Social and Emotional Functioning in Children with KS

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    Ho sbobinato la presentazione della conferenza:

    Social and Emotional Functioning in Children with Klinefelter Syndrome
    Dr. Lara Foland-Ross
    Dr. Allan Reiss

    from our local amazing research team at Stanford, so some of the people that will be giving the talk are people that are super supportive of our support group and a lot of us know because we’ve gone to them either to participate in studies or for help <risata> so < risata > I think I’ve done both, so < risata >so I’ll start with doctor Allan Reiss. He is a professor of psychiatry and behavioral sciences, radiology and pediatrics at Stanford, and he’s the principal investigator for the BGAP study, which is we’ll be hearing about, and you know he’s been he has spent his very long career not to age you dr Reiss but long career doing a lot of amazing research on genetic, biological, environmental factors and how they influence brain and behavioural development; and he also is a practicing child and adolescent psychiatrist, and he’s you know actively looking for what is the most effective intervention for individuals with extra chromosomes so and he’ve gotten tons of honors.

    We also have dr. Lara Foland-Ross, who is a senior research scholar at the center for interdisciplinary brain sciences and research at Stanford. She has her PhD in neuroscience from university of California (Los Angeles) and did her postdoctoral fellowship on neural and cognitive mechanisms of risk for anxiety and depression. And let’s see here she is also focused on brain and behavioural development in children and adolescents, and has been a very wonderful active part of our community. So we’re really thrilled and, last but not least, so we have…I have to change my slide for a second one second.
    Here we have Vanessa Alschuler: she’s the lead clinical research coordinator at Stanford, and knows a lot about this study and she’s happy to be answering questions and also is a wonderful part of our team. So we just… we have the best here. So I think I’m leaving out some things about Vanessa because it’s on a different screen, so I’m gonna have to come back and add that, but we’re just thrilled you guys are here on a Sunday, and we are so thankful and so with that I’m going to mute myself and welcome you, guys, and let you share your screen so Katie that should be working right. Yeah. Thank you Allan, you should be able to or Lara to share your screen right now.
    Yeah I think I think Larry you’re going to share but one thing I should add about Vanessa is that she should have a little applause. She’s just accepted into wonderful clinical psychology PhD programs, that she’s mauling over to which one she wants to go San Diego or Minnesota; so if you have any thoughts or feelings about that you can chat with Vanessa during our talk. All right Lara, are you gonna share am I gonna share. I’m happy to share so you’ll have to you’ll have to work the slides. I’m going to just do the first two introductory slides and then turn it over to Lara, and then I’ll pick it back up later on.
    Okay, it’s great to see you all by the way we’re we’re excited to be here even on a Sunday and some international representation too that’s particularly nice.
    Thank you all for doing this it’s wonderful
    happy to do it.
    Okay, so .. you’ve already heard the title of the talk that Lara and I are going to give today, and we’ll try and I think get through this, and Lara you can give me a thumbs up or down in about 30 minutes there about, yeah, and our studies are called the BGAP1 study (Brain Genes And Puberty) and I don’t take any credit for coming up with that nice acronym.
    I think it actually was Vanessa is that right Vanessa? Did you do it? Yeah it was Vanessa. So we have little contests sometimes in our lab, just to see if someone can name the new study. This is a study that’s funded by the National Institute of Child Health and Human Development as part of the NICHD, it was a study that I just absolutely had to try to get funded, so when I find that I just think there’s some important critical unanswered questions in the field regarding groups of individuals with whom I’ve interacted or treated as a physician, or worked with families on previous research studies, I have to write that grant and Lara helped me write that grant.
    We were very happy to get it funded now three years ago, and it’s pretty much one of a kind at least in the United States. I think probably also in terms of the world and we’ll tell you more about what the study actually entails but let’s just go to the next slide.
    If you don’t mind Lara and I this is a really important slide that I thought we had to put in here and it’s not just for parents or families: it’s actually for anyone you’d be amazed at how many people in science or who practice clinical medicine having to do particularly with genetics, don’t think about this necessarily. So in this talk we’re going to be referring to risk associated with the presence of a specific biological factor; in this case it’s variation in X and Y chromosome number and in particular the 47xxy genotype. Genotype meaning that’s associated with Klinefelter syndrome but, of course, many of you know that when we’re talking about Klinefelter syndrome or 47xxy we’re also talking about secondary effects on hormone levels and so, for either of those think about this as risk. Okay, and that’s really different risk is related to altered probability of an outcome or a range of outcomes, so height, fertility or attention problems, and you’ve already heard several people say “wow when I read about this in some old textbook, I was just absolutely terrified for my kid” I can’t tell you the number of times I hear that and then when I went to the meeting I met all these really cool people, and it made me feel a lot better and that’s all about that’s what we’re talking about with risk. It’s a probability of an altered probability, but you still have a very large range of outcomes it’s just shifted it either a little bit or maybe a little bit more than a little bit when you’re talking about things like fertility in a particular direction, but having a particular genetic variation, is not the same as destiny. Okay. So it’s there’s never a one-to-one correspondence between having virtually any genetic variation for that matter, not even those associated just with X and Y chromosome variation, so that don’t ever think about it as one-to-one correspondence. If you ever read, okay, Klinefelter syndrome is associated with this or that, it’s an association, it’s a risk, it’s not destiny, so that’s really important for you to know. I’ll give you one other example of this: when I was doing a great deal of work on a different X and Y chromosome variation syndrome called Turner syndrome. Interestingly Turner syndrome has its own parent and national/international groups and so that’s probably one of there as reasons why it’s not part of access but those girls with Turner syndrome have 45 chromosomes instead of the typical 46, and they have one X chromosome instead of two and they’re female in their sex and almost always in their gender as well. But it’s associated with very short stature so most girls with Turner syndrome are quite short, but once I was we were doing a study and a girl with Turner syndrome walked in my office and she was like five six, five seven, and she was like 14 years old, and I thought what’s going on here, is this some strange mutation or this or that and so and she and most girls with Turner syndrome, by the way don’t break five feet unless they get growth hormone, and even then that might not occur. So I was thinking what’s happening and then her parents walk in the room and they’re like six two and six seven, so it’s just there’s lots of things that affect outcome including many of the areas that we’re going to talk about today, so remember: not destiny risk. And I’m going to hand it back to Lara, at this point, to tell you about Klinfeldter syndrome, a little background into psychosocial function and brain function, and then I’ll take it back up talking about the study.

    Great thank you, okay,
    So as most of us here know, Klinefelter syndrome is a genetic condition quite common it’s estimated that as many as one in 448 males have Klinefelter syndrome, and this a condition where there’s an extra X chromosome. And there’s lots of physical characteristics associated with KS, so things like tall stature, reduced testosterone, impaired sperm production, and large breast tissue or gynecomastia, and a lot of boys often start puberty at the same time as their peers, but then kind of sputter on, and don’t complete their pubertal development. And so oftentimes families will get referred to their pediatric endocrinologists, who will prescribe testosterone supplementation, to help kick-start the body back into pubertal development and the development of the physical characteristics of becoming a team. But in addition to these physical alterations there’s also some cognitive alterations in KS, so things like motor dysfunction, language based learning issues, and also alterations in executive functioning. So things like working memory you know, rehearsing a phone number in your head, sustained attention so keeping focus on Allan and I as we speak to you today, and then inhibition so overriding that impulse to do something that you probably shouldn’t do. And all of these things put together can be really hard on boys with KS in the classroom, so there’s a lot of documentation of reduced academic achievement, and so it’s really important to make sure that we have new and better treatments for these boys, so that they can succeed as much as possible in school. So there’s also social symptoms that are present in many but not all boys with KS so things like increased shyness, more introversion, difficulties with pure relationships, social impulsivity, reduced self-esteem, and there have been studies showing that in as many as two thirds (2/3) of boys who were studied in a particular research investigation, two thirds had altered social communication skills. Another study found that that was the case in up to 47% of their participants, and other studies have found that many boys and then with Klinefelter syndrome have social communication alterations that are consistent with a clinical diagnosis of autism. So in addition to these symptoms there’s also increased rates of depression and anxiety in boys with KS and men with KS so up to 12 to 18 percent of generalized anxiety, so that’s anxiety that’s clinically significant to warrant a diagnosis by a psychologist or a psychiatrist. And there’s also depression at higher rates so 14 to 24 % is the current estimate and many more males have some level of depression that’s not clinically significant per se, but that is just elevated nonetheless. And we’re even finding this in our study, so far so in boys ages 8 to 14 we’re seeing some elevations and anxiety depressive and social communication symptoms. So this is really hot off the presses we’re still collecting data but it seems that these types of patterns are present even at these early ages.
    So these types of these aspects these behavioral aspects of Klinefelter are often dismissed as a consequence of living with KS but there’s actually a lot of important work showing that these types of behaviors and symptoms are actually the results of some basic differences in how males with KS perceive process, and express social and emotional information. So, for example, the eyes of a face are the most salient they express the most emotion out of all the other areas of the face, and so it’s a really important area to watch in someone else, so that you understand how they’re feeling.
    There’s one study that showed that males with KS don’t pay as much attention to the eye area suggesting that that might feed in to difficulties with emotion processing. Along these lines there’s also another study showing that males with KS have difficulties in the perception of emotion; so this is a very common task, that is used in psychology, where you morph a face from a very neutral expression, very slowly, to an extreme expression, and an individual is asked to press a button as soon as they know what the emotion on that face is. And in this study at least they found that males with KS had difficulties in the perception of anger, which is really interesting because it’s also the same finding that we see in studies that are risk for depression. There’s also interesting work showing that males with KS have problems understanding the emotional tone of spoken language, and this is even after controlling for baseline differences in verbal fluency. And then here’s a test that we love that we use in our study it’s a task where you have to process this whole first picture so when the faces look away, the two running objects look further apart than they really are, likewise when the two faces are looking towards each other they actually look closer together than they really are. And so this is an optical illusion that depends on the accurate processing of that face area, and so it gives us a good sort of insight into subliminal processing of that face so if we don’t see the optical illusion then we know that there’s some processing difficulties of that face area and that’s what we that’s what others have seen in adults with KS.
    So what does testosterone play in all of this so there’s areas of the brain which are very dense with testosterone receptors so these are regions such as the prefrontal cortex the amygdala the hippocampus. These are all regions that are very important to executive functioning but also important to emotion, and these regions of the brain also go undergo a huge wave of remodeling during puberty, when there’s that natural surge in testosterone. Specifically, the outer areas of the brain, known as the cortex, undergoes a process called pruning during puberty, so when you get that rise in testosterone you get this pruning away or a reduction in synapses between neurons, and so that reduction in the synapse number actually leads to an overall reduction in how much tissue you can actually measure using with using MRI . And so testosterone is really critical for this process and so when you don’t have it it’s possible that you don’t get that normative pruning in the brain.
    There’s also many studies of men without KS but that have very low testosterone when you treat them with testosterone their positive moods go up and their negative moods go down, they also have increased self-esteem and better social functioning, and there’s also research in males with KS showing that when you’re on the younger side, you have similar levels of testosterone to your non-KS peers, though when you get older, you have little testosterone significant reduction.
    Testosterone compared to non-KS men and this was further found in the study to have a direct correlation with your social anxiety level; so the more reduction you had in your testosterone, the more symptoms of social anxiety you reported. And this was in a study of all males that had never received testosterone supplementation.
    So what about in boys with KS? So there’s only one study, to date, that has actually taken a very hard look at this question. So this was a study conducted by our collaborator on the BGAP study, so she’s <?? minuto 19:24 ??> This is Judith Ross, and she leads the Nemours extraordinary kids program on the east coast, and she conducted a double-blind longitudinal study of young boys with KS, so these are ages 4 to 12 and she placed these boys in either a placebo arm or treatment arm. If you’re in the treatment arm you’ve got a very low dose of a synthetic testosterone, known as oxyanion, for 24 months. If you’re in the placebo arm, you took a sugar pure pill every day for 24 months. And then she assessed a whole range of symptoms at the beginning the middle and the end of the study.
    And what she found was really exciting so she found that in the aux angelo group you had increased freedom from anxiety a decrease in interpersonal problems, a decrease in anxiety and depression, and an overall reduction in social problems. She also had a subset of boys from her study get scanned with MRI, and we analyzed those data and found that in males that were in the placebo arm they had very small hippocampi, so hippocampus is shown here in blue, and it’s really important for not just memory but for emotion as well, and when you treat with oxandralone you have an increase in hippocampus volume, that’s almost the same as typically developing voice. There’s also a retrospective report from Allan’s group which finds that in men with KS, if you have been treated with testosterone in the past, you actually have an increased volume of the temporal lobe which is shown here in green. So again if you have treatment, your temporal lobe volume is similar to that of non-KS controls, whereas men with KS without that treatment have lower volume.
    So there’s a lot of exciting data, out there, to suggest that testosterone is really critically involved in executive functioning mood, social functioning, and also has a very robust effect on the brain, but really no one has taken a hard look in comprehensive look at what’s going on with testosterone supplementation and adolescence of KS. So, again, this is a pretty standard treatment for boys who are entering puberty, with KS, but what it does to the brain executive function, and social emotional functioning. We have yet to understand and that’s what we are looking at in our study. So I’m gonna just share my screen, now, with Ellen. Okay.
    I think Allan needs to unmute.

    Good, I didn’t have an unmute button. This is like an executive function challenge for me: first the link didn’t work for me to register for the meeting, then I had to change my name from Lara Foland-Ross-Doppelganger to my actual name, and then I had to mute and unmute. Anyhow, thank you, So Lara is a nice nice job, that’s what I was saying in pantomime. One of the things I want to tell you is that, in the now 25 to 30 years that that Hannah alluded to, in which I’ve actually, it’s longer than that I’ve studied children adolescents and adults with X and Y chromosome variations. The landscape has changed so much, I mean, amazingly so in terms of prenatal identification of children. But what’s interesting is back: when we did early studies, we all knew in the field that when you took only those individuals, and this is before a lot of prenatal identification. If you only took individuals who are presented to you for their clinical problems, you were going to have a bias group, and they were going to be more severely affected. So what some investigators did at various locations, particularly one in Europe and one in the united states and Denver, is due; this is again before high throughput genomic sequencing, and so forth they just tested the chromosomes of tens of thousands of newborns, and so that was one way to try to get rid of that bias of someone presenting to a doctor with clinical problems, and you’re assuming that that represents the condition.
    So that study that Lara showed you about temporal lobe volume, was actually in people in young men who had been identified as having 47XXY at birth, and no other reason. Clinically so it’s actually a very nice study in terms of its lack of bias in that respect. Okay. So, well, let’s see if I can actually control the screen, there we go. So as Lara alluded to, we feel there are huge gaps in understanding of the brain effects of testosterone on adolescence with KS, and this project is all about trying to clarify that role TRT (is testosterone replacement therapy) on pubertal brain development function, and to test whether initiating this treatment in boys and young adolescents leads to improvements in executive and social emotional functioning. But it’s not just whether it does. So what changes or improves and, perhaps, just as importantly what does not change or improve. I’ve talked to now hundreds, if not more, families who have children who have 47XXY, and even though many of them say things do improve when they start testosterone supplementation. It’s not the magic bullet, so it’s up to us in the study to really try and figure out what is improved and what is not. Another question that’s really important is: does the timing of testosterone supplementation matter, with respect to a child’s age or their pubertal level, at which point it started. So why is this even a question. Well, as Lara showed you in a previous slide, our brain is chock-full of all these receptors, which means that there’s these little entry points for testosterone to interact with our nerve cells. And they’re not there consistently are constantly throughout development. There are these critical windows of brain development, when a brain of a human being expects to receive, to recognize, a particular neurochemical or steroid, or have an environmental experience. And so if you kind of are off too soon or too late for that critical developmental window, you might not get as much of a positive effect as you would hope. So that’s really important too. And then, once we have really identified the areas that don’t really change with testosterone how do we address them. So we hope, our intention is that this study will lead to much more Klinefelter 47XXY specific treatment approaches, which is not the case right now. It’s not that we can’t improve outcomes, or do things to improve outcomes and children with with KS: it’s just there the interventions were not built for KS to begin with they’re built for a general symptom approach. Okay. So, what is wrong with our current approaches? Well really nothing. There’s nothing wrong with them again. They’re just not they weren’t created for 47XXY. So if you’re thinking here, you know maybe, I should wait until dr Reiss and others in the field find these Klinefelter syndrome-specific treatments, don’t do that: always use the best treatment approaches you have available to you at present, and hopefully those treatment approaches are what we call evidence-based.
    So it’s not just someone thinks, that they work someone has actually done a clinical trial to show that they work, for example in language based problems, or reading based problems, or executive function or attention deficit based problems. I’ve already said this that current symptom-based treatments are going to be limited they weren’t developed for KS, and we should recognize that persistent problems with cognition learning particularly exactly executive function can, potentially. This is again risk, right have long-term significant effects, or increased risk of problems in terms of outcome, and there’s this group, in Canada. We have some canadian folks on our call, don’t we you should feel very nationally proud for about this study they looked at. Very young children, four or five years of age, I believe, and looked at the types of very early executive function intentional problems, social emotional problems, that they had in a range of children a very large number. And found that those kids who had these executive function, social emotional issues, very early on, had increased risk for reduction in employment earnings, long term 20 years later. So that’s really an important thing to keep in mind, that we need to try to constantly, consistently, improve our approach. So that we don’t have this happen to our boys who have Klinefelter syndrome. So, what are we doing in this study? Well we’re doing MRI (magnetic resonance imaging). We’re also looking at brain anatomy, that’s called structural. We’re also looking at how the brain functions in real time, that’s called Functional Magnetic Resonance Imaging. We’re also using a different technique in the MRI scanner, called diffusion weighted imaging DWI , DTI and that shows you the connectivity, the wiring of the brain. So it’s this very nice triad what does the structure of the brain look like, how is it functioning, and how do those relate to the wiring or connectivity. We do a lot of clinical interviews and questionnaires, and computerized testing and neurocognitive testing, and all this is really great for us in terms of having the associations with testosterone, and the brain and so forth, and physical features. But it’s also great for you, potentially, if you’re trying to figure out you know how can I help my child, have the best adaptation, or the best school classroom structure, to have him succeed? So a lot of the parents who participate are very happy about getting this information, because it does relate specifically to potential accommodations to IP (??? Minuto 31.23) and so forth. That can help tailor and modify their school program and, of course, we’re getting hormone levels in doing physical exams, so there is a blood draw to this as well. For those of you don’t know MRI is not associated with radiation exposure in any way so it’s not like doing a CAT scan or an X-ray or something of that nature. We’re doing a study which we call “accelerated longitudinal design” and all this means is that we’re not like re recruiting a gigantic group of boys with Klinefelter syndrome, who are five and six years of age, and following them for 10 or 15 years, most importantly because we would never get funding to do that. They don’t do that anymore at the NIH or any funding agency private or government. So we take a broad age range to begin with, and then we follow them over an additional time period or two, and then we kind of stitch that together all that information together, to statistically do the equivalent of a cohort design where you follow them for many many years. This is one of the most widely accepted approaches for doing longitudinal, in other words time-based studies. So the other point I would make is that this is not a clinical trial. We thought a lot about this, we thought “okay should we and and my friend and long-term colleague Judy Ross, who I have great admiration for you, know really say well why don’t we do a clinical trial? why don’t we just you, now, recruit boys with Klinefelter syndrome in our study, and give them testosterone at various times?” And we thought it’s probably not the best approach for the first study. Let’s do this as a naturalistic assessment of how testosterone is administered in typical clinical practice, and you might say “Well why am I doing that?” Well as it turns out, testosterone is administered in typical clinical practice with a huge amount of variation, some of the kids start it early you know 11 years of age others don’t start until they’re 18. Some of it is also somewhat based in terms of the health care systems in various countries, and so we were talking with someone. I think it was in Canada isn’t that right Lara? Where most of their population is not given testosterone until they’re 17 or 18, and you know I had to bite my tongue a little bit, because these folks were really great they were really good people the the scientists and the doctors. But I was thinking to myself “well what about critical developmental windows are you missing those?”. So typical clinical practice we’re not administering testosterone but we’re sure measuring it, and monitoring its administration by the participants doctor. As I mentioned it’s a first of a kind study it’s a longitudinal design, we’re looking at multiple different dimensions of outcomes, and we think that this will be a unique data set for informing more specific treatments for KS in the long term. So what do, we what are we looking at in terms of kind of an overall view. Well we know that having chromosome variation in the form of XXY, we know it in most nearly all boys who have this variation, have alterations in typical hormonal secretion patterns. We also know that in many, it affects early development pubertal development. And not only from the standpoint of genes affecting these areas but the hormonal alterations also affecting these areas. So we’re going to try to dissociate, disengage, these two major areas of effect with our study design. And, of course, we want the outcome of the boys in our study, and for that matter those who are not in our study to be as optimal as possible in all the various dimensions of social, vocational, et cetera. And, of course, you can’t ignore the environment, you know, has a huge effect on outcomes. Every study where we’ve looked at how environment interacts with genetic influence and so on, shows that you know environment makes has as big a bang as the genetic risks. So keep that in mind always. Particularly if you’re finding yourself despairing at times thinking oh you know my son has this my daughter has that you can do an awful lot with the right approaches from an environmental perspective, as well as hormonal therapies. Okay, so what .do we want to do? We call this intuition. Can you see my pointer here? Yeah. So the the studies of yesterday, the approaches of yesterday, are symptom-based treatments. Intuition medicine. Intuition medicine means I think it works. I’ll tell you a really funny joke really quick if we have time. So, you know surgeons have jokes about psychiatrists and we have jokes about surgeons. And my joke about surgeons is that you know how does a surgeon tell, I hope there’s no surgeons, Not, well. It’s okay they’ll laugh at how does how the surgeon tell a colleague that a new surgical approach research approach, they’re really excited about they say. In my experience this new treatment approach works really well, so how do they describe it to someone if.. if there’s two cases that seem to go really well, they say, in my series this new treatment approach works really well. And if there’s three, they say, case after case after case. So that’s intuition medicine, that you think it works, but you haven’t done your due diligence to show that it really works, like versus not doing or doing a different one. So today we’re doing what called “cohort based studies” and we’re trying to develop this evidence-based medicine, as I’ve been describing, but tomorrow, this is what we want to do, precision medicine. We want specific treatment approaches for specific conditions. Many boys, for example, with Klinefelter syndrome are treated with medicines that are supposed to be for ADHD, and sometimes they work well, sometimes they don’t. But those medicines weren’t developed for Klinefelter syndrome they’re developed for something else. I could tell you that actually the story of that it’s interesting. So we want to go to precision medicine, where we survey and interrogate all the different aspects of functioning and we come up with our precision medicine approach to KS. Can we optimize testosterone treatment, in terms of dose, duration, and timing? Are there going to be KS subgroups in terms of response? I actually think there will be. I don’t have any evidence, yes, it’s my intuition. But we’re going to look at that possibility as well. Can we develop new cognitive behavioural social emotional treatment? Treatments I’m talking about environmental treatments. I’m not talking about gene therapy that we can take advantage of, and target the specific profile strengths and weaknesses in KS. For example computer-based cognitive training to enhance specific executive functions can we develop more sci-fi-ish type treatments <<<(trattamenti fantascientifici?)>>> and they’re really not sci-fi. They’re really we’re doing them already. We’re using this thing called functional, near-infrared spectroscopy. There we go. Functional near-infrared space spectroscopy to do real-time imaging feedback in naturalistic environments, to give individuals more volitional, voluntary control over how they utilize their brain function in particular circumstances. It really does, sound like it belongs in a science fiction movie, but it’s not it actually. It’s here now, and we’re doing these studies not yet inclined Klinefelter syndrome, but in other areas. Okay. So this is the sales pitch part of our presentation. This is where we try to convince, beg, cajole. However we can capture your attention to participate. We really need your help in bringing your own children, or helping find other children, recruiting other children to come in, and participate in our study. I’ve already gone over what our participation involves, but what you don’t know as I may have mentioned in passing, is that these days, because of the pandemic, most of our non-in-person requiring components of our study are collected via remote visits. So and we’ve gotten so good at this, and I use the term we very liberally here it’s really Vanessa and others and Lara have just done a fantastic job, moving our assessment, part a lot of our assessment, to online. So it’s not as much time at Stanford as it used to be here are our criteria: eight to 17 years, english speaking now. Why do we say english speaking? Because we otherwise would have to really change a lot of things in the study. I’d love to have it be multilingual, but right now we don’t have the people to do that. No history of severe brain trauma seizures, diabetes, and if we have a participant who has XXY and they have a brother that’s in our age range, bring them along for the ride. We’d love to have him be in our control group. What do you get? You get, first of all, a visit with some really nice people who happen to know something about Klinefelter’s syndrome and other X and Y chromosome variations. You get an in-depth written report of the results from the testing, you get hormone testing results that can be useful for your endocrinology visits. Your kid gets a picture of their brain. How many kids have a picture of their own brain? All my kids have pictures of their brains because they participated in studies when they were really young. There’s an honorarium of up to 150 dollars per year, and early access to study findings. So you know we would be doing this talk, no matter what, but with the pandemic we have just you know gotten really into tough difficulty, tough times, because we had started to bring people in by air, with hotel stays and so forth before the pandemic kicked in. Now we can’t do that. We’re hoping to restart that again. I mean a lot of it depends on what direction the pandemic takes in, not only California but other states in the U.S. .
    But we really really need help in bringing people in. We’re starting the fourth year of our study of a five-year study, so we’re kind of a little bit in desperate straits. I’ll be honest with you and I’ve never faced this in 35 years of conducting these types of studies ever. This type of, you know, pandemic related thing. So thank you for your attention. Here’s a little box that you can snap a picture of barcode with your smartphone or you can just take down the information that’s in the box, and if this is being recorded. Well you can just go back and and pull it off of there. But we’re happy to send you study materials. We also have a screening site that I believe is at that BGAP study. We’re on facebook, we have a telephone number, we’re completely accessible. Okay that’s it. Okay so why don’t we stop the recording, and then we can start our Q&A. Does that sound okay?
    Yeah sounds great to me.

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