I think we're mostly reassembled, looking pretty good. Too excited about the candy. Wow, that doesn't take much. Well, I would have thought it was this incredible amount of money you're earning today as a special government employee.  A lot of candy. Yeah, it's worth it. That's right, you doubled the amount that we're rewarding you. That's right. Well, in any case, it is a pleasure for me to make a few introductory remarks about a new colleague, a long term friend of mine and many of you, Diana Bianchi. I noticed immediately that there were multiple people around the council table and around the room that in fact she knows and probably has a long history with the reflection of her longstanding involvement in the genetics community. It is thrilling to NHGRI to have another geneticist slash genomicist as the head of an NIH Institute. And so when we learned of her recruitment, it was met with great happiness at NHGRI among many of us. Just by way of background, before I turn the podium over to Diana, those who don't know her background, she got her undergraduate degree at University of Pennsylvania, went to medical school at Stanford, did pediatric training at Boston Children's and then did a fellowship both in medical genetics and then in neonatal and perinatal medicine all at Harvard Medical School. Found her way eventually to Tufts University on the faculty where she was for many years when she departed just a few months ago. At that point she was a full professor of pediatrics but also founding executive director of the Mother Infant Research Institute and also vice chair for pediatric research. She regards herself and has a long term involvement as a practicing medical geneticist with a focus on reproductive genetics. And I think she's also gonna say a few things about her own personal research which NHGRI is particularly interested in because I think I told this council last meeting or whenever I introduced her recruitment. Her research laboratory is actually now being housed within NHGRI's intramural research program so she has now moved her laboratory from Tufts into our intramural research program and she has a number of components of her own research program including prenatal genomics and particular noninvasive genetic testing but also development of approaches for diagnosis and treatment for genetic disorders in the prenatal period. She has served in various roles I know extensively for the American Society of Human Genetics she was a member of their board of directors. She's editor in other service activities for the community editor in chief of prenatal diagnosis and she's been recognized for her outstanding research contributions and other contributions to the field in a number of ways including election to the then Institute of Medicine now the National Academy of Medicine in 2013. And on top of everything else you'll see her smiling a little bit more today because she's a Patriots fan having spent that much time in New England and so we are delighted that she's here at NIH we're delighted that we are going to see hopefully some incredibly fun and productive collaborations between the two institutes on the extramural side of the house and then we're also very excited to have her within our own family by being a member of our intramural research program that is her own research lab being within our program. So I'll just turn the podium over to Diana thank you for coming. Thank you Eric for that great introduction and it's just such a pleasure to be here and I would have been wearing my Patriots jersey but we had to meet with Congress earlier this morning I wasn't sure how they would react to that but in fact the male Congress members all came in talking about the Super Bowl so probably would have made an impression of some kind. No none of them were from Massachusetts although representative Delores from Connecticut and she's a Patriots fan. So and the other thing I want to mention is listening to Lisa's talk we didn't integrate our talks at all but you'll see that we touched on a lot of the same themes. So without further ado I know it's late and there are no windows in this room which is kind of deadly. I was sworn in on November 8th otherwise known as election day which was an auspicious day actually selected that day but anyway I won't say anything more about that only to say that it's been less than three months and it's been an enormous education and a great pleasure being here. Actually the only disadvantage of being here was that I couldn't be in Boston this morning and Tufts Medical Center is right at the corner where the parade goes for all these sports championships so I'll have to miss that this year. I'm gonna talk in the beginning and I was asked to talk for about 45 minutes for those of you who are wondering when the next break is gonna be but I'm gonna talk a little bit about my vision for NICHD. We had our council meeting last week but I'm gonna emphasize much more in the second part of the talk on areas where I see NHGRI and NICHD interacting. And just from this picture you can see that we have an extremely broad purview for our research. It's in some ways it's almost too broad and it's historically been added to. And in trying to wrap my head around what is our focus and what should be our focus I started with our name which in and of itself is kind of confusing. I mean the Unicek Kennedy Shriver part is pretty straightforward. In 2007 there was a congressional act that actually recognized the fact that Unicek Kennedy Shriver persuaded her brother President John Kennedy to found an institute and I'll show you the quote from him at the beginning of the institute. So the Unicek Kennedy Shriver is kind of an important part of the name and in fact her son Tim Shriver who is president of the Special Olympics and a number of other activities for people with intellectual disabilities he's on our council. But the child health part is interesting because I think it would surprise you it certainly surprised me and I served on NICHD's council that only 18% of child health research at NIH is conducted at NICHD. So collectively there's a lot more pediatric research going on elsewhere. The human development part is clear we are involved in all aspects of human development but there's nothing in the name about women or pregnancy and importantly I don't know how many of you realize that the National Center for Medical Rehabilitative Research is housed within NICHD and even other institute directors didn't realize that all of the adult rehabilitative research is in NICHD. So they kind of thought well maybe pediatric rehabilitative research. So we have this incredibly broad mission and how do you tie it all together. So I went back to the history and this is actually a quote if you come to visit me in my office which I hope some of you will there's what looks like somebody's shop high school shop project. It's like a wooden plaque with a carved out picture of President Kennedy and this quote which was at the time that the institute was dedicated. Interestingly I believe we're twins with NIGMS because I think they were dedicated the same day but for NICHD he said we will look to the National Institute of Child Health and Human Development for a concentrated attack on the unsolved health problems of children. The underlining is mine and of mother infant relationships. This legislation will encourage imaginative research into the complex processes of human development from conception to old age. For the first time we'll have an institute to promote studies directed at the entire life process rather than specific diseases or illnesses. Now at some point I'm not exactly sure when but the Institute of Aging was spun off. So we really don't take care of conception to old age and we take care of conception to some undefined time point. So last week I spoke to our council about my vision. I'm just gonna give you the highlights now. I think it's a good time for us to redefine the focus of our research. We've gotten so broad that we're effectively shallow in many areas and we have a strategic question to address is that the best use of our funds? And once we decide what our focus is we need to communicate our message and we're lucky that one of our council members is actually a vice president for Sesame Street and she's an expert in marketing so we're gonna take advantage of her skill set. I don't think that we do a particularly good job of listening to the voice of the patient. We incorporate some patient input into our protocols but I've been impressed by particularly how NCATS uses the patient advocacy groups to determine their research activities. We do have scattered patients involved but not in an organized way and I'd like to increase that. Importantly much of the research at NICHD historically has been siloed and there are areas in which obstetrics and pediatrics which should be talking to each other and integrating their research really aren't. An example of that is in our networks where we have neonatal research networks and maternal fetal medicine networks even at the same institution and they are organized as completely separate activities. And there's so much to learn from taking the long view this whole area of developmental origins of health and disease. Your birth weight is one of the most important predictors of whether or not you will develop an early heart attack for example. I know in this room we all think it's genetics but actually it has a lot to do with how you were programmed in the womb and whether your placenta was working correctly or not. We all know about the all of us program but and I know that Jay was involved in some of the early planning stages but one of the things even before I was thinking about applying for this job I was surprised there was no mention of children. And if you think about this conceptualized very very long program of 20 30 years who is going to get the major benefit from this personalized approach. It would be children and you could take that even farther back into the womb and go via obstetrics. And there was nothing specifically mentioned about rehabilitative medicine. We are involved with an Eric Gnosis with other IC directors investigating the importance of data science and sharing our investments as well as other IC's investments and this is a big discussion. I was listening to your sandbox discussion. It's very relevant. Our training activities are somewhat different from other institutes in that we fund a lot more institutional grants as opposed to individual training grants. So we are gradually based on very impressive evidence and success rates of individual trainees versus trainees in an institutional program. We're gradually shifting our training dollars but we are analyzing that we're going to I think provide the community with some very interesting data showing the importance of writing an early individual F grant or an individual K grant and how that correlates with later academic success. We want to catalyze innovation like other institutes and we need to emphasize the A for the advice in the advisory council. I know the reason why I wanted to come today was I wanted to hear I had heard from my spies Tony Monaco and David Walt two Tufts colleagues former council members how active your process of concept clearances and it's very different from ours which is a very top down one minute per concept before lunchtime. So very different. So we're going to be looking at how our council works to get a lot more interaction and engagement. And I'm not just saying this because I'm here but I said it last week too that a big part of my plan is to build bridges with other institutes but especially with NHGRI. Now I already mentioned all of us no it's if you're not thinking about it it's very easy to forget about pregnant women children and people with disabilities and a lot of these programs are focused on adults adults with cancer adults with chronic disease. So one of the things you're going to see from me is I'm going to be a little bit annoying reminding people that these are very very important populations to include in these studies. And I've been told that pregnant women can be enrolled as soon as all of us goes live adults with physical disabilities can be enrolled as well but adults with intellectual disabilities can be enrolled once some of the consent issues have been clarified. And now there is a plan for children to be enrolled in the second phase. So I'm happy to say. Melissa Parisi is in the back of the room. She's also on the front of the slide and I just wanted to put her picture here to acknowledge and thank her for her help in this next section about building bonds because she helped me with a lot of the background in terms of areas in which we already interact and areas in which we can interact. And I I'm not shamelessly promoting my book because all the chapters in this book are available free through PubMed. But in conceptualizing this I realized that a lot of the last few years of my life have been thinking about where genomics intersects with both reproductive health as well as pediatric health. And in this particular book but again each chapter is available freely through PubMed. We looked at aspects of particular areas of research from gametogenesis to fertilization to implantation to normal pregnancy abnormal pregnancy neonatal health, et cetera. So it is in a sense almost the framework for the bond. Well as Eric said I'm now a proud member of the medical genetics branch as an intramural researcher. We've started a new section. It's always nice that we can we can also bring something in exchange for the home where we are being provided. So we've started a new section called the prenatal genomics and therapy section. Our laboratory's in building 35 and we have two areas of focus. One is on prenatal treatment of Down syndrome to improve neurocognition and memory in several different mouse models of Down syndrome. And then I have a separate interest in humans particularly in incidental findings following noninvasive prenatal DNA screening and I'll be touching on both of those briefly. Well just to start with the obvious I don't know how obvious it is to the council that NICHD has four ABMGG boarded clinical geneticists so Melissa Parisi who's in the back of the room myself. Denny Porter who is the director of our intramural clinical research program and Constantine Stratakis who is our scientific director. And this I mean there's a critical mass here I'm sure we're adding to the what I learned was the largest medical genetics fellowship program in the country and I assume the world. And that this should be an opportunity to look at increased ways in which we can collaborate in training and also do clinical research. And I'm hoping that at least I can participate on walk rounds because I do miss a little bit seeing patients. So Melissa helped me identify some of these existing collaborations and they're different models. So NICHD for example has funded some aspects of the ClinGen project. There are common fund projects kids first which I'll talk about a little bit and UDN which you know about. And then there's the equal model where both institutes have financially contributed to the NSITE program. This is a figure from a paper that was just published in the February issue of Pediatrics describing essentially newborn screening and the collaborative research between NSITE and the newborn screening translational research network. And I think it's kind of helpful because I know that your mission is more on the technology end and it's kind of your intramural program is pushing over towards the patient side whereas our research is more on this side trying to apply some of the technology to actual patient care but also we have a big developmental biology component. So together it seems to me that it's a very very natural bridge, natural circle where we should be able to share information and collectively advance knowledge for human health. So let's just talk about the Gabriella Miller kids first program. I don't have to tell this audience how big a problem birth defects are but the problem as a geneticist and also as a genetics researcher is that individual phenotypes are rare and many kids are N equals one. So some cohorts are really too small to get meaningful information and yet collectively birth defects are the leading cause of pediatric hospitalizations and certainly neonatal deaths at this point as well as enormous medical expenses. Never mind the diagnostic odyssey. So the Gabriella Miller kids first program or GMKF creates an interdisciplinary research infrastructure and it's congressionally mandated. So it's the common fund, doesn't come from either of our budgets but it provides up to $12.6 million a year and has now been going for a full year and a little bit over a full year and NICHD is the lead institute. So like we were hearing about with the sandbox the goal is to provide an infrastructure and a place for sequence data but what's a little bit different is that this program will also give you well-curated medical, genomic and clinical data from a large number of children with both structural birth defects as well as childhood cancers. So it was originally started to look at childhood cancers but there's also gonna be the opportunity to look at the intersection between birth defects and cancers and by the end of this fiscal year 15,000 samples are expected and the idea is to integrate just like the sandbox, different data sets in one location and then provide support for analysis and then the funds allow for new sequence data and facilitate deposition in this one place and I know that NHGRI as well as NHLBI and NCI are also involved. So that's an area where NICHD takes the lead and other institutes are involved. Now N-Site is a different model so like I said it's equally funded by NHGRI and NICHD and the goal is to explore the challenges and opportunities associated with the use of genomic sequencing in the newborn period and so there are four different programs and they are comparing sequencing with known newborn screening results and these four programs which by the way have summarized some of their initial structure, their study design, their organization in that February article in Pediatrics, they are funded through August of 2018 and so there is an opportunity, this is being discussed, I don't know whether it's written in stone yet but there is an opportunity to have a joint workshop to determine key questions for the next funding cycle so because the first iteration ends in August 2018 now is the time to be thinking about what comes next. And then there's another program now that applications have been received but it is something that also will relate very closely to some of the work being done by NHGRI and that's this new U24 program that is a genomic clinical variant expert curation panel to look at specific diseases that would be of interest to NICHD. So these would include a focus on reproductive and gynecologic health, particular mutations that might result in poor pregnancy outcomes, any conditions that are high risk in the newborn period, structural birth defects that might be recognized prenatally intellectual and developmental disabilities and susceptibility to infection. And the goal is to systematically determine the clinical significance and utility of genomic sequencing in these clinical settings and it will really partner with ClinGen and ClinVar using those tools to determine the strength of evidence supporting the clinical significance and then the final adjudication regarding pathogenicity will be deposited into ClinVar. Now, one of the things you might not think about is 15% of pregnancies end in miscarriage. We don't really know a lot about the genes that might be involved there, presumably some of those cases are due to chromosome abnormalities but particularly some of the data coming from the highly inbred consanguinous populations suggests that there are specific genes that if they are mutated affect fertilization, affect implantation, et cetera and you never see those cases clinically. So there's probably a lot of hidden pathogenicity out there that you wouldn't recognize unless you were specifically looking for it. There'll be three panels, there's a total of a million dollars a year so each panel will get approximately a third of that for three years. Quite a number of applications were received in January and they are out for review with the intent of going to the next council. Now, we also have opportunities for future collaboration. I noticed that Lisa was talking about the SEER programs. So in prior competitions, NICHD did provide co-funding and funded one SEER group and we have historically signed on to some program announcements if they pertain to topics of relevance to NICHD. So I noticed that Lisa had listed some of the topics and some of them were definitely related to work that we do. But I'd like to spend the rest of the time talking about prenatal genomics because I do see that as a gap area in both NHGRI's research as well as NICHD's research. And I'd just like to remind you of a quote from Francis Collins from a number of years ago as we learn about effective interventions for genetic risk factors and recognize that interventions early in life provide significant advantages, it will become more and more compelling to determine this information at birth. Well, I would argue that really the technology has moved such and because of industry involvement, the opportunities are increasingly appearing to determine this information before birth. And if we don't at least begin to discuss some of the ELSI issues associated with this as well as the clinical utility and significance, it's gonna run away before we have a chance to really provide expert recommendation. Now, I think part of the reason, I know that Jeff and I served on a Hastings Center panel a number of years ago. And it really hasn't changed. There are some unique channels in prenatal genomics. Now, number one is there's really no individual medical history and there's really no physical exam either. There's an indirect physical exam which is acquired through imaging. It's either prenatal sonography or maybe MRI, but it's not as good as examining a person. There's also a lack of knowledge regarding natural history of some variants. I would say, for example, I've had my genome sequence and I carry a pathogenic dominant mutation. I should have acromegaly according to that mutation. Now, I am five foot three in my high heels. I don't have acromegaly, but my mutation would certainly suggest that. So, we really don't know what you're gonna, if you find something prenatally, is it really gonna translate to pathogenicity in an adult? Now, part of that has to do with annotation, but it's even scarier when you're getting this information prenatally. I think it's a little bit different if you're doing it in the setting of a known fetal structural anomaly. There's also the problem that prenatally, you have the possibility of irrevocable action. So, you wanna be very, very careful and provide extremely well-curated information to couples who are anxious as a baseline. And then there's the role of industry and of social media, which is not unique to prenatal genomics, but it has been exploited, I would say, more in the prenatal setting, as I'll discuss in a minute. And pregnant women are extremely active on social media. So, there's this pressure to get as much information as you can about your pregnancy, and if you don't find out your baby's genome in certain communities, then you're a bad mother. And this is, I mean, I know some people in the room know this very well, but I always tell Eric that prenatal genomics is the success story of genomic medicine. It is truly transformed medical care. You can talk about neonatal sequencing, but it's not routine yet, and it's still a relatively low number of cases. The current estimates, and this is when non-invasive prenatal genomic sequencing using maternal plasma DNA, which contains placental DNA, which is a marker of the fetus, it first became clinically available in 2011, and it's just shot up. Over 3 million tests have been performed worldwide to date. The estimate is that it's available in over 90 countries. It's reliable for some of the whole chromosome aneuploidies. It's the best screening test for Down syndrome. It's also had clinical utility. The red line shows you, compared to the 2011 baseline, the reduction in the number of invasive procedures. So there are 70% fewer amniocentesis and chorionic villus sampling performed nowadays compared to 2011 because a negative result for trisomies 13, 18, 21 has a 99% negative predictive value. So most women say that if you tell them there's a 99% chance that your baby does not have trisomies 13, 18, or 21, they'll stop there even if they're over age 35. The testing is best for the whole chromosome aneuploidies and it is best for chromosome 21. The area where it starts to get less predictive is for copy number of variants. And that's a whole other discussion that I don't have time to go into today. But part of the reason why it was adopted so quickly in six years, it's truly transformed care, is the involvement of industry. So these tests were essentially, they weren't completely developed by industry, but they were certainly popularized and marketed by industry. And it's unfortunate because I mean, NHGRI at least has funded a few LC related studies in this area, but NICHD hasn't really funded any, I think they had one technology grant in the last six years. So here's an area that's transformed care and yet there hasn't been a huge amount of NIH involvement, which I think is a disadvantage because the normal checks and balances on the companies are not there. So just for those of you who may not be familiar with the prenatal sequencing, it differs from what you're used to because it's basically a counting algorithm. So DNA in the maternal blood is already fragmented. You've got a combination of maternal DNA and placental DNA, which serves as a proxy for the fetus. The fragments are sequenced, the sequences are aligned, and then there's a counting algorithm. And different, there are different methods for the counting, but the general principle is you're looking at your chromosome of interest and comparing it to some sort of reference. If you have more of, say, chromosome 21, compared to chromosome nine, it would be flagged as a possible trisomy 21. If you have less, it actually might be reported as a monosomy 21, but generally it's not monosomy 21. It's probably that there's an aneuploidy of the reference chromosome. One of the things that we're working on right now is big study showing that there's a lot more trisomies of non-target chromosomes than we previously realized, and those have clinical consequences. So 2011, the trisomy 21 test comes out every year after that more tests were ordered, and I've circled the chromosomes that are available for aneuploidies, and the arrows refer to different micro deletion tests, pink refers to the United States, blue refers to what's available in China where they're actually looking for copy number variants in chromosome 16, and one of the companies, I'm totally unaffiliated with any company, but one of the companies is now looking for copy number variants at the seven megabase level. So the concern in the prenatal sphere is can you offer whole genome sequencing in a timeline that would give clinically useful information while the woman is still pregnant, and you all know this very well. Now you're not counting, which is very quick, just takes a few days, now you're actually looking for individual base pair changes, and so you have to not only interpret that, but you have to do a lot of bioinformatics analyses, and then you have to figure out, is this a variant of unknown significance, or is this something that's actually been associated with pathology? And the ranges are enormous in terms of different labs, some labs will give you a result nine days and some two months, well two months is an enormous amount of time in a pregnancy. However, there are units now that are offering this clinically for pregnancies in which there is a fetal anomaly, so Baylor Maraca has probably the largest experience, and they are reporting a two to three week turnaround time, and they are looking for genes that are basically in OMIM, and they are reporting that they are getting a diagnosis about a third of the time. Gene DX is also offering clinical sequencing for products of conception if a pregnancy miscarried, and they have a little bit less success, but still they are getting some information. So the idea behind offering whole genome sequencing and perinatal care is that you would prenatally now diagnose a single gene disorder and then somehow have early warning, you might decide to deliver in a tertiary care center, or if there's a metabolic disease, you would have that information once the baby's born, you wouldn't have to wait a week for newborn information. You could start treatment minute one. You have a definitive diagnosis for fetuses or newborns with anomalies and a normal karyotype or microarray, so there are a number of groups now that are using this reflex mechanism clinically after the other studies have been done. The idea is you have overall better reproductive health, so once you know that there's a recessive condition in the family, you can do better counseling, you can offer pre-implantation genetic diagnosis or prenatal diagnosis in a subsequent pregnancy. I thought I'd give you one dramatic example because I suspect some of you are not clinicians and there's quite a dramatic picture associated with it, but I wanted to mention this is not work from our lab, it was actually a case reported in the, a multiple cases actually reported in the New England Journal of Medicine last year. But it's X-linked barter syndrome. So most people are familiar with the older child or adult form which involves salt wasting and a hypokalamic metabolic alkalosis with secondary hyperalphosteronism. The classical presentation, as I said, is what most people learn about, but there's a prenatal presentation. And it presents with severe polyhydramnios, meaning excess fluid around the fetus. And because of that, because the pressure on the uterus results in a preterm delivery. But it's interesting because some of the cases resolve spontaneously. So I thought I would show it because it's a very dramatic presentation. So this is actually a woman in the Netherlands who was part of this study reported in the New England Journal of Medicine. And when a pregnant woman goes to her physician, they take the old tape measure and actually measure in a very retro way, I would say, the amniotic fluid pocket. And there are normal standards, just like everything else in fetal medicine. But there are people who are way, way over the 95th percentile. So in this study, they actually analyzed fetal DNA from all of these people with this dramatic polyhydramnios. Now I should say that when we see a case of polyhydramnios, we basically think of three things. Normally the fetus is swallowing amniotic fluid and peeing out amniotic fluid. If there's a block in the esophagus, the fetus can't swallow. So that would be one reason why you would get polyhydramnios. Also, if there's an underlying neuromuscular disorder, the fetus can't swallow for that reason either, and that results in polyhydramnios. And then in this case, there's excessive urination. So the fetus is basically urinating constantly. And in these cases that were collected, it was determined that there was a distinct X-linked phenotype in a gene called MAGID2, which maps to the short arm of the X chromosome. And it turns out that the protein is expressed in the ascending loop of Henle. And this prenatal gene sequencing determined that there was a new role in fetal renal salt absorption. So this actually resulted in a very cool change of management. These kids, when they survived, were on supplements for months and years, and they were also on all kinds of medications. And it turns out they really didn't need it. And knowing that this was a possibility, particularly in a family with the positive family history, it's now recognized that this is probably one of the more significant underlying genetic causes of polyhydramnios, especially in male fetuses. So it's now recommended to test women who present with this kind of clinical scenario for mutations in MAGID2. So, you know, I'm bringing it up because we're now appreciating more and more that there are these scenarios where if you do prenatal genomic sequencing, then you actually can change management, but it's really not been a major focus. The other thing is, you know, if we're gonna be doing prenatal diagnosis, can we intervene and treat conditions that were formerly thought to be not treatable? And this is our vision for prenatal treatment of Down syndrome. So currently about 40% of women in the United States continue their pregnancies following a definitive diagnosis of trisomy 21. It varies depending on the geographic location. Remember that the plasma DNA sequencing is only a screen. If the screen is positive, it's universally recommended to perform a diagnostic procedure. The reason why the overall procedures have gone down is the majority of women have a negative screen. But for women who have a positive screen, they need an amniocentesis or CVS. And so our vision is that we hope to be able to offer prenatal treatment. And the reason why we want to do it prenatally is so much of the brain is developing prenatally. And it has been shown that starting in the second trimester, there's actually death of neuronal progenitor cells in the brains of fetuses with Down syndrome. So our hope is if we can reverse that, we can contribute to a more typical pattern of brain growth and connectivity. So the idea would be to give the mother an oral medication that then crosses the placenta and treats the fetus. So a lot of these data are summarized in this article from our laboratory, but this is some of the work that we will be doing in Building 35. We've been looking at what we've called the integrated transcriptome of, we're basically looking for common pathways that are atypical in humans with Down syndrome as well as different mouse models. And it turns out that the mouse models are very different from each other, and that's a whole other story. But comparing, notice we use microarrays because we started with microarrays a few years ago and we decided to finish the study at least till we got here, we'll be doing sequencing. But looking for common dysregulated pathways and specifically treating those pathways. And we already have proof of principle using a flavonoid, a natural compound known as apigenin which is an antioxidant. And by treating the dams prenatally, we've been able to already show improvement in memory in some of these models. Well, we heard about LC. There are enormous number of LC issues raised by prenatal genomics. A big one is maternal incidental findings and I've written extensively about lack of consent with prenatal genomics. Over three million women I've said had these tests. In many cases they are not giving consent. Their physician is consenting that they've been informed. Even when women give their consent and I've reviewed the consent forms for many of the companies, they don't specifically say that there's the possibility that something could be detected about your DNA. And the sample from the mother's blood is 90% her DNA, her cell-free DNA and 10% placental DNA. Copy number variants, Jay's lab had a paper in the New England Journal of Medicine about the problem with maternal copy number variants leading to a false positive diagnosis of a false positive result of trisomy 18.   And a big one was we've now realized that you can detect genome-wide dysregulation with these tests and it's actually a biomarker for the fact that the mother has a solid tumor. So again, the concern is that with a positive screen, a woman can take irrevocable action and that would be really difficult to explain if the underlying problem is really that the mother has a lymphoma, for example. So I just want to, I'm almost done, just show you the richness, the rich opportunities for LC research. So this is an actual case from Canada that was published in prenatal diagnosis, a 37-year-old woman who had protein, serum protein screening, which is still the standard of care, and it was negative. She was given really a lower risk than her age of having a child with Down syndrome of one in 280. But then she had an ultrasound, which showed bilateral acycloid plexusis and borderline cerebral ventricular megalae. And she was given the choice of having an amniocentesis at that point or noninvasive prenatal testing. So here's the pro band. Here's the woman. So the NIPT, the noninvasive prenatal test result was positive for trisomy 21. And it turned out when they eventually did the amniocentesis that there was partial duplication of 21Q21.1. It turns out that's a copy number variant that's outside the Down syndrome critical region, but it includes APP. So the fetus is probably gonna have early onset Alzheimer's disease. The mother, who was a healthy woman, has now been identified at being at risk. You can't make this up. She's an identical twin. And indeed, when they took the family history, there was a strong family history of early onset Alzheimer's disease. So as a result of seemingly benign prenatal screening for Down syndrome, three asymptomatic people were flagged as being at risk for early onset Alzheimer's disease. So this is just one of the many, many, many cases. So very, very rich area for LC research. So the baby, sorry, thank you for, it's outside of the Down syndrome critical region. So the baby does not have Down syndrome. That's the good news. Sorry, I should have mentioned that. Good news, bad news. So, and the other thing is obviously this, the prenatal screening is really not indicated for this woman again, because she'll always be positive. So again, I mentioned earlier that we will be increasing our listening to the voice of the patient. This happens to be a stakeholder group that was organized by one of your grantees. And I believe NHGRI paid for this in which women who had not themselves had NIPT but were directors of various patient advocacy groups gave us their impressions of how their work and their lives had changed since prenatal screening had become much more routine. So in summary, you know better than I that NHGRI's mission is to understand the structure and function of the human genome and its role in health and disease. But I would argue that understanding the human genome and the context of human development and early childhood disease will have the greatest impact. So it's one thing to sequence tumors, but if we work together earlier in life, I think that we will be able to interpret the information better. And although the widespread implementation of prenatal genomic screening is certainly the most, you know, the largest implementation, it's the largest success, I would argue with caveats. It shows us that you can't wait to discuss and develop some of these LC concepts because there's this constant drumbeat from industry. Industry, they're all competing with each other and they're all pushing technology out before clinical utility has even been shown. So there are numerous opportunities to build bonds and as a first step, we are going to convene a meeting of key extramural leaders within NHGRI and within NICHD to discuss some of these things further. So I'd like to thank you for your attention and I'd be happy to take questions. I'll just show you my first go-around at NIH. I never thought I would come back in this context but I did find this picture from the archives. Thank you. Questions, Anita? Thank you for a great presentation. I just wondered about one of the issues with NHGRI and LC research in particular is diversity and racial and ethnic disparities in terms of access to care. And I don't know this literature but it just struck me that there might be significant disparities in terms of access to the emerging technologies for non-invasive prenatal testing and other types of strategies. And I wondered if you could talk about that. Yeah, so I think that's a great question. In general, prenatal testing is testing that is associated with people who have insurance. I mean it is at the state level, although some state Medicaid programs at least until now, I don't know what's going to be happening in the future but there are some state Medicaid programs that do offer the prenatal screening, independent of who you are and what your background is. But historically, much of the screening, certainly the extended screening, things for which there's no current medical indication like copy number variants, that is purely associated with people who can pay for it. Insurers will not pay for it unless perhaps there's a rare ultrasound indication that might allow them to pay for it. But in general, it's all self-pay. So I think it's a ripe area for study. I think there would be opportunities because there are, I mean, I know that Texas, California and at least until recently there were several other states that state Medicaid programs were paying for it. And then there are other programs where there are large HMOs like Kaiser Permanente in California where there may be people who have a range of socioeconomic background. So I think there are populations available for study. There hasn't been a lot looking at that. There have been some studies looking at how the technology has been accepted worldwide, but not specifically related to disparities in the United States. I would mention that we have a new director of our Office of Health Equity at NICHE. There's been an extensive review of the Office of Health Equity. And this is one of the areas where we could certainly look at it from our end. Great talk, thank you. You look the same. So given the very nice description you gave of the challenges of prenatal testing versus postnatal or childhood, can you give some flavor of how you would balance the portfolios of prenatal versus postnatal particularly given like the example of acromegaly in yourself which might have been misinterpreted prenatally but postnatally. Clearly it's not a fully penetrant area. Yeah, so I mean, I think that's a great question right now. There's very little in terms of prenatal genomics. And I think we will, I'm sure we're expecting some applications in this new ClinVar, this NICHD sponsored version of ClinVar. So that will ideally begin to give us some information but I think there's opportunity for more because as I said I'm concerned that this is creeping into clinical care. And that's been the history. The technology creeps into clinical care before it's been adequately researched and never mind the education part. I know that ASHG as well as SMFM are really trying to help with the education piece. There's an enormous gap there where these, because there's a gap, physicians will just believe whatever market reps will tell them and that's difficult. Yeah, this is particularly a concern of mine is that bad medicine will be practiced. So for example, in the Barter syndrome case, they actually had a differential diagnosis as you outlined. Plus they had family history data pointing to the X chromosome. So they could ask a pretty defined hypothesis. And it wasn't just looking globally at the sequence. But many people are interpreting it the other way. They're saying, oh, all we need is a sequence of data where in reality, you need the clinical data to interpret this. I think that's a fantastic point and it should be emphasized that most reproductive geneticists feel more comfortable if you have the indication, which as you said, the Barter's case did. Some people would say if you have a well-defined prenatal phenotype that you see on imaging, that would be somewhat acceptable as well. But it's this, if a little bit of sequencing is good, more is better. And that's the whole question of non-invasive sequencing, which I'm sure Jay is very quiet about this, but you may want to weigh in. But should, so that's a whole different situation where you have no indication and now you are prospectively non-invasively determining the fetal genotype. And that's fraught with all kinds of issues right now. Nevermind, I mean, right now it's a little bit too expensive to do it, but the time will come, yes, Sharon. Well, just on behalf of full disclosure, so Baylor has already launched a test that involves sequencing of circulating DNA for about 100 severe genes and severe congenital disorders. And it's actually been an interesting issue with regard to indications for testing because if you know the child has severe anomalies, then one would argue you should go to more invasive testing. So it also has to do with how you launch a test has to do with the indications and then how Americans practice clinical medicine. But I think that one thing that comes up a lot in discussions about ClinGen and ClinVar is we have to be very realistic about the incredible dynamic range of our information about genetic diseases. So there are genetic diseases like hemophilia or VRCA1 where we have decades of experience and dozens of years of sequencing. And then there are newly described syndromes where there may be three papers and people often equate analyzing variants in those two scenarios where in fact your baseline dataset is so different that your ability to be predictive I think is quite different. And that's something I think sometimes when we get these variants and then like I don't know what variant you actually carried that for severe disease you don't have but a lot of that often has to do with how little we actually know about that disease compared to some other situations where we know more. Right, but the problem is that it's now being offered. So I mean there's a certain group of women who and couples actually who they want to know everything possible about their fetuses and they're willing to pay and we've seen this phenomenon all around the world. And the other thing we've learned from NIPT is women don't really wanna have an invasive procedure during pregnancy so that's part of it. I mean there are colleagues in the genetics community who will say well everyone should have an invasive procedure and a microarray or an invasive procedure and sequencing but in reality we hear it over and over again that women if it's a blood test they will have any blood test and then there's this sort of test creep where you go from the whole chromosome aneuploidy to the copy number variants to the single gene disorders to the whole genome sequencing. So I think we have to grab the bull by its horns and start analyzing but we may have already lost the opportunity but anyway Jay you gotta say something. Yeah, so that was a great summary of I think a really exciting but also fraught area and I find it just wonderful that you're heading this institute and probably know more about this topic than pretty much anyone on the planet I can think of. So the thing that, I mean like you said I think it's a great line. This is the success story of genomic medicine but it also I think provides a early, like you were saying, an early highlight of the things that can go wrong. And one of the things that's bothered me in this period of the last few years is the way that companies market these tests. I mean no one's lying necessarily but it's really coming close to the line and you encounter a lot of people. I mean some people are getting these tests that you encounter them both professionally and personally who are misled in one way or another and you go back to actually what's being told to patients and what's in the marketing and it really is depending on how you read it, deceiving and I'm curious for, I mean whose responsibility is this and especially as things go further and it gets more and more I think the fraught in such a high stakes area, whose responsibility is this? Is it ours? Is it the FDA's? Is it, you know, I just curious what your thoughts are about that. Yeah, so that's a great question too. So these are all laboratory developed tests. That's not to say that the FDA hasn't been involved. The major groups have gone to the FDA. I don't know exactly what the status is at this minute because the FDA is in transition but whose responsible will the professional societies make professional recommendations? I think the difficulty here, there's several things. Traditionally genetic tests were developed in academia and then translated to industry. So there was already kind of a set of checks and balances. If you think about collagen disorder testing for example and how that evolved over years and then translated. This is different because it just sort of came in all at once from industry basically. And so there was this gap in time before professional societies had enough information to make recommendations. I don't know if Joe wants to comment on ASHG's involvement but there are some things that have been good about the professional societies. They're almost all consistent. They're all consistent in recommending a diagnostic test. I think the difficulty was in the initial marketing when the company said it's so good, it's almost diagnostic and OPGYNs misinterpreted that. And there's still a lot of confusion in the practicing physician community about what's the difference between a screen and a diagnosis and what's sensitivity, what's specificity and what's positive predictive value.  What's the chance that this test result means that my baby is gonna have Down syndrome? And it turns out that's very complicated and medical schools don't really emphasize that. So there's an education gap. So Joe, do you want? Yeah, sorry. Just to clear, ASHG, all the time. Education, right, sorry. I don't know, Judith, do you wanna comment from ACMG? And then I'll say about it. Sir, ACMG series has been is the lower, the physical risk of the procedure, the less the patients think about the implications. So we're very, very interested in the value of the related questions patients should be asking before they even make a screening test decision. And I'm really less concerned about them memorizing a whole list of numbers to be feedback than the implications of the results and how those fit into the framework of who they are, their preferences. So I think that's a great point. And I just wanna mention that ACOG has made professional society professional recommendations as to how this technology can be used. And they're pretty concrete about what they are recommending and they're not recommending. And then the whole thing about the NIPT, NIPS versus cell-free DNA analysis, which is actually the most precise way. I have to say I slang-y use NIPT just because it's faster, but because I don't think there's, I mean, yes, screening and diagnosis are different, but there's other kinds of non-invasive pre-nail screening. So it's not, it doesn't clarify the issue where a cell-free DNA analysis does say what you're doing. So, but that's a whole other discussion, sorry. Yeah, thanks for such a wide-ranging talk. I was pleased to hear earlier today that the HGRI is renewing interest in patient education, professional education with the GLI program. And so your comments about the really critical situation with respect to patient education tools in this domain is really, from my perspective, very much on target. And so what we see out there is a lot of brochures and for the most part, they're developed by the companies. So the educational tools are poor and people's understanding is worse. So is this an area that we might anticipate your institute putting some resources in the sense that what we need here is evidence-based tools out there? Yeah, I think if it's research-based, yes, because we do research on other forms of education. But we, and we actually do have a component, it's a small component of NICHD that's related to child wellbeing education like safe to sleep, sleep on your back type of things. But I think that there's an opportunity for research in what's the best way of educating both patients and providers. And we're not so much worried about the genetics community or genetic counselors, we're worried about the family practitioners or the primary obese who really don't have a lot of training in genetics. Here we go, Carol and then Jay. Carol? Thanks for the overview, it was very, very informative. And a couple of the examples you gave really illustrate the grand challenge of interpreting genome variation and putting it into some sort of clinical practice. So I wonder if you say a few words on your vision for how to bring basic science into the functional characterization of these variants to maybe accelerate the ability to go from variant to clinical use.  So there are definitely opportunities either through individual research program grants or working with the intramural organizations to interpret some of the variations and then perhaps use experimental models. You know, we fund this enormous zebrafish facility which is just amazing, you should get a tour of it someday. So do you see the role, do you see a potential path that may be prioritized? I mean, you take in grants from basic scientists based on their research interests. Do you see an opportunity to do more, here are our high priority variants that we need to really know? Yeah, I think it's a little premature to get that specific. So I think when we have a meeting of both, I think start with extramural, but there are also opportunities with intramural to talk about, you know, are there certain things that we should prioritize? I mean, there are clearly mutations that result infertility, for example, should we prioritize that? Because that would be so central to NICHD's mission. It just occurs to me that, you know, with the massive projects that are underway or being planned, this concept of penetrance and trying to really systematically quantify penetrance seems like a really important one to get ahead of, right? Especially since that, you know, it seems inevitable that the things you're talking about are coming down the line and we will be faced, you know, increasingly with these kinds of problems. But it's a, you know, it's a solvable thing. It's something you can quantify, right? And, you know, thinking back to my first kids, when, you know, you got the report from a quad screen that had a pre-test probability and a post-test probability, and now it's gone to kind of a yes or no, right? And it seems like, you know, for many of these diseases, we need to go back to really having a pre-test and a post-test or just more of a mathematical framework for thinking about how to communicate with patients, even, as we have, right, around these issues. Good point. Yeah. Well, you can follow up. Just to educate me, maybe, Jay, what data do we need to calculate those and are we collecting it? Does I question whether we're actually collecting the necessary data? And maybe this is something we can talk about later. Because I fully agree with what, in fact, I'm extremely enthusiastic about it. Sequences and phenotypes, I presume, right? Well, yeah, but the problem is we ascertain based on disease. Absolutely. And that makes that calculation extremely difficult. Yeah, and you're going to lose the, you know, you've got to collect the products of conception, the pregnancies that don't make it to full term. I love this theory. Yeah. I mean, I think that in Emerge, we think about this a lot and everybody around this table has thought about this a lot. If you're collecting based on a phenotype, then the calculation becomes easy and I use that word in the loosest possible sense. If you're collecting based on a population and you find a variant, there is no phenotype that's driving that and then you're always left with this thinking feeling that maybe it's important, maybe it's not. I'm with Eric. I'm not sure we're collecting the right data and I'm not sure we'll ever be able to collect enough electronic health records or detailed phenotyping or whatever to couple to genotype data that is obtained without regard to a phenotype. And I guess my question is, how much of that is your institute's problem and how much of it is much more than your institute's problem?  I mean, I think an important thing that everyone needs to do is to link the maternal and the fetal records. I mean, that's a huge problem now, particularly because oftentimes babies don't have the same last names as their mothers. So, you know, in some organizations they're linked, but in others they aren't. But there's an area for, you know, a rich data set that could include placental information, for example. So it's a bigger problem than NICHD, but we're trying to do what we can within NICHD. Yeah, I couldn't agree more with the question about, you know, population prevalence and penetrance being really different than when it's ascertained through phenotypes. I think that's a really great comment. I just, I'm doing a screening project and that's a really big issue for us. But in any case, that wasn't why I raised my hand. So, your talk was just so interesting. I just wanted to point out that the CSER projects have spent a lot of time lately thinking about how to educate non-genetics-trained clinicians. And they have children in their studies as well as adults, and it just really struck me that there's possibly lots of overlap. And I don't know if you know about those, but, you know, Lucia Hindorf is the program manager and, you know, she can tell you everything. But some of them are, I think, really exciting novel technologies to educate. So that's one thing. And another is I just can't help but put a plug in for an LC branch in your institute. And, yeah, because you've got, I know you've got a lot of extra money lying around. Oh, yeah. Right, but failing that, how exciting to hear about your interests. That's just thrilling. Well, great. Well, I hope that I've, you know, gone some way towards building the bond and that feel free to contact me. Those of you who don't know me, it's Diana.Bianchi at NIH.gov. And actually this week, speaking of LC, I will be heading to the Hastings Center, we're actually meeting in New York City. But I, even before I took this position, was part of a new Hastings project that's been looking at the role of genetic testing in the prenatal period. There are a number of people from HGRI who are involved, but I was involved as an academician. Now I'm coming in as an HGRI person. Thank you. Thanks so much for coming. Like you heard Diana say, there's gonna be a meeting. I'm sure many more than just one meeting, but we're gonna have a major one fairly soon with some of the extramural program directors from each of the two institutes and think about how to take some of the ideas that you heard about today and operationalize them into something highly collaborative. And we really look forward to that. I'm sure we'll be keeping council updated about this. So thanks for coming to see us today. Thanks for your question.


contact with his body and go to the rim. Had five points and four boards at St. Francis. There's Streus and he buries his first shot of the night. Really far away from that rim. 25 against Bethune Cookman and using his right hand. Gage finding Kane. And now Jalen butts with the finish. Morgan State doing their damage all inside. Eli Kane from distance and he rattles one through. And a tough day from the floor so far. Eli Kane trying again from three. Nothing but the bottom for Eli. From the floor. Devon Gage inside and Femi. That's the point of emphasis this year, is that hook and hold down in the paint. Turn around by Jordan Little. He's in the score column. A Femi finishes on ice feed from Eli Kane. It's got to be a record in somebody's book. Might be in his. And a nice shot from his back into this game. They were sharing the ball. Jumper that time in the Chicagoland native. Martinez camera for the Bears. Ball moving nicely now inside. Streus beautiful feed from Jalen butts. From three point range from Morgan State. Underneath Paul Reed. Easy Paul for three and that one finally goes home for more. Whether it's a product of some poor shooting or a better defensive effort by DePaul. As Eli Kane fills it up double. There's Kane wide open look from three. And he buries his first shot of the second half. Davis starts on the floor as well. Devon is Prince finding the open man. Three ball and that one is good for DePaul. Devon Gage nice move. Wow. Butler lost to Keelan Martin as well. Inside Paul Reed. Nice fall rest. Media time out coming. The 12 minute mark. Schreiner nice pass inside the Max Streus. Now Coleman Lam. Schreiner with an offensive rebound. And his tip is good. Depends on what you get. Stepping in front. Flint Cameron up ahead. Schreiner, Euro step to Gage. Engage with the lead. Paul Reed nearly coming up with another turnover. This time the three is up and good by Malik Miller. Trying to weave their way through this zone defense. Another three. And Malik Miller back open. Devon is Prince and his jumper has been off the mark all night long. Morgan State's going to be able to get it back on the turnover. Stanley Davis playing the NBA for the Milwaukee Box The first round pick had a huge championship game as Max Streus for 13 from the floor tonight for Kane for those 18 points. Seven rebounds and six assists as Max Streus. Streus one on one on the freshman. Nice crossover finds the open man, Eli Kane. Knocks down with Morgan State. Four on two. Now Eli Kane trying to force the turnover he does. Up ahead Devon Gage. Down as Flint Cameron pushing the temple. One on three. Trying to finish it.


So Ken, do you think we will see something like 50% renewables or more in the electricity system in 2030? I think we might even get there before then. You know, the latest data from the Clean Energy Regulator shows that we're on course for reaching that number if nothing intervenes by around the middle of the 2020s. Of course, a lot of things could intervene, but by and large, our industry has shown the capacity to deliver the world's highest rate of renewables per capita and we're just going gangbusters in that area. Yes, we've seen a massive improvement in the economics of renewables and the competition is really on now between wind and solar and existing coal let alone any new coal-fired power stations that would just simply not be competitive but nevertheless there's issues because the more renewables we have the more we need to invest in transmission and also in storage. That's right. And so that's the areas to my analysis that we'll need looking after from a policy regulatory sense in the 2020s. Indeed, and I think this is the key issue that Australia does need a policy that aligns energy and climate targets, particularly electricity sector reform and transmission and storage are a key element of that but I think also having a policy certainty around environmental issues is also very important. And of course the big word that no one dares utter in the political sphere in Australia these days is price on carbon and so that would make for an economically effective and cost effective outcome but of course there's other ways that you can achieve relatively similar outcome with different policy approaches that could apply in individual sectors and I guess we see both major parties moving in that direction perhaps at differing speed but clearly that is the direction that things are moving in. I agree and I think you know the world is moving that way as well so Australia you know is in an international context when it comes to trade if our major trading partners are moving in the direction of carbon pricing whether it be in a particular sector or across the board then Australian export industries will obviously have to conform with that and that will then feed back into the domestic circumstances as well. So I think you're right eventually that will happen. I decided politics will have to address that and that will mean that in Australia eventually we'll have a carbon pricing system of some sort or another in the future. One of the topics that are of extreme interest in our conversations in particular with state governments but also federal governments and local communities is the transition that we will see in the energy system. So we have a very clear picture of how in the long term we will see coal replaced by renewables plus storage but of course that means less employment in particular regional localities where the coal plants are, where the coal mines are and new opportunities springing up but not necessarily in the same place and so we've seen that happen in the Littrow Valley we'll see it happen again in Victoria, in New South Wales and further down the track probably in Queensland as well. So to our mind this is an important area for future governments to look into and not just to look into but to help proactively in making that transition happen and in helping create predictability around that so that the next batch of closures of large coal fired power stations don't just happen with very little notice but so that they can happen on an anticipated time scale with time to prepare for the local communities time for companies to put in place safety mechanisms social safety nets and also for that replacement investment to be there at a good time scale. That's right I agree and you know this massive transformation that's going to happen in our economy and our energy sector in particular over the coming decades needs to ensure that nobody gets left behind particularly the people as you mentioned that are in industries that are going to transition into new industries but also from the consumer perspective the consumers aren't left behind as well so you know it's great to have the world's highest level of solar PV penetration on rooftops of 20% in the world but we want to make sure that everyone can benefit from that and people on low income should be a participant in this transition process as well as people on higher income so I think the transition social equity issues are very very important and both sides of politics have to look into that. However I would say that on the renewable side of things that because of this capability the Australian industry has demonstrated and the very rapid roll out of renewables that we could find unexpected closures of coal-fired power stations just simply because economics is driving this without a plan beforehand. So there is a clear need for governments to be involved in brokering these discussions because without it we could just find that the sheer economics of renewables is closing plants much earlier than anticipated and this could provide significant dislocation issues. It could very well do so and what we've seen in unanticipated closures is price spikes for electricity because the replacement investment isn't there on time and so consumer prices I think are very rightly in the headlines and of course part of that equation is the gas price which has risen a lot so Ken how do you see the future of gas in Australia's energy mix? Well that's another interesting question because gas quite clearly is regarded as a transition fuel by many people that you could replace coal with gas at the generator level and this would reduce our emissions by roughly half in terms of the amount of electricity being produced but nonetheless you have to look at the price side of things as well and this is where coupling to the international price on gas is an issue because the domestic price will follow that and the other thing that's coming up of course is the potential for gas to be replaced by hydrogen that's a very long term prospect it again might be driven by external factors like Japan and Korea mandating a hydrogen economy by a particular point in time and Australia being a major provider so we might simply provide them with a hydrogen they need potentially generated by renewables through electrolysis from water and this would create an international price and if we wanted to do the same thing in Australia to replace gas then we'd be price takers in that market as well so again very interesting questions following on from our experience and lessons in the LNG industry and there we're getting to a very exciting topic that I think all major parties in Australia would actually be behind and that is Australia as an energy superpower in a low carbon world so we have all the natural prerequisites for this we have the lows, the sun shines, we have the ports we have the land, we have the experience in energy markets and as an energy exporter and increasingly this is something that people come to realise this is no longer just in the universities of this country but increasingly that's a topic for governments and business Australia is a massive producer of hydrogen and higher order synthetic fuels based on renewables and the other thing to think about too is prospects for directly exporting electricity through undersea cables to Indonesia and beyond and indeed this is part of our ANU Grand Challenge to look into these prospects for exporting electricity exporting hydrogen, exporting value added renewable energy embedded in other products like refined metals so there are huge opportunities to transform the way Australia trades with the world based on renewable energy and simply shift from a largely fossil fuel based trading system coal and gas as well as carbon intensive export of iron ore which eventually uses carbon to create steel and we could transform that completely into an export industry based on renewables and that transition will inevitably happen over the next decades as fossil fuels become less and less a part of the energy mix worldwide and I think we have huge opportunities that we can grasp in this space as well and the research that we and others have done shows quite clearly that 100% renewables or close to 100% renewables in Australia as possible but there's actually no need to stop there it could be 200% renewables with the other 100% for export through the region we can be the exporter the region supplier of renewable energy indeed and why not 500% renewables if we use it to turn iron ore into steel and other products so yes absolutely and if we can arrange that in a way so that Australia actually reaps a lot of the economic benefits from this as well so big challenges for future governments in that as well that's right and you can see in the long term future that Australia is moving into a position where we can value add to all these wonderful resources that we have in this country in a way that we've never done before and potentially we could set ourselves up with a sovereign wealth fund that could see our future generations not having to worry about infrastructure and many of the other aspects of investment in our society based on renewable energy and Ken where is nuclear and all of this? so I think probably the window for nuclear is rapidly closing or is maybe closed already there requires at least a mandate from the population to make this happen this might take five years it would take maybe five years to set up a regulatory framework as well and then if you're going to build a nuclear power station on the basis that we're going to go ahead with this it would take another five years after that so we're talking sometime in the 2030s before we'd ever see something happening and by then the cost of renewables plus storage might be so much cheaper that it simply would price nuclear out of the market so I think that probably the window is closed or almost closed but there is the prospect of one opportunity arising perhaps even in remote areas which is the use of small modular reactors and these are at the scale of 100 megawatts or several hundred megawatts which are self-contained they could be used I don't know to power a mining operation out in the middle of the desert and you can add to those one by one by one just to increase the capacity so there may be an opportunity there for the social licence for us to do that I think even more importantly is the role that we might play in the international nuclear fuel cycle not only is one of the world's largest uranium producers and the largest repository of uranium in the world but also potentially to store other people's nuclear waste in the future and this was raised for example in the South Australian raw commission into the nuclear fuel cycle so we might be a participant in that we're a very stable country geologically, politically, economically there are great attractions in that sphere for other countries to make us the good citizen of the world in storing nuclear waste in an environment which should all remain in for a long time Frank I mean you know we've discussed this before that we've been in a policy free environment now for more than a decade in terms of energy aligning with climate or maybe a policy confused environment indeed so is this election an opportunity for that to change? Could it be a tipping point we might end up with an alignment of energy and climate policy that will see us into the future what are your thoughts there? Oh my, I mean industry and investors are just crying out for that for some not even policy certainty but policy predictability and stability and there is a chance, yes but what that requires is for climate change policy and energy policy to disappear from the front pages of the newspapers and once that happens some better work can be done there's different scenarios for how that could happen for how we could see the politics being taken out of these issues or at least put in the background and the policy and economics of this being put in the foreground and let's hope that might happen after this election Indeed and it'll be up to the voters in the long run and they have the choice now I guess and if they look at the opposition and they look at the government and they look at all the other parties they might see that there are differences there and I think the interesting thing and the unique thing about this election at least at the moment is that here we have one side of politics talking about policies to align energy and climate and the other side with no policy and so I think it's very unusual circumstance to find ourselves in this close to election maybe it'll come out in a few weeks but as an academic, most academics are unwilling to make a call on to vote for one party or other but when one party has a policy and one doesn't I think there's a very clear choice for the electorate


Let me tell you what it is that we want to do, what we want to do, what we want to do. So, as you are saying, let's leave it in a strategy. Let's say, who has filtration and infiltration from this place? I mean, it's not the whole group. So, that's what we're going to do. That's what we're going to do. That's what we're going to do. So, colleagues, I don't understand the whole thing. The main effort, there's a gate there. We're going to have to breach it. Execute. The gate's already cut. Do you need to find them? Come on. We're going to go ahead and post up right here. Like all locals. We're going to clear from the south. We're up to three more. So, that's what we're going to do. With a primary direction. Charlie, before going to RMP, you're going to help us.  Get to hold for other adjustments. Loading up. Put your weapon on top of things.  You're creeping out. We're moving behind the truck. Then they quickly breach for them. Then they quickly breach for them. One day, one or two. Then we'll do artillery. Then I will put another two guys. One day. The sector is secure, right? Because that's the biggest thing, right? Glad everyone know. Hey, this building has completely been cleared. Establish SDF. End state. Framely forces. Posture for follow-up operations. Civil. To minimize casualty. F-dose that can boost and support medium-special force regime. Kill, clear, and search. Establish SDF and gain food on the object. I mean a warning order. It was given 31, 13, 00, August 2022. Yes. For our state relations and the Greeks. 1800 to... 1600 to 1700. 1900. Release point. 1900 to 200. Actions on object.


Yeah, we on boss talk one-on-one one-on-one. Yeah, we gonna talk. Yes. Yeah, I held it That's that's how I did it on the thing.  You got a ear. That's all that and you mimicking but you listening That you gotta have an ear to do that man It's a lot of kids listening, but they only listen like you and they don't produce man But when you sing a song and you make it your own have anybody ever said that your version sounds way better than Oh man, and it kind of it irks me sometime because I get that a lot and it's that shout out to my boy Jason Man, if he's listening if he gonna catch this man my boy Jason say look ma'am You sing Anthony Hamilton song better than him. I say not on do that That's my boy, man. That's Anthony. How about that's my boy? I'm compared what him the most and I'm like man I don't accept that because I wouldn't be able to do it if it wasn't for him So that's how I look at it.  He never tried to you see I'm saying he understood his place. I Understand my place. Hey, man Anthony Hamilton set that tone. I matched it. Bam. We good. I'm not for the city and say I'm better than him That's the humble side and you give me homage to who you respect But at the same time people have their own opinions I can I can solve this right now. Go ahead and point of it all of it all So I do it a little slightly like I said, I make it Like this I can't stay from you too long Even if I do I'll always come Check in on you make sure you're okay And be the Underbright to know up your day Yeah, yeah, and the point of it all Is I love you And that's how I roll I can't make no decision Get back with me man. You know I'm saying I'm gonna do it too.  I'm gonna come right on in your trip. They'll live in room. Yeah, no, yeah, but I couldn't do it Yeah, yeah, now you're very talented, bro. I appreciate you. Yeah. Yeah. Yeah. Yeah. God is bless you with a gift You see this is a lot of people that yeah, they they they sing but you sing Yeah, it's a totally different thing. Yeah, and then you from Texas. See that's what really got me see. Yeah, that's it Right. So Park, Texas. Yeah. Yeah. Yeah. Yeah, that's it. That's you see this right here. Look right there good Yeah, yeah, I don't play and they say don't mess with Texas. Yeah, not at all.   I don't care where you from I'm gonna bring mine.


Good morning, and welcome to our Facebook Live event of Gregson Hall. It is an upperclassmen dorm that holds around 200 kids and students. It was opened back in 1948. It has been renovated since, so it's not that old. I actually thought it was one of the newer dorms on campus, but it's not like. Yeah, the inside has been renovated a lot. What's your name? My name is Molly Schuchlin. I am a student here at the University of Arkansas. I'm from Rogers, 30 minutes up the road for those of y'all who don't know Rogers. And I'm studying advertising and public relations here at the University. I'm about to start junior year and hopefully be done soon. Thank you. Thank you for giving us the tour. So let's see what we have here in the immediate neighborhood. Okay, so we are just right outside Gregson right now just kind of showing you what's out here and what's about. So if we go over here, we're going to see Humphreys Hall, which is the tall older dorm and it's a freshman, mainly dorm. And then we're going to have rough with quiz noses there. You're going to have Starbucks there. You're going to have a go-go, which you can go in between classes to just do a quick meal swipe and get that lunch that you need. Did you ever hit this club red? Yeah. So club red, fun fact about club red, have the best cinnamon rolls in your life. But you have to go early in the morning or else they won't be there because everyone loves them. Interesting. I did not know that. Super good. Best cinnamon rolls. I don't know where they come from, but they're really good. So you said rough and then founders and Kemple right there and then straight out. We're on Dixon Street right here. We're at the end of Dixon Street. We're at the top of Dixon. Top of Dixon. You guys are the point of Dixon. Yes. That's actually where Dixon ends, I guess. Exactly. Right here. Right here. Literally right there. Right here is going to be Gibson. It's another of our classmen dorm. And then we're going to have the music, buildings. I don't... Yes, yes. And then very through the trees, you can see the Argentine Union best place to go, especially fun fact. If you don't know this, they have breakfast meal trade at Au Bon Pan in the mornings from 7 to 8.30. Nice. So definitely check that out because you can get a strawberry lemonade, a cinnamon roll and a banana for meal trade. That's all you need. Very cool. Yeah. So we'll just go inside. We'll start our tour. Why don't we point out too where Class Plus is? Because I guess you have to access it from here. And kind of what is it? So Class Plus is a program on campus that... Ah, spider. Program on campus where you can go to get tutoring if you need it. So it's going to be, you're going to walk around to the end of Gregson and you're going to actually go down until like a basement. And you can go to class.ur.edu and it's going to... You can schedule tutoring appointments. I went to French lesson or French tutoring appointments. I've been to math tutoring appointments. They also have the SI. Some of your classes will be down there and SI is usually... It's kind of like a lab for business people. It just kind of depends on the class that you're in. And that will also be down the stairs. So it's a really good tool to use, especially since it's included in all of your fees that you pay for on campus. So you're paying for it. So you might as well just use it. Yeah, great. Okay, well thanks for pointing that out. Of course. We'll head inside. A regular bedroom and so be able to ask some questions in the comment box and then we'll show you a bathroom. And we're going to get to the basement right now. Okay. So we are at Gregson Lodge. Gregson Lodge, that was the original name of the building back in 1948. Interesting stair structure.  We're going to go down. And then we're going to go up. It's really pretty. Nice details in here. And you cannot access class plus from down here. You have to go on the side of the building. Completely separate but shares the building but not access. So you're down this way. And down this way, we're going to have like a common area where you can come hang out with friends if you need to do some homework. That's a good place to study. Super comfortable furniture. There's a TV, there's some games. Here in Gregson, this area is a very, very popular, this sort of den area. You kind of got a little library right here. You might catch that light over there. I mean it's a big space down here in the basement area. So when they say Gregson basement, what they mean is this, not like some sort of dingy basement. Not a dingy basement. Super nice basement. It has a little fireplace. Cool table. Coming here, you can turn on the TV if you need to. You can watch some movies. We have a pool table over there. There's vending machines. Vending machines, you can't use your card.  You can if you load money onto it. But it's pretty much not going to be included in any of your housing fees. So you'll have to pay for that with cash, card, or Apple Pay. So, we're going inside the kitchen. Okay, we're in the kitchen area. So we're going to have an ice machine in here. You're going to have a fridge right here. And then that's just your regular counters with a stove top. Just make sure to clean up after yourself. It is, you do share this building with 200 people. So definitely clean yourself afterwards. This is going to be a microwave right here. You don't need to bring your own. I would just suggest using this one next here because you pay for it. Molly, did you bring your own microwave for your first year? I did. Me and my roommate, we shared one. Okay, what are your thoughts? Did you use it? Yeah, kind of. But I didn't know about the kitchen until I lived in Yolkup. So I didn't know about the little kitchen until midway through the year. And I was like, why did I bring this? It's taking up so much space. So I don't think it's really, you don't really need it. And then there's just a sink where you can wash your dishes. And you don't have to bring any pots and pans. You can check that out from the lobby upstairs, which we'll show you after we finish the little basement part. Absolutely. Just remember to return them all clean. It's one of those things where like the kitchen is continually dirty, then everybody as a group gets penalized sometimes. So it's always good to keep it clean because it's a shared space. Okay. And the next fun part is the laundry. Okay. So this is the laundry room. You're going to have five washers, six dryers. You're going to have some racks over there where you can fold. Here's another folding table. So in case you all don't know, we do have a laundry alert system with all of the laundry no matter where you are. And so basically you can download the app on your phone or Android, or you can just scan the regular QR code that's going to be on the washers and the dryers as well. And you'll scan that and it'll actually tell you when your clothes are done being washed. And then if you were to be in the dryer, I'll tell you when your clothes are done drying. It's a good way to, if you're wanting to go back upstairs to study or you have somewhere to be, it's something good and useful to use. And you also do it on your computer. You can log into the website. And in case you completely forget about what I'm saying right now, it is right here on the wall. So you cannot miss it. It's a great way to get your questions on how to do it. It'll also tell you if there's one that's open. So if you don't want to come down here and you've come down here several times and they're always in use, download that and I'll tell you when one's open. And there is, it's a three-floor building and there is not an elevator. So you don't want to have to go back and forth too many times. So it's always nice to check it from the comfort of your phone. Exactly. To see if one is open before you come down. Great. So you don't want to miss anything that's included in your housing fees. So we have about seven or eight people watching. Feel free to chime in, say hello, tell us where you're coming from. Maybe you lived here in the past or maybe you're going to be living here this fall. We'd love to talk to you about Gregson. Yeah. Just ask any questions that you may have. We are happy to answer them. This is why we're here. Okay. So we'll tour. There's another kind of common areas. You can get water or you can get orange crush. And then this is a really nice vending machine right here. It's fancy. It's got a big display there. So you can get some misnots, you can get gum, you can get chips, anything like that. And then this is going to be your pool table. Like we said with the pool table, if you need any, you need to borrow the pool sticks, you're going to have to, the pool sticks are right there, but you're going to have to ask someone to borrow the stuff usually in the pool tables too.  There's a restroom right here, just basic restroom. You've seen one, you've seen them all, right?  And then right here is going to be the ping-pong table. We're going to have to go and rent that equipment from, you can just come here and come play with your friends and stuff and just make sure that you do have to fall a bit into every single residence hall here on campus.  So make sure you don't do that whenever they're coming. That's a good point. And then here's going to be, it's not a classroom, it's just a nice little study area. So we know there's a lot of girl projects here on campus. We're all upperclassmen. We all know that. So always can come here. There's a whiteboard that you can use. Two whiteboards, yeah. Alternate board and a mini whiteboard. Great thoughts will be five. Really good picture. That's funny. Was that a face? It's kind of creepy. So the good thing about breakfast are so many study spaces. So you don't have an excuse not to do anything. And then just right here is our little recycling. Bottle's only right here. Plastic, aluminum cans and paper. Fantastic. And there's some yearbooks over there. There's some board games too I saw some puzzles. Do you ever do puzzles? I like to whenever I'm like it's a rainy day but not on a nice day. Okay, okay. Or if I'm bored, you know, I really just pin it because if you get past a 500 puzzle you will not catch me doing it. Too much. So we'll go back upstairs. This is the same way that we came down so you're not getting confused. This is a beautiful staircase. I think we have like T minus 30 days until we move in. Yeah, we're getting very close to move in time. A little bit more than a month. It starts as soon as August, I believe, 11th. Yeah, so about a month or so. So this is going to be your main lobby. You'll just walk up one flight of stairs. Not a breath. Walk up one flight of stairs. And this is going to be a little lobby area right here. We're going to point out the mailboxes right here. So get an email to here at our console account though you and your roommate will share a mailbox. And you'll have a code in there and that will be what you use to get your mail. So this is just going to be like regular letters and stuff like that. Packages you'll probably get from the front desk. Which we'll show you. Yeah, we'll show you the front desk. You're right. Climbing the stairs in the hot weather. Climbing the stairs. Speaking. It's going to be our front desk right here. The front desk. Hi, how are you? Welcome to Gregson. My name is Jerry Gale. And I'll be helping you with your packages or keys, any issues you have during the day. Just come see me and I'll be glad to help you. Thank you, Jerry. What are some things that people typically kind of check out from the different desks? We have irons. If you want to iron your clothes. We have pool sticks for the and the ping pong table downstairs. If you want to play games in your downtime. Cleaning supplies. I was just seeing those vacuum cleaners behind you. Is that something that If you're a neat freak, we have cleaning supplies to check out. And cooking utensils and pans. If you want anything like that, if you want to cook. We also have game boards, movies, and sometimes video games.  Fantastic. Well, thank you, Jerry. I'll ask and we'll see what we can help you with. All right. Well, thank you so much. Thank you. Okay. So we'll keep another and this is just going to be like a hallway where there's door or yeah, rooms on either side. We'll go check out a bathroom and then a room. Is that okay? Yes. Okay. I thought there was something about this just working outside. So this is empty right now, but a lot of times we have summer camps and things like that that come in. Let me see. Let's just make sure right now. Okay, okay. Let's go ahead and we'll just pop in real quick. This is just going to be like a typical bathroom. We're going to have vanities on this side some sinks over here. You got any pressure before? Are you here? And then there's going to be restaurants on this side. Sure. I think you had a fun fact about the urinals, actually. Yeah. They're in times where we've had women live on this floor. We have used flower pots in there to make sure there's a little decoration in the urinal area. The showers are back here. We'll take a look at a shower on another floor and show that to you. It just pretty much can be like a basic shower. You know, you're going to have a changing area and you have the actual shower. Yeah. They're pretty big. I guess maybe we won't go up to the second floor and look at it, but they're fairly big. They're doing cleaning right now. They're doing your cleaning everywhere. If your room is 105, congratulations. We are too young. We're 105. There we are. Right here on the door. This is going to be a typical room laying out for Gregson. All of the furniture is movable. So you can adjust to however you may want. You're going to have desk right here with overhead tops. You're going to have three drawers and you'll have the pull-up drawer right here. And then you'll have this chair and you'll have something really cool. Okay, so no one knows this. Oh, my God. All right. It's a rocking chair. Nice. So in case you need to you have a bunch of friends in here and you need a little bit more seats, you can definitely do that. And then your bed, you can loft it. You can always loft it yourself if you didn't want to do a maintenance request. However, maintenance requests are usually easier. You can do that before you get here. So when you arrive it's already lofted to a T. You can go to housing.uogh.com You can go to housing.uogh.edu forward slash fix it. And you can put another request to have them loft your bed. You can loft it all the way up to here. I mean, you can loft it even lower than the height that you want. And if you don't put in a maintenance request, we have rubber mallets that you can borrow to do or we suggest bringing our own just because there's so many people trying to do everything it might be easier to do that way. The question that comes up a lot during is should we bring a dolly? And I would say that very much like the rubber mallet we do recommend that you bring a dolly. I mean, you'll know how that works the best. We do have some limited dollies that you can borrow but there's a lot of people moving in pretty quickly so it's always best to bring your own. Yes, everyone's trying to move in. Three drawers right here that you can use for dressers right here. We'll show you this one. You can put your towel right here after you get done in the shower.  It goes pretty deep in here. Pretty good closet space in here. You're going to hang anything up. You can put shoes and stuff up here. It's a pretty good closet size. You know, you don't need a whole lot. There's also the up above. Yes. So there's an upper-head compartment up there. Short. I don't know if for you it is. You know what? There's an overhead thing though. Right. It's meant to be used by you. Yeah. Okay. Well, are there any questions about Gregson? I know a lot of people who are trending in have probably either lived in Gregson or, you know, you've been on campus already one year so you know a lot of what's going on. So I don't necessarily expect a lot of questions but if you have them now is a perfect time to ask them because we are happy to help. There is a really good view off these ones. The best thing about Gregson is there's so much natural lighting that's coming in so it really feels cozy and happy. It's a good place to be. It's really center of campus. You don't have to walk up many hills. Very few like baby hills maybe unless you walk up Dixon Street and bless your heart you're going to get a good like workout. But other than that it's perfect location. What's a good place to go? What's obvious my personal favorite is a Chinese Asian kind of food place. You can get sushi there. The Razorback Roll is really good. It has tempura shrimp tempura and it's called the Razorback Roll. Super good. They also have California Rolls for all you basic people. Chicken fried rice there's also a really good restaurant. And then of course you have a place called Chipotle which we all know up. Chipotle, Kadoa, Rady Costa Street nothing but some good business right there. There's also the campus bookstore we have one on Dixon Street. That's not actually affiliated with the university. There's a bookstore there. The university bookstore is at the corner I believe Douglas and there's some good shops over there there's Southern Trent there's Elyse which is my personal favorite and you're really not too far from downtown. You just go on center street once you get down Dixon kind of where our safe is where the Walton's Art Center is and you'll take a ride. Very nice thank you. Well if there's nothing else and no questions we'll just go ahead and sign up. We're also going to be doing tours later about how to move in how to prep for tech so make sure to tune into those as well. See ya.