This was Navy photography, one man, and a machinist mate at that. Walter L. Richardson took his own graph-flex camera aloft at one of the first naval aircrafts, and someone in Washington saw the pictures. Richardson never turned an engine valve again. He became the Navy's first photographer, and all Navy photography, afloat as well as along, has been a part of naval aviation ever since. The photographer became an officer and a naval aviator. Ensign Richardson established the School of Aerial Photography and became its first commanding officer. He introduced motion picture photography to the Navy, one of the first to recognize its potential, and he led Navy photography into its first scientific investigation. With Walter L. Richardson, officer, cameraman, pilot, Navy photography was born. Since Walter Richardson pioneered in photography, the Navy cameras have become increasingly sophisticated. Methods and techniques more refined, and the uses of photography many times expanded. The basic principle, however, remains the same, the perpetuation of an image, the stopping of a moment in time. The moments in time stopped by Navy cameraman today ranged from a single frame, high altitude perspective of enemy territory, to the heart of an explosion at the rate of millions of frames a second. Film tells us about the environment in which the Navy operates. It analyzes the tools the Navy uses to get the job done. It makes a permanent record of the Navy's impact on this day and age. The Navy camera, whatever its size or special purpose, shows the face of the Navy in a thousand ways every day. Captures on film the vital elements of the Navy's day-to-day operations, contributing to the combat effectiveness of the fleet. The Chief of Naval Operations sets photographic policy and establishes requirements. The Chief of Naval Materiel provides guidance and direction, and has assigned the Naval Air Systems Command as the principal naval technical assistant for photography. This command, through the director of the photographic division, develops, evaluates, and buys the equipment and supplies. It sees that Navy photographic personnel are professionally able. It designs and fits out shore-based and shipboard photo labs, and serves as program manager for the Navy film programs for training and information. Because Navy photography is involved in a broad spectrum of land, sea, and air operations, a number of fleet commands and major field activities support the overall photographic effort. The Naval Air Development Center, Johnsville, Pennsylvania. Development of aerial cameras. Technical support center, Suitland, Maryland. Photo intelligence. The Pacific Missile Range, Point Magoo, California. And the Navy Weapon Center at China Lake. The job of using photography to develop and sharpen our firepower. The Naval Ordnance Laboratory, White Oak, Maryland. Aerobolistic research and undersea warfare. And the Naval Photographic Center, Washington, D.C. Volume still and motion picture production. Film library for the Navy and film distribution. Research and development in handheld cameras. In film. And in film processing. From the Navy a photographic pioneer, Walter Richardson. But aerial reconnaissance is still the prime mission of Navy photography. Besides an analytical record of the Earth's surface and of everything that moves on that surface, that's aerial reconnaissance. Barriers are completely equipped and staffed for every step in photographic reconnaissance from operation and maintenance of the cameras to complete film processing equipment and stereoscopic devices for viewing and interpreting the photographs. The fleet's photo reconnaissance system, a float and a loft, is backed up by the Navy's shore establishments. The Naval Air Development Center tests and develops aerial cameras and other airborne reconnaissance equipment. A gigantic collimator, testing a 40-inch lens many times larger than the aerial camera to which it will be fitted. The development center's own aircraft run flight tests of cameras, camera pods, and devices for night photography. Photo intelligence techniques and systems are developed at the Naval Reconnaissance and Technical Support Center. Photo interpreting equipment begins here as an idea. The idea becomes reality in the form of a prototype, which is then tested, not just for technical performance, but for operating efficiency in the bouncing, salt-laden, humid environment of a ship. The equipment that reaches the fleet is practical, workable, indispensable in the job of analyzing enemy activities and of briefing the attack pilots for their strikes. The pilots see their targets in advance. They build graphic images of checkpoints, enemy defenses, the final objective. The Navy has prepared the airmen for their strikes, and it has contributed, too, to the aircraft they fly and the weapons they use. At the Naval Ordnance Laboratory, photography is a specific science, part of the research on missiles, explosives, and underwater weapons. In this 1,000-foot ballistic range, a complex electronic and optical system films a missile's trip down the tube at over 7,000 miles an hour. Color-slearin photography makes turbulence and changes in air density visible as a ballistic missile moves through the tunnel. The color techniques give an observer three factors to evaluate. Hue, color saturation, and brightness, not merely shades of gray. The pattern of shock waves, the pitch and yaw of the missile, speak volumes to the photographic interpreter. Underwater high-speed photography, an evaluation of a submerged explosion. Photography documents the wind tunnel behavior of a ballistic missile, encountering air speeds of up to 17 times the speed of sound. The instrumentation camera follows the flank path of a mine from time of release until it hits the water. Photography documents an event from beginning to end, even though the life of the event may be reckoned in microseconds. These scenes were made with a Jacobs camera, developed at the Naval Ordnance Lab. It produces pictures at the incredible rate of over a million frames per second with no loss of information between frames. Deep in the Mojave Desert of California at China Lake, the Naval Weapons Center conducts a program of warfare analysis. Ride the weapons and the test slits or observe from near and far, registering changes and movements imperceptible to the naked eye. Photography tries to show the why of every malfunction. It can be projected in ultra-slow motion. They can be stopped, backed up, viewed again until the engineers know why that parachute failed to open in time. This can begin again, with equipment modified through the lessons of photography. The action system which can save astronauts even when used from ground level. Specific missile range at Point Magoo. Every firing is photographed. Every type of missile checked before it's released to the fleet. Fans prove themselves here, too, at the Navy Missile Center. Cameras track the flight of a new missile and check its behavior pattern. Pods developed here are used to record combat strikes as well as test runs. They must perform without attention. The pilots have their hands full with other matters. This pod carries a television camera and its transmitter in addition to a conventional high-speed camera. Missile launching 100 miles at sea can be televised back to the engineers at Point Magoo with instant playback, too. When these planes strike, their weapons will function properly because photography has found their weaknesses and proved their strong points. Now photography records the strikes themselves for intelligence, for tactical information, for training. Pilot is probably the most photographed American fighting man. When he returns to his ship, he is the subject of a special camera, part of a television system called PLAT, or Pilot Landing Aid Television. Every recovery is televised. As the aircraft approaches the carrier, the PLAT television cameras pick it up and keep it in constant view, recording the landing signal officers running talk with the pilot. Later, each pilot can study his landing performance on video tape. In the event of a mishap, the tape becomes a valuable investigative tool. Training film production is another mission for Navy photography. Professional filmmakers from both the Navy and commercial studios produce hundreds of motion pictures each year for fleet distribution. The Navy's own photo crews often mix service personnel with civilian employees, all contributing to a single goal. Whatever the subject matter, simple or sophisticated, each training film finds its viewers. Any group of men with a need to know and a need to learn, whether at a stateside shore station, aboard a combat ship, or at a remote outpost. Navy photography informs as well as teaches. Picture supplement words, amplify ideas, clarify policies. And pictures are the stock and trade of the more than 400 Navy photo labs from the Arctic to the Antarctic, aboard ship and ashore. The largest and most modern of these laboratories is the installation in Washington, D.C., the Naval Photographic Center. Here under one roof is the central photographic facility for the Navy. NBC has complete motion picture production capability from the inception of the film idea to the release print for distribution. The photo center's still facilities are geared to the mass production of photography, serving a variety of purposes in the Navy. A still picture library and motion picture film depository assure that valuable film records will be safeguarded and available when needed. Specialists in the research and development department test, develop and evaluate new photographic chemicals, films and photographic equipment before volume purchases are made by the Navy Department. The Atlantic and Pacific Fleet Combat Camera Groups headquartered at Norfolk and San Diego cover combat operations and special assignments in their areas. Wherever the Navy operates, Navy photography is at hand to record, to inform, to document. The cameramen have reported most of what the world knows of conditions on the great white continent of Antarctica. Posing film under the most extreme conditions imaginable, Navy photographic personnel, accompanying explorers and scientists in their search for evidence of the Earth's history beneath the polar ice cap. The Navy records the daily life of South Polar citizens and the hazardous behavior of ice and weather. The Navy is vitally concerned with man's ability to live and work beneath the sea. Every step of the Navy's research in the ocean depth is recorded by Navy photography, which has had to develop its own techniques for work on this new frontier. Photography in the Navy is no less a weapon than a missile slung under the wing of a fighter bomber. With this photographic weapon, the Navy learns more about the physical forces it must use. It explores new approaches to old problems since its capacity to carry out its statutory mission. Walter Richardson made his first aerial photograph. The need for photography has continually expanded. New uses have been discovered. And new cameras and processes developed. The growth of photography reflects the growth and change of the fleet itself. As long as man continues to cross new thresholds in the sky, continues to probe the frontiers of the sea, seeks out answers to the eternal questions posed by his planet and universe. There will always be a need for some way to graphically record that moment in time. Preserving our place in history, our moments in time, as others have done before us, is Navy photography.


My name is Dr. Sean Meredith. I'm an assistant professor at the University of Maryland School of Medicine. I'm an orthopedic surgeon. I specialize in sports medicine. And I work at a variety of locations in and around Baltimore, spanning from north of Baltimore and Hunt Valley all the way south into our Capital Region network and down at College Park. I take care of patients a wide range of ages from kids up to adults. I take care of hip, knee, and shoulder problems, sort of the full spectrum of problems with all of those joints. And like I said, I specialize in sports medicine, so I take care of lots of active people and lots of athletes of various levels. As an academic surgeon, I have sort of a range of things that I do on a daily basis. So I'm definitely a busy clinician taking care of patients, seeing patients in the office and operating. But I do clinical research. So we work on clinical outcomes and looking at how patients are doing, basically, and trying to track different metrics and seeing how we can optimize results. I also teach a lot. So as part of my job at the School of Medicine, I teach the medical students, musculoskeletal medicine. And I teach our residents a lot about becoming an orthopedic surgeon and sort of training our next generation. My goal for patients is largely to get back to doing what they want to do as quick as they can in a safe manner. So most patients come in because they have pain in one of these joints, and they can't do what they want to do. And my job I see is how can I get them back to doing what they want to do? And I try to never limit anyone, and we try to get them back as best we can. And the majority of time that means without surgery, which is certainly what we want to do, because usually that's faster, and that's a good way to get people back. But sometimes it requires surgery and basically making the patient's experience as good as possible, going through that and getting back to doing what they want to do. You know, I'm a physician that people go to because I'm willing to talk to you in an honest manner and try to make it as simple as possible. And I think that's one thing patients tell me is helpful is that I'm sort of explain things in a normal manner so that it makes sense to help them along through their injuries or issues.


Welcome back to the Video Game Storytime Advent Calendar, where today we ask a question that nobody really wanted to ask. Why don't Waluigi and Wario have girlfriends? Mario Tennis is perhaps one of the more significant titles for Mario Law, having brought characters like Princess Daisy and Waluigi into prominence within the Mario canon. According to Camelot, the developers of Mario Tennis, their development team wanted to round out the roster with mixed-gender partners for the game. Mario has Princess Peach, so who could Luigi have? They asked Nintendo, and Nintendo then suggested that Princess Daisy from Super Mario Land on the Game Boy could be Luigi's partner. Then, Camelot asked about partners for Waluigi and Wario, said Hiroyuki Takahashi. We asked Nintendo about girlfriends for Wario and Waluigi too, but Mr. Miyamoto said that he didn't even want to see their girlfriends. This suggests that, somewhere at Camelot, there might be concept art for Waluigi and Wario's scrapped girlfriends, but Shigeru Miyamoto didn't dare look at it. Oh well. At least Wario and Waluigi have each other. Join us tomorrow for the next Video Game Storytime Advent Calendar video.


Came a couple of the guys talked about just like how special it was to have these two days and a practice You know how good was it did just to get a day off and then a practice and then in a season That's always so busy. It went fast. That's for sure.  Yeah, I have I have Uh Yes, it's not bad weather was okay yesterday, so you know better than you know better than has been a past couple days So yeah, I was able to get out and get a nice walk With today's practice how important is it to kind of get back to those principles, especially with the game? Coming up against the Hawks that team that you just saw a couple of weeks ago That was over time very important, you know things to clean up. It's working. It's a work in progress And it's always a process Get into where you want to go Seen a lot of things from the game last time we played them that we can clean up Obviously, we got a lot of points so a lot to look at and we're looking at it and getting ready for the game Had a couple crazy games. Yeah with Atlanta.  You can bring to the table You got it. All right, how's it been with with Spencer? He's last few games just seeing him settle into this I guess facility or score when necessary But just the ability of knowing when to assert himself as a scorer more of these last few games How's it been kind of same as last year as I feel like this kind of what he was doing last year So it's not foreign. It's not something new Everybody knows just capable of that Very very it's very helpful Takes a load off a lot of guys and he's capable. He's he's a high-level scorer Your skilled player so anytime he brings us to the table is it's positive for us I mean last year when the trade went down, obviously he'd left one role in Dallas and came here and filled a different role All right, but this year I Mean, he's had to change roles on the fly in the midst of the season Oh Ben's gonna be on the ball.  What does it say about him that he's able to? Change on the fly like that and still be just as effective He has a lot a lot of you know dimensions to his game a lot of elements to his game And you know it's definitely tough to ask anybody but but he's P processes a game at a high level He understands it so he is able to kind of move around I know it's been four months since August since the feeble world cop But when you were playing when you were over there, what did you notice about the passion for basketball in the region in the Philippines? Oh, man, they absolutely love basketball. I'm talking about the hotel every entrance exit You could think of was to warm with people so you'd kind of be careful in that regards But they were they're just they're a passionate fan base over there. They're pretty knowledgeable And they showed a lot of love I'm curious because the last time he played in Atlanta McKell mentioned about how he's never won in Atlanta It's something that he thinks about for you since I imagine it's the same That's something that you think about as well. Yeah, that's why we're glad we had this one You know schedule Is there something that makes it land out hard plays the plan not necessarily? You know, we've had close games there. We've had games where they've shot the ball really well We've had games like last time where it comes down to the very end. We played them at Atlanta last year And and and lost on a buzzer beater. So they've been close games. I just haven't really swung our way But it's definitely one that we're looking forward to finally getting over the hill of You see me kill since the beginning of his career for tours when he's playing angry like he played Against Charlotte Saturday. I guess what does that mean for him when you can see him? Just kind of channel that anger into a performance like he did where he has 26 and a quarter It's you see him moving fast, you know, he moves pretty pretty quickly when he's angry and You know, I think it gives him a little bit of a speed boost is what I'd say, but yeah He plays well plays aggressive, but he's taking good shots. You know, he's not taking a while out of control shots He's slowing down when appropriate get into his midi getting all the way Able to knock down the three so as it's the school to watch and then lastly for me Heard assistant coach Kevin Alley gave you all a pretty rousing speech. Mikhail mentioned it Dennis Smith mentioned it What does it mean to kind of another voice on that staff on the staff that you kind of just kind of keep it real with You guys the way that jocked us. You love it. You love it And we responded to it and I thought it was a you know a great a great scout a great message by him to get us ready for the game Obviously a lot of people thought you may struggle coming into the air in that regard Just what have you seen from you guys that whether schematically or just from a mindset That's allowed you to be there even with all the moving pieces injury was I think an element of it is guys playing free And playing for each other and getting quality looks and shooting it with confidence


Well, unless we won tonight, tomorrow night doesn't mean a thing. If Lebanon Valley would have been able to beat us tonight, then that would have really, really hurt us and we would be in a big mix for who's going to be the number one seed in our conference tournament which means we get to play at home for the semis and if we win that we get to play at home for the finals, which is huge to us and we play very well on our own floor. So tonight's win was a big one. I thought that Lebanon Valley was very scrappy. I liked all four of our pin hitters. Both our right sides, Lauren Weaver, Mariah Savage, both hit above 300. Katie Leffridge, what did Katie hit over 500? That's getting to be her match. It's above 500, but Katie had a really good match too. And to tell you the truth, the one I was most impressed of was our defense. When we can hold a good team like Lebanon Valley to 077 and their best hitter to 000, it's a good night for us. And so I was impressed with how hard we played on defense. Yeah, we had a number of service errors. We had a number of hitting errors. We were in the net. We were having some issues. You can't play great and perfect all the time. So we made some errors and it was 20-20 and we got a block and a kill and we're able to pull away there at the end. Well, that's a great question because Katie Leffridge started off that match, five for five, and I mean, they were thunderous. She was nailing the ball and that gave Mariah Savage and Chelsea or Victoria, who was ever in the middle, gave them single blocking. They were sure we're going out to Katie and then all of a sudden Caroline's setting against the green. And Julie and Emily did a great job getting the ball to Lauren Weaver tonight. She had been struggling a little bit and she comes out hitting over 400. So they can't sit on anyone hitter. Today, we're going to double block Annika. They can't say that. Annika had one of her regular games that we expect from her.


All right. So I just have five slides, so it should only be maybe 45-50 minutes. So it's a little bit about the breakout session yesterday in pharmacogenomics, and Alan Shuldiner wasn't here, but this is on behalf of the group that met, including the three that have some responsibility. This was our charge from last December, identifying one or more collaborative demonstration projects that would advance the implementation of pharmacogenomics into clinical practice. And I'll mention briefly one of them in the next slide, but very little time was spent on that, mainly because the RFA is out, people are already thinking about those actual projects from the past discussion, and if you haven't started thinking about it now, it's kind of too late, so there wasn't a lot of time spent on this part of the charge. Now this is a slide from Alan. I'm not sure exactly what it says, so I'll just talk and not even look at it. But basically one of the things that is coming out of the last efforts is this collaboration that has been heavily driven by the Pharmacogenetic Research Network, where many of the PGRN investigators, including Julie, Dan, others who are probably here that I'm not seeing at the moment, have been involved in getting their version of the must-have genetic variants. Debbie Nickerson, who was here yesterday, is involved in putting together that platform. And there's a custom drive panel, the VIPGX or PGRN-Seq or whatever it ends up being called, will be applied probably across some of the eMERGE network sites, which also is heavily represented here in the room. And so the idea that a more focused platform for looking at pharmacogenetic variants can be tested in a broad population, looking at what is the incidence of these variants, looking at some of the initial association with outcome, is part of the idea that's coming forward. And this is mainly driven because many of the off-the-shelf platforms do not do a great job. Many of the off-the-shelf whole exome, next-gen, sequencing type platforms do not do a good job when it comes to pharmacogenomics. And I think many of us have had experience using the several of the different next-gen platforms, fantastic coverage, except for SIP2D6 and the 3A family, and some of these other regions where there's a lot of pseudogenes, high homology, and those kind of issues. And so one part of that is really trying to tackle this. Now, I think that some of the off-the-shelf, if you want to use that term, tools that are coming out now are starting to overcome this issue. There's also other labs that have their own custom version of this that seem to give very good coverage. So I think this is a problem that technically is being solved. But where this comes in is really jumping the hurdle towards doing a broader application, taking these platforms and trying to think about what is the instance. You know, when I talked to, I love that Pearl had such a primary care focus to a lot of what she was just talking about, because when I talked to family members who are in the primary care area or collaborators for that matter, first of all, they want to know just in time. But they also want to know what are the areas where they should care. It's really kind of what is the minimum amount of information that can be delivered as late as possible. And I think some of the work that's happening here will help identify things like how many patients actually have these variants. You know, is this a one-in-a-lifetime experience or every other patient? I don't know if Josh Jean is still here, but yeah, right there. There he is.  Congratulations. So I know you got a paper that will be coming out sometime soon. The editor of the journal is back there, so maybe I shouldn't say anything. It's probably an embargoed. But just looking at, well, what are the frequency of some of these variants? What are the frequency of some of these variants in a Vanderbilt medical home? And it actually occurs in a lot of people, and it's not this rare event. And I think some of that, some of what's coming out of this pharmacogenomics working group, are getting some of the simple descriptive proof of principle that would cause a generalist, whether they're an internist, family medicine, pediatrics, to realize that they might actually care someday. And they can wait until they have to care, but they at least might care someday. And so I'll stop rambling about that. The other thing is we spent a lot of time on non-RFA issues because the reasons I already said. And one of them was around the areas of publication. And so one of the things that really came out somewhat from Ned's talk yesterday and from also general discussion is this idea that in pharmacogenomics there are elements that are not usually included in genetic assessment analysis. And we talked some about that. I mean, it's not just EGAP. It's really across the board with, I guess, one of the exceptions being Mary's CPIC program. But the idea of going and looking at across these, doing kind of a, Mark called it a meta-meta-analysis, a meta-analysis of the meta-analysis, is not really that. What it is, is basically assessing the different assessments and saying, well, what are some of the categories of information that are consistently missing and try to inform the assessment community about those? Because there are just a small number of categories, things like dose or concomitant medication, that if the EGAPs and others knew about them, they would become part of the normal process and would allow the interpretation of the pharmacogenetic component to be a bit clear. The answer still may be that they're completely useless. The test, not the assessors. But the idea that we can do this and have an outcome that would cause people to maybe be disgruntled but not have a good reason would be ideal. Because right now, you get a lot of feedback about disgruntled and they use this as an excuse. It would be nice to go through that. The other, and really so we can just define some of the rules to aid these groups. The second is looking at some of the advantage and disadvantage of the current platforms for pharmacogenetics. And there are a number of platforms out there. This is something maybe done best with the sequencing group. There are a number of platforms out there and we're starting to learn a lot about the nuances of where they're useful and where they're not. And there are a lot of general laboratorians who maybe do molecular diagnostics but also do a bunch of other stuff at the mid to small size centers that are starting to get into the space. They're taking off the shelf products and hoping doing the best they can. Now, maybe the point should be they shouldn't do that. But they're doing it anyway. And so we could come up with some output that would help put them into context. Because there are some major differences across these platforms when you get to the practical side of that. And we talked a lot. How is it was was was was kind of to join our group and get all the glorious benefits of being in our group last night. We had the free car and all that all the booze. And really was highlighting some of what's going on at LabCorp where they have kind of every platform possible and have to figure out which one to use in each case. And many many times that is the situation. The last thing is that amongst amongst the different genetic areas there there often is a a single or a small number of sugar daddies that are pushing a particular area might be inherited metabolic disease might be in cardiology etc. But in pharmacogenomics there really isn't a body that way. And if you expand it further and look at imaging, imaging happened rapidly because there were two bodies that were involved. One was the manufacturers making sure that everyone was trained up on how to use the latest scanner had access to it had experience to it. And the second was the the radiology is a discipline that exists and say depended. It's a discipline to depended on to translate complexity into simplicity. And genetics does not have that that in most centers. And so this this idea of trying to really look through who should be pushing this, including trying to engage the payers a little bit more. Because when it comes down to it, the payers are the ones who are likely to benefit first, even before the patient in in many of the things we're talking about. And then lastly, we really highlighted some of the endpoints that we were interested in academically. And they often don't match what insurance companies care about, and certainly don't match what even our own clinical leadership might care about within our institution. You know, it was wasn't until meeting with our CEO that I realized how important bounce back in the first 30 days was. That was not an endpoint on my radar. It is now. The you know, half a day of delayed discharge for because adequate pain control huge deal. And also, I think it was visiting some of the folks at Cincinnati, one of their colleagues is anesthesiologist, and he mentioned that 22 minutes in the recovery room was equal to $1,500. And you know, minutes matter in that context. So we had talked about going amongst the institutions involved at this, either at this meeting or just with that committee, and starting to define those endpoints better and getting them out in the public domain. Because certainly most pharmacogeneticists are looking at academic endpoints and because that's what study sections recognize. But often they're endpoints that are really not very useful to the people downstream who need to be using it. And then I'm going to end this slide of Rex's barriers for genomic medicine. These are basically copied down from your slide yesterday Rex. And just highlighting this point that many of these things on here are not primary endpoints to our academic studies. And part of that is a education of study sections and selection of study section members. But you know, if you really right now wanted to go for funding around areas that really matter, it's very hard to get this funding in any of the study sections that I've been on. And those of us that are on council, when we think about the fights that would happen at council, with some of the people who aren't in this room right now, because they don't care about things this far downstream, they would be immense. And so there is a challenge both in terms of academics and the process at NIH in terms of trying to really tackle this. And then I'll stop and take questions. Okay, Rex, you first. You're going to argue with the last slide? No. Okay. It was literally his slide. I mean, I just marked it down. So Mark is going to argue with the last slide. No, actually, I'm going to say this is something that I think we'll be coming back towards the end of the meeting in terms of this whole issue of what are the outcomes that we need to be looking at. And I think that's a really important point. And I'm glad that it arose in another setting then in the planning committee setting. I think the other thing, you know, we've been focused a lot on payers, but you know, the point that you made about going to your institutional leadership, it's important not only from the perspective of them as your institution, but also remember the fact that the people that really will benefit from making breakthroughs here are the employers, because they will benefit not only from reduced healthcare insurance premiums, but they also have to deal with absenteeism, presenteeism, all these sorts of issues that affect worker productivity. And then the studies that have been done looking at self-insured plans by ComEd here in Chicago in Illinois, their return on investment for things that work is about five to six dollars for every dollar invested. And so I think that's another community that we should think about when we think about payers is because almost every large company is self-insured. So they are in fact their own insurance company and they stand to benefit and some of them are very interested in exploring new ways to do care. The MedCo studies that we've seen so far have all been paid for by employers, not by MedCo. They get all the credit, but they get the employers to pay for it and because they believe there's something there. Mark. I don't know. I want to comment on Rex's slide. Okay. Okay, thank you. And that is that given the definition of genomic medicine that Terry presented yesterday, in other words, using that information, genomic information in direct patient care, those barriers all make sense. I think other people have a broader definition of genomic medicine and if in that case one of the things that's missing would go right up at the top and that is lack of information about the underlying biology of disease and the ability to use that information to design better therapeutics, better strategies. So I think from at least my point of view that when we talk about implementing genomic medicine, I think we really need to be very clear that we're all agreeing on the same definition because I think a lot of the issues that the disagreements that come about are probably this definitional basis. No, I think that's a good point, Mark. And I think certainly I wasn't trying to, my apologies, Rex, I wasn't trying to get in trouble. I use this as just kind of, I was just trying to anchor with the kickoff of the conference, but the way the slide from you and Eric's paper is it's those five boxes, the graphic artist tried to make them a continuum. And if we end up with people working in each of those boxes, we really haven't gone forward. We need to be people working across those boxes. And that's the challenge is that as humans we'd like to be in a box for some reason and we need to be looking across there. And so if we don't have good discovery, if we don't have good validation, including in some of these clinical trial samples, if we don't have biological plausibility at the least, if not actual mechanism, then you're right. We can't drive this forward. And we can't get any extra added value from it. I just want to add to that. I mean, Mark and I have talked, and I'm used to being in trouble, so no problem there. But one of the things that strikes me that we don't emphasize enough to build on Mark's point is all of these variants of unknown significance that we see in these sequencing projects are likely to be highly informative in terms of the biology at some point. And so we really need to be making sure we're not just moving left to right in that diagram, we need to be moving right to left in that diagram as well. So I think there's a really important opportunity for us to figure out how, and we've emphasized at this meeting a lot, the need to capture these variants of unknown significance and then feed them back into the biology. So I think that's a really important point. Julie, and then... So Howard, the one thing that you didn't raise that I think we talked about and that Mary tried to bring up yesterday is that the idea that pharmacogenetics is a bit different than the disease genetic stuff and that, for example, putting a group of genetic data into a medical record as it relates to pharmacogenetics, none of the actionable variants for which really are associated with disease is probably not gonna have the risk of leading to additional diagnostic tests and workup. And so it really does seem like a better starting place to begin to get things into the record in a preemptive way because it's very unlikely to kind of have that extra workup sort of downside potential negatives because they really are specific to drug response. Well, thank you very much for that. I put that X down at this bullet here because I knew I forgot some stuff, and I was hoping that people would fill in the X. So thank you very much, yes, that we just have a discussion. Scott, and then John. So I just wanted to briefly explore your concept that some of your favorite sites in the genome are not accessed well with, say, exome, but that they will be accessed well with targeted genotyping platforms. So I mean, if you think about it, you mentioned processed pseudogenes and maybe repetitive, difficult areas. I mean, some of the reasons why mapping might fail in an exome study or why capture might fail, I would think would give you trouble in some of these targeted genotyping platforms as well because they involve oligonucleotides. Some of the cheapest platforms are done on whole genomic DNA. Yeah. Well, I think that, so I would look to someone else to give the details about the specific output that Debbie and others have generated, but I think the difference has been the use of a general algorithm across the entire genome versus almost hand-crafting the probes used for the selection tool for these. So one can get around these pseudogenes if you design the probes appropriately, but if you use just a general genome-wide analysis or probe generation strategy, you end up falling into trouble. And so they're all solvable areas, but not if you don't take into account the pseudogenes and such. So the- But presumably you could give that feedback to the manufacturers of exomes in here. I don't know what platform, I assume it's an aluminum platform that Debbie's using because she tends to go that way, but it's not like some magical new method is being invented. It's just the selection tools are more carefully crafted for this specific indication. So I didn't mean to overstate it as some amazing new breakthrough that we're all gonna wanna run out and buy stock in. Or sell stock in. John? Is it still the orientation of the pharmacogenomics group that you have the opportunity for large effects, high odds ratios instead of the situation in common disease where you have small effects or rare, small effects for common variants or large effects for rare variants. And in the pharmacogenomics space, you have ample opportunity for large effects for common variants because there's no previous evolutionary selection that's ever occurred for these environmental compounds that we've never seen before as a species. So I think that that has been the wish for pharmacogenomics. The hope is that it would be easier than the disease genetics, for example, because of that. And there are some examples. The most dramatic are some of the HLA's with these odds ratios of 2,500 and such. You don't even need a statistician or genotyping. You just throw it on the wall and there it is. But the reality is that there are many examples coming out now which have an odds ratio of two. And maybe when you add them up and put in some clinical factors, suddenly you get some prediction. So I don't think it's going to be a case where pharmacogenetics will have odds ratios of 10 and disease genetics will have odds ratios of 1.1. But the other thing is that certainly Mary's published recently on this as of others that there are rare variants that matter. And at least the most recent paper that I know from Mary was with one of the SLC transporters saying that there were rare variants that did contribute to the effect of methotrexate. Now there was an effect of some common variants too. So it wasn't an all or none. But I think that most of the lessons that we're learning from the disease genetics people are being found in pharmacogenetics, even though we wished it was going to be simpler. Does someone else from the committee? I'll just say that for many of the drug response phenotypes we just don't have the data yet. Well, you know, that's a, you know, I presented at the NIH in their, I can't remember what your, the genetics course was, but what it's called last year. And before that did a little analysis of the NHGRI GWAS catalog. And it was 4% of the GWASs that had been done at that point had any drug endpoint at all. And it was only a minor percentage of those that it had more than 500 patients in the whole thing. And so if you look at the criteria that we would recognize as being useful for GWAS or other discovery approaches, and look at what's in the catalog for pharmacogenetics, there's very little. Now, of the ones that are there, they've had dramatic impact. I mean, you know, the IL-28B being one of them. But it's almost like pharmacogenetics hasn't really started in some ways. Of the top 200 drugs, it's only about, I think it's about 15 of them that it had any pharmacogenetic analysis at all. Much less negative or positive. So it's a long way to go. Howard, I'm sure you're working to fix that. No, it'll be available to fix it first. It's probably instructive. So I think as many people in the room know, the eMERGE sites are in the midst of trying to think about genetic variants that they would actually measure in an experimental way, put back in electronic health record and test what the implications are for outcomes or for at least process in terms of that. So at least at the Northwestern site, we've been very actively engaged with our physicians group that's gonna be implementing our genetic variants. It's a general internal medicine crowd that's very engaged and interested in quality improvement. And it's really interesting to me that overwhelmingly the things that they are excited about doing are pharmacogenomic variants. And the things that they're less interested in doing are disease risk scores, common disease risks with relative odds ratios of 1.05. But the pharmacogenomic variants, they're quite enthusiastic about. And Dan will appreciate this. We even reached out to some of our interventional cardiologists and they were very excited about actually doing this. That's because they've heard from their friends at Vanderbilt that it's not gonna kill them to do it. But the other piece of the implementation stuff that we've been thinking about in eMERGE is not disease prediction. So nobody, I mean, we've heard that this morning already, but if you have disease X, what's your outcome likely to be? So if you have hypertension, are there predictors of increased risk for renal failure? If you have diabetes, are there increased prediction for ocular complications? And we think that that might have, number one, increased odds ratios, and number two, might catch the attention of the provider and the patient more than telling some 20-year-old that you're at increased risk based on some genetic marker of type two diabetes when they're sort of sitting in your office eating French fries or something. I guess I give myself the last word. Just one, if I could make a comment to your last one. Although the increased risk is certainly important, the payers will be looking for the next step, which is does the intervention and paying for extra drug, et cetera lead to an improved outcome before they'll want to pay for that. Okay, that's a really important comment. We'll stop there. So we're not really on time, but we're sort of on time. So let's have a 20-minute break. We'll come back at 10.50 by the clock on my computer and then we'll have the short updates from Howard Murray and who's the third person? Jeff. And then we'll get back on schedule sort of.