Good morning everybody, no, hello everybody, I recognize it's not the morning anymore. My name is Serene Haydar. I am the clinical pharmacy, one of the clinical pharmacists at St. Jude Children's Research Hospital and I did the implementation along with my team members for the implementation of pharmacogenomics at our institution. What we're going to talk about today is about the clinical, just clinical pearls for implementing a pharmacogenomics if you're interested or are about to start or have recently started implementing pharmacogenomics, what are things that you should keep in mind or things that we have learned along the years that may help you as you're going through your implementation story. So throughout the next hour what I'm going to talk about is really, I'm going to discuss three stories. The first one is going to be how to report incidental findings and have a process for discussing familiar implications of pharmacogenes and pharmacogenomic testing. The second story we'll talk about is how to update pharmacogenomic test results and considerations for that and finally we'll end with adapting and migrating to a new electronic health record which is something we had to deal with at St. Jude over the past year and a half. Just quickly before we get started I just wanted to give you a landscape of what St. Jude's pharmacogenomic program is. The protocol that we currently genotype patients or the majority of our patients on a protocol called PG4Kids, the goal of this research protocol is to migrate pharmacogenomic tests from the laboratory into routine patient care for the results to be available preemptively into the medical records as well as for clinicians to utilize this information routinely as they are thinking about pharmacotherapy in our patients. Sorry to interrupt, your video is off.  Can you see me better? Can you see me? Yes. So we elected to return and genotype patients on a protocol instead of clinical care because we started this program about 13 years ago and we wanted oversight from the IRB for incidental genomic findings that could have occurred as well as oversight from the IRB to have a process because we were currently are also withholding results for pharmacogenomic tests that are on our array until they become clinically actionable. So our process is as follows. Patients who are eligible for genotyping are approached by a group of trained research nurses who approach the patients and discuss pharmacogenomic testing with them. Patients are, there's a consent discussion that occurs with the patients and their parents at their minors after which genomic DNA is obtained from a blood sample. The patients are then genotyped on an array of pharmacoscan array by Thermo Fisher. We receive about 1200 gene test results on this, on this array. The majority of the genes remain in a research database and are migrated into the electronic medical records when they are available, when they are clinically actionable and then migrated into the EHR where they are available for clinical use, available for clinical decision support, and at that point we return results to prescribers and provide patient education about the results. We currently return results for 15 pharmacogenes. We did not release every, we did not return all these gene test results at once. We started with two genes in 2011 which are the two genes we were the most comfortable with and then added on over time and availability of CPIC guideline and as the evidence for pharmacogen, for relationship between a pharmacogen and the drug became strong in the medical literature. So we are at 15 genes that are implemented. We currently, we have implemented length 74 drugs to these genes over time and we'll talk about them. We've had to update pharmacogenomic information. So we've genotype, we've linked 74 genes to, 74 medications to 15 genes but over the, over the years have had to unimplement certain medications and these are the ones that are in red that are crossed off with a year that they were D or unimplemented at our institution. The first story we're going to talk about today is how to deal with familiar implications of pharmac, after pharmacogenomic testing. So just to kind of understand where familiar implications comes, these are the genes, these are the most common pharmacogenes that are available currently in clinical practice. The first one that I'm going to talk about related to familiar implications about pharmacogenomic testing is related to G6PD because G6PD is located on the X chromosome and this allows us or causes us to be able to identify or have suggestive findings of sex chromosome abnormalities. So the only gene that is currently the only pharmacogenes that is on the X chromosome is G6PD. So just a quick overview about what G6PD is. G6PD deficiency is an X-link disorder that manifests as patients developing hemolytic anemia most of the time when they have a triggering agent or exposed to certain stress, foods or medications that can cause hemolytic anemia. It is the most common genetic disorder worldwide about 400 million people globally are thought and estimated to be G6PD deficient. It is most commonly seen in Africa, Southeast Asia, the Mediterranean area, and the Middle East. So why are we talking about G6PD deficiency as a pharmacogen? So as I mentioned, G6PD is located on the X chromosome. So males will have one copy of this gene. So it's easy to assign a phenotype for these patients. Males will have a single allele and one allele will determine the phenotype that the patient has. Females have two alleles, which means that we will... That the relation... Both X chromosomes are important in determining genotype for patients, for female patients, and then when we find... When we have a patient who reports as a female and we know how to X chromosome, it is expected that we will have two alleles for the G6PD gene. And then what usually happens is that... And not usually what can sometimes happen is when we have male patients who are phenotypic males and we have two X chromosomes reported on them, which means that these patients are supposed to have one X chromosome, they have two, and then the question is what do we do with that? So just defining that the patients may have an extra X chromosome after confirming, obviously, that the results from the lab are actually correct and there was not a sample mix-up. So what does it mean for a male patient to have two X chromosomes? This is a syndrome known as Kline-felter syndrome. So 47 XXY is one of the manifestations of Kline-felter syndrome. It is a chromosomal condition that affects males, physical and cognitive development. These patients tend not to produce enough testosterone, they have delayed puberty, they have breast enlargements, and fertility is also a hallmark of Kline-felter syndrome. Children who usually are younger tend to have learning disability, delayed speech, delayed language development, and compared to individuals who have an XY karyotype, patients who have Kline-felter syndrome are at increased risk of female-related disorders such as breast cancer, systemic lupus and osteoporosis, and throughout their lifetime will have to be monitored for these conditions, which is something that you also would evaluate in a male patient that probably less, because of the lower incidence, it is not something that people will tend to think about. So we consider, and the medical community, considers Kline-felter syndrome as an incidental finding when you're genotyping patients for G6PD and you notice and you find an extra X chromosome. But what is really an incidental finding? By definition, an incidental finding is a result that is not related to the indication why the test is being ordered, but nonetheless it may have medical value or utility to the clinical team and to the patients. Incidental findings are commonly referred to have different names. The most common terminology that you will see would tend to be either secondary findings or unanticipated findings or an unexpected positive finding. Incidental findings in pharmacogenomics are more likely to be discovered when panel pharmacogenomics testing is ordered, as opposed to single gene, because when you're going to do a single gene test, it is easy to explain to the patients what are the possibilities of us finding certain results that we may not have expected. When you do a panel test, there's a lot more genes that are going to be reported, and this tends to be the context in which patients are discovered to have client filter syndrome. Our experience at St. Jude has been with X chromosome abnormalities. We have genotyped about a little bit more than 6,000 patients on our PG for Kids protocol. We have had four phenotypic male patients who have had a suggestive finding of two X chromosomes. They had a 47 XXY karyotype. All patients were younger than 18 years of age. We discussed with their parents the possibility that the patients may have client filter syndrome gave them the option of confirmatory testing and also patients have been confirmed as having a client filter syndrome. We have one phenotypic female patient with one X chromosome and one Y chromosome who has diagnosed, who also had a flyer syndrome. If you are going to consider genotyping your patients to determine a G6PD phenotype or their G6PD status, this tends to be our recommended steps of action for managing patients who may have either client filter syndrome or any of the other sex chromosomes related abnormalities that may occur on, in our case, the X chromosome because of G6PD. So, first step would be that if a patient has a suggestive finding for G6PD to inform our process, it's to inform the genetics team as well as the primary care teams of the G6PD genotype finding. Pharmacogenomic testing at most institutions, including ours and most clinical laboratories, is a clear certified test for pharmacogenomic testing. It is not clear certified for karyotype testing, so there's a need for confirmatory testing to confirm that a patient may have client filter or confirm that a patient may have an extra or missing X chromosome. So, after the genetics team and the primary care team are informed of the finding, we sit down and offer genetic counseling to the patients and their family members. If they do consent to consultation with the genetic counselor, then the genetic team will counsel the patients on client filter syndrome offer confirmatory testing, and when confirmatory confirmation of client filter syndrome is obtained, the patients are referred to a specialized team for follow-up care, such as with endocrinologists or follow-up for other age-appropriate follow-up tests for patients who may have client filter syndrome. So, this is the first case that I wanted to discuss, patients in whom we may discover sex chromosomes abnormalities when we're genotyping for G6PD. The other case I wanted to discuss is the case of malignant hypothermia and familial implications to pharmacogenomic testing. So, let's discuss this as a case. A six-year-old boy who undergoes preemptive pharmacogenomic testing is found to have a high-risk variant in the RYR1 gene, and this high-risk variant predisposes the patients to developing malignant hypothermia when they're exposed to triggering agents and we'll get into that in a minute. The patients and the three siblings have not had pharmacogenomic testing ever in their life. So, for those of you who may want to refresher on what malignant hypothermia is, it is a potentially fatal disorder that occurs due to an acceleration of metabolism in skeletal muscles. It leads to a prolonged contraction of muscles which can cause muscle destruction. Rhabdomyolysis can lead to tetany, fevers, and patients can die because of it. It is a genetically-inherited disorder in two genes that we know of at this time, RYR1 and CATNA1S. These two genes have an autosomal dominant pattern of inheritance. So, people who have a high-risk genotype have inherited one high-risk allele are at risk of having that susceptibility. And if a person has that one high-risk variant, it means that one of their parents has passed this down to them, meaning that one of these parents is also susceptible to developing malignant hypothermia. So, as we were thinking about how to return RYR1 and CATNA1S, there were some key considerations that we thought that we had to think about. So, it's important if you are going to return these two pharmacogenes to have a process set up and approved at your institution before you start returning these results. If a patient, should your institution offer genetic counseling for the patient's family member because this is a gene that has an autosomal dominant inheritance pattern. If you find a patient who has this high-risk, potentially fatal condition, what is your responsibility? What is our responsibility as an institution? Should we offer counseling to the family members and let them know that they may be at risk? So, should we offer counseling? Which family members should we offer counseling to? Should genotype testing of family members be offered at our institution? Or should we just inform them that there's an option for genotype testing and who will perform that? Where will that be performed? Where should the testing occur? And again, who is going to pay for the genetic testing for the confirmatory testing in the family members? So, what we elected to do at St. Jude is that we will offer genetic counseling and confirmatory testing at our institution We will offer cascade testing, which means testing of all the patients first-degree relatives, so mom and dad, and full biological siblings. And testing will occur at our... The testing cost will be assumed by our institution. So, this patient that we had, the parents decided to undergo pharmacogenomics testing and confirming pharmacogenomics testing to the whole family. The patient had two sisters, a brother and obviously, and at the time mom and dad were available. So, they all opted for genotyping, and it was found out that dad and one of the sisters was also a carrier of that high-risk R1 genetic mutation that the patient had, which meant that all three individuals were also genetically predisposed to developing malignant hyperthermia if they're exposed to triggering medications such as inhaled fluorinated anesthetics or succinylcholine. So, after we found out about the results, we counseled myself as well as the genetic counselor, sat down with the patient, and discussed what it means for the patient, as well as the family members to have this R1 genetic mutation and offer genetic counseling related to that. So, again, what are our recommended steps or the steps that we have created for managing pharmacogenomic test results that may have familiar implications? Once we receive the pharmacogenomic test result, if it has a familiar implication and it's a high-risk result, the first step for us is to inform the primary care team and the genetic counselors of that high-risk pharmacogenomic test result. We return the results to the patient, offer genetic counseling to the patients and if they would like to speak to a genetic counselor to learn more about family inheritance patterns of this high-risk result. And then if the patients agree to genetic counseling, genetic counseling is performed as well as confirmatory testing within our institution. So, these are just two examples of familiar and incidental findings that are related to pharmacogenes. There are others that I wanted to quickly mention. Genes that have dominant expression patterns include MTR and R1, HLA and NHLA, in addition to R1 and CSNZ1S that we discussed, and then the gene that is linked with X-linked inheritance is D6PD. What are key takeaways to take out of this first story for familiar implications of pharmacogenomic testing? So, just remember that most pharmacogenes have a co-dominant inheritance. They are not dominant genes, so there's no direct implication for family members. Some pharmacogenes, as we discussed and showed, have dominant inheritance patterns that have familiar implications, and it is important to have a process set up and approved by your institutional leadership and oversight committees before you start returning these results to patients. So, moving on to story number two, how to update pharmacogenomic test results. So, we have been genotyping patients for about 13 years, and as you can imagine, pharmacogenomic testing and not just the testing platforms, but information related to interpreting pharmacogenomic test results has changed over time. So, we currently report pharmacogenomic test results in the lab sheets and the flow sheets of our medical records, and we made the decision many years ago when we started this process that clinicians may not necessarily understand what a, let's say, CIP-2B6-STAR-2-STAR-5 genotype is. So, every single one of our results is coupled with an interpretive consult that is written by a pharmacist that is associated with each one of these results, and for example, you will explain what the phenotype assignment is for that patient as well as explain clinical implications of that test result. So, also, what we do is that whenever we return the results, place them in the medical record, in addition to the consult, we also add phenotype-specific genomic indicators and problem miss entries into the EHR as applicable and when it's applicable to add that information. So, over time, we've had to create a process for updating pharmacogenomic test results, and this process is led at our institution by the pharmacogenomics program, and it includes information such as updating the patient's phenotype when applicable, updating the interpretive consult note that I just showed you. We, once that interpretive consult note is updated in the medical record, it shows up in the EHR as a corrected result. This is the only capability that you have in the medical record system to update information that is already posted, and so the information that we update in the consult note includes the phenotype, the activity score, as well as the ideal function, as applicable to the update and to the specific updates. We also update the genomic indicator if the phenotype of the patient has changed and also update or add a pharmacogenomic problem is when applicable, depending on the change in phenotypes. Clinicians and patients are notified of the update only if a phenotype change occur. If an activity score changes but the phenotype hasn't changed, we tend not to inform patients and the prescribers because it's going to confuse them a little bit more and it's not clinically actionable. So, we have worked on updating phenotype-specific results in the medical records for the clinicians, so in our current EHR, but also made it a point that the patients also be able to see their updated results in their online portal, so they are also available in the portal and when the results are updated, patients get a notification in the portal that says that their pharmacogenomic results have been updated. We decided that we will update any results on any patient who remains enrolled in our protocol and is alive, irrespective of when the original test results was generated. We had a lot of discussions about this through discussing what is our responsibility. Should we update the results from 10 years ago? Maybe the patients are not looking at their portal. They don't even know that they still have a sentient portal. What should be done with older results? We decided that we will update results independent of when they were generated at the institution. We published on this about four years ago. In June 2019, most of the results that we had updated were related to CYP-2C19 and a phenotype change in CYP-2C19 for the ones of you who are in practice then, if you remember, there was no CYP-2C19 rapid metabolizer phenotype. There was only a CYP-2C19 ultra rapid metabolizer phenotype. About 3% of all of our results had to be updated to assign the new CYP-2C19 rapid metabolizer phenotype in the patient category. Again, we went through all the updates and updated the consults, the genomic indicator, the problem list, as well as notified clinicians and patients about this update. Flash forward five years, four years now, and we are again dealing with an update to the CYP-2D6, so not CYP-2C19 this time, but a new update. In November of 2022, there was an update to the ideal functionality of some CYP-2D6 variants that are listed on this slide. The platform that we currently use, which is the Pharmacoscan platform by Thermo Fisher, interrogates two of these ideals, Star-9 and Star-41, and this update led to a downgrade of activity score for CYP-2D6 Star-9 and CYP-2D6 Star-41, where the activity score was downgraded from 0.5 to 0.25. Nearly 16% of the patients that we genotype for CYP-2D6 would have had an activity score update based on this Star-9 and Star-41 change and an allele functional assignment, and so this is where you can see it on our patients. We would have we will have a process to update these consults and the wording and the activity score that is mentioned in the consult for the 1,000-plus patients who are affected. However, the good news is this does not result in a phenotype change for 1,000 patients. It actually only resulted in a phenotype change for three patients out of the 1,030 patients who would have had the Star-9 Star-41 and yellow. So it's not a huge change a huge number of change in phenotypes it is mostly a downgrading of activity score that does not change phenotype and so it's not very at this time clinically burdens for clinicians as well as patients because they're not going to have a phenotype change. So the question I get routinely asked about is well, how do you know that there are patients genotypes? How do you know that there are updates that are available? How do you know that Star-9 and Star-41 were downgraded? And so there's two places free to go if you want to do this. The first place is if you go to the CPIC websites on the bottom right of the screen click on contact which will be as one of your tabs and you'll be directed to this page that shows you options for CPIC communication click on the where it's under I want to get announcements. This is a link. This is a sign up email that functions even if you're not a CPIC member. So sign up you'll get email notifications whenever there are new guidelines that are published, whatever there's CPIC news or whenever CPIC wants some feedback. You don't get a lot of these emails so don't think that you're going to be spammed. It is only tailored to whenever there is something that is important to announce through the CPIC website through CPIC. Another place to get that information from is going to FarmGKB. So if you were on the earlier MedGNED talks and NHGRI talks from this morning you would have heard Dr. Cotto and Dr. Will Carrillo talk about CPIC and FarmGKB. If you go to the FarmGKB website again bottom right of your screen here scrolling all the way down to the bottom of the website there is a link there is a button that says get latest news by email and you'll receive the latest FarmGKB blog news and again you don't get tons of them you won't get spammed it is just when there's information that is important to circulate out to the membership and the people who have signed up to email. So this is usually how the majority of us in the community know about an update in phenotype changes or updates to guidelines or new CPIC guidelines that are published. So key takeaways for update of pharmacogenomics test results keep in mind that over time as information matures in the medical literature there is a possibility that the leo functionality and phenotype assignments of certain pharmacogenes may be changed. Consideration should be in place for when to update results, how to update results and interpretation of these results as well as how to discuss them with prescriber and patients and how to notify patients about them and how to update the CPIC and FarmGKB communication emails are a tool to learn about these pharmacogenomic updates. So last story we're going to talk about is lesson learns from adapting to new EHR so at St. Jude we started returning preemptive pharmacogenomic test on an institution-wide basis back in 2011 as I mentioned earlier we genotyped to release two genes into the medical records when we started the EMT and CYP2D6 so and then and then quickly added eventually added other genes by the time we migrated to a new EHR in October of 2022 we had 14 genes that were already fully implemented into the medical record system and then we were told in October 2022 that this whole thing is changing we were going to switch to another EHR add these 14 genes that we had already implemented we were implementing a new one at the same time at the EHR switch and then there was the shift to the new EHR so what was asked for us and it took about 18 months was really recreating a 10 years period worth of implementation from one electronic health record into another one we created about 200 close to 300 post-test alert rules that had to be recreated in a new medical record system about 30 pre-test alert rules were recreated and then other in-basket notifications had to be created and this was something new for us something that we quickly learned is that the logic to create notifications and interruptive alerts in the medical record system although the logic is the same there are specific things that are different between one EHR and another we learned that we could not combine multiple drugs into a single rule meaning that if we were going to write a logic saying if a patient is an ultra rapid metabolizer of CIPTC-19 for example there are recommendations to adjust the dose of voriconazole and proton pump inhibitors but the alert could not be written so that so that each PPI and voriconazole were embedded in one alert and we had to create new ones which is something that was we had to create individual ones which was something that was different for us the other thing that we had to switch from was transitioning from problem lists into genomic indicators so we previously had used only problem lists to return pharmacogenome to post and display high-risk pharmacogenomic test results in the medical record we now display all pharmacogenomic phenotypes in the genomic indicators section so this was a switch for us because we used the only return high-risk pharmacogenomic results in the problem list whereas the genomic indicator we would also return normal metabolizer phenotypes to normal risk phenotypes and so we thought that's a great place for any clinician so one stop shop to see the phenotype of every patient did that on every patient and then on probably week one of implementing a new medical record system we had a patient who had a g6pd activity test that was returned as deficient so previously in our old medical record system we would have returned we would have placed a g6pd deficient problem list in the medical records in this case because we moved from problem list to genomic indicators we put we added on this patient a g6pd deficient genomic indicator and then as we did this because the patient had a deficient activity test a deficient genotype test we quickly noticed that the things that we had put in place did not really work for patients who were deficient by activity testing because our genomic indicator section as it indicates is an indicator for genomic testing and all the information that we have related to our genomic indicator relate to patient education and prescriber education about genotype testing including a statement in the result in the notifications that we sent patients and where we tell them you have been the test was performed to look at variations in certain gene and g6pd was one of these genes which made this note incorrect in our patients so what we did notice is that we needed a problemless entry for g6pd deficiency and not a genomic scenario where there would not be a genomic indicator needs in patients who are found to be g6pd deficient without having been tested for g6pd by genotype testing so we did that and then noticed that when we created this we also had to have our decision support alerts fired differently we wanted a patient who was g6pd deficient to have an alert notifying them that they should not receive high risk medications that are related to g6pd however our current CDS alerts do fire off of genomic indicators so we had to modify the logic for our decision support alerts in patients who are g6pd deficient to also look for a problemless entry because you could be g6pd deficient either by testing a few g6pd genotype but also more commonly by g6pd activity testing in the same scenario applied to malignant hypothermia where a patient could have been susceptible to developing malignant hypothermia either because they had a strong family history of that or they had a personal history of being exposed to a triggering agent and develop malignant hypothermia or maybe just because they were susceptible to developing malignant hypothermia because they had been genotype for pharmacogenomics but had not had the MH episode themselves but still we needed to notify clinicians about it the same also scenario applies to TPMT where there are institutions that perform TPMT genotyping and others perform TPMT activity testing if you do perform TPMT activity testing this activity test is a surrogate of whether the patient has a mutation or a variation in their TPMT gene but again it is not a genotype test result and you have to accommodate for that when you are working on different scenarios for notification and for return of results for patients key takeaways for adapting to new EHR section is really to look at to consider CDS alerts when so the logic for CDS alerts are pretty similar but you have to early on when you are thinking about changing electronic medical systems to work with your informatics team to work with your CDS experts to be able to for them to to work closely with you to explain the capabilities, limitations and enhancements of the new system that you are going to work on and also consider how to display results that have pharmacogenomic implications but are not obtained for pharmacogenomic testing and in this case it would be in our case it was G6PD, malignant hypothermia as well as TPMT activity so this concludes the end of my talk I wanted to just mention a couple of things I am one person sitting in front of you guys talking about this but this is a group effort there are many people who contribute to the pharmacogenomics program at St. Jude's some of them are mentioned here but it is definitely a team effort that everybody works together and so for my end this concludes my session but I just want to quickly thank you for attending and being part of NHGRI's health care education week there are many more education sessions throughout this week there are today's only Tuesdays so Wednesday, Thursday and Friday also have specific topics if you go to the NHGRI website you will be able to see that information if you check on the chat Donna has placed a link to the NHGRI recordings that are available one of which tomorrow is nursing genomic education day and so there is an FAQ about there is recording and presentation about what nurses should know about genomic testing as well as on Friday related to rare diseases and rare genomic diseases so with that I will conclude and check to see if you guys have any questions and thank you very much for listening in so the first question that came up is that is thanks for this great talk. Approximately how many patient family members require confirmatory testing at St. Jude per year and what is the institutional budget for this? I would say that about we probably have one patient a year or one patient maybe every other year who has to have confirmatory testing for this for mostly RYR1 and CACNA1S G6PD activity, G6PD testing for confirmatory tests because G6PD testing is a common test that can be easily performed at many institutions we do not perform G6PD activity confirmatory testing until patients to go see their prescriber for that for RYR1 and CACNA1S it's about a thousand dollar per test for both tests for RYR1 and CACNA1S so about a thousand no more than two per year or every other year. Any other questions? What EHR system? We are currently in the EPIC EHR system we were previously in the CERNR medical record system so this has taught us to be able to talk about both medical record systems and have a great collaboration with both of them actually. So while we are waiting to see if there are other questions a couple of things that we have learned over the years is that the return of G6PD results the return of results related that may have familiar and incidental findings is something that patients ask questions about the advantage of pharmacogenomic testing unlike Mendelio genetic testing is that patients are genotyped for pharmacogenes meaning that we will we explain to them that pharmacogenomics is a test that really will only tell us how their body is able to handle medications rather than this test will this test may tell us if they have if they're predisposed to developing a certain pregnancy or Huntington's in the future so we've had pretty good acceptance rates for parents to want to genotype their children because we're a pediatric institution and and so there's advantages to performing pharmacogenomics testing that is targeted rather than disease genomics because it is just related to medications and this is something that has helped us another question is is your CDS and response information in all epic systems nationally are you sharing content so we at the time that we went live with epic we a couple of institutions that we're already implementing pharmacogenomics epic EHR system have gotten together along with epic and we created and under the oversight of epic created a pharmacogenomics brain trust that comprises groups of institutions who have implemented pharmacogenomics within the epic EHR system and we are working with epic to make to work on their pharmacogenomic package and to make it available in the foundation system for epic so that it's available nationally and internationally content yes is being shared by us being shared by others and epic has a lot of this content at this time if it is not yet in foundation system it will be it just depends on what information you're looking for and whether it has already been rolled out into the epic foundation system with the epic quarterly update I think we're going to end with that if you have any questions my email information is available on the slide is available you can always email me I've ready I posted it on this earlier at the end of this presentation I'm always happy to help and thank you very much for NIH and NHGRI for hosting the session it's always interesting and really nice sharing information and comparing information with all other healthcare practitioners thank you and have a good day everyone


Hello, yeah, can you hear us Dave? Yes, I can. Thank you for sending another week. Yeah. All right, we're we're about to go live and record and stream and get going. Okay. Also, great. Good morning. Today is Monday, December 4 2023. This is the third public meeting for the screening committee for the executive director search. I'm commissioner Eileen O'Brien chair of the subcommittee. We are doing this meeting using remote collaboration technology and so I am going to do a roll call to make sure we have a quorum. So commissioner Maynard. I'm here. And CFO Lenin. I'm here. All right. And director Heather Hall. I'm here. And director Dave Muldrew. I am here. All right, so we have all five present. Second item on the agenda is a discussion of the process and the general questions for the first round interviews of selected candidates as we go forward. I am going to pass this off to commissioner Maynard, who has worked on very, very high level in terms of topic areas for us to have a conversation with. I would like to go into in terms of anything pertaining to a specific candidate that would be handled in executive session. So this is purely a high level conversation. Thank you chair O'Brien. If I can have Jacqueline help actually circulate this due to the open meeting law. We put this together commissioner O'Brien and I did, but want to circulate now to all the members. And perhaps even. I don't know if I can share my screen. I'm not. That technologically savvy, but. Perhaps someone can share the screen and we can kind of talk through some of the topics we were talking about. In terms of what we want to bring up. When we interview screening interview. Potential candidates. Commissioner Maynard, I just circulated that document to all on attendance. If you'd like me to share my screen and you could walk through it on my end. You can do that as well. I would appreciate that. Yeah, just give me a holler when you want me to change pages. Perfect. Okay, so the idea here for all the members is first of all, this is a living document. It can, we can change it here in this forum. But the idea is that we want to make sure that the public is aware of some of the interview topics. That we expect to go into when we do our screening interviews. A couple of things came to commissioner O'Brien I as we were going through them. And it was trying to track and make sure that we were following the job description. Right. So those who did apply for the job. Have some expectation of what's coming their way. So the core topics included, I'm not going to read this. All right, but I'll go over the headings. Management experience. And that's really to capture any management experience that a candidate would have. We understand that candidates can come from the private sector, the public sector in state out of state, and just really try to see what a candidate has. Then we thought about the regulation experience, obviously being a regulatory body, we have a lot of regulations that we deal with more, more so than, than we would like to this last year. But, you know, what experience do you have as a candidate, if any, on regulations. I'm just going to go over these and make a point at the end to legal experience. You know, are you an attorney? Do you have background as attorney? If you're not an attorney? Have you worked with attorneys?  What's what's your understanding of what a legal department looks like? If you can scroll a little day. You have communication experience. You know, this is a very outward facing agency just as much as inward facing. You know, we always have stakeholders we have to communicate with. What's your, you know, what's your experience developing or leading a communication strategy or communications team? We can go down to the next page. To that point, external stakeholders. We were thinking about those within the industry, right? Gaming, sports, wagering, horse racing. Also, those within state government or federal government. Various branches. And basically just this is a constituent services agency too, right? It's a public protection constituent services. What what level experience does a candidate have on those issues? Then we drilled into the gaming, racing and sports wagering experiences. And that that goes through a list of, you know, have you worked with other bodies? Have you worked with vendors? Have you worked with other commissions? What's the extent of that work? Same thing for budget experience. You know, have you set a budget? Have you hit a budget? Have you had to make sure that a budget has been followed? The OML and PRR experience is really important. Obviously, why we had to circulate this document right now in public, right? Have you ever dealt with open meeting law, public records law? We talked about this and we really thought about Massachusetts specifically, but the more we thought about it, almost every state has some version of this in the feds. So, you know, have you worked with any of these? So we made it a little less specific. And to what extent? And then finally, we think obviously diversity is really important. We push it on all of our licensees and it's something we do internally here and Dave, you've had, you know, you've done a fantastic job. We want to make sure that any candidate that comes through the door, you know, is able to detail their experience working with diversity, diversity plans. And that's not just the people side of diversity, but also vendor diversity, spend diversity. And so those are sort of the key topics we were looking at. Now, a particular candidate may be strong in one of these topics and not in the other. We would say to any candidate who's listening, this is not a, you must check everything off of this list. This is a menu out of options that we think we should be able to pull from and it's bare game for us to ask questions off of as we approach these interviews. So that's kind of my high overview. I'll kick it back to Gerald Brian to add in any detail. No, thank you, Christian manner and I think you covered it. So, in terms of the public discussion. And I'll have Dave take it down unless you guys would like it up. Let me know. Otherwise, what I'd like to do is just hear from the other three of you that are getting this for the first time that obviously the idea that getting ready to interview each individual candidate we can do a more specific dive questions that are particularized to that candidate but this is the high overview. And again, the OML requirement that we do as much as we can in public that we felt like this gave us sort of the parameters without going so deep that we were sort of, you know, going to be going into someone's identity in terms of who they were because once you get really specific with the questions, it may become very obvious who the potential candidates are so I open it up for comments. I think that it's a I think that it's a good area to work through I think that all of the major areas that we've kind of looked at on the resumes and on the job posting are covered there. I do want to take a little more time to review it see if there are any bullets I'd like to add but you know at first blush I think it's a very good starting point. Dave Muldrew, you were unmuted I didn't know if you wanted to say something. I think it's a very good approach. And I know we can't talk too much about process now but I thought it was a cover the areas that we need to cover. So I liked it. Yep. So if there's a general process question and connection with this they've actually feel free to ask it now. I understand you like Derek probably want some time to digest it and be able to come back but that needs to be discussed now. Yeah. Okay. And Heather, did you have anything or you said. Thank you I think it looks good. My only thought at the moment and I agree with the looking at it a little bit further but I think that respect to the management experience I think not only should we be asking about direct reports and indirect reports but also experience with reporting to a body like this. That would be worth exploring as well. Right. Okay, so if we're all done in terms of that general discussion. We did put on the agenda, the option of going into executive session to start getting more specific with candidates as we're going to start to line up the first rounds of interviews. And I wanted to just gauge people's appetite in terms of whether you want to. And I'm going to save the moving into executive session until we've gone through the public topics but whether you want to potentially go in on specific candidates today or whether you want that to be done I know there are some instances that's done right before the candidate comes in that sometimes you'll go into executive session, firm up the questions right before they get there so have a buffer between that. So just gauging the appetite for whether you want to have that open as a possibility today or defer that to the next meeting. Anyone have thoughts. I think to the set we can leave it open as a possibility I think that would make sense. All right, so we will circle back to moving into executive session on that which would be to a, but I want to move on to number three which is continued review of candidates for the position of executive director we did get some additional candidates between the last time we met and today that have been forwarded to us. And so I would also anticipate that we were going to go into executive session have specific conversations about those candidates as well. So, before I circle back to reading into the record in terms of those two potential areas for executive session did anyone else have anything they wanted to bring before the body of five publicly before we consider moving into executive session. No. Okay. So, we would go in and part of this and Dave. I know that any Dave you're on the line part of what for full disclosure part of what might be continued review the candidates and the questioning would be the possibility that we start scheduling some of these interviews once we go into executive session today in terms of the particular questions. So moving into the record to a, in terms of the rationale for why we would go into executive session relative to talking about the question the interview questions of specific candidates. The committee anticipates it may need an executive session in conjunction with the initial screening process to consider specific questions relating to specific applicants for the position of executive director. So, I'm going to go into the final 30 a section 21 a eight. If the chair declares and I do in this open meeting that we believe it will have a detrimental effect on obtaining qualified applicants for the position. The committee would not anticipate reconvening the open session at the conclusion of the executive session. So, I don't have motion and a second on that. I just want to move that we enter into executive session for the art at the reasons you articulated here and discussed in this meeting. Second. And motion and second commissioner Maynard. Hi. And CFO Lenin. Hi. And director hall. Hi, director Muldrew. Hi. And as to three a, which is the continuity of the candidates I likewise read in the committee anticipates it may meet an executive session in conjunction with the initial screening process to consider specific applicants for the position of executive director in accordance with a subsection 21 a eight. If the chair declares and I do in this open meeting, the doing so in the open meeting will have a detrimental effect on obtaining qualified applicants for the position. As stated earlier, the committee anticipate the open session will not reconvene at the conclusion of this executive session. And again, move that we enter into an executive session on this matter for the reasons articulated by you the chair and discussed here today. Okay. So, commissioner Maynard. Hi. See if a Lenin. Hi, director hall. I, and director Muldrew. Hi. And I am I, and I don't think I voiced I on the last motion, but it would be five zero on both motions to go into executive session. So at this time this would conclude the public portion of this meeting and we will go into the executive session, either link if you are remote or in person in the conference room. Thank you to everyone who phoned in or watched for their time, but we will not be coming back. Excuse me to the public session after executive session.


Τα στεγμή που εγγραφήσαμαι στις ασφαλήτων εξαιρίας με εξαστηριάτισμι. Τεχνί 20 λεπτά, είναι τώρα το κομμάτι της λαμπιστικής εξωτερίας που εξαστηρίζω στος λαμπιστικής λεγιάρου, Τώρα είναι πάνω από 5-6 χρόνια που είμαι ο Επιτουαστικής Κασμόνας για τη Κομμύτειο Φραδιές Προτεκτώνα, δημιουργίας της ετικουνίας της UCD. Από την κομμάτι που βλέπεις, η εμμάρια,1000 επόμενα εγγραφή μετά έλεγε, ή τις προβλήματα για να πω, που μπορώ να δώσω also ήißtη για την εερρήνη της σπίτις, ή δημιουργία της σπίτις, ή λασκότητας, ριθμό, κομπτήρετε μαςτα. Είναι δύσκολο να μξιωθεί, πώς είναι η δύσκολη, γιατί είναι δύσκολο. Είναι δύσκολο. Άρα, ήθελα να δώσουμε κάποιες πιστήρες για τη διεγραφία γιατί διεγραφία, γιατί διεγραφία, γιατί διεγραφία, κάτι σημαντικό κομμάτι. Γιατί διεγραφία, γιατί διεγραφία είναι part της αξιλίστας. Δεν μπορείς να βρεις ένα αξιλίστας, να το κάνεις γιατί θα το χρησιμοποιηθεί. explanation How you are going to manage. How you are going to face some problems. And it depends, of course, of the kind of accelerator, of the power of the accelerator, of the ions that we are going to accelerate. So the first thing is what's radiological protection and what is dealing with what? Radiological protection is a very complicated discipline και ο αδερφός που δημιουργείται για την προστασία, όμως για την οικονομική προστασία, για την προστασία, για την προστασία, για την προστασία, για να έχουμε κάποιο χαρμό για τη φυσική, την κεμιστοσύνη, η μυαλόγη, η λόγη και τα εταιρετικά κομμάτι. Όλα τα προστασία ιαλόγη είναι βέβαια από τρεις πρινσίπλες. Αυτό είναι ο καρδυναμός οικονομικής προστασίας. Η δυνατότητα της προστασίας δημιουργείτες, δημιουργείτες με μυαλόγη, με αδερφός αδερφός, αν πριν, προς την very beginning, δημιουργείτες, και δημιουργείτες ότι δεν μπορείτε να κάνετε αυτήν την προστασία, διδημιουργείτες, δημιουργείτες, δημιουργείτες. Δεν δημιουργείτες, να prac cage με πο galleries, να INTROκουλgangen οι θεωツές να τησίσει," Αυτό που λέμε μία θη 어�ού είναι για να επι nutrient to retain ...司 On, μ инструмент to consolidate after some years just to understand if there are changes in the knowledge. The second principle, δημιουργήσει τη δημιουργία. Πρέπει να κάνει κάτι, να παρακολουθεί οικονομικής και οικονομικής σχέσης. Πρέπει να δημιουργήσει να δημιουργήσει το σχέσης. Πρέπει να δημιουργήσει κάποιες σχέσεις, as they are considered, ότι they are far below the limits. Και η third one is individual dose limits that in any practice is someone, a person or a group of individuals cannot go over the dose, the limit of the dose that has been fixed. What is the main problem of radiation protection? The main problem of radiation protection is to define quantities that they have to quantify the exposure risk to the different type of ionizing radiation. What I have to know if I'm exposed to neutrons or gammas or a mixed field, what I want to know is what's the biological risk that I'm going to have. These quantities, therefore, serve as indicators of radiation risk and allow a satisfactory preventive structure to be given. That means that based on the quantities I have to think about what kind of a set I have to give. Which are these quantities? There are physical quantities, radiation protection quantities and operational quantities. The physical quantities are quantities that they are exactly measurable. You can measure them. The radiation protection quantities defined by ICRP are not directly measurable. It has to deal with average values and give you an idea about the biological effect and the operational quantities that they are defined by ICRU they are used for environmental and personal monitoring and on the basis of these quantities I can define the radiation protection quantities. The physical quantities, you know them, it's the fluence, number of particles per surface and the rate per second and this is perfectly measurable. The absorbed dose, that is the ratio between the average energy imparted or transferred by the radiation to the matter divided with the mass of the volume considered and the unit is grey, one joule per kilogram mostly used is the rate of the absorbed dose in grey per second or under multiple like milli grey per hour or micro grey per hour and so on. Then the Kerm of course that has to deal with non with indirectly ionizing particles like neutrons and gammas and it's the kinetic energy released in the matter defined by the quotient between the sum of the initial kinetic energies and all the charged particles produced by indirectly ionizing particles in a certain volume element of a specified material and mass dm and the unit is the same and passing to radiation protection quantities there is the average absorbed dose by an organ of the body or tissue and it's defined as you see as the average absorbed dose in an organ indicated by the DTR and this is the reason it's not a measurable quantity because you have to deal with an average absorbed dose in an organ that you cannot measure it. After this you have to deal with the equivalent dose that means that comes out from the question if I give an equal absorbed dose like for example one grey of neutrons or one grey of gammas what will be the biological response will it be the same or will it be different? The answer is that it will be different that means that the radiation have different quality for imparity of dose for biological effects and this is exactly saying by this quantity and by this product were if D is the same this one change according to the values of the waiting factor for radiation if you are in a mixed field of course you will have the sum the unit is severed or under multiples like micro severed per hour the rate, micro severed per hour or milli severed per hour and so on to pass to the next quantity the question is ok but if I gave the same dose to an organ, to different organs I will have the same response or not that means there is any different sensitivity, sensibility of the organs or are all the same to take into account excuse me before just take a look about what's the value of WR for photons and gammas by definition is 1 electrons 1, alphas 20, protons 5 and then on neutrons it depends on the energy having from 100 kV to 2 MAV a maximum of 20 and then goes down and then goes down the value of the waiting factor why because the energy of the neutrons is so high that did not see your body pass through without interacting so if the absorbed dose is equal to one grey and you have different waiting factors the equivalent dose is different and you have to multiply one grey with one of these numbers so you see that for photons one grey is one severed but for alphas is 20 and for neutrons depends on the energy you will have a greater number anyway going to the difference sensibility of the organs also here we have a waiting factor of the tissue of the organ according to his sensibility that means like before you remember this waiting factor for radiation now we have a waiting factor for organ for tissue or organ whatever and this value is different according to different organs of the body you can see it here according to ECRP 60 it's 0.20 then from bone marrow colon lung and so on and of course the total body is one these are the reminders that means different organs or tissue and every one of these is 0.5 on this column you see something interesting that have to be understood in the sense that if I have an exposed worker and we take 100 persons and they give him during their life one severed that is a very big quantity only 6 of them will have a fatal cancer due to the radiation taking into account that in a work dangerous like constructing buildings and go up in hate you have one death every 10.000 people working yes but these factors were measured experimentally or not they are WT you mean? WT coming out from calculation but also from the experience from radiation therapy during many years and also from workers that they are exposed in different miners and so on the ECRP quantities and GCRU quantities are non-measurable not measurable these data was collected over the many years no we will see how they do it I will tell you after ECRP 60 there is ECRP 103 some importance of the weight factor for tissue you see one of the most important is that the gonad goes down from 0.20 to 005 these are experimental results coming I mean you know that also from the survivors of Nagasaki in Hiroshima there are a lot of commissions that during years they review all the data and they give different values on a lot of things like weighting factor for neutrons weighting factor for tissues and so on I am coming to you to your question what they do really one is thinking about when someone tells me what's my dose the quantity is the effective dose and the effective dose is by definition non-measurable and the question is if it's not measurable what are you giving me ok but now we will see what is given to you in effective dose is something coming from here from the monitoring in the sense that your dose is related to ambient dosimetry that means I put near you a monitor so what I am going to take from the monitoring let's suppose what you got or I give you a personal individual monitoring so the read if I read it what I get is very close to what you got but not only what they are doing is if you ever read ICRP you will see that the job is done by Monte Carlo calculations they have the phantoms or ICRU sphere or other anthropomorphic phantoms like Adam Medeva where according to the type of irradiation that they have if it's direct irradiation or from the back to the front or lateral and so on they use these kind of phantoms and they make calculation about the dose they get factors that can they have to be multiply with the fluence to get the dose and what they know and this is according also to experimental data coming from a lot of facilities is that in all cases of gamma radiation except the part of the X-rays that they are near 30, 40, 50 kV in a mixed field you are always you are always underestimated the dose when you talk about effective dose only in the case of more energetic photons of 30, 40 or 50 kV you can have an underestimation of the dose and the same for neutrons because for you it's extremely difficult to find a place where you have more energetic neutrons generally out of the reactors, out of the accelerators you have continuous spectrum of neutrons and there they have except again some cases of low energy, more energetic neutrons you always underestimated the dose with effective dose so when you measure the operational quantities the protection quantities is always underestimated so in the process of radiation the source what you have personal dosimetry and you have ambient dosimetry in the environment what you measure with the monitors what are the quantities in these two cases it's the ambient dose equivalent what it said H star D and personal dose equivalent HPD this D it's not other than you measure the dose because when D is equal to 10mm you are considering penetrating radiation so gammas and neutrons in the case of D equal to 0.07mm you are talking about a skin radiation on the tissue because for example of soft x-rays and so on just understand what is ambient dosimetry you have to have in mind some definitions what is a real field, an expanded field an unidirectional and expanded field otherwise you cannot understand what is dealing about the ambient dose equivalent because the ambient dose equivalent by definition is the dose equivalent in a point and when you are in a point and not in the medium of a tissue you can measure in a point of radiation field that would be produced but the corresponding expanded unidirectional field of this urus sphere at a depth D on the radius opposite to the direction of this unidirectional field the recommended as I told you before distance is 10mm and this defined penetrating radiation in the case of directional equivalent dose Aka HD omega like solid angle you are talking about surface radiation and also radiation of the lens of the eye and you have recommended depth 0.07mm and you are dealing not anymore with expanded and unidirectional field but you are dealing only with the corresponding field in the ICRU sphere about personal dosimetry personal dose equivalent also here you have D with 10mm recommended as 0.7 for skin and eyes lens of the eye and the last one is what is going on when you introduce in your body your body radioactive material so when you introduce your body you are dealing with internal irradiation and so with effective dose that takes into account also not only external global or partial radiation but also the contamination in this case the quantity is the committed equivalent dose and this is with respect to time it's defined in a tissue or organ T that will be received by an individual and this kind of time from introduction up to the calculation of the dose is taking into account that it's 50 years so if someone introduce in the body let's say 1 bacharel of americium and one is saying for this introduction you got 10 microsieverts means that you got taking microsieverts from now up to when it will be 2069 ok if more than one organ is involved of course you have the sum of the committee of effective dose and of course this committed effective dose goes inside the total effective dose that is composed from external radiation and internal radiation if the internal radiation is zero because you don't have for example not shield material you will only have external radiation but if you have also introduction of radioactive material in your body you will have the sum external plus internal and the question is let's suppose that for example someone in a lab has no external radiation something is happening and introducing his body only radioactive material someone is making the calculation and saying you got 10 microsieverts ok another one is exposed to gammas or to neutrons only like external radiation and somebody is saying your effective dose is 10 microsieverts these two people that they get effective dose one from internal and the other from the external the same effective dose they have the same risk to get a biological effect or different risk because one is internal and the other is external must be must be why because if it's internal you have a very high probability of that particle interacting with your body what do you think you agree it has nothing to do it's the same from the definition of effective dose the effective dose like a definition if I go back the effective dose take into account whatever happens in your exposure internal external whatever it's the sum of all of your exposures it's a number that is related with risk so it doesn't matter how it comes out if it's because of internal or external exposure of course it's not taking into account the toxicity of the element because there is also the chemical toxicity of the element but it's not taking into account in this case once you have defined the effective dose you have defined everything that is related with your exposure internal external it is or the sum doesn't matter ok so this is important let's go down to see something that I don't know if you know about what are the limits there are the workers and there are the people the population, the public the exposed workers they have an effective dose limit of 20 millisievert per year at least in Italy that means that the exposed workers they have the same limit it doesn't matter if they are catalogized in A or B it's a question of other type of things let's say one can be visited by a doctor every one year the other one 6 months every year and so on but the limit of those that they have it's the same 20 millisievert per year non exposed workers it's not a very good definition that someone is not exposed to radiation is someone that because of his job he can take one millisievert per year and this is the same of the public then there are some partial limits on lens of the eye this is also changed with the new directive that considers the lens of the eye more stochastic effect and not any more deterministic effect and this value is from 150 becomes 20 then arm legs they have as you can see a very high value why they have a very high value because they have a weight factor for tissue 0.01 and then there is equivalent dose due to contamination due to exposure excuse me on the surface of the tissue and it's considered in one centimeter square where you can get 500 millisievert per year very often this is related if you have an accident with X-ray tube or something very focused like a beam on your skin and so on so these are the main limits that at least in Europe according to ECRP 60 are now in we working with them let's go one saying this part general part and we are going to see radiation protection at low energy from the proton accelerators because going to accelerators you have heavy ions it's another part but depends of course of the type of the ion energy and current but it's less dangerous in some way from the proton accelerators the overview of the presentation then what's prompt radiation the interaction of protons with matter nuclear interactions, characteristics of problem radiation field attenuation, this is extremely important for example to design your shielding induced radiative activity once your machine is working the activity when the beam is off remains induced radiative activity magnitude and prediction it's extremely important but you have to plan how to make maintenance on your machine then environmentally packed when you work like the phenomenon of neutron sky shining and that means the shielding of the roof of the accelerators, some aspects of emission of radioactive effluence and the summary what we call in radiation protection low energy and intermediate energy we are here up to 100 up to 1 JV maybe less to 1 JV of protons in energy then it's considered high proton accelerators the schemes of the accelerators that are very extremely different from earth use to first cyclotrons and very big cyclotrons like this one vancouver, then vantagraphs that you have already seen and DTLs and so on there are many applications of the accelerators from research to radiotherapy, industrial and medical radioisotoproduction waste augmentation like ADS and also detection of contraband you see a typical scheme here where from the reaction P on carbon 13 you have a gamma of high energy if I don't mind more than 8 MeV and so you can with this reaction you can you can search for contraband explosives and so on difficult to do it outside because all the farmers use a nitrogen for fertilizers so you can try to find bombs but you can find other things so I don't know what is the meaning excuse me the interaction of proton with matter the interaction of proton with matter low energy energy loss by ionization in higher energy you have energy loss by nuclear interactions in nuclear interactions you have diode interactions per equilibrium and equilibrium evaporation characteristics of the prompt radiation field there are, I'll give you some also equation or rules of thumb that can be interest to solve some quickly some to some problems that you can face interaction of protons with matter in low energy protons we define a range that in very high energy the range is not meaningful anymore the range is in iron you can see it here and for other materials you can calculate it from this equation the probability of interaction of nuclear interaction as you see here it's in the function of proton energy from let's say low energy sub 1 JV the probability is growing up and you see here the different materials where the proton is impinging on and you can arrive almost to 1 where at high energy every proton undergoes nuclear interaction if the target is thick enough so to stop the beam inside the target of course in the case of the protons that stop the beam inside the target we are referring also to black peak that is extremely interesting in application of proton therapy because you know exactly you know let's say exactly where you lose the maximum of the energy of the beam and let's go to characteristics of from the radiation field because when the proton interact with the target you have secondary particles that they are produced that they are going from neutrons up to gamma gamma rays passing from protons depending on the energy more than quite 500, 450 MAV pions, muons, electrons, neutrinos that they don't have charge and muscle they didn't give particularly problems in radiation protection and going to nuclear interaction you can see that the first part is the evaporation here with the direct directions up in energy this schematic spectrum of emitted particles and the energy spectrum of evaporate particles especially neutrons you see it's focused up to the first 8 MAV energy I mean when evaporation of neutrons coming out in a two step process first you have the particles that they are directly emitting from the interaction and then you have also neutrons coming from evaporation the neutrons coming out only from nuclear reactions then in these cases because they have charge you have energy loss by ionization the same electrons here you have no charge so you lose energy between the three processes that they are known and neutrinos practically you have no interaction and the interaction of proper radiation coming from an accelerator with the matter the most important thing are the neutrons in the shielding that goes they can penetrate very efficiently they have no charge and all the other charge particles they are stopped inside the thickness of concrete for example like in shielding so that's why often we say that when you have you have shielded the accelerator for neutrons you have also shielded the accelerator also from other radiation like gammas or charge particles because anyway they are arranged out like if you use adam meters of shielding against the neutrons for instance maybe you are using low weight material to shield the neutrons would you be shielding the protons and the rest as well yes yes yes but in an accelerator proton accelerator when you shield neutrons you have shielded also gammas if someone is going to ask me but why even if 3 or 4 meters of concrete I can find some gammas outside how it's possible or some neutrons if you have neutrons of high energy you have a probability that the neutron will undergo inside different interaction and some of them they can arrive just in the surface of the concrete with a thermal energy that can be absorbed for example from the material and when you create a nuclide that is excited then the gamma that's coming out will did not find a sufficient layer to to be shielded and so you have gammas in the same way even if you have 3 or 4 meters of concrete you can find neutrons outside because it's a statistical process some neutrons of high energy even if they go interaction they will have sufficient energy to go outside of the shield in a complicated situation for the shielding of accelerators you cannot use any more ncrp51 even if it's a very good book of reference book but in the scheme complicated of shielding you have to use Monte Carlo codes without Monte Carlo codes it's not anymore possible to work most of them like mcmp or mcmpx or higher energy than 20maV or light or fluca or mars they are doing different jobs or they use different nuclear models but they are they are the tools that they have to be used anyway here you see an example for example a 30maV radioisotoproduction from a cyclotron and in the different colors done in a geometry that you create inside the Monte Carlo you can have an idea let's say in the point of interaction of the beam what is going all around your shielding once you have defined the thickness of the shielding and you can have an idea what's the rate that you can expect when you are dealing with shielding calculations and remember always that the pen of the paper and by your hand I mean it's always valuable in some situations the main equation for shielding is this one where this is the dose rate that I need but the ambient the ambient equivalent dose rate for neutros for example that I need, the energy of the proton the angle between the target here is the proton beam and I want to know what's going on here this is the angle and this is the reference value of the dose that means what's the dose that I have and then you have the lambda that is the mean free path and and this is the distance between the proton beam and the target the point of the source and the point of my detector, the point of interest and always and as we'll see these numbers lambda is already calculated for most of the cases and so you can find it in the literature in the case in which you have a shield and you want to know something in this 90 degrees this name test is a famous German radiation protection man that you can search in internet and you can find his publications so at 90 degrees from the source what you have is this expression to calculate the dose and this cascade it's not other than this value that you can calculate it expressed in pico-sever in the fraction of proton energy also this value density multiplies lambda in concrete here and as you see many people have made calculations and they are very near to this curve so they are dose attenuation length in the fraction x-axis you have the proton energy in MAV here you have also a value of density multiplying lambda 10 but lambda 10 is not other than 10th value later that means that means the thickness from 1 to go to 1 tenth of the dose and you see for various reactions that are type PN or DN or helium 3 N reactions where they are in function of the particle energy here we are here you have some equivalent formulations of dose attenuation that means reference at one meter and what I have what I need or what I want to have so that I can calculate my thickness of the shielding and you see attenuation length half value layer and 10th value layer and these are the relationships between them this is the dose attenuation length in concrete given by NCRP 51 and also by other researchers that they have made the calculations dose attenuation length versus proton energy and this is a famous coming from also NCRP more recent about accelerators that give you the neutral attenuation length up to the higher energy limit where you arrived at a certain value where you don't have any more and increase and let's pass now to radioactivity induced in target and structures just two rule of thumb just to have an idea in accelerator the saturation activity coming from 0.1 to 1 megawatt that means multiply energy with current of the accelerator you are near to 110.000 tbk that means 6 tbk per kW when in efficient reactor the at saturation you have 50 tbk per kW of power residual fields of components in total radioactivity produced in thin targets you have here some some ideas what you are going to expect per proton current in bkg per square centimetre and in the range of current from 1 to 10 when you go up from 1 to 10 micro amp of current when you are in some tens or hundreds of maybe remote handling of the piece that is activated is needed and of course this goes up with the cost of the facility how I can determine induced radiation field I don't know if you know this guy of 1950 50, 50, 54, 55 barbie you can find the book in internet there is an extremely detailed procedure how you can go to calculate the total dose rate starting from the input target element or compound activity from cross sections look up gamma ray library flaxes and so on and so you have an idea what kind of activation can you expect in different cases in different materials how can you determine induced radiation fields in experimental way if you have a monitor and a chamber you can measure the total dose rate from the piece from the block of whatever it is then if you have a high pure germanium and you shield it just to take only the part that is coming from the activated part you have the gamma spectrum and going all around this procedure you can have the possibility to calculate the induced radiation fields for arbitrary radiation history and this is useful for what for shutdown and maintenance planning and for decommissioning planning of your facility for example here is a 500 mebsyclotron exam coming from triumph where they have they have here the rate in milli grays and the time in days and here you have the beam current in micro amps and the last part is the two an extremely interesting part on environmental impact including sky shine of radiation and release of effluence in air and water what's the sky shine you know that if you don't have a shield up your facility and you have a high production of neutrons the neutrons from the source coming out interact with the air and you can find your neutrons your detector in a certain distance from your facility that can be also hundreds of meters away this is because you have the interaction of the neutrons in the air with nitrogen oxygen and so on and this as you see these cross sections are not so low especially when you have high energy neutrons you can have distances that goes up and up meanwhile low energy neutrons can stay inside this sphere in first approximation the dose that you are going to have in a certain distance is this is the source term in neutrons at the point of emission and in a certain distance you will have a dose rate coming from this equation the spectrum of course hardens with the distance if you have high energy neutrons as we said we will find them very far away so be careful we need all ways to have to calculate the shielding at the roof of our accelerator otherwise you will find problems and if you are in a situation that you cannot shield with blocks your target inside the room you will have a lot of problems because you could not anymore put a roof at the roof but you will have to keep the distance of your building emission of radioactive effluents near water since this thing this is dealing with a typical active cooling water system where you have a high active circuit cooling circuit coming from a target collimator and here you have resins that exchange this is a double system closed exchange the water with the resins of course tritium is not is not absorbed with the resins because hydrogen in the water and you can keep only this kind of radioactive elements to create inside the water and then there is another active of low conductivity water another system that gives cooling to beam line magnets, vacuum pumps cavities and so on that is made in such a way that you can also evaporate the water and leave the radioactive the radioactive elements inside this containment because the water evaporates of course and the radioactive parts remains inside in the case of some kind of losses of the material it has to be you have to think about a containment where the water can finish because will be activated and show a closed sample and all these things to create them is not, you have to foreseen before because otherwise it's not so simple to create after in the facility a typical design of drain system is this one where there are different as you see some from a local to a central so on with level alarms when you arrived at a certain height there is a level alarm you can measure here if you don't have if you don't have so much of the activity is decay you can set it to the central active somewhere it can remain stills with level alarm in case you can take some of him you can take it out and if you don't have you are under the concentration of the activity that the law of the country where you are permits you can also throw it away this operation in Italy is extremely strict you cannot send anything that it's overrun bacharel per gram so it's quite nothing and the last last transparency is with with a vacuum exhaust system complicated especially in facilities where there are objective beams where there is a two barrier vacuum a primary one and the secondary one and then storage tanks where the pumps along the beam or from the source or from the secondary vacuum takes the gases and they put it in these tanks where you can calculate the time of decay and then to put some of the gases to another and to another one waiting long term period so the radioactivity high level can decay and so in a certain way you can throw it away or by using HEPA filters for particulates or if you are in the presence of iodine or of halogens that they are radioactive or you can use charcoal filter to trap them and then if it's permitted the measurement that you do before the chimney permitted you can send it to the environment where exactly here well here the primary vacuum is the vacuum of the target but what's the radioactivity for example in the rib facility you have fission you have everything you have everything means all the iodine if you make fission from neutrons on uranium for example it's the same as you do it by protons the same means you can have some difference in the fission curve it could be more and ten way more going down or more flat but you will have all the krypton the xenon the iodine the halogens but in terms of radioactivity normally when you make a nuclear reaction the amount of particles that you are generating is let's say in the order of 10 to 8 in this case I can tell you that with 35 grams of uranium carbide you can have a thousand and irradiated 14 days with protons of 14 maV and 200 micrograms you have 10 to 13 fissions and you have 1000 queries after 14 days of irradiation the number for example of of noble radioactive gaseous that you produce is 10 to 13 so it seems but it's enough this is important generally speaking when you have the possibility to have release of radioactive material you must be under pressure or better you have to create at least two barriers of under pressure for example in our case in our lab in our facility for what we are doing we have main in the bunker of irradiation minus 80 Pascal in the room before minus 40 and then atmospheric pressure so if you are going to lose a barrier there is another one otherwise the activity is going around and this is what is what is sketching here radioactive air you are in low pressure to create low pressure you have to have a fan that takes out the air to create the under pressure so the question is this one how many number of air changes I have to do a lot in an hour for example or not the answer is here from these two graphics where this one you arrive to one because as fast as you take it out it is creating and you see that high refrigeration rates reduce the reactivity level in the room where you produce it but you go up increase with the amount of reactivity that you are bringing outside of the facility so you have to find the gold number where you are creating the pressure that you want with a minor number of air changes this is a mathematical approach that if someone of you is interested we can change it you can send it to you so you will see exactly which are the equations and how you face it so in summary we have described some specific application proton therapy direct interactions of operations shielded and mediate energies semi-empirical types measurements sky-side emission effluents remember that when you have when you have a reaction with a proton beam impinging on a target most of the time it is in the direction of the beam that you will have concentrated the major number of neutrons in the case of the evaporation of neutrons because of the excited state of the system the evaporation is going of the neutrons with maximum manager of FATMEV it's going to be distributed in an isotropic way and not pick up in the zero degree direction compare it with a beam ha! I go out at least 15 minutes please I'm wondering my first question is what is the timeline of a timeline of a central nuclear reactor central when you have a facility but how long how long it lasts first and do you include into the system of radiological protection the commission the commission this is a very interesting question I don't know if you heard what he said he said if you have a facility a radiation facility of a certain importance radiological importance how long this facility is designed to operate and of course if you have to think before about the commissioning of the facility this is an extremely important issue not only how to manage it after but also from the radiological point of view when you create a facility at least you are thinking to make it work at least for 30 years especially if it costs millions of euros taking into account that a nuclear reactor is thought to to work about 30 years but then nobody stop it so they go they take periods of 10 years 10 years to go to go on so this is the first part the second part that is not second but it's also first of the first is when you construct a facility you must to think immediately about the commissioning of the facility and this is asked for example from the Italian law to make a plan or how you think to the commissioning of the facility why in our case for example when you have 40 MAV of neutrons 40 MAV of protons with 200 micrograms 10 to the 14th neutrons impinging on the walls of a bunker first then you have uranium carbide inside there so you have fission you are able and you are so um let's say technically good to confine all the material but it's not the case because some of the material we are going to lose it all around the bunker so you have to think how can there are any actions that I can do from the very beginning in the phase of building the facility so to make the costs less and the answer is yes for example in Italy you cannot throw away concrete that it's activated and if you go to search in the literature you will see what you imagine that concrete produce because concrete is made carbon hydrogen and some element trace element materials one of the strength element material most important is europium europium change in europium 152 that has half life of 12 years or so on so when you create europium inside the concrete and you have so low concentrations of one becquerel per gram otherwise you cannot throw it away you have to keep it so you have to think that if I make a wall all together of 5 meters of 4 meters or 3 meters then what I'm going to make this kind of wall but if I can calculate with Monte Carlo after a certain period of time like say 20 years with 5 or 20 thousand hours a year of operation I can calculate up to what thickness I will have this kind of products so I can build my shielding in slices so if I know that up to one meter and a half I will have this kind of problems after that if I make a slice of 1.5 meters and then another one it remains and the other throw it away I make something else not only but in our case of radioactive beams when you will have contamination and you have also alpha contamination because there is a fission inside there you have also neptunium you have also other things that they are alpha emitters if you lose it in the concrete downstairs it is going to go inside inside and you cannot take it out in the contamination anymore but if you think to paint the whole bunker with appropriate material that it is easy to decontaminate it then you will take it out when you finish your facility and the other thing will be clean otherwise you are going to spend so much money that you cannot imagine that the commissioning is one part extremely important from the money point of view can cost more than the bill thank you