This morning there will be a few little changes as there always are in our programs and a couple of I hope interesting surprises along the way But not in Rick's session Rick session is as built Thank You mark. Good morning everybody to Quick introductory comments, and then we'll be introducing our speakers The first is it when Mark asked me to organize the panel I got excited because there is I think a groundswell of activity in pediatric ethics It just was not here in the late 80s when I was training here in Chicago. There are several Pediatric ethics programs around the country that are uniquely Dedicated to the questions that come up in the health care of children So I'm excited to have a panel that looks at that relatively new development the other piece of that is the second comment the Future-looking nature of the title The the panel as a whole is called what is the future of pediatric ethics? Biowethics has always had a tendency to try to stay ahead of the courage to look toward the future without necessarily Thinking in terms of a crystal ball because none of us have a crystal ball But I think part of our job in biowethics is to anticipate what's going to happen So I'm really excited to have for the most distinguished pediatric ethicist in the country here to Think a little bit about the future of that field our first speaker is Roman Faust and the MPH Norm has been at University of Wisconsin since 1973 and I have to say that in the 1980s when I was a medical student went to Madison spent a very nice month with He's a professor of pediatrics and biowethics director of the program in medical ethics and he founded that program in 1973 he is vice chair of the department of medical history and biowethics, and he is a general pediatrician He's been chair of the ethics committee for 24 years and chair of health the health sciences IRB for 31 years a Variable font of wisdom and experience He was director of the Peds residency training program for 20 years And he founded the child protection team, and he was vice chair of the department of pediatrics at the home of the Badgers For 10 years from 1985 to 95. So please welcome Roman Faust Santiana said those who do not study history are doomed to repeat it in newborn screening It doesn't really matter though whether you study history. It just keeps getting repeated anyway So I'm going to Review some of this history, which just keeps happening over and over again As Yogi says it's hard to predict the future But I think that's not right. I think Dr. Phil got it right When he said that the best predictor of future behavior is past behavior pretty much everybody has said that and So I'm going to just briefly discuss the past behavior of newborn screening and give you a very current example to show that the Problems just keep happy the same exact same problems keep happening. So I'm going to say a little bit about the PKU story, which was the first newborn screening program and then some brief comments about some non-genetic screening programs Involving by carbonate oxygen and bilirubin say more about that and then a brief summary of Wisconsin's experience with a rare disorder called embed and then make a prediction, which is not going to be very difficult So PKU as most of you know is a very rare inborn error of metabolism causing profound retardation Virtually all affected children in which phenylalanine, which the amino acid that's ubiquitous in protein gets turned into lots of good stuff in the body But if you have this disease that enzyme is deficient and instead the phenylalanine accumulates and turns into bad stuff that causes brain damage and other problems This was well known for almost a hundred years and It was known that if you put children on a low phenylalanine diet, phenylalanine diet would ameliorate the brain symptoms But the diagnosis was inefficient. It depended on getting a urine sample from infants at their first-world baby check Which was inefficient and too late children who were on milk even for a few weeks had irreversible damage The diet was very expensive and unpalatable and hard to comply with In 1960 there were three big breakthroughs Robert Bethry discovered an ingenious Test that was cheap simple sensitive That made it possible to diagnose this condition for the screen for it For every newborn on a single drop of blood Second the me Johnson Corporation developed a milk called the phenylac that was more palatable and affordable and third John F Kennedy was elected president with his interest and stamping out mental retardation and Kennedy and Guthrie and a handful of others formed a PKU lobby to create a mandatory newborn screening program Which was initiated without any systematic studies about the test characteristics or about the diet The assumptions of the PKU program were that a positive test Confirmed by a whole blood assay would lead to mental retardation in nearly all cases and second that a diet With reduced phenylalanine would reduce the severity or possibly even prevent mental retardation Program had two problems first the first Assumption was false and second the second assumption was false other than that it was false It turned out the test was one of the worst tests ever devised that had a 95% false positive rate It is a positive Guthrie test gives is 20 to 1 likelihood of being normal And that's even when confirmed by a whole blood assay that is having hyper phenylalanine In most cases is of no clinical consequence And second it turned out the dietary restriction Is as harmful as dietary excess withholding this essential amino acid means you can't build proteins in your brain or anywhere else in your body The consequences of these false assumptions was first a false positive impression that the diet was working It was in some cases But there were many normal children enrolled in the program and they turned but you didn't know they were normal They were labeled as having a disease. They turned out to be normal everybody said fantastic The more serious problem was that some of these normal children were made retarded by the diet because of excessive restriction of phenylalanine and in rare cases Profound protein malnutrition cases at quashioca began to develop in these clinics and there were some deaths The number of children who were harmed by the program of normal children is not known because this was not being studied in any systematic way It was one other late surprise, which is that the girls who were successfully treated Went on to reproduce in the normal Rate and we're back on a normal diet So they had astronomical levels of phenylalanine in their blood which exposed the fetus to profound Terrigin is probably the most potent heritage known to the human organs Virtually a hundred percent of such babies are profoundly damaged We have a mother in medicine who's now made three such infants So what are the lessons from this story? That keep repeating first genetic disorders or heterogeneous There is no such thing as a single gene disorder not sickle cell disease not cystic fibrosis There is just one mutation for sickle cell disease But the fact that children can die an infancy or can live to a ripe old age Cystic fibrosis as we know as a thousand diseases not just one So when you screen for a disease with a phenotypic test like a chemical assay you're going to wind up with a Hodgepodge of different disorders and therefore treatment programs are going to have different risk-benefit Ratios for each child point one point two new screening programs, which are proliferating Our experiments are should be thought of as experiments Subject to clinical trials or at least systematic scientific studies with the usual protections of institutional review and high standards for consent There is no FDA for newborn screening So anyone who has an idea can just start these things if you can get it through committee or two third we learned that mandatory programs are hard to stop when the Problems with the PKU program that I described came to light and it took a decade for these to be elucidated Nobody wanted to stop routine screening other than the state of Maryland Which was the only state which had enough sense to slow it down and reconsider And the fourth is that zeal clouds critical thinking zeal of course is essential for progress all great Accomplishments are usually the result of one or two zealous and I mean that in the best sense of the word But zeal is not the same as critical rational thinking so that when the American Academy of Pediatrics Committee on Nutrition in 1965 sent a letter to the secretary of DHHS Then DHEW urging that the mandatory PKU program be stopped because we didn't know the significance of a positive test And we didn't know what the right dose of the diet was it was suppressed And the programs continued and it was seven years later before some of these facts that I mentioned began to attract water retention There are many other examples of screening newborns for treatment not all genetic Just quickly three examples that collectively have harmed I would say conservatively thousands and probably tens of thousands of children Prematurity the most common cause of death and children which causes lung Dysfunction high lung memory and disease or respiratory distress syndrome carbon dioxide retention Acidosis and death if not treated was quote solved by a Leader in the inuitology who said oh, this is no problem. There's too many hydrogen ions Just give a buffer by carbonate that'll combine with the hydrogen ions and produce carbonic acid Which will turn into carbon dioxide and water the water will get excreted and carbon dioxide will get exhaled My mentor and colleague Jerry Adele said this is nonsense just with a pencil and a paper This is nonsense. This will create more carbon dioxide, which is nowhere to go and produce more He proved this in a rat that by carbonate made the problem worse But every single newborn with this disorder in North America got by carbonate for a decade or more Until another disciple of dr. O'Dell's Mike Simmons published a landmark study unethical studies that is withholding standard treatment from affected newborns because it had never been proven effective and Mike Simmons showed that in fact by carbonate made you worse and of the that's the mortality It was higher and of the children who survived There was a very high incidence of massive intracranial hemorrhage because this is a very concentrated Osmotic solution that sucks water out of the brain and makes the brain shrink and lots of vessels rupture There hasn't been a baby that's received by carbonate for this condition in 30 years But for a decade everyone got it. This is that his children this subpopulation was screened and treated with no systematic studies Oxygen for a hundred years was given indiscriminately to new warrants who were blue They were screened with a simple inspection test you looked at them and if they were blue you gave them oxygen We learned to refine that with expensive technology and actually measure the oxygen But we still gave that is the level of oxygen, but we still gave indiscriminate oxygen for 80 years Until Arnold Patz one man at Johns Hopkins began to wonder why so many of these babies were blonde And found that the oxygen was a major contributor to retinal fibroplasia or retinopathy of prematurity So finally studies were done to an oxygen was treated like a drug and dose response curves were figured out We now know what's too much and what's not enough that we know how to measure This was a screening program The subpopulation with treatment with the hypothesis that it can't possibly be harmful because it's just a natural substance That's available everywhere I'm going to skip the billion room story because of time problems So screening for treatment is now a phenomenal growth industry the American College of Medical Genetics in 2005 recommended it in 54 tests to the newborn screening panel because of the Advenaptendant mass spectrometry, which made it cheap and easy to screen for 50 or 100 However many tests you wanted on a single drop of blood of these 54 tests that they recommended 25 produced abnormalities that were not too Known to cause any disease as they were simply abnormality and abnormalities Biochemical abnormalities and nobody knew what the clinical significance was but they recommended testing for 24 of the tests They were known to be associated with disease But nobody knew what the sensitivity or specific for city of the test was how many false positives false negatives and the treatments for these disorders were largely untested Yet the National Institutes of Child Health on the recommendation of the ACMG panel Same chair of both panels recommended supported this recommendation to add these tests to newborn blood squads I want to just give you one example of the consequence of this recommendation Here's a disease called M-Bed. It's an extraordinarily rare disorder of isoleucine metabolism Causing severe mental retardation failure to thrive seizures and death By 2004 there had been eight cases in the world Wisconsin in 2001 pioneered and became first aid to start screening for M-Bed and in four years Wisconsin discovered 23 cases Well, you say that's great. I mean here's a screening program that's picking up this what was thought to be a rare disease The interesting part was that all of the cases were in families of mung descent As an essence of one and two hundred births We should make it one of the most common maybe the most common genetic disorder other than maybe sickle cell disease Fortunately for these children their parents didn't believe in Western medicine We had no interest in complying with the recommended diet and none of these children received any treatment Five to ten years later now close follow-up these children show that they're all normal one has a mild speech delay Which probably has nothing to do with the metabolic abnormality? None of them has been on the diet as I think I said Compliance was not poor.  I think if we keep doing it. I think in a thousand years. We'll probably find a case And that child will get on a diet and will be helped But in the meantime Thousands of children will be falsely labeled some will go on this diet for life And who knows what the complications of that will be This is exactly the same problem as the PKU problem an assumption that this was a homogeneous disorder That a single test could detect Very zealous political advocates to stamp out these rare causes of death lobbying To have it tested for no scientific studies. No systematic review. No standards for informed consent and This now is going completely out of control and will be the subject of I think any roses talk Because as you all know the genome project has now identified a thousand or more genes associated with Disorders with their diseases or not is uncertain conditions whose natural history is unknown Conditions for which the benefits and risks of treating the phenotype are unknown Gene therapy, of course is still a dream We know what the basic defect in sickle so disease was since 1945 there hasn't been one extra unit of progress and finding a Molecular based treatment for that and yet the National Institutes of Child Health in 2005 sent out a request for proposals to figure out a way to screen for these thousand conditions with a single micro-arrange it so that I Almost no doubt that that's going to happen and Every parent in the country will get a letter in the mouth saying congratulations Your son slash daughter has two hundred and seven recessive conditions and eleven dominant conditions We have no idea what this means or what to do about it, but have a nice day And by the way your pediatrician won't know any more about it than you do In some way I think the future of newborn screening will be like the past and present with newborn screening that new tests and treatments will be Introduced with little information on test characteristics the natural history of the disorder or the safety and efficacy of the interventions Many children will be harmed from false labeling and stigmatization and in some cases harmful treatments Some will be helped. We just won't know who they are. We just won't know who really had a disease and who didn't And so when normal healthy children come out of this program, it would be very difficult to know if they were children who were destined to be healthy Anyway, and simply survive the treatment. Thank you very much Thank you Professor Faust our second speaker is Mark Mercurio Mark is the director of the Yale pediatric ethics program associate professor at Yale University School of Medicine and a neonatalogist at the Yale New Haven Children's Hospital He's coming up to the podium. So I will abbreviate his Introduction. No, no, that's fine. I'm not sure this crowd knows you as well as they might So let's just take another minute to tell you he's the director based on a true story Medical ethics courses for the physicians associates and pediatric residents And he's a member of the executive committee for the Yale University Interdisciplinary Center for Bioethics his academic work is focused on ethical issues in pediatrics particularly in the newborn period and Mark's title Is the future of ethics in neonatalogy. Please welcome Mark Mercurio So does anybody here remember Al Spangler? Nobody here in Chicago So Al Spangler was a base. He came to mind a few minutes ago Al Spangler was a base. I grew up in Chicago and he was a baseball player on the Cubs He was not a remarkable necessarily remarkable player. He had zero. He was a nice guy. He had a zero home runs so as The story goes at one point he was standing with Ernie Banks and Willie Mays and said, you know something guys between the three of us We have over a thousand home runs and I thought of that when when Mark said that we have here the collection of some of the finest pediatric Bioethics in the country and I thought as the Al Spangler of the group and he was saying absolutely we do So I'm here to talk about the future of Ethics in neonatalogy Interestingly enough just this month the AAP vision of pediatric 2020 task force published a paper about The future they identified eight mega trends and I thought that two of them were interesting and in keeping with what I wanted to Talk about today one the dynamics of the pediatric workforce and the other about ongoing medical advances They also discussed what they called wicked problems, which has kind of a nice New England sound to it So I thought I'd bring it here as a tribute to John Parris So a lot of people don't even know what I look like without the beard But this this was And this doesn't help So the pediatric workforce back in the day when I was training in neonatology in particular This is a this is what most not all we weren't quite this handsome But this was your pediatric workforce and your neonatology workforce in particular, but we can do better than this This these are the fellows the neonatology fellows and first-year attendings at Yale University And you'll notice that they are all women and this is a huge trend in the pediatric workforce to be sure Over the past generation and we'll be into the future it would seem And certainly in neonatology and we've seen this shift. So what does this really have to do with anything ethical? Well, I don't know will this have any effect on the way ethics is done in the future and the answer is maybe The picture on the bottom is a Rosalad who's a philosopher at Brown University in recent years and she was one of my mentors and she got me to Stop thinking just in terms of principal based ethics and to think more broadly and introduce me to the work of Carol Gilligan among others who in 1982 had written the voice and that's Professor Gilligan on the top slide wrote a book in a different voice and In this book she pointed out that it would seem at the time based on her work that young women Did ethics if you will differently than young men That the emphasis was more on relationships and less on a principal based approach and the emphasis was greatly on Decisions within the social context Now where those findings truly valid where their nature versus nurture are they relevant today or in the future? I'm not here to tell you. I think it's an interesting question though And we consider the future of ethics in neonatology because if I walk into the ICU and ask myself What's different from the past? What's different is that the young people in charge are nearly all women Is that going to affect the way ethics is done in neonatology? I don't know it's an interesting question though the work of Carol Gilligan and many others suggest that it that it might So that's one thought on them on the megatrends. The other was the new technologies that I wanted to mention on this they identified Wicked problems and said these are going to be messy multi-faceted and multi system There will lack clear-cut solutions and are insoluble by conventional means Well for pediatric ethicists, and I suspect from all this is this is just another day at work But they had commented in the AAP a comment that this is going to require ongoing in-depth dialogues Or permanent strategic confrontations that confront status quo assumptions to which I say amen I Think that the status quo or the standard of care has stood to be a Tremendous enemy to not just progress, but to ethical evaluations The way that it's the status quo and I think no one touched on this a bit to the status quo reaches a certain Elevated exalted status and it becomes very difficult to get away from I Would suggest to you that this in medicine not just in ethics But in medicine we have the standard of care and we say that for this particular treatment And when we're deciding about pharmacology, there's a standard of care I would suggest that our obligation To adhere to that standard of care the strength of that standard of care is based on the evidence that supports it specifically Though if there are randomized controlled trials if there are no decent trials are there at least Good physiologic reasons to believe that would be the appropriate treatment There's an analogy to be made not a perfect analogy, but an analogy to be made with ethical issues I would suggest to you that the standard of care with regard to ethical questions in pediatrics Should we resuscitate this group of patients? Should we provide this technology to this patient that the standard of care? Is only as strong as or should only be viewed as strong as the ethical reasoning That stands behind it and so often the ethical reasoning is based simply on well here. We see this is the Yale Symbol here looks at Veritas. I put that there for those of you who read Latin looks at Veritas means because we say so and and That unfortunately is so much of what the standard of care is built upon I Think what the future holds? Hopefully what the future holds is communication evaluation and consensus regarding the use of new technologies and old ones and Considering the ethical reasoning a rationale behind use or non-use of a given technology and a case in point specifically bringing us up to the present over the past couple decades is ECMO So this is a study done by our group I was the senior author on this but the all the other authors were the ECMO team at Yale We surveyed all ECMO centers in the Yale cell registry. So everybody who's doing ECMO 81 of 124 centers responded And we found out many things about what's done and a tremendous disagreement over some of the basics What's the lowest gestational Asia it's safe to do ECMO at or would you do ECMO? Tremendous disagreements. The patients who have had an intracranial hemorrhage. Are they still candidates for ECMO? No consensus. How much of these things actually been discussed? Somebody set up standards way back when and the standards some people follow them some don't But with regard to ethical questions among the other questions we asked in this survey was how often would you seek to override parental refusal of ECMO for a neonate you feel is likely to survive with a Favorable neurodevelopmental outcome if he received the proposed treatment. This is something seems to me like a fundamental ethical question So if parents say no and you really think ECMO is the best thing for the child, how often would you seek to override it? So this is what represents the consensus. I don't know if you can read it. That's never rarely sometimes usually or always This is ECMO as is currently offered in in mainly in the United States where most of the centers are but in the UK and elsewhere As well you can see that the never or rarely group is almost the same size as the usually or always group There is no consensus on this There has been no discussion of this So the future of ethics in neonatology holds if we wanted a Discussion about this question a discussion about new technologies in general not just what they should cost or how we should plug them in But a discussion about when they should be used and about how they should be applied in ethically murky situations Now for the bad news The big problem in ethics in neonatology borderline viability that will still be with us It's an old wicked problem, but it's not going anywhere Just two months ago the ICHD neonatal network, so 21 major academic centers in the country Published recent data and showed us that survival at 23 weeks was 26 And survival at 22 weeks was six percent So this shows us kind of where the edge of viability is for these newborns Now the line may move it may not move but what to do with the edge is going to remain a difficult question and when we need to face What i'm hopeful for in the coming years is that we will address openly and consistently the self-fulfilling prophecy So not long ago when trying to figure out what to do about this I talked to a colleague from another center a Break guy and I asked him. What do you guys do about 22 weeks? I said, do you guys resuscitate at 22 weeks? And he said no, we never do I said, oh good someone's thought this through and figured it out. I said, well, why not? He said because we've never had a survivor Hey, you can use that argument at 26 weeks So Here's the fascinating question at 22 weeks for example or 26 weeks at 23 weeks 26 survived But mind you they tried to save two-thirds of those kids 68 percent At 22 weeks only six percent survived But it was only attempted resuscitation was only attempted in 19 percent It doesn't make sense to say it doesn't work Because we don't try therefore it doesn't work This is not limited just to extreme prematurity and by the way just as a point of information There are still centers many in the united states that will tell people it's impossible to survive if being born at 22 weeks I'm not here to tell you that it's likely Or that it's advisable This is a whole nother talk as they say We could get into that except to say that when we say it's impossible when we say That it simply ignores the fact that it's only impossible if you've never tried For those who try it seems like it is sometimes possible Moreover by the way in japan Where they are very aggressive at 22 weeks to survival for a large series multicenter series was over 30 percent Doesn't mean it's the right thing to do It means that for us just to say it's impossible is fundamentally wrong and dishonest But the problem is not just What about the edge the problem is also about just using gestational age John tyson and the network showed us in a paper published a couple of years ago That we shouldn't just be talking about gestational age because that's not all that predicts how these kids are going to do The girls do better than the boys bigger kids do better than smaller kids Singletons do better than multiple gestations kids who got antinatal steroids Do better than kids who didn't So what we find is that on the left you see a boy who's a twin who didn't get his steroids His chance of survival is nine percent If he's put on a ventilator, which kind of gets to the question of the self-fulfilling prophecy a bit It's better. It's 14 percent his chances of survival without neurodevelopmental impairment is only three percent Now on the right you see a girl who's a little bit bigger, but she's only 22 weeks Her chance of survival is 11 percent But if she's put on a ventilator and remember that the vast majority of kids at 22 weeks No one even tries If she's put on a ventilator her chance of survival is actually 30 percent Chance of survival without neurodevelopmental impairment Is 11 percent You can see that there would be a fundamental injustice for us to tell the parents At 22 weeks Resuscitation is not an option for this girl, but at 23 weeks. It's an option if you want it And the same thing holds at the other end at 24 25 weeks that if we just use gestation age alone There will be a fundamental injustice because kids who actually have a better chance of survival will be denied that chance Or you could look at it the other way and say parents suffer an injustice because at 22 weeks Those parents were given a choice At 23 weeks they would as well, but as we get to 24 25 weeks Where do we no longer give parents a choice and just say the resuscitation is obligatory? We run into the same problem where we remove parental preference We remove their control. I think in an unjust fashion as well So hopefully as advised by john tyson and others we will move beyond gestational age when we have these conversations Now we're going to have the same problem, but with different diseases trisomy 13 and 18 has entered the conversation And the next decade will be big in the conversation These children Almost never survive past the first month of life some do most don't The question is raised. Well, they're not survived because we don't try to save them often. They have heart disease such as vsd What if we tried to save them all it's the fundamental question when parents ask you whatever a diagnosis is What are the chances he could survive? they're not asking The fundamental question they're not asking what are the chances he could survive if you didn't try anything They're asking what are the chances he could survive if we tried everything we knew how And just because they're not savvy enough to ask it by the way Doesn't mean that we're not obligated to try and address it even if sometimes the answer is i don't know Well, the question that has come up again and again. You've got to be kidding me too It's okay the question has come up again and again is trisomy 13 and 18 These kids are going to have significant major major cognitive deficits. Should they be offered? Cardiac surgery some centers do it and some don't when I raised this issue with a large leadership group in neonatology One of the common responses was can we please just not talk about it? Let's just stay away from this Why does neonatology get a separate session when we're talking about the future of ethics in pediatrics? I don't know but thank you in any case I would say that perhaps one reason is that this is one group where people are still arguing over whether or not our patients are persons Regardless of their mental Of their future mental status their current mental situation It occurred to me some years ago when I encountered a case of a child who was Two months less than two months old. This child had a terrible terrible Congenital defect and was predicted to have profound cognitive deficits forever Was in a function at the level of a two-month bullet the best et cetera and it was determined that it was acceptable to withhold Artificial nutrition and hydration in that setting Not long after that a conversation was had about a girl who was older Maybe six or eight years old who had the same deficit who came in with a pneumonia And we're talking about what should or shouldn't be done and I asked the question years ago as a lad Well, are we going to offer the parents the option of withholding artificial nutrition and hydration? People looked at me like I was crazy This kid has what you're afraid the other kid's probably going to have but for the baby, it's acceptable But for the older kid, it's not It's fascinating There and there's evidence to show which we don't have time to get into That people see the lives of a newborn particularly the pre-term newborn as in some ways more optional Resuscitation for example with the same prognosis is considered Less obligatory in the newborn than it is in older kids. This has been shown I think some people in the audience have taken part in these studies Years ago I wrote on the question of saving versus creating Is it because when there's an older child who has a near drowning in a swimming pool and has major neurologic deficit We think that that's a child that we are saving But in the newborn unit when there's a child who's born and has a severe cognitive deficit That that's a child that we're somehow creating we take more responsibility for it's a fascinating question This is a fundamental question that we're going to get to and in this decade if I want to be an optimist and why not This is something we need to talk about the moral status of newborns as compared to older children We've been talking around it and around it and I will tell you that good Academic neonatologists will say I tried to talk about this once with some with the ethics committee And they wanted to talk about personhood and stuff like this. Who has time for that prayer? Well, we need to take the time So finally What's going to happen in the future in the future in many ways clinical ethics education Is going to come of age the first generation is going to come of age Most members of my generation who are now The leadership positions in academic medicine and in clinical medicine in general are held by people of my generation Some a bit older some a bit younger Most of them had no real ethics education in medical school. Some did but most did not But for many years now we have been teaching clinical ethics And that in the future those who are exposed to this These people who has residents and this I come to the mecca of clinical ethics education That these disciples now will be in charge I think what should come of this if we've done a good job is that ethical analysis Of clinical problems will become increasingly accepted It'll become something that everybody buys into as part of the natural Discussion part of the essential discussion of the cases we consider if we've done a good job If we've just turned them off to the whole subject, it's not going to make things better or worse It's not going to make things better. It will make them worse One other question about ethics education Is could it make things worse? And I would say the answer is yes, it could Yes, it could make things worse and here to tell us why Is alexander pope who tells first of all that there's no substitute for a good head of hair And I'm not sure that's really his hair Um and who said and we read it in high school That a little learning is a dangerous thing He was talking about the period spring where our all knowledge comes from in greek mythology A little learning is a dangerous thing Drink deep or taste not of the period spring There shallow drafts intoxicate the brain While drinking deeply sobers us again The risk in doing ethics education is we give ourselves and our students shallow drafts We need my friends to drink deeply And we need to drink deeply together and with our students And then I think ethics education as those who have been exposed to it take over not just this I know I'm preaching to the choir or if we're talking about drinking deeply Maybe I'm preaching to the fraternity here, but The point is that those who don't come to ethics conferences They need to see this is a fundamental part of their job and they need to have To go on beyond the surface to go on past the four principles, which I think are marvelous in which I teach But we need to drink more deeply With our students that's the future and I thank you very much Thank you very much mark Our third speaker is lanie ross ladies the carolin and matthew buxbaum professor of pediatrics here at the ufc And uh, she is uh currently serving on the secretary's advisory committee on human research protections Finally known as sacroop the american college of medical genetics social ethics and legal issues transplant committee and the ethics committee of unos the united network of organ sharing Lanie is going to circle back to the topic that norm began us with a very important one in pediatric ethics the future of pediatric genetic testing Thank you lanie When I thought about what is the future of pediatric genetic testing I asked myself and the answer is Newborn profiling and this is actually a great thing for the future of pediatrics because all of the people who are adult doctors You also have to think about it because before we do newborn profiling. We're going to be doing profiling on adults So what is genetic profiling it's actually the analysis of your entire genome in order to reveal the majority Of your genetic variations and it can be done anytime in the life cycle In fact 99.8 percent of all of us have the same genetic information And what we're going to be focusing on is that 0.2 percent where we're different and those are called snips And you get some small variations for when you have three billion base pairs and 99.8 percent similarity means we have about a million differences Currently only two famous people actually have their entire genome published and they are dr. James Watson and craig mentor We've actually done about six or eight of them in the whole world More will be coming. This is a graph that actually shows the timeline when we first started the human genome project And it was launched. It took three billion dollars to sequence But in about 2007 we were able to do it for about several million and the plan is by 2010 2012 We're going to be down to about 5000 and everyone talks about the future being the thousand dollar genome Newborn genetic profiling is not newborn screening Norma suggests that this is the future of newborn screening And it may be but newborn screening as nor has shown Identifies both genetic conditions as well as non-genetic conditions hypothyroidism and it's gone beyond that it's doing here in screening And most recently there's even been a suggestion for example of doing cardiac testing in the newborn period Newborn screening at least prior to tandem mass spectrometry, which is what norm focused on focused on conditions for which early diagnosis Reduced the risk of morbidity and mortality Newborn profiling actually is not going to just be looking for diseases It will discover some uncover some diseases some that will present in childhood some that will present later on But it's actually focused on looking at genotypes and not phenotypes So it's trying to look at all of our variations and how they may interact How they may lead to disease but how they may also lead to many other aspects of our lives Some things that we might call recreational genetics Whether we're the type of person who's thrill-seeking and things of that sort And what we need to know and it's actually true in disease genes But also in all other genes is that genotype does not equal phenotype meaning that We're going to learn a lot about genetic variation normals 100 right? There is no such thing anymore as a simple Mendelian condition Newborn profiling is also not the genetic multiplex testing that already exists on these Gene chips because again those are focusing on rare conditions But what we're really looking for here It with a multiplex testing is again looking for very specific genetic mutations By contrast genetic profiling is going to focus on genetic mutations whether or not they're associated with health So what will the newborn genetic profiling look like? It'll be mapping all of three billion base pairs of children at birth Probably using the sample from the newborn blood spot at right now It's going to be a real investment in time and money But that those costs are going to decrease and it is going to be less than a thousand dollars within the decade The interesting thing is that will make it that will no longer actually store newborn blood spots We will actually just do the entire genetic profile and we'll store it in a database and storing three billion base pairs Will cost cents and so once you've done the test it'll be there and it'll be there for the rest of your life And that actually raises huge issues of who's going to be able to open it for what purposes and things of that sort So what genetic profiling will not be here's a cartoon as you can see from your genetic printout You only think you're depressed whereas you are in fact a jolly happy full of joy spring type person That's not what genetic profiling is going to be It's not going to be able to predict health or behavior. It's more likely to be able to describe propensities We're going to be talking a lot about odds ratios. We're not going to be talking about diagnostics That we're going to come to understand a lot more of the role of other factors including social economic and environmental factors And our understanding of these interactions right now are at a primitive level And that's going to be my one caution because we are talking about newborn profiling But we really need to be thinking about it in the adult world. We should have adults as our research subjects first So what are the benefits of profiling the first is I've already pointed out We can generate this data one time and it'll be cheaper in the long run It will not require getting repeat samples and it can be stored quite cheaply It will allow us to understand much more fully the genotype phenotype correlations and of genotype environmental interactions at the society level So right now we know that there are over 1600 mutations in the cystic fibrosis gene And we know that some of them are quite mild and some lead to pancreatic insufficiency and some lead to lung disease and some lead to very Minimal symptoms or just male infertility. So we've come to learn single gene disorder quite variability in a phenotype And then we're also going to learn a lot more about genotype environments And these are all always plus minuses If you realize you don't have the genotype that will lead to lung cancer, does that mean that smoking becomes okay? There's also the benefits of profiling is that the real hope and why we're doing it is that the hope is that the Data generator will be used throughout our lifetime to tailor our prevention and therapies Right, so we're thinking about pharmacogenetics But we're also thinking about Given that we know what our risk factors are how much sleep how much exercise What do we really need to eat and that it can be personalized and tailored to the individual But when we talk to you that in the newborn world We're then assuming that informing parents of increased risk will motivate changes in lifestyle I always view genetic testing I always call it the new year's resolution Because everyone says if I knew that my teams did x that I would change my behavior to y And we all know how long our new year's resolutions last But it could I mean in the idea it could allow us to modify our lifestyle Starting early regarding adult health problems because we will know what we're at risk for an adult We know that adult health problems begin in in pediatrics. In fact before pediatrics in utero But what are the risks of profiling? One concern is genetic determinism beliefs that our health and behavior can be explained solely by our genes They're going to be psychosocial harms Being in many ways what norm was saying But at a much larger scale because the significance of results in low-risk populations may be different than similar results Again, there's not going to be as much focus on these single gene disorders It's going to be multiple genetic environmental interaction disorders And what a gene means in a high-risk family may be very different from what that gene means in a very low-risk family And we may be creating much more Anxiety than we need to and may be giving people wrong information This is also the potential of discrimination harms misused by insurers employers in schools We may be seeing this currently today with the nc double a policy of testing all athletes for sickle cell trait and of course The the beauty um and the burden of genetic testing is that they run in families And the implications when one person gets profiled for other family members Other risks of profiling is particularly in the in the newborn period is that parents now will have access to health risks That may not express in their children for decades. And then what right does the child have to privacy as an adult? Since genotype phenotype correlations are really poorly understood Um And we will then find things that we think we know today are true will be disproven And this may lead parents to overreaction gun proven therapies. And again, as norm suggested do more harm than good We also now have a concept of pleotropy, which is that some genetic changes Which we thought were only associated with one disorder are actually associated with more and the classic example here is apoe Which actually we think about with respect to All-timers disease, but it's also relevant to cardiac disease autoimmune disorders What type of long-term implications you will have after head trauma? And many other conditions and so you could imagine that if a family wanted to know a child's apoe status because of cardiac risk It's also though giving them information about their child as an adult and risk for Alzheimer's And so how do you tell parents only part of the information? Or knowing that they'll just go on the web and find out all of its other implications So why are people even talking about profiling when there's so much unknown and we really don't understand? Uh, we're really an infancy in the sense of understanding genotype phenotype correlations And the answer is because newborns are convenient. They spend 24 to 48 hours as a captive population in the hospital Um, and so the pro for that perspective and the reason why newborn screening has been mandatory is because it ensures equal access And yet currently given that such screening is not clinically useful Not talking about newborn screening here talking about newborn profiling can only be used for research purposes So the access arguments of equal access are much weaker The big con and the big fear is the data security systems are not 100 secure And it'll be critical to have these before we start testing all newborns But there are special problems in profiling newborns. There's the issue of informed consent Should there be uh constraints on parental requests for data? So remember if we profile we're collecting all three billion base pairs and it now all exists And the fact is no one's going to stare at three billion base pairs. They're going to say i'm worried about condition x Or i'm worried about this. Let's look at that part of the um of the profile And the question is will there be limits on what parents can look at? Will we restrict them to only looking at conditions that are going to present in childhood? Most genetic statements that currently exist say we shouldn't be testing children for late onset conditions So we could restrict parental access to conditions that only pertain to health and childhood Most genetic statements also argue though against giving parents any carrier information because it's about the child's reproductive History future reproductive plans and yet all newborn screening programs Inform parents when carriers are found both in sickle cell disease and cystic fibrosis And often using the argument that will actually inform the parents of their own risks So using the child as a canary in the coal mine Of course this information may also reveal misattributed paternity Another special problem in profiling newborns is the question of since it is research And traditionally we always have said we should do research on adults who can consent for themselves Maybe we should be thinking about doing it with adults again the big advantage of newborns is they are a captive population It does raise these special issues about who should have access to it and by whom and it's going to be very difficult to draw the lines As we realize that things aren't about adult onset or childhood onset conditions, but that it's all over continuing And finally there's going to be this need to deny access to the parents when the child becomes an adult So it's not like we can be able to hand parents A cd disk carrying the three billion base pair information because if we do Then parents have this information about their child when they're adults when these individuals have a right to privacy against them And the interesting thing is insurers are clearly going to be interested in those three billion base pairs But they're also going to be interested in environmental data as in genetic data And much of this will end up being stored in bio bags But we're trying to collect as much information as possible to understand genetic environmental Interactions and so risks of discrimination and stigmatization are real and we need to be really careful about how we think about creating these databases The last set of issues that are special problems and profiling newborns is what do we do when this child reaches adulthood? Can the child withdraw in a sense? Can the child say you know why I no longer want everyone being able to access My three billion base pairs of course they exist They've already been in multiple different records and databases And it's not going to be clear what it means to withdraw from any research using genetics that that ends up in databases We have huge issues of confidentiality and privacy. How do you secure ensure secure databases over a lifetime? We're going to have to answer questions that who is the right to know who is who has the right to access this information and then the concern is To what extent can we keep this secure within the health care world? Or to what extent is it going to end up being used for forensic purposes for employment purposes and for other non-medical uses? So in summary clearly many issues need to be addressed before newborn genetic profiling should become routine I'm going to end with this cartoon embryonic DNA tests indicate a future domestic terrorist You may choose late term lethal injection or the electric height chair And the bottom of the cartoon says waiting for ethics to catch up with science It will be important to address these issues before large-scale routine newborn genetic profiling is adopted. Thank you Thank you very much. Lady mark was good enough to open the door to a baseball analogy So I will introduce our last Speaker as a cleanup hitter. He's John Lantos He is the director of pediatric biorethics at children's mercy hospital in kansas city And he spent a few years down here at the sat side And his talk is entitled do we still need pediatricians? And I hope the answer will be yes It's always great to follow norm frost because I sometimes think of myself as a cynical and pessimistic person Now I feel positively Reagan s. I mean it's morning in america I also It's trepidation on a correct norm And I'm usually wrong when I correct norm and we'll find by noon 18 messages in my email box with documentation, but I think the yogi very quote is Predictions are hard especially about the future Okay This is seen in a novel by Irwin the alum the name of the novel is when Nietzsche wept In which dr. Joseph Brower One of the pioneers of psychoanalysis tries to convince Friedrich Nietzsche to have himself admitted to the hospital under Brower's care The situation is a little complicated Brower has agreed to see Nietzsche only after getting a letter from a woman He doesn't know named lou saliban Asking him to see Nietzsche and suggesting that the future of german philosophy hangs in the balance Brower had never heard of Nietzsche nor of this woman though She would be going to become a sort of late 19th century combination of Angelina Jolie and Martha Nussbaum Beautiful brilliant controversial headline grabbing and romantically entangled with some of the most famous and brilliant men of her time Salome though has heard of Brower particularly of his fledgling experiments with a talking cure for patients suffering from mental illness She knows that Nietzsche who had once been her lover is suffering from both excruciating migraines and depression That's interfering with his work as a philosopher So she wants Brower to take him on to treat his migraines Brower's a neurologist But then sneak him into this new psychotherapy in order to help him deal with his depression Nietzsche this might be expected does not want any medical treatment after all his world View suggests that whatever doesn't kill you will make you stronger So his task is to overcome pain and suffering not to relieve it.  He also senses correctly that Brower is himself having a sort of midlife crisis Partly as the result of his discovery of psychoanalysis and his work with his young protégé Sigmund Freud through which he's starting to explore his own motivations for doing the things he does At one point Nietzsche challenges Brower's motivations.  I offer it. I am a doctor. That's what I do Far too simple Nietzsche answers back both of us know that human motivation is far more complex And at the same time more primitive I ask again What's your motivation? It's a simple matter professor Nietzsche one practices one's profession A cobbler cobbles a baker bakes a doctor doctors One earns one's living one practices one's calling and my calling is to be of service to alleviate pain Those are not satisfactory answers to my question. Dr. Brower when you say a doctor doctors a baker bakes That is not motivation. That is habit You omitted from your answer consciousness choice self-interest I prefer when you say one earns one's living that at least one can understand one's drives to put food in one's stomach But you don't request money from me Hmm, I might pose the same question to you professor Nietzsche. You say you earn nothing from your work. Why therefore do you philosophize? Ah, Nietzsche was ready for this. There's one important distinction between us I do not claim that I philosophize for you Whereas you doctor continue to prevent pretend That your motivation is to serve me to alleviate my pain such claims have nothing to do with human motivation They are part of the slave mentality artfully engineered by priestly propaganda Dissect your motives deeper. You will find that no one has ever done anything Holy for others all actions are self-directed all service is self-serving and all love self-loving Nietzsche's challenge to brewer resonates for all of medicine, but particularly for pediatrics today Why do we do what we do and how do we know where to focus? How does it change as technology changes pediatricians take care of children? It's what we do, but how exactly do we do that or should we do that? What sorts of problems in which children and to what end? The answers are by now means obvious and become less obvious as children in general enjoy better health and less disease Where most children are In a world where most children are healthy, but for those who are sick have rare diseases that are expensive to treat And usually can be treated with only partial success Pediatrics much more than any other field than medicine surgery obstetrics Is in a peculiar historical moment in all those fields the burden of disease is increasing not decreasing people are Living longer and as they live longer, they are sicker and more weighed down by the burdens of chronic and complex disease There are more things to treat and they are more complicated to treat obstetrics may be an exception. It's a little complicated pregnant women have better outcomes, but their Obstetrics has achieved its success in ways that differ from pediatrics. They haven't eliminated diseases They've found complex medical interventions who alleviate problems and pediatrics by contrast Our efforts at prevention have been phenomenally successful Many of the most common diseases that I treated as a resident just 30 years ago do not exist or virtually non-existent today Children today don't get chickenpox. They don't get H. Flu meningitis. They don't get epiglactitis We never see pneumococcal bacteremia. Rotovirus is on the way out and even the ones that still do exist The treatment has changed. We don't treat otitis anymore gets better by itself. It's all viral rheumatic fever Main thing pediatricians do culture those throats We still do it But in a number of cases of rheumatic fever Has dropped dramatically for reasons nobody understands So to ask whether we still need pediatricians or to think about the implications for ethics is really to ask What the pediatrics of the future will be now oddly in spite of the success of pediatrics And the the energy that goes into it has not decreased everywhere people are building these new children's hospitals That are stunning palaces to something bigger fancier more technologically sophisticated than ever before with double beds for parents to sleep in and 42 inch flat screen TVs where you can order room service on the touchscreen and What's done in these wonderful new facilities? Well, everybody knows that about half of what's done is neonatal or neonatal related Fully half of all admissions in most tertiary care academic centers are either nico bed days or bed days for NICU follow-up. So we could imagine One friend for the future of pediatrics is everything else will get smaller. NICU will get bigger They'll start saving 22 and 21 weekers and children's hospitals will become Large NICU's bill will be very happy. The rest of us will kill ourselves But imagine an alternative future which seems not entirely Unimaginable that we will make some progress in figuring out how to prevent or at least lower the prevalence of prematurity And so maybe there will be half the number of extreme preemies As before and developed countries then the leading causes of death Beyond prematurity are congenital anomalies and trauma of one disorder another the causes of trauma very motor vehicle accidents Child abuse homicide and suicide and adolescence Both trauma and congenital anomalies have three possible outcomes children either die completely recover or are left with lifelong Disabilities and chronic health problems. Now, we have a name for these impaired survivors children with special health care needs And there are studies of how many they are what they need how they do in various health delivery systems And they need a lot They need attentive medical attention attentive social work nutrition psychology physical therapy Their care during adolescence is enormously challenging Our pediatric health care system as designed today is not Very good at taking care of these our children's hospitals are designed primarily for crisis intervention But not the long term management that these kids need they need Pediatricians but a different sort of pediatricians than the ones we have been training to date And they comprise maybe five to ten percent of all children in the united states The other 90 percent have very different needs They need the panoply of preventive treatments that have been developed over the years And that are partly responsible for the worldwide outbreak of pediatric health Though any student of public health will tell us that it's not really the medical interventions It's economic growth and better segmentation and limitations on family size and all that which certainly are a large part of the Reason for improved our health. But for this discussion, it doesn't really matter These children too need a different type of pediatrician and pediatric health system than the one we have now And the one in which we now train our young pediatricians They need convenient affordable point of service care They need ready telephone or internet access to knowledgeable professionals Who can help them sift through the information on what preventive treatments make sense What signs need attention and how to deal with the psychosocial problems that are the bulk of the problems These children face anxiety bed, wedding, temper tantrums school problems, obesity, smoking Sexual activity during early adolescence, etc And their parents need genetic counselors To help them deal with the information that Laney was talking about that is about to be coming online And to think about the sophisticated gene screen tests that will be offered Either by their doctors or direct to consumer for 35 bucks on the internet But in any event, they don't need doctors with the skills that we teach most doctors today in most pediatric residency programs So why don't we train the pediatricians? Why don't we train pediatricians to face the problems of the future? I come back to Nietzsche's question to Dr. Brewer What's in it for us? And this reflects a little bit on the panel we heard yesterday We're caught in systems of education and systems of finance and systems of professionalization That simply cannot adjust to the problems of today or tomorrow We continue to train pediatricians who are good at responding Exquisitely well to the physiologic crises of individual patients And that's an important task And an important part of pediatrics But it cannot be the main part if our goal is to promote and protect the health of children generally For that we need a different approach altogether But one of which today there is no business model for either medical education Or health services delivery Even the bioethics questions As asked primarily make jobs for bioethicists Who should have access to genetic information? What sort of policies should we develop? Where should we set the threshold for resuscitation? Implies that we are the ones who get to set the threshold But it seems like what's going to happen in the future as more information is available is People will start to make in runs around this stultified and stultifying Delivery system for both medical information and bioethical counseling models are already developing Outside of mainstream pediatrics genetic screening is going direct to consumer quite rapidly Acute care pediatrics and even prenatal care and ultrasounds are available now at shopping malls The care of children with special health care needs is more and more becoming the task of parental support groups Who teach parents how to teach pediatricians to take care of their children with special health care needs So we may need a new type of pediatrics and a new type of pediatric bioethics In which empowered and informed consumers look for pediatricians Or teams of child health professionals to be their partners in figuring out what combination of prevention Screening and intervention both as therapy and as enhancement will help them create And raise the children that the parents want to create and raise Or to help them let those children die as the parents want them to die Thanks Thank you, John. If John can scoot down toward the end and I can invite our other three panelists up who have About 15 minutes for Some q&a My god I just want to add one thing that One of the Mental health As john said the problem is this business model of medicine that we have in this country Used to be a agency called the office of technology assessment Before the check had the privilege of participating in was a study of health supervision as pediatrics and concluded that It's either Proving to be useless that is there are studies that have no effects on the health of an immunization For which you don't need pediatricians Whether it was there were some parts of it that just weren't studied. I was practically convicted from the aap for Sorry not for this report, but as a president of the aap of the town sent a letter Complaining about this and said how are pediatricians going to make money if they don't do both supervision It's about 40 or 50 percent of what they do and the aap has been systematically adding visits to the health supervision schedule And to help pediatricians keep up. So It's just a One question one comment from john But they also probably still want some wisdom and some advice and some doctor spot sort of And I do think that in an effort to accommodate people's different Views and approaches and wishes. I don't think we need to throw the scientific method out the window And I think it's okay to say that, you know, somebody wants to do to do Something to which now that we can't imagine how we're on the child or not the child I don't have a problem with that, but for things that are actual interventions I think it means a little bit less Of course, the problem is that we have our standards of care Some of which are based on good science and some of which are based on intermittent electronics and some of which are based on So what you're based on just the standard here is that's how it's always done So we can sometimes tend to be a little bit critical by saying it's supposed to do a complementary or a false complementary alternative medicine, you know There's no scientific rationale for what you're doing. We recognize that that's sometimes the case for what we do as well No, I just want to Say again, as I said in my earlier count, it's just because something is complementary alternative or natural It doesn't mean it's safe oxygen was If you've been there, it's happened to possibly hurt any care But for 80 years, we we harmed a lot of people, but we've been impossible But that's a good example of not alternative medicine That's a good example of traditional standard of care that turned out to be a mistake because there's never problems still I mean The families of children with special health care needs And part of the reason they're doing that is because The pediatricians aren't well suited for what they're looking for Unfortunately, sometimes they're looking for a cure which nobody really has But it's also they want much more of a partnership in an ambulance That's totally a theory of use And in fact, the AAT states when we're talking about countermeasure in alternative medicine We almost suggest that it's older than children with special health care needs But there are plenty of parents who are using it now, for example, for an aspirin Yeah, I'll use the creatinine Precise for muscle growth and things of that sort So we are seeing some of that developing in the AAT And the obligation to protect children from that toxicity That sort of independent obligations to children that pediatricians have separate from Parental discretion is always one of the real interesting areas in pediatrics Question The AAT is an end as a result of the childhood of the pediatrician who is an adult or as we heard yesterday We do have enough in early childhood elements and simple interventions of life And I don't want to just hear about it, just how does it want to be for the first six months of life Or I should have a much bigger impact on how the American Academy of Pediatrics Congress is now working on And it doesn't even have much from by then And we remain with a 15-minute visit and a teacher-old in the pediatrician From the outlet and the pediatrician You know, who's going to be able to tell their patients To last, let's put back a long fact Because the desert government is able to just want pediatrics to go And we do really have to change our structure of our education So there is a close-by I'm going to send a few in there, I've seen several of them trash in pediatrics You might want to have at least two tiers of doctors, one type And you might want to have a medium in the outlet But you're going to have to have that The third tier is a much more vocational environment for pediatrics And that's really, in a sense, what we're going to have to do And then, of course, no one's feeling the problem with that But also, it is a large world of populating for pediatrics needs We're going to have a very brief comment by Mark, last one by Mark The last comment? Second the last, because we need to respect our elders And I think this is what Lanny's, I don't think Lanny's already had one step further to say That I don't think it's necessarily carpets known as pediatricians in the end That maybe pediatricians are the ones that do treat kids when they get sick And maybe there's people who deal with issues such as childhood obesity, etc Things that require a very different approach Maybe not going to be pediatricians It's obviously a huge problem for kids as a fact For so many kids, I like as a teacher It's that a huge number of kids can't read and write well But that's not a problem for pediatricians to fix There are others who are better suited to fix that And I don't know if I can, I can't say that I would say some of these huge problems that we identify as pediatric problems Maybe they're not going to best be fixed by pediatricians Maybe that's not going to be our role I'm going to close with an optimistic comment So, we believe John is the most mental of the best pediatrician person in the room The University of Wisconsin School of Medicine and Public Health Changed its name five years ago And it wasn't just a name change I spent the last two years with a whole bunch of colleagues With the whole first year of class Essentially, it's become a public health curriculum And the case that we discussed the last two days Was a bad date And having this baby turn out so bad And what were the causes of it And it was exhilarating I mean these students spent two days And they went to the legislature And looked at the genealogists And looked at our driving law A hundred different things And really were a plus With all the different ways of trying to Produce better babies Apart from the medical office Trying to treat him or her after three years Or just doing abortions and things like that So, and there are other schools That are starting to do things like that So I think there is starting to be a shift In looking for social, political, public health And solutions to these problems Instead of an entire old doctor Patient who would guess the truth I would like to thank our spectacular panelists We're going to have a very brief break now I'd like people to gather back at 9.50 For the next session Thank you