You've been out on the field quite a few times here at the start of things. I know we're still early here in spring training, but what's your first impression of this 2024 squad so far? I'm excited. I think these guys really believe they have something to prove, and they're ready to do it. I will tell you, we had a large number of guys the entire month of January over at the Himes Complex voluntarily working out, getting in shape, ramping it up more so than I ever remember, and I don't think it's a coincidence. I think they're really ready to go. A couple of your players had talked about how embarrassed they were last year and how that motivated a lot of them to show up really at the complex, et cetera. Organizationally, how much of a motivator was that for you guys? I was embarrassed. We were all embarrassed. I mean, not only as one person in this organization, I wasn't embarrassed. I have no doubt for them that it was a big motivation. Like I said, they believe they have something to prove after that disaster last year. And they're going to be, I mean, look at some of the guys. I mean, they just, they're already in great shape, a lot of them, because their spring training started six weeks ago in earnest, almost every day they were there. So we take it seriously. Last year was an embarrassment. We're all embarrassed. In your mind, why will things be different this year? I just think it's a different mindset, I think, to his comment. I think they really, I don't want to keep repeating myself, Meredith, but they, I'm just telling you, they feel like they have something to prove to the fans, because they know they let the fans down. It was embarrassing, and it was embarrassing for everyone.  The luxury tax payrolls are already over the highest threshold. Do you feel like you have something to prove to fans with the way this off season has gone? I think we have something to prove to fans after last year, absolutely. No doubt. When you look back on last season and evaluate it with some hindsight, what do you think went wrong? Well, look, clearly we had a lot of injuries. That's, all teams have injuries. We had, you know, not the most in baseball perhaps, maybe, I don't know, I didn't look, but we had a lot. But the position players, I mean, too many of our good position players did not play up to their potential. We couldn't score runs, and we had a near zero run differential the entire year, and you're not going to win a World Series with that. You're just not. What do you think Juan Soto adds to this team, and do you think you can keep him long term? Well, I don't want to get too much into that because, you know, he just got here, and I just met him two days ago. He's going to mean a lot. I got to talk to him briefly on the field, very intelligent young man, and obviously very motivated and very successful already, already a world champion, and already has just went right into the clubhouse and fit right in. So I think he's going to be great. And, you know, seeing him and Judge and Stanton, two, three, four, whatever the order in the lineup, it's going to be pretty special. Wow, there is still free. Do you think that you have enough on this roster? Are you, some free agent out there is still looking for work? I think we have a championship caliber team right now, but we haven't stopped looking to improve, and we never will.  That's a long time from now. So what's your feeling about SNL? I'm not going to get into free agents. I'm just going to tell you that we continue to look at a lot of different options. And, you know, given where we are payroll-wise, any addition to the club is going to be a costly one, but I'm still willing to consider anything that comes my way. Anything cash in this team brings my way. I'll leave it at that. But we are not done trying to improve this team. How do you feel about that? It shouldn't take that $300 million payroll to win a championship. I still agree with that. Yes. Pushed you over the edge. Well, we didn't have a whole lot of money come off the payroll. I think we started this off-season at $250, right around $245, $250. So it's not going to take much to get up to $300. Do you feel like you have enough pitching right now? I think our starting rotation is very good, yes. Depth, injuries, we lost King. And we lost some pitchers in the SOTO trade. And that's why a lot of the other trades we were looking at, everybody seemed to want guys like Warren and Hampton. And I just wasn't willing to part with them. So the depth is somewhat concerning to me. But the rotation, as it stands, is a very good one. And we still have Warren at AAA. At some point, you're going to see him this year, probably. Louise Hill and a few others. I was wondering what you're thinking on the SOTO trade. Obviously, it was a big price to pay. Why did you say yes?  The opportunity arose where the Padres needed certain things that we had. And I don't know how you can say no if you're able to do it financially and able and willing to give up what they're asking for, which was not easy for me to give up those guys. But I don't know how you could say no if both those things are possible to get a player like that, even if it is for one year. Hopefully it's not. But that's not something I was going to say no to if both those factors fell into place. There's still things we're looking at. Whether it's trades or signings, I'm not saying anything's going to happen. I'm not saying something's not going to happen. But I'm still willing to improve this team however we can. Why so fast? Is it last year that really motivated you to be so throttled down, as far as that mindset? Because I know you've been leery of it at least in the past of going. Well, look, again, we didn't have much money come off last year. So when you start the postseason at 250, I start the offseason at 250. It doesn't take much to start working your way up. Do I think you should have a $300 million team to win a world championship? No, I don't. But again, we started at a pretty high level already. And soda was a big addition, but big dollars as well. To retain soda, it's probably going to cost more than what you gave Judge last offseason. Are you comfortable paying someone more than your captain? I guess that's an interesting question, but not one I've thought about. I'm not sure Judge would care if we got one soda for many years to come. But look, the market is what the market is, and he's going to cost what he cost. We'll just have to wait and see. Was that something you considered with your offer to Yamamoto with regards to Garrett? No, I wouldn't say that. I mean, I just think sooner or later, as all of you know, in these things, you've got to go pencils down, right? I mean, and I probably went higher than some of our baseball people would have gone. But I felt it was important to the fan base and to our chances this year to really make a run and try to get them. But I just felt $300 million. I just felt right or wrong that the bidding was going to continue. And $300 million was a very good offer. And I think a lot of our fans agree with that. So is there anything ongoing right now that's close? You said that you're willing to do anything that cash comes to you with or consider it.  Well, we're looking at possibilities. Is there anything that's close? I would not say there's anything that's close. No. And I would also reiterate what I said earlier, which is we've already given up some very good prospects. And the Major League are in King this year. And I'm going to be very hesitant to give up the kind of guys like Warren and Hampton and Spencer Jones that have been asked about a lot. Don't forgive me for repeating that. But every 24 hours is a fresh room and that you guys are about to sign snow. I mean, it seems not going to get into any specific players. Not going to get into any specific players. Does it affect your thinking when Aaron Judge says he thinks and hopes the team will continue to act? Well, he and I talk about it. But he also understands where I sit and the decisions I have to make and the reasons I have to make or not make those decisions. So we have a very good relationship. Just one year of SOTO and given that, how much you had to give up to get him. Does that up the thinking of adding to this year's roster? No, no. I want to add to this year's roster if the opportunity arises, because we are always going to continue to try to improve. No team's perfect, right? There's no perfect team. So there's always work to be done. And opening day is not pencils down, right? I mean, August 1st or whatever the date is, is pencils down. So we got a lot of time during the season if we have a need to fill it. And we're going to just keep exploring possibilities and considering things, as we always do every year, as the days and weeks progress. From your impressions of your meetings with Yamamoto, if you offered $325 million, do you think it would have made a difference? That's pure hypothetical. I don't know. I honestly don't know. I don't know. Was it too much for you to consider $325? I felt the $300 was a very, very good offer. How disappointed were you that it didn't go that way? I mean, they did. I mean, it was worth it. Yeah, we were disappointed. We had a great meeting with him. He's a great young man and obviously a great player. But again, for a player that's never played in the major leagues before, that's a lot of money. And sooner or later, you have to have a limit. You have to have a limit because of circumstances like that. I haven't said at the start of this, I think we have a championship caliber team right now. That being said, then where would those additions potentially to improve the team? Well, I don't think you're going to have enough pitching. Whether it's bullpen or starting. Look, we've got a great in-field. We've got a great out-field.  And I say that every year because somebody asked me the question every year. But we'll see what remains to be done or not done. I know you don't want to talk about individual players. Would you talk about individual agents? Have you talked to Scott Morris recently? I will not talk about individual agents. But I have talked to certain agents recently, yes. And obviously, any agent that wants to reach out to Cashman, Cashman's phone is always on. And he's great about talking to anybody who wants to talk to him. Are you surprised that a handful of his guys are still free agents? I haven't pondered that, to be honest with you. I mean, they're all incredibly talented guys. And I'm sure they're going to land somewhere eventually. And you know, is what it is. But I haven't really pondered whether or not I'm surprised. And it seems like every year there's guys still around this time of year. But definitely some high-profile guys. I get your point. There's a lot of uncertainty around RSMs. Around RSMs, I'll swear. I know you guys are in a different situation. But is that something that looking into the future concerns you, the model? I don't want to get into baseball economics about RSMs and all that. I'm really here just to talk about the season and all that. But look, I think Rob's made it pretty clear it's a concerning situation. But he's all over it. And baseball's all over it. And the clubs that are involved are all over it. So hopefully it'll turn out good for everyone in the end. Aaron Boone said you guys were hell bent on winning a title.  I think so. And I think the attitude is that these guys are hell bent to win a title. But look, we all know when you get in the postseason, competitive balance being what it is today compared to 10 years ago, let's say.  I mean, look at the clubs that got knocked out round one last year. Clubs you wouldn't have thought. But we got to get there. That's the whole thing. That's why last year was a failure on every level. We didn't even get there. Once you're there, most teams have a good chance. If not all teams. Things happen sometimes for the better and sometimes for the worse. But that's the way the postseason is. In a year that you don't make the playoffs like last year, do you watch the playoffs? I did. I watch them. I watch them. It's like I'm a lifelong Vikings fan and they're never in the Super Bowl. So I don't watch the whole Super Bowl, but I watch some of the Super Bowl. So same thing. Same thing. How would you describe your conversations in the offseason with Judge and Cole and some of the concerns that they might have expressed to you about? Yeah, they were involved. And Boone was very involved. He met with our coordinators at the Heinz Complex twice in January about things we might do differently in the minor leagues or might teach differently. All good conversations. And for instance, with Judge and Cole, and I was just talking to Cole today in the dugout, there were some concerns that both of them raised last year about not so much the information we give them, but how it's presented to them. How it funnels down, I think, with Judge's words. How it funnels down to the players. So we've added a new person in the clubhouse, a guy here from Tampa that is unbelievably versed in intelligence and analytics, but also was a coach. College coach, actually, I believe. Great working with people, great explaining things and teaching things and listening to what the people he's dealing with have to say. And Judge already met with them one-on-one over there for an hour or two working with them, and he likes them. So he's going to be a great addition. And again, so many questions about significant changes, significant changes. We're introducing somebody new into the clubhouse. That's a significant change. This is Boone's last year under contract. What do you need to see from him to continue to get a new deal back? That's something I deal with when the season's over. Really, it's not something I'm pondering right now. So there's just so much baseball. Take one or two more. Is that a best guy? Hal, historically, you guys have not done extensions. You let contracts expire. Would you make an exception? And you have made some exceptions over the years of at least engaging guys. You did it with Judge. You did it with Cano years ago. Would SOTO be in that category of one you would be open to doing that with? Yeah, I'm not big on extensions. As you know, we've really done them. My concern dealing with that during a season is it's a distraction, or at least it very well could be a distraction. But having said that, if both talking about SOTO, if both sides feel very strongly about it and cash feels very strongly about it, then that's something I would consider depending on how the season's going. We just can't have it be a distraction. We just can't do that.  There's more pressure on all of us. Look at me.  There's pressure on all of us, man. We're feeling it, and that's a good thing. We deserve to feel it. And that's going to make us stronger this year, I think. How excited are you about the renovation and the stadium and everything that is going on? Very excited. Next year is going to be a whole different building. Brand new training room, wet room, weight room, dining room. And then we're also doing a big renovation up at Yankee Stadium, too. That'll be done on time for opening day, and it's going to be a lot of new things in the clubhouse for these guys. And the feedback so far has been very positive.  Just do they like the new clubhouse? There you go. OK. Good to hear. Thanks, sir. Great. Thanks, sir. I appreciate it. Appreciate it. Yeah.


Every year there are thousands of movies released and I see like 40 of them So I think who better to do a top 10 greatest movies of 2021 Then I yeah, this is not going to be the be all and all for movies Don't stick around if you're looking for some deep insight into a movie that passed you by these are very Mainstream affairs they went to theaters for the most part Nothing groundbreaking and even some of the big mainstream movies I miss like House of Gucci Spencer and of course what I assume is a cinematic masterpiece Boss, baby, too with those caveats out of the way. Let's begin at the number 10 spot Yeah, that's right. I have two movies in the 10 spot.  They both they're both here MCU movies. No no eternal. Sorry that one That one didn't make the list Here's the deal. This wasn't a great year for cinema in my mind a lot of movies really Disappointed me especially in the streaming service category So the fact that these are even on here is like a blessing for them. They're fine. They're they're both fine movies I enjoyed they have plenty of action interesting characters We were introduced to Yulana and of course Shang-Ci himself and Aquafina wasn't even annoying to me for once I really loved the crouching tiger slash Jackie Chan-esque fights that Shang-Ci provided that bus fight I mean come on That's one of my favorite of the MCU so far and although black widow rubbed a lot of comic book fans the wrong way by what they Did the taskmaster? I mean I had no qualms. I had no understanding of the comics going in so it didn't bother me I can totally sympathize though. I've been there I've seen how movies have ruined characters from different properties So if you hate black widow because of it, that's fair game It also came out about 15 movies too late in the MCU, but I still think it did its job I did look at Scarlett Johansson's black widow is more than just a nice asset Catch my drift now. There was sexual some character there I get why she was crying into a sandwich during endgame part for the course for the MCU sure Absolutely, but part for the course in 2021 is Sadly a good thing If Edgar Wright comes out with a movie I'm in the theaters for it last night in Soho had the potential to be my favorite of the year But it's bumped all the way down to nine because of the ending which I just couldn't get on board with it goes a little Too loony tunes for me in the final act a little too Mickey Mouse Edgar writes a director that takes chances though, and I respect the hell out of that This isn't your par for the course like the last two movies I talked about It's got some interesting ideas at play the cinematography is on a different level I love the way they're playing off the mirrors reflecting the two lead women There's deeper commentary than just what you see on the surface. I loved the horror aspects of the film I just wish the whole thing would have tied up a little bit nicer Edgar writes Not only known for his beautiful cinematography, but his phenomenal soundtracks featuring some really awesome tunes This one's no exception. So if you slept on last night in Soho I suggest waking up and giving it a shot The Daniel Craig James Bond movies have been pretty flaky for me over the years They go back and forth between greatness and and kind of patheticness here Thankfully we're on the good end of things I think no time to die does a really good balancing act when it comes to the James Bond property It takes some of those sillier aspects like the cars shooting missiles out and marries them really well with the Darker more gritty tone that these Daniel Craig movies have going. It's also the deepest We've dug into the character of 007 usually everything's very top level. He likes his martini shake and not sturdy bangs chicks He goes out and kills bad guys wash rins repeat sometimes not even a wash in between It's gross Guys got to have a lot of diseases Although M probably has a pill he can take for it just about everything This is another one of those movies that probably will turn some people off due to its controversial ending I myself enjoyed where they took the character and I'm glad they weren't afraid to just go for it We do unfortunately have an underbaked villain here with motivations that seem suspect at best by the time the film wraps But there is an awesome amount of action some great newcomers to the lineup and Daniel Craig hasn't shown his age here He's still kicking ass.   It's got some vague dialogue that hopefully will lead to something in part two And I just everything about its bonkers and shouldn't work yet I think the director fully pulls it off and that's because of gorgeous Cinematography some really seamless CG top-tier acting especially from Zendaya. Oh my god Zendaya is so good in this Okay, I'm being sarcastic Why were people going off about her? Is it just like a requirement that you have to gush over everything that actress does? She's in this film for like eight minutes and has four lines of dialogue Let's move on. Let's move past Zendaya. Oddly enough Jason Momoa the worst actor of the bunch here I thought was the best. He was the more relatable guy. He's going off to try to find out what's happening with the spice mines He was the blue collar down to earth guy that I could relate to the film takes the pages of the book brings them to life I like the idea of the chosen one being almost cliche on purpose. There's this whole secret Organization of which like people I can't remember what they're called But but they know that this is like a red herring of sorts that he's not actually the savior it everything about it It's got it's got some really good layer to it a film I absolutely need to watch again and I will when that second movie gets out, which is in like four years Oh my god, they're gonna take forever on this. What's even more amazing is this is a Warner Bros. Movie who has been missing so much more than they've been hitting lately You got one right here for me The Mitchells versus the Machines was another movie that came out of nowhere landed on Netflix I think it was produced by Sony you have two companies that consistently disappoint me coming together and Presenting something that's just fun Engaging humorous full of heart. I really dug this movie It reminded me of like the Incredibles if none of the characters had anything remarkable about them The movie has the played-out robots taking over the earth apocalyptic plot going on It gives off vibes from a lot of movies wall-e springs to mind as well But the movie knows it does it embraces it. It has fun with it.  The only animated movie. I thought was better was Luca did anyone see this movie outside of my family? I really hope so. It's a treasure folks You should watch Luca if you haven't they kind of sent this one out to die on Disney Plus It didn't get a theatrical release really didn't get a marketing push at all Beautiful to look at the animation is top-notch We follow a young sea monster who realizes he can step foot on land and turn into a human unless he's wet Luca is the sea monster. I'm referring to it's his relationship with Alberto That just really makes this movie stand out They go on a quaint adventure together to win a Vespa the staple vehicle of Italy Even though the premise is very simple and childlike for kids to easily enjoy parents can also see past the facade to a deeper Sadder undertone Alberto struggling internally with who he is and where he belongs while Luca is more naive to the world around him as The movie progresses these two will form a relationship That's just very special and when the final credits roll if you're not holding back some man tears You're heartless inside and you probably didn't even make it this far into the film If you're looking for an animated movie for the whole family That's not trolls world tour or boss baby two that maybe has a bit more richness to it Please check out Luca. It deserves your time From a lot of the same teen that brought you John Wick comes nobody Another John Wick movie and that's a great thing while it's not exactly one-to-one with John Wick There are a ton of similarities between the two yet It has just enough differences to separate it from the other property that doesn't mean I don't want to see a team-up film Because God would that be awesome or at least a cameo just a cameo would be nice Bob Odenkirk kicks all sorts of ass in this as nobody a Family man who's rebranded himself after getting out of the seedy underbelly He was once a part of no There's no dead dog in this one to get Bob Odenkirk off his leash a couple of inept crooks break into his house and steal Something that belonged to his daughter this puts him in a precarious situation as he befalls into a bunch of bad Circumstances one of which involves him kicking the living hell out of a bunch of dudes on a bus Unfortunately for mr..  I completely forgot that a quiet place part 2 came out in 2021 this has been a wild last couple years and by wild I mean incredibly boring in a lot of ways It seemed like a lot happened in 2021 yet nothing at the same time. It's it's very bizarre Anyway, I really like to quiet place part 2 just as much as the first it is missing John Krasinski He only gets about 10 minutes of screen time, which is a shame for those 10 minutes It's good stuff it reminded me of Tom Cruise's war of the worlds where he's running away from the threat the alien behind him Shit's getting taken out chaos ensues. I'm all in the film picks up right after the events of the last movie Emily blunt once again a powerhouse here doesn't have to say a lot It's all happening through her actions. Killian Murphy joins the crew. I believe is how you pronounce his name I've said it wrong so many times and people have corrected me that I don't even know what's right and what's wrong anymore But we're going with Killian. He's he was a great addition to the family if you're a fan of the last of us It's hard not to see the parallels between the movie and the game And I know they're doing a TV show on HBO Max, but we already kind of had it right here We also had it with Logan the father daughter type dynamic works so well in these types of situations There's nothing to cling on to except for each other. They ratchet it up the action They ratchet it up the horror and suspense I'd say the only place where the movie suffers a little bit is the ending It feels very abrupt a little jarring and doesn't quite have the conclusion I was hoping for clearly Krasinski wants a part 3 and I'm there. I'm all for it Spider-Man No Way Home makes the number two spot on my list, which means the Matrix 4 must be number one, right? No Look for that in my next video top 10 worst movies of the year Even though I and many others have a problem with the entire plot of the movie revolving around Dr. Strange helping Peter Parker erase the memories of everyone who knows he exists Everything around that plot is really well executed. So let's talk about why this is the number two spot on my list Well fan service, baby. If it's done, right It's done, right? I should say Spider-Man No Way Home hasn't been out that long. It's been a couple weeks There's still people that haven't seen it.   I've just I just I'm selfish, okay? I really liked what they had going here with these characters and their dynamic and I would love to see more of it Probably won't which is unfortunate, but the fact that we even got some of it. I guess I should be grateful for It's more than we got with those new Star Wars movies never got to see Han Luke and Leah together in a scene So yeah, this is a win. Plus we get those iconic villains back Dr. Octopus hasn't missed a step the green goblin Willem Dafoe so good here just carries all the scenes He's in I thought for sure Dr. Octavius would be the show stealer. No Dafoe man Dafoe some people didn't like the Aunt May stuff thought it was cringy didn't work. I loved it I I was legitimately sad when she died I I thought they handled it perfectly people did have no problem correcting me when I brought up how she says the with great power Comes great responsibility line. I said she said it a little weird She added a couple words to it and I guess it's for comic book accurate. Well to you. I say no To you I say nah, we're not only referencing the previous two spider-man universes But we brought these people and their villains in so now's not the time to quote the comic book You should have quoted the line how it was given off to really resonate and hit home with the movie audience I don't know why they decided to flex now on getting the comic book line, correct But it was I still disagree. I think it was a bad move So I'm a sucker for the drama and the movie delivered it had a couple of cop-out moments where we thought people were gonna die And they didn't that's fine. It elicited some response from me And that's what a movie should do these spider-man homecoming movies are lighter than the other spider-man movies I've accepted that they are a little more childish. That's why the plot isn't very serious It's it's kind of like and yeah, we can erase the mines no big deal Oh, we probably could have used this ability to erase Thanos's mind You know, he could have forgot about the infinity stones, but whatever this is new You you have to like set that stuff aside because even though all these Marvel movies are connected in some fashion They're also separate. They're also they also have their own tones and spider-man is clearly a sillier family adventure It can still have drama. It can still have some stakes. They're just kind of cushioned. They're protected There's some airbags on this thing. The action is the best homecoming has delivered so far the jokes landed I'd say 90% of the time. It was great seeing some of those high schoolers back from the other two films They're still very much keeping the tone the same and that's a hard thing to juggle. It's a hard balance to keep but These movies have done a good job of it. So wow, we got three Marvel MCU movies on this top 10 list Talk about a Marvel fanboy, right? What's he gonna put it as number one spot? Let me guess something else by Disney or Marvel Now Zach Snyder's Justice League isn't on here But I do have the Suicide Squad which is far better than that thing and it was far and away my favorite movie of the year I had a blast watching this from beginning to end.  I mean, what are you doing James Gunn? How are you getting this all so correctly? I've seen this film already three or four times and I have a blast every time I watch it really looking forward to the peacemaker spin-off show on HBO Max and man I can't wait for a sequel to this film. Well, there you have it my 2021 best of movies list I again haven't seen everything that came out. I missed a lot. I did my best I really did but now it's your turn.  Give me your top 10 like the video if you had a good time Subscribe if you haven't already and I hope to see you around That's right my next video is gonna be the top 10 worst movies of 2021 this recording session went long already So I'm gonna need a day or so to recuperate for the shitstorm that's gonna pile upon these 10 movies I talk about it's gonna be ugly.  Those are opportunities for you as well and with that I bid you adieu adieu


Many of you may be familiar with AT&T beliefs. Our company-wide effort to combine employees' passion, creativity, and resources to make a positive impact around the world. So I'd like to start by sharing three beliefs that AT&T is passionate about. First, connectivity matters. Second, higher education is an engine for innovation. And third, innovation always requires an impetus. I think we can all agree the last couple of years definitely fit the definition of impetus. The pandemic has not only redefined connectivity and our need for it, but it has also accelerated the digitalization of our society. It has ignited new innovations and a rapid advancement in technologies like 5G. 5G is the next generation of network connectivity. It will power our digital, data-driven future. And for AT&T, 5G isn't just about speed, it's about being transformational. And higher education has an important leadership role in all of this, today and well into the future. Colleges and universities across the country are at the forefront of exploring this new world of connectivity. Through unique research partnerships, we're helping institutions unlock the value of 5G and next generation technologies in new and unprecedented ways. In addition to benefiting industries that drive our economy and society at large, these innovations also support the mission and operational goals of our higher-end partners. Just consider 5G's impact on research, recruitment, and retention. We're working side-by-side with institutions to help increase their research capabilities by launching cutting-edge 5G testbeds and labs. As a result, these colleges and universities are able to attract additional funding and create new learning opportunities for students. And in return, positively impact recruitment, retention of the best and brightest students and faculty through advanced programs for robotics, healthcare, and cybersecurity. The possibilities are endless. From advancements and virtual learning environment to help close the digital divide to green energy initiatives so we can grow a more sustainable future together. We're honored to work with you and to support the critical role you lead in shaping the future and inspiring the next generation of innovators.


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If we don't want to use it to solve systems of equations, why do we even care about it then? Turns out that Kramer's rule is a formula that has great theoretical benefits, even if practically you don't want to use it for computations. And so I want to show you an example of how one can use Kramer's rule in a theoretical sense. So again, we have an in my in matrix and we're going to define now the etiquette of the matrix. In some linear algebra textbooks, this is called the adjoint of the matrix. But unfortunately adjoint can be used to describe other things like for example, sometimes people use the adjoint to describe the choice. So because adjoint is a little bit ambiguous in linear algebra, we're going to choose to use the word etiquette here, which seems like a made up word. I would recommend you not use that in Scrabble, unless of course your official dictionary for the game is this textbook. But etiquette does have the advantage that the abbreviation ADJ is the same whether you use adjoint or etiquette. So it kind of helps clarify the context here. The adjoint of the matrix will be the matrix whose entries are cofactors. So the one, one entry is the cofactor one, one. The one, two entry is going to be the two, one cofactor. And this progresses onward, right? The last entry, the one in entry is the in one cofactor. And so I do want you to notice that this right here is the transpose of the cofactor matrix. That the cofactors will look like they're in the wrong spot right here. That the one, two position has the two, one cofactor. And the two, one position has the one, two cofactor. The reasons for that will be a little bit more, make a little bit more sense in the next. So as an application of Cramer's rule, we can actually compute a formula for the inverse of a matrix. So if A is an in-by-in matrix, then the, then the adjutant has the property that A times the adjutant, well actually the adjutant commutes with the matrix. And this will equal the determinant times the, and so in particular, if the determinant is non-zero, it's a non-singular matrix, then you can divide by the determinant. And this gives you a formula for the inverse because now we found a matrix whose product with A is equal to the identity. If it walks like an inverse and quacks like an inverse, then we have the inverse matrix right here. The inverse of A will be one over the determinant times the adjutant of A. And so again, this formula, this equation we saw above, it works even when the matrix is singular. And so I wanna kinda point your attention to a two-by-two matrix. Take this to be our matrix A, just a generic two-by-two. So if we go around start computing the adjutant, the adjutant, the adjutant of A is gonna look like the matrix where you're gonna get C11, C1, sorry, C21, make sure you do them backwards here, the C12 and C22. All right, so what happens here is that if you're looking for adjutants, we have to do cofactors and the one-one cofactor means take away the first row, first column, you're left with just a D. And so I'll record that right here. If you do the two-one cofactor, two-one means take away second row, first column, you're left with just a B. But remember that cofactors have signs built into it. Some of them are posms, some are negative. And so you end up with this negative B right here. The next one, the one-two cofactor, take away first column, sorry, first row, second column, you're left with a C. But this likewise will have a negative, this is a negative cofactor, so you end up with a negative C right here. And then finally, if you do the two-two cofactor, second row, second column, you're left with just an A. That one is positive, so you get the matrix A right here. Now it feels like I've seen this before somewhere, right? Don't we know the formula for A inverse for a two-by-two matrix, you take one over AD minus BC times by this matrix right here, D negative B, negative CA right here. Now this number in the bottom, we've mentioned it before, this is none other than the determinant of the matrix A. This matrix right here is none other than the adjo kit of this two-by-two matrix. And so this inverse formula we had for, this inverse formula we have is none other than just this theorem five of the special case of two-by-two matrices. So what I want to show that this works in general real quick. We've been using it for two-by-two matrices a lot, but we actually could do something like this for even larger matrices as well. And the argument is basically the following. The jth columns of A inverse is gonna be a, it's gonna be a vector X such that, make sure my color's right. A X equals, A X equals E J. And so in this here, X is the jth column of A inverse.  So therefore, if we take the jth column of A inverse, times it by A will give you the jth column of the identity. So A X equals E J right there. Well, if we apply Kramer's rule, so by Kramer's rule, which we saw before, by Kramer's rule, the ith entry of X is given by the following. So X I is given as the determinant of A I evaluated E J over the determinant of A. So we're thinking of this right here, A X equals E J as a system of equations we have to solve because we don't know the rule, we get a formula that looks something like this. But if we think of it in terms of cofactor expansions, by cofactor expansion, if we expand across column of A I E J here, because we know that the ith column of A I here is gonna look like this vector E J. If we cofactor expand the ith column, we end up with the following, let me slide this up a little bit. We're gonna end up with the expression that the determinant, the determinant of A I E J, this is gonna equal negative one, plus a negative one to the I J power times by the determinant of A J I right here.  If you cofactor expand across this column right here, since you just have a bunch of zeros in the one eventually, all of the cofactors for these ones are just gonna disappear, except for there's the one right here. We have to pay attention to the sign, and so you're gonna get negative one to the I plus J position, because that one right here resides in the I J position. And then if you look at the minor, everything that cancels out, the associated minor is gonna be the A J I minor, because once you take away that ith column, A I E J looks just like the minor will look, and so what you see right here is this negative one to the I plus J power times the determinant of the minor A J I. This is just the cofactor of A, although the entries got swapped around, it's a J I instead of an I J. And so because of that, we then get that X I right here is equal to C J I, and as this was the ith entry in the column right here, when you put this all back together, we see that the I J entry of A inverse, this is gonna equal C J I over the determinant of A, coming back up to this formula right here. And so that verified the formula we had before. So using Kramer's rule, we're able to compute a formula for the inverse of the matrix, one we've already been using. For two by twos, it's not so bad. I wanna show you how this would work for three by threes. This one's a little bit more involved, so I have a lot of the details already presented to you on the screen. Suppose we have a three by three matrix A, which is giving us two, one, three, one negative one, one, four, negative two. Well, since it's three by three, there are gonna be nine cofactors and to find the etiquette, you're gonna have to calculate each and every one of them. So there's the one, one cofactor for which you take away the first column, first row, sorry, first row, first column. That'll be positive. By the usual determinant calculation, you're gonna get two minus four, which is negative two. We're gonna do the one, two cofactor. So we take away the first row, second column, then you're going to get this two by two determinant. It's gonna be negative this time. You're gonna get one times negative two minus one. That gives you a positive three when you're done. You then will do the one, three cofactor. Then you take one times four plus one. That's gonna be a five. And you do this six more times. You get all the different cofactors. The two, one cofactor is 14. The two, two cofactor is negative seven. Two, three will give us negative seven. Three, one will give us four. Three, two will give you one and the three, three will give you negative three. So those are all the cofactors. You can double check the details yourself. So with this in mind here, with the co, with the etiquette, you're gonna take the cofactors with the transpose of where everything goes. So for example, the one, two cofactor is gonna go in the two, one position. And likewise, the two, three cofactor is gonna go in the three, two position. Make sure you get those on the right locations. So we get this, this is our etiquette. There's a lot of work that goes into computing all those cofactors. I don't wanna minimize that calculation, but there's these nine cofactors. And then once you have this etiquette, we can double check. If we multiply this matrix by the original matrix A right there, you can double check there. Negative two times two, that's a negative four. 14 times one, that is a 14 and four times one, that's positive. Positive four cancels with the negative four giving us a 14 right here. Next, if we take this row times the second column, you're gonna end up with a negative two minus 14, negative two minus 14 plus, plus 16. And so yeah, 16 minus 14 minus two, that gives us a zero. Sorry, I kind of stumbled there a little bit. If you take this first row times the third column, you get negative six plus 14 minus eight, that gives you zero again right here. You can go through the arithmetic and see that this matrix, which we computed for the etiquette, multiplies by A to give you 14 down the diagonal and zeros everywhere else. So this is just 14 times the identity matrix, I3. And so if we divide the etiquette by 14, which 14 is the determinant of this matrix one, we end up with the inverse matrix, which you can see, all right? That is a way of computing the inverse matrix. It's a little bit more drawn out than what we've seen in the past because we can take A, augment the identity and row reduce this, you'll get the identity, augment A inverse. This method I think is gonna be the more preferred method in general, but be aware that one can use Kramer's rule to calculate inverses of matrices. So while in practice, it's not very practical to solve systems or compute inverses via Kramer's rule. I wouldn't recommend doing it. You will be asked to do it in the homework and you do need to do it that way because those are the instructions, but that's mostly to kind of see the comparison why this one doesn't work as effectively. The method of row reduction is actually in general much more effective and we've mentioned that already and that's why I'm not a huge fan of Kramer's rule. You should just use row reduction. It's gonna be more effective here. It's only in the case of a two by two where it's almost the same, even though row reduction still is more efficient. On the other hand, it's the application of Kramer's rule that's really important here and the application of adjudicates in the theory of linear algebra. So for example, if A were an integer matrix, like you see in this example right here, all of its entries are integers, then its determinant is gonna be an integer and all of its cofactors are gonna be integers as well. So if A is an integer matrix, I can actually predict, I actually know for a fact that its adjudicate, which is just a bunch of cofactors, will likewise be an integer matrix as well. Because to compute cofactors, we just have to do multiplication and add and subtract. We never do division when we do cofactor computations. Same thing with the determinant. The determinant's gonna be an integer as well. And so no division's required. What about the inverse here? There is a bunch of fractions there. That's because I had to divide by the determinant, which was 14, and some of those numbers were not divisible by 14, as you see in terms of the computation. But what if the determinant turned out to be like plus or minus one? If the determinant of A was equal to plus or minus one, then when you divide by one, that doesn't do anything. And when you divide by negative one, that just changes the sign.  And in this situation, if the determinant was plus or minus one, the inverse of that matrix by this formula would also be an integer matrix.  Hum, I wonder if there's a math instructor who's ever used that to create homework questions for his students so they can feel happy when they get whole numbers at the end. Hmm, hum, hmm. I wonder if you looked at some past homework questions if you computed determinants, would any of those be determinant one or negative one? You'll notice I've actually used those a lot in the homework. Now, that's sort of like a one application of this. That's not how people use it all the time. But I just wanna kind of point out to you that it's the theoretical benefits of Kramer's rule that are really why we care about it so much. This book focuses more on the computational aspects of things, but we should always be aware of those theoretical aspects as well. So I do want you to have some exposure to Kramer's theorem and you'll see this in the homework as well. And so that ends our lecture today. Thanks for watching. If you haven't done so already, please do subscribe so you get updates about future videos, particularly about linear algebra and other projects I'm working on. Feel free to like this video if you have any questions, comment below. I'll be happy to answer those questions. And other than that, I'll see you next time. I have some fun with Kramer's rule here. I've done my job correctly. You'll hate using it as much as I do. Wink, wink. See you next time, bye.


video if you're new here my name is Carol do not forget to like comment subscribe so we are gonna get into this little body care video cuz I just came back from the DR and I got so many compliments on my skin and how I was looking in the sun it was looking very glowy hydrated so I really wanted to give y'all like a body routine and also I'm getting ready to you know have a quarantine date so I wanted to just you know go ahead and let y'all know like what products that I like to use on my skin and all these products you can get at Sephora and they are sponsoring this video so thank you so much Sephora for partnering with me on this video y'all know like I love Sephora that's like my go-to beauty store anything that I need perfume makeup just like any beauty essential like I'm on my way to Sephora period so thank you so much Sephora for sponsoring this video you are not a VIP member you need to sign up being a VIP member has so many benefits so and I love being a VIP member because I get to add up points and it helps me save a lot of money so don't forget to click the link so you'll be able to sign up to become a VIP member the four is making it easier to shop how you want and they are doing free shipping right now so all you got to do is use called free ship when you're at checkout so you can get free shipping grow up because you know that little shipping fee just be too much also all the links to all the products that I'm using today will be in the description box below so yeah like I said thank you Sephora for sponsoring this video so I just got out the gym it's been a long day I've been working and now I really want to just wind down and do somebody here just take those extra steps so I'm about to hop in a shower and the first thing I'm about to do while I'm in the shower is I'm going to use my Olaplex shampoo and conditioner y'all if y'all have been following me for a while you know that I suffer from a lot of heat damage and Olaplex is literally the only thing that has bounced back my hair my curls are more like curlier just because I've been using this but I do need to get my inch trim like ASAP and my hair is really crusty right now so like I said I'm getting ready for like a little quarantine day so I want to have my hair fresh because my hair has been going through it okay and then also while in the shower I'm going to be using my bum bum body scrub I've been trying out the bum bum body scrub just to exfoliate my skin and I really been loving it like I really been loving it it's making my skin very very glowy and I just love to exfoliate my skin we tend to sometimes forget our body like we so we are so focused on our face we tend to forget our bodies but don't forget to exfoliate your body girl because it needs to get that extra dead skin off too as well so yes so I'm about to I'm about to take a bath yo I'm about to take a bath I'm gonna soak when I take my extra steps in my body here I really like to soak in the bathtub just take my time with it you know what I'm saying especially because I'm exfoliating my skin I just want everything to you know I want my skin to just lather everything up girl so so yeah I'm about to start my bath and we are gonna get into it and I love taking a bath y'all especially after a long day like I just love it so let me just start my bath water and get these subs going okay because I deserve me I had a long day so I'm ready to just line them up soft right now but I don't like to do I don't like to do my body moisture and stuff until after I get done with my skincare just go I don't like you know put whatever I put on my body on my face so I just did some skincare and but wait let me put something on my lips this is the L Y S this is the speak love glossy lip treatment oil this is a black on company they are now at Sephora and y'all know I love me some black on and I love the applicator it's so cute so this is then my go-to lip product and they just make your lips look so glossy but I just did my face wash and stuff like that so I am going to be using the Dr. Dennis Rose alpha beta extra strength daily peel if y'all have seen my skincare routine y'all know I live by these and I'm never switching up period when I stop using these y'all I swear my skin was like going through it and I started back using these just like two months ago and my skin has been on fleek ever since and if you see my skincare you know you know the tea you know the transformation and I know a few of my supporters have used it as well like I followed my skincare routine and they said their skin has changed drastically and I love that for them so make sure y'all go ahead and shop these if you're if you want to change like your skin texture or you know you just want to enhance your skin care routine make sure you go ahead and get your hands on these because this is literally like a game changer it has helped me get rid of like because when I was when I first started using these I had little bump acne I don't know where it came from like it was like a rash looking I don't know but instantly when I started using these my skin it like got better the next day and I'm not even like being dramatic I'm dead serious like I use this every single day every single morning and I like to you know use the right products on my skin to treat my skin I don't like to just treat my skin when I'm breaking out I like to prevent things so when you treat your skin with the right treatments you'll be able to prevent any imperfections or anything like that so yeah so the first one is the exfoliator and then the second one is the anti-aging neutralizer I just like to give like 30 seconds in between the two and my hair is dry y'all but look at how curly my hair is like the olaplex really does help I gotta give my ends trimmed but as you can see the curls really start from like my root and I have to cut these like damaged pieces out it's been a minute since I've been to like someone to treat my natural hair which is on the way yeah y'all make sure y'all go pick these up cuz I literally live by these like every time I run out I'm always going to Sephora and re-up in pills and I like to give my neck to expensive with the anti-aging girl so yeah that's that and then another skincare product that I'd like to use from Sephora is the summer Fridays CC serum and this is the brightening and illuminating this one is just has vitamin C in it so it's gonna like even out your complexion I tend to have a lot of discoloration especially down here at the bottom I don't know why it's like girl so I like to just even it out with vitamin C so I'm gonna go ahead and apply and I like to put it under my eyes too cuz girl we be having long nights okay okay y'all now that my skin is looking so good now it's time to go into moisturizer my body so I like to use okay I use two different lotions y'all one to help with like bumpy rough skin because I do have eczema I haven't flared up that much just because I use the skin fix I really like this brand um this I have the eczema one but I've been using this skin fix resources AHA renewal cream it helps with to smooth out your skin and you know get rid of like rough dry skin so I'm just gonna use some of this all over my body and it doesn't smell like anything it's fragrance free so so it's basically like something I like to use before I go into the sentence stuff cuz I don't know about y'all but I like to smell good so especially when it comes to like lotions and stuff like that I like to layer my sense to you know make a lash all day and like I say I got a little company coming over so I'm gonna just smell good and like that's the best compliment to me like when somebody tells me I smells smoking so after I applied the skin fix AHA renewal cream I like to go in with this Laura Marciere Amber Vanillae body cream y'all so when we were in a DR this is really what helped me have that that hydrated moisture moisturized look my home girl we actually have this in her suitcase and I smelt it on her and the smell smelt familiar and I was like oh girl let me get some so then I instantly fell in love with this I love the smell of this it smells so good it smells exactly like the bum bum cream but better it is very moisturizing to the skin which I like so like I said I suffer from my dry skin y'all so I need something that's really moisturizing and also it does smell good so that's just a plus and then I'm gonna top it off with this time for so they blunt y'all this is literally going to give you that glowy hydrated look all type of like all your lotions and moisturizers this is going to you know make you look so glowy and make your skin look so healthy and on top of that this smells really really good so I highly highly recommend I highly recommend the summer time it's coming so this is going to be like your perfect like body oil moisturizing illuminating shimmer so I highly highly highly recommend this because grow up this smells so good and like I said it looks make sure skin look very very glowy illuminating healthy so I'm just gonna go ahead and moisturize my body with all of these and then I'll come right back so we can get into the hair and this other stuff because I'm ready to take my hair y'all because she needs a little TLC freshly exfoliate it's just no better feeling but anyway so I'm up to do my hair so I like to my hair first before I even get into like any base stuff makeup whatever first things first I'm gonna be taking my hair oil and I'm gonna part my hair and apply it I don't know this brand but this brand is black on and now Sephora I do use it quite a bit because I've been doing a lot of buns lately and this is just gonna give my hair that extra shine and I love the way it smells y'all it smells like candy or something but it gives my hair like that shine that I need because obviously my hair is very dry and damaged so I like to keep oil in my hair and this doesn't make my hair look greasy or anything like that it just makes it look hydrated in my opinion so I'm just gonna part my hair and this does smell so good y'all so good and then I went on their Instagram one day and I don't know y'all like somebody was applying it to their body I'm like what there's like extra dry in the middle so moisture so I'm gonna give y'all a quick little bun tutorial I guess because obviously that's how I like to have my hair especially when it's in its natural state um I do want to start doing different like protective styles because girl we got to protect our hair and I'm trying to you know roll my hair honestly I'm really want my hair to be long and healthy so I'm gonna wear so the first thing I like to do when my buzz is my baby hair first thing I like to do is my baby hair so I'm just gonna go ahead and play around with it I really got my baby hair to be dramatic people ask me all the time how I make my swirl so basically all you gotta do is just play with they and make a swoop when you do your baby hair like go like that swoop it up and then you have this long extra piece right here I like to take the normally on my baby hair I think it would be like a rat tail or whatever but curl it okay y'all so now I got my baby hair is laid she's a very very cute so now it's time to do the bun part so go ahead and take my edge control and just lick everything back my hair looks so good I love when like it's oiled up I've been doing my bun a new way just to add I do it this way to add volume to my bun so it just doesn't look that small two ponytails two ponytails and when you are a real hair ronja boo it just is different they appreciate your real hair you gotta let people know sometimes that you got real hair so make sure your hair is on point she's like so now I'm just gonna twist my pony hair tie y'all my bun is so fire like so fire and it's so easy such a go to hairstyle but okay so now we're gonna get into a little bit of glam just a little bit like I don't want to do too much cuz we're staying in house but I do want to look a little a little more into my face so I'm about to go get my makeup real quick and I'll be right back so like I said I just want to put like a little um you know a little extra you know cuz you know boo coming over so I want to be like somewhat looking decent even though the natural state is cool don't get me wrong I love the natural state but I just want to like you know do a little extra so I'm gonna be using this Lys the same brain that I used the lip product with this is the triple fix serum foundation by Lys like I said this is a black on brand this just came out it's a brand new I love this foundation it literally sinks into my skin and it looks like skin I wore the other day I got so many compliments on it they were like oh my god your skin looks so good I was like girl this is foundation period and I love that this is like a serum foundation cuz it has hyaluronic acid in it I don't know if y'all know the benefits of hyaluronic acid but it like you know reduces the appearance of wrinkles and it just helps out your skin a lot and then it has to work in it and then um it's culture-free vegan and also gluten-free so this foundation is a very very good to the skin and so and I like that it looks like skin like it doesn't look like you have foundation on I'm gonna show y'all that's why I'm putting this on right now because it's not doing too much you know I'm saying it's not gonna give me like a cakey look so I'm just gonna use a little bit and this is in the color tg7 so I'm just gonna use a little bit literally with my fingers I'm just gonna um dot this on like if it was concealer or something so I just really want to put it like um on the lower part of my face and my under eyes I really don't want to use concealer just cuz I don't want anything to look brighter I want my it to look like my skin cuz it's literally me and my boo just chillin so I really don't want to do too much and I know I'm gonna be like doing the most so I really don't want some makeup smearing everywhere so I wanted to do like a little effortless little slide okay the skin is looking very very good it looks so low in effortless I just love these kind of things so I don't want to do too much so I'm just gonna brush out my lashes yeah and now I'm gonna apply some more um of the time forward so like blank up here because I just want to look more low on the chest area so then that's just happen off with fragrances y'all know I love my fragrances and this is the Santel Vanille by 7 Virtues this is their new scent they literally just came out with it y'all this smells so good like when I first smelled this I was like oh wow like I was speechless and I love 7 Virtues cuz they're clean ingredients and y'all know I wear the vanilla woods so I had to try out the same scent and I am in love this scent is like the perfect scent for the summertime it smells so good but I'm definitely all ready for the night I'm like cute bundled skin moisturized like I'm ready so I'm gonna go pour me up some wine and I'm gonna change into a different outfit so do this okay y'all so I just change into this little two-piece set super duper cute I'm not gonna turn around for obvious reasons um but yeah I just feel so glowy and just so moisturized like I'm telling y'all these products are so good I hope y'all include them in your body care because my skin just feels so good like all of my body I just feel so soft and moisturized but it's hold on we better make a cheers because girl I need some wine to top off everything like you know what I'm saying I love to here y'all that wraps up this video I hope you guys enjoyed don't not forget to like comment and subscribe to my channel I love y'all so much like y'all means so much to me and thank you so much for sponsoring this video without y'all these videos when I happen these opportunities will not happen for me but I love y'all so much and I'm gonna see y'all next video I love y'all oh and let me know what products you're gonna include into your body care routine let me know I love y'all


Well, thank you, Francis, for that terrific opening talk. I'm Eric Green, Director of the National Human Genome Research Institute. And I want, as a co-host of this meeting, I want to thank all of you for coming as well and joining the others in saying what I think a spectacular opportunity this is to gather all of you. And thank you so much for traveling far distances in some cases to join us for the next two days. What I was asked to do was to describe the National Human Genome Research Institute's portfolio in genomic medicine. Now, Bayway of History recognized that we are one of the 27 institutes and centers that make up the National Institutes of Health. And we were created by the U.S. Congress just before the beginning of the Human Genome Project to lead NIH's efforts in the Human Genome Project. And for many years, that was the major focus, of course, of what our institute did. But about 11 years ago, when the Human Genome Project ended, of course, we reoriented our mission in many ways to take on the spectacular opportunities afforded by having sequenced the human genome, and in many ways now focus on advancing human health through genomics research. What I want to tell you about, in particular, is the more genomic medicine-oriented aspects of our portfolio. And one of the things we have done, in particular, over the last couple years, is make sure we have a very clear definition of what we mean by genomic medicine. In fact, we went through a formal process, both internal to the institute and involving some of our advisors, to make sure we all agreed upon what we meant when we said genomic medicine. And this is the definition we settled on, an emerging medical discipline that involves using genomic information about an individual as part of their clinical care, for example, for diagnostic or therapeutic decision-making, and other implications of that clinical use. And there are several things to point out about this definition. First of all, it's purposely narrow, and we wanted to make it that so that it wasn't all things to bring under the umbrella of genomic medicine. And by genomic, we mean direct information about nucleic acids, DNA or RNA. And while we recognize downstream products are important, they're just outside of this immediate view that we have in downstream products such as proteomics, metabolomics, and so forth. We keep this strictly focused on analyzing and information about nucleic acids. And finally, we really metaphorically view this as a key destination for taining our mission for improving health through genomics research. This is where we are heading, and very much where the institute is focused on is a journey that began with the completion of the Human Genome Project and aims to realize genomic medicine broadly defined. But as Francis alluded to in absolutely the case, there's going to be many, many steps involved in this. We can see some of these steps, and some of them we haven't even anticipated yet. But our institute is focused on trying to travel this journey, figure out what the barriers are, and do research that would allow us to make this progression in a productive way. And so what has the institute done? Well, literally the day the genome project ended, as was very much part of the culture of genomics, we published a strategic vision of what was needed starting the day the genome project ended, and that was in 2003. And while that was a very effective strategic view at the time, it certainly didn't even last the decade, and in fact, in last day full decade, and we found ourselves in need of a new strategic vision a couple of years ago, and so indeed in 2011 we published one. And the key distinguishing feature of this strategic vision was an absolute clear articulation of the clinical applications of genomics, which I don't think we were quite prepared to do in 2003, but by 2011 we felt the phrase genomic medicine and the reality of genomic medicine was in close enough view that it was time to be more descriptive of what we thought was going to be needed in terms of a research agenda to get us to the point of practicing genomic medicine. And what we finally settled in on as part of the strategic planning process was a recognition that there was a series of progressive domains of research activities that were very logical and that were very effective in leading us down this path towards realizing genomic medicine. I'll briefly introduce you to these five domains. Some are quite familiar to us because we had been involved for a long time, such as understanding the structure of genomes, and then going on in efforts like ENCODE, understanding the biology of genomes. But probably a little more new to our institute was a clear articulation of research objectives related to human disease, recognizing that doing genomics research to understand the biology of disease was a critically important next step. And then moving on and looking at genomic research to advance the science of medicine, but also recognizing that we needed to demonstrate that this was going to truly improve the effectiveness of healthcare. So these five domains became, if you will, a research framework for almost everything I think that the institute is doing now. And a centerpiece of our strategic plan we published in 2011 was this figure, it was Figure 2, which depicted these five domains of research activity over different time intervals, and these density plots simply represent, in a graphical fashion, different stages of, or different sets of accomplishments and when they occurred and where they occur relative to these five different domains, including predicting into the future. So these first two domains would largely be regarded as more basic science-oriented activities, understanding genomes both structurally and functionally. And these three domains bring us more into, if you will, applied genomics, either looking specifically at disease processes or more clinical applications in the fourth and the fifth domain, and this starts to focus in much more on what we mean by genomic medicine. But let me clarify further, because we certainly find in discussions that sometimes people will lump all three of those in and call them genomic medicine. What we mean by this domain three is discovery research, establishing genotype-phenotype associations for human diseases, and I list several such examples that one would easily consider to fall under this middle domain, domain three, of discovery research. The fourth domain puts us more into the clinical realm in terms of doing clinical validation studies to assess the outcomes from using genomic information for clinical care and digging deeper to do research to demonstrate that truly there is validation associated with the use of genomic information in this way. And then domain five is really clinical implementation, truly developing processes for using genomic information for clinical care. Interestingly, we don't regard domain three as genomic medicine, even though at the moment it's probably the largest single block of funding we are doing is in disease-oriented work using genomics, but this is not what we mean by genomic medicine. What we truly mean by genomic medicine are domains four and five. So this is absolutely much more in the clinical validation and the clinical implementation stages of this five-domain progression. So with that in mind, let me give you examples. I'm going to give you six major areas of NHGRI programs in genomic medicine, mostly you're going to hear about this from other speakers. As Francis alluded to, some of sort of the cutting edge, leading edge or lowest hanging fruit, if you will, in terms of opportunities in genomic medicine are clearly in the cancer genomics realm. Many activities we have going on in this, including some of the pilot projects you're going to hear about later, but also we coming out of the Cancer Genome Atlas, a joint venture between our institute and the National Cancer Institute, are new discussions between those two institutes about new opportunities one can envision in the future for doing more real, truly clinical applications of genomics for cancer care. So this is clearly an area we are involved in. Another low-hanging fruit, if you will, cutting edge relates to pharmacogenomics, one that I think many, many investigators around the world actually are certainly pursuing. And coming up later this morning, you're going to hear from Dan Rood, who's both going to tell you about the Emerge Network, but also a component of the Emerge Network that now represents NHGRI's investment in pharmacogenomics research. A third area of programs for our institute, I regard as I call them test drive programs, taking out genomics in the clinic as a test drive, if you will. And you're going to hear from others about two such test drive programs. Lucia Hindorf is going to tell you about our clinical sequencing exploratory research or CSER program. And Jeff Ginsberg is going to tell you about a brand new effort called Implementing Genomics in Practice or the Ignite Consortium. We're also very interested in opportunities such as in the newborn period, and we have a new program on newborn genomic analyses, and particularly you're going to hear from Anastasia Wise going to tell you about a new program we have in partnership with another institute at NIH, the National Institute of Child Health and Development on our newborn sequencing program. Two other, the last two areas, the first one relates to what I would call clinical genomics information systems, and here is something we hear from many people, from many of our grantees and many of the people when I travel around and talk to people, the recognition that there is this onslaught of information about genomic variants and as they relate to disease. And these are pouring into the clinic in principle and eventually will find their way into electronic medical records, but practicing healthcare professionals are overwhelmed by that incoming data and information about publications. We need to develop better knowledge bases, better processes for establishing those knowledge bases that will simply allow practicing healthcare professionals to know what it means when they encounter a genomic variant in a patient. And so just out of the gates is a new initiative called ClinGen, or Clinical Genome Resource that we are creating, and we're not going to have a talk about this because it's something you clearly will want to be hearing about and be monitoring. It's our investment in this important clinical information arena with respect to genomic variants and genomic information. And finally, our last area relates to sort of the ultra rare genetic disease diagnostics, and here you need to look no further than the literature to recognize the remarkable number of review articles that are now appearing, where clinical sequencing is truly being done as part of diagnostics, especially for ultra rare genetic diseases. And Francis introduced you to the Undiagnosed Diseases Program, and indeed this is an NIH-wide program that is now going beyond just what's happening at the NIH as a program to a network of centers around the country. And NHGRI is one of the lead institutes in helping lead this both with respect to what's going on at NIH and with respect to this network. So just to add a few more details to what Francis mentioned, we're going to build upon the successful experience with the Undiagnosed Diseases Program, which was just at NIH to now build a network of these centers around the country to improve the diagnosis and care of patients with undiagnosed diseases, facilitate research into the etiology of undiagnosed diseases, and create a highly collaborative research community to identify best practices for the diagnosis and management of undiagnosed disorders. So in summary, those are the six major areas of genomic medicine programs that NHGRI is carrying out. You know, historically and even right now, the major emphasis of what we're doing very much is in the arena of understanding how genomes are put together, particularly how they're working, how genomes function, and this will continue to be a high priority for the rest of this decade and beyond. But as I alluded earlier, probably our biggest investment right now, if you follow the dollars, is using genomics to understand the molecular basis of human disease. The six areas I just introduced you to, the genomic medicine portfolio of the Institute, is very much about the future. It's not so much about advances that are going to happen this decade. It's building a foundation for what we think are going to be spectacular advances in the application of genomic medicine beyond 2020. Finally, if you are interested in monitoring or following what's happening at the Institute, just a few months ago I created a monthly email update that I sent out to anybody interested, and I guarantee you we will be chronicling our programs, both current and future ones, in these monthly newsletters that I sent out. If you are interested in receiving them, especially with I'm delighted to communicate to international audiences, if you just go to the simple urlgenome.gov backslash director and down there you'll find a link that will allow you to sign up for our listserv, and you will be able to get these monthly updates for me if you're so interested. Finally, I just want to say a couple words about the special thing that's going to happen tomorrow morning for this group. We thought it was too good of an opportunity to have you here in DC, especially downtown, and not be able to see something that NHGRI is particularly proud of. It relates to what I was just talking about. Part of the responsibility of seeing a genomic medicine research program grow with time is the recognition that part of the success of this is going to require public engagement, public education, and public literacy in genomics. And one of several things we're doing, but certainly the flagship now, is a partnership we developed with the Smithsonian Institution, in particular the National Museum of Natural History, to create an exhibition at the National Museum of Natural History. This came out of some discussions. We had them a couple of years ago, and then ended up in a decision to create such an exhibition. And that exhibition just opened fairly recently and really just down the street from here. And we thought it was just too good of an opportunity, so we rearranged the schedule and have all of you have breakfast there and be able to tour the exhibition for an hour, hour and a half. So you'll be entering that building tomorrow morning. This exhibition just opened earlier this year. It's at the National Museum of Natural History. It's a fairly sizable exhibition, as you'll see. And it's in Hall 23. If you don't remember Hall 23, there's two ways to remember it. First of all, humans have 23 pairs of chromosomes. That's one way. But if you get lost, although we want to allow you to get lost, because you're actually getting into the museum before it even opens, but all you got to do is find your way to the Hope Diamond and take a left. That's all you do to find it. We're immediately adjacent to the Hope Diamond, the number one visited exhibition. I'm at this museum. You'll meet tomorrow the director of the museum, Kirk Johnson, and he will proudly tell you it is the number one visited natural history museum in the world. It is the number two visited museum in the world. And only to the Louvre in Paris. This will be resident at this museum for one year, and you will see it tomorrow morning. And then it's going to tour North America for four to five years.   So with that, and if you're interested in learning more about the exhibition or read about it or see a preview before you get to tomorrow morning, a simple website that we've got, not a simple website, but a simple URL, unlockinglifescode.org, brings you to a spectacularly wonderful website associated with the exhibition. And so please look at that and tell your colleagues about it, especially those in your home country who can't travel here to see it. They can take a virtual tour of the exhibition at this website. Thank you for your attention. I look forward to spending the next two days with you.


When I was 15, I got my first real job working as a house painter. I got to work one morning. It was a beautiful day. I had decided to skip breakfast that morning and I told the other painter that I was working with that I wanted to do the high work up on the ladder. So that meant I was two stories up on that ladder. I had been working for maybe five minutes when suddenly I felt faint and next thing I knew I woke up on the ground to the sounds of screaming from the other painter who had found me and then a cast can was done that showed me I had broken my neck in four places. The biggest thing that I think about the new legislation is that a 12-year-old does not have the capacity to make potentially life-threatening choices for themselves. It's kind of our responsibility as British Columbians to remove some of that choice from those young people and help guide them in terms of at least allowing them to mature to an age where they can make those decisions safely for themselves. When I first saw rugby, I was a little bit intimidated I guess in the beginning. It's full contact so there's a lot of smashing of chairs but also really excited about the prospect of having a sport that I could sort of dive into again and find that place to be competitive and it definitely is a huge piece that I attribute into why I am at where I'm at in terms of independence and in terms of happiness in my general life. I think that there's a maturity that comes with age so knowing now that BC legislation is changing to raise the working age from 12 to 16 is definitely reassuring to me just to know that people are hopefully going to have just that little bit more of maturity and the ability to make those potentially life-threatening decisions for themselves I think is going to be a really great change.


We are told, automation is inevitable.  The two most mentioned places for automation will come the quickest, at least here in the UK, are that of cars and trains. Personally, I think cars are a long way off as how can an automated system deal with our pretty narrow roads here in the UK? I mean, just look at some of this video. Well, trains have to be easier to make automatic, right? Well, yes and no. Like everything, it comes down to cost. Just look at the money pit the four lines upgrade has become on the underground. It's much easier to build an automation right from the start. And that was the case for today's subject, the Washington DC Metro. However, automation would be the cause of today's disaster in which a train operating automatically would speed right into the rear of another train requiring the system to be operated manually in the aftermath. Today, we're going to have a look at the Washington Metro crash of 2009. And my name is John. Welcome to Plainly Difficult. Forward. So I've got a real soft spot for 1960s and 70s Metro projects in the US. When they were built, many tried to incorporate the cutting edge of technology. This was, and still kind of is today, automatic train control. But microprocessors and computers weren't really powerful enough at the time. So they exist in a weird realm of modern yet old. The networks used fixed block signaling principles and were made up of individual subsystems. Unlike, say, the modern day cell tracks moving block system where movement authority, supervision and control are all in one neat little package. Raging hard ons for networks like the barter side, this period of rail technology for me is at least a very fascinating one. And one such interesting network, which I hadn't really considered until working on this script, is of the Washington Metro. It really sits in that golden era of US Metro building. So as always, the video will be making use of a few different sources. Most notably the NTSB report, as well as a few other things along the way. And as always, the linkies will be in the description below. Background. So our story begins in the 1960s. The network's beginnings were, as said, on the WM-ATA website. The Washington Metropolitan Area Transit Authority, Metro, was created by an interstate compact in 1967 to plan, develop, build, finance and operate a balanced regional transport system in the national capital area. You see, the capital city needed a better public transport system. And an all new and shiny rail network was planned to provide this, as well as integrating buses, connections with the new metro system. Think like transport for London. Building began in 1969 for the Metro rail system, opening its first section of five stations of the red line in 1976. And over the next few decades, the network would expand with a new station as recently as May, 2023. But we aren't here for a full blown history of the network. We are here for the geeky stuff. Well, I am at least. And this is in the system in which trains are signalled and controlled. Right, so from the start, the network was envisioned as modern as possible for the time. And that was an automatic train operation system. That is, train control was taken out of the hands of the operator. Although manned with the driver's cab, normal stopping, starting and driving was done by the automatic train control system. The system in use on the Washington Metro gets rid of the majority of associated track size signals, opting for an in-cab system. So the whole ATC system comprises of three subsystems, each taking care of an important aspect of signalling and controlling the trains, ATP, ATS and ATO. So the first and most essential is the automatic train protection subsystem. This essentially is the signals that the trains run to and the detection along the line. This is done by track circuits, which detect the presence of a train. The ATC system takes this information and gives the train a maximum safe speed. The track circuits used in the network are like this. Each block has an impedance bond on each end. One transmits a coded modulated sine wave audio signal from a local train control room, along the rails and to the end of the block, where the other impedance bond receives the signal. If the signal reaches the receiver and matches the transmitted signal after it's been filtered and amplified, a relay is energized. Then this will tell the ATC system that the block is unoccupied and a speed code can be transmitted to the next train. Now if a train is in the section, the train's wheels will interrupt the audio signal and the relay will de-energize, thus telling the ATC system that there is a train in the section. Now this is a really basic explanation. It's pretty much as far as I can understand it anyway. So with all this happening, the ATC system will give the maximum speed a train can run to, which if the next block is occupied, will be of the speed of zero miles an hour. The ATC system also takes into consideration any diverging or converging sets of points, and if the route is not set for the train, then the value of zero miles an hour will be generated. The speed signal is generated and transmitted via the rail to the train from the train control room, of which there is usually one at every station. This system is meant to be fail safe in that if a train loses its speed code, it will default to zero and basically stop the train. The next part of the system is the automatic train supervision subsystem or ATS. This system is not fail safe and is tasked with regulating the service, that is to set a maximum speed in which the train will travel to enforce the schedule. I should say that in the cab, there are three speeds displayed to the operator. The first is the maximum safe speed, which is set up by the ATP. Then there is the maximum allowed speed, which is set by the ATS. And then there's the actual speed of the train. The ATS speed can't be higher than the ATP speed. So at the beginning of each trip, the train's journey is transmitted to and stored on the train. At each station, if an adjustment is needed, the speed profile, acceleration profile and dwell time is transmitted to the train from the local train control room. And finally, the final subsystem is ATO or automatic train operation. This does the actual driving of the train. When a train approaches a station, line side equipment tells the ATO system to initiate a station stop. Stops are controlled by tuned passive calls on the track, which tells the train a distance remaining before a station stop. And that's a very simple explanation of the ATC system on the network.  I'm already going to mark off complex system as my head hurts after reading about the Washington Metro's ATC system. The disaster. So it is the afternoon of the 22nd of June, 2009. And trains around the Fort Totten area on the red line are backing up. This had been caused by an earlier fault on the train. And due to the congestion, it caused several trains to be lining up, waiting to move along the line. Strangely, as trains had gone over a section of track, they were receiving a spurious zero mile an hour code. However, these dropouts were fairly short as trains entered the next section they received the continuation of their 55 mile an hour code. And this brings us onto train 214. It's been operated in mode two. Basically means it's being driven manually but under the protection and supervision of the ATC system. It's closely following the train ahead. And as such, the operator is having to regulate the train speed. Soon enough, train 214 gets that owner a zero mile an hour speed code. Train 214 runs into block 304. And due to the slower speed from the operator working the train manually, doesn't get to the end of the block to then receive the needed resumption of speed code. The operator of 214 was now stopped in block 304 and was awaiting a step up in code. But what no one that day knows is that block 304 has a fault that is not detecting trains. Meanwhile, the next train behind is being operated in mode one, i.e. automatic mode. This is train 112. It's following as train 214 was ahead. And before entering the failed block, 112 also got a zero mile an hour code. 112 came to a stand. But 39 seconds later was given a code of 55 miles an hour. This was because 214 was now fully in block 304. And was pretty much invisible to the signaling system. Train 112 speeds up to just shy of 50 miles an hour. As the train goes around the corner, the operator of 112 sees the tail lights of 214. She hits the emergency stop button, but it's too late. 112 slams into the rear of 214, riding the leading carriage over the rear of 214. The following carriage then telescope. The resulting crash pushed 214 forward. This was at around two minutes past five in the evening. Soon after, the first 911 calls started coming in. The controller noticed traction current going out in the area. He attempted to contact train 112, but no reply. At around the same time, the operator of 214 was making his way to the rear of his train to investigate the impact. He raided into control and informed them of the collision. The controller got a track worker to go to the accident site to confirm the report. And sadly, he saw two mangled trains. The controller then held all trains in stations on the red line, which would create crazy amounts of congestion for passengers trying to get home in the evening rush. Fire engines and ambulances were dispatched to the scene. Access was difficult, requiring a block on the nearby CSX lines and for the boundary fences to be cut. By the time the first responders had reached the site, some passengers had self-evacuated out onto the tracks. In order to get to some passengers, workers had to cut away at the train's bodywork. By an hour and a half post-event, all living victims were recovered and sent off for medical treatment around the capital city. A crane would be employed to help with the search and rescue, which would lead up to the next day. And finally, around 9 a.m. on the 23rd, everyone was recovered, including the dead. Nine would be confirmed dead, including the operator of train 112. So, with such a public disaster in the nation's capital, of course, the cause had to be found out and this would enter the NTSB. Investigation. In the immediate aftermath, the crash site was photographed and inspected by the FBI and Washington Metro's engineering team. This allowed the NTSB to investigate whilst cleanup work could be conducted. The NTSB would need to find out how an automatic train could rear-end another. This would lead investigators to look into the system's past as a tragically similar near-miss incident had happened just a few years before. In 2005, a track circuit between Foggy Bottom and Roslyn failed to detect the presence of a stopped train. The near-collision was avoided by the actions of the train operators, but it showed that the train could just disappear off the signalling system. After looking into this further, the NTSB found that the track circuits could be susceptible to a thing called parasitic oscillation. So remember how the train detection is done via an audio signal sign wave running through the rails and if this signal is interrupted, then the signal system knows a train is occupying the section? Well, if there is a fault with the ouster module then a spurious signal could enter the circuit which mimics what the receiver is looking for, basically a sign wave and thus report the block as clear when it actually wasn't. What's bizarre is that in 1999, the Metro undertook a program of track circuit replacement with the aforementioned Alstom system. Interestingly, after 2005, incidents Washington Metro and the module manufacturer Alstom didn't bring in enhanced tests to check the network's track circuits. The NTSB would even say this in the investigation. Contributing to the accident were, one, WMATA's lack of safety culture, two, WMATA's failure to effectively maintain and monitor the performance of this automatic train control system, three, GRS Alstom sign inks, failure to provide a maintenance plan to detect spurious signals that could cause its track circuit modules to malfunction. Four, ineffective safety oversight by the WMATA Board of Directors. Five, a tri-state oversight committee's ineffective oversight and lack of safety oversight authority. And finally six, the Federal Transit Administration's lack of statutory authority to provide federal safety oversight. The NTSB set out several recommendations, such as regular inspection of track circuits and a replacement of all 1,000 series Metro cars. This is because of the telescoping issue the Unix experienced in the crash and the very unsatisfactory crash-worthiness that had been seen. The Washington Metro would note this in an update. Retirement of the 1,000 series cars, the oldest in the fleet is Metro's number one safety priority. The NTSB recommended that Metro's 1,000 series rail cars, the oldest of the fleet be replaced with more modern vehicles that will be equipped with advanced crash-worthiness systems technology. The disaster ended up costing millions of dollars for a Metro as well as nine lives. In its wake, the disaster undermined the public and operators' confidence in the ATC system as such, all trains would be operated manually, albeit with the protection of ATP. Ironically, if the following train was operating manually, it was still very likely the disaster would have still have occurred as the failure was with the ATP system and train detection and not the automatic train operation. So what did you get on your bingo card? I got this and I'm going to give it a four on my disaster scale. Do you agree? Let me know down below. This is a plainly full production. All videos on the channel created commons that we should share like licensed. Plainly full videos produced by me, John, the currently wet and windy corner of Southern London, UK. I have Instagram and Twitter as well as the second YouTube channel to check out all the links in the description below. And I'd like to say a very warm thank you to my Patreon and YouTube members for your financial support as well as the rest of you for tuning in every week to watch my videos. And all that's left to say is Mr. Music, play us out please and thank you for watching.