 Thanks very much Lawrence. So it's really my pleasure to be here. I know that I'm coming on the heels of presentations by some real top people in the in the fields like Michael Meany for epigenetics and other people. So I am very humble in presenting myself as a former school psychologist in West Virginia who recycled herself into a postdoc in psychiatry after marrying a French Canadian and moving north to Montreal. So I under no circumstances would I ever say that I have a background in anthropology or culture. Lawrence knows very well that I just don't understand culture, but so my point today is coming to a question that has really biological implications from the point of view of a social scientist and then bringing in colleagues that have more of the expertise in biological questions and biomarkers and how I've tried to use that over the over the last several years. So my main interest is really schizophrenia and the development of schizophrenia. So approximately 25 years ago, I created this model that just reflects the literature on the genetic and environmental risk factors for the development of schizophrenia. We know that there's genetic loading, the closer, more closely related you are to somebody with schizophrenia, the higher is your risk. We also know that the pregnancy and birth are very critical periods that anything that might interrupt development to the fetus during the pregnancy, infections, famine, complications and prenatal maternal stress can increase risk, especially if there are things that happen during the birth, these increase risk. And because schizophrenia is considered to be a neurodevelopmental disorder and because neurodevelopment does not finish until the early 20s when the prefrontal cortex finishes myelinating, really anything that happens during childhood and adolescence, such as maltreatment, substance use, these things could also interfere with proper neurodevelopment. So as I'll be explaining today, I really zeroed in, whoa, that was not expected. I zeroed in on one of these risk factors, prenatal maternal stress. And 25 years ago, I developed an interview based on the leads, if you're familiar with the life events and difficulty schedule, in which I was interviewing the mothers of people with schizophrenia, the mothers of people from the community, interviewing the moms about various stressors and difficulties, so punctual stressors and extended difficulties that they may have had during their pregnancy. So it was a pretty good, it was a pretty good interview. We did a really good job taking people back in time, but a lot of times we were asking these moms, do you remember what happened during your third of seven pregnancies? Remember that was like 35, 40, sometimes 50 years ago. We tried to take them back there, but absolutely not ideal as a measure of prenatal stress. So I found a way really, rather than looking at schizophrenia as an outcome, to look at prenatal maternal stress as a risk factor, first of all, for other risk factors, like pregnancy complication and for substance abuse, but then also as a risk factor for a number of what we call intermediate phenotypes. So people who develop schizophrenia may have motor and sensory functioning difficulties in childhood. They tend to have more problems with attention, they tend to have slightly lower on cue on average, other kinds of cognitive difficulties, inhibition growing up, and then some physical markers, such as asymmetrical finger prints. So why was I looking 25 years ago at this question of prenatal maternal stress? Well, it was based on some of the research. I'll give you a couple of examples of studies in which people have looked retrospectively at administrative data in their community, in their country, in their state, and so on. So the Netherlands was invaded on May 10th, 1940 by the German forces. They bombed Rotterdam. There were 900 people who were killed, 85,000 people left homeless. So obviously this created a great stress in the population and even among pregnant women and their unborn children. So decades after the war of Jim Van Aas and and Selton, took a look at the psychiatric records in the Netherlands to see if the stress of the invasion may have somehow increased risk for schizophrenia in the population. So as you may know, the risk for schizophrenia across the world is more or less one percent. One in a hundred people will be diagnosed with schizophrenia at one point or another. What he found was that those that were exposed while they were in utero had a 15% increased risk of schizophrenia. So an odds ratio of 1.15. If they happen to have been exposed to the invasion in the first trimester, then risk increased to 28% above the 1%. And then if it happened to me, males and exposed in the second trimester, risk went up by 35%. And then there was no particular increase in risk for those that were exposed in their third trimester. So this is obviously they did not talk to these mothers of patients. This is purely an empirical association between exposure to this invasion and ultimate risk for schizophrenia in the offspring. Dennis Kinney at Harvard was very much inspired by this work and did something a little different. Rather than looking at schizophrenia, he was looking at autism and in the state of Louisiana and the United States, the prevalence of autism is about 5.2 per 10,000 live births. So Dennis hypothesized that for people that were in utero during major hurricanes or tropical storms, that this would increase the prevalence rate of autism in the state of Louisiana. So he identified 10 tropical storms or hurricanes that occurred between 1980 and 1995. These were rated in terms of the severity of the storm by the National Weather Service, not by Dennis Kinney but by the National Weather Service. And he had two basic hypotheses. First of all, that the more severe the storm, the higher would be the increase in prevalence of autism in the state of Louisiana. And in fact, that's what he found. So by looking at the prevalence of autism for births at various times, so being exposed to a very high, a very severe hurricane, increased risk or increased prevalence to 13.3. So remember the base rate is 5.2, people who are exposed in utero to a severe hurricane was 13 per 10,000 births. His second hypothesis was that there's something special about mid to late pregnancy that renders the fetus vulnerable to autism. And so he hypothesized that there would be a timing effect. And indeed, that's what he found. So down here we've got exposure in months one to two, three to four, five to six, seven, eight, and nine, ten. And the prevalence rate for autism in the state of Louisiana for people who were exposed in utero to one of these storms in months five to six increased to 17.7 births per 10,000. And again, that's relative to a base rate of five. So the basic idea here is that there's something about mid gestation and something again at the end of gestation that renders the fetus vulnerable to the stress in the mother. And so this kind of invokes the idea of an interaction. So indeed, again, that's what Kenny found, that remember the base rate is 5.2 per 10,000 birth. And he separated the data into people that were exposed to storms in other months of the year and to this target month, or these target periods of five, six, and months nine, ten. And we see that for people who were exposed in utero to a severe hurricane in those months, five to six, nine to ten, that the prevalence rate of autism went up to 26 per 10,000. So this is really setting the stage. Both of these studies and others like them set the stage that there's something about stress in pregnancy that is increasing risk for mental illness later down the line. So what's the thinking about pregnancy and the relationship between the mother and her fetus? Well, long ago, people used to consider that the fetus was actually the perfect parasite, that it's in there in the uterus, it's enveloped in amniotic fluid, it can't see anything, can't hear anything, and if it needs any kind of nutrients or anything, it's going to take it from the mother, even if it's at the mother's expense. Well, that thinking has changed over time, where researchers now know that the fetus is a lot more sensitive to the mom's environment than was what once thought. And there's this idea now of fetal programming, which has kind of morphed into the idea of the developmental origins of health and disease. Doehead is the current buzzword. So the basic idea is that there's something going on in the mother's environment and that this is impacting on her physiology, probably her cortisol. So her cortisol increases, it heads down towards the placenta, but inside the placenta there is a barrier enzyme called 11 beta HSD2 that converts cortisol, which would be noxious or would influence the development of the fetus, converts that into cortisone, which is benign, which is inactive. But in times of really high stress, that barrier enzyme breaks down and the cortisol gets through to the developing fetus. But there's something now that is kind of on the heels of all this research that is really suggesting that this can only be a bad thing for the fetus, for mom's cortisol to get through. And that fetal programming is really results in a negative outcome for the fetus. There's a new idea which is called the predictive adaptive response. You may be familiar with something called the Dutch famine study. So also during World War II in the Netherlands, the Germans had a blockade on food and people's caloric intake went from, you know, I don't know from calories, but let's say like 1,800 calories a day down to 700 calories a day. People were eating tulip bulbs just to survive. So what happened was that the babies that were born who had been exposed to this famine were born really tiny. But then they grew up to be adults who had obesity, heart disease, diabetes and so on. So the basic idea here, this predictive adaptive response is that when the famine was happening, this signal of that famine is going through the placenta. The placenta acts a bit like a sensory organ, where your eyes are sensory organs that keep you from tripping over things that help you to negotiate your environment. The placenta is capturing the mother's environment, sending that signal through the placenta to the fetus in order to somehow modify the development of the fetus so that it will have at least short-term survival on the other side. So for these famine babies, they were programmed, their metabolism was programmed so that once you get out there, baby, if you see food, eat it. And if your body eats it, hang on to it. So this is the development of diabetes and so on. So had the famine continued, these people would have been very well adapted to their environment. There are all kinds of examples in the animal world and the insect world about how the external environment can change from one generation to the next, even the physical characteristics of these animals. And the whole idea is to attempt to, God's idea in doing this is to assure initial survival of these offspring. So where the problem comes in is when there's crap happening in the mom's environment during the pregnancy, but then after the child is born, the environment has changed. But there has been a permanent programming of that person. So it's the same with the famine. So had the famine continued, it would have been great, but these Dutch children were brought into a world of plenty and that's where the problem started. So in all of this research to date, the whole idea is stress. There's something about the stress of the famine, of the invasion, of the hurricane. There's something about the stress and there's a huge literature on prenatal maternal stress. Most of it is with animals. And with the animals, it's very easy to randomly assign animals to be in a stress condition or not. And all you have to do is, like with rats, you need to, you can do a restraint stress, a forced swimming stress. You can bring a stranger, a hostile stranger into her cage. With non-human primates, all you really have to do is remove them from their social their social friends for 20 minutes a day. And in all of these cases, those that are exposed to the prenatal stress, the offspring, will have effects that are visible in the brain, in the immune system, in their metabolism, in their cognitive development. And one of these mechanisms may well be through DNA methylation, because in these animal experiments, you can show that the prenatal stress is changing things like DNA methylation in the offspring. What about humans? Okay, what is stress? I mean, we all use stress in multiple ways and in ways that mean very different things to different people. So in order to get a handle on, you know, what do we mean by stress and how can we measure it? How can we break it down into its components? I looked to Lazarus and Folkman, who have this model, and I'm simplifying here, but their model suggests that a thing happens, some kind of objective situation or event occurs to a person. And then they go through a two-stage process of cognitive appraisal. And in the first stage, the person asks to themself, is this thing that's happening? Is this a threat to me? If they conclude, well, no, it's not a threat to me, then there's no stress. If they say that, yes, there is a threat to me, then the second stage is to say, do I have the personal and environmental resources to cope with this threat? If the person concludes or believes that they do have the resources to cope, then they may have stress, but we may call it a positive stress. It's energizing. Whereas they fear that they do not have the resources to cope, this is what we would call a negative stress or subjective distress, and that is what should kick in the cortisol. And if this person happens to be pregnant, then as I mentioned the idea is that this, the cortisol will go through the placenta and some way disrupt or change fetal programming. So when we look at these studies of invasions, there are studies of, you know, using administrative data, people whose parents have died while they were pregnant or hurricanes and so on. We know nothing about what was the stress that those women were under. And what is the active ingredient? What was it that caused that change in the fetus? Was it just objectively how their lives changed? Was it what they thought about the invasion or what they thought about the hurricane? Was it their level of distress? Was it how upset they were? So the conventional wisdom is that it's how upset the woman is because that's going to kick off her HPA axis. That's going to send glucocorticoids rushing to to the fetus. We've got this in animal studies. They can measure that, they can chop their little heads off, and they can measure those things in their brains and so on. But we can't do that with humans. So here's the basic problem in prenatal maternal stress, research in humans. We know from those studies that yes, prenatal maternal stress, one way or another, does increase risk for major mental illness and health outcomes in the offspring. But what is it about that stress experience? Is it objectively what happened to them? Is it their mom's cognitive appraisal? Is it the mom's level of subjective distress? We don't know that. We also don't know what are the kinds of things that would moderate that association between the prenatal stress and these child outcomes. Two kinds of moderators that I'm thinking of. One is there's the whole idea from Belski of differential susceptibility. So some people by virtue of their genotype, by virtue of their physiology, maybe their HPA axis development, by virtue of some some other unchangeable factor, will be more or less vulnerable to the effects of prenatal stress. Another kind of moderator that I think about, which I'll talk about more in a second, is what we can do. What we can do to buffer or what we might be able to do to exacerbate these effects. So that would be, so when we're talking about moderators, we're kind of talking about in whom is who are we talking about? Then we also want to know how does this work? And this is where we're talking about mediators. So these could easily be mediators at the level of brain development, of immune function, of epigenetics, a number of different biological mechanisms. And all of these may influence intermediate phenotypes, like I mentioned before, so cognition, behavior, BMI, all kinds of things, which then may set up a situation that will increase risk for mental health and illness. But what I'm getting into more and more at this point is where along the way can we intervene to break this cycle, to break these pathways so that the fetus is not programmed for for a temporary environmental stressor that is not going to be there anymore after the birth. So in order to really conduct this this research program, in order to really respond to these problems in the literature, what we need is some kind of a stressor, some sort of a thing, some sort of an external event that, first of all, it has to happen to pregnant humans. Second of all, it has to be outside the women's control and as much as possibly randomly assigned to them. There is a huge literature that talks about prenatal maternal stress that refers to the research as prenatal maternal stress, but what they're talking about is depression or anxiety in women during pregnancy. However, it's they're not using stress in the same way that I am since being pregnant and being anxious, being depressed, or in terms of life events, having your husband leave you while you're six months pregnant, women are not randomly assigned to these kinds of stressors. So this kind of stressor would need to be applied to large numbers of pregnant women because, as I mentioned, there are a number of different moderators like the timing in pregnancy, maybe sex of the fetus, maybe a number of different things. So the more variables go into the equation, the larger sample you need, it has to be something that will affect pregnant women to varying degrees. So we need a dose-response relationship and not necessarily just comparing two groups. But if we can look at a gradient of stress, we may be able to say, aha, this is the line at which we'll get obesity, this is the line at which we'll get some other outcome. It would also have to affect women at various stages of pregnancy because, as I've shown you, the timing is really important. It was important for the invasion of Holland and schizophrenia, important for hurricanes and autism. Timing has to be very discreet. So even in some of these administrative studies, administrative data studies where they're looking at bereavement, they've got the date that the parent died, but they don't know for how long was that parent ill. So the timing is very important. So we need something that will affect women at different stages and hopefully be punctual enough that we can be quite precise about the timing. It also has to be the kind of event that that would allow a researcher to get in there fairly quickly to assess people's levels of distress and assess their levels of exposure. So disasters kind of fill this bill, whether they're natural disasters or man-made disasters, these fill the bill. So what we know from people who are exposed to disasters is that there's like about a seventeen percent increase in diagnosable mental disorders following a natural disaster. Of course, that depends on the severity of the disaster. We know that those mental health problems are likely to change for a lot of people. They're their health behaviors, so they may tend to drink more. There's increases in domestic violence and so on. And we know that if a person is pregnant that those unhealthy behaviors, drinking, drugs, domestic violence, are going to have some pretty direct effects on the development of the fetus. We also know from a large literature that stress and pregnancy tends to increase risk for preterm birth and for outcomes and those have effects on the fetus as well. And then as I mentioned, there's something about a disaster that seems to have some kind of a direct or indirect, if you will, via the placenta effect. So then that fetus is going to become a child maybe with preterm birth and ultimately have a number of different problems in terms of mental health, cognitive development, obesity, even diabetes. And then there's another huge literature showing that the mental health problems in the mother, depression in the mother, tends also to be associated with a number of developmental problems in the child. So given this scenario, how are we going to, you know, Lauren's kind of tossed the gauntlet or tossed the challenge to me. Usually I present to people who really care about the prenatal stress. Now he wants me to care about the method. So I had to kind of alter the talk to say so how do we go about doing this and put more of the emphasis on the method. So in today's talk you'll be seeing a lot of graphs and figures and results but I want you to think less about prenatal stress and more about Suzanne King as a researcher being confronted with a disaster and then having to go go go go go get these data. That's kind of the that's the challenge. And I've got one now that I'm dealing with so. So the way I went from interviewing moms about their pregnancies 40 and 50 years earlier to studying prenatal maternal stress prospectively, basically the idea came on January 12th 1998. So for the first week of January 1998, we had a series of three different weather systems that moved through southern Quebec and the surrounding regions dropping freezing rain. So we always have freezing rain. We lose power for a couple of hours, maybe a day, but with with five days of constant freezing rain, the ice that built up on the power lines, the high-tension lines was so great that it toppled almost all of these high-tension pylons in the region and that deprived more than three million people in Quebec from electricity for as long as 45 days in the coldest month of the year. So when you've got freezing rain, the temperatures are hovering around freezing a little above a little below, but in the weeks that followed it went to minus 10, minus 20, minus 30 Celsius, ladies and gentlemen. So it was it was cold and people were struggling. There were more than 454 shelters that were established. These housed as many as 17,000 people on a single night. The economic costs of the ice storm were the greatest natural disaster in Canadian history. There were about 27 deaths that were attributed directly or indirectly to the ice storm. This is mostly people attempting to stay warm by lighting fires in their fireplaces and creosote fires burning their house down. Some people were killed by live wires that had been knocked off telephone or powered poles. Some people were killed by falling ice off of buildings and bridges. Some people hypothermia and carbon monoxide poisoning. Do not bring your barbecue into the house. Something to take home. So Project Ice Storm was started in 1998 and we started with about 200 women who were pregnant during the ice storm or who came became pregnant in the three months afterwards. So publishing was a little bit difficult. People didn't getting funding was extremely difficult. It took me five years. Nobody believed that the ice storm a little storm like that could have any effect. But then when I would go to publish I would get this comment. Oh, it's all very well and good that you've got these women who were exposed. But how come you didn't how come you didn't recruit those women before the ice storm that would have been even better? And I'm thinking I have many skills, but clairvoyance is not one of them. But this this comment wore on me for several years and one day for reasons unbeknownst to me MSN was like my home page and it came up and there was big flooding in Iowa and I only know one person in the state of Iowa and that's Mike O'Hara whom I know from the Society for Research and Psychopathology and Mike studies postpartum depression. So I called him up. I said Mike, are you okay? Yes, his house was at the top of the hill. It's a very nice house. He says yes, we're fine. And I said are you studying pregnant women right now? And he said I have a student who has just has is recruiting pregnant women for her study on stress and and obstetric complications. She has already recruited 135 women and while they were pregnant she assessed their their mental health, their social support, their coping styles, their perceived stress, all of these things. So what what is novel about the Iowa Flood Study is that we have a pre-post design. So this really makes it a beautiful natural experiment where you've got the pre and the post. But what we really wanted, and I had a placentologist on standby, what we really wanted was the placentus. I know nothing about placentus. I touched one once. But the idea is that if everything is going through the placenta we need to capture what is it that goes through and what triggers it? Objective, cognitive or subjective stress. So then three years later, well actually we got a big grant from the CIHR for the Iowa Flood Study that included getting all those placentus. By the time we got the money there were no more placentus. They were all in the garbage. In 2011 I saw, aha, three-quarters of the state of Queensland in Australia is under water. It's the size of France and Germany put together the flooding. It's a state of emergency. So within days I was contacting a woman named Sue Kilday, who is a midwifery professor. In Australia all babies are born by midwives in hospitals. She was in charge of midwifery research in the largest maternity hospital in Australia that births 10,000 babies a year. So I contacted her. Turns out that they were currently running a randomized control trial of two different forms of prenatal care, group midwifery practice and standard care. So in that trial they had they had one measure of depression in these women. So we were able to call those women back. So we've got pre-flood data on part of the sample and randomized control trial in another part and because she was the head of midwifery she could make sure that we collected placental samples. So my colleagues, master's student who had never been on a plane before, flew to Australia, lived across the street from the hospital and was on call 24-7 to go over there and paste the halls to get the placenta and sample there. So that's what's special about the Queensland flood. So I thought I was done. I thought you know, I've got these three big plates you know, I'm juggling these three balls in the air. That's about what I can do. But then in May of 2016, I have pictures of these. So then in May of 2016, the city of Fort McMurray and Alberta. So if you start from the U.S. border you go up to Calgary then you go up a ways to get to Edmonton and then you go up further you get to Fort McMurray and a little ways past it's the end of the road. Surrounded by Borrell Forest, they wake up on a Monday, blue sky and at midday everybody is told the fire they didn't even know there was a fire. The fire is surrounding the city you've got to get out, get your kid out of school from across town, try to connect with your husband who is working up at the oil camps and everybody's got to get out within 24 hours and this picture is pretty typical of what people were facing trying to get out of their homes. So Dave Olson from the University of Alberta contacted me and said let's do a study and I said I'm not going to do another study just to show that prenatal maternal stress has an effect. I'm going to do something about it. I want to see if we can't interrupt this cycle. So we implemented an intervention a few months after the fire to women who were pregnant or preconception and I'll tell you a little bit about that. But again in all these first four studies we started out each time with about 200 women and by the time the first people fall off because they always do once you come with a second wave of assessments we were dealing with really small numbers. So August 2017, Hurricane Harvey hits Texas and floods Houston and it is I believe it's possibly the worst natural disaster in US history is the flooding of Houston in August 2017 and Houston and the surrounding county Harris County, they have 72,000 births every year. So it seems to me here we can have the numbers that we want. We can take what we learned from trying this intervention in Fort McMurray and apply it now to a much larger number of women from Houston. So the the flooding was actually August 24th 2017. We got a grant application into CIHR by September 15th. So I contacted somebody there right away. So within two or three days of the flooding, I was in contact with Johanna Bick who does infant neuroimaging and has studied with Charles Nelson at Harvard looking at early life stress and brain development. So someday I'll actually get a grant to do that study and that's what I'll be doing when I leave here is trying to get one. So the so that there are a number of so here's the here are the new slides on the challenges of studying disaster stress and pregnancy. Number of challenges not for the faint of heart. The main thing is that there's no time to lose. So women will not remain pregnant. There is no pause button. They will not wait for you to get ethics approval before giving birth. So trying to capture them while they're still pregnant is important because once they've given birth if they've had a difficult delivery they could be thinking why did I have a difficult delivery? Maybe it was because of the disaster. This could shape the way they tell you what happened to them during the disaster. So the fastest response we've had in any of those five studies is in Iowa because they were already recruiting pregnant women. So they just added an amendment and we kept going. The next fastest was the Queensland Flood Study in Australia. They were also already recruiting women. So we started April 1st. We got the flooding was in January mid-January. We got ethics approval April 1st and the reason it took that long was the biological samples was going in and getting placenta. So that took a little more time. But ice storm and the other ones we usually have been getting in five to six months after the disaster. So timing is a real issue and then also you almost never have the funding available to do what you need to do right away. Which can be a problem. So I had no money to start Project Ice Storm. I think I got $7,000 from somewhere but really no money and then the ethics approval takes time. The other thing is if only for the ice storm was I actually a victim myself of the disaster. In all the others I've had to go elsewhere and finding a collaborator on site is key. As we're finding from Fort McMurray because there is no university there is not even a college that is interested in Fort McMurray. So if ever you want to do something make sure you've got somebody right on site who can take care of things. So I put here that Skype is my friend. I was pretty new to Skype in 2011 I guess but I was able to connect with Sue Kilday in Australia by Skype and there's something about being able to see a person face-to-face and talk about something and share your enthusiasm. But I think it's the face-to-face that conveys whether or not that person can trust you. So Sue Kilday who was couch-surfing because her home was under water she was couch-surfing but she managed to Skype with me and say okay I'm gonna put everything else on hold and we're gonna go go go and get this study. So it's important to realize that not only are your pregnant women victims of a natural disaster so are all of the people that you're gonna be counting on to be on the ethics board to do anything else and local infrastructure may be in disarray at that point. So coming back to the whole idea of you know doing the field work and the methods so with Project Ice Storm, you know, I myself had been through it. We were without power for seven days. It was somewhat stressful. I knew what was going on. I knew what the issues were. I was glued to the radio so I knew what other people's issues were. So I was able to construct a measure of the objective stress exposure. But I did go back to the literature to say well, how do other people who know about disasters? How do they characterize the extent of objective exposure to a disaster? And this paper here was a review paper on psychiatric epidemiological research on disasters and they listed 10 different factors or experiences. They just listed them, but then I grouped them into four categories. So certainly a person's level of threat in a disaster is an important measure, their actual threat and not so much what they're afraid of but their actual threat. This scope, so this would be how long does this disaster last for this person or for that person? Also, what is the proportion of their community that is affected? So this is one thing that has been very different between the different disasters where the ice storm and the wildfires affected everybody, everybody in the community, even if you never lost power from the ice storm, your appointments were canceled, you couldn't get anywhere, your car got stuck on the ice, so everybody was affected. Whereas in flooding, it's very often around waterways, but almost always you can get to higher ground and be safe. So the proportion of the community affected is, it differs by by disaster. Certainly loss is an important component and change. So we know that change is inherently stressful, so a lot of people were displaced from their homes from all of these disasters and they may have change in contact with their sources of support. So following the ice storm, I created a questionnaire and tried to put the various items into these categories of threat, loss, scope and change. So this is just about the number of items that I had. So each of those items, like the extent of damage to the home or the number of days without power, was on a continuum. We would create categories and give points for different numbers of days without electricity and so on. And very arbitrarily, I sat there in my office one Saturday afternoon and created a scale and just made it so that each of these would add up to a maximum of eight points. Added them up and created the storm 32. So my original idea with having a measure of the objective stress, the objective exposure, was for sure everything is going to be carried by this mom's subjective distress, but people are going to ask me so what actually happened to them and can you just kind of control for what happened to them while you show that distress is the main thing. So I wasn't all that interested in it when I made it. So this is what I had for storm 32. Following the Iowa flood, we created the IF-100, the Iowa flood 100. So we expanded. We talked to the people in Iowa. So Mike O'Hara talked to his neighbors and colleagues. We spoke to people to find out. So what were the real challenges that were part of being in this flood? And some of it was that people lived on one side of the river, but most people worked on the other side of the river and the bridges were underwater, so they had maybe. So we found out what were their challenges and then adjusted the scale from the ice storm scale to something that would fit a flood. When we had the Queensland flood, we took the Iowa flood study scale, the IF-100, and then expanded on it. So everybody was saying, you know, how you dealt with the insurance companies and how much they would pay and whether or not you were insured, that these were also important. So we added a number of different extra things and came up with the Q-Fos, which had 200 points. But because it was built on the IF-100, we could still pull the IF-100 out of the Q-Fos 200. We are still working on the Harvey objective stress scale, the Haas. We included all the items when we recruited people following the floods, so we can pull out the IF-100 from the Haas. And so far it looks like the Q-F-2011 scale is or the Q-F-2011 floods in Australia had the highest exposure. But I'm pretty sure that once we start looking at Harvey, they will be the greatest exposure because in Queensland, nobody had to be rescued off the roof of their house. So that wasn't in that scale but because people were rescued by boats and by helicopters in Houston, I'm pretty sure that in the end it's going to be somewhat higher. For the Fort McMurray wildfires, this has been the biggest challenge in this research program because it's not like an ice storm. It's not like a flood. And all of the context was different. There's a single road that goes through Fort McMurray. I mean, it's almost like they design this city to kill people in the face of a fire. So you've got woods all around it and most of the residential areas have one road in and then there's a big circle where you've got hundreds of homes and that same road to get out. So if that road gets blocked, you're trapped in there or you can't get in to get your families, it was horrific. So designing that scale, it's taken a long time and we haven't figured out how we haven't gone through the whole process of scoring it. Cognitive appraisal, I will make a confession to you today. I hadn't actually thought about cognitive appraisal until long after the ice storm. I discovered the whole Lazarus and Folkman thing a bit too late. And so I went back through our original recruitment questionnaire to see, did I include any items that could be construed as cognitive appraisal? And there was this one item, taking into account all of the effects of the ice storm crisis on you and your family, what would you say have been the overall consequences of the event? Very negative, negative, neutral, positive or very positive. And I was very surprised to find that there were as many people that said it was positive as who said it was negative. And it all had to do with what they wrote in afterwards. We realized that people who said it was a positive experience. It was because I went and I stayed at my in-laws. They had a wood burning stove, but no electricity. So there was no TV, no radio, we played games, we talked to each other. We told stories and it was a great time. I got to know them better. So the whole experience was positive. In the negative side, some people said we had to go and stay at our in-laws. I learned within four hours how much I hated them and I just hated them more and more as the time progressed. So a lot of it had to do with the interpersonal relationships and situations around these families. To look at subjective distress, I use this impact of event scale revise, which measures post-traumatic stress symptoms, which asks the mom, right now, how are you feeling? Do you have, do you avoid thinking about the ice storm? Do you have intrusive thoughts and images about the ice storm? If you are confronted with anything about the ice storm, does your heart beat fast? Do you have hyperarousal symptoms and so on? So we use this as our subjective stress measure in project ice storm. But then I came to learn more about PTSD and people are not randomly assigned to become, to have PTSD after a disaster. There's something probably physiologically different about them before the disaster so that when confronted with a disaster, they respond with PTSD symptoms. So we needed something else to assess their stress. Also these PTSD measures are being asked five, six months after the disaster. Ask them how they feel then. So these are people who may have had all these symptoms, but they have stayed high on those symptoms all along. So we wanted to know, and the whole idea is that it's at the time of the disaster that their stress hormones may have gone and affected the fetus. So we included in there two other measures, the peritraumatic distress inventory and the peritraumatic dissociative experiences questionnaire. And these ask the person at the time of the flood or the fire. How distressed were you? Did you have dissociative kinds of experiences? So we use that in the other studies after project ice storm. And because it's hard sometimes to have the sample to use all three of these questionnaires separately, we created a composite maternal stress scale using principal components analysis. So this is the composite subjective maternal stress scale, COSMOS. And we've got an Iowa version, a Queensland version and now a Harvey version. So the first question that I wanted to ask is, so we've got all these retrospective studies, these administrative data studies. But what is the aspect of stress that is doing this programming of the fetus that people see years after birth? So I'm going to go through a series of these slides kind of showing, you know, what are we seeing? Is it objective exposure that has the effect? The mom's cognitive appraisal as negative, neutral or positive? Or is it the mom's subjective distress? So when we look at IQ in childhood, we have only found that is objectively what happened to the moms that influenced IQ at ages two, five, eight and 11. The mom's subjective distress had no effect whatsoever. The cognitive appraisal, so a negative cognitive appraisal of the disaster was associated with lower IQ at age eight only. So this graph that you see up here, the yellow is the low objective stress group, the red is the high objective stress group. We didn't have much money. So we left the middle objective stress group, let them stay at home. And then these are IQs. And we've got a 15 point difference in IQ, controlling for socioeconomic status, controlling for subjective stress and everything else. If you don't know about IQs, the average is 100 with a standard deviation of 15. So we had a full standard deviation difference between low and high objective stress. And this was maintained in Project Ice Storm at age five and eight and at age 11 for the boys. What about the mental health in the kids? What about their internalizing problems like depression and anxiety? Here we had significant effects of objective exposure and a negative cognitive appraisal and the mom's subjective distress. And that continued throughout childhood and adolescence. And we're actually seeing that over time as a group that they're going from below average to above average internalizing problems. When the kids were starting at about the age of five, we started including a questionnaire to the moms about the child's autistic like symptoms and none of the kids are autistic. But this is on a continuum of autistic like traits. And we had equal effects of both the objective exposure and mom's subjective distress at the age of five and a negative cognitive appraisal by the mom of the ice storm predicted autistic like traits at age 19. So we've been following those kids for 20 years. Again, this is less supposed to be a talk about prenatal stress and more about the method and about the importance of really teasing apart what happened to those moms. When the kids were age 15, we tape recorded an interview with them and we went through and very systematically counted the number of times there were disturbances in their communication, which is a very kind of low level trait from schizophrenia, kind of a thought disorder trait, but these kids are not psychotic, but it's on a continuum. And what we found was that it was only the objective stress of the mom that predicted these communication disturbances, but there was a huge effect of the timing as we saw in those first examples that I gave you. So in the preconception group, there was not much of an effect of the objective exposure. It started becoming significant in the late first trimester, very significant around those months four, five, six, and it's seven and eight. And then still significant, but less so at the end of pregnancy. So the so the idea here is once again, it's objective stress, which was a huge surprise to me rather than the mom's subjective distress that had the effects. So along the way, we also, you know, why not measure these kids? They're heighten their weight. So we did that at age five, got their heighten their weight and found these kids whose moms were without electricity for a long time. They're more more more likely to meet criteria for obesity, according to the CDC. So then we started looking more and more extensively at these kinds of metabolic issues and found that so the objective stress, but not cognitive appraisal, not subjective distress, predicted BMI at ages five, eight and a half, 11, 13 and 15. And surprisingly, while I thought that the effect of the stress would only last for a few years after the birth, that the environment would take over, what we've seen is that the correlation just gets bigger and bigger and bigger as they get older, surprisingly. Because of the whole obesity thing, when they were 13, a few kids came into a school in their neighborhood to give blood and do a glucose tolerance test. Once again, it was only the objective exposure of the mom that correlated with the kids' insulin levels after this glucose tolerance test. OK, so I think at this point, we see it's really important to tease apart. For one thing, I used to study something called expressed emotion and schizophrenia, which was hugely blaming of mothers not of causing schizophrenia, but of maintaining their their symptoms and causing relapses. And I really wanted to shy away from that here. And the objective stress scale did it for me. So mothers who might say, Oh, I was so embarrassed. I was ashamed because I got upset and that's bad for the baby. Ma'am, it's Hydro-Quebec who kept you without electricity for 45 days and you were not responsible. So kind of relieving some kind of guilt that some moms had. So after a few years, it was really obvious. OK, prenatal maternal stress is having an effect on these kids. But how is it doing it? What are the mechanisms? So that's where being at the Douglas Hospital Research Center and being at McGill has been a huge advantage because there's there are people here that are experts in some of these mechanisms. So at the Douglas Hospital, we have Jamal Luheshi, who studies immune function. And I had seen papers on schizophrenia in which people schizophrenia of higher levels of pro-inflammatory cytokines. So when we got the blood from the kids, my student, Frans Verrou, rushed back to the Douglas, stimulated the blood with various chemicals and looked at the cytokine response. And it was the objective exposure and the mom's cognitive appraisal that predicted what's called a TH2 shift. So a shift towards more pro-inflammatory cytokines. And this is the kind of shift that is associated with asthma and allergies and that kind of thing. So this might be a mechanism. And then with Moshe's shift here at McGill, we also got blood from these kids when they were 13 to look at DNA methylation. Did Michael Meany show heat maps like this? He didn't describe what they are. I will. I'll do it. OK. So this is Leigh Cow. She was the postdoc that we hired to look at the epigenetics. So this heat map. So each column is a different kit. OK, so these are their ID numbers down here along the bottom. And then each row is a CPG site. So it's a little point on the DNA. And the more red the cell, the greater the methylation and the more green, the darker the green, the less methylation. So in fact, what this is, is this is showing you the correlations. The correlations between storm 32, the objective stress, and the amount of methylation. So a very red cell would mean there's a really high positive correlation. And a really dark green cell would mean there's a really high, strong negative correlation. OK, so when Moshe's shift looked at this result and saw that the storm 32 objective stress questionnaire correlated with 1,675 CPG sites, he said he had never seen anything so clear except in cancer in humans. That this fell out very well. So we saw that the objective stress was associated with this DNA methylation. Then we saw that the cognitive appraisal was an even better predictor, so where before we had 1,675 correlations, here we had 2,872. And you can see up here all these kids down here, their mothers had a negative cognitive appraisal of the ice storm. It was very negative or negative, and the ones in red had either neutral or positive cognitive appraisal. So again, a very clear definition there. So it's one thing to be able to predict DNA methylation. OK, we've shown that there's an epigenetic signature of this stress. But in the end, who cares? You know, nobody ever got, you know, was refused from a job, rejected from a job because their DNA wasn't methylated enough, right? You want it to predict something on the other end. So that's been Leigh Kau's job for the last few years. So what we found, again, was objective exposure, cognitive appraisal, but not subjective distress, predicting the DNA methylation. And then that goes on to mediate the effect of the prenatal stress on obesity, on insulin secretion, cytokines and a number of different things. So now we're showing some of the mechanisms by which the prenatal stress is influencing these outcomes. So since there I think there's a neuro, the word neuro is somewhere in the title of this workshop. So I thought maybe I'd tell you a little bit about the brain. So we did brain imaging structural MRIs with the kids at ages 11, 16 and 19. And this is just a couple of examples that I'll show you where we looked at the cerebellum. So the cerebellum is developing at the end of pregnancy and it's generally thought to be associated with smooth movements and coordination. So we showed that the more severe the objective exposure and if there was a negative cognitive appraisal, the larger the cerebellum in these kids at age 11, and then that mediates the effect on bilateral coordination and balance at age 13. So not just predicting the brain but going the next step and saying yes it's important to something that you can actually see and measure in the kids. Where subjective distress is making a difference. So the greater the mom's PTSD symptoms, following the ice storm, the smaller the surface area in this particular part of the brain at age 11. And then when we looked at cognitive development at age 13, we only had effects on more verbal intelligence. And these correlations are like 0.3, 0.4, 0.5 between the surface area and there with a significant mediation effect but no effect on more behavioral or visual outcomes. Okay, so then I think, you know, that I'm preaching to the choir at this point. I think you're all convinced prenatal maternal stress is having an effect on development. But what might we be able to do to counter that, to somehow interrupt this signal that is going to the placenta and to the fetus? So what might we be able to do in pregnancy? So I mentioned that the Queensland Flood Study piggybacked on a randomized control trial of women who were going either into a midwifery group care where each woman has a primary midwife and then knows the other midwives in her group so that when she gives birth, there's somebody she knows well or standard care which is basically you show up at the hospital and you get who you get, whoever happens to be on. So after the, so we had the Edinburgh Postpartum and Depression Scale that's administered routinely in Australia to pregnant women. So we had an assessment before and then at six weeks after the birth as part of that RCT, they administered it again. And what we saw was that it was especially in when the objective hardship was moderate to severe that we saw that the prenatal care made a difference. So the dotted line is standard care and the blue line is this MGP midwifery group practice. So for women in standard care, the greater their objective hardship, the higher their depression at six weeks where that was not the case. So women appear to have been buffered by that midwifery group practice for their own mental health. And if you talk to Sue Kilday, she'll tell you stories about how these midwives had established such a bond with the pregnant women that sometimes they would drive, they would go and save them and rescue them from wherever they were. They would really go the extra mile and then they were also there to listen to them because you've got a known midwife. So this is how, you know, in setting up a society where we have better prenatal care for everybody all the time, we would be preserving at the very least the mental health of the women and I have a slide that I'm not showing you, but the infants are doing better as well of these moms who were randomly assigned to get the midwifery care. What about during a disaster? So you'll recall that from the Iowa Flood Study, we had assessments on a number of women from before the floods happened. So this is a study that was published using 145 of the women that had a social support questionnaire that they filled out before the floods and while they were pregnant. And yeah, I think I said everything I had to say. So they were, yeah, I did. So we looked at the IDAS General Depression Scores. The author of this study was looking at trajectories of depression over time starting in pregnancy then in postpartum months to 16, 18 and 30. And she found that the greater the received support from her husband or from her partner, the faster the decline. And depressed of symptoms after the birth. And then what about post-disaster? So this is what I'm working on with in the Hurricane Harvey Study with Johanna Bick at the University of Houston and using the online, simple online intervention that we established for the Fort McMurray Fires. So we, using red cap, women are recruited. They answer questionnaires. Then red cap platform randomly assigns them to one of three intervention groups. The red group, A, they do Jamie Pennebaker's Expressive Writing Intervention, which is they go online. They're prompted and they write for 15 minutes, 15 minutes a day for four days about their deepest thoughts and feelings on day one about the flood, on day two about relationships with other people related to the flood. Day three, the worst trauma that they've ever had in their lives and you get the idea. So they're writing their deepest thoughts and feelings. Group B also do 15 minutes a day for four days, but they write about neutral topics like diet and exercise and things like that. And then group C does no writing. So these are preliminary data from the first 300 women or so that answered not only the recruitment questionnaire but also the two-month post-intervention questionnaire where we repeated the assessments. And a zero up here means that they did no change and negative numbers, this is the amount that their PTSD symptoms declined. And from before and after the intervention. And at first we had absolutely no main effect of the intervention and I was ready to be very depressed. But then I thought well maybe it's the people who were the most impacted for whom the intervention would have been the most helpful. And so we have this one item on how much was your flood, how much was your house affected by the flooding from completely untouched down to a continuum of totally destroyed. And we saw that the more severe the damage to the home, the greater was the positive effect of the intervention. We also saw, I didn't put it in, we also saw that the lower the household income, the greater was the benefit from the intervention. So there is something that we can do afterwards. What about in childhood? So a woman has been through a horribly stressful experience in her pregnancy, now she's got a toddler. Maybe the toddler has problems, maybe not. But what can the mom do to help the situation? So controlling, so when the kids were 16 months of age, they did a little task with their moms. We videotaped it and rated the moms emotional availability and one of those subscales is structuring. So to what extent does the mom help the child structure their task as opposed to telling them what to do or doing it for them or not doing anything at all? And we found by looking at the children's language scores at age two and a half that if we break it into high structuring moms, which is the black line and low structuring moms, which is the red dotted line that learning to structure or moms who structure more, their kids actually improve even in the face of high maternal distress from the floods. So I'm almost done. I just want to leave you with one last idea and that is the real importance of prenatal maternal stress and trying to mitigate it. And that is because one thing I didn't happen to mention before when I showed you this model is that inside that fetus, so not only do you have the mom who's got mental health, right, and we want to preserve the mom, and not only do we have a fetus that we want to reach its full potential, but inside that fetus, if it's a female, are all the eggs that she will ever have in her lifetime. And so all of the grandchildren that will ever come from that fetus are also being impacted. If it's a male, then all the progenitor cells that will produce all the sperm that that boy will ever have in his lifetime are also being affected. And in animal research, they have shown that stress to a pregnant dam will be visible in their children all the way down four generations. So what I hope to end my career with is some knowledge translation, some knowledge mobilization to get out there and make pregnant women be cared for and be seen as a highly vulnerable population following any kind of stressor. So in conclusion, I hope I've convinced you that, first of all, you never, ever want to do natural disaster research because it's really hard and stressful, but also the importance of separating mom's stressful, mom's stress experience into different components. And I think we're coming up with conclusions that are counterintuitive but important for the moms. We also see that the fetus is highly sensitive to what's going on in the moms' environment and that there's a real value in combining a social science approach, which I think I am, with neurodevelopmental mediators and psychosocial interventions to really try to put this whole model together. Also, as a social scientist, I will say that it is very humbling and frightening to go and talk to somebody about DNA methylation or epigenetics, and they go on about histones and stuff you don't understand. And it's very humbling to say, slow down, I don't understand, explain it like you would explain it to your 12-year-old nephew. Yes. So there's something humbling but really, really valuable in reaching out to other disciplines. So obviously, I couldn't do this alone. Lots of people along the way have weighed in. And then I wanted to leave you with a slide that I stuck back here. These are, this is a list, a partial list of all the things that we've measured in one or another of these disaster studies. These are a lot of the moderators, whether they're biological, social, psychological or whatever. And these are a lot of the outcomes and mediators and moderators. So I'll just leave you with that. Thank you very much for recent news I was just looking at. So there's 93 deaths in COVET alone were due to the heat wave. So people, like children and pregnant women, will also be sensitive to the heat wave effect. So would this be like something that could also be studied? Because I think you could also look at people who are, let's say with the Montreal, you can say you look at people who have air conditioners and yogurt air conditioners and see like, say, what are the comparative effects there as well, right? Yeah, sure. So I think animal research, especially where they can randomly control like the climate in their cages and so on, shows that heat is a stress. So when we talk about heat stress and does affect the offspring. So how would you, how would you go about tackling that research question? Does the does the recent heat wave influence pregnancy outcomes? I guess serving serving the city or hospital clinics. Seeing. Seeing what are the women who have gone to clinics and complain about like adoption or something. Recruit them in a city. Which will we take women who complain? No, no, because the fact that does become a certain. So I don't know how the rest of the recruiting happen. Yeah, I mean, you can do this different way. So one of the one of the problems with Project Ice Storm is that I had a 15% response rate to my initial questionnaire. So I sent it out to 1140 women and got 227 back. And the women who responded were highly educated, high income families. So they're the ones that are interested in science. So everything that I've presented is is valuable in a dose response. So the more days without electricity, all of that is quite valid. But it's not generalizable to the population. So we could we could attack the the heat question in the same way that I'm actually attacking or going after the Project Ice Storm study. So the grant that I'm working on now or that I have now is to get all of the health data for everybody that was born in 1998, the three years before and the three years after in the Monterey G, which is over the bridge, the hardest hit area. And then also in a comparison area in near Quebec City, everybody that was born in 1998, three years before the three years after. And then because this is Canada, you couldn't do it in the states, but because this is Canada, we've got every visit to a practitioner, every diagnosis that a doctor is given, every hospitalization, every drug that they've been prescribed. So there we can see if there's a blip. So we could do that same thing. We have to wait for everybody to be born and to have some problems. But you could look at birth outcomes. You would not know, you would not be able to bore down deep necessarily to whether or not they had air conditioners. So maybe you would do something qualitative on top of it. But to really answer the question, you'd probably want to look at the administrative data. You could always look at SES levels by neighborhoods or GIS or something like that to see if, you know, maybe the effect will be greatest in lower SES that maybe have less access to air conditioning. But that's a good point. I'm just wondering, it seems like the, I think some people would be really hard to get everyone's, you know, like life of history. How do you, you know, begin to talk about it for this, for the, like what you were just talking about, the ice farm. Right. So Quebec has a commission for access to information. And it's quite a lengthy process to apply. So of course we will, we will end up getting the data that is anonymized. And we have to go to a special place where we can do the analyses on their computers, you know, and I don't know if they're going to pat us down and make sure you don't have a USB key or something on you. And there's no access to the internet. It's very, yeah. So they make sure you're legitimate and, yeah. You talked about now, the disasters, these disasters are often quite complex, actually. They consist of a lot of components. Sorry, so do you, do you read the social answer, what part of the disasters that you're making, do you think it's going to be, for example, 10 to 20, like, contribution by someone, can you say one, one, one, one, one, one, one, one, one, one, one, one, one, one. First, first, first, it's time and then the next, and then the next. And so, you want to assume, for example, a lot of people don't understand or I don't know what is the time. Do you really need to be kind of on what part of this is going to be like? I think so. And so in all of these studies, we've got threat, loss, scope, and change. And in the threat, we could bore down and say, you know, what type of threat. So one of the things that we'll be having in the Hurricane Harvey, because we haven't created the objective stress scale yet, but a lot of people saw dead bodies or saw people be killed. One woman wrote that she and her her friend were going to cross a small stream and they didn't realize that there was an electrical wire that was in it and her friend went in before her and was killed in front of her eyes. So this kind of thing, you know, I don't know if we knew that that was, you know, that's the worst thing that can happen. Yeah. Your example is great. You can see there's a puncture there. Yeah. It's a very good situation. The radiation, the anxiety, the radiation, you know, it will have to do with what's happening and how it will make sense. It's a very different kind of conflict. Yeah. With Hurricane Harvey, there was real concern about contamination from the Houston Ship Channel. And we found somebody at Texas A&M who actually had done a study. She had been sampling soil samples around Houston before the flood happened, and then she went around after and she could show, you know, where were the hotspots and they know where all the contaminants are and so on. So she'll be able to give us by zip code, not only the flooding level, but also the potential for contaminant to get in there. So but you're right, there are a lot of different levels and some disasters are simpler than others. I mean, to me, one of the significant things is the site of the radiation has been going through, but one of the consequences that I didn't think you might have been able to keep in control in some instances is that the subject is stressed out a lot, because it will have to explode. And it's often weird to look on the way around it. Just calm down. Just calm down. Thank you. I was probably maybe a little bit upset, but you might have said a few things to people. Yeah. Who's at the point where it can't please the person in front. Yeah. There's one interesting result that has come up in Project Ice Storm, Iowa Flood and QF 2011. We haven't done analyses on the others, which is that very often the worst outcome in the child is of mothers who have a mismatch between their objective exposure and their subjective distress. So it's normal that overreactors, so moms that had very low objective exposure but high subjective distress, you'd say, okay, I can understand that their kid has more problems. But we have equally severe problems in children whose mothers had high objective exposure and low subjective distress. So underreacting moms. So it gets complicated. Actually, he had his hand up first. Yes, sir? I just have a question. Is there a factor about the confusion? Like, in some cases, you can have some big, big gains. Like, you kind of, you know, like, a little bit of story and kind of, like, you state that in the next few days there are some highlights and some biases that could influence basically this kind of like this. And do you have any measures on your object related to these kind of things? So one of the, in the beginning of the talk, I showed that paper where they're talking about 10 different aspects of a natural disaster exposure. One of them is the speed of onset. And so we, especially in the floods, we ask, and the fire, we ask, you know, when did you first know there was a problem and so on? How much time did you have to get out of your house? I know that with the Iowa flood, it was four days before it got to, the flooding got to Iowa City, which is where we did the study. So, you know, I have a book that lays it out where, you know, on, I don't know, June 4th, you know, it was flooding up here, then on June 5th it was flooding here, and it moved down. So I think that there is something really important about speed of onset. Speed of onset and exposure. I don't think we've looked at that item in particular. That is just one of many items that go into our scale. But hey, if somebody has a hypothesis, come on down. We've got plenty of data and you can test it. So when you say that mismatch between high objective and low subjective, the low subjective, did you look at any internalization measures like in mothers, or was it only the tactic to explicitly recognize that I'm stressed and I'm being stressed? So we had, so in Project Dysdorm, we had just the measure of PTSD symptoms. So it is normal. I mean, it's normal to have these avoidance, hyperarousal, intrusive thoughts and so on, immediately after a disaster. What's not normal is to have that sustain five or six months later. So that's the only measure that we have in Project Dysdorm, but in the others we have peritraumatic distress and dissociation. I'm trying to remember your exact question. How is the objective distress as measured? If there were any measures of internalization of distress? Well, in internalization. So in the peritraumatic distress inventory, they're asked about symptoms of anxiety and depression. So the PDI, the peritraumatic distress inventory, I think gets at the best what you're looking at in internalizing. Jeff. I was thinking, one thing, I was just thinking about this question of the question about pre-disaster measures that was raised during my talk, and also you mentioned sometimes the urgency that you go in. These events just happen, you know, out of come out of nowhere and so you don't have all the data that you might like to answer the questions you're trying to answer. So as an example, the village that I worked with, the non-dysplex village Verruda, there's talk that they will be displaced. So I just wanted to make the point that if you're an ethnographer if you're working in a region and you have longer term kind of relationships with these places, as a researcher and also addressing the question of complexity, if that were to happen to Verruda, for example, now you have all this pre-human induced disaster kind of measures on the biological level and subjective level and all those things. So just another thing to talk about, the depth, the bad things are always happening all the world all the time, right, and the more research you do and the more you commit to a given place, you're certainly going to be able to understand things more deeply and have more information as you go forward with just different things. Okay, very good. Yeah, so almost any ethnographer, you know, they're going to, these events are going to be hitting the community you're working with in some way. These are the kind of issues that you're interested in. I was in Dubai in April. They're going to be underwater in 30 years, so get started. So it's an interesting question, the notion of prediction, what really they do, they experience in the past. I think that I just see what happened in the game, the social prediction, could be kind of a more stress or more impact. Yeah, I mean there's another component of the stress experiences, whether you have experience with the event, you know, in Florida they don't bat an eye when there's another hurricane warning, but if it's your first hurricane warning or if you just move to Los Angeles and you feel the ground shake, you know, it doesn't bother them, so your experience is another component. You had a question? You live into certain values about how important it is to express your self, but the writing intervention, for example, talking about the charm of her life or you and her life in yourself, or the idea that mismatch which is where you're under expression or distress, that would be bad for health, bad for health, but you yourself might create the reality that it is bad not to express it, but not how every culture has the value of it and self-destruction is going to be healthy. I don't know if you have any thoughts about that. No, no. I don't. The point that I just like, the issue of control is kind of for Western there, is the key... the issue of stress, often, I mean, one of maybe several factors, do you have control or not? I've always thought that is very Western, the thought that we should have control over our lives, or maybe it's very wealthy or something. And through some of the methods I was talking about, I think there are ways to get at alternate kinds of... I mean, in this case, like stress measures, for example, I think that's very important, because I wouldn't necessarily... I love that issue of control. I have the answer that's what's connected to some of the even objective kinds of stress responses that we're seeing. I think it's a very good question and very important. There are ways to develop, like I say, some of these alternate metrics to get at some of that stuff. So we can look in like... certainly in the Hurricane Harvey study, we have a large enough sample and a large enough diverse sample that we could look at differences in, say, Hispanic and non-Hispanic whites. So the whole white Anglo-Saxon Protestant, you know, work ethic and control and everything is quite different than the more Hispanic focus on family and people. And, yeah, I don't know. We could do that. So this is actually a great place to end. These questions being... definitely this afternoon because it's just a big question. I thought with parents, we're going to also learn about the study and the animations going back to the beginning and we're going to be able to take it to the end and talk about it right now. Thank you very much. I just want to show before we go to lunch the sequence of presentations that I've already got there. The sequence of presentations this afternoon. So we will know when you're... ... So thank you very much. Thank you again. Thank you.