 Good morning. What I'm going to talk about today is our efforts to enhance our research by incorporating data from the periodontal microbiome. So we all know that we're in personalized medicine. We take into account, of course, genetics and also environmental exposure. The microbiome is one of the most important environmental exposures that we have. And the oral microbiome, the periodontal microbiome, is known to be rather important in many of the diseases that we're interested in. So we're building on our previous work in the personalized medicine research project, which is a population-based biobank that we have that has over 20,000 subjects in it. For each of these subjects, we have DNA plasma and serum samples, access to electronic medical records that the Marshfield Clinic has pioneered, and these medical records go back an average of 30 years. We also have the ability to recontact our subjects, and we also have various advisory boards, including community advisory group, ethics and security, and also scientific advisory board. And I'd like to add that in terms of institutional support, this was all done with Marshfield Clinic funds, which were literally millions of dollars to set this up. And this population has been instrumental in many of the studies, for example, through the eMERGE network. So a lot of our studies are funded through eMERGE. We'd like to, as I said, we'd like to add to its utility, and in doing that, we're creating this oral and systemic health research project. So we really would like to understand the connections between oral and systemic health. It's interesting that among many of our medical colleagues that the mouth is not even considered part of the body, so we think it is, and we think the microbiome is very important. There's tremendous evidence now out there of a mutual enhancement of periodontal disease and diabetes. So that is, if you have diabetes, you're more at risk for periodontal disease, and if you have periodontal disease, you're at higher risk for diabetes. Other common diseases linked to periodontal disease include heart disease, hypertension, osteoporosis, and each of these has genetic and environmental, other environmental risk factors. So understanding, also understanding the causes of oral diseases are important. What are the genetics of periodontal disease and dental carries? What are the effects of genetics in these particular disorders? And also if we take into account diet, water source, and of course this microbiome. So our goal is to understand really how improving oral health will aid in systemic health, and that could be through comparative effectiveness, and to bring a personalized health care to the dental arena. So the Marshfield Clinic has opened up seven dental centers, two more are planned. We provide dental services to all counties in Wisconsin. We employ 39 full-time dentists, and in 2010 saw over 30,000 unique dental patients, and then this year saw an additional 40,000 unique dental patients. In our virtual data warehouse, we have currently about 190,000 medical patients, and then the 70,000 dental patients. In the past year, seeing both by our medical facility and our dental facilities, we have 26,000 patients, and in this past year, 72% of our dental patients are also our medical patients. Just as we've pioneered electronic health records, we've also done the same for electronic dental health records, and combining these two records together. So we're among the first in the nation to implement an integrated medical dental electronic health record environment. So in creating this research resource, we will recruit additional patients, and actually some of our dental patients are already in our personalized medicine research project, but we intend to recruit an additional 2,000 patients on top of those that are in both. And this will, in these patients, we will have, just as we do with PMRP, DNA, plasma, and serum, plus a standard periodic test for fasting glucose, hemoglobin A1C, serum microalbumin, and also we will be taking samples of oral bacteria, including the periodontal microbiome. And these individuals will also answer a detailed questionnaire on their environment and diet, et cetera. And so we're building on previous work that we've done with our personalized medicine research project, and currently we have about 1,500 individuals who are both dental and patients, and also in PMRP. And again, we're going to be recruiting 2,000 additional subjects. We also have pilot projects going that are funded by the Marshfield Clinic. Two of those are on diabetes. And we've received significant funding from Delta Dental to help in this recruitment and build this cohort. So like the other medical centers represented here, diabetes is one of the larger problems that our population faces. In our over 65 age group in Wisconsin, about 19% are diabetic. And among all ages adults, about 10% diabetic. So in 47,000 unique patients in which we've had both dental and medical data within our integrated medical dental enterprise data warehouse, we have about 9,000 moderate to severe periodontal diseases and about 2,700 diabetic patients. And we have about 1,900 diabetics who have had a dental visit within the past year, but almost 900 have not had a dental visit. In one of our centers, the Chippewa Falls Center, these are the kinds of data that we have currently, including tests for hemoglobin A1C, cholesterol, fasting glucose, et cetera. So we have among these dental patients, we have in just the one center, we have about 800 people who we could get data from. What we'd like to do among the lowest of the low hanging fruits without even considering genetic information is to have alerts for people who have say periodontal disease to be screened for diabetes and vice versa. So this resource will combine our electronic medical record data with electronic dental record data with genomic data and other biofluids, blood and serum samples as well as oral microbiome samples. And we hope that this will enable us to better understand the contribution of oral bacteria to diseases. And I'd like to refer you to a really great review that Jeff Ginsburg and colleagues have just published in oral diseases and I've reconstructed one of their figures here that just illustrates how the oral microbiome can play a role in various diseases. So and in answer to Terry's question, I've kind of made some notes as to some of my colleagues here, what kinds of things that you have available. And just as we've done with PMRP, we're very open to collaborations and setting up joint research projects in this area. So I look forward to discussing that with you later on today. So be happy to answer any questions that you have. Great. Comments for Murray. So Murray, in your background, you noted the importance of environment. And in the slide that you were talking about data collection, there wasn't anything that specifically mentioned environmental factors. I know that you do collect environmental factors for the personalized medicine program. So the two questions I have is what is your intent in terms of collecting environmental risk factors that may impact some of your hypotheses for this program? And the second question is, it seems that if in fact there are some specific environmental factors that this would be a nice target for the collaboration aspect of it, presuming that the cheese level in other collaborators may not be quite as high as Marshfield, Wisconsin, or some other environmental factors to be named later. So could you comment a bit on that? Yeah, so I like the part about the cheese. So yeah, we will be collecting the same environmental questionnaire data as we do for PMRP. These individuals, these subjects will be within PMRP. So all the data that we have on PMRP individuals will also be collected on these new individuals as well. And we've also been working through the Fenex Collaborative to standardize a lot of these environmental effects such as smoking and alcohol consumption and things like that. In addition, we're gathering a lot of data in particular about water sources and fluoridation and things like that in terms of this cohort. And also various aspects of animal exposure and things like that that may mark our population differently than other populations. Yes, Pearl. Are you looking at the microgene, yeah, are you looking over time or is it a single snapshot of the microbiome? Right. Thank you. We're going to be looking over time. So our dental patients, what we're focusing on are kind of naive dental patients. Patients that because of economics in our state and other places are underserved. So Wisconsin like all other places, we have a large population of rural poor who are not served currently for dental care. So we can actually, as these patients book at our dental clinics, we can see, okay, they haven't seen a dentist in two, three years, something like this. We also capture their health records, their patients to the Marshfield Clinic Medical Center as well. So we're going to focus on those naive patients first and collect Peridonal and other microbiome specimens at their initial visit and then at follow-up visits every six months. So included in that are really some of the standard tests for diabetes that I've talked about, hemoglobin A1C, microalbumin, fasting glucose, and we'll have that periodically at six-month intervals. And that will be important in looking at effectiveness of having good dental care. How is that going to affect their diabetic status? How are you going to characterize the microbiome? So we're going to be taking samples from four different places in the mouth, saliva, and then also more aerobic surfaces and then anaerobic surfaces. And then specimens that are associated with Peridonal disease. And then these will be subject to 16S sequencing to characterize the community. So you may be aware of the whole genome sequencing that's already been done on the dental and that certainly gives you a lot more information. Yes.