All right, let's jump in I you know as I've talked about before What this is is really an introduction We're really just talking about an introduction. We're talking about the application In in life and in business of the various virtues if you really want to dig in on the virtues If you really want to understand them fully and really have a chance to chew on them and really have a chance To really integrate them into your life. I strongly recommend a number of resources by Dr. Elena Pigar first Opa Objectivism the philosophy vine Rand. There's a whole sub chapter on justice that is just brilliant It's really really really really good. So I recommend that Lenard also has a number of talks that cover justice that you can get at the Andren Institute a YouTube channel He's got of course a whole series on moral virtue and actually lesson one is the virtue of justice so Moral virtue is a course that Lenard Pigar gave We covers each one of the virtues and the first one is on justice so you can find that He also has lectures on egoism and justice. He has a has one on judging feeling and not being moralistic we'll talk about the importance of of moral judgments and importance of having moral judgments, but not being moralistic and You know and that's That is an I think a really really important course particularly for the application of this Virtue how to actually implement it in your life. So I highly recommend that that's on the Inren Institute YouTube channel. There's one on justice and objectivity. I Think I said egoism and justice egoism and justice what judges Judgment requires in judging feeling and not being moralistic and justice and Objectivity and of course moral virtue lesson number one the virtue of justice by Linda Peacock and of course you can If you if you'd rather read then opa objectivism the philosophy of Ein Rand Is a an essential resource for anybody who wants to gain a deeper understanding of the philosophy of Objectivism and of course the moral virtues. There's a section on each one of them in the section on virtues So I highly recommend all of those as as resources if you really Want to be Deeper into this and I think you should because all the virtues are crucial And the virtue of justice is complicated and it's complicated for simple reason What what makes it complicated complicated to apply not complicated in theory? It's it's either complicated. Just hold one second Let's get some better lights. Yeah. Yeah, it was kind of yellow before this is much better It's it's complicated because it deals with human beings it come justice is about judging human beings and In many respects and we can talk about why judging human beings is particularly Difficult it's particularly hard. It's particularly challenging and yet It's the most important thing you will judge. It's the most crucial thing to judge You can receive the greatest Pleasure joy happiness or you can't receive happiness with pleasure and joy from other people And you can also get the worst kind of harm Damage From other people so judging other people knowing and evaluating people is good or bad staying away from some and embracing others is Crucial to life And you're not easy. I mean in some cases easy, but not easy and and we all make mistakes When it comes to judging people people are Complex they they can disguise their true nature. They can hide their true nature and it's it is it is definitely It is definitely difficult to do and therefore worthy of spending some thought and integrating this virtue into your whole Approach to life into your life and into your approach to business. We'll talk about judgment and business and particularly one of the courses I really like is as egoism and justice Which is a course that Leonard Peacock gave called Objectivism through induction Where he shows how you induce an idea like justice? What are the concrete in reality that make justice a? Necessary virtue What? Concrete's in reality make justice a principle of morality So I highly recommend highly recommend Generally the course objectives and through induction. It's a different approach to typically the way objectivism is presented But what Leonard is trying to do is show you Give you a glimpse into how I ran must have come up with these ideas because knowledge new knowledge is inductive knowledge and is is gained through induction and that's That's what he goes through he goes through the inductive process of arriving at Philosophical principles, which was really hard. He gave homework and the homework is really hard What we need today what I called a new intellectual would be any man or woman who is willing to think Meaning any man or woman who knows that man's life must be guided by reason by the intellect Not by feelings wishes women's or mystic revelations Any man or woman who values his life and who does not give want to give in to today's of the spare cynicism and impotence and does not intend to give up the world to the dark ages and to the role of the collectivist roads All right before we go on Reminder please like the show. We've got a hundred and sixty three live listeners right now 30 likes That should be at least a hundred. I figured at least a hundred of you actually like the show Maybe they're like 60 of the Matthews out there who hate it, but but at least the people who like it You know, I want to see I want to see a thumbs up. There you go start liking it I want to see that go to a hundred all it takes is a click of a click of a thing whether you're looking at this And and you know the likes matter. It's not an issue of my ego It's an issue of the algorithm the more you like something the more the algorithm likes it So, you know, and if you don't like the show, give it a thumbs down Let's see your actual views being reflected in the likes But if you like it, don't just sit there help get the show promoted. 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I'm Lauren Rushing, I'm an Urban Mobility Planner here in New York City, but I actually moved to New York earlier this year from the Netherlands where I was working as a consultant with a focus on active modes planning and particularly cycling. So I want to talk to you guys today about what's going on in New York in terms of mobility during the pandemic, but I also want to touch a little bit on the Netherlands since my mindset is still very much embedded in this Dutch context and I'll talk about why we should be drawing hope for our future from their past. So if you look on the screen here, you can see on the right this is a picture of New York during the pandemic. This was taken in March just after the lockdown went into effect. Not a lot of cars on the road at that time, but unfortunately that space is still being reserved for vehicles. And then on the left you can see the Netherlands during a similar crisis situation back in the 1970s and in this case that street space has been opened up to people. So we'll talk a little bit about that, but first, what's going on in New York City right now? I'm sure as many of you have seen, we are the global epicenter of this pandemic. We have about 200,000 cases right now and that's just in New York. So that doesn't include the closely surrounding areas of New Jersey where a lot of people also live and commute into New York for work. We're also on a stay at home order still that's been extended until June 13th. So non-essential businesses are still closed and most people are working virtually, those that can. But the governor has recognized this need for New Yorkers to get out of their homes for the purposes of maintaining their mental and physical health during this time. New Yorkers are not used to staying inside. A lot of us have small apartments with no balconies or gardens. And we're really used to using the city as our living room. And for now that ability to move throughout the city has been significantly reduced. We're struggling with limited space on sidewalks. If you go to sidewalkwits.nyc, you'll see that especially outside the denser areas of Manhattan, the sidewalks are not wide enough most of the time to properly social distance. So that's been a problem. Our parks have also been very busy the past few weeks. The weather is finally starting to warm up and we've been doing this for two and a half months now. People are getting antsy. People have cabin fever. It's definitely getting more and more difficult to be motivated to stay inside and we're seeing a lot more people outside in the last weeks. New York's been a really interesting place the last couple months though during all of this. We've actually seen some really interesting statistics come out of New York as a result of the lockdown. So we saw a 60% decrease in congestion on city streets. We also saw a 67% increase in city bike ridership. The bike share system here in New York. We saw a 52% increase in cycling across the river on the bridges into Manhattan and a 68% decrease in cyclists injuries citywide. And I think we're also at something like around 60 days without a pedestrian death, which is really unique for New York and that's definitely a record. So in terms of mobility, we've actually seen a lot of positive results from the lockdown. And what we're seeing is this sort of transition into what was a car dominated environment, even though it was New York, into this new environment where the car is no longer dominant. And these statistics are from the peak of the pandemic, so late March, early April. We're now starting to see some of that traffic coming back. We're nowhere near pre-pandemic levels, but it has risen by 58% since the end of March. So we are seeing a lot more people on the roads these days. But having lived in the Netherlands myself and learning a little bit about their history, what's really interesting to me right now is we're able to draw some striking similarities between what's going on in New York City during the pandemic and what went down in the Netherlands back in the 1970s, which was when the Dutch sort of jump-started this bicycle culture that they're so famous for today. If you follow UCI, I don't need to tell you what it's like in the Netherlands, but what's funny is that many people who visit the Netherlands, and this includes actually some Dutch people themselves, often assume that it's just kind of always been this way, that it's always been this amazing bike-friendly culture. But that's actually not true, and if you really dig into the history behind what went into creating this people-friendly, bike-friendly society, you'll see that that wasn't always the case, and that there was this sort of recipe that came together and led to the permanent policy and and infrastructure changes that we see there today. And you know, of course this is always evolving and changing and being improved upon, but the 70s was really when we saw these more purposeful and concentrated efforts to creating this culture. So it began in the Netherlands, it began with local activism. If you actually, if you look to the left of the screen here, you can see what I like to think of as sort of the three ingredients that went into this. And in the Netherlands, it started with local activism. So back in the 70s, the Netherlands was very much following in the footsteps of the U.S. in creating these more car-dominated environments. They were tearing down buildings to widen roads, there were more cars in the city, driving at faster speeds. Even in Amsterdam, they were talking about filling in the historic canals to build more roads and about building highways into and through the city center of Amsterdam. And what happened is that as a result of this new approach to development, a lot of people in the city were getting killed. They weren't used to there being so many cars, they were used to having a right to the streets, and unfortunately a lot of these people were children. And so this was the birth of the Stoke to Kinder Mord or Stop the Child Murder Movement, along with a number of other citizen-led collectives at the time. So demonstrations were held, people laid in the streets with their bikes to occupy places where people had been killed. We saw people setting up their own, what we now know as play streets, where they closed off the residents, closed off the streets themselves to let their children play, to have dinner outside. And this is really just a part of the story, but the point that I want to make here is that this whole process in the Netherlands really started with this fierce local activism. And similarly, in New York last summer, we saw advocates organize a die-in to protest the the spike in cyclists deaths seen in the city in 2019. I believe inspired by the Netherlands, people laid down in the streets with their bikes to bring awareness to the unsafe conditions for cyclists in New York, and this being a part of a larger livable streets movement that's been going on in the city for years. Next, we have the crisis. In the Netherlands, it was the oil embargo of 1973 that led to gasoline shortages. And now, of course, in New York City we know it's the coronavirus pandemic that is preventing people from using transit. And while both of these crises were very different and they affected different modes of transit, modes of transportation, they both resulted in this same need to think differently about mobility, and to reduce the dependency that we have on the mode that we're used to most, and to also think about improving resiliency in our cities. And in the Netherlands, this led to very quick temporary policy and infrastructure changes that addressed the immediate urgency of the crisis. So most famous is the car free Sundays. So every Sunday for three months, people had to leave their cars at home, and people really took to the streets. You know, we saw more people cycling. There were people using pedestrians using the full width of the streets. We saw more play streets. And now, of course, in New York, as a result of the coronavirus pandemic, we're seeing more pop-up bike lanes. We're seeing more cases of now what we call DIY tactical urbanism, where people are bringing their own cones or chairs from their house, so close off the streets so that they have room and space to play. And then, of course, we've seen the open streets plan from Merida Blasio. And going back to the Netherlands, these temporary changes eventually led to permanent change, and these are the changes that make up the bicycle culture that we see today. So this includes this use of shared street space that is so central in the transportation strategy of the Netherlands. This includes the famous separated bicycle lanes, the extensive network throughout the country that everyone loves so much, and then also just a general prioritization of cycling in city plans and policies. And of course, in New York, we have yet to see what will, what permanent changes will result from the pandemic. And one thing that I didn't mention here yet, which I like to sort of think of as the secret ingredient to the recipe, and what I think is the most important, is this idea of having the political will to get this done. And in the Netherlands, what we saw was that this combination of the local activism and the urgency of the crisis really came together to push this, to push first the temporary and then permanent changes. And this is what we've been struggling with the most with, this is what we've been struggling the most with in New York in the past months, especially when it comes to the open streets plan. We saw activists act very quickly in recognizing the opportunity here and making suggestions for streets that could be used as open streets. But the mayor has been very slow to act. So I'll talk a little bit about that. It started first with an open streets pilot, and that started as a call to action from Governor Cuomo, who was concerned about the parks being so crowded. So he tasked Mayor de Blasio with coming up with ways of getting creative on how to open street space for people so that they could get outside and be properly socially distanced. And de Blasio responded to that with his open streets pilot, which was at four locations in the city, one street in Manhattan, Brooklyn, Queens and the Bronx. And this totaled 1.6 miles of open streets. And just for reference, the city has about 6,000 miles of streets. So we could definitely do better. And this unfortunately was canceled after just 11 days. So there were a number of challenges cited for why this pilot couldn't continue, the number one reason being the need for policing. Advised by the NYPD, the mayor felt that we needed at least a couple of police officers per intersection or per block to direct traffic and to manage proper social distancing. And at the time, this was the beginning of April, at the time 20% of the NYPD was out sick with the coronavirus. So the mayor really felt that this was an unnecessary strain to the police force and that those that were healthy, their efforts could be better applied elsewhere. The DOT was also concerned about overcrowding. New York is obviously a dense city and we didn't want to create a situation where people would be congregating. Access to emergency vehicles was also cited as a challenge. I mean, that's especially important in a time when so many people in the city are getting sick. And what was kind of most interesting to me being new to New York is that there seems to be this attitude of, you know, New York is different, we're unique, we have unique challenges. What works in other places isn't going to work here. And that seems kind of silly, but in attending city council meetings, it really does seem to be quite a barrier to implementing this open streets program and pushing this forward. So I think this really all circles back around to this idea of having the political will to get this done though, because we have seen cities like Oakland do this without policing while maintaining access for emergency vehicles. Paris is on the forefront of this movement and they're a very dense city. And, you know, while New York is unique, I think that there are certainly lessons to be learned from other cities. And as I wrote recently in a streets blog article, you know, whether it's a long-term transit closure in Vienna or the transit strikes that Paris experienced last year, you know, we can be learning from cities who not only are acting fast during the pandemic, but have experienced similar situations in the past. So while it's true that we've never been through this before, there are plenty of cities who have had similar situations where transit or normal travel behaviors have been disrupted and they've used cycling as a solution. So yes, New York is unique and that's why a lot of people love it, but there certainly are things to be learned from other cities. And so we actually have seen some really positive change in New York in the last few weeks. So just as we saw in the Netherlands, this combined pressure from the local activism together with the crisis has actually led to political change in New York. So Mayor de Blasio was not enthusiastic about the open streets pilot, but after he canceled it, the advocacy community here really spoke out about how they were unhappy about how this had been handled, how this had been implemented. And then there were also two members of the city council who have been sort of spearheading the slivable streets movements in New York and together with the community, they really put pressure on the mayor until finally at the end of April, they came to the mayor came to an agreement with the city council to open up 40 miles of streets. And that's in the month of May with a possible extension to 100 miles. So we're at 30 miles right now. That's 21 miles of open streets and nine miles of new protected temporary bicycle lanes. And at the request of the council, this is also some of these streets are managed by local partners to deal with the need for the policing. So this is a huge win for the livable streets movement in New York. Everyone is very excited. This is a great first step, but that's exactly what it is. It's the first step. And we're still dealing with a number of challenges. While some of these are managed by local partners, that's only about three miles of streets right now out of the 30 miles. So we definitely could be leveraging that resource better. And in general, it's just not enough right now, or yet. We've really kind of picked the hanging fruit. A lot of these are in or adjacent to parks or in sort of quieter residential areas. So and they're kind of spread sporadically throughout the city and what seems to be the least disruptive areas. And there's really no system, right? And we know that for this to work, we really need a connected system so that people can not only get outside and enjoy fresh air, but that essential workers can use this system to get to where they need to go. And as we also open back up, this can be used as a way to keep the city moving while also staying properly social distanced. There's also been some equity issues with the current set of streets. So for example, Staten Island has the second highest number of cases in New York City, but they only have two open streets right now. That total 1.5 miles and 0.7 of that is inside a park, right? And we're seeing a similar story in some of the outer borough areas like southeast Queens or the Bronx. So I think if the main purpose of open streets is to help eradicate the virus and helping people stay socially distanced, then we definitely need to see more of a pairing between the areas that need it most and where the open streets are located. So what's next? Moving forward, as everybody is saying right now, this is really a critical moment in our history. Actions taken in the next months are going to set the stage for mobility for the years and probably decades to come. So this is really an important moment for us where we have a big decision to make. And this could go really one of two ways, right? We can make the necessary changes, provide mobility options for people. And in that case, I think we'll see the an open streets movement come out of the pandemic similarly to how we saw tactical urbanism come out of the Great Recession. Or we could go the other way, we could do nothing, in which case I think we'll see this sort of regression back into a Seinfeld era in New York City where there's more traffic, more pollution, more noise, as people retract back into their vehicles for fear of using transit for the next year. Also, as we're thinking now about what is life going to look like after the pandemic, how do we open back up? Local businesses are really starting to speak up. Again, we've been doing this for two and a half months. And local businesses are starting to speak up about needing to reopen and are wanting to use open streets as outdoor dining zones. So there's really, we're seeing this need to think about open streets not only as a way to maintain our mental and physical health, but also looking at it as a form of economic development in a way to kind of re-jumpstart the economy during the pandemic and as we open back up. So I think we'll see this transition into sort of a more alfresco economy where our lives are really being pulled out onto the streets. New York already has a street seats program where partners can apply to use underutilized sidewalk or street space for outdoor dining or for streets for leisure and recreation. So I hope that in the next weeks at the very least we'll see an expansion of that program in New York. So in conclusion, I just want to say that I think this is a really awesome and exciting time for the livable streets movement and for both existing and new cyclists. We're seeing a lot of people pick up cycling for the first time during the pandemic. And I think there's really an opportunity here to learn from the Dutch and from Dutch history and learn how they leverage their crisis to lead to permanent change in their culture.


You happy on your phone during this true. What do you mean true chains? You know, it's like 2019 New Year's Eve everyone's tagging you and the like highlights from the whole year and like You're just really popular cold memories and like social play pretty popular. I'm not I'm not like the members guy But I've got one Okay, they're like really into anime and I don't know anything so they just keep roasting me For the anime like I don't even know what it means. Hey, if you watch Naruto, let us know but can't use so Sakura just Hello everyone. Welcome back to my channel today We are doing a boyfriend versus best friend video. I'm not really super into doing relationship you videos We're doing this because Not in trap my best friend of 10 years at this point. Um is now finally starting a YouTube channel It's been a long time coming it has never thought we'd make it here, but here we are here. We are I've been trying to get her to do that all right meme. Hey, look at us. We thought we'd be here not me Cheers, here we go. Cheers our star. So we're gonna be doing best versus boyfriend Maddie's channel will be linked down below We also put a video on her channel where we go through the Enneagram and we basically like roast ourselves It's very fun and very cool. You guys should go over there Subscribe comment tell her I sent you if you guys have been watching my channel since I live in Texas Maddie was like she's been in my videos for years. So and yes We also have a podcast episode together. That's really good that I'll link down below Yeah, and I'll link her Instagram down below. She's really into vampire diaries now. So yes, please let me know What's team Stefan or team Damon? It's not a lot about you. We're not gonna judge you, but we might more than the Enneagram says well That's a lot. Okay, so if you guys are new here subscribe happy new year I don't know what this video is going on but first question. How old was I when I had my first kiss?  I'm young Maddie one. He's really competitive zero zero What is my current profile photo? Oh? A picture what Instagram is currently a picture that you did with your office photo shoot and you're laying down So it's an overhand picture and your hair is kind of like floss down stuff It's a very boss very GQ very Forbes girl very business insider to be fair. I knew that but I want to know which profile What color do I wear the most often black? She oh she I don't know she said before but she should be canceled to one Okay, I'm with and you can't make up the rules as you go Oh, wait, what face do I usually make when I take selfies and you have to do it? Let's see it when you wait, but we have to make the face. Yeah, let's do this. Yeah When you do something Things It's very like I was gonna say that like right there is what I was gonna say just like that Yeah, that's I don't really take selfies off smile, and that's right three one. Okay, what? What song do I turn off whenever it's on the radio? I'm submitting a random answer. What is it? Old Town Road? I don't know I Think you would be over that song. I will because we listen to it so much when we do big bear Okay, if you can think of a song I'll decide which one I'm gonna turn off first if like you immediately like I can't listen Yeah, I can't think of a lot of music that you dislike to be fair.  Yeah? Wow five one cuz I normally don't wear makeup. I just put mmm cute. What nickname do my parents have for me? Her dad calls her boo. There you go. Oh two five Um, what's my favorite store in the mall or it's here three five, okay? There's no Oh, that's a point for sure What drink do I order whatever I got to eat? Depends. We're talking about Lemonade, well, no, I mean I did it too, but like I said like depends like are we going alcoholic non-alcoholic? non-alcoholic What surely yeah, I know I think I ordered them equally so you both get a point That's one taco diners one. I don't eliminate. Okay. Honestly actually to be fair. I've been ordering Okay, then give time four or five. We're still winning. When is my half birthday? I Don't know where the bathroom is about his birthday. Oh February 1st, I'm Kenzie's best friend. I don't know her birthday August 1st. Yeah, 10 years Yeah, I don't know. I know my mom my dad and my sister.  Yeah? What's my favorite girl name, I know I have actually told you it's what I want to name my daughter and it's actually really obvious I've said this before to both of you Piper yeah Okay, she never told me that to see I have told you that before No, you didn't say with a daughter thing you said you really I think I don't want to do my first daughter Piper How many times have I broken a bone? Ah, man, it's what I think it's a once once or twice Yeah, I was gonna say three zero. Oh, who do I look up to most in life? Oh, there's a couple people I think you're dead, but yeah, I also casey mushrooms me. Yeah So It's a cute content what website do I visit the most often um, I mean besides Facebook the majeuret thing What's your job? Forward she's always on the secret Facebook and second will be Facebook for the Facebook group I'll listen to you to you guys out of the face. I don't know Facebook and no podcast I hope because you're keeping score. She said I have six. Yeah, okay How many times have I moved home after we did the math over here? I think is it I think it's like it's like 11 Is it 17? Yeah, I think it is like we tried to go through and I think it's 17 Honestly, that was only in McKinney in Texas. Yeah, I thought that would be including LA What was the last social media picture I posted? No, I did I did it first. It was you two Cheers in LA And on your leg and you're like but I Responses Do people ever call me a different name? Yes, it can One of my favorite kind of jobs to work So well, yeah, but from where? You both said it okay, um Pretty sure hip first have a point or should we just do points? We both know the answer or no who does it first? I don't know. This is we've gone way off track here. Yeah Let's just keep answering Now that you're losing That is your I can find self-worth without winning competitions Can you 100% but if you could win or lose, what do you want to do? You know I'm in Okay, what was my favorite subject in school history. She hit first History Kind of history Yeah, I said it this morning My most embarrassing moment at school what I don't know You're most embarrassing moment at how I know this one It was when they did the like we had brought in broadcasting.  Yes Yeah, I Literally shook my head. No, you know cuz the answer is no no Once no, it's not so weird. I thought you would I know right? How old is I when I got my jabber's license 16 Yeah Morning of my 16th birthday. Yeah That was really iconic I was the first one to get my license and it changed our lives forever She drove us everywhere. Where do I online shop from the most? The real real Did she hit you first or did I I don't know just answer. What's your answer? Like the most yeah, I Mean based upon what you've been getting recently. I mean, yeah It would depend. Are you taking like clothes or what clothes? It's I mean for sure. It's yeah, you've got you get multiple sets though It would be Princess Wally. Oh, I love you so much. Yeah, you can't buy it anywhere Okay, what was my first tattoo First tattoo you got was a little text thing. I Had no idea about that. No, it was my star Dang it. Yeah, okay. What is my relationship status? She's in a relationship with your boy single Single And it should be 12 to 8 because she wouldn't have known of his history, but it's fine I could have guessed that it was his wrong incorrect and conceivable I was really gonna say have I ever been suspended from school. No It's great. I didn't know that for why I want to be in France. Do you smoke? No? No, I hit first No, and her knee is lower than that knee. Okay. Yeah 12 to what are your parents names? Make it Melissa and Beth. Okay. What is my dad's real name? This this wall of Michael. Yeah. Oh, I'm right Okay Okay, she'd be 14 8 because once again she wouldn't have got that one, but it's fine What is my favorite number?   No, it's 23. Oh, it's close What color hair does your crush have? Dark dark dark brown point for Maddie. He's like not mad cuz it's about him. Have I ever left the continent? Yes, do I have I ever used the hoverboard? Yes 15 to 9. Do I know anyone that has the same birthday as me? Yes How long does it take me to do my hair? Five minutes because now you've a dicing hairdryer. Yes Thank you, Maddie Honestly, if I'm curling it it takes 10 if I'm drying curling it takes 20 So neither of us were right. No, I said less than five Less than five minutes, but I wear in a bun every day If you can't tell that's how long it takes me What superlative Would I have gotten in high school? I did get a superlative. I did win an award. Oh I would say I mean, I don't know if it's like in Texas, but like dreamer and do a word type deal like for being like business I was just gonna do what I got. No, I don't remember because I didn't go to your high school though I was just gonna say most likely to be famous President most likely well is that what the superlative is? I got class favorite. Oh I know right? So I think that is it for today's video. You guys are both winners in my heart. No In the words of Ricky Bobby The first your last Just kidding. We got into more detailed questions. I think 100% and I told Kenzie this that Maddie would win. Wait I have more questions. Okay. What is my favorite child or my favorite thing to do in Texas? 90 water burger Shop at North Park. Yes. You got it. Okay Yeah, what is Well, the points are both like favorite year of school growing up Junior I Yeah, I hated junior low sophomore year. Okay, great. So anyways, everyone's a winner in my heart Hope you guys enjoyed this video go check out Maddie's Video down below her channel. We also vlogged up a little bit together We have a vlog up that I just posted so watch that vlog Subscribe watch this video. Hope you guys enjoyed. I'll have all of our Instagram stuff linked down below Love you guys so much and I'll talk to you soon. Bye


So, one of the biggest challenges to engage youth into the innovation ecosystem on a global scale is to ensure that there is free mobility, opportunity for mobility for youth. And I think this is a huge barrier from a variety of sources, lack of resources for highly talented young people to get to the destination where the talent can be put to use, to visa policies, to other kinds of impediments. So, this is why a number of organizations that have started to collaborate, I mentioned the Global Research Council as an example of top funding agencies from around the world. One of the agenda items for them for this year, next year the meeting will be held in Beijing, jointly organized between China and Canada here in Beijing. One of the focal points will be providing access to young people and ensuring through policies and practices and funding, providing access to young people to travel freely to participate in the innovation ecosystem, at least from the viewpoint of academia and research.


Yeah, Matt, you talked about Kyle throughout, you know, as you're all on the brink of the first game, could you just summarize how the rookies handled everything before you all get ready to go here against Eagles? Yeah, I think he's done a good job. I think he's in a good spot, you know, coming into game one. I thought training camp was really good for him, you know, I thought from understanding the offense to where he was at at the beginning of it to now, he's come a long way. You know, I know all those rookies, you know, your first time, it's new, it's exciting, you're nervous, you're all those things, but my point to him is it doesn't change in year 14 either. You know, this first one is, it's always exciting. And so, you know, let's make sure we have good week of practice, enjoy the moment, and I think it'll be just fine. Tony yesterday, and he said one of the reasons for good things for a kid is that you know how to use the tight end. You know, he talked about how you told him where you wanted to ball, and all that, he kept going through all that. Yeah.  For sure. I think every player is different, you know, everybody's got their own unique skill sets, but I think from having played for a while, played with a number of different guys, you know, you try and get a feel for guys' strengths as quick as possible. And I'm clear with him about, you know, where I think certain throws are going to hit versus certain coverages and how he should expect it. You know, I think he's done a great job. He's a sponge. There's no question about it. He listens and, you know, he's constantly taking in information. You know, one of the things you do with guys like that is sometimes you just give them what they need to, you know, because sometimes it can be overwhelming, but I think he's really done a good job for us during camp. Thanks.   Any different for you when you're playing the Eagles, though, considering... I think early in my career it was. I think at this point, you know, I don't know how many... We've played them quite a few times, playoffs and regular season games. I think this might be the third time I've opened with them for a season opener. You know, the longer you play, the more they're very much just the same week to week, and I try and approach that with that mindset every week. Do you get more like outside people, like friends from Georgia, like reaching out this week or no? Yeah, I mean, here and there. You know, maybe a few more text messages or something like that. I've got a handful of tickets. There's no doubt about that, but it's really not that different than other weeks. The first time you sat down with the officer and really talked about this, did you feel like you were immediately talking the same language? Did that take some time? Did you feel like you were coming from the same place? Yeah, I think, you know, I think from a macro standpoint, we were very much on the same page. I think from a micro standpoint, some of the terminology here and there is a little bit different. And it's just trying to sort those differences out, you know, at the beginning. But I've said it, you know, before, I think he's worked on different staffs with a lot of people that I've played for. And so, you know, I think there is a lot of, you know, things that we've both done at certain points of our career that are very similar. And, you know, I think that helped in the transition process. Do you feel like there were things that you may have liked more or liked more than he did and you had to win him over or he won you over in certain ways of thinking? Yeah, I think there's a little bit of that, you know. As you go through it and you watch certain things, you know, you make suggestions. I've certainly made suggestions of things that I've done throughout my career that, you know, might fit the personnel that we have right now. And he's certainly shown me a lot of things that they did in Tennessee which were different from what we had done. And, you know, they had great success there with it. So I think that worked both ways. Gord? I asked Arthur this, but I wanted to get your opinion too. What are some of the indicators for you that kind of show you that you and Arthur are in sync in what you want, I guess, just, you know, what you want to be going into a legal term? Well, I think, you know, I think you talk about as we went through probably the second half of training camp, the type of execution, the type of pace, you know, that he wants during practices, you know, being aggressive at certain spots, wanting to know to get rid of it, check it down, do certain things like that. I think really the second half of training camp, that part started to come along and you can feel like there was less, you know, here's what I'm thinking here. It was more, you know, that's what we talked about, good job. We'll go on to the next one. And so, you know, I definitely feel as we continue to move along, you know, we're in a better spot. You know, certainly they'll be growth throughout the year though too. I think, you know, the key, I think, haven't been around, you know, for a few years is that we constantly got to be growing and evolving and getting better and our relationship has to get tighter. You know, if we do that, I think, you know, we'll give ourselves a chance to be the kind of football team that we're capable of being at the end of the year. I remember you talking, gosh, this is probably months ago at this point, you were talking about the noise is a lot more difficult to drown out now than maybe ever before. And I'm just curious, kind of at this point in your career, what are the challenges of kind of throwing off the labels that, you know, other people put on even going out there week one and being, you know, who you believe you are?  And then, you know, the opinions of the people that matter to you. And, you know, I really feel like I've got a good support system for myself. I feel like I'm in a great place and have a good routine and process and, you know, I find confidence in both those things. What are your expectations just going into this first game of the season? Kind of that learning curve with Anchor Jordan Smith being it's his first NFL game as well? Yeah, I think, you know, for us, it's about going out and operating on offense and, you know, making sure that we're detailed in our plan. We're doing what we're coached to do and that we're efficient. And, you know, I expect us to go out there and operate that way. So that's got to be the expectation for all of us going into the first game. What is different? What do you learn the most about game day preparation? I know Calvin's talked about wings from a car wash. So what is your preparation? Yeah, what's your preparation? What do you learn from year one to now to year 14 going in? Man, I do a lot of things different. I think a lot of them, you know, come in terms of, you know, when you're young, you're getting advice from all kinds of different places because you don't really know. And you do, it takes a period of time to learn what works for you. And so, you know, I think in my film study, you know, in my going through the game plan and studying it that way, I think I'm more efficient with my time. You know, I have a better understanding of what actually matters to me and what doesn't. And I think the same in terms of my physical preparation too. You know, I feel like the way that I train, you know, the days that I train, what exercises and what certain things we're doing on certain days is much different than it was earlier in my career. And it's come from a place of constantly evolving, you know, and trying to get better and also learning from a few mistakes along the way too of, you know, things that have come up in my career. Kind of respect Allison's first question. But how hard is it in week one not just facing a team that's going to have unscathed looks like everybody but also a new coaching staff and a lot of new players? Yeah, I think there's always challenges in that. You know, when you're facing an entire new coaching staff, new play caller, you know, coming from a different organization, it's always, you know, it's always hard to know what exactly you should be watching in terms of your film. I think the biggest thing is making sure that we know our plan and what we're trying to do and make sure, you know, that we're all on the same page offensively. You know, I think if you know your rules and you trust what you see with your eyes and you trust the rules that we have in place, you know, it helps when you're going to see some things that are unscathed. We'll get some looks on Sunday that we haven't seen in the preseason from them and it'll be about adjusting to that and making sure that we're on top of our keys. There were fans in the preseason, there were fans of training, can't there were some fans last year, but how different is it going to be? What are you expecting out of the crowd? And also a rowing row crowd of history than the importers?  And so it was cool to watch college football last week and see, you know, the atmosphere. I mean, that part of it was missed for sure from the player standpoint. And so, you know, I'm hoping it's a great atmosphere for us on Sunday. You were talking earlier about the advice that you gave Kyle Piss, schematically and on the field, but what would be your biggest piece of advice to a rookie like that where there's a lot of conversation, a lot of spotlight, and now he's just getting started?  It's different from how much you get pulled in different directions and, you know, those kind of things are different.  And so, you know, just prepare all week as best you can when it comes time to play, cut it loose, have fun, and enjoy the moment. Marcus, what are some of the challenges that you can present for you? I think they're talented in the front four. You know, they've got some guys on the defensive line that are disruptive players, guys that I've played against a number of times, and you know that they can take over a game. It's a great challenge for us, you know, to see where we're at against a really good front four.  A lot of people talk about how, you know, balance is key on offense. Like, what does that look like for you in this office? Because you've got a lot of success in, you know, any wonderful ball and play actions and stuff like that. So what does that look like for you in this new office? Well, I think, you know, it's making the defense defend a number of different things. You know, defending the run game inside, outside, misdirection, all kinds of different things. And then same in the pass game, you know, marrying up your play action pass, making it try and look like your run, you know, so that they struggle there, having all kinds of different things in your drop-back game, stressing them on different levels vertically, horizontally. I think, you know, you want to have great balance and you want to try and, you know, make it as difficult for defense to key in on what you're doing. Listen, I got a text from Matt Shaw about Midway Through the Game. He said, B.C. is doing good against Toothpaste U. So we'll take it, though. You can only win the games on your schedule. Thank you. Seriously, you sort of alluded to this a little while ago, but you also sort of live unsure about what you expect in the first game in terms of, particularly from the offensive perspective, how in sync you guys are with each other since you've come in. Can you get a sense first, for instance, what's going on? Yeah, I mean, I think you get a sense for what it's like, but there's definitely unknown. You know, there's always unknown going into the first game, whether it's a new staff, a staff you've been with for a long time, you know, whatever it is, there's definitely unknowns going into any season. And, you know, I think we'll be a very different team in November and December. I hope we are. I hope we're a much better football team. We've continued to improve. But there's definitely unknowns going into the first game. I think people actually knew him when he was in Philadelphia. I on the other hand, he was flying under the radar at high school, so yeah, it'd be cool for him, you know, I'm sure, you know, growing up there and, you know, family and friends still back in that area. I remember, for me, we played up there in my rookie year, and so that was a unique experience. Michael asked about it earlier. Back then it was like, it's much different than it is now. And, you know, it'll be, you know, a really fun experience for him.  No, no, no, no. You can't give any of the trade secrets away. Yeah, time for one more secret. Just to go through one different subject. Just go on. Be sure, if you've been written down, you guys might not be as good as this. Six words I think has been out here, but you might win. Does that ever get old when people already say how not good you're going to be? Oddly enough, I think most of the time they're wrong. So, you know, good or bad. I don't, I don't worry about it too much. You know, there's, there's 17 games on our schedule. There's a lot of football to be played between now and then.  I feel like we've got a good team coming into the season. Thank you. Appreciate it.


Good morning, everybody. Thank you very much. I'm Larry Thompson, the Chief of Communications and the Public Liaison Branch at the National Human Genome Research Institute, which is one of the 27 institutes and centers at the National Institutes of Health. I'd like to welcome everyone to what I know will be an interesting telebriefing. Embargoed materials, including videos, illustrations, and photos related to this announcement will be available on our website, genome.gov, forward slash proteus. That information is available right now. It's not available to the public. Generally, it's not hooked up to the website, but if you go to that, genome.gov, forward slash proteus, you'll be able to find all the background information available now. We'll start with a brief opening remarks by Dr. Eric Green, who's the Director of the National Human Genome Research Institute, and Dr. Leslie Beesiker to my right, who's the Chief and Senior Investigator of the NHGRI Genetic Disease Research Branch and the Senior Author on this paper. In addition, we'll have, with a spy phone from Colorado, Kim Hoag, who's the Founder and Executive Consultant to the Proteus Syndrome Foundation in the United States, and from London, we have with us Tracy Whitewood Neal, who's the Chairperson of the Proteus Syndrome Foundation in the United Kingdom. During the call, we will discuss a paper that will be released at 5 p.m. Eastern Time Today, Wednesday, July 27th, in the early online edition of the New England Journal of Medicine. Please note that the contents of this press briefing and the contents of the paper are embargoed until that time, 5 p.m. Eastern Today. Now, let me introduce Dr. Eric Green, who will make some opening remarks and provide some context for this gene discovery story. Dr. Green. Thank you, Larry, and good morning, everyone. I'm Eric Green, Director of the National Human Genome Research Institute here at the National Institutes of Health. We're here today to talk about the discovery of the genetic cause of a very rare and profoundly complex disorder called Proteus Syndrome, named for the shape-shifting Seagod from Greek mythology. Unlike the Seagod who could select his form, the bodies of Proteus Syndrome patients change against their will because of a single letter is altered among the billions of letters that make up their genetic code. This single letter change causes parts of their bodies to grow out of control, becoming misshaped, enlarged, and painful. And for many, it is life-shortening. Few of us will ever meet someone with Proteus Syndrome. Moreover, few doctors ever see a case in their medical practice, since there are fewer than 500 known cases in the developed world. So why does NIH take such an interest in a disease that is that rare? The answers are actually rather simple. First, rare diseases provide important windows into how the human body works and often provides valuable clues about the causes and possible treatments for more common diseases. The gene involved in Proteus Syndrome, for example, is also mutated in some forms of cancer. And second, even though these individual types of disorders are uncommon, as a group, rare diseases actually affect a large number of people. More than 25 million Americans suffer from some 6,000 rare diseases, and the burden in human suffering is tremendous. Fewer than 300 rare diseases have useful treatments at the present time. Relatively few places in the world can afford to study rare diseases. The Clinical Center here at the National Institutes of Health in Bethesda, Maryland is one of them. And in cases like Proteus Syndrome, that can make all the difference. NHGRI clinicians brought Proteus Syndrome patients to the NIH Clinical Center to participate in medical studies and for treatment, oftentimes involving surgery to remove uncontrolled growth. As a result, NIH staff collected tissues for analyses that ultimately led to the current discovery. In addition to a world-class research hospital, my NIH colleagues could also turn to the expertise and technologies within the NIH Intramural Sequencing Center, where researchers perform genome sequencing of Proteus Syndrome patients and tissues and then analyze the resulting data. It is the power of the new genome sequencing technologies as well as the unique resources and collaborations common across NIH that make today's announcement possible. As we sequence the genomes of more and more individuals, the medical value of genome sequencing will grow. Discovery of the genetic causes of diseases, like the one today and many others earlier this year, will become more frequent and eventually help us in understanding the genetic basis for more common disorders from diabetes to heart disease. We're just starting to capitalize on the new leading edge of this genomic revolution. But like X-rays peering into our bodies in the previous century, the power to routinely and robustly peer into our genomes will prove revolutionary. To tell you what was done in studying Proteus Syndrome and what has been learned, I'd like to introduce Dr. Leslie Bisiker, a board-certified medical geneticist, a human genetics researcher, and chief of the Genetic Disease Research Branch in NHGRI's Intramural Research Program. Dr. Bisiker. Thank you, Dr. Green. Today's report in the New England Journal of Medicine is the culmination of a 15-year-long search for the cause of Proteus Syndrome in my research group here at the National Human Genome Research Institute. But much of the credit goes to the Proteus Syndrome Foundations of the U.S. and the U.K. and physicians and hospitals around the United States and around the world that have referred their patients to our study here in Bethesda. And while the American taxpayer funded most of our work, critical financial support also came from the Proteus Syndrome Foundations, both in the United States and the United Kingdom, which not only provided funding, but helped us to recruit and they supported patients from around the world who participated in our study. You will hear from Kim Hogue and Tracy Whitewood-Neal shortly about what this discovery means for members of their communities, but first let me tell you about this disorder. No two patients with Proteus Syndrome are exactly alike. Most of the affected individuals appear healthy at birth, but typically during the child's first year some parts of their bodies begin to grow faster and larger than they should, becoming progressively and sometimes startlingly pronounced with age. Our clinical studies have shown that the overgrowth can affect just about any part of the body, but most commonly affect the skull or arms and legs and a variety of skin lesions including thickening of the soles of the feet. For some patients, neurological impairment can occur and others have suffered fatal blood clots and lung disease. It is for many patients a truly devastating condition. Participants in our Proteus Syndrome study came to the NIH Clinical Center where for some our team performed operations to help stop bones and tissues from overgrowing. While certainly helpful for those patients, these surgeries also provided vital biological materials that we could bank and then later study for genetic changes. These studies proved to be critically important because the gene mutation that causes Proteus Syndrome rarely appears in blood samples. In the clinic we must have tissue biopsies to genetically diagnose the disorder. Not only did we need the tissue samples for our research study, but we also needed genome analysis technologies to mature. With the advent of what is called next generation sequencing, it became affordable to send DNA from biopsy tissue to the NIH Intramural Sequencing Center where our colleagues performed whole exome sequencing on seven patients affected with Proteus Syndrome. Whole exome sequencing analyzes just the protein coding sequence of the genes, allowing us to discover a point mutation, a single letter misspelling in the three billion letters of the genome's DNA in a gene called AKT1. This activates the sporadic tissue growth in patients with Proteus Syndrome. A more standard sequencing strategy then went on to confirm that same gene mutation in an additional 20 affected individuals, and I really want to emphasize that all patients so far have exactly the same mutation in the same gene. The AKT1 gene mutation has never been found in unaffected people, as our survey of several genomic databases and other populations we study here at NIH. But here's the really surprising part, which is that the mutation is not inherited. Instead, it occurs anew in a single cell in each affected individual during embryonic development, and the severity of the disease depends on when during embryonic development the mutation arises. Once the mutation happens, the cells that descend from that mutated cell display the uncontrolled growth that characterizes this disorder. This explains why the mutation was difficult to detect. When we take tissue samples from an affected individual, some of the tissue is affected by the mutation, and some of the tissue is affected by the mutation, and some of the tissue is essentially normal. A mutation that occurs in this way at some time during embryonic development is called a genetic mosaicism. The consequence is that only some of the body's tissues and bones display the overgrowth, and other parts of the body are not affected. The affected patients are thus a mixture. Parts of them have the disease, and parts of them do not. This makes sense biologically with what we know about this gene. The AKT1 gene mutation creates an oncogene, the kind of mutation that can drive uncontrolled cell division normally associated with cancer. In fact, the AKT1 mutation has been found among a group of mutations that cause cancer to spread. The research on this gene mutation in cancer may turn out to be beneficial for patients with proteas syndrome. Work that has been done by others to inhibit the activity of mutated AKT1 has shown that it may become possible to treat patients with proteas syndrome with a drug originally developed for cancer. There are a number of other potential drugs being developed to inhibit the pathway involving this gene. I can answer questions you may have about the science of the AKT1 gene, but I would also like to mention that proteas syndrome has played an important role in our cultural history and arts. The most famous person we know with hallmark features of proteas syndrome is the 19th century Englishman Joseph Merrick, formerly known as the Elephant Man, who gained renown during his life and well afterwards due to his profound overgrowth, which included a very large skull, an overgrown arm and leg, and numerous other complications. Through the cooperation of Professors Martin and Syndicom Court at the Royal London and Bartz Hospital where he died in 1890 at the age of 27 years, we have begun a study to test DNA from Merrick's skeleton for the genetic mutation of proteas syndrome. We will be testing DNA in our lab and hope that our tests will answer the more than a century old question of the cause of his condition. This will not be an easy study since his DNA is quite old and degraded by the way the skeleton was prepared. So at the moment we do not have results to report, but we hope to be able to announce an answer in the coming months. So let me close there and ask Larry to introduce our proteas syndrome foundation representatives who have joined us today. Thank you Drs. Green and Busicker now to speak on behalf of the Proteas Syndrome Foundation of the United States and the United Kingdom and to represent the families of those of Proteas Syndrome are Kim Hogue and Tracy Whitewood Neal. So I'd ask Kim to go first and make your opening statement and please go ahead Kim. Okay, good morning. Today I would like to give you a brief understanding of what it is like to be a parent that has a child with Proteas Syndrome and what this finding means to our families. This is obviously a syndrome that is shared by only a several hundred people in the world and it's very scary as a parent to have one of those children. I gave birth to Alex, my first child in 1990. After one full year he was finally diagnosed with Proteas Syndrome. I was handed an article with numerous cases of children with horrible, horrible overgrowth. The article spoke of amputations, disfigurement and Joseph Merrick's Ellison Man. It was positively a nightmare come true and the real kick was no one knew what caused it. I had so many questions and I had no idea where to turn because no one knew much about Proteas Syndrome in 1990. I mean imagine getting the flu and no one had ever heard of it or seen it. Just you with the flu not knowing the course it would take. It was very much like being lost in space. In 1990 there was not a clear cut diagnostic criteria for Proteas Syndrome. Most doctors would never even see a child with this syndrome so who could be an expert? I myself had to become the professional to the professional making sure that each of his six or so doctors was aware of what the other doctors were doing, thinking or guessing. It was a very scary place to be. So in 1992 I started the Proteas Syndrome Foundation, the USA. I did this for several reasons. Two of which, one of which is in order to pull families together so that a database of Proteas patients could be made in order to make research into Proteas Syndrome a more manageable task.  Over the past 19 years I've had families come to the Proteas Foundation in many different states, scared, worried, ashamed, unsure of how to raise their own child and always scared of death. Unfortunately, I did not accomplish my goal of saving Alex. In 1999 at the age of nine he died of a pulmonary embolism, pulmonary embolism or DVTs we now know are common to these kids. Back then the pieces hadn't been put together quite yet so we weren't looking for DVTs. Now thanks to Dr. B. Secker and his work and the other wonderful doctors at NIH, in 2011 there is a clear diagnostic criteria for Proteas Syndrome making it easier to diagnose. New Proteas patients are immediately told about the foundation to give them support and guidance and now parents can understand what has caused their child to have this syndrome. This discovery opened the pathway for research to find a medicine to regulate this growth of these cells. This opportunity was not available before the finding of this gene. The next chapter for the Proteas Syndrome Foundation is to stay committed to the NIH and Dr. B. Secker as we move forward with therapeutic research. Great. Kim, thank you very much. And so Tracy would you like to make your opening statement please? Of course. For me and the families that I support, this is so much more than a scientific breakthrough. This is personal and this is real. It's the light at the end of the tunnel and that glimmer of hope that we've been waiting for all these years. Many of the families that I talk to have dared to dream for so many years that a cause would finally be found and they would have a chance to actually stop Proteas in its tracks. I actually started the support group in England after meeting Les and meeting Kim and for many of the same reasons that Kim has explained about the lack of information, the isolation and the wanting to find answers. Of course this news is so exciting that it could be very easy to forget the 15 years of dedication, hard work and commitment put in by so many people by Les and the team at the NIH, by Kim and the Proteas Syndrome Foundation that you started all those years ago. If you think about it, all these years have been about all the presentations we've given to groups and schools and organisations, the documentaries, the meetings, the fundraisers, it's about the families that have travelled from all over the world to take part in the study. The children that we've had to watch, they've gone through countless tests and examinations and it's about the doctors that have supported this research by sending tissue samples after operations. But it's also about the lives that have been so tragically lost and Kim has just talked about Alex. I never had the pleasure of meeting him but I have met many children one year and then heard of their passing away the year after. And we are so lucky that Kim and the other families that have carried on despite their tremendous loss and I'm very aware that how we must be very sensitive to that. Lastly, I must mention my son Jordan who has Proteas Syndrome. He is 16 now and I'm grateful every day that he is still here with us. He has endured a lot of pain in his life and various operations since he was actually two weeks old. Jordan had his first leg amputated in September 2009 and the other leg in February 2010. That was a very, very difficult decision for him but he's happy he made that decision and he starts college this year and hopes to go to university to become an architect. It's inspired many people and I'm proud of what he's achieved and I'm proud of the drive ambition that he has. Now as Kim said, we need to start a new chapter and turn a lot of energy into finding treatment options. And just last, it's been an honor and privilege to work with everyone involved. Thank you. Thank you very much Tracey. So what I guess what we'd like to do now is open up the phones to the reporters to ask questions for any of the four members of our panel here. Please identify, give us your name and tell us what your news organization is when you ask your question. And Leo, would you remind everybody how they can indicate if they'd like to ask a question? If you'd like to ask a question, please press the star and one keys now on your touch tone telephone. We'll take our first question from the site of Michelle Cortez of Bloomberg News. Thanks so much for taking the call. I am wondering if you can tell us about this, the idea that the cancer drugs might be afford some type of a treatment. Do you have a steady plan to do that and how do you envision that might actually work? How would that benefit these patients? And I'd ask you guys, everybody who's speaking on our side to identify themselves also since we're on the phone. Right, and I'm Michelle Cortez with Bloomberg. Thanks. Thanks, Michelle. Michelle, this is Les B. Secker. So as you're aware, there are a number of steps involved in getting from the discovery of a causative mutation to an effective therapy. We are extremely fortunate that because this mutation has already been known to be a mutation that is involved in some cancers that a substantial amount of work has already been done studying the effect of this mutation, as well as a number of companies have begun programs to screen for small molecules or therapeutics that are active against this protein or even better the activated form of this protein as this mutation is. So that allows us to leapfrog a number of steps, and however there's still much to do with respect to the fact that Proteus Syndrome isn't cancer, it's an overgrowth disorder. And so it will be a challenge to adapt treatments which are designed for cancers to work for overgrowth because again these patients are mosaics and part of their body has this mutation and part does not. So the trick will be to balance, have a treatment that balances slowing down the mutation in the overactive cells without excessively slowing or inhibiting the activity of that protein in the normal unaffected cells which would probably have negative connotations for their health. Follow up Michelle, does that answer your question? Yeah, I guess I'm just wondering what the theoretical, you know, how it theoretically would work. Is the idea that this kind of treatment would stop the cells from dividing and slow down the process? Is that it or would it actually kill those cells? Great question. So this protein does a number of different jobs and a number of different cells. So the answer to your question will depend on exactly which cells are involved. So it's a really interesting and challenging question. Most of what the protein does is slow down apoptosis or programmed cell death and so the cells don't stop growing or die when they're supposed to. And so what we would hope is that by inhibiting this protein that we could make that process start up again and so that the cells would stop growing. So the hope would be that by inhibiting the protein you will see the slow replication or stop it in cells that in fact should have slow or no replication and the mimic the effect of the unmutated protein. But there are other effects and one of the other effects is that this protein is active in platelet activation which as you know is important for blood clotting which relates to the problem of thrombosis and embolism. So reducing the activity of platelets will be another task that we will want to try and do. So it'll be challenging to inhibit the multiple effects of this mutation in multiple cells. Great, thank you very much. So we move to the next question please. It looks like Brendan from Nature would like to ask a question. Yes, Brendan from Nature, your line is open. Hi, yes, this is Brendan Barr from Nature Magazine. I was curious what this discovery means for previous findings that a P10 mutation was associated with Proteus syndrome and Cowden syndrome and others. Does it kind of clinically delineate further what these different disorders are in some way or shape or form? Brendan, this is Luss. Thanks for the question. It's a great question because it turns out that AKT1 is in the same pathway as P10, the P10 gene and that this explains why mutations that knock out P10 function cause a similar phenotype to mutations that activate AKT1 and that explains why patients with these two disorders have overlapping but somewhat distinct clinical manifestations which is what we had concluded from our clinical research work on the patients who've come to NIH. That is that the patients with the P10 disorders and there's two names for that disorder. It's either called the P10 tumor hematoma syndrome or the Solamon syndrome, S-O-L-A-M-E-N. And patients with that phenotype can also have overgrowth but the character of the overgrowth is different than it is in patients with Proteus syndrome. But it does again explain why there are, there is overlap between these two disorders because the loss of one protein should cause the same effect as the gain of the other protein. Cool. Anything else, Brendan? No, not right now. Thanks. Okay. Can we move on to Matt Jones, please? Matt Jones of Genome Web, your line is open. Thank you. For Dr. Besiker and Dr. Green, first of all, I'd like to find out if this was, this project was under the Rare Neglected Disease Program. And second, I'd like to hear a little bit more about the genomic analysis and how the process worked and whether or not you knew you were hunting for a single mutation. So this is Eric Green. I'll answer the first question and then Les can answer the second. This project was not done under the auspices of the Rare Neglected Disease Program. In fact, it predates that program by probably a good dozen years or so of effort, if I remember the full history or some large number here, well over a decade. So no, it's not formally part of that project and it's not been at all associated with that program, at least up to the present time. The other part, Matt, restate the second part of your question about how the sequencing was done. And any analysis and if you thought or suspected that you were looking for a single mutation? Okay, it's good. Matt, this is Les. Thank you for that. Actually, I would say that all bets were off as far as what kind of a genomic aberration could cause this disorder. That is to say it could have been a point mutation. It could have been a large genomic aberration, such as a copy number variant or a structural genomic variant. It could have been a change in the imprinting or methylation or histone modification of a gene. There was just no way to know in advance and therefore we worked through a number of possibilities, one of many of which was a point mutation and because exome sequencing has become affordable now and with the support of the Proteus Syndrome Foundations, it became a tractable problem to sequence exomes of a number of patients and then compare the affected tissues to the unaffected tissues within the same patient. And as well, our study included a pair of monozygotic twins and in those twins, one of the monozygotic twins has Proteus Syndrome and the other one does not. And again, leading to this mosaicism hypothesis. So this is a different kind of a sequencing study. Most sequencing studies, you compare affected patients to unaffected patients, but here our primary comparison was comparing within patients the tissues that have the trait to those tissues that don't have the trait. So it's kind of in between what you do for inherited diseases and what you do for cancer sequencing. Does that answer your question? Yes, thanks so much. And is it fair to say less that the degree of genetic homogeneity that you've found was not expected necessarily? Going into it, you had no idea what you were going to find. Exactly, and as in many traits we study, some of our traits can be caused by mutations in multiple genes in addition to multiple mutations in the same gene. And again, all bets were off, we just had no idea. Once you know what the mutation is and understand the biological pathway, then it makes sense that it is a single gene because in general it's more specific of a mutation that leads to activating a gene than it is mutations that lead to loss of function of a gene. The latter are typically much more heterogeneous. This is Larry. Actually I have a question that's occurring to me. Were you surprised that it was a single letter that was being changed? I mean, this is a hugely powerful effect for switching a single letter in the genome and we know that there are snips all over the genome that have no effects like this. So why is this one letter changed having such a profound effect? So this is less, there's a huge variation in the correlation between genomic variation and health and disease. And as you say, all of us have thousands of variations in our genome, some of which cause little and many of which cause absolutely no consequences. But a few mutations in a few genes can have overwhelming and profound effects on our phenotypes and our physiology. And this is one, and it's in a key protein that is important for regulating growth and activation of multiple pathways. And so this is one of those few that just has a huge effect because it is a key player in physiology of growth and development. Very interesting. So we move on to the next question. I think Brendan has another, has a follow-up. Yes, we have a follow-up question from Brendan Mayer of Nature Magazine. Go ahead. Yeah, getting on to the idea that this one mutation seemed to affect so many in your sample group or almost all in your sample group. Is there any ideas to the biology of why this one gene seems to be mutated in this one specific spot? Why that's potentially tolerated in the cell in the embryo and why it causes this disease? Okay, thanks Brendan. This is less. In general, activating mutations are much more limited in their spectrum because again there are fewer ways to turn on a protein than there are to turn it off. And what we would predict is that loss of function mutations in this gene would be more variable and scattered throughout the gene but they would be predicted to cause a phenotype in an individual that is in many ways the opposite of Proteus Syndrome would probably cause undergrowth of cells and early apoptosis, etc. may actually cause early embryonic severe fetal growth restriction or fetal loss and cause a completely different disorder that we haven't even recognized yet. The mutation spectrum, the limited mutation spectrum that we see in patients with Proteus Syndrome exactly mirrors what we see when the researchers who have done the previous work on sequencing cancers for this gene and this gene is most commonly mutated in breast cancer. It's not a high fraction. I think it's about 5% of breast cancers but when you look at those cancers it's almost all this single mutation, exact same mutation in those cancers as well. So I think that mutations can probably occur throughout this gene. It's just that this one mutation is the kind of mutation that can cause this kind of an effect in the cell and so that's what we have found because nature has filtered out these other effects and left us with patients with Proteus Syndrome or these cancers and so that's what we see when we look at it from that side. The thing that's interesting, this is Larry, the thing that's so interesting about it though to me was the severity of the disease in Proteus is dependent on when during embryonic development the mutation occurs, right? The mutation is spontaneous and so what, I mean, what is the, what is the, is there a way to linearly project how severe it's going to be based on when or do you guys have an insight into that? So we obviously don't have the ability to go back and determine when and where this mutation occurred in the affected patients. That'll be work that we will need to do in animal models to try and model that phenomenon and see if we can understand that better. But it's once you understand and have proven the mosaicism hypothesis you can predict that the earlier the mutation is the more diverse will be the tissues that are affected because those cells will go on to potentially contribute to more and more diverse organs and tissues in the developing body. And conversely, the later the mutation occurs you would expect the disease would be more mild and it would be more restricted to smaller areas of the body. And in fact, there are rare patients reported in the literature who have just a quarter size lesion on their foot that looks like it's Proteus syndrome but they don't have any other manifestations of that disorder. And so one would predict and we were going to start working on this predict that those patients have a very late mutation limited to just one tiny part of the body but it's the same mutation and the same disease process just later and lesser than it is in patients with Proteus syndrome. The converse of this is that it's a mosaic disorder and there are no cases known in the world of patients who have this disorder who have either an affected child or who have an affected brother and sister. The hypothesis for that which is now supported by this work is that this is such a key growth regulating gene that if you have this mutation in all cells because you inherited it from a parent that that would be an early fetal or embryonic lethal disorder and therefore we do not see any such affected patients clinically because all those pregnancies are lost. Very, that's really interesting stuff. So I don't, do we have any other questions in the queue? Leo would you ask the group and invite the group one more time please if anyone has a question left? Please press stone one if you would like to ask a question. And if not we can bring this this briefing to a close for now and certainly anybody who has any other questions can call the media office here at the Genome Institute the number that's on the release that went around and you can go to genome.gov forward slash Proteus to see the paper itself and other background materials that are available to help you guys tell the story. I would especially like to thank our two colleagues from the Proteus Foundations in the United States Kim and Tracy and in the UK. Your participation this was really quite wonderful and we are grateful for you taking the time. Is there any closing remarks anybody has would like to add or I think in that case we'll bring this briefing to a close and I'll thank you all for your participation. Thank you very much. Thank you.


Have you been feeling more and more nervous lately?  It alerts us to danger and helps us prepare for a variety of situations. However, according to the Diagnostic and Statistical Manual of Mental Disorders, DSM, anxiety becomes pathological when it begins to greatly impair daily functioning and different aspects of life. And even though more information about anxiety is accessible today than ever, there are still a lot of misconceptions about it. So, if you're worried that you may be developing anxiety, there are six things you didn't know are related to it. Number one, imagined threats. You may already be aware that anxiety is a response to danger and uncertainty, but did you know that it doesn't need to be triggered by a real or actual threat? Anxiety can be triggered by nearly anything as well as nothing in particular. The mind is a powerful thing, capable of inventing a threat that, regardless of how irrational, feels very real. For instance, people with a certain type of anxiety may completely avoid all social settings because they are convinced that others will automatically judge or ridicule them, even though they have no reason to believe so. Number two, physical manifestations. Anxiety does not limit itself to your thoughts. It can affect your body as well, which is another testament to how powerful the mind can be. Some common physical manifestations of anxiety include chest pains, hives, gastrointestinal issues, muscle tension, and sleep disturbances. Anxiety can also have lesser known and more subtle physical manifestations. You might have jaw or facial pain from a developed habit of grinding your teeth or clenching your jaw during the day or while you're asleep. You might also experience persistent hiccups due to pathological distress. Number three, health conditions that can put you at risk. While physical symptoms may occur from anxiety, having chronic or serious health conditions can also put you at risk of developing anxiety. This can stem from the constant worry that is commonly associated with experiencing illness, aches, or the threat of death. This may be particularly true for people who suffer from diabetes, heart disease, or have had a heart attack. Even the worry caused by other conditions like living with asthma or severe allergies may lead to anxiety. Number four, dissociation. Anxiety can also cause dissociation, which is a defensive response to stress that alters your memory, consciousness, or sense of identity. The most common forms of dissociation are depersonalization, which is when you feel disconnected from yourself or derealization, which involves feeling disconnected from reality or your surroundings. Dissociation is often thought to be associated with dissociative disorder, but it can also occur from heightened anxiety or stress. If you experience a dissociative episode, this might be your fight, flight, or freeze response to anxiety taking effect. Number five, certain personality traits, neuroticism. Certain personality traits, particularly neuroticism, have been found to be related to anxiety. Neuroticism refers to the tendency to experience negative emotions such as anger, irritability, and self-consciousness. It is characterized by a chronic level of emotional instability and vulnerability to psychological distress. This trait is closely tied to perfectionism, which in turn is related to anxiety. While perfectionists may often seem incredibly put together, they may only appear so since they're often preoccupied with avoiding failure, expending energy on worrying about potential mistakes and their imagined consequences. Additionally, people who possess the neuroticism trait also have a tendency to respond to experiences with negative emotions, which provides a gateway to anxiety. And number six, depression. Two of the most commonly discussed mental disorders are depression and anxiety. And awareness of both of these has been increasing. However, some people may still consider these as separate mental health issues. In reality, these often co-exist and people who have or are prone to depression are also vulnerable to anxiety. This is because the two conditions have a lot in common. People with either or both disorders tend to have experienced a history of maltreatment or a difficult childhood and both disorders involve a malfunction in similar brain regions such as the amygdala and prefrontal cortex. So did you relate to the points we mentioned? It's important to be aware of some of the risk factors of anxiety so you know to care for your mental health and to find ways to better manage your anxiety. If you or anyone you know is struggling with an anxiety disorder, please don't hesitate to reach out to a qualified mental health care provider. And if you found this video helpful, be sure to like, subscribe, and share this video with those who might benefit from it. And don't forget to hit the notification bell icon to get notified whenever Psych2Go posts a new video. The references and studies used in this video are added in the description below. Thanks so much for watching and we'll see you in our next video.


For me the concept of inclusion is one of the most important. Inclusion helps us to better understand intersectionality and I think this is actually critical in pushing gender equality forward because none of us are two-dimensional beings. An ideal world, so also an ideal university, is I think inclusive for all who want to be in it. The inclusion is very important but I think that only in safe and respectful environments we can become creative and innovative because we do not need to subordinate, to suppress our potentials, to feel inferior or to be afraid for ourselves, our careers and so on. Equity enables the creation of environments based on fairness and justice and freedom that tackle the existence of discrimination and allow everyone to have equal access to and participate in all spheres of the community. I would choose intersectionality because it forces us to consider many aspects as once in all of their complexity and how they shape and inform each other. Also I think this is essential because people are never only one thing at a time. I think it's intersectionality. I know they are competing conversations in terms of do we lose priority if we focus on other elements of identity as compared to gender and I think it's actually the opposite. I think one, I think they feed each feed the other and it's never about competing priorities because gender is always interrelated to other social categories such as ethnicity, functional impairment, age, sexual orientation and social class.