Good afternoon and welcome. My name is Alex White. I'm delighted to have been asked to chair this afternoon's event, which is the second presentation of the 2022 environmental resilience lecture series co-organised by the IIEA and the Environmental Protection Agency, the EPA. And I'd like to recognise at the outset and thank the EPA for their sponsorship of the series, very much hoping to hear from them in the course of our event this afternoon. And we look forward to that. But thank you, as always, to the EPA for their support and sponsorship. Today, we are delighted to be joined by Professor Joseph Allen, all the way from Boston. And I'd like to thank him for being so generous with his time to speak to us this afternoon. Joseph G. Allen is director of the Healthy Buildings Programme and an associate professor at Harvard CH Chan School of Public Health. Before joining the faculty at Harvard, he spent several years in the private sector, leading teams of scientists and engineers to investigate and resolve hundreds of indoor environmental quality issues, including sick buildings, so called sick buildings, cancer clusters, and biological chemical hazards. His academic research focuses on the critical role the indoor built environment plays in our overall health. In other words, leading experts on healthy buildings. Dr. Allen is a regular keynote speaker and advises leading global companies. He's the co-author of Healthy Buildings, Healthy Buildings, which is a reasonable title for a book, given his area of interest. The title of Professor Allen's presentations after tackling air pollution. He's going to speak to us for about 20 minutes, after which we'll move to the Q&A session. You'll be able to join that discussion using the Q&A function on Zoom, which you should be able to find easily enough on your screen. Feel free to send in your questions throughout the session as they occur to you. We'll also make that point at the outset if a question occurs. Don't wait until you think there's now time for questions. Just put it into the system and we'll have it there ready to go when we come to that part of the event. Please identify yourself, if you wouldn't mind, and your affiliation to any organization if indeed you have one. Today's presentation to remind you is and the Q&A are both on the record. And you can also join us on Twitter, by the way, if you're minded to do so. I can see on my screen that thankfully we are joined by our good friend and colleague, Dr Mihal Lahan, Director of the EPA's Office of Radiation Protection and Environmental Monitoring. And I'm going to invite Mihal now, if I may, to offer some opening remarks this afternoon. Mihal, you're more than welcome. Thank you, Alex. That's great. And just, I'd like to also echo that welcome to this second event and the Environmental Resilience Lecture Series is co-organized by ourselves and the IEA. I mean, you've mentioned there that Professor Allen, you know, will be highlighting the strategies today in combating air pollution in indoor environments. The ability to be hitting health effects of poor air quality and substandard housing conditions are often overlooked, but indoor air pollution leads to millions of premature deaths every year. And, you know, he'll be outlining the key findings, as you mentioned from his book, Healthy Buildings, how indoor spaces drive performance and productivity, which was recognized as best book of the year in Fortune Magazine and the New York Times for two consecutive years. And from our perspective, the EPA, we don't monitor indoor air quality, but we have established a national, extensive national ambient air quality monitoring network for outdoor air quality. And this network will be completed this year and consists of 116 stations located right across Ireland. And in addition, we've improved both the availability and the accessibility of air quality information from the network and thus an association with the health service executive, you know, developed and generated this national air quality index for health. Separately, and linked, though, is a true and EU funded project called Life Emerald. The EPA is developing models based on the monitoring data that we are collecting from our network, the variety Irish public with a three day forecast of ambient air quality, and they meant probably to make informed choice about their daily activities and now cast, which is providing modeled air quality information to fill in between the stations that are on the network and historical maps to give detailed information in local areas. So following the success of a citizen science project called Clean Air Together in Dublin, which had over 1000 citizens monitoring air quality, in this case a traffic related pollutant, around their homes, offices and schools. The EPA with on Tashka have recently launched the Clean Air Together in Cork. And if we've had a great response for the public there were over 900 participants taking part, and they've just begun that monitoring now. And for me, you know, this is all about yes it's about collecting valuable information about air pollution, but it's also about getting the people and the public engaged and involved around air quality and air quality issues. And the link, you know that the link between solid fuel combustion for home meeting in our towns and villages has a negative and the negative effects of the fine particulate matter PM 2.5 in ambient air is well understood. And it's been highlighted by ourselves in many successive reports over the years. The understanding of those impacts at low levels as well as this pollutant PM 2.5 has also informed the World Health Organization to reduce and significantly reduce its annual ambient air quality guidance level. And I think in addition to this, this is where today really is important I think for us and for everybody's interest in air quality. There's a growing volume of research and the impact of solid fuel heating systems on our indoor air quality. So really looking forward to listening more about the impacts air pollution on our indoor spaces and the strategies to combat air pollution indoor environments to make our homes or schools and our offices healthy places to live study and work in. So now invite Professor Allen to deliver his address. Thank you that was a really nice introduction and I'm looking forward to the conversation is quite an honor to be to be invited to hopefully set the stage for a rich conversation and question and answer session. On the topic of environmental resilience and specifically the role of buildings, right as we think about outdoor air pollution of course the dirty secret of outdoor air pollution is it penetrates indoors. Because we spend the vast majority of our life indoors, even as that outdoor air pollution concentration is reduced as it comes inside the majority of your exposure to outdoor air pollution occurs indoors. That should surprise that does surprise a lot of people to hear that majority of your exposure to outdoor air pollution can occur indoors. So this session is kind of set the stage for a rich discussion but also place buildings at the center of a lot of these problems we're talking about buildings consume 40% of global energy in some cities at 70 or higher 70% of global energy they're at the center of our climate crisis. We spend majority of our time indoors and we see an indoor, how the indoor environment influences our health. So because buildings as I hope to show are the center of the problems that means they're at the center of the solution center they have to be as we think about long term climate mitigation adaptation, and also healthier indoor environments. So I'd like to start my presentations with a little thought experiment asking people. What you know about healthy living. So if you ask a general audience, what do you know about healthy living and also how do you know what constitutes a healthy lifestyle. If you ask that question you're going to get good answers around things like this, I know I should exercise every day that's good for my health. I know I should eat healthy, and we know what healthy foods are we know what unhealthy foods are. We know that outdoor air pollution is bad for us, we know we shouldn't smoke cigarettes. And so, how do we know all of this. I'd argue that we have much of the knowledge or what the public understands constitutes healthy living comes from these great human epidemiological cohort studies. They follow tens of thousands of people for years decades and look at their lifestyle environmental factors genetic factors and health outcomes. And if you look at all of these great studies though you see a glaring hole, none of them talk about the role of the building. And because we don't look at the building in these great big studies these long term cohort studies. We have a knowledge gap, and the public therefore has the knowledge gap. So in its place what we have is a relatively small field of indoor air quality scientists, relatively under well underfunded grossly underfunded compared to other aspects of environmental health and public health.  We don't actually have to go much farther than look right at what happened with coven and why, and why this was such a problem, besides being novel to our immune systems. We had a failure to recognize that the building plays a critical role in keeping us safe from this respiratory virus and others. I've been writing about this from the beginning of the pandemic. Here's an article in the New York Times March 2020 placing buildings at the center of our response to the coven 19 crisis. Yet if you recall that time period, much of the guidance and it's still persist today was around full might transmission or shared surfaces or droplet transmission, and this idea that if you stay just two meters or six feet from somebody you're going to be safe and we were cleaning our deep cleaning buildings and people didn't want to handle the mail or be careful with groceries. We fundamentally missed that this virus is an airborne virus, nearly all spread happening indoors to spread through the air, all spread indoors nearly all. I mean, well buildings had to be the centerpiece of our response. And for much of the world miss this for a year or more. So I don't want to dwell on Kobe but I want to talk about four fundamental shifts that are coming out of Kobe as it relates to our buildings. The first is this, as we are here.  When you're with other people you're out at school the office the grocery store, we are constantly meeting emitting respiratory aerosols. These aerosols are all different sizes. The majority, if someone's infectious the majority of that virus travels in the smaller aerosols that trouble well beyond two feet two meters. This is a work we did with the New York Times visualizing respiratory aerosols in a classroom. Same thing would hold in any office conference room bus airplane. Very quickly you see that the aerosols of everyone in the room are mixing and they're traveling beyond this. They fill up the room. So we have all spread happening indoors we have aerosols that travel beyond two meters and a buildup of aerosols in under ventilated or under filtered spaces so the first key way is that the scientific and medical literature is being rewritten really was decades of over focused on droplet transmission these these large droplets that fall out of the air within two meters. That's being rewritten in the top medical journals the England Journal Medicine the Lancet Jamma. Global scientists agreeing on this. And it's this principle that as you have an infectious person, relatively quickly, these aerosols travel very quickly beyond two meters or six feet fill up an entire room and the concentration of infectious particles. Viral particles in in the air is dependent upon the size of the room, number of people infected and ventilation and filtration and with relatively simple strategies, increasing ventilation enhancing filtration, you can decrease the concentration. So that's number. First fundamental takeaway is this airborne transmission being recognized as the dominant mode of transmission we should have gotten this right in year one took several years to get there. And second key takeaway that says the focus on buildings now is not going away. We have a very savvy public now. Everyone is an effect is very knowledgeable and infectious disease infectious disease transmission. I always say my neighbor now talks to me about filtration and ventilation. The first thing I pulled from the website called glass door, which is where people talk about their jobs. Usually, they talk about salary and culture and what job title they have and what the work is like. Well they're also talking about their building. In my book I talk about it as your employees are interviewing your building. This is the first time that I thought was really quite interesting. This company now has this statement linked to their company forever, where someone says how is being in this office any different than being on a virus infected cruise ship for eight hours a day, five days a week. So employees are recognizing that the building is playing a role in their health. So if you've ever spread awareness of this, you have an entire media and social media media ecosystem focused on this. That's not going away anytime soon. And in fact, you have people now monitoring indoor air quality and reporting on it. I showed this on CNN this monitor, I have several monitors behind me right now, they're relatively low cost. So we're sharing this the same device now that used to be available only the scientists people can go in and they measure in the school the classroom in a coffee shop and they report on this in social media. So hyper aware public that is now has the tools to measure and verify indoor air quality. Okay. It has finally been recognized that buildings are central to this fight. I'm proud to have been an advisor to the White House for the past year in the US. As of February 2020 President Biden elevated buildings this clean air and buildings challenge elevated it on par with vaccines therapeutics testing in the pandemic response. That is a major shift and it will lead to a continued long term shift. And here's the what's coming next. The problem has been that you have buildings built designed for low ventilation rates. This is a figure showing 100 year history of ventilation rates. I'll go through all the detail but I want to point this out the dotted red line is the level at which we knew 100 years ago was sufficient or helpful in reducing or mitigate infectious disease transmission indoors. In the past 100 years globally we have decreased the ventilation rate. So is it any surprise, we have a novel virus that spread through the air. It's fairly indoors meets a building stock that is under ventilated we choked up the air supply in our buildings these respiratory aerosols build up and if you look at every single super spreader event. You'll find that same thing time indoors under ventilated under filtered. This is by design. We designed our buildings incorrectly for the past really been the past 40 years in particular, we've decreased our ventilation rate. If you about this, I want to highlight a report from the Lancet COVID-19 Commission, I chair the Lancet's task force on safe work safe school and safe travel. We put out a report just a couple weeks ago trying to simplify this, the first four strategies every building should pursue one, give your building a tune up, just like you do for your car. We do this every year for a car building similarly start to perform worse over time, we need to give them a tune up to bring them back to where they should be performing. So minimize ventilation rates, upgrade your filtration, deploy portable air cleaners where necessary. That's the third big change coming to fourth is this. This issue of COVID and ventilation air quality has now opened a much more broad conversation about all the factors in the indoor environment that influence help. So here's a report my Harvard team put out called the nine foundations of a healthy building. We're talking about water quality, lighting, biophilic design, the influence of dust and mold and acoustical quality and thermal conditions. And what I've seen is that the entry point to be thinking differently about our buildings was COVID ventilation air quality, and now major multinational organizations companies, the White House in the US are rethinking our entire strategy around how we can improve the condition for everybody indoors with a wider lens on what constitutes healthy buildings. I tell you I have more content, but I'm right at 820. And I want to be sure we have a lot of time for question and answer and discussion. But some of the other things maybe I'll just tee up before I finish here is that there's a great convergence happening. When you had a green buildings movement focused on energy efficiency and climate. You have a smart buildings movement, talking about sensors and smart buildings and maybe indoor air quality. You have the safety professionals and the safety and security community over here. Well there's this great convergence happening now that has to happen and it's converging around healthy buildings. Because we have to design buildings that are both optimized for human health and safety and comfort, without ignoring the building buildings contribution to climate change. And there's been this false dichotomy presented for decades that we have to have either a healthy building higher ventilation rates use more energy or energy efficiency. We choke off the air supply and have an unhealthy building. That's false. And there are many examples of how we can actually optimize both optimize indoor health, while making sure we're protecting health beyond the four walls of the building through better energy decision There's a lot to talk about on the climate side sustainability side, healthy materials, the business case for healthy buildings. I want to see what you all want to talk about. And I'll say this last thing before we get to question answer and wrap it up on a high note here. Like I said that buildings are the center of all these problems that means they're the part they're centered to the solution set is not just that we don't know what to do we actually have the tools available to us. Nothing less than this is at stake. The decisions we make today regarding our buildings determines our collective health now and for generations. That is said without exaggeration. So I want to thank you for letting me open up just a few comments hopefully to see the nice conversation here and I'm looking forward to what questions and comments. You all have thank you. Thank you so much. And, in fact, you did a lot better than 20 because of course you, you could have, you could have taken a few more minutes because you were giving you credit for the fact that are my introduction and beholds introduction were there as well. So we're only just up on 20 past and our people I'm sure are very interested but they're a little slow coming with their questions but we've got some already. If that occurred to me I just ask you, and you did an interesting contextual reference at the outset so during COVID so much of what the public health advice and the, you know, government advice had to do with proximity of individuals and all the stuff that we were told you know two meters and support. And whereas some so many other things were not in fact referenced or at least not referenced sufficiently early on, or in a sufficiently robust manner that seemed to come into the debate, although there were some voices perhaps some lone voices even here in Ireland and furnace, and who were saying that these were that this was the agenda we should be looking at. And just that I wonder had to do with the kind of imperative of, you know, getting the advice out so that stuff that could be done quickly, you know, stuff that people felt they could do quickly, maybe was in the area of proximity and you know, handwashing and all the hygiene, and that there may have been a perception and really I suppose this is my question I wonder how fair is that perception that really the things we need to do with buildings are going to take longer. They're much more obviously at the design and build stage well then that's, that's to do with the design and build of a building, and even some of the adjustments that might might usefully be made to buildings they take time. I'm just wondering, could you reflect for a few minutes on that whole business of like the kind of the the timelines are the sort of change that you say are most important perhaps mitigating against the public health advice is the fear that these things just take too long to rectify. I think it was a couple of really good points there and, and we could talk about really what implementation looks like. I think that's fair. I tell you the first piece I wrote before that New York Times piece in March 2020 was early February 2020. In financial times, and it placed buildings at the forefront of the response, but acknowledge that there was a lot of uncertainty. And until that uncertainty was resolved, we should do a lot of everything. Which meant, yeah, hand washing makes a lot of sense distancing makes sense there's in your cone of emissions is greater at close distance. So that makes sense. My real issue was that in the, in the totality of response in the early days and early months in fact the first year, the buildings were ignored so it was very much a, we should do all this stuff we tried everything flatten the curve we did a little everything but we didn't do a little thing when it came to ventilation and filtration. And my goal like many scientists around the world wasn't just me there are plenty of voices out there trying to raise the alarm I co authored a piece to the WHO in science with an international group of colleagues all over the world. Great scientists and indoor equality, raising the alarm on this thing. Well this has to be part of the discussion. And we don't do these other things masking was important all this was very important, until we resolved it, right it's precautionary principle but we had evidence before SARS cope to, for example, SARS one, we had evidence was spread via the airborne route. So there was a lot of pushback that so we don't really know. In fact, if you look at my fields scientific literature we know that ventilation and filtration are key to reducing risk from influenza indoors and measles and TV and SARS one so we had plenty of we had everything we needed to know. And if you look at that first report is very similar to this last report I mentioned the first four. So what were the first things we're calling for better ventilation better filtration, and portable air cleaners. So let me address the implementation question. This fair. Well this is too expensive to overhaul my mechanical HPAC system or it takes two years to do this. It's too expensive. I don't think that's the case one on the expense side. There was, and if you had billions of dollars of stimulus globally. Right. And we the money was there in terms of the response is also not expensive to do these fixes. And we also laid out a plan for what you can do in the short term, while you address let's say the building level systems that might take longer. For example, written 50 articles and New York Times Washington Post in the US saying, we could deploy portable air cleaners, and I talked to all the manufacturers they had the stock available portable air cleaner with the HEPA filter. You could put in this room or any room and if you size it right. You can get four five six air changes per hour of clean air typical home in the US has half an air change per hour typical school has one and a half air changes. One and a half hour of air with a simple plug and play device that costs a couple hundred dollars let's take schools for classrooms US dollars. That's a couple dollars per student per year. You could clean the air, while you're thinking about how to spend stimulus dollars on an overhaul of your mechanical system if that's what's needed. So we have the short term solutions, while we could build to the longer upgrades if needed. If you look at this first four report from the Lancet, I think it's really important because we got our expert group of international scientists. And we got together and said, What are the four things if every building did it's very doable, not expensive and would really move the needle or you know improve the condition of people in buildings residential offices at factories. And the first one is really important that tune up idea. Because that's something every building can do right now, and buildings have are built to a design standard not a performance standards they slip over time. And if we just brought buildings back up to the way they were performed. That improves empirically studies have been shown improves overall indoor air quality, and saves energy good for climate and saves money. So it's actually a cost saving approach that improves indoor air quality. That's the absolute first thing that has to be done and then you could think about how do I go above and beyond with filtration ventilation and use these portables as a stop gap measure. So I don't think it's the case. I think it's a fair question. A lot of people have that question I don't think healthy buildings are expensive I don't think they're hard to do, and we have short term things we can do to respond while we work on longer term improvements. And so plenty of questions coming in now and plenty of interest. I'm going to put, I'm going to pitch two questions at you. First of all, a Theodorus van Veltovan asks a simple and straightforward question. What's a cost effective and easy measure that many people could take to improve the air quality of their own dwelling. And I suppose ally to that is the fact that so many of us are are working from home so much as as indeed I am today for example and many people do so. Simple and easy measure cost effective and easy measure and then I'm going to put the other one to you as well at the same time if you don't mind sort of memorizing both short question as well. Certainly Joseph Brogan says that research has shown that plant based ionizers are effective in significantly reducing aerosols indoors. Is this hybrid approach the way forward he's one. So a couple thoughts there I like the question about the home and I'll take it beyond COVID how do we prove into our quality first. Let's take the source control. I think we have to do a better job at thinking about the products we put in our homes. We have to be low volume organic chemicals, thinking about other semi volume chemicals like these forever chemicals if you're not familiar with them the stain repellent chemicals that actually associated with the whole health, whole host of adverse health effects. So do a better job. In terms of our, the source control, switching out natural gas stoves for electric stoves natural gas stoves and then a whole host of indoor pollutants that are bad for respiratory health exacerbate asthma. So that's number one, to I think some simple things if you don't have mechanical air should be opening up the windows as much as we can increase ventilation rate so I'm a bad example here. So my CO2 levels I have my meter somewhere, you know, generally very high in my in my office unless I crack open the window a little bit. We've really tightened up our buildings. We can when the weather's nice open up the window some really simple things. I'll give people a tip on that one. My Harvard team wrote a report called homes for health. And if you just search on this look up Harvard healthy buildings, homes for health. We have 36 expert tips for a healthier home, kick off your shoes before you walk in the door, ventilate make sure you're above your stove you have exhaust ventilation. You're capturing these these pollutants and particles when you cook simple things really written for the public simple things you can do. So there's a lot we can actually do to improve our health, and especially in our homes. Great second question on ionization. I think there's a lot of new technologies out there in terms of ionization. I am. I'm usually cautious when I'm sorry I'm not anti new technology I'm just cautious I think we have to evaluate any new technology across these three questions. Does it work. Simple enough. Does it is it doesn't produce any potentially harmful by products. And three, what problem is it solving is it replacing one of those first four measures, because they're not sufficient. So the first one I think on the ionizer question depends on the technology depends on the exact tool but I think there's lots of debate about how effective they are. To say I think for me the idea of releasing anything into the air constantly whether it be a chemical or ions. We have to be careful that we're we are fundamentally changing the air you can create secondary pollutants, like ultra fine particles, or you can you can convert complex VOCs into other VOCs that maybe respiratory hazard. So that is it changing the air and is it safe. I think it depends on the technology how it's deployed at things like this. And third what's it replacing. So we just solve this with better ventilation better filtration which we know come with a lot of other benefits. I can talk a lot about plants and biofueled design if that comes up another question but I would just be. I would think about those questions and think about new technology, those three questions. Does it work. Is it safe, and also fundamentally what is it solving that can't be solved through these other methods that have decades of science behind them supporting their benefits. Patrick Kenny asks whether you'd comment and on current US research on impacts of mold and spores on indoor health and how building design can either mitigate or worsen their impacts. Yeah we've been doing a lot of research there. And this is my decades old old field but it's one of the nine foundations of a healthy building. There's a lot of moisture control specifically for that reason. And I think, you know, I, the, the evidence is really clear, or, you know, across the different species of fungi and mold. The health concerns and the irritation they can cause and also but the control measures there are relatively straightforward, right if you're monitoring or monitoring. If you're controlling water damage or respond to water damage controlling moisture, such that you have you're limiting the conditions for mold growth that can mitigate the problem also if you see it you remediate I think that the remediation is really quite clear and the guidance is clear and how to mitigate or remediate if there's a mold issue. One of the areas we've been really interested in we started new research here that I can share maybe next year. Research funded by the National Science Foundation in the United States looking at water damage and mold and moisture specifically after natural disasters like hurricanes. So what happens when you have an event like we just had hurricane in in the United States of devastated parts of Florida. And what do you do as people start to reoccupy these places, and now you have severe water damage, and amongst all the other hazards. You have the potential and real threat of mold growth indoors so that's where we're moving our research to to think about climate events and these indoor threats. So the presentation here health and safety review and it's called and we've got Margaret Kirby from health and safety review asking just to clarify what is meant by bringing buildings back to performance standards. Could you explain that further. Yeah, sure. So, I quickly talked on like the hundred year history of ventilation rates so one of the standard setting bodies for ventilation and buildings let's talk about this is ash rate and and largely. And then followed internationally gets into building codes, ash rate, these ventilation standards are named the standards for acceptable indoor air quality, ventilation for acceptable indoor quality. That shouldn't be acceptable, we shouldn't be taking bare minimums I want healthy indoor air quality. In addition the standards of design standards not performance standards such that by built a building 10 years ago. The standards says 18 cubic feet per minute per person nine liters per second per person. So some volume some amount of air right some number of air changes. So I built my building to that that became code wherever it is in Ireland US rivers. Over time, I don't give my building a tune up performance is going to slip. Right just like your car performance would slip if you don't give it a tune up. So now you have a design standard that's not designed for health. The building is falling even further below that. Now, let's take air change per hour to explain this little bit. Let's take classrooms and schools in the US I've been thinking a lot about schools, three air changes per hour. Over time, most US schools are now at one and a half air change per hour despite the design standard being here, and despite the target being four to six. Well, I'm very much interested in getting the buildings that are already getting 456 air changes even higher and better filtration. The majority of our benefit right now. If we would be just focusing on those buildings that are chronically under ventilated and bringing them back to the way they were designed in the first place, then we can say, I've given my building a tune up. So it's back to the way it was designed. And what else can I do? Can I bump up ventilation? Can I bump up filtration? Do I need a new fan? Do I need to overhaul the system? Maybe it's something simple. And so, but all of the most of the benefits going to come from bringing the poorest performing buildings back to the way they're designed and then go above and beyond. I also like the idea of performance based standards. I think that's where real time sensor technology comes in. Because how do you know if you're building slipping? Well, it's taking the pulse of the building. So you go to the doctor, right? What's the first thing she does when you walk in? No matter what you're there for, they check your pulse, blood pressure, maybe your weight. So we need to do this for our buildings to say, how do you know if it's slipped from that standard? Well, we have to measure it and think about performance standards that says it's designed one way but we can measure now with low cost sensors, indoor air quality performance and make sure it's staying where it should be and then also target these higher standards. So getting a whole bunch wrapped up in that. The standards are not designed for health. They're performance, they're design standards. We forget about them. They're not performance standard. And we have the tools and technology to do performance based standards. I would relate that because obviously a lot of people here are thinking right across the world. I'm sure thinking about their domestic buildings and having them assessed in terms of their sustainability and respect of heat and ventilation and so on and they're thinking about what they might do to improve that. How do we link this tune up that you're talking about to the sorts of assessments that are done by people and that need that are required to be done for people, for example, who are looking at maybe solar panels are looking at do something to improve the, to improve their homes from that perspective. I mean, should the two be part of the same process or what's your reflection on that? I think they have to be part of the same process and I think they haven't been. So clearly, right, it's a residential, we all spend the vast, vast majority of our time. And maybe even more so now for a lot of people since COVID. So, if you think about, so you can have energy efficient improvements to our building. So we mitigate or we put on solar panels on a supporter of what's called the electrify everything movement where we have to get off fossil fuels and our buildings that improves indoor health and also improves outdoor health. So we can when we make, we have to be making those improvements. Right. And we released a paper in the US is showing as the US has moved away from cold fired power plants, the dominant source of health damages in the majority of states in the US is from on site fossil fuel combustion within building fossil fuel combustion. So we're going to have to do that and it comes with the health benefit for people indoors comes with a climate benefit. And because the dominant emissions are now coming from buildings in a lot of places. It becomes an equity issue it's a commute you're reducing the air pollution emitted in your local community or local region, no longer just regional coal fired power plants and regional air pollution localized impacts, real localized impacts. So we have to do all that where I think we have to be careful is that sometimes in our green building efforts or energy efficient efforts, we have tightened up our building envelopes. So much that we've stopped letting our buildings breathe. If you look at what happened in the US in the 1970s global energy crisis in the 1970s. In response, we started to tighten up our buildings, save energy. That sounds great. It also ushered in the sick building era. That's when that term started to appear the early 1980s. It makes sense we had, we have products that admit high levels of off gas and chemicals we have our gas stoves emitting into the home, and now we're not letting our buildings breathe you have an end up build up of indoor pollutants tied to good and important energy efficiency goals, but they were at odds with each other. But if you look at new technologies that are available they don't have to be at odds. You can bring in more outdoor air using energy recovery ventilation for example. Where you're retaining the heated or the cooled air and you're not wasting all that energy. But I don't think we can have a future where we say we're going to sacrifice indoor or health indoors for energy efficiency goals, just like I don't think we say we have a healthy building that doesn't do well for the environment by our energy choices. And there are great examples out there in the residential sector in the commercial sector advised on JP Morgan's new headquarters in midtown Manhattan, all electric tower, double the ventilation rates. So it's beautifully sustainable, all electric and higher ventilation rates better filtration better indoor air quality real time indoor quality monitoring. And that's really where the future is going. We have to marry these, these disciplines that have been at odds for 40 years and not have to really important public comparisons, maybe pulling against each other or at least the risk that they are seen by people as being in conflict where in truth they're not in conflict at all the opposite is the case. So brolic on and the IEA member of the IEA here he says he was asking, and you can comment on this but in fact you've touched on it, should the installation of mechanical ventilation heat recovery systems be part of public policy for domestic residents, as is the case. In relation to the installation of heat pumps now. I think absolutely I think it's a smart comment. Yeah, clearly right we have that. I love the idea of heat pumps, ground source heat pumps air source heat pumps network we just had a networked ground source heat pumps in Massachusetts we're piloting. I think there are all these clever ideas but yes clearly as we do a better job of heating and cooling our buildings we don't waste all that that energy so energy recovery ventilation heat recovery ventilation is just really smart and the technology is ready. And it kept me down. Yeah, two questions they're going to put you and they're not related at all but just because they're short we can take them together. Peter Murphy wonders whether I mean this is maybe it just a rhetorical kind of question that he has, which is fair enough, do you think that employers are fearful of measuring the indoor air quality of their workplaces. Then Dr Sean Orion asks you directly, is it dangerous to live near a motorway. How far away from a motorway is safe. Two great questions. Okay, so the first one, our employees fearful. I said, I think yes some some right there's some organizations that just want to do well and and and they're not fearful but I'll tell you a quick story about my own field so I'm a certified industrial hygienist done this kind of work for decades. I'd say in the past here's how it's gone. You've had an indoor air quality complainer company, you'd hire an expert. They would go take some measurements would end up in a report sometimes to go to the legal department would never see the light of day. Right. Maybe they took corrective action. Maybe they didn't. And companies a lot. I'm not sure I want to measure because what if I find something good company say I want to find something if it's bad and then fix it. Some not great companies say I don't even want to look. Here's a massive shift that's coming where that paradigm is being blown up. The proliferation of these low cost sensors means that the, the information asymmetry is over companies held all that power. Now if you're not measuring in your building, I'm an employee, I go in I take my handheld device. I go into your office, and I'm telling you what the problem is. I'm in control of the data. I'm going to share it on glass door on Facebook on tiktok whatever it is social media I'm going to say hey company X, why aren't you dealing with that indoor equality. That is a major shift so the power has shifted you have a highly knowledgeable public now about indoor air quality because of cove it. And now they have the tools they don't need a $10,000 scientific instrument anymore. A couple hundred dollars, and that'll keep getting cheaper. So that's really important I don't think employees and companies can hide anymore from indoor equality in fact I advise them to get on top of it start monitoring now so that if somebody comes in with a device that they can manipulate. You can say well that's your reading but we have the whole system over here and we're verifying that air quality is good. That's a better strategy. Good question. So about motorways yeah you know there's a lot of research on distance to roadways it depends on the distance. Wind direction all of these factors but yes there's a lot of studies showing proximity to roadway is a risk factor for things like asthma, or higher or asthma exacerbations. The exact, I can't give you an exact distance but lots of studies have been done on distance and particle pollution and transport. Let me let me turn it into a positive though, even if you are near roadway. You can design an operated building such that you minimize that impact. The indoor air pollution penetrates indoors I opened with that the dirty secret of outdoor air pollution. But if you use some of these same strategies I talked about that are good for coven. Good ventilation and filtration. Good ventilation you still want to bring an outdoor air but now you have high quality filtration you're capturing a lot of those air pollutants before they enter the space. And we see this, even in, we just finished a global study of indoor equality. And even in the buildings in China with terrible outdoor air pollution. So not specific to roadways just place with bad outdoor air pollution. You saw buildings that have good filtration strategies could disentangle that effect, meaning outdoor air pollution was high indoor levels were low like you'd find in a good building anywhere in the world, because they manage ventilation filtration well. Now the opposite was true to there were many buildings that didn't manage ventilation filtration and the indoor pollution levels were really quite high. So similar thing with the roadway thing I leave it on a positive that yeah distance the roadway matters but we could also mitigate that depending on the choices we make in terms of our building strategies. Thank you, Martin McCarthy is wondering about the. What he describes as the trend for open plan offices, and he says also open plan dwellings and what do you think they're generally better or worse for indoor air quality. Yeah I've seen a lot of talk about this is a big report recently in the US and the New York Times on this and lots of bait with the companies. My answer is this, I think like anything there's good and open, there's good and bad open floor plans, just like there's good and bad close floor plans. So let's take, but let's get a little more specific, I think there's a lot of concern about open for plans being higher risk for covert and other infectious diseases. I don't think that's the case. I think it depends on what your ventilation filtration strategy is. I worked on a designed open floor plans that are that are great. It could be bad you could overpack people into a space high occupant density with poor ventilation that's going to be a problem from an infectious disease standpoint. I've also seen that happen, but the opposite happening closed office spaces where you know is that the answer where you box everybody back up. Well in that case I've seen low ventilation low filtration bad lighting detachment of the core of the room from access to natural light as a whole host of other factors that come into it. And I think that conversation on open floor plans has gotten too narrow it hasn't taken the holistic view short answers I think you could do good open floor plans and bad open I don't think there's one straightforward answer despite I think what people have taken really really hard line positions on one, you know being good or bad. I just think it's in the implementation of it really and controlling these. I'm very much on the nine foundations of the healthy building you control those factors. Then it's going to be a healthy space and I think you could do it either way with closed offices or open floor plans. Interesting. Let's go back to Patrick Kenny of the EPA, and he's asking you to comment on the US experience of the impacts of different heating systems in particular solid fuel heating systems on indoor air, especially fine particulate matter concentrations. Well, this is really it's a great question. And, you know, even some of the most aggressive and good building energy efficiency laws like in New York City has local on 97. Fail to recognize or, or legislate against biomass or, or, or wood burning, which has the hot one highest emission rate for particulates which causes, you know is not can be the dominant source of health damages localized health damage or localized health damage from emissions. So, I think this is critically important it's well documented that these are these are these have a big impact on air quality indoors and also a study by my colleague at Harvard graduate school design, showing that emissions of the solid fuel burning does actually impact air quality, even you know just neighborhood air quality. So I think it's a big, I think it's a big problem and we and we and we so we can make some mistakes here and my another colleague talks about it this way, we can we can choose some carbon neutral fuels, you know renewable biomass right carbon neutral fuels that aren't health neutral. I think that would be a mistake, right as we think about our renewable energy goals, we have to be careful that we're not using something that's good for carbon, but may cause a health concern. Yeah, really, that's a really good, really good question I think a lot of legislation around a building energy efficiency sometimes ignores that point. Lydia from OSA had a question earlier and I'm hoping it's clear and that's not not a criticism Lydia I'm just not sure if when I read it, it makes total sense to me but hey, what how would it make sense to me it probably does make sense to you so I'll give it a shot. And she says we have lead LWD certification systems, and there is a credit for indoor air quality. Could you please give examples of best cases in the USA or elsewhere where this is taken, she's taking with us taken beyond construction and indoor air is at the core of the construction. I imagine that the end of that question is really is the core of the question as well. So, could you address that. Yeah, it's a great question so lead is from the US Green Building Council but there are global green building standards that are similar leadership and energy and environmental design. Really you had a, you know a 20 year great run a lot of buildings have the lead plaque on them saying their energy efficient and absolutely correct in let's say whatever the total points that are available there are some credits and available points. If you focus on indoor air quality. I don't think lead goes anywhere near far enough in terms of indoor air quality. So it's mostly energy efficiency there's some part of indoor quality probably can't have too many points if it's about energy efficiency around indoor quality it's the absolute basics. So when I see a lead building I don't necessarily think it has to be great indoor air quality because you can just score a couple of points on their scoring. I like it for what it's done on the energy efficiency side. That said they're great examples of companies that have placed health at the core of design for new buildings and even existing building so in the new buildings encourage you to look up that JP Morgan headquarters right in midtown Manhattan. So focus on both energy and health and goes way beyond what lead would have an indoor quality in fact goes way beyond what anybody else is pushing right now in terms of healthy building so their examples like that there's examples on residential. There's also great examples on improving on existing buildings. So I work with a lot of big multinational companies names you would know that are overhauling their entire portfolio. So first benchmarking. What does my portfolio look like in terms of indoor quality I don't mean a handful of lead credits, I mean, all around the nine foundations of the healthy building whatever other score, or whatever system you want to use or whatever reference you want to use, but basically saying let's do a deep dive on lighting, water quality, biophilic design acoustics indoor air quality ventilation filtration, the whole thing go deep and say, Well what are the current standards, but really what is the science saying we should be doing right now. Well beyond standards. And in that case you see entire portfolios being redesigned around new healthy building standards or retrofitted to new healthy building standards. So I think lead is maybe a good starting point I give them credit for acknowledging indoor quality. 20 years ago and lead started really grow. I don't think it's nearly far enough. I don't think it's comprehensive. And I wouldn't use it as the basis to say I did lead in my building I have, you know, leading class indoor air quality. It's good starting point but that's where that's where that's it is a starting point. There's been quite a few questions about asking you that you've done we're already asking you about best practice in the US and so on and you've been very generous in terms of saying you know, there, there is information available there are resources there. You have been responsible for yourself and you know that the book and various other sources of information. You mentioned some buildings even high profile market Kirby kind of came back on that point. And I feel a little bad that we may have curtailed you a little bit too much when you were doing your slides. And I'm wondering, because market is wondering, what can companies do in relation to the four strategies mentioned in the slides and you know, she was wondering because you give examples in relation to the four. I imagine you'll say look, you can pursue that further. I mean if you can give any examples in relations for strategies please do we're probably coming up on time now but where would people go to look for more detail on those four strategies. Yeah yeah so I'll give you so you can look at our Lancet COVID-19 Commission Task Force, SafeWorks, Safe School, but let me just do it quickly because it'll give you some resources so that first one right called commissioning your building at a tuna. So you want to look for a local engineering firm HVAC contractor and tell them you want to commission your systems do continuous commissioning, which means they go out there and they check to make sure it's working are the filters installed right already fans burned out, just, just making sure your building's performing. And here's how we know it works. This great study at Lawrence Berkeley National Lab in the US showing that it saves money improves indoor air quality. And it's actually going to it's a process going to save you money, and it's the baseline it establishes to let you know what your systems are currently doing. And you asked that same contract how can I improve it. So look for a good HVAC contractor environmental engineering firm. As that starting point other basics, increasing ventilation that could be opening up the windows increasing the amount of air flow into your space on filtration number three minimum standard right now should be Merv 13 filters. So Merv eight captures about 20% of particles. The way I describe it is that a Merv eight filter designed to protect the equipment, not people and Merv 13 filter designed to protect people captures 80 90% of airborne particles. That's particles from outdoor air pollution from roadway or particles generated by respiratory system. So upgrade to Merv 13 filters, fourth one portable air cleaners simple portable air cleaners. I give you a rule of thumb, look for one with a good HEPA filter. And what's called a clean air delivery rate, my rule of thumb look for a clean air delivery rate, CADR of 300 for every 500 square feet, they got to convert that to meters for 300 CADR for every 500 square feet of space will give you between four and six air changes per hour. So really simple strategies hope that sounded simple. It is that report is really short. Lots of guidance out there and the book goes into a lot more detail around all the nine foundations of a healthy building if you're thinking about what my recommendations are for ventilation or lighting acoustics these other factors. I was astonished at what you said about the majority of the exposure to outdoor pollution occurs indoors. And I suppose when you when you think about it, perhaps we shouldn't be as astonished because it does a logic to that but still it was quite a stark statement that you made at the And it's interesting and keep so going from business to the back to the domestic Keelan O'Sullivan as a researcher here at the IIA points out that Ireland is one of the highest rates of asthma prevalence in the world and the most common chronic disease affecting children and the most common chronic respiratory disease in adults. So wondering again, how can I'm coming up on the air but how can Irish people manage their indoor spaces to reduce asthma triggers. Yeah, I think that's a big question. But they're a handful of things and I'll go back to the source control right it's a whole bunch of asthma triggers outdoor air pollution allergens and dust in the home right so managing dust and allergens and cockroach allergens mouse allergens things that are all around us all the time can be triggers. We have indoor triggers like gas stoves that trigger asthma or exacerbate asthma. We have the penetration of outdoor pollutants inside. So I actually think I take it on this big level question so improve our climate goals want to electrify everything remove fossil fuel combustion indoors that's going to help against asthma. So definitely do a better job with our material selection, lower chemical loads, avoiding some of these asmogens that are in the space, better cleaning with HEPA filters control the dust level and the allergen loading, improve filtration, the same portable air cleaners that reduce particles. These particles penetrate from indoors these particles that we know are associated with asthma. You reduce that concentration. And of course big picture. We continue our push or climate goal push of cleaning the energy grid, because major source of outdoor air pollution a major source of mortality and asthma and health are coming from these, you know, from coal fire power plants natural gas power plants we need to continue our push to reduce fossil fuels for the climate goals long term health benefits but it provides immediate benefits provides immediate benefits in terms of better health including emissions and asthma for kids and adults. And isn't that just to finish up is isn't that a really rich source of kind of public policy and public and encouragement of conduct, where we can say look when we're talking about the climate agenda, and pressing for rapid change in that in that on that agenda that we can. Isn't there a need to communicate more perhaps to people that there's also a gain and immediate gain in terms of things like air quality. And I know that's something that, you know, governments are trying to do, because the communication of so much of what needs to be done on the climate agenda has got actually negative connotations to it you've got to stop this you've got to stop you know you must be change your lifestyle, no more turf number, the more cold obviously no more oil. You know you've got to you've got to change things around and it's a long term people think well that's maybe if I can do it I will if I can afford it I will but it's going to take investment. You shouldn't part of I will finish on this and you said it really but just to emphasize it. Part of the communication of what needs to be done on the climate agenda really needs to fold in and much more clearly to the immediate gains that people get in their daily lives in relation to something like air quality. I'm exactly right and I'll end it really quickly and we make this case in the book. But we want to improve conditions for everyone's health want to act on climate. It's also just good for our health in the immediate and it's just good business if your business owner out there, I co authored my book with Harvard with a Harvard business school professor john McComber for a reason. So just good business to help us think better work more productive reduces asthma attacks yes while addressing the long term challenges of climate change and helps against coven and whatever whatever else threat comes it's just. It's a really a win win on all levels it's good economically good financially good for climate good for immediate health so that framing is exactly right there immediate benefits and we can act selfishly for own health our own business at the same time will actually be helping collectively and acting for everybody at the same time we can have it all. Thank you so much. I want to thank Joseph Allen Professor Joseph Allen for joining us this afternoon here on this webinar. It's been most interesting and stimulating. I think we could go for another hour we've done so much interest in it, particularly that point towards the end how we integrate these you know different imperatives that we have in terms of public policy but your concentration on buildings. And the points are just so well made this afternoon want to thank you for that. Again, thank the colleagues at the Environmental Protection Agency for sponsoring and supporting this event. And thank you for joining us. If you happen and many of you have for the last hour and we'll see you all again before too long. Thank you very much.


When schools begin to rely more heavily on natural supports, that really challenges schools to think differently about the proper role of educational assistance in classrooms. In many schools right now, the educational assistant is viewed as an individually assigned support to that particular student. And so they're always there right next to them ensuring that all of the students, academic and social and behavioral needs are met. So when you begin to think about peer support arrangements as an alternative to that, that means the roles of educational assistance start to shift. Rather than just being that one-to-one individually assigned support, their role shifts to a broader support within that classroom. So instead of just working with that student, they may start to help the teacher in meeting the needs of all students in that classroom. So as peers start to take a more active role in supporting their classmates with significant disabilities, the educational assistant's role might be to model some of those support strategies for the peers. As they begin to fade back their support over time, they still assume that facilitation role where they're looking for opportunities to make connections among the student with disabilities and their classmates. So they might be making sure the assignment that's coming up is appropriately modified for the student so that when it comes up in class, the peers are ready to participate in that class activity. One of the other roles that they can assume in the classroom is to take a more active role in data collection. Initially, educational assistants might be somewhat reluctant to assume these new roles. Often when we've defined their role as being a one-to-one assistant, if we're asking them to fade back the support, they tend to think, well, what are other people going to think about me?  And so it's really important to clarify for these educational assistants that the goal is for students to become more independent. And actually, their fading back of support is a desired outcome.


Hey everybody, this is Brett the Ford guy and today I'm going to show you how to find your door code off your 2011 2012 2013 and 2014 Ford Raptor pickup truck This is going to be the driver's side door code entry to get into the truck This is the factory code and you're going to use this code to program any of your personal codes This code can never be erased and it comes with the truck So you're going to run a open up your passenger side door here And the first thing you're going to want to do is grab your format The only tool you need for this door code find is a flashlight. So I got the flashlight on on my phone right now So basically there's a kick panel right here. You're just going to grab that kick panel pull that away and Then your door code is going to be right around the corner here That's your door code. Don't worry about the L It's doesn't really mean anything pertinent to the door code so this just kind of Slides right back into there you swing it in and it will pop in the place like so and It really is that easy Put your floor mat back in and you're all set to go Once again, this is to find your door code for your 2011 2012 2013 and 2014 Ford Raptor pickup truck and You can use this to program your own door code In fact in a second You'll see a link to subscribe or to subscribe to our YouTube channel in the upper left a link to how to program your own door Code and erase door codes in the upper right a link to our 2000 to the 2015 to 2021 F-150 door code fine and a link to one of our latest YouTube videos in the lower right click those And check us out remember to like subscribe and share and thanks again for checking out the video to how to find your 2011 2012 2013 and 2014 Ford Raptor driver side door code entry. Thanks again for checking out the video


So, thank you Jessica for the nice introduction and thanks to the organizers for inviting me here which actually was quite a surprise because I'm not a neuroinformatician, I'm a biologist by training. So what you can expect me to do in the next 45 minutes is to actually add to your task load. I'm going to try to define the questions that can be asked from genetic and imaging data and the integration of those and the regions where improvement of data analysis and data sharing for example is still needed. So the question or the goal of my research, the ultimate goal is to improve the diagnosis and treatment of patients with psychiatric disorders. You can start this such research from many different angles, we've heard imaging etc. But a good place to start is also by genetics because as many of you might be aware, most of the psychiatric disorders that we know are very highly heritable. For example ADHD which is the main focus of my own research which has a heritability of 76% meaning that in an average patient about three quarters of the phenotype is explained by genetic factors and this is quite a lot. So the way we approach our research is by trying to identify the genetic factors that underlie these psychiatric disorders and on the other hand also trying to map the biology that leads from the genetic defect or genetic variation to the disease, to risk for disease. So what I want to show you is both sides of the coin by first going into gene finding and psychiatric disorders, show you what the models are and what the some of the findings and then move into pathways from genes to disease with different approaches that we can use here. So while being highly heritable, the genetics of these psychiatric disorders are highly complex and that has made gene finding very, very difficult. Highly complex meaning that in every patients or at least in most patients, many genes act simultaneously and if you look at different patients, different genes can be involved and we now think that in many of the psychiatric disorders we're dealing with involvement of more than 1,000 of our 23,000 genes and in every of these genes many different independent genetic variants can be involved in increasing your risk for disease. In addition to the genetic contribution, there's also an environmental contribution meaning that either environmental factors can act independently on disease risk or they can interact with genetic factors and increase disease risk in this way. Most research on the genetics of psychiatric disorders has been done on genetic variants that are common in the population so they are not restricted to the patient population they also are found in healthy individuals and all of them are of individually small effect size and that is also depicted here where we're dealing with the common variants down here that are common in the population and have a very low effect size. So the way to find these genetic variations is by doing genome-wide association studies and we've been doing these over the last let's say 10 years. What we learned from them is that neither of us or none of us can do these studies by themselves so data sharing in genetics in complex genetics is essential. Only by sharing our data and putting our data together in mega-analyses or meta-analyses we can reach the sample sizes that start to make sense and these are examples of the psychiatric G-WAS consortium which is certainly the most successful consortium in the field of psychiatric genetics where people are putting together sample sizes of nearly 30,000 or even more individuals to find genetic factors involved in psychiatric disease and for schizophrenia that is I guess the disorder that is most advanced in the first stage they found seven different loci to be involved there's now second paper in press which looked at 21,000 cases and finds 22 independent genome-wide significant loci and I've heard through the great vine there's already 35,000 patients now assembled and this gives you more than a hundred independent genome-wide significant loci with in many of these loci different independent factors contributing to to increasing disease risk well as I said my own specialty is ADHD and there we're not right there yet even with data sharing in the psychiatric G-WAS consortium we're not yet there we have five more than 5,000 cases more than 13,000 controls but we don't find a single genetic variant yet that can be called proven so what you see here is the way we plot these data where on the x-axis you have the different chromosomes and on the y-axis you have p-values for single variants being analyzed from these different chromosomes and what as well what we do in doing is we analyze more than a million genetic variants independently so we're doing more than a million tests that in of course increases multiple testing burden extremely so if we want to accept something as being genome-wide significant we only do so if it reaches a p-value of 5 times 10 to the minus 8 so that yeah makes you humble if you think about the numbers we're now even for ADHD we're now doing better we I think we're crossed the 10,000 cases line so we hope we find a single at least a single variant now being genome-wide significant even if we have 35,000 cases our analysis such analyses are still underpowered so people have been thinking about how to improve power for the studies and as I said what is generally done is that we analyze each genetic variant individual individually but knowing that there are different genetic variants in different patients at the same in the same gene contributing one might think that taking a different entity like a gene or even a genetic pathway and asking the question whether these are involved in disease might increase the power of your your studies and in my group we have been doing such studies Janita Braulten is a PhD student in my group who has been working with the data from the International Multicenter ADHD genetics or image study in which more than a thousand families with at least one ADHD affected individual were very strongly phenotyped or phenotyped in a very deep manner for ADHD related phenotype so what she did was that she took well established genetic pathways for ADHD like the dopamine pathway the serotonin pathway and also a pathway that we found to be involved in that I will come back to later the new red outgrowth pathway and she asked the question whether these together are involved in increasing your risk for ADHD in addition to taking the genes together she didn't look at ADHD as a category but she disassembled ADHD into inattentive symptoms and hyperactive symptoms and that is because modeling studies have shown that only part of the genes that cause inattention problems and hyperactivity overlap with each other so what she found indeed was that this joint group of genes of pathways was involved in increasing increasing your risk for hyperactive symptoms but not inattentive symptoms and this was confirmed in an analysis using a different radar in which we looked at quantitative stores for hyperactivity and inattentiveness and they're the same result was also found when she disassembled the different pathways she found that all of them contributed individually to to this association so all of them were involved and by integrating them or integrating the genes within the pathways we get more power to analyze genetic association so this was a study in 900 individuals whereas for the genome-wide association studies we need tens of thousands so can we use this information to improve the diagnostics of patients with a psychiatric disorder well that is a region of research where there's a lot of development at the moment we know that we can use these data to make personal risk profiles but for that we need much more genetic information from the from the different psychiatric disorders and also the possibility to distinguish between them so far even with with a hundred independent hits we can only explain 10 to 15 percent of the habitability of a psychiatric disorder like schizophrenia so we're not yet there but this is definitely a field where more research is required and that can lead to the use of genetics in in the clinic which is our ultimate goal so is there something else is there the possibility that other models underlie the occurrence of psychiatric disorders and people have been working on that trying to find whether there is Mendelian forms of psychiatric disease and there are families where you you could think that this is really the case and I've also looked into the possibility that there are genetic variants that have give you a higher risk individually so that you would need only need two or three perhaps instead of of like a hundred of them and the first results on this from this field where surely the rare copy number variation studies where people looked at copy number variants which are large genetic variants that encompass entire genes and you can have for example so normally you would have two copies of a gene and from these copy number variants you can either have one or zero or you can have three four five etc and from all the different psychiatric disorders there's evidence for all these disorders there's now evidence that these indeed there is an enrichment of rare copy number variants in psychiatric disease so if there is really copy number variants involved and people are also thinking that other types of more rare genetic variants in the genome human genome can be involved in psychiatric disorders and this is a field where next generation sequencing so the sequencing possibilities that we now get for sequencing the entire genetic information instead of genotyping just a million of the three billion base pairs for example is moving fast and helping us to find new genetic risk factors for psychiatric disease and there are now a number of papers out already on autism where people have been trying to make sense of next generation sequencing data which give you huge data sets so this is really big data science which show that about 10% of autism spectrum disorder cases might be explained by rare genetic variants that you can find with exome sequencing so exome sequencing is using or sequencing the information that is in the coding part of the human genome and the coding part of the human genome is three to five percent of the entire human genome and we concentrate on this part because we can understand it we can see well is there a protein formed is this protein non-functional because of a minor acid change is it expressed differently if we look at the entire genome there's so much so-called junk that we don't know what its function is that we cannot interpret the data at the current time so many of us are focusing on exomes well also in ADHD we have some nice examples that would lend themselves definitely for for next generation sequencing like for example look at this family where you have a clear segregation of ADHD through the family and where you would say well one gene one genetic defect should be enough to cause to cause such a segregation pattern but still we do this type of analysis we have now eight different families where we did exome sequencing of on three to five individuals but in none of them we find one single variant segregating through the through the family with with the disease so the models that we need to to analyze these data with are not the Mendelian models that are used in in monogenic disorders where only one single genetic defect is enough to cause a phenotype and the analysis of exome sequencing data or next generation sequencing data and complex diseases is a very active field of research at the moment and that there well the models for monogenic disorders won't fit so we have to find new models and everybody's struggling with that and we're we're setting up a unit to do this type of analysis if you're still looking for a post-op position and are interested in this please come and see we're very interested so in general when you think about identification of underlying genetic factors for psychiatric disorders I guess we're doing quite well we at least have the tools now in hand to do this type of analysis what we do with the data is a different thing we we the interpretation of data is really what is the bottleneck but we're moving we're moving further with regard to the mapping of the biology from gene to disease that is that is a different a totally different thing and this is something we definitely need if we want to understand what is going on in psychiatric diseases and want to develop treatments that really treat the causes and not only the symptoms of these diseases and I want to show you two approaches that are used to map pathways and one is what I call bioinformatics but this is really just in silico analysis of data that is already out there and that might be useful so what we did and this is work of a PhD student now a postdoc in my group here Pumans who has been looking who has been taking the genome wide association data that are out there in this case for ADHD and looked even though he didn't we didn't find genome wide significant data whether there is something that makes sense something that converges in these data so what he did was he selected genetic variants or genes that had a p value a study specific p value of 5 10 or 10 10 to the minus 5 sorry and and smaller and he looked at different softwares that tell you about enrichment of genetic functions in biological processes what he found during this analysis is that many of these softwares that you can use are very incomplete so that when you do a systematic literature review you end up with much more information and I understand that yesterday there was a workshop on data mining I think this is also a point where data mining or text mining is something that that can be improved to make these softwares much more efficient so he selected 85 genes from the different genome wide association studies and actually found that half of them well where could be involved in a process called the red outgrowth and he put this into a network and this is not a network as you see it in in in general network science but it just puts all the genes and or proteins that are involved in nerd outgrowth into a growth cone of a developing neuron you have different processes here like sensing the environment changing the cytoskeleton changing the extracellular matrix changing the the transcription and translation so the gene regulation within this this grown neuron to make the the the neurite grow out into a certain direction so for ADHD it gave us a new process to focus on new biological process to focus on on in understanding what ADHD actually is here to also build networks for for autism and these networks are based on much more data than we have for ADHD so there's exome data exome sequencing data for autism already around there's much more GWAS data etc so here what you found here was that three different processes could be found to be involved and enriched in the data but what what is most important is that with these data he found sort of hops within the networks and also between the networks that make excellent candidates for for new leads for treatment development and this is I think the strength of this network approach or this yeah enrichment approach that we can really find new targets to to to turn to when we think about innovation of treatment and this makes this for me makes this very interesting and and rather yeah a shorter term from understanding biology to going into treatment development than I would have thought myself so another approach to to understand what is going on when you have a genetic variant and you you and how it leads to to increase disease risk is Cognomics and Cognomics stands for Cognition Genomics and actually is a science that tries to map the genetic the effects of genetic variants on behavior through the through via the brain so when I talked to somebody this morning she said that geneticists tend to see the organism as a black box and I hope that this can assure you that we're not treating the organism or seeing the organism as a black box we're very well aware that there are things between the gene and the disease that are worth looking at so when you think about a genetic variant how it can affect your phenotype your behavioral phenotype it probably alters together with other genes alters gene function or cell function sorry and then hasn't why this way has a has an effect on the morphology and or the function of the brain and together with other genetic variants doing the same thing you end up with an effect on behavior so integrating these data towards disease symptoms so when you think about to explain these pathways one one place to look at is really brain morphology and brain function and that is what I want to show you in the next few slides in Nijmegen we set up the Cognomics program in which we now have data on more than 3,600 individuals and Cognomics really is an umbrella across a number of different studies including the brain imaging genetic study which is a study on healthy individuals from which we have mainly structural data of the brain then the impact and L study which is the the Dutch part of the international multi-center study for persistent ADHD so these are adults with ADHD and there is neuro image which is a study on child children with ADHD I want to show you one example from from impact where currently four PhD students are working and within the international study we are focusing on functional and structural neuro imaging in these patients with adult ADHD so what we do is we bring them in on two days for an excessive analysis both on the clinical phenotypes the neuro psychology imaging data we get from them and also genetic data Martina Hoffman is one of the PhD students former PhD students I have to say and she did a study using one of the um uh candidate genes for ADHD called nitric oxide synthase one or coding for nitric oxide synthase one which is known to have an effect on striatal activity and impulsivity so NOS one is a candidate for ADHD both from candidate gene based studies and from the genome wide association studies and it is known to be highly expressed in the striatum for ADHD the striatum is important structure it is involved and reward and impulsivity and is known to be hypoactivated um in patients with ADHD so Martina used a task called the modified monetary incentive tasks task also in the nuts and task um where people were in the scanner were told that um they had to click on the button as soon as they saw a target a wide circle but before they saw the target they were informed whether or not they can earn a reward so a monetary reward um by pressing as soon as possible and the she then looked at the contrast of reward over no reward what you see then is a robust activation of the ventros striatum and Martina could replicate earlier literature indeed showing that ADHD patients have a lower activation due to reward than healthy individuals have but when she looked at the effect of a genetic factor known to be involved in ADHD so NOS one where the SS genotype is the risk factor for ADHD she saw actually the the opposite so those with a with the SS genotype actually had a stronger activity in the striatum than those without and this was the case both in the affected individuals and in the healthy controls so we were quite puzzled by that but then we used another task for impulsivity the delay discounting task which is a behavioral task and we analyzed it in a behavioral way um and there we should we saw actually the same so here the more impulsive you are the lower the bar is that you see and here especially the the patients with the risk factor had a much lower activity than those without the risk factor the same was true also for the controls but this didn't reach significance so what this told us was that NOS one was not actually tagging ADHD but was tagging impulsivity and this very well correlates or is in concordance with a paper showing that this NOS one variant is actually not only a risk factor for ADHD but for different impulsive behaviors in humans so it tells us that the the effects of genes can be quite indirect affecting traits that feed into the disease rather than the disease itself so this was an example from the function of a brain unit we can also look at morphology of the brain unit and I already told you about the brain imaging genetic study where we now have 2,500 individuals included these are healthy individuals most of them are healthy young adults most of them are also students from our own university who come to do our experiments and what we find there is indeed that we can find effects on specific brain regions due to genetic risk factors for disease and this is a study of BDNF which is a risk factor for depression so not ADHD in this case and we were able to show that this has an effect on the anterior cingulate cortex volume in the healthy individuals but it only has this effect when there is also an environmental factor present that also is a risk factor for for depression namely childhood adversity so the people in big are scanned at different field strength some of them are scanned at 1.5 Tesla others at 3 Tesla and we were able to replicate our findings both at 1.5 and 3 Tesla so also on the on-brain structure you see effects of individual genes that feed into disease risk in big we can do candidate gene studies but we also want to do genome wide studies on looking at effects of genes on brain structure and if you want to do that you need international networks again and for that reason in I think it was in 2010 Paul Thompson and Nick Martin founded the Enhancing Neuroimaging Genetics through Meta Analysis Consortium or the Enigma Consortium we became one of the first members and part of the central support group of Enigma and the first Enigma project that we did together with a lot of different people was to ask the question which genes contribute to hippocampus volume and measures different measures of total brain volume so the way Enigma works is not by asking everybody to give us their data and doing the analysis across the entire data we're using a crowdsourcing method in Enigma to get to our results so what we do is that the Enigma support team writes protocols and tests these protocols and these protocols are for both the segmentation of the brain and this uses things like free surfer and episode first but also for the imputation of genetic data and how to do the association studies then every group can perform their analysis on their own sample by themselves at their own centers so no need to share the data which is often a problem because of ethical approval etc and the Enigma support team only collects the summary data does an extensive QC on them and then performs meta analysis the first Enigma study in this way brought together more than 13,000 data on more than 13,000 samples from I think up to 20 different groups and we indeed found effects of genetic variants on brain structure so we found one genetic variant being significant so passing the threshold of five times ten to the minus eight for hippocampus volume and one for intracranium volume we replicated our data in another consortium the charge consortium which added another 10,000 individuals to this analysis and we ended up with p values of six times ten to the minus 16th which is very nice interestingly the genetic variant associated with intracranial volume was also associated with IQ so there is a link between brain volume again a link between brain volume and behavior and that is the most interesting thing for me in this analysis well Enigma this is to show you that Enigma not only wants to do the analysis they also want to have people use the analysis so we have a website where we have all the protocols that you can use and we also have a tool where you can look up the genetic effect so you can put in either a gene name or a genetic variant name and it will tell you whether what the p value was for association with hippocampus or intracranial volume we're now putting together a new project which will not only look at hippocampus and intracranial volume but will look at all the different subcortical brain regions and this currently has a total of 18,000 participants or samples involved as i said the interesting thing for me to look at is really whether these genes that we found find for brain structure also have an effect on behavior and behavioral abnormalities in this case like that we find them in psychiatric disease and in this to answer this question we're making use of the strength of Enigma and trying to combine it with the strength of another consortium the psychiatric G was consortium that I told you about before so we're trying to meta-analyze and to link the data from PTC and Enigma and trying to find out whether there's overlap between the genes for hippocampus volume for example and schizophrenia and this is currently ongoing and we're going to start the analysis within the next month so if I have to put out say where data analysis and data handling can still be improved then it is definitely in a region where we combine data on multiple brain regions with data on multiple genes so what I've been showing you is that we can use candidate brain regions and integrate and data on multiple genes with them we also can do it the other way around we can use a candidate gene and look at multiple brain regions but we cannot yet do this combination because the dimensionality of the data really gets prohibiting so this is an area where there will be a lot of I foresee a lot of development needed in a method development so looking back what can we say about where we are with in terms of our ultimate goal of research well we have still have to go quite some way to identify all the underlying genetic factors that are involved in psychiatric diseases we need to optimize multivariate methods or use multivariate methods to maximize the power of our analyses we need to generate personal risk profiles to be able to use them in the diagnosis and we have to make next generation sequencing work for complex disorders on the side of the mapping of the biology from gene to disease we need more complete databases for in silico analysis so the bioinformatics tools that are around their pathway software is too incomplete currently to answer our questions also something that I haven't shown you in this presentation is that we need affordable model systems to really where we don't have any data yet we need to generate data and we can do that only in model systems that are affordable fast and flexible and my own group is currently doing analyses of ADHD and fruit flies trozophila and this actually works quite fine so if you knock out a gene that gives humans ADHD or that increases risk for ADHD in humans it will also make your fly hyperactive last but not least multivariate analysis methods for cognomics research is also something that is really needed so I was faster than I thought I was because this is already you didn't need your five minutes slightly this is where I want to thank a number of people of course the number the list of people who are involved in these large-scale projects is is huge so I'm putting here those of the enigma support group the cognomics people and the pgc participants that are play a role in the analysis of both the enigma and the pgc data together thank you very much for your attention so thanks for an interesting talk I wonder about these these different psychiatric disorders do you expect that like some genes are involved in many of them so that can give you some help in like more statistical power in your analysis yeah yeah so the what the psychiatric g was consortium has also done is is a quite agnostic analysis where they just put everything together that that had a disease so everybody whether they had schizophrenia or ADHD or autism they put them all into the patient group and compare them to controls and indeed in these analyses a number of genes pop up that give you an intrinsic susceptibility to psychiatric disease of course that makes your power that improves your power to analysis to perform the analysis but it reduces your your ability to use genetics in diagnosis because the specificity is just lacking so what we see more and more is that the clinical definitions of psychiatric disease are not very well related to biology so what I foresee is that within five years we will have to look at at these psychiatric definitions again and try to come up with a categorization that is more biology based yeah hi thanks for the talk that was great and I've got two questions I mean one is on the data sharing aspect I mean it's great to do a meta analysis but it would be even better to be able to share the data and you mentioned that there are ethical problems and but it is also kind of non-ethical to not try to share the data in the sense that you with all the data around we could you know advance much quicker in those disease identifications so what do you think are the path the path for for actually being able to with you know the appropriate informed concerns and think that that would be able to actually share the data as as almost as a moral obligation somehow so that was my first question and the second one is there are a couple of multivariate analysis on you know brain versus genetic multivariate analysis in the literature why are they used more is that your software problem is that interpretation problem okay so with regard to to the data sharing I I agree entirely that sharing of primary data will increase the possibilities that you can of the ways in which you can use these data so already with with enigma and pgc now we are definitely limited in what we can do what the approaches we what approaches we can use to combine these data with each other so that there is definitely a point in improving this and getting people to really share the primary data absolutely absolutely in terms of getting the field forward this was the best way because that makes the threshold for people to share or to participate in these analyses much much lower but I agree definitely that we need to to come to a model where people really share and there are also I know for example at mrn there there are preparing software in which you don't really need to place your data at a different site but analyses can be done remotely on your data so that is another model that might also work for for this type of data sharing keeping the data in the place where you want them or where you need to have them and having other people trying to do data and analysis on them with regard to the multivariate analysis you are right there is there is a number of methods now coming available to do this type of analysis and indeed the interpretation of the data is much more of a problem than finding the new methods but still this this is still a problem that we need to solve yeah it's a very nice talk thank you very much with regard to the disease description do you think there is a possibility that we could throw away dsm 5 or dsm 4 and see if we could find a way where the 29 35 50 000 patients could express their own disease so starting from the data instead of the categorizations it's a very good point I think that is the way to go definitely on the other hand the the input data is is a little bit of a problem because they were collected using these categories so you don't see the entire spectrum probably that that makes it a little bit more difficult but it's a good way to go to to start from the data yeah yeah more task load for the neuroinformaticians