So, I have the pleasure of introducing our scientific director of NHGRI. I want to give you a very brief history just to sort of set a context. We asked this council's main responsibility is to worry about the extramural side of the institute. But for now 25 years, the institute has had an intramural research program. It is under the stewardship, if you will, in terms of external oversight of something called a Board of Scientific Counselors, which is like all of you, fully certified, whatever you call your advisory roles and same kind of approval process, et cetera, et cetera. And so they worry about the day-to-day and the year-to-year aspects of it. But we do like and actually we're asked to make sure that advisory council has some familiarity with the extramural program. And so about every couple of years, we ask the scientific director, who's the director of the Division of Intramural Research to come and just give an update. And so it was time and maybe a few months too late, but we decided this was a good council to do this at. And so the other thing I would like to say is in the 25 years of the intramural program, there's been three scientific directors, roughly a third, a third, a third, not precise within a couple of years. Jeff Tratt was the founding scientific director and served until 2002. I then served before the current position I have as a scientific director. And then when I became director, it was one of the first things I did as director was of course launch a search to find my replacement because we needed to have somebody step into that role. And it's always, Dan likes to always talk about how on 10, 10, 10, October 10th of 2010 is when he started as a scientific director. He's come and presented a council at least a couple or a few times. I can't remember exact number, but it was time. And so we brought him here to just give you a broad-based overview, update what's going on the intramural program. And I'm sure I'll be happy to answer any questions you have so you hear about that side of the institute. So, Dan, I'll turn it over to you. All right. Well, thank you so much, Eric, for that kind introduction. And thank you all for having the patience to be here listening to what I have to say even after a fairly lengthy discussion. So in any case, as Eric pointed out, the intramural program of NHGRI is now 25 years old. Just to give you a little bit of background in terms of the intent in establishing an intramural program, the intramural program was founded by Francis Collins back in 1993 when he became the director of what was then the National Center for Human Genome Research and CHGR. And I think that it was one of his, in fact, conditions for coming here was that there would be an intramural program in NHGRI. And the vision that he had for the intramural program was somewhat different from the vision he had for the Hall Institute, which was basically to conduct the human genome project. And so his goals were, first of all, to capitalize on the unique resources of the intramural environment to establish a world-class program in genetics, genomics, and genomic medicine. So this was, from the get-go, oriented more towards the clinical kinds of things than in establishing the sequence of the whole human genome. The second thing was to catalyze the genomic transformation, if you will, of the intramural programs of the other NIH institutes. And I can tell you, having been here as a part of the Arthritis Institute, that was something for which there was a great deal of enthusiasm in the intramural program. And then over time, what's happened is that the intramural program has also become somewhat of an incubator for programs that could be exported to the broader genomics community. And in order to sort of jump-start things and get the intramural program up and running relatively quickly, deliberately the size of the intramural program, at least in terms of its budget, was larger than it is for the intramural programs of other institutes, where the average for other institutes would be on the range of 10% to 15%, whereas for NHGRI it's around 20%. So in any case, just to talk a little bit about the distinctive features of intramural NIH so that you can get a sense for what it was that Francis was hoping to capitalize on. And it's sort of apropos of the discussion that we've just had. The institutional commitment to researchers over projects. And so essentially the idea what has been for the intramural program of the NIH writ at large is that there is this commitment to individuals over projects. Second thing is that the review process is different from the review process for extramural investigators, in the sense that the review process is quadrennial and heavily retrospective. In NHGRI we have about a 50-50 ratio of prospective and retrospective review. But in a lot of the other institutes, in fact, it's more like 70-30 or 80-20 in terms of retrospective to prospective review. It also has the feature of more stable funding perhaps because of the fact that people aren't on R01 grants so that people can do longer-term studies that would be difficult to do elsewhere. And so for that reason there has been the preference for, and certainly we ask our intramural investigators to at least to some extent to embark upon high-risk, high-reward projects that would be difficult to do with R01 funding. And then finally there are certain specialized resources that we have in the intramural program that people can capitalize on in their research. Probably the one that is paramount among the specialized resources is this that is pictured here and that's the clinical center of the NIH. It's basically a 230-bed research hospital in which all of the patients are admitted on a protocol and where there is no cost either to the patient or to the investigator for being admitted to the hospital. So this is something that should be, anyway, a great incentive for people to do clinical research and in the context of NHGRI to really embark upon genomic medicine-type projects. So in any case, just a little bit about the NHGRI intramural program. Currently we have 22 tenured senior investigators and it's a fairly distinguished group. Five of them are in the National Academy of Medicine. Two of them in the National Academy of Sciences. We have currently three tenure-track investigators. So we're a little bit right now short in terms of tenure-track investigators. Part of that has been because we have had some budgetary issues over the last several years. We also have three senior scientists who are non-tenure-track investigators who are still very senior in terms of their standing in their respective fields. And then we have 13 associate investigators. These are individuals that are sort of like research faculty, either research laboratory faculty or research clinical faculty. And then nine adjunct investigators who have their primary appointment in other institutes. We also have a number of cores, which are very strong cores in the intramural program that makes it so that people don't necessarily have to have huge labs in order to conduct the work that they do. We have a sequencing center, which is really outstanding, it's sort of a medium-sized sequencing center that has really some of the latest technology in terms of both production sequencing and in terms of research level sequencing. Our total staff is about 540 individuals, at least right now. And our appropriated budget is around $114 million. And currently, the intramural program is spread amongst seven buildings on campus, plus we have off-campus facilities both in Rockville and in Baltimore. The intramural program is also distinctive in the sense that it is the home to at least some of the leadership of the NIH. And the NHGRI intramural program has been really a haven for a number of institute directors and NIH directors over the course of the last several years. And in the past, Harold Varmas, who was first the director of the NIH and then the director of the Cancer Institute, who was also housed in the NHGRI, and then Betsy Nabel, a past director of NHLBI. So in any case, going back to my own history in the institute, actually before I became a member of the institute, I was a tenure track investigator in the Arthritis Institute. And really, it was something that had a catalytic effect on my own career. The advent of the NHGRI intramural program at the NIH, in the sense that really it brought the tools of genetics and genomics to several of us in the intramural program who were doing various positional cloning projects at the time. So back in 1993, we had mapped the gene for familial Mediterranean fever, but at that point had not yet identified the gene. And so having really a group of people who had expertise in various areas of mapping and transcript identification and other parts of the effort of finding a disease gene actually was extremely important both to us and to other investigators in different institutes as well. And so that led in 1997 to our finding the gene and then sort of to flip it the other way around in terms of then utilizing some of the tools of the special tools of the intramural program of the NIH. We then established a clinic in which we have so far seen over 2,000 patients with various disorders that in some cases it's FMF, but in other cases it's other inflammatory conditions other than FMF. So this has really been something that has been catalytic for us. This is just a table from a review that one of my fellows wrote last year just itemizing the list of diseases that we now recognize starting from FMF as the beginning point and about half of them the genes were discovered here at the NIH and the other half have been identified elsewhere. So it really has been something that has had an impact across the scientific community. We've also used some of these tools to be able to discover new treatments for patients, in one case, a disease that we discovered back in the early 2000s, a disease called NOMID, neonatal onset multi-system inflammatory disease. Patients have recurrent fevers and have chronic aseptic meningitis which usually leads to severe intellectual disability in these patients over time. Once we had found that mutations in NLRP3, which is a gene that regulates IL-1, were important in this disease, we started a trial of Anna Kinra, the IL-1 receptor antagonist, in patients with this condition and 18 patients with this condition. It really is sort of a vindication of genomic medicine in terms of the fact that it is like flipping a light switch in terms of the clinical manifestations of these patients. And in fact, just a couple of weeks ago I saw one of the patients who was a part of this protocol, whereas the natural history, as I said, is usually severe intellectual disability. He had just finished his freshman year in college in biochemistry. Another example, a disease that we discovered back in 2014, or published back in 2014, actually a disease where patients were referred to us because they were thought to have NOMID, but actually they had strokes rather than aseptic meningitis. It turns out to be caused by mutations in adenosine, deaminase type 2, and these patients have strokes on the order of one every four years or something like that. And based on some of the findings that we had made with regard to the biology of this condition, we thought that perhaps treating them with inhibitors of tumor necrosis factor would be a reasonable thing to try. Before TNF inhibitors, in a group of 15 patients, there were 55 strokes over the course of 2,000 or so patient months. Since being on TNF inhibitors, these 15 patients, we've observed for about 600 patient months, and the number of strokes is zero. So in any case, again, is something where using the clinical center, one can have a big impact in terms of human disease. And then finally, a case that we're involved in more recently is a kid, 14-year-old boy from Bangalore, India, who was referred to us with recurrent fevers, with keratitis, with polyarthritis, and colitis. And it turns out that by exome analysis, he has a mutation in a gene that's involved in regulating ubiquitination. And it also turns out that there's a naturally occurring mouse knockout of that gene. Where if you cross it with a TNF knockout, essentially all of the clinical findings go away. So we brought this patient to the NIH, these are just some images. He was in a wheelchair at the time that he came to us a few months ago. So we put him on a TNF inhibitor, and here is a picture of him now, standing, as you can see. And I don't think that the audio on this particular clip works, but if it did you'd hear some music, and you would see that he is now dancing a few months after going on TNF inhibitors. So really this is something where using the clinical center has a huge impact in terms of both understanding the biology of human diseases and having an impact in terms of treatment. There are many, many other examples of this sort of thing going on in our intramural program. Here's Ellen Sudranski, one of our tenured senior investigators, who has been a student of Gaucher disease for a number of years. And she noticed that occasionally, in some of her patients with Gaucher disease, that Parkinsonism developed. And what's more, that Parkinson's disease was seen at least in a few of the relatives of people with Gaucher disease. And so actually she did a large study, which is summarized in this New England Journal article shown here, basically demonstrating that mutations in gluocerebrosidase, the cause of Gaucher disease, can also lead to Parkinson's disease. And in fact, this is now known as the most common genetic risk factor for Parkinson's disease and related disorders. What's more, Ellen has used NCATS, the Chemical Genomics Center, which is housed here on campus. And certainly it's another of the resources that people in the intramural program have at their disposal to develop a small molecule that actually can inhibit the biology of the genealogic process in Gaucher disease. And they're also now testing this in IPSCs, in dopaminergic neurons in Parkinson's disease. And so this is another example of using the Clinical Center to good end. Philip Shaw is one of our tenure track investigators in the Social and Behavioral Research Branch, who's a child psychiatrist and an expert on ADHD. And so he's used the Clinical Center to basically scan a cohort of kids with ADHD in the same scanner, the same MRI scanner, for the last 14 years, a real feat just to get a couple hundred kids with ADHD to stay still in a scanner every year for 14 years in a row. But basically Philip has identified now rather than just using clinical phenotype as the hallmark of ADHD has actually found that there are differences in the way the brain is wired that are heritable that one can look at in ADHD.  Another of the people who have really capitalized on the Clinical Center is Lass, Beesekker, who has been a student of Proteus Syndrome and other overgrowth syndromes for many years and through those studies, through the careful study of patients with those diseases, eventually made the paradigm shifting discovery that in fact patients with Proteus Syndrome have somatic mutations in the tissue, a non-malignant disease with somatic mutations. Lass has of course done a number of other things of great note, such as his leadership in the return of secondary findings in research protocols. And of late, he has developed a project with Richard Siegel in my old institute, the Arthritis Institute, the Genome Assertainment cohort in which there are a bunch of patients, about 1,000 patients who have undergone genomic sequencing, where essentially investigators in the intramural program can query those individuals, the sequences of those individuals, for mutations in their gene of interest and the patients are consented for callback, so that then deep phenotyping of those patients can be done. Bill Gaul, I think you're very familiar with Bill's work and the impact that it has had broadly. The Undiagnosed Diseases Program just turned 10 actually about a week ago and has had a number of milestones and of course it has been a case where the intramural program has been approving ground, if you will, for something that then has been exported to the extramural community and of course starting at the NIH, the UDP, whoops, but now of course we have a number of centers as part of the Undiagnosed Diseases Network. Similarly, the National Chemical Genomics Center was a part of the NHGRI intramural program up until the first year that I was the scientific director. It's now a part of NCATS and is something that is broadly available for investigators in the extramural world. Larry Brody, another of our intramural investigators, has been the leader of CIDR, the Center for Inherited Disease Research, which has certainly had a huge impact in terms of both sequencing and genotyping more broadly. Charles Rotimi, the head of our Center for Research in Genomics and Global Health, has certainly had a big impact in terms of health disparities research and the study of African ancestry populations in genomics. And Max Munka, another of our investigators, has now in the same vein started a training program in which individuals from all over the world come for a month-long training program in genomics and genetics. The social and behavioral research branch has been sort of a pioneer in the sense that it is the first branch in the intramural program for social and behavioral research in any of the institutes of the NIH. Julie Segre, I think you heard in Eric's summary this morning that Julie has a paper that's just come out with regard to detecting various flora in the plumbing of the clinical center hospital, and really that's something that is very difficult to do in a hospital, particularly in a hospital that may be concerned about lawsuits and that sort of thing. And so certainly the clinical center has taken the lead in terms of those kinds of studies. Jim Mulliken, the head of our sequencing center, has been a pioneer not only in running the sequencing center but in various collaborative studies with the Vaccine Research Center and the Anti-HIV antibodies. Adam Philippi, another of our tenure track investigators, has taken the lead with regard to developing new algorithms for assembling sequence from long-read single molecule sequencers and has had a big impact in that regard. Sean Burgess, one of our zebrafish aficionados, has developed a line, an HDRI-1, of zebrafish for CRISPR-Cas9 modification so that there's a standardized zebrafish line for doing this and has developed a tool that one can search on the web basically for designing guide RNAs for developing CRISPR-Cas modification of the zebrafish genome. And then I'm almost done with the litany here, but Elaine Ostrander certainly has taken the lead in terms of canine genomics and Dave Bodine has generated a resource for people who are interested in the epigenetics of erythroid development in the mouse. So in any case, there's a lot of examples. These are just a few and certainly the faculty of the NHGRI has been very, very engaged in terms of developing tools for the broader community and in the process doing things that advance their own careers as well. Just in the last couple of years summarizing at least some of the papers that have come out from the intramural program, you can see that really there's a long list of papers published in very prominent journals and certainly there's a number of others besides the ones that are listed here. In terms of the review of the intramural program, Eric talked about the Board of Scientific Counselors and I'll mention that in a little bit too, but we also have a decennial in every 10-year review of the intramural program by a blue ribbon panel. And we had our last blue ribbon panel review back in 2011 and 2012. It was chaired by David Page and other members were Wiley Burke, Nancy Cox, Bruce Korf, Rick Myers, Bob Waterston, and Huda Zogby. And they both site-visited the intramural program but also reviewed a lot of written materials as well and had very positive things to say about the intramural program with regard to its scientific productivity, mentoring and training programs, dissemination of genomic technologies across the intramural research program, internationally recognized research faculty, robust research infrastructure, and collaboration and collegiality. What they did recommend was, number one, to continue to adhere to the model of investigator-initiated research, again coming back to that theme from the previous discussion, allocate resources based on rigorous reviews by the Board of Scientific Counselors, embrace a risk-taking culture, insist on excellence, and continue to be a change agent on the NIH campus and beyond. And in terms of the day-to-day evaluation of things, the Board of Scientific Counselors currently is made up of nine extramural experts, Brandon Lee is the chair, and you can see the other people who are currently serving on the Board. It's a rotating service. And each investigator is reviewed every four years. It's a quadrennial review process. What I ask the Board, the site visitors to do, is to address these questions with regard to investigators. Does the work fundamentally change the way that we think about or understand relevant areas of biomedical science? Through the development of new methods, does it change the way that we do science? For clinical research, does it change the way that we practice medicine? Certainly the deletion test, whether clinical or basic, how would the field look if the intramural investigator had not been active for the last five years? And then finally, is the research worth studying with the special resources of the intramural program? To date, we've been using a relative rating system for the last several years. And to date, we have 60 evaluations that have been done. Some people have been evaluated more than once with this system. And 63% of the investigators have received the highest rating of outstanding. In terms of planning for the next century, the next quarter century anyway, but maybe the next century too, we certainly want to maintain a strong commitment to the things that I've already mentioned, risk-taking, scientific excellence, and leading genomics in the NIH, a merit-based resource allocation, strategic tenure track faculty recruitment. Because of the fact that we don't have a top-down system in which I or anyone else tells investigators what they should be doing for their research, if we want to shape the intramural program, then we do it basically through our recruitment. And so if we want to have a more bioinformatic-oriented or basic science-oriented that-have-you faculty, then we do that through the process of recruitment. Certainly, succession planning is something that we do have to think about. About a third of our investigators are now at the point where they could retire sometime in the next five years, and so we do have to think about those issues. And then engagement in an institute-wide strategic planning process, which Eric has already, I know, talked about a lot, and a new round of Blue Ribbon Panel Review, which will be upcoming probably in 2020 or so, that we would start that process as well. So anyway, that's the overview. I guess I did go exactly half an hour. So in any case, I'd be happy to answer any questions that you have if you do. Yeah, Trey. Thanks for the really informative update. With regard to the extra budget bolus that was sent the NHGRI's way this year, I think Terry might have said a few words about intramural extramural this morning, but could you comment, did you guys benefit from a few extra dollars this year and how did you-or how do you plan to use them? Yeah, that's a good question. So as-I mean, we can break it down into, you know, sort of the overall gains for the NIH for NHGRI and for the intramural program. So NIH, as you may know, got an 8.8% increase in its budget. Some of that money was earmarked for particular projects like the Cancer Moonshot, et cetera, et cetera, so that NHGRI, I think, got about a 5% overall increase. Eric and I have talked about the idea that probably the intramural program being at 20% but that's higher than what it would be nice for us to be. But if you do the thought experiment in terms of how you would fix that, so if the institute were to get a 5% increase this year, which it did, and the intramural program didn't get any increase at all, then we would go from 20% to 19%. And if we wanted to get down to 10%, you know, which is, you know, sort of the goal in a lot of institutes, so it would take us 10 years of the intramural program not growing at all, and the extra-and the rest of the institute growing at 5% a year in order to redress that. So basically, that would be very hard to do. Eric and I talked about the idea of building a 3% increase into the base of the intramural program so that the intramural program would grow by $3 million and actually this year, but it's not something that's a long-standing commitment, we did get an extra $2 million as well so that we actually have grown by 5% this year the same as the average for the institute. But the commitment would only be 3% for out years. In terms of what have we done with it, well, you know, there has been a lot of scrimping on things because of the fact that we went through a period of time where there was sequestration and then a flat budget. And so actually there's a number of pieces of equipment, capital equipment that have sort of gotten old and needed to be replaced and so we've spent a fair amount of money on that. We are recruiting a new investigator and actually we're sort of close to having a deal with him and we're excited about the possibility of recruiting other tenure-track investigators in the next two or three years. Certainly, you know, we have to have some balance, you know, with regard to, on the one hand, because genomics is a technologically-driven field, we have to stay up-to-date in terms of technology, but on the other hand, we certainly do need to have smart young people with energy and ideas as well, especially as the faculty grades. Okay, sorry. Other questions for Dan? Steve, go ahead. I was just curious, how did you, when you were talking about the ending deaminase? Adenosine deaminase? Yeah. Yeah, and then you jumped to that, to anti-TNA. Yeah, how did we make that connection? Well, you know, it's a very good question and certainly it's not something that's sort of an obvious this-than-that kind of conclusion. So it was really sort of a fortuitous thing. The patients came to us, a lot of them having already been treated with a lot of different things, high doses of steroids, cytoxin, IL-1 inhibitors, et cetera, and had not responded to them. It just happened on skin biopsies that several of the patients had perivascular TNF, and so we thought, well, maybe TNF inhibition would be a worthwhile thing to do. And as I mentioned, these kids have strokes every four years or something like that. And there are patients. They do come, they see us, we continue to follow them. And so it's sort of like sitting under the sort of Damocles or whatever to be taken care of these kids. And so it was just a try, and it turned out that it was fairly successful. But there's no real connection to the mutations of ADA? Not that we know of, at least as of yet. Well, Dan, thank you for coming and giving the presentation to the council. We're grateful for your time. So we have more of the open session, but I think we need a break. Run upstairs and get your caffeine boost and probably be back at 340, please. We'll resume then.


Thank you Rochelle go ahead. Let me so yeah, this is why when I did that broadcast about The kind of women high-value men avoid Hello Yes, I'm here. Hi Rochelle. How are you? I'm fine. How are you good? What do you got for me? Okay, so this is actually my first time listening to your show or watching your show And I actually was having this conversation Tonight with a friend of mine who sent me the link and everything so I'm 38 And so I know you've had a lot of younger women on but I'm 38 I am single. I have no children So I know you were talking about when women get to that 40 plus Rains, you know it starts to go downhill. Luckily. I'm so fertile Because when you get my age you start to see a fertility doctor and make sure you're good But I guess my question to you would be For women that are over the age of 35 or like myself approaching, you know, 40 in two years It is very difficult out here to find Men that are that are really ready to to settle down and take things seriously I've met plenty of guys that are really great, but then they have these insecurity issues or They're just there's just Showing it up showing it up showing it up showing up you're 38 and you're ready to get married and you're good But the problem is you can't seem to find a man that's ready to marry you I don't say necessarily ready to marry me, but ready to at least Do you want to be married do you want to be married? I Do how long should it take you to how long should it take a man to marry woman? How long how how long should it take a man before he knows he wants to marry one? I think that most men probably know within six months to a year. So again, so you want to be married So you want to be on that path cuz you're 38. What's it anyway? I'm in Chicago. All right, so When I talk about no man's land Danger zone also the thing I say it not to be Pejorative it's just a focus I Just because you're over 35 doesn't mean it's over. I mean, I know women that are that age I'm actually gone out with women that age But it's different It's different in the sense that what's the longest relationship you've ever had My longest relationship was five years How long ago was that hi Jessica? Hi Monika. See you in there five years. How long ago was that? That was in 2017 2017 five years to ended in 2017. Yes So you've a 2012 2017. Were you guys in the same city? Yes Why didn't you guys get married? He he was a serial cheater. I mean And you're one of your five in year Three So, why'd you stay? I think that I curious. No, I understand I think that I had to do a lot of self-reflection in order to understand that after the relationship and it was a lot of That's okay. I mean I've got four more people. I need to kind of get through this And that's fine, you know, you don't spy I mean three years People need to go through the process, you know, just get rid of somebody. I get it. Um, how tall are you? I'm five five dress size What's my my dress size, huh? Did you say my dress size? Yes I'm a size six or eight So I six right and how much did you weigh the last time you were just up? I Way myself every day. So I was 148 this morning. Cool The last question if you had to give yourself a rating just your face Fresh face right out of the shower your natural hair What would you give yourself on a scale from one to ten and you cannot use seven? Oh, I'm not gonna use seven I would give myself at least 8.95 Okay So around here we now Beyonce is roughly an eight Kelly Rollins roughly at nine But you're on the Kelly rolling into things. Yes, I am All right In the last three years, how many men have you had us seriously wanting to date you? What is this 2020 well, I had just gone out of that relationship in 2017 so I've been on Right, but when you go through something like that, you got to take some time now you don't No, you do if you've been in abusive relationships. You do have to take This is not okay. Hold on now Recognize what you're at That's you know, I am I'm just I just okay. Let me explain something. Okay. I'm nice to you If you're nice to me, I have no particular dog in the fight, but you can't talk over the host All right, so in the last three years Um, even after your detox from your relationship, what's the longest time you've dated anyone since their breakup? Uh, three months three months. Um, had you guys gotten intimate? Yes, we had who ended it who ended it Um, he did uh, do you happen to know why? Um, yes, um, he was going through some personal issues that required Therapy so he said I don't I mean, I call bullish. I don't know if people curse on your show, but I call bs Um on that to me.  You don't need to lie to you about it Oh, no, he doesn't have to lie to me about it.  All right, and what were you diagnosed? What what what did your therapists or counselors say? Anxiety and depression. Yep Yeah, yeah, yeah, yeah, so is an issue really that men aren't necessarily ready for what you're um I don't think that that's necessarily that men are not necessarily ready. I mean, I think that I am taking that this time now to process and heal the the wounds that I have so that I'm also ready, but I've just noticed that um I don't I don't know if I necessarily agree that you just have to stop cold turkey with meeting people and and in dating While you're going I never said you had to stop cold turkey, man, but your relationship was over in 2017 right all right, um And if you're going into relationships, are you going into them just casually just saying hey, I'm still in process So I just want to keep this, you know very light Because I'm not looking to get married because I'm still got some things going on with me No, I don't I don't get that personal, you know when I'm first meeting somebody Then I don't understand Um, what is it? What's the outcome that you want to achieve? You want to get married and you've been in therapy for how long? I'm just a month not long. Okay. Um, I have to ask If what you were saying happened is so traumatic Why did it take you three years before you two two plus years before you started counseling? Um, I have a a very public-facing career. So and I have moved um quite a bit In in those three years. I've lived in three different cities. So, um So, I mean that was also part of it But now I'm having time to kind of reflect and then my father died Um in september. So all of that compounded is So in three so in three years Okay, I'm going on what you said that it was a traumatic relationship Um and having a public career public-facing career Uh celebrity stars people get counseling all the time. It would have been wiser to do it Back then so we wouldn't just be because you're only you're only a month into it now You're not ready Okay, and I'm and I'm telling you in the interaction I'm having with you You're you're editing yourself right now, but I can feel that I can feel What you're doing Um Look, I'm good at what I do. I don't have thousands of people watching me because I don't but what I'm telling you Even if you're as attractive as you say you are Um, you're you will be difficult to date Why? Because you're still broken Mm-hmm You want to go back and forth and me over some things and I'm like man five years And if it hurt that much that means between 2017 and last month the guys that you've interacted with were getting pieces So the problem isn't finding men who are Ready to do whatever even if you met a perfect man. You're not whole enough to be a wife Which is what I talk about often on this show professional attractive successful women whose relationship skills are completely unfit for the things they say they want And it's because We have such a stigma in the black community about therapy Um, so where the last people to go seek it then when we do go seek it We don't want it to take as long as it does Um, and then the sad part is we start diagnosing everybody else When you're novice in therapy um If you know you ultimately want to get married the best thing to do is Um, when's the last time you saw your ex? Um, he came from my father's funeral so in september. I see in the same city. No, okay. Um And when you date now, um Well, I have to ask how do you get your itch scratched? Do you have an itch scratcher? Uh, yeah, okay. I'm okay with that. Does he know you're in it? Does he know he's an itch scratcher?  No, I'm sorry. Honestly.  I'm not intimate with anybody. It was the last time you were intimate with someone Uh last month What is this never? But yeah last month Okay, but all right, and that was okay. So You don't have a friend with benefit that who you can have sex with On a consistent I mean I I do but it's they're just not in chicago, but I do Okay, uh, it sounds very chaotic, ma'am It's not it's not chaotic Uh, I okay Now you're I think you're absolutely right when you talk about, you know Being a whole woman and having broken pieces and things to fix which is why I'm seeking the help But my life is not chaotic. I'm saying that uh, uh, and say you okay um She's whatever word you fits. It just doesn't sound very simple. Um If you have someone and that you have there's a friend that benefits somebody that's have sex with but they're not in town They're not in same city. I don't need it like that. You know what I'm saying? Like it's not that serious to me So that's why that I don't think that that's a complicated part of my life because it's not that necessary So sex is so okay So then why do you have a why do you have a battery operated buddy if it's not that necessary? I mean the physical touch of a man is not that necessary for me to have a file to la and thank you right there. Thank you Thank you The physical touch of a man is not that necessary because you have a better operator buddy and see that's the brokenness Which is the chaotic part What I'm saying is is that I just because you just because okay? All right, um, this is this could possibly get very messy at the end of the day man at 38 years old the issue is not me The issue is not men The issue is not men Especially men in chicago In international city, there are plenty of marriageable men that are damn sure earning Well, who are marriage minded? No, I gotta Excuse me. I said there there certainly are. I mean I literally just moved here on saturday, right? So But I will tell you Without a shadow of a doubt um, the you know, if you're What kind of what kind of income do you want your potential husband to make? um You know, honestly, I've never been That much of a stickler when it comes to that. Give me a ballpark. Um, this ballpark. I would say I would say maybe 200 $200,000. Do you do you care if he has kids or not?  I mean as long as he's Maybe five nine and up How tall are you? five five five five um All right, um, what percentage of men in this country earn over 200,000 dollars? Oh, Steve, um, well if we're talking black men, um, nope just men period just men um Maybe six percent, right? So and men who are making that kind of money six percent roughly um They for the most part are the cream of the crop of financial earners. They have their pick of the letter So I ask the question I ask you I ask the question of you that I asked all women Why would a man who's earning 200,000 dollars plus who can have any woman want you? Well, I think that I would be coming in with also my own, you know six figure salary and give a shit about your money I know they don't but I'm just saying I would be coming in with my own So it's not like I'm coming to them with my money, but I know that I have A really we don't care about your money or your careers or anything like I'm just being honest, man I get it you have it, but it doesn't let me tell you why let me tell you ladies why this doesn't matter Because you're not gonna we don't have access to it anyway, and you're gonna be spending it on us So your money didn't say that um Okay, do women in general Who who who in general funds the relationship? I would say men in general right the relationship, but why would a woman not want to do for her man too? um, well This is gonna be another problem, man um, what is your Your vertical your career path, you know, I'm telling you the exact title Um, I work in higher education all right um Women typically don't spend money on men period point blank end of sentence Uh, I do very well for myself and it's not a surprise. We laugh about how In how you can buy a Birkin bag over here, but they think they bought you a video game. It's something Mm-hmm.  That's not a birthday Christmas or anniversary type.  That's what I mean I say that man because when I say stuff you ladies want to push back and like well, I make it It don't matter if we don't have access. I wasn't pushing back. I didn't even I say ladies in general We don't have access. We don't have access to your money We don't have access to your money and we're not going to be able to spend it and that's fine So what else do you bring? What else? He said, why would he want you and you were going outside of your money and your accomplishments? What else do you bring to the table? Um I bring I think that for me I think that I'm a very very supportive woman when it comes to I know in my past relationships when it comes to their Dreams and their goals. I know that I am able to speak life into them. Um, I'm extremely submissive in a sense. I actually sometimes when you're in These senior roles as a woman and your life is dominant figure all day long It's nice to come home and be able to just be Submissive. It's being submissive helps me to relax honestly in relationships Um, your five-year relationship. Did you live with him? Yes, I did um And he out-earned you No, I out-earned him Is that again? No, I out-earned him. Okay. Um Substantially, um, yes Did he go to college? Did he or did I did he? Um, no And where'd you graduate from? Johns Hopkins You need to book five sessions I'm gonna leave it right here, man because you you Go my website is by kevin samuels.com. I don't want to do this right here In incredible


Hello everybody! This video is about resetting a regular password or graphical password in Android. If you've forgotten the password or graphical password for Android, it's too early to give way to panic. You can restore access to your smartphone in a quick and easy way. There are several ways to unlock the device, so here we go. Hello friends! If you need to recover deleted data, view or restore removed browser in history. Hetman software products will help you. Follow the link in the description. Download the necessary program for free. Reinstall it and analyze the disk. The utility will show you the data you can recover, so you will be able to view it or get it back. In our channel and blog you will find solutions to any problem, from installing an operating system or configuring it to fixing possible bugs and errors or optimizing mobile gadgets. Our specialists will answer any questions you ask in your comments under the videos or articles. The first, the easiest and probably the most correct way to reset the regular password or graphical password in Android is to enter the data of the Google account with which your smartphone or tablet PC is synchronized. To unlock the device, just specify the email and password. To try this method, enter an incorrect graphical password five or more times until the device shows you a warning that it will be locked for 60 seconds. A button appears asking you if you forgot the graphical password and when you choose it, you can enter your data and unlock the device. Please note that this method requires internet access, mobile connection or Wi-Fi. If you've forgotten the password to the Google account, follow the link in the description to see how to learn it or hack it using one of the ways described in detail in our video. The second method is for advanced users, as it suggests connecting your device to a computer and using Command Prompt and ADP tool. ADP is a part of Android SDK. That's why for installing ADP to your computer you have to download SDK from the official website. To do it, go to the website developer.android.com. I'll leave the link to that page in the description. Download Android Studio by clicking on the corresponding button and install it. Android SDK, which includes ADP, is a part of Android Studio. Earlier, you could install it as a standalone application, but now it's impossible. After installing this tool, run it and wait until it downloads and installs missing components to your computer. It will take some time. Now go to the following folder. See Users, username, app data. This folder is hidden by default. Local, Android, SDK, Platform Tools. The file ADP.exe is the ADP tool you are looking for. Connect your smartphone or tablet to the computer. Don't forget, your device should have USB debugging enabled. So when Android smartphones or tablets are connected to a computer, this option can be enabled. Watch the command prompt as administrator and use it to go to the folder containing the file ADP.exe. Type the command ADP devices. As a result, you will see your Android device with the status device or authorized. If the status is unauthorized, USB debugging is not enabled for your device yet. In that case, disconnect it from the computer and then connect again. If you are asked to enable USB debugging, confirm a choice. If there is no such question asked, it means USB debugging is not enabled on this device and you can't reset the regular graphical password with ADP, so you may go on to the next method. After you receive confirmation that USB debugging function is active, type the following commands in the command prompt one by one. I will leave them in the description below this video, as usual. After the command reboot, your smartphone or tablet PC will restart and boot again with its password or graphical password reset. That's all. The password is reset, while all data and installed apps are adjust in place. The third method is to reset the locked device to factory settings or, in other words, to make a hard reset. To do it, switch off your smartphone or tablet PC. After that, hold down a certain key combination. It differs depending on the device model. In the recovery menu, select wipe data, factory reset. In our channel, you can find a very detailed video about how to reset a device. Follow the link in the description, as usual. Remember, though, that using this method you will lose all data from the internal memory of your Android device, including installed apps, connected accounts, SMS and so on. Only photos, audio files and other files in the memory card will be left intact. Now let's move to method 4, with the Google tool Find My Device. It's the same good old hard reset, but made from the Google account your device is connected to and without pressing any key combinations. To do it, go to the page of Find My Device by Google. Find the link below this video. Log into your Google account If you've forgotten the password to the Google account and you can't access the Find My Device tool, follow the link in the description to see how to learn it or hack it using one of the ways described in detail in our video. You will see all devices connected to this account. Select the one you need. If there are more than one device, choose Erase and Erase again. When the device is connected to the Internet for the first time, if it's not connected now, it will be factory reset. The password or graphical password will be reset too, and access to the device is now restored. Please remember that all data from the device will be erased. If you're a Samsung user, Method 5 is there for you. Owners of Samsung devices can unlock them if they have an active Internet connection and added a Samsung account. Samsung features its own service with the name Find My Mobile. I'll leave the link in the description. To use it, you should connect your device to a Samsung account and enable the Remote Control function. So to reset your Samsung device, go to the web page of Find My Mobile by Samsung and sign in. Use the login and password you have given when you signed up. By the way, you can also restore them if you forgot them, or hack them in the same way as you can do it with a Google account. The panel on the right will show you the status of the connecting device. Select Unlock. Unlock again. Enter the account password again. After synchronization or when connected to the Internet for the first time, the regular password or the graphical password will be reset, and all data will be safe. Of course, these are not all possible ways of resetting a regular password or graphical password on Android devices, however, they may be the easiest and simplest for anyone to try. There are other ways as well, like reflection for wear, deleting password files, gesture.key or password.key, using TWRP recovery and so on. However, each of them should be a topic for a special video. That is all for now. Hit the Like button and subscribe to our channel. Leave comments to ask questions. Thank you for watching and good luck.


Is there somebody you know who you find is always helpful to you? You enjoy who they are Well, if that person were to ask for your help on something wouldn't you readily come to their aid if they Were seeking to build their business and they had they they needed more clients Would you look around to see if you know somebody who could use their services? probably yes because that person has Connected with you in heart You enjoy who they are they enjoy who you are they've been helpful to you and of course you want to find opportunities to be helpful to them as well So this this this is seems to be This is kind of this kind of heart connection and these friendships seems you know, it's it's becoming more and more rare, unfortunately I think especially in the age of only being people You know connecting with each other online, etc. But why can't we take that same kind of friendship? Online as well Okay, and that's kind of the message I have for you today I want to encourage you to do is to think about building your network of kindred spirits Even if you don't live next to each other and you can't see them a lot But if you can connect in this, you know using social media and create a network of kindred spirits Then when you need business when you need some help You'll be able to reach out and the reciprocity is natural so of Right now if you look at your social media your Facebook friends your LinkedIn contacts the people who follow you on wherever other social media you use Instagram You know, maybe use Twitter or Pinterest or whatever There are already There's probably hundreds of people by the way, right in your social media network and Out of those hundreds of people there are probably at least a few people Who you would love to be in that kind of friendship with? Where you know, you enjoy their company. I mean at least online you can you enjoy the kinds of things they kind of They they share online they seem to be open to you and and seem to enjoy who you are as well and You are relevant to each other professionally in some way like that, you know, they might be a referral source for you They might be a potential client. They might Know others who are potential clients or referral sources and similar to you like you might be a potential client of theirs Or might know others who could be potential clients. So you're relevant You're related professionally not that you're competitors or whatever, but that you you could help each other professionally as well besides enjoying each other's personal Characteristics, right? So there are probably at least a few people in your in your existing social media network who are like that Now the question is are you keeping in touch with them regularly? When it comes to social media, it's easy to get distracted and just Be paying attention to whatever Facebook serves us, right? Well Facebook is doing their best with their algorithm, right to try to Show you postings of the people that they think you you like and like you back, right? But it's not always it's often not accurate I find so So my encouragement to you today is to have a thoughtful mindful look at your Facebook list of friends When was the last time you did that you go to your Facebook profile? You click on friends and you start looking down the list of friends or again linked in contact same thing When was the last time you look at your LinkedIn connections, right? Probably not for a while. So have a mindful look at your list of Facebook friends your LinkedIn contacts Even the people you email with like look go to your email inbox and click on the sent folder You know the people you sent emails to Right look at these places and online groups you're in offline groups You're in but look at the places where you connect with your network and ask yourself to start writing down the names of the people that you just Feel personally Connected with or you wish you were personally connected with you like who they are they seem open to who you are and they might Like who you are and you're connected professionally.  Okay, write these names down All right, and then make a plan to keep in touch with these people Not because you need something from them But because you care about them and this is the radical idea. This is why networking Doesn't work for most of us who are heart-based entrepreneurs is that networking most of the time is really really fake Right you hear from somebody that you haven't heard from in a long time and you get the sense that they want something from you It's awkward and it's forced. It's fake and nobody likes it Not the person reaching out. They don't like it and you don't like it either, right? But when you have a real friendship and I'm when I say friendship I don't mean that you know, you're you're talking every weekend or whatever I'm just saying that you you do keep up with each other every now and then you do try to help each other as much as possible Then when you need help when you need referrals when you need ideas for your business It gets it becomes natural to reach out to that person. I hope it is if it's not natural Maybe you're a helper and you just help everybody and you never ask for help and that's that's something that is A practice that you need to develop is reaching out to the people who whom you've been helping And let them know that you need that help not that you're expecting that they must help you because you've helped them But at least give them the opportunity to help you because friends like helping friends and I think if some people who are always helpful to me I would love the opportunity to help them. Of course I would You know So same thing. There are some people who would love the opportunity to help you, but you're not reaching out for help So how can they help you right? So that's it's very simple So look at the places look at your Facebook friends list LinkedIn contacts, etc the list of people that are in your network who Has do you feel mutual connection with and is relevant to to you professionally and you to them and Are you I have you made a plan to keep in touch with them regularly? So Simple plan right I use something I called social media caring up with the link in the comments later of how I do it But basically on Facebook you can use a friend list You can create what's called friend lists a list of clients a list of whatever it's called friend lists They don't know they're part of the list, but you can then look at your newsfeed only with the postings from those people You could select which you know which newsfeed you want Oh, I only want the newsfeed from these five people then you're only seeing the postings from them So that's a very simple plan where you're surfing Facebook anyway You might as well look at your friend lists postings their postings instead of just random postings from what Facebook wants to serve you The other thing of course is you know once a month you look at this list of people and Say whom have I not whom haven't I reached out to you recently just to see how they're doing Maybe you go to their Facebook profile you go to wherever they're active on social media see what they're up to just say hello and say Hey, I really liked it when you post about that If there's anything, you know, what what what are you up to and you know share what you're up to So just kind of keeping in touch. You don't have to keep in touch once a month But even if you do that Thoughtfully once every three months you're doing a better job of keeping in touch with that person than most people in their network I promise you right so that's all if we if we all Were mindful about who those kindred spirits are in our network and we kept in touch with each other on a thoughtful Basis and a truly caring basis not because of networking, but because we truly care Then everybody would have enough connections. I believe and everybody would have enough business, right? So that's that's all that's all I want to say I Encourage you to go take these steps and any comments or questions. Let me know below. Take care


200 years ago, it was pretty late that they got around to discovering EEG. It was discovered during, it wasn't recorded from a patient, just sitting in the patient, it was first discovered during a neurosurgery procedure. And it wasn't published until years and years later, which was 1929 by a guy named Hans Berger. And it got over to the United States within two or three years and they noticed pretty quickly that if you flashed a light at a patient and while they're recording their EEG, you could actually see the signal in the EEG from occipital scalp. So visually evoked potentials came out of EEG and similar to an ERG, retinitis pigmentosa was the disease that the ERGs were first applied to. Visually evoked potentials were first applied in neurology to verify optic neuritis and multiple sclerosis. Like ERGs, equipment to do it was not available commercially that you could buy until the early 60s for visually evoked potentials. I used one of the first, in the beginning, you had to have an EEG machine. So you had the write out from the EEG and then after that, so they used the EEG amplifiers. After that it went to an averaging machine to produce the visually evoked potentials. There was no programming it. There was no keyboard. There was nothing. It only did one thing and it had three buttons. Start, stop and print was all it was all I could do. So this is the south view of a northbound human and the sites indicated are the international 1020 system that's used in neurology based on measurements of the head, the nasium to the inion and the ears over the top of the head. All the placements are 10 and 20% measurements of that. So it's called the 1020 international electron system. You can get a visually evoked potential from anywhere on the back of the head. When I'm talking to patients, I'll put my hand on the back of the head and tell them, this is all visual and the middle's the middle. So the middle is the calcare and fissure, which is indicated by the OZ location, which is a 10% measurement of the back of the head from the inion that's the bump right here. So it's about three centimeters plus in an adult and a couple of centimeters in an infant. I don't measure the heads. I know about three centimeters. But EEG labs measure the head. The machines all come with measuring tapes. The most common electroplacements used are either the middle or 0102 or all three. Some labs think that they can lateralize pathology by recording from both hemispheres. Not, but they still do it, the majority of them. There is so much variation in the human occipital pole. And once you get off the surface, the poles start to reverse sometimes. You'll get false lateralization. So it looks like the left electrode is picking up pathology, but its origin is really the right side. But still there are labs that put an array all across the back of the head. Imaging, which tells you the lateralization, not that. So I routinely only record from OZ, the middle location. Inion, this is an example, I want to show you. This was recorded here by Jeffrey Anderson using a special functional MRI setup where he stimulated similar to the way we do clinically with a pattern that reversed at about three per second and looked at what are the hottest areas in a functional MRI with red being the hottest. Look how it jumps around, the hottest area jumps around depending on the slice level where it's only on one side at one slice, asymmetric most slices, deep below the cortical surface, other locations. So you can't depend on what you're getting from the surface. That's the downside of visual evo-potentials. The upside is anything that messes with the pathways after it exits the eye, to and including the cortex will affect it. And usually there's no confusion over what you're looking for. You know the child has meningitis. You know there's been trauma to the occipital pole. You know there's a pituitary tumor. And so it's not confusing. The visual evo-potential will quantify the delivery of flasher pattern information to the visual cortex. This is another one too complicated. This is a multifocal visual evo-potential showing how if you do use several electrodes on the back of the head, how you can get evo-potentials from an area of scanning. As I mentioned at the beginning, in fact most evo-potentials are extracted from EEG, whether it be auditory or visual or somatosensory. Have you ever seen cases where they do spinal cord monitoring like during rotations?  Well they nowadays monitor somatosensory evo-potentials through most spinal surgeries. If you present a signal, whether it be a flash of light or a clicker in the ear or a peripheral stimulus to the median or tibial nerve, if you present any signal and then grab with a computer a set time period and grab a similar time period and you add them together over a period of not many presentations you get and evo-potentials because the background average is to near zero because it's random. The software, the computer program to do this was the second application of computers during World War II over 70 years ago. It was used to extract radar signals from jamming. So the random EEG is the jamming, the pattern, the person of views or the flash of light is the signal. I've lived through all of these, this is the generation of these. They visually evo-potentials started out using the grass, the most common is the grass brand in the United States of Strobe that they use for photic driving to try to induce seizures in EEG recording. So in the beginning this grass lamp was used, in fact, yes, here's the grass lamp and they haven't changed much for the last 60 years. In the beginning, this was used for the stimulus starting in neurology and then in early evo-potential recordings when they first got, you could buy a computer in the early 1960s and then started adding patterns to that flash, pattern reversal I'll talk about, pattern onset I'll talk about. So after the pattern flash they started putting patterns on top of the strobe, the same diameter as the strobe and then in the 1970s a neurologist at Queen Square in London, the National Institute for Neurology and Stroke in Great Britain came up with, I've met him, I've been to his lab, I've been back in the 70s and saw how he did it which was interesting. He took two Kodak projectors and put camera shutters in front of them and he had one slide that looked like this and then one slide that looked like this and by changing the camera shutters he induced this pattern reversal like I'm imitating here and he lined them up and back projected them onto a translucent plastic screen and that was the first application of pattern reversal which is now the worldwide standard. Why is it a standard? It has the less variability for the potential, the look of the potential it produces between individuals whereas a flash has a lot of variation between individuals. The normal pattern reversal visually of a potential, if I tested all of you they would all look like this unless you have some unknown pathology. You have a negative wave around 70-75 milliseconds, a big positive around 100 milliseconds and then a following negative around 145-150. This is about the maturation, you have a pretty good visually of a potential within six months in an infant even a pattern one and it improves up to about school age and by about age six or seven it doesn't change much until after 55 or 60. It's a very stable response. When the child is first born instead of it being a peak of around 100 which is the fourth dotted line the response will be out here and if you tested a child every six months or so until they got into school you would see this peak just march in like this so that by the time they were about seven it would be around 100 and stay there for the next 50 years or so. This shows the variation of take age seven that's about, there's about 20 people in each of these average age groups and look at the mean, there's not a significant statistical change until after 55. Like up to seven years old it varies a lot and after 60 when aging kicks in you get a lot of variance of a scattergram of that. So once you get into mid teens things tighten up pretty well until you get past 55 up to 60. So this is variation in aging and prior to that is variation in maturation, this is between a child that rides a bicycle at four or five versus one that can't ride a bicycle till they're seven or eight, a child that walks at eight months versus a child that walks at 14 months. So you get the greatest variation in the first five, six years and then again even a greater variation in aging after 60 or so. The pattern onset offset is gray screen, pattern pops out, goes back to gray screen. Any patient that has nystagmus for any reason at all the pattern reversal exacerbates their nystagmus. So you can't use it, you'll get no visual evoked potential. A degree had a patient a couple of years ago that was sent from California with the diagnosis of optic nerve disease based on their visual evoked potential. They had only used pattern reversal. So they were guaranteed this patient had nystagmus, they got no VEP. So they said, oh well they must have bad optic nerves but you just needed to use a different stimulus. Unfortunately most labs don't think this through. The technicians hook every patient up the same way and if you're lucky they even pay attention if they're watching. I've been in labs where once the tech pushes go they start texting their boyfriend. And then they look at everyone's file, oh the screen stopped. They don't even know if they're looking at the monitor or anything like that. And they do the same thing every patient regardless of they have nystagmus, they don't have nystagmus. Their vision is 2400 versus their vision is 2020. You've got to think those things through and apply the different stimuli to fit the patient. The pattern onset is also best for poor fixation, eye movement, lingering, deliberate defocusing and nystagmus. Adults really can't deliberately defocus. Children have plastic eyes, they can deliberately defocus. But adults usually can't but they can not cooperate. When I have a suspicious patient that's an empty cardboard box hit him on the head about the size of a shoe box and they're looking, they see early retirement and they come into the room like this and stuff like that. And then later you see them texting. And I've had patients look at, they'll look at the corner of the TV instead of at the center of the TV and stuff like that. This is upside down for the normal presentation but it shows those age groups of how the time slows with age a little bit. You can estimate acuity with visually vote potentials but you guys can do a better job. It looked like years ago a friend of mine named Sam Sokol invented back in the 70s that he presented pattern within cartoons. And just little babes in arms like this, they look at it and because the cartoon is random they get visually vote potentials from it. And you can estimate acuity by changing the check sizes within the pattern. As you know, everyone floats through, do these under anesthesia. All you have to do is work with the anesthesiologists and tell them to get them, I tell them to make them as light as they're comfortable. And my lines are that and anything short of setting up works for me. Not yet a good visually vote potential if under surgical depth anesthesia because you get a flat line to EEG. I use these goggles who are going to be switching to a little handheld thing that they took on the Micronesia trip when they come back that we can produce any colors with. These goggles just have red LEDs inside. As I mentioned at the first the classic initial application was through neurology was to confirm and look at the progression of optic neuritis and multiple sclerosis patients. What happens is, what is the purpose of myelin on the neuron? Speed, speed. So if you get plaques on the myelin on the optic nerve neurons, you're going to get slowing. The classic patient, there are no absolutes in the universe, the classic patients which would just be one out of 100 or 200 would be, one nerve is still completely normal, the top one in this case, the right, and the left is slowed, usually not this dramatically. The classic, not sure they're MS patient, the slowing is usually only 10, 12, 15 milliseconds at the most. So one eye will be right around 100 in a peak time and thousands of a second. The eye with the episodes of optic neuritis will be 110 or 12 or 14 or something like that. But sometimes both are affected at the same time. No absolutes. Over time, when enough myelin is lost in one of the optic nerve pathways, you'll also start to lose amplitude. And if you would follow a patient from that first 110 milliseconds or so and test them every year or so for the next 20 years, you would just watch it march out like 115, 120, 125, 130, 140, 150, and then when they're like really debilitated and they're in a wheelchair, it's 106, 106 keeps going, and then after the first decade or so, the amplitude starts coming down too as more and more of the optic neurons and the nerve are affected. So it's a way to quantify the degree. Also, the effect will be more dramatic during, if you catch them during an episode. When they say they can't see anything, it's like looking through a veil. Another optic neuritis patient. Both nerves affected, but the left barely 112, the other 120. Just running through, different looking, every individual. A patient, is there a reason we see so many neurofibromatosis type 1 here? I see a lot. I mean like almost like MS patients. The best way to quantify neurofibromatosis effects on the optic nerve, unlike what the MRI people think, it's not the MRI. The MRI sure will show you the size, but it tells you almost nothing about the degree of function and the effect on the optic nerve pathway. If you look at a neurofibromatosis patient visually of a potential, you can't tell it from a multiple-storosis optic neuritis patient. They look similar. The initial issue is slowing. I can't, I'm sure there's one, but I've tested hundreds through the years and they all, even if they don't develop the gliomas, have slowing of the optic nerve pathways by about school age. So this is a sad case. This is an initial VEP of an NF1. This is three years later. These are gliomas growing on the optic nerve pathways. This is four years later. This is the worst case scenarios, although the very worst case scenarios is they'll lose an eye because they'll have malignant gliomas. I'm going to run through some different kinds of patients to give you examples of the application of visually evoked potentials. Cerebral palsy with pale nerves and orbital mass. Let's see, I think I have a follow-up on this here. There you go. Sometimes you can get no, the top, the right, you'll get no visually evoked potential with a large mass before it's removed or sometimes in trauma cases. You'll get no visually evoked potential. This is after decompression. It starts to come back a little. Look at the top. Again, look at the just no visually evoked potential. The right eye, those two traces at the top start to come back. Do I have a further? No, neuroblastoma, ambitol, nerve toxicity. Also, it looks just like MS. Here's the slowing. Once you get it past about 110, 112, that's two standard deviations. Slowing, the slide doesn't go out far enough, but anything. Halfway, past halfway between the fourth and fifth eye to the line is this, the middle here is 112, that's two standard deviations. It's not going to go in a cardi syndrome. We occasionally see these in exams under anesthesia. Usually it's one eye only with nerve affected. Vocal VE visually evoked potentials similar to multifocal electroretanograms give you more potentials that can be more discriminating in detecting the degree of pathology. Our system is roughly similar to this one, except in, in the patients, most patients view them like this for other manufacturers, ours is inside. They use a different kind of stimulus than the multifocal electroretanogram. This uses a dark board stimulus like so. This was also invented by Eric Sutter, the guy that invented multifocal electroretanograms. And everybody copied his stimulus like they copied his multifocal ERG stimulus. So normal visually evoked, visually evoked multifocal, visually evoked potentials from each eye superimposed. Starting out with an episode of severe acute optic neuritis in the right multifocal. During severe, you off, during the episode, you often lose a lot of amplitude. So that they're, can't tell very well, but the lower, the lower line is the right that's red. And then, let's see how much later. Two months later, it recovers the amplitude, but the slowing, the slowing almost always is maintained once a person has a significant episode of optic neuritis. And then three months after recovery, some of the times you've been recovering in part of the field, the lower field, you can see them match up pretty well on the lower field. Ischemic optic neuropathy, back again to that, highlights the area affected where you can see the difference between the two hemis, two eyes. The rest of them are superimposed pretty well in this ischemic attack. It maps within the optic nerve affected nerve pathways. Optic nerve glioma. So what I'd like to get out of this is that you can use it to quantify anything that has to do with the optic nerve pathways, whether it be something like birth anoxia, near-death, surviving near-death drowning, pituitary tumors. I test patients pre and post pituitary tumor removal, anything that messes with it. And again, there's even more information on the web vision site. Back to, there we go. Top right for you to start. Here. Or over, I guess maybe to your left. Top left. Top left. Oh, top left. This one? Keep going. This is from current slide. The play button. One more. The play button? Yeah. Traditionally, for the previous 60 years or so, a German piece of apparatus called the Goldman Weekers dark adeptometer was used for determining dark adaptation. It's the Creole monster in a Goldman Weekers dark adeptometer. Very German. Very solid. It had, it was just indestructible. It was a great thing. It had a built-in weighted calibrated. It had a rotating disc. It reminds me of the tracking of walk-in coolers that measures the temperature. It had only electronic parts. It was that disc rotating based on time. And the light. Other than that, it didn't have anything else that could fail. What the patient viewed inside was a stripe and a fixation point. Your best night vision is about 10 degrees off of center, which would be your fist at arm's length if you looked at the middle of the handout. It's your best. So you ask the patient to just look at the little red light, which wasn't an LED because the machine was old. It was just a little red light. And then you would turn off the white in the stripes to zero and slowly turn it up and it blinked to about once per second. And when they can first see the stripe, and then you pulled a little trigger and it punched a hole in that rotating drum. That's really neat. And I think the Germans would come up with it. And you could control rotating the stripe so that you would ask them which way the stripe orientation, because bad patients will guess. There's two different. Because of having rods and cones, when you dark adapt a person over time, you will get cone response or pathological response. This is congenital stationary night blindness with myopia up there. And the normal person will dark adapt about three logs a thousand fold, because rods are three logs more sensitive than cones depending on the color. Three or more logs more sensitive. So this is what you got out of that machine, this rotating drum on time and you'd punch holes in it and then in the end you'd put it on an X-ray light box and connect the dots with the pan. The concept of rods versus cones and separating the two is similar as in electroratnograms. The peak for rods combined is about 505 to 510 nanometer bluish-green. And all the cones combined is about a 560 nanometer, 555, 560 nanometer yellow, tennis ball yellow. So you can do the same kind of dark adaptation using blue dots and red dots to produce two different This phenomena of the little bit of a break here about seven minutes out is called, I don't know why it's called the cone break. I call it the rod break, but it's when the rods really kick in. They call it the cone break. I guess it means breaking away from the cones. I don't know who named it. So you can test people separately like this. And this is the way it's done now with LEDs in Gonsfeld's. So now they're done in a Gonsfeld that can produce any color. The patient has a button to push like they're doing a Humphrey visual field and asks to push the button if they see any flash. And the program alternates a red or a blue really dim flash. And the program knows if the patient doesn't push it to make it a little bit brighter, if they do push it make it a little bit dimmer so that over a period of 30 minutes or an hour, depending on how long you want to test their dark adaptation, it produces two curves. So the red light curve gives you this for the cones. The blue light gives you this curve for the rods. As you can see, most people are about 90, 95 percent there within 20 minutes. You're just there 15, 20 minutes and there's very little improvement after that. If you put a person in really complete darkness, not the approximation we have in the rooms here where we try to make them completely dark, people will improve actually for about 45 minutes if your measurements are sensitive enough. And there are labs in the world that test for 45 minutes or an hour. We did a study here once that they wanted an hour. I mean, just tedious. They wanted poor patients to pay attention to push this button for an hour. This is a patient of Bernstein's that had a little small intestine and prior to vitamin A therapy, they had no dark adaptation. Just stayed up there all the way across and then this is after vitamin A therapy for two months and then four months and got down into not the best possible normal range but into normal range. That's Dale. Dale and I have been friends for 40 years. Dale is now a woman in San Francisco. Dale is a type, the classic type one kind of albino. He's a sax player in San Francisco. And I have permission to use his photo. In fact, it's pinned on my office. I have it that I can use his photo for anything. Albinos eyes get a lot more light into them. So he told me a story from here. He told me a story of hiking at dusk up Mill Creek Canyon. So by the time they got up wherever they were going, it was completely dark. And there's very little light up there because you're pretty far away from the city lights. And he and his friends said, let's race back to the car. Well, his night vision is so much better because his eyes let more light in that to him, it was just like dusk bell. And he could run back and the other guys were running into tree lamps. He showed up the car and about 10 minutes later, the first guy showed up and he had cuts on his face and stuff like that from falling off the tree. I'm running into things. I don't know if I have it here, but they gave me an idea of doing a study. So I studied their dark adaptation and they are better. I mean, even because you test people, normal people, you test them dilated, but they still have some pigment in their eyes. But let's see what do I have. These are panagal, bainos type. These are two different kinds of albinos. Those that have some pigment, those that don't have any pigment. And almost all of them were at the very best of a normal person you'd ever test or a half a log or a log or a log. What time is it? 741. Contrast sensitivity is another way to measure optic nerve function. There are particular channels, neurons, that are sensitive to contrast sensitivity. What is contrast sensitivity? These are the guy who invented contrast sensitivity as a perceptual test and was the one that visually both potentials based on contrast sensitivity was a guy named David Martin Regan. And this was the original Regan charts. So you would test a patient on this chart for their acuity, like you were testing for acuity normally. And then you would test them on this chart, how well do they do, how many lines do they get on this chart. And then, take my word for it, it's not very good in here. If we had a darkened room, this is another level of contrast sensitivity. And there's another one but it's too light in here. And then this was the scoring chart and everybody does poorer on each success contrast sensitivity chart. The question is how much poorer do you do? So the scoring was, most of you would score that you could read 10 of the 10, 20, 20, 15 line and then at 9% you might drop a little bit. But if you drop greater than the dotted line, that's pathological. It agrees almost completely with degree of optic neuritis, for example. The results of this fit with the visually potential results you get was slowing of the optic nerve. And I think there are some, I know there are some studies, they have a different system on the fourth floor in that study room, in the clinic or off of plastics there. There's some study that's using them, using a different version than the Regan studies. So what you get in pathology would be the person would drop, the person that dropped that dramatically, the dark lines when you get. And sometimes they can only do the first one. When you go to the really dim ones they don't get anything at all. That's what contrast sensitivity is. The end is near. You're going to live, it's going to be close. As you're all aware there are three kinds of color receptors plus rods. A really good source you want to pursue this further if you have any reason you have to is also web vision. A guy has like a 40 page chapter on color vision in there. Oh I love the mantis shrimp. They have, I forget how many do I have it here. 16 types of color receptors including UV and polarized light. Do you know the mantis shrimp? The mantis shrimp that has the acceleration of a 22 caliber bullet for killing prey. 22 caliber bullet. One of his little clubs here. You have to use super high film to catch it. Give you an example of where we are. Creatures that have this extent. They're not number one. There are animals that have even more receptors and UV and infrared and polarized light receptors. These are the three kinds of receptors and they're approximate peak colors in real approximate colors that I picked. If you combine them all together you end up with tennis ball yellow. Here's some more realistic colors that we've worked with. So we have the cones in the eye that are receptors and then sent on to the lateral geniculate. There are plus minus cells that fire that are red, green versus and yellow, blue cells that's processing so that it's cleaned up a lot before it gets to the visual cortex. Again, the same if you lump them all together and they have the various sorting that you see in neuro for detecting color problems. Then you have the sensitivity difference between all of your cones as a group versus rods and there's at least three logs difference in their sensitivity. Ishihara plates. Test for red, green color blindness. Sample. It's misspelled. Farnsworth. There's two versions. There's the 15 and 100 which isn't really 100. I think it's 88. It's called the 100. I don't know why it's called the 100. It looks like this. So the patient is given them mixed up and there to put them in sequence of color. It's like a rainbow. Ishihara plates. Again, picking things out of dots, triangles, squares, paths. Those are the most common ones used in ophthalmology. You lose. You win. See you next week.