 So, here's our little group and it was a very frisky group. So, one of the projects we chose to put forth is the infamous LYNS syndrome screening and we heard from Maaren how relevant that is. And just to remind everyone, because in our group that came out, so three to five percent of all comers with colorectal cancer have germline mutations defining LYNS syndrome. It's also a goal of healthy people 2020. So, our goals include improving the implementation for IHC and MSI screening of all colorectal and all endometrial cancers. And to create a resource we value how successful implementation of this screening is. Then we thought that we would also tag along a mini pilot discovery, so this implementation evaluation, a little discovery, and that is can we aggregate or integrate germline and tumor information, I used the word information, with treatment and outcomes, including maybe surveillance, with family pairs in order to understand the variable penetrance, expressivity and clinical outcomes. And Gail's point here is that individuals from the same family or individuals with identical germline mutations can have different phenotype, both in general as well as the somatic phenotypic outcomes, so that's what that's getting at. So one type of design, and we will pick up the theme of different things work for different centers, and we heard that from Maaren again as a theme, that all colorectal cancers and at the Cleveland Clinic this seems to work not without banging of heads and so on, but it just goes into the pathology workflow and the patient knows this is happening. MSI, MMR, yes, no, and if it's null, we now have added BRAF analysis as well as MLH1 methylation, and if not, so if it's MSI high, I see null, and there is no BRAF, no somatic methylation, the list will go to our colon cancer genetic counselor who scans the list and actually calls the patient and invite the patient to the clinic, and the patient comes to the clinic, receives counseling, and has single gene testing because that is guided by which of the proteins are null. So when that happens and we take it out of the hands of the clinicians at the bedside, the uptake is 80%. So that's the LYNS syndrome. We also chose the neuroendocrine cancer screening, and yes, I illustrated it with pheochromocytoma and paragenioma, and it goes down a little simple, but I slipped in medallary thyroid cancer, so the implementation of routine screening for every single medallary thyroid cancer patient, every single field, every single paragenioma, doesn't matter what the age family history, they can be 2,000 years old, doesn't stop go. For MPC, I should say that it's very simple, it's just rat testing, and the various ways of doing, including integrating a genetic counselor. That has been incorporated into the American Firefighter Association Practice Guidelines published in 2009. As I made the clip, I did write the guidelines, but there is a whole panel. And as with every implementation, the evaluation phase is important, and the scurry phase is can we link it to your family history breakup group, because it will be wonderful to get that type of family history collected electronically. And we just heard that the TCGA projects are asking for certain types of rare tumors to be a sequence, whole genome sequence, and that's thanks to Cates and a whole group's efforts. So I showed you this yesterday, but I did forget two genes, so I slipped into your right, Max and NF1. And there's a little asterisk, because Peter Cobb reminded me that one of the questions to think about is, do we capture and do targeted re-sequencing versus whole genome sequencing and targeted analysis? Because each of these genes has its different risk factors and different phenotypes, which can be surveillance for, in the case of rat standard of care, is prophylactic fireidectomy. And we also wanted to give a nod to the very important crumbs that are left behind, and you heard some of it today in David's talk and so on. And we'll be facing even more of this, these moderate risk variants. What do they mean, clinical utility? How do we screen? How do we treat? There we use it as a predictive test, whether it's negative. And then touch upon today, there's something wrong genetically in our case. The cancer genetic syndrome, all right, but we can't find the mutation in the usual suspects. So the rare phenotypes, no known associated genes, germline and somatic variation for tumor progression and drug resistance. How do the two interact to predict that? And cancers that rarely have somatic alterations, which is discussing in our groups here, isn't that strange that Casanoids and pancreatic endocrine tumors, even though they are apparently sporadic? If you look for somatic genetic alterations, it's very, very rare compared to say your usual lung cancer or breast cancer. Does that mean that it's this epigenomic? Or does it mean that there will be multiple variations in the germline? And that's how they give this type of low level, apparently sporadic tumor genesis. And with that, I'll stop and take questions. Like, as usual? Yes, that's my full name, Mark, as usual. I really like that you were reaching out to the family history group for the neuroendocrine tumors and that I would suggest that even with the Lynch syndrome project, one of the things that I think would, we're missing an opportunity is that while we're doing systematic tumor-based screening, I think we would also do systematic family history ascertainment at the time of admission to identify those individuals that have increased heritability. Well, family appears, yes, but I think that also we need to remember that two to three times the number of patients that actually have Lynch syndrome will have increased heritable risk for colorectal cancer that's not necessarily based on a highly penetrant single gene. And that there would be benefits that could accrue to those folks that they're identified and offered enhanced surveillance and family contact. So I think this would be a nice opportunity also to tie in with the family history group to do some type of a systematic ascertainment of family history along with the systematic ascertainment of tumor markers. I think that would be an opportunity to expand our knowledge. And certainly that was the intent of the group. And we're trying to implement our family history tool in the dreaded primary care. And exactly as Marin says, if we geneticists have hung out long enough, the sub-specialists are a bit more sensitive, but you know, there's a huge primary care practice at the Cleveland Clinic. I can say I've probably received three referrals from them in six years. So it's three better than Marin. Infinitely. These suggestions are right on target. But based on what we heard yesterday from Howard Jacob with his passionate plea for finding ways to make more data from particularly whole genome sequencing available to everyone doing it, and you're doing it for children with rare diseases, and what we just heard from Tijan, as you look at the broad landscape of where this type of technology is being applied in cancer, it's common cancers, and there's an awful lot of sequencing going on. And is there a way that NHGRI, obviously working with NCI, could act as a catalyst for bringing these data together in the same way that DBGAP has played such an important role with regard to GWAS? So what you're suggesting is exactly the sort of thing that should be done, but in the broadest possible scheme, I guess I'm just asking a question, is someone on the outside looking into your group talk about this very broad issue, which Howard highlighted in a microcosm, don't get mad at me, Howard, yesterday, and which Tijan highlighted in a very definite way just a few minutes ago, and Mark was saying, wait a minute, we really want to find ways that we, those people who are doing these randomized trials, which are going to be necessary, can go back to a database and say, what do we really see in breast cancer, colon cancer, prostate cancer, and those sorts, you must have talked about that. Oh yes, we started with that, in fact, and if the chairs did not stop it, we would still be in our breakout group, and we decided that, that exactly as you say, that the higher body be NHGRI or something like that, the higher body should make this happen. Other comments? My day job is managing TCGA, and so I would say we, as you're right, right now it's all common cancers, late stage cancers, but right now you can go in the database and find 4,000 exomes, over 100 whole genomes, and we're going to greater than 10,000 specimens in the next three years, but there is an attempt to now think about the next stage, which is getting to the clinical questions, the response to treatment, and so on, and- TCGA is great, don't get it wrong. But fortunately, we're in a lot of discussions with Harold Varmas about just doing exactly this sort of thing, about expanding into clinical trials, and taking a TCGA genomic approach to clinical trials, and so I think we'll see some action in that direction. Excellent, two higher bodies. Anyone else? Okay, thanks very much. I think next is Murray, and the periodontal microbiome.