next our next speaker is Dr. Larry Dower. He's an attending physicist in the Department of Medical Physics and Radiation Radiology at Memorial Sloan Ketter set cancer center and serves as their corporate radiation safety officer He serves as a member of the Nuclear and Radiation Studies Board of the National Academies And he is a former board member and current council member of NCRP and is a scientific director of the million person study He has served as chair or core chair on several NRC and see Rp Scientific communities committees associated with radiation protection of workers patients and members of the public He served seven years on the ICRP Committee three ready radiation protection of medicine He is also an active member of the Health Physics Society the American Association of Physicists and Physicists in medicine and the radiation research Thanks very much. Thanks for the opportunity to talk about the what we're affectionately calling the NRC cohorts I'll hopefully will weave in and dovetail nicely with what Dr. Held has presented so far and go into a little bit more detail on how we accomplish the Both the assessment for the nuclear power workers the first assessment I'll explain what I mean by that and then the current Assessment of the industrial radiographers that will be submitted for publication within the next few months So you're seeing brand new information presented Memorial requires that I included disclosure. So I was 12 years at Indian point three nuclear power plant I was the radiological engineering supervisor there and then more than 20 years at Memorial Sloan Kettering Cancer Center I'm on the NCRP and I'm associated with the million person study though myself in a voluntary role But the NCRP receives funding as Kathy said from several agencies the Topics I'll briefly cover some of the topics Kathy Kathy dr. Held discussed and I will try to concentrate a little bit on the on the NRC cohorts themselves Especially about how did we do do symmetry etc? And then go over a few selected results for these cohorts So who who are we talking about? Well the the NRC cohorts the nuclear power plant workers and industrial radiographers make up 25% of the overall million person study. So they're a key really important part of the Assessment of the study especially for those who are mainly exposed to external radiation So how are they different from other MPS cohorts well Dr. Held mentioned it already the the dosimetry is exceptional The if having worked at a nuclear power plant any of you who have ever done any work there You know that you can't get into the radiological controlled area without an HP saying where's your badge? What were you doing? you know so you have a dosimeter on the way in and hopefully you have it on the way out and So the the dosimetry really is exceptional the the reconstruction on these cohorts has been rather easy compared to other cohorts and We're able to do organ doses assessments that are fairly accurate For another reason especially for the nuclear power that I'll get to The follow-up has been exceptional. We we had what I mean by follow-up is vital status follow-up We've been able to identify these individuals because of the exquisite information Captured in the rears the system by the NRC So we have over 99% which is just about unheard of for an epidemiologic study So that's exquisite for both of them. We also get career doses Not every nuclear power or industrial radiographer worker worked their whole career in those industries, although many of them did But several of them came out of the Navy. We have all their Navy doses We know what they did when they left so we have career doses for these individuals which Allows us to life lifetime work doses We also have a broad distribution given in both of these cohorts and we'll talk about them separately And then a couple of times will give you some preliminary pooled results so far But the it's important if you're doing an epidemiologic study that that you have doses that are low But you also have those high doses so that you can understand what's going on in between as best as we can and so These cohorts are are unique in that we have very broad dose distribution Some of the organ doses go up past one gray for example in a lifetime of work And part of that is the limits that were set early on allowed such doses So just to briefly talk about the nuclear power plant workers How do you do such a study use any of these any of our 30 plus cohorts that we're evaluating in a million person study? It starts by defining the cohort very carefully in most cases Evaluating work that's been done already for example in the DOE cohorts and then bringing it forward Dr. Held talked about the good example of the radium dial painter painter cohort So then you do population vital status Understanding the cause of death for those who are no longer alive pulling together the dose data Getting from a badge or a film badge or a TLD or some kind of area monitoring down to Organ doses in a given year a lot of time and effort there Understanding what the exposure source term is for the cohorts understanding what the exposure conditions are etc etc so Why did we how did we get the nuclear power plant workers going? We knew there were over a quarter of a million that were hired prior to 1985 and most of the TMI Modification work was really kicked off or ended there. So we have a lot of dose before by 1985 and and so we decided that that would make a really good cohort and we know that we have exposure sources from Fission products and activation products. We understand them the NRC publishes yearly Summary information on this every year certainly from the 70s on and we understand operational history We understand if a plant had fuel integrity issues. We understand that shifts the source term in most cases Most of the exposed individuals in nuclear power plant worker cohort were exposed Externally to something in the range of point six to one and a half MEV It depended on what the fuel integrity was at the time and what the specific tasks were And the activity weighted Energy looks more like about point seven which you can kind of expect it looks similar to cesium overall In the exposure conditions most of the dose remember we're talking about a hundred and fifty, you know 135,000 workers over their entire career So you got to put on a career hat for a minute But most of the doses received during an outage and that's pretty true throughout throughout the data that we've seen And the other thing is is there was excellent engineering controls and PPE used throughout and so that really limited the internal exposure which makes it a little bit easier to study this cohort overall And in fact most of the dose that we have in this cohort is external Exposed most of it from AP, you know the valve the hot valve you're working on is in front of you Although of course there were some that were PA and if you're walking through to get to the work Maybe there's some lateral in the rest, but we Adjusted for those and if you're doing refueling then you'll be cranial caudal or caudal cranial if you're standing on the refueling floor getting dose and Or if you're jumping in a steam generator then the dose is going to flip and it's going to be mostly from the head And so we evaluated those as we went through and there's a plethora of higher dose outage tasks And we'll go into those in detail probably all of you know or have been involved in some of these already many times Now on the industrial radiographer cohort the exposure sources are a little bit different Most of the time it's either iridium or cobalt 60 and it's at a ratio of about 200 to 1 on the use That's in in existence in other words if you were to pick up any Industrial radiographer source 200 times out of 1 it's going to be iridium Which makes it a little bit easier although there are less typical Selenium and x-ray tubes that are utilized in the industry neutron For example for well logging and others is very low use when you look at a big cohort But it is available in most cases we can utilize an AP geometry with about an awaited average Energy of about point three and we'd be pretty close now from 1965 on and even before it was in a different format Part 34 has had very strict requirements for industrial radiographers in the wearing of dosimeters and Inspection and RC inspections and state folks have been very careful in that regard Which is very helpful Now the dose distribution for nuclear power plant workers you can see here. This is in milley seaver So this is bad dose just kind of looking at bad dose And so there were several that are you know as high as a thousand milley seaver Across the population, but you can see we have a significant number that are below 10 milley seaver So we sampled that it's very expensive to do epidemiologic studies cost for example $5 to find out what you died of so a million persons it starts to get really expensive So in the lower dose region we sample randomly from that and then we utilize all of the above 50 milley seaver Folks in all of our cohorts We try to do that so that we can have a harmonized population when we get to pool these together a similar dose distribution for industrial radiographers just to point that out so Dr. Held referred to getting to the organ dose is really important So it's very different than the regulatory recording of dose So when we record dose when we're a licensee We want to show that we're lower than a limit or we're recording the actual doses But our aim is to say and we're below the regulated limits But here we're not going to use waiting factors Because we're running an epidemiologic study to see whether or not there are waiting factors that should be used So we have to put a different hat on and we go to gray So we have organ doses in gray and then based on that we can run different Well, what if we assume alphas are really a factor of 10 or what if we assume the organs have this risk factor? What we're really trying to see is what is the risk factor for the organ? So we're evaluating that across all of the cohorts Definitely for the nuclear power industrial radiographer cohorts So basically in your picture in you know in your mind think we're trying to get from that badge dose Wherever it's located most of the time on the chest to an organ exposure and so we rely on ICRP guidance NCRP guidance and lots of NCRP guidance has has happened across the years the middle document for example is Specifically, how do you do this for a medical worker cohort who are wearing lead aprons some of them So there's a wrinkle when you do that one, but for nuclear power. It was a little bit easier industrial radiographers much easier So we've already published the first study of the nuclear power plant cohort I say that because the million-person study one of the things that we need to do is every three to five years go back and Retrace and find out that there will be new people. It's an aging workforce These are fairly young cohorts and we'll have more information as we continue to do follow-up So they'll be you know million-person study number two for nuclear power plant cohorts coming up soon Where this study reported our follow-up through? 2011 so that's the results that I'll be showing there and the industrial radiographer cohort We are submitting to radiation research within the next month or so so a lot of it is preliminary But you'll see it in the in the publication form. Hopefully within the next several months Just letting you know what you're gonna see here So just to clue you in this is a standard mortality ratio analysis It's the first step we do once we've compiled all of the information and in this case We evaluate the work population against the US population and we see whether or not there are any signals that show up so for example lung and Plora mesothelioma show up for this is the nuclear power plant worker cohort And also you can look for example at ischemic heart disease. It shows up going the other direction And part of the reason is that when you evaluate? Healthy workers against the rest of the population. There's something about being healthy and a worker that is really good for you Right, so we can't rely on SMR analysis alone to inform on whether or not there's a risk So what we do is we assess whether or not there's the potential risk and then we do internal cohort analysis and Within the cohort with those who are getting no dose and those that are getting higher dose and evaluate within the cohort Now, what would the plural mesothelioma which is not related to radiation and asbestosis be from? peeling appealing pipes peeling the insulation off of pipes Especially remember these are early cohorts who work from the 50s through 1985 So it's not related to radiation, you know It's not correlated with radiation although it is correlated if you think about it There's a confounding the the more you are around a pipe the more likely you are to be exposed to the asbestos That's around the pipe. So these are these are complex bits that we have to tease out of the and The industrial radiographers actually have a much stronger signal when it comes to asbestosis for example So I'm going to give some selected results out of these cohorts again The best place to go are the papers for all of all of the results and additional files that Supplementary data one of the key things a doctor held Mentioned but it went by really quickly. So I'm going to just just emphasize One one thing we're doing in the million-person study is being very transparent with the data All of the data is being shared the analytic data is being shared by the DOE in their Comprehensive epidemiologic data resource so people can be picking at the data after as we develop it We're putting it into that resource and once we pool all of the data will be doing the same there So this is non-cll leukemia results and for each of these the nuclear power workers is on your right and the Industrial radiographers on your left so blue and green just to clue you in but I thought it would be interesting to put them next to One another I list the mean dose for each of the cohorts and I also list the maximum dose for the cohort for that organ So in this case the organ is the red bow marrow dose that is instructive for non-cll leukemia And you can see that both of these dance on Significance in other words that lower line dotted line if that lifts above the zero line there Then it would be considered a statistically significant Result so in this case there is positive trend we would call it non statistically significance But there is a positive trend now dr. Held mentioned that if we were to expect any Signal in a cohort we would expect leukemia Why why would we expect that the atomic bomb survivor risk data shows that leukemia is much higher on the risk than any Other solid cancers so the fact that we see some trends in these smaller cohorts and when we roll them together It's very likely this will become slightly statistically significant if we saw no trend at all in leukemia We might actually think that we were doing something really wrong with the epidemiologic work Right at the something wrong with the model So we the fact that we see this signal at all kind of lends a little bit of okay We think we're heading in the right in the right direction But the results speak for themselves and when we pull this all together will have the most The most information on a healthy u.s. Worker population In both cases it's a positive trend and it dances on statistical significance. In fact the the Industrial radiographer would be considered statistically significant Nuclear power workers. This is for all solid cancers. I Caution I almost hesitated to put this slide up. I wanted to be very open because Not all cancers are radiation related And so this is not always the most informative thing to look at a lot of studies publish on all solid cancers and use that, you know As as information and we're giving it here But just to recognize for example prostate cancer there there hasn't been a link But so this includes those right so But in in the end just we're providing the information Here and you can see that The nuclear power is rather flat response on all solid cancers and the industrial radiographers has a positive trend But not statistically significant now What's interesting? Let me just try to go backwards here If we take lung cancers and mesothelioma out of the industrial radiographer Cohort remember I said that that was a really big signal for them. We would expect Some kind and remember I said that being exposed to pipes and asbestos and radiation are all related What would happen if we took that out? And so we took it out and it became a much flatter response for the industrial radiographers as well For all solid cancers in other words when we exclude lung and mesothelioma, that's the picture Now for lung cancer itself. This is a very interesting Result we have the mean doses are always a little bit higher for the organs for the nuclear power worker advice the industrial radiographers And in this case there it's a rather flat response overall Again the industrial radiographer. There's the hint that maybe it's it's statistically significant But when we combine both of these into a pooled analysis, it's a very flat response Which if you kind of squint your eyes at the last slide you can kind of expect that that would happen As we pool that and in and the other thing to point out I'm doing this on purpose I don't know if you can squint and see the confidence intervals They're rather wide-ish here, and then once you pool they get more narrow And that's exactly what we expect as we pool all of the million persons into what I would call Million-person study number one when we you know in the next three or four years when we can finally Pool the whole thing and see for every outcome what what the picture is So we should get more refined information the confidence interval should shrink over time And if we include nuclear power industrial radiographer and medical workers all together you can see that it gets even narrower and What what that suggests is that there there doesn't appear to be a lung risk effect when you look at over 350,000 340,000 workers on the information that we have so far And when you look against a male and female for all of the cohorts in the million-person study the blue the light blue is For the NRC cohorts There doesn't seem to be that three times higher risk for these chronically exposed folks You know for the females against them the males in in fact, there's little evidence of of lung cancer risk overall and There's no difference between the two that at least so far in the data that we've done This is dose response for ischemic heart disease This is the beginning of all cardiovascular disease So in million-person study, we're now going back and we're going to look at every one of the cardiovascular outcomes to understand Exactly what the the potential correlations are if any And in this case you can see that it's a very flat response We don't see a significant increase in risk from ischemic heart disease as you get higher doses at least in the dose range that we're talking about and In the meta-analysis, I just wanted to point out something important for the NRC cohorts Those are some of the highest statistical power cohorts we have and therefore they really drive a meta-analysis So you can see those two arrows on the top are pointing to nuclear power and industrial radiographer And then you see the meta estimate down below it looks an awful lot like a combined nuclear power and industrial radiographer, which is what you would expect given the the amount of dose and the exquisite follow-up Dr. Held mentioned Parkinson's disease. Frankly, we don't have a biologic understanding We have pitched out a lot of different ideas We also are very skeptical when you come when you do these studies the first your first response is wow Look at that your first response is oh, I wonder what's going on and in this case it We do know something very important on a population level that that Parkinson's is inversely Related to smoking so if you've ever smoked your risk is actually lower for Parkinson's We're not sure what that means If you're a breast cancer survivor your risk of getting brain You know a chemo brain is actually lower if you've ever smoked So maybe there's a dopam, you know, we're pitching out all kinds of biology I maybe there's a dopamine switch. Maybe we don't know so it but the point is is Understanding smoking is that important for Parkinson's we've we have corrected and adjusted for smoking in the best way that we know How maybe there's something associated there. We don't think so But we're we continue to pull on the data to understand better this potential trend So the the summary of the NRC cohorts are except for ischemic heart disease Most of the risk coefficients are positive though. Not many of them are statistically significant There is no significant difference between male and females for industrial radiographers and nuclear power cohort When we pool everything together into MPS one, it'll be the most informative the Parkinson's disease finding warrants additional study frankly and to understand really what's going on with the epidemiology and the response and One thing that we haven't mentioned much here is we're entering an exciting phase So far all of the data that we've presented is on outcomes that are mortality outcomes What did you die of what you know? What was the cause of death and the contributing cause of death? So we have just submitted over 800,000 600,000 Workers to the Medicare data system to get linkage from that now of course you'd have to be in Medicare from 1999 and the rest but we think it would be extremely informative on incidents and related confounding chronic conditions Obesity some are you getting treated for smoking? You know these sorts of things So we think that's an exciting area that will will really refine the million-person study overall one thing We could do better on and the NCRP has suggested perhaps we could do this is To understand better how we do heart dose so I've talked about the heart outcomes and really we're sort of drawing a volume around what we consider the heart and We do mean dose in that region perhaps heart Maybe there are sections of the heart that would matter more or maybe it's related to you know for a brain The cerebrovascular maybe it's related to carotid dose. Maybe it's related to kidney dose Maybe it's an inflammatory response that the whole chest dose is better So we think that we should pull together a scientific committee to understand better What should we be giving as dosimetrous to the epidemiology community for doing that? Before we go change any radiation protection suggestions based on the heart Just acknowledging the over 100 investigators associated with the million-person study Thanks very much for the opportunity Thank You dr. Dower I appreciate that and that was that was good to see that all summarized like that Appreciate the effort there. So our final speaker for the panel is we're gonna go to space Dr. Steve Blatnick. He's been He's worked on a wide variety of different aspects of space radiation research for the last 20 years at NASA He graduated from the University of Wisconsin Milwaukee with a PhD in physics His recent research focus has been on the development of probabilistic risk methodology in Radiation biology modeling for effects including acute radiation syndrome Cancer cardiovascular disease and degenerative central nervous system diseases He was the project manager for the space radiation Transport and measurement project and was the PI of the space radiation risk assessment project Dr. Blatnick, he's joining us remotely. There he is Thank you. Can you hear me? It's it's not we can hear you but it's not real clear Okay, though headphones work fine. So okay, I'm like he can see me good. Yes, you're doing great I can't see you actually I can't see my slides. I can see you though. Okay, so I'm gonna Talk talk a little bit about the importance of radiation Epidemiology to explain space exploration Well, I NASA's interested in overall topic of radiation and I'm gonna touch then a little bit more specifically on the the million-person study activities and a little bit more an overlap between space radiation research and Terrestrial radiation research So can you go to slide number two? Okay so the there's actually a lot of Radiation in space and the space radiation environment is relatively complex coming from Several different sources. One of the the main components that are of concern is called the black the cosmic rays And this consists of ionizing particles Primarily ranging from protons to nickel and with energy ranges from KV to TV So you have a very wide range of energies and particle types the intensity then varies with 11-year solar cycle so this that that's the activity of the Sun as the the Sun becomes more active the magnetic field expands and that the interplanetary magnetic field actually protects the Near near Earth and Mars from the galactic cosmic rays, which are of extra galactic origin The other main source that we are concerned with our solar particle events so again, the Sun is active and There are periodically eruptions from the Sun and then those will propagate out through interplanetary space and Accelerate various different ions in the interstellar medium and and from that come off from the Sun itself from a radiation protection perspective the the main particles are concerned our kind of medium energy protons and so medium energy in this context would be Mev to hundreds of mev to maybe a GV and they come out in hours to days and in quite large amounts And their probability of occurrence varies with the solar cycle So you can't really predict when they're they're happening, but they're more likely when the Sun is more active Those two types of particles can then interact with planetary surfaces lunar surface the Mars and Basically because they're high energy there's going to be a lot of fragmentation in that surface and you're going to get Basically neutrons Diffusing out of the surface and so you have a base a neutron flux coming out of the cloud You're both a lunar surface and the Martian surface that goes into the atmosphere The third main environment is we have low Earth orbit and that's where the International Space Station currently is it It is very just slightly above the Earth's atmosphere and within the Earth's magnetic field So the GCR it still gets hit by the GCR But it's modulated by the magnetic field So it's not as intense in in free space and there's also trapped proton belts then Allen belts that you get exposure to and in particularly the What's called the south Atlantic anomaly? So Space Station is actually was put below the main part of the belt But there's an anomalous part where the the belt dips low and it passes through that and gets a significant exposure So those are the the main sources of radiation and then You then have them interacting with the spacecraft and the body and so you you get a large range of particles including lots of neutrons With very large energy ranges and so the the main thing here is that you the space radiation environment is really quite complex Consisting many particle types orders of magnitude and energy varying in time and by destination Essentially where you're going and what your mission looks like So can you move to slide three So I'll go over here just an example of some of the missions current missions planned missions And in what the rough exposures are one thing to keep in mind is that NASA is very active in doing some of these plans So so the planned mission profiles are changing these exposure estimates are from Lisa Simon said at all in the reference at the bottom And then to you do do the analysis for a given mission, but a person's career will Potentially consist of multiple different missions to in the future to different location locations including Lunar in the near future and then Potentially Mars in the farther future So right now missions are currently going to to the space station ISS and and they're typically of have been a Six months or your durations and you can see one mission to ISS if you do a year mission puts you above what's considered typically considered the low-dose region and you can get 100 millisieverts to 200 millisieverts and that'll depend on the solar activity as well as other factors in the mission and Then people have completed multiple space station Mission so so those doses can accumulate and then some some some of the crew have accumulated already just to significant exposures And and now the the big plans are really to go to the moon and then eventually on to Mars and so the mission profile the current plans which are somewhat influx the way this is going to work is they are going to Send up what is essentially another Space station in lunar orbit and that is called Gateway and then from that gateway station They will descend to the to the surface and then re-ascent back to gateway to come back to earth But the the missions kind of Build up so you might just go to gateway first before you go down to the surface and you can do different combinations All those plans aren't set. This is more to just give a feel of some of what the exposure Profile looks look like and so Sardis Sardis a quick mission. So if you just go to the lunar station gateway station, you won't get Very large exposures And then you'll build up You'll descend to the surface and a two-week surface stay again Not not that much, but then the idea is is you will build up stay time over time and as an infrastructure gets developed in Near near lunar space and and on the surface And so once you you look at, you know, potentially a year mission on the moon You're getting up to significant exposures 300 to 400 Dose equivalent and then a year a deep space habitat again, there's there's different Mission profiles here, but this could be in the gateway Station or there are plans to actually in the future potentially do the Mars transit habitat and attach that to gateway for a while But if you look at potentially a year mission there, you're 500 to 600 millisieverts and then if you look at what a Mars mission might look like you're you're up near Seaverts and all these things depend on a lot of factors That go into the mission analysis. So so the detail the importance here isn't the details so much as that You know, you can get a lot of variation, but NASA's Concern isn't really low-dose radiation in the future and even currently with some of the Multiple stazons face station. You're really more in the intermediate dose region and you know somebody who has Experience and then goes to a Mars mission might be receiving quite a bit of dose in their career Okay, next slide slide for So because there's these Gonna be these exposures so there's there's NASA's research strategies to analyze and Try to mitigate the Impact from space radiation and so there's right now the health effects of primary concern our cancer cardiovascular disease and potential central nervous system impairments One of the ways to constrain the potential health effects is through permissible exposure limits, which most of this audience is familiar with for NASA the primary Pell which really impacts Most things is It has recently been updated and now is basically a 600 milliliter seabird effective dose Limits and that's over the career and this is intended to limit the risk of exposure induced the death from cancer to less than 3% Inclusive of age and sex So it's it's set to protect the most vulnerable to less than 3% There are also exposure limits to prevent Currently CVD and CNS and these are currently not risk-based, but assume a threshold dose And so if you look at those limits from our mission Estimated exposures are currently above the set Pells and so that that then and potentially above both Possible thresholds for cardiovascular disease and central nervous system impairments And so there's a need to try to mitigate the effects of radiation and and shielding shielding is the main Strategies that's used on the ground. It is of limited effectiveness in space because of the high energy nature of the particles so you can A fairly effectively shield from the solar particle events and you can from Trap particles, but the GCR which go up to such high energies shielding Can't can help a little bit, but is not going to significantly address the overproud problem because you would just need to Just massive amounts of shielding because the energies are the particles are so high and really the cost constraints and the difficulties of Sending huge amounts of mass in the space really prevent that so one of the The parts of the strategy is to look at potential medical countermeasures that might Be developed to in the future reduce the impact of radiation And so that's the overall strategy and so radiation epidemiology fits into this in order to really to Establish what the risks are And and then To reduce the uncertainties associated with the overall strategy and we're targeting mainly cancer cardiovascular disease and central nervous system impairments Next slide slide 5 So that leads into risk modeling and what we're currently and planning on doing to estimate the The risks from space radiation And so you can't get really risk estimates from the current astronaut Not cohort because of the small numbers if you just look at it Very few few people have flown in total and and really you didn't get start getting large exposures until really long Duration ISS missions where they're up there for substantial amounts of time For example for the Apollo missions, they were out in free space But very short durations and most of the shuttle missions didn't go for very long So they weren't up there long enough to really get significant exposures So you can't do it from the cohorts you're interested in directly. So you need a different approach and the approach For cancer is is quite similar to Risk models used for other applications like the NIOSH risk model or the NCI risk model for cancer And it's currently developed And the one that's currently developed in in use is using the the data as the baseline from Hiroshima and Nagasaki lifespan study And then we have to scale those Results, which are primary gamma exposures to the very complicated space radiation environment. And so that that's those you have A lot of work that will have been done to develop quality Models in particular And then those rates are differently And so that's one difference where these these scaling Factors are actually the the largest uncertainties and then that's a cancer risk model and are more important Then for some of the other applications for example, where you can actually study The the populations that you're interested in when you're dealing with some of the cohorts on the ground And and we're that's Currently in use and was used to set the the the recent update to the permissible exposure limits and it's also Currently used for communication purposes to the astronauts and flight surgeons for informed consent and other other applications We have also developed cardiovascular disease risk models They are not in operational use But they're currently a research activity and the initial approach is to essentially We're the same overall framework as the cancer model where where you look at results from double AT exposures and then a skillet to the complicated radiation models And then if you look at where we are for essential nervous system effects, there's just no risk model Available and really the primary question that we want to answer um initially Is whether space radiation poses a significant risk for late cns effects In humans, uh, and so there's uh Already initial results from the million person study that they're intriguing and um, uh, there there's also been a lot of radio biology Data showing that there's short term central nervous system effects And so that was really what kicked off some of the activities looking at that next slide slide six so, um just some of the the Recent current and possible future things uh that we've done with the million person study and and a little bit with the ncrp more generally What one task that's just finished up is is an examination of the sex dependence of lung cancer And so this was started when the permissible exposure limits were actually risk based So the um this sex difference was actually impacting the time, uh females could fly versus males. That's since Changed um as as I mentioned before but it's still important question And so the when you look at the overall cancer sex dependence In the risk estimates, they're dominated by lung cancer. And so we really which is a little bit counter intuitive So there's the the question of whether this was real Or some artifact of uncertainties in the data in the models So we uh, there was a task Actually two two part task that was set up one was with a million person study to update their models to um Address this question Directly and then also to uh ncrp committee Uh that was then also uh stood up to look at that and then the wider evidence range of both epidemiology And uh radiobiology to kind of weigh in on that question. Um, and then give also give recommendations on uh future Work research that needs to move forward on that topic. And so that has just Relatively recently come out and that's ncrp 32 and which was uh In my opinion very very well done and and I think that was uh, um Overall very good good activity. Um, that was very beneficial to nasa and probably to others as well One other uh major areas was really uh, the cns task or um central nerve looking at central nervous systems tasks and and this was really set up in True components. Um one looking at uh, high let exposures from uh internally deposited radio nucleos and and the other looking at More low let exposures So so here um the question the initial question to to focus on is really as um, uh, both Larry and kathy mentioned some of the results already for example for parkinson's disease But to really just establish whether we can um See whether there is a risk and whether it can be seen in um Humans and then that can then uh, once we get an answer to that question We can to determine the research strategy forward better and and the the Environments of these exposures are quite different from the radiation environment But they're they're very relevant and in this sense particularly in answering that initial question for example, if you see A risk in both high let and low let exposures it is almost certainly going to be in the space environment No, excuse me. My throat's getting a little dry And then one thing that we're looking at um as a possible future efforts is focused on nuclear submariners And the idea here is that you know radiation isn't the only um Stressor in space you have um, you know, particularly if you look at a mars mission People are going to be away from earth potentially for years So you have confinement and um, you're in a small space and uh, there's just a lot of different factors and so the Nuclear submariners is one of the closest analogs That that you can find really on on the ground And so uh, this is a way to potentially study not just the radiation component But these other components and then how they interact Because again, if you go back to the fact that there's not going to be enough people flowing in space Any time in the new future to do direct estimates very well from from that kind of data. We have to develop ways to um Uh develop models to project out these risks and develop countermeasures Based on what we can get from uh combinations of like the terrestrial epidemiology and then integration created with radio biology so this can might become a very very important piece in in uh, eventually relating the radiation risk estimates to the more the fuller environment in space And then overall All the radiation epidemiology results that improve the understanding of radiation effects are of potential use to nasa Because the radiation environment is is is so complex We have to put those pieces Together and and we will take the information that we can and make the best use that we can of it So just um Some final thoughts uh here and so again So we we we can't estimate these risks directly. So we have to make use of all these different Information sources the radio biology the terrestrial epidemiology other Other stressors from the submarine airs the million person uh study provides valuable information here It's low low dose rate and both high low lat exposures and then now we're looking at potentially some of the other stressors as well and just uh, uh, we leave off with one, um uh Final final comment here is that um, I think there's potentially more more overlap between some of nasa's interests and low dose research Generally and then possible some interest uh overlapping the interest with the nrc as well in terms of the research and um There's a few main aspects um that that come to mind and the improvements and risk assessment methods That that's going to be important to all all of these areas And one particular piece is You know, you you have the radio biology information. You you have epidemiology From individual studies and meta studies. How do you really integrate that in a systematic way? To directly answer specific questions For for regulatory applications development of countermeasures and and other things and really tying the information in the best way You can to the specific question you're trying to answer and then also to uncertainty quantification Including one of the big things is the shape overall shape of dose responses And then that that that can impact the overall risk assessment in multiple ways and developing methods to uh Better include that that that is currently done And then I think there's also the the question of just generally with cardiovascular disease Uh and central nervous system diseases Are there significant risks at doses lower than previously thoughts? Um And then in terms of overall research strategy, um, this is on the radiobiology and not the epidemiology and But the development of research models, whether it's cell tissue chips or animal bundles to better assess, um The overall biological The overall biology Changes from radiation at low and moderate doses Uh and that is It thank you Thank you so much. That's that's fascinating when you think about all the the launch risks the habitability risks and then All we're up to All the different things we have to think about on these long missions very very very interesting I thought it was a nice addition to the panel. So now we have questions that we've received through the qr code I was told we're not doing the phil donahue style Question asking anymore. So everything is on this tablet right here. So i'm gonna i'm gonna I'm gonna divvy up the goods here I'm gonna ask Kathy one here and that came in and it is on the the slide on the radium girls mentioned dna methylation Right radium girls. So does the analysis of dna methylation provide any clues to cancer incidents among the affected women? That that's a study that has been suggested by some as I understand it from some evidence that has shown that methylation In dna increases with aging and it increases with oxidative stress And so there would be some interest in in what that might help us understand mechanistically From these studies and it it's an endpoint that could be measured We're certainly in the million person study and in a lot of the nasa related research Looking at at improved as as steve just showed mentioned in his last slide improved Endpoints that we could get as surrogates for the ultimate endpoint of death by some some Endpoint whether it's cardiovascular disease or or cancer or whatever. So that really is a speculative Endpoint that could be looked at And i'm not sure that we know the answer to that one at this point Okay, steve. This one's for you What are some of the potential medical countermeasures that nasa is researching? um so Let me start there's there's a couple so there's uh, uh A few that are kind of very uh early clinical stages where they're looking at Potential drugs that might limit the effect and there's been a couple tests on Which might be surprising on aspirin and warf warfarin these came up because of basically just Some of the epidemiology that's been done on them where the cohorts have significantly reduced cancer risks In the background and so there's been some animal studies that looked at Those to see if it reduced the the radiation risk Unfortunately, the results to date are that they do not one of the other Methods that we're really looking at is to try to leverage basically And starting with cardiovascular disease kind of terrestrial methods of cardiovascular disease risk management so we're taking the tact of trying to include the radiation risk into A overall cardiovascular risk assessment and use that risk assessment in the same way it's used for in clinical guidelines for Primary prevention of cardiovascular disease currently so you might make Recommendations to take statins early or for example because you have this extra risk from cardiovascular disease However, in order to do that you need to really develop Risk models that are personalized targeted to the person. So that's an area of ongoing research that we currently have Okay, thank you. Larry this one's for you Uh, when do you anticipate results being presented from the linkage with Medicare information? That's going to be more for the cancer incidence piece So as you can imagine the million person study has quickly once we did that linkage Become a big data study if you think about it. We have 50 million person years of data Give or take that's that's the maximum And every one of the organ doses And what they've done and now you add on to it the potentially billions of claims based Medicare information. So we are seeking assistance From several other researchers to help us sort through that from a computer standpoint However, we we have a path forward We think that in the first two years or so or three we could Get informed information on Outcomes on mortality first while we're sorting through literally billions of data points And so we expect Maybe five years you'll see Some incidence data Folded into the million person study But as we get more information say on a particular cohort or a particular outcome We'll be sharing that data as as it comes out in in publications as it goes But our plan is really two years proof of principle On on some of the con you know those chronic conditions that I talked about Obesity Diabetes smoking and others first and how they inform on the mortality outcomes And and that's to give us time to pull together the incidence data And just one thing to note on the cms data. It's claims based incidence data So we have to understand that if somebody got paid for it, then we'll know And so we're sorting through what does that look like and developing algorithms right now to go back in time as early as we can within that data set so three to five two years maybe a hint and Five years we should have real results to share Thanks Larry this one's for you Kathy Interesting it's from questionnaire from looks like australia I wonder about the feature of continuous radiation exposure for submariners Is there a reduction in their exposure to background radiation when at sea? I would expect some shielding of cosmic and terrestrial radiation by seawater and almost zero radon exposure of course So if you think about it, there would be lower doses because you're surrounded by water And that would take care of some of the cosmic Doses and Radon would very much be reduced if there was any So we recognize that but remember when we do these and that would show itself perhaps in That smr analyses maybe maybe But that's part of the reason why we do within cohort assessment So we're going to evaluate anybody been in the navy anybody in the navy. Okay, so how many of you are navy nukes What did you call the guys in the in the front of the boat that we're not navy nukes? Yeah, or forward Pukes or something like that right so in other words there's a cohort of folks who are in our submariners who who receive very low dose if any And we'll be able to use them In performing the study so they're going to be exposed to very similar Situation very similar multiple stressors, but without radiation So we think that that will be helpful and informative overall, but that's a great thought We we considered that a little bit when we got going on the submariner study. Good question Thanks larry. I could never be a submariner all my grades are at sea level Nothing nothing. Okay All right, here's uh, I always anticipate the lnt question And they always come so i'm going to let all three of you have a crack at this one because it's always of interest and It's entertaining usually um Anyone want to comment on the implications of the mpp and other results on the lnt model? Well, larry you want to start I'll start with a few considerations So so far the million person study results that we've been showing and several of the meta analyses and the rest You have to recognize those are based on Smallish cohorts though some of them are as big as some of the cohorts that are studied right the nuclear power study cohort That's a really big cohort of 135,000 and 125,000 and industrial radiographers And yet we need all of that power when we roll everything together into the million person study So hold your breath give us a few years to pull together the pooled to give us the real data So i'm i'm couching the that way a little bit Of course, that's part of the big reason we're doing the million person studies to understand what the data really shows In the cohort so far The because they're small and and generally the doses are low with the exception of perhaps the nuclear power cohort and the industrial radiographer cohort frankly The confidence intervals are rather wide For those individual cohorts So it's hard for me to say at this point or any of us to say at this point Well, if we look through the glass darkly we see this as as what's coming I can say a few things definitively based on the results so far In general the confidence intervals still include on the small cohorts They still include about the same estimates that come out of the atomic bomb survivors However, I gave you a hint when I showed you the linked together group when we pooled medical worker industrial radiographers and the the nuclear power Those confidence intervals start to shrink as we as we would expect we get a lot more data a lot more power Where is it going to end up? We won't know until we do the pooled study And the the second thing that we can say is in general if we see a positive trend Right now for the smaller cohorts that trend line seems to be Lower for the central estimate than what the atomic bomb survivor data I'm I'm couching that in care, right? That's just these small cohorts with wide confidence intervals But those are things that we have seen we've seen generally a lower Slope But the confidence intervals could include the estimates from the atomic bomb survivors so far Sure, I can say that from kind of the the nasa perspective Look at it a little differently and particularly when looking at cardiovascular disease or central nervous system effects where there's not really as much Very little evidence on what the shape of that that dose response might look like And I think the the question if you look at things from trying to answer questions From a risk perspective you can frame it in terms of probabilistic risks And then the question becomes is what is the uncertainty associated with the the shape of the dose response? So in terms of our strategy moving forward in the research group that we're doing It's to try to then quantify that uncertainty and there's different methods that can be used So so the the question isn't really whether it's linear no threshold or not It's what is the the shape of the what is the uncertainty due to the shape of the dose response And we're pursuing in particular ensemble methods where we can fit multiple shapes and then propagate that through a risk methodology Great Just two other points to to add on to that one is of course We're evaluating all of the dose response shapes as we do these so far and so that's an important point And in most of the cases linear fits as well as Linear quadratic and any of the other models So we we do include that information in the supplementary data for the the studies And of course we're going to be doing that part of the reason we're doing the overall study For as we pull together we'll have more informed Information the other thing to point out is the million person study is of healthy u.s workers Most healthy u.s workers receive low doses chronically over their lifetime And and that is exactly the group that we're trying to regulate with policies and the rest so We just have to remember the framework of the dose distribution up to about a gray Right a gray and a half or so we have to and we're really that that is the group that we're most interested in And and so whatever the results are should really inform our our policy moving forward as we transparently share the information and We're trying to put the science together and then and then we can chew on it together in informed conversation Okay, thanks larry and I want to thank our panel members for this session I thought it was very informative and I appreciate you coming down to the nrc rick to to talk about your important work and How it applies to uh, not only nrc, but also across The whole radiation protection world. So it's very interesting to see so I want to want to thank you again And thank you for the questions. They're good ones