So, cancer is a disease of the genome, and although arguably you can make that statement about a lot of diseases, part of what makes cancer fascinating is that there are two distinct ways in which that statement is true. Like many other diseases, there are germline risk variants that confer a lifetime risk to developing cancer, but there are also somatic alterations that develop in the cancer tissue that directly contribute to tumor genesis, metastasis, drug resistance, and other phenotypes. The heritability of cancer has been known for a while from family and twin studies, and it varies quite a bit from tumor type to tumor type. We know that the inheritance and the heritability of cancer is not simple and it's mediated very likely with a complex polygenic inheritance. Part of the genetic revolutions of the 80s and 90s was the use of positional cloning and family studies to discover rare, highly penetrant variants that mediate familial cancer syndromes, and the sort of highlights of these were discovery of P53 and leaf romani syndrome, APC and familial colon cancer, MLH, MSH genes in Lynch syndrome, BRCA1, BRCA2, familial breast cancer, and RB1 retinal blastoma. Together all these high-risk, high-penetrant variants explain a small percentage of the heritable risk for various tumor types. Recently the emergence of genome-wide association studies examining common SNP variation in case and control cohorts have yielded a host of loci in both cancer and non-cancer disease analysis. Sorry, can I use this for a later point, or is this... Oh, here's the point, okay, great, thanks. So over the last five years there have been a number of cancer GWASs that have yielded over 300 loci in over 20 cancer types. And together these loci can explain as much as 10, 23, and 6% of the heritable risk for breast prostate and colorectal cancer, respectively. So here's a sort of a large-scale picture from a review in 2010 of cancer GWAS loci, and we see that there are a number of these loci around the genome. The majority of the GWAS loci have been discovered for prostate, pancreatic, lung cancer, hematopoietic tumors, and breast cancer. A lot of these loci lie in endogenic regions, and their role in disease has not been functionally elucidated. In familial germline loci there's a lot of precedence for genes that are mutated in germline families but also are somatically altered in cancer. And of course among these are P53, APC, RB1, CDKN2A, VHL, NF1. A lot of these are tumor suppressor genes which undergo a two-hit alteration whereby they're inactivated in the germline and then undergo a second hit in the tumor tissue to become lost, to undergo loss of function. So we decided to examine the interplay of common variant loci discovered in GWAS studies and somatic copy number alterations to examine this hypothesis on the genome scale. So we took 297 cancer loci documented in the NHGRI GWAS database from over 80 GWASs and then took a list from a recently published study by Burhim and colleagues at the Broad in 2010 examining somatic copy number alterations across over 3,000 tumors and over 20 tumor types. And this study yielded 258 copy number peak regions. And our approach was quite simple to basically examine the overlap between these two regions of loci and determine whether it was significant against a null model built using permutations. So briefly the way we assembled the data was obtaining these loci from GWAS database. These are usually reported as a single SNP. We of course had to handpick the cancer related GWASs and then for each SNP defined a locus using the linkage disequilibrium neighborhood of that SNP. And with that sort of collapsing loci into unique regions we found 219 unique GWAS loci covering 1.1 percent of the mappable genome. On the SCNA side we took all the loci reported in the Burhim and colleagues study in 2010 and basically we took the PAN tumor analysis combined with all the tumor type sub-analyses and found 258 total SCNA peak regions comprised of 8.4 percent of the mappable genome and that included, sorry, 198 amplification hotspots and 67 deletion peak regions. So crossing these two loci we see the plot shown here and this is a genome wide plot where the GWAS loci are represented. They lie on the chromosome as these little dots and then we see the SCNA peak regions hovering over each chromosome and then the intersecting overlapping loci are shown in red. And so among these intersecting loci we have a lot of known cancer genes as well as novel loci. So to determine the significance of this overlap we performed a genome wide permutation, actually a number of permutations. And what we found was a strikingly significant overlap in GWAS loci and frequently altered or frequently amplified regions of the genome and cancer. In contrast when we analyzed, when we compared cancer GWAS loci against commonly deleted peak regions we saw the distribution of overlap as shown here in the left plot and following permutation we found actually that this intersection was not significant. And so this is quite interesting. We pursued a second line, a sort of orthogonal line of investigating this overlap by comparing cancer related loci versus non-cancer related GWAS regions and we found that cancer related GWAS regions were enriched, significantly enriched in overlap with amplification peak regions but again did not frequently overlap with deletion SCNAs. So one feature of the GWAS findings across all the cancer germline analyses is that there's a hotspot of association where there's multiple loci and prostate cancer and GBM and other cancer types on the region of 8Q24 near the mycologus. So to examine whether our results were robust to the removal of this region which is also frequently known to be amplified we did a separate analysis where we excluded these loci and we still found a significant colloquialization of these amplification peak regions with cancer GWAS loci outside the mycologus. We applied this analysis to different subtype analyses and we also saw a significant association in the lung and hematopoietic overlap with lung and hematopoietic peak regions and cancer GWAS loci. So these results show an interesting correlation or colloquialization and they could be explained very simply by regions or genes that tend to undergo somatic alteration frequently in some patients and then in other patients are mutated in the germline genome and confer lifetime risk. But it doesn't really suggest any kind of germline somatic interplay. For example in commonly the classic model of tumor suppressor loss involves a germline inactivation followed by a somatic alteration that results in loss of function. So we wanted to ask this question of whether a germline SNP status actually confers risk for specific somatic alterations in this case amplifications and a really interesting precedent for this was published a few years ago where a common variant SNP conferring risk to myeloproliferative disease located in Jack II actually was shown to be predisposed to the development of the somatic point mutation in Jack II in these same neoplasms and what was really fascinating was that the actual risk conferring germline common variant SNP would occur on the exact same on the same haplotype as the somatic mutation. So we wanted to pursue this question in the context of copy number alteration so how would we detect this? Well if we have a heterozygous SNP in a tumor in a patient's tumor tissue this is a germline heterozygous SNP and a tumor decides to undergo a copy number alteration in this case amplification at that locus. Well it might sometimes choose the C locus containing the C SNP to amplify but other times it may choose the locus containing the A SNP to amplify. And if the tumor is sort of equivocal it does not care about the status of that germline allele well then it'll amplify these two different alleles at an equal proportion. However if there's something special that it sees on that C allele that maybe it likes it's positively selected for then we'll see it amplifying that C allele time and time again. And so the way that you can test this is something using something called allele distortion test and this was first proposed by Duol and colleagues in bioinformatics in 2009 basically at each heterozygous SNP that undergoes a copy number alteration we can measure how frequently one allele versus the other alleles amplified or deleted. And then we can test the significant deviation of this frequency from one half just using a chi-square distribution or a Fisher's exact test. So basically if we see that the tumor amplifies an allele in allele A in 30 out of 35 sets may be evidence for some kind of allelic bias and a germline somatic interplay. So we examined this in several data sets including the original GCM data from which the global cancer map data and TCGA data using 6.0 SNP arrays and we were sort of disappointed to find that zero of these 36 loci, cancer GWS loci that intersect the somatic amplification peak showed significant allelic distortion. Before we applied this scan genome wide and we found a significant allelic distortion at 11Q13. This allelic distortion occurred zooming in on this locus we found that this is a SNP that lied a 100 KB upstream of the cyclin D1 locus and near the myov gene and examining the individual events that contribute to this signal we found that 44 out of the 50 tumors that amplify this SNP choose the C allele over the T allele and we can see here the individual tumors that support the signal and we see that across many tumor types we're seeing many tumor types that amplify this locus which is of course a frequently amplified region and they tend to choose this C allele over the T allele. We applied the same analysis in the TCGA 6.0 SNP data spanning over 2,000 tumors and again we saw many tumor types ovarian breast lung amplifying this locus and choosing this C allele over this T allele and this was strikingly significant. We saw the same effect in the Brodenovardus cancer cell line encyclopedia this is a set of over 900 cell lines that have been profiled with both expression copy number sequencing we saw the same effect which was quite significant. So this is an interesting result partly because it does actually lie in obviously a frequently amplified region it lies not too far from a GWAS peak but does not lie in an actual significant GWAS region. So the question is what is the biology that may be driving this? We clearly see that these tumors tend to preferentially amplify the C allele over the T allele at this locus does this C allele, germline C allele carry some kind of selective advantage that the tumor is really going after for example is that cyclin D1 associated that's nearby more expressible or somehow has a selectively advantageous genotype or perhaps maybe there's some kind of interaction with the amplification machinery that maybe alters that local amplification rate somatic amplification rate and that phenotype is carried somewhere on you know by that C allele or is tagged by that C allele. So we took some steps to examine this hypothesis looking at the cell line cyclopedia and examined the interaction of the allele status of this SNP with total copy number and expression to examine whether there was an expression quantitative trait locus at this SNP and we found a mild but significant effect whereby with increasing doses of allele C when we control for total copy number we actually see increased expression of cyclin D1. We did not see this EQTL with any of the other genes in this locus. So in summary we see a significant overlap of germline GWAS peaks or loci and SCNA peak regions across cancer types and this is predominantly with amplifications also what I didn't show in amplifications plus deletions but not with deletions only. As far as we know this is the first evidence for germ genome-wide collocalization of germline susceptibility variants and somatically altered loci and cyclin D1 is an interesting candidate CIS somatic trait locus or CIS STL and we're investigating that further and I'll take any questions next oh and sorry I'd like to thank the my collaborators on this effort Scott Carter, Rameen Burkheem, Craig Murmell, Gaddy Getz and my mentor Matthew Meyerson. Thanks. Thank you Marcine that was a great great talk question Susan. Hi why did you choose to just use the heterozygotes not use the two homozygotes as well? So the the in the setting of the heterozygous SNP we can come up with a simple statistical test that would determine some sort of selective advantage that or some sort of effect I think we've also so that test I think is is a good test because it's less so the the other alternative is to use a trend test or sort of a case control test where we look at amplified and non-amplified or patients that are amplifying versus non-amplifying that locus and compare it for example minor little frequencies that test this tends to be more prone to population stratification and and yields a lot of yields messier results although it is potentially powerful so both are good ways of approaching this problem the ADT is more similar to the TDT in germline genomics which which again is also less prone to population stratification but it's perhaps less powerful requires more samples but we've actually tried both we just achieved cleaner results with this test. Yeah just a question have you taken the copy number variation into account or have you considered that as another possible way that you could get amplifications or deletions? Oh germline copy number yeah germline polymorphism right so in in in the context of this data we are only looking at somatic copy number events but that that certainly could be another driver of this kind of effect and I mean we're only looking also at germline single nucleotide polymorphism a more general application of this strategy would be to look at large other kinds of somatic variants and other kinds of germline variants and that's certainly a great direction of additional exploration. I have a quick question so for the GWAS peaks have you attempted to further stratify them by looking at the heterozygotes and trying to discern whether or not they the mode of inheritance is dominant versus recessive among the GWAS peaks and then repeating your analysis to see if there's a difference. That would be a great analysis unfortunately a lot of the the GWAS data that we're using we don't have the the underlying genotypes those are either not accessible or require additional we haven't been able to access yet so definitely that's a that would be an interesting analysis also analyzing the summary stats of some of these GWAS to examine a low side that perhaps fell under the genome-wide significance threshold but but happened to collocalize with a copy number somatic copy number region would be an interesting way of finding additional germline effects okay thank you thanks


Welcome to Toffy TV, it is my three things from Everton, one nottingham for us, one a goodersham park today, the Blues, dropping two-pointer home in my opinion. It was an opportunity to get off the mark with a win and we needed a late goal to rescue a point and it's a disappointing result, that's what I feel, that's the way it is right now. First thing I want to talk about is the lack of options in the final third. It still makes me, it still scratch me head when I think of the money we've had at our disposal and our options today with Salomon London or No Strike. I honestly cannot believe we've gone through that much money and that's what we're left with, it's crazy, it's crazy. I know Dom's injured, you can say it's bad luck, yet maybe it is, but there's no other option and that is crazy for me. We've ended the game without a striker or front, we didn't bring Delyon because I imagine they didn't want to scupper any move to Besiktas for him and it's left us short in a game where we really need the three points we've got, three very tough games coming up now, Remfordd or Ilead or Liverpool or home, and there's an opportunity, would anybody really say it without saying you're being too negative? Would it be a massive shock if Everton had one point after the next three games and therefore would have played six games and had one point? I don't think it would be a massive shock, I'm not saying that will happen, I think Everton are more than capable of getting the results of Remfordd and at Leeds, Liverpool are home and the Derby match with the crowd is obviously, we can influence that and hopefully the players will be and will be up for it, we know they will. We've put ourselves in a position where we've had two narrow defeats and we've had a draw and in all three of those games we've had opportunities where with a proper striker, a mobile or a better striker we've got a result, I feel we've scored goals in. Other teams have got three or four options in the final third, teams are a mid table have it and we don't, we might have fast players like Anthony Gordon or Demarie Gray and they may chip in with five or six goals a season and he might, but that is that enough? I feel two don't score goals, they just don't, you know we had Alex O'Wobee who I think we'll talk about him in a bit but he was brilliant again today but doesn't score goals, never looks like he's going to score a goal, Tom Davis the odd goal this season maybe. Onan is new to the country so we've no idea whether he'll get goals but historically he doesn't get a lot of goals. D'Corey maybe gets four or five, Alan's not score the goals since he's been here so it's not like the team is blessed with lots of goals and if anything's going to put everything in trouble it will be that and therefore the money or the impetus has to be now, the focus has to be on bringing two players in at least in those forward areas who can get goals. Got to be, it's got to be, I've said it before structurally I think we look fine, I do I think we look like a better side this season but we've got nothing in the final third and that is arguably that's where it all that matters really isn't it, I think we look much better defensively, I think sometime we get caught in transition because we haven't got a target, a hitter, we haven't got a runner that we can play through and we hesitate and we wet and then the ball gets nicked off us so it's really frustrating it's something the club has to address very quickly and we've got 12 days that's it and then it shuts and if it was to shut today I would be worried whether we'd have enough in us to stay up or to certainly be in a position where we strengthen when the next market opens because there's just no goals in this team and three games have proved it, we scored two goals and three games, one was our own goal, we've got one in the 90th, 80th, 90th minute today, needs addressing. Second thing I want to talk about is Alex Oboby, I think he needs talking about it, I think he was fantastic for me today's man of the match, I think he started the season really well, playing in that central midfield he's everywhere and I'd like evidence that if we're going to stick with five at the back, three at the back, five at the back whatever you want to call it, if that's how we're going to play and there's every indication there is then I think we forget the two midfields, three frontmen or three wide or whatever it is, it's not working whatever it is, it's not like our wide players fly down the wing and whip cross after cross you know, get in and have loads, it's just not working. So I would have three in the field if it was me I think I'd think if we're going to get the most out of Omnana we're going to have to give them a little bit of protection and I think that comes by having two players in that midfield with them. And then I would have like if there being today I would have had maybe Damari Gray off Salomon Rondon or Anthony Gordon off Salomon Rondon and then whichever one wasn't in the team would have come on after with maybe half an hour to go and used a pace that way. We don't know whether Anthony Gordon's going to stay, I'll come on to that in a minute but that's how I would go and have three midfield plays because I think what you want to try and do is you want to try and free up your two midfield plays to break into the box and Omnana will do that. It all comes down to personal of course it does have everything, you know if the garner move come back you know back to the table and he was going to play in the six then you'd have him sitting and he'd look after that and you'd want a woe being you'd want Omnana to be breaking into the penalty area as well giving you more bodies. I just think with the way we play two in midfield it's asking a lot, I think we have three up front or three supposedly in the final third but like I said they never link up really. Don't get balls flashing across the box for people to get on the end of so I would have a little bit of a change in midfield but I think a woe be has been fantastic and I think if he was in there with two other players I think he'd see him getting into the box more and hopefully then weighing in with gold but he's going to play. The way he puts in you know he's trying to get us going with little passes I just thought he was brilliant today and you know he hasn't had a great time since he comes to Everton of course he hasn't but certainly since Frank Lampard's been involved at Everton and coming and he's got a woe be into the side. The Newcastle game last season was a huge turn on point four and he scored an important goal in that and I think since he's been involved like that and I think he's just got better and better and he can play anyway now but I think in midfield I think he's fantastic and he's been brilliant today and was my man of the match. And then the third thing is what to do with Anthony Gordon really. I think he started the game so well today. They opened in 20 minutes, I thought he looked lively.  So the lad was away, there was only one outcome so why didn't he just use his brain and just carry on sprint and he's fast. We know he can run a good distance at a good top level pace. I think he's a court day player and should have just ran with the lad. He threw a challenge in, got himself booked and then knew he couldn't put the same kind of weight rating off the ball in case he clipped one of them and the referee and you know when it was Andre Marner who couldn't have waited to send them off. So for me he is frustrating Anthony Gordon, I think he's got a lot of talent. There's obviously all the talk about his career as in what does he do next, does he stay at Evan, does he move to Chelsea. Chelsea won him. There's links to Manchester City, there's links to Manchester United, Newcastle. What do we do with Anthony Gordon? Do we sell him and take the money? If Evan got an offer for £50 million would he ever be worth more than £50 million? That is the question isn't it? If he's never going to be worth more than £50 million in his career then why wouldn't Evan take the money and reinvest that £50 million going back into the side. Would give Evan a lot of freedom to spend and he could probably really reshape some of this team and maybe get goals in it. I don't know, I'm honestly, I don't know. I don't know, I just look at that team and think we need goals from somewhere and I don't know whether loans are going to cut it. We'll have to wait and see and obviously Anthony Gordon and you know we might want to stay. My only thing with Gordon is normally when there's this kind of interest and they go back and forth and bids coming, normally the team stays at the table because the player is interested in making the move. Now he might look and go, I'm 21, it's a Champions League club, I can go and get experience and play with better players and play in the Champions League and develop and that might be of interest soon because all players want to play in the top competitions. He might turn on and say I've got no interest, but normally when a player has no interest in leaving, the club doesn't come back after the initial bid. So we'll have to wait and see what happens, I've got no clue which way it'll go. It'll be a very interesting. One of Chelsea do come back with £50 million, I think it'll give the club a big decision to me because quite clearly they haven't got the pot of money they've needed to get the former players they won in at the moment. So we'll have to wait and see what happens, I've got no clue what to do. I mean what would you do? That's the big thing, what would you do without Gordon? Would you keep him or would you sell and say we're going to reinvest that money into forward players with goals and try to restructure the team? It's a tough one because you never want to lose, go plays and you never really want to sell young players when you're trying to create a young side. It's a tough one. So let me know what you think, thanks for watching, give the video a thumbs up, subscribe if you haven't enjoyed the rest of your weekend. See you later.


Prop, DoorDash has a problem. Something's going on with the app. New shout out to everybody tuning in. If you are subscribed, make sure to submit that subscribe, but give me a thumbs up and do not skip those ads. Today is March 18th and we already getting to this bag. Order number one and order number two, what to do? Order number one is all the way sparked up. Two orders, 7.4 miles for 2085, stay alive, let's drive. Order number two is Starbucks, 3.6 miles for 7.45 with the Gucci interior, baby. We about to put up the Starbucks right now. We about to get busy. I hope you guys are with me. I hope you guys have a great Friday. Also, make sure you submit that subscribe button, give me a thumbs up, do not skip those ads, and hope everybody up there getting to this bag. Let's go. It's time to get busy. How you doing Tyler? I have a pickup for Julie D. Thank you very much. I'm a big one. Baby, it says leave it under the door, the mailbox. That's what we're gonna do. Drop it like it's hot. Hit it with that photo, but y'all right now don't smack. We gone. Order number three, get it with me, baby. We got another Starbucks order, baby. 4.5 miles for 7.85 stand live. Let's drop. This is the player stand. I'm about to go back to Starbucks, pick that up.  It's all the way on the way, baby. I hope y'all get to this money because it ain't funny. Let's go. How you doing? I have a pickup for Rachel B. Alrighty. Yes, man. Thanks, you guys have a good one. Where, baby, to drop off the Starbucks. I run the doorbell. I still have to bring it up to the actual house and meet at the door. So, I run this, here we go. You have a great day. I'm here to drop off order number one. Let's get it done, baby. These problems are so confusing to get over here. It always sends you to the back. Hey, how you doing, man? This is Jerome. I'm here with your Walmart order. Alrighty, thank you. Okay. I'm getting the game, coach. Elevators right here. Don't get me, doggy. Hey, doggy. Hey, doggy. Charlie, don't get in trouble. There you go. Thank you so much. You're welcome. Is this all? No, I have the rest of it right here. Charlie. Hey, Charlie. I can hear, buddy. What are you, unloading our straw? Yes, ma'am. I hope they give you good money today. I hope so, too. I'm gonna find out. Yes, ma'am. I really appreciate it. If you want, I can sit them in here. The rest of them so you don't have to clear all of these at one time. Yes, ma'am. We have to eat those apples. Eat that. Be careful, huh? You want me to sit it? I can sit here like right here. If you want, I can just take it in the kitchen. Okay, okay. I'll sit them right here by the dishwasher. Okay. There you go. Thank you so much, ma'am. All right, you're welcome. You have a great day. Stay warm. Is it gonna be the next, are you gonna be the one that's gonna take care of hers from now on? No, it switches. It just sends it out to different people. Oh. Yeah. I don't like that. I'm gonna throw money in the trash. That's how I am, too. I would like to go with the same person, but I wish it was like that, but we can't. But they don't, they determine who's gold. It's like the orange just pops up and then you just take it or leave it. But if I see your name, I'll definitely come back. Thank you, you have a great day. All right, bye-bye. Order number four, we about to get to this door, baby. Mickey D's, baby. 3.1 miles for nine, 10. We about to get it in. Let's go. We're here to jump up this Mickey D's, baby. This says, do not ring the doorbell. So we gotta follow directions, baby. Hit them with that photo and smack. We're gone. Order number five, stay alive. Let's drop, baby. Jewel Osco. Four items, 3.5 miles for 775s. Let's drop.  This is how you supposed to do it. Put the bread in the bag and the other bag, baby. Come on, man. I got to lose your head sometimes. So we gonna drop this right here. Bop, bop. Open that joint up. And we gonna place all these things right here. Then we gonna put the bread on top. Get them right, get them right. Make them look nice and pretty. Bop, bop, bop, bop, bop. There we go, put this bread right here. This bread right here, see that? Hit them with that photo, but you're already know those. Smack, smack, smack. Jewel Osco. Order number six, we in the mix. Starbucks 1.9 miles for 744s. We about to put up and get this dough. We in here, baby. Hope they got it together. Hope that they got something to go with it. Are you in line? No, I'm out. I'm have a pickup for Rachel S. Thank you very much, you know how to go, bro. Baby, we come to this house literally like every single day. They eatin' that Starbucks. That Starbucks. Let's go. Order number seven, thank God for his blessings. Order number seven is on the way sparked up. Two orders, eight miles for 29, 18. We about to get this green. Order number uno, dos, tres, cuatro, cinco, seis, siete, ocho. Order number ocho, baby. We about to get this money. McDonald's, three miles for 736s. We puttin' that right now. We tryin' to get rich. Let's go. These, baby. Hope they got it together. Oh, I see an order up there. I don't know. Guess what? We got another one, baby. Panera bread, three items, point eight miles for six dollars, we a holla. I'm about to go to Panera bread, pick up this order. Then I'm gonna jump that one off first because it's only point eight miles, less than a mile. And there we go. Jump off this Mickey D's, baby. I hope you guys are enjoying the video. Again, make sure you subscribe, but I'm in here lixin' the podcast and all that. Let's get busy. Order 10, we already get it in. My business partner got this order. Chick-fil-A, five items, 3.7 miles for $7, we a holla. Let's get it. Hey, guess what?  About to go in here, grab this order, drop it off and continue to get busy. I hope you guys are with me. Let's go. Probably get this bread, baby. Hopefully they got us together. Is that how it's, that is how it is. Excuse me, sir. Can I get this bag right here? I don't want to reach over you. Thank you, you guys have a good one. Hello. I'm gonna have a delivery for Kate Tuber. Kiwi, yeah. Shall I leave it right here or is it for you? No, it's for one of our co-workers. You can leave it up here. Okay, thank you. Uh-huh, thank you. Thank you. I have to take a picture of it really fast if you don't mind. All right, you guys have a good one. Let's go. Mickey D's, baby. Hopefully they have a way of messing up the audio. We saw it good though, baby. We're getting to this money because it ain't funny. We kind of wish they could get this on the way, spark filled water. Hit him with that photo of a charter right now. Doorbell. That didn't work. We're here to drop off order number one. Let's get it done, baby. I got to drop these, take these gallons of water and everything first.  If you're with me. Drop it like this, huh? They got the kombucha, too.  They kombucha? Dang it. Order number 11. We getting money. We ain't stressin'. Bendys, two items, 5.8 miles for $12.40, shorty. We're here to drop off order number two. And what it do? Drop it like this, huh? Put the bread. Right here, by itself. We got some good cereals. Lemma. Step back. All right, no, fade away. Jordan hit it with the photo. Let's go. Order number 12 is Tom Preveo, baby. Starbucks, 2.2 miles for 5.85. Stay alive, let's drive. Order number 13, we hot light score chain. Popbelly, one item, 2.1 miles for 5.75. Let's drive. We're here in Starbucks again, baby, trying to get these divin' in. There you go, right there. Hello, have a pickup for a Janelli? Yeah, I'll check it up right now. Thank you very much. Thank you, you have a good one. Let's go. We're gonna drop off this. Dang. This for a riser for a Janelli? Oh, baby, she gonna open the door for me. Let's see somebody call her. Janelli, here you go, you have a great one. Order number 14, we about to get this green, baby. Japone, Lay and Teriyaki Madison's two orders, four items, 6.6 miles for 10.90. Let's go. Hopefully you got us together. See, there's two of them up there. Oh, that's her. Dang, I don't know what we're doing yet, man. We're supposed to have me ready, so I can get busy. Party's gonna be at 11.15 in a minute, so. Thank you. Hey, can you have a good one? Thank you. Order number 15, we getting this green. Polk Rose, one item, 3.4 miles for 6.75. We actually got 8.25 for it, baby. I'm on my way to Teriyaki Madness, so we can stop this madness, baby. We still got a few more orders to go. Hopefully we get all the way sparked up, man, because we need that so we can go ahead and complete today. It's only 11.15, just so y'all know we're getting this green. So I hope you guys enjoyed the video. Make sure you smash that subscribe button. Make sure you give me a thumbs up. Do not skip those ads and congratulations, everybody. We are almost done, and we are almost done getting to this bag. I thought we was close, and I see we wasn't close enough. Thought I could cook, and I think I won't post the cook. Little bro. So guess what, guys? I think we have a problem. DoorDash has a problem. Something's going on with the app. I don't know what it is, or it could be Google Maps. So boom, I get to deliver, and I get the orders. I get to Chipotle, boom, and I go get to Teriyaki Madness. I leave out Teriyaki Madness, I hit direction. They're supposed to send me to the house, but it is like it's just blank. The whole screen is just blank. It's like it has the streets, but it's not telling me where to go. Turn left onto North Evergreen Drive. So after that, five minutes, I'm trying to fix that. It's still not working. I go to Google Maps, try to do it that way. It's not working that way. So what I had to do, I had to go to Maps and my phone, and then put it in there, and it's working now. I don't know what's going on with the app or whatever, but comment below and let me know if this happened to you.  Jump off this Chipotle, baby. Since we've got a doorbell right there. He didn't want that photo, but you already know. What's next? Next one, I mean. Doorbell? Let's go. Number two, what it do is it's heading to my bedroom. Sometimes I can't hear the doorbells. A lot of times I think they don't work. Hello. There you go. You have a good one. You're welcome. Order number 15 is Walmart's 54 items, four miles, for $9.50, get with me. This still ain't held branded with no type of direction. This is Walmart midi, this is a handed tool. So that's exactly what we're going to do. I like this little set up right here. I put a little screw right here, even in the rain, you can block it in. It's nice. That's a 15, you're still listening to that, y'all too. Hello, this is Jerome with DoorDash. I'm outside with your order. It's okay. Would you like me to just leave it here? Or, okay, no problem. I'll just leave it here. All right, no problem. Bye-bye. She said they told her it was going to take two hours. So she left. She went to the store. So we can leave her here. She didn't leave her there. Step back, I didn't want the photo, but you already know. That's enough. Let's go. Order 16 is Chick-fil-A 3.9 miles for 707. 707, three of them. We're here, baby. It's time to get busy. I hope y'all with me. Talk about the Chick-fil-A bae bae. Drop it like nine, bop, bop. They about to eat good, ain't they? Good food. Good food. Photo, y'all ready to know, though? I don't know, this one works. Last three, baby. Order number 17 is Panera brand six items, 0.6 miles for 675. Let's drive. Order number 18 is Chick-fil-A. Six items, six miles for 675. Let's drive. In order number 19, last one, let's get it done. Chick-fil-A 3 items, 1.6 miles for 525. Stay alive. Let's drive. It's time to get busy. I hope y'all with me. Let's go.  Hello. Have a good look at her. Stephanie, there you go. Can you ever tell us your YouTube? Oh, y'all gotta go to my YouTube. Go over to the phones. I need the phones. Come on with the phones. What's the phone? The phone. Cars and Cribs. Cars and Cribs? Yes, ma'am. Okay. Let me make sure you go into the right thing, because you know. This one? Yes, ma'am. I guess that. Go ahead and hit that right there, hit that. Go ahead and hit it. We gotta tell you. Yeah, because she was in the way, y'all. Oh, you don't remember me? She wasn't here? Yeah, she wasn't here. Jessica? It was her. It was me and her. And Nancy. Nancy, she's not here today. I remember everybody. Are we going on straight YouTube? That's what we're doing. Yes, ma'am. All right, but. You're having a boy or girl? I'm having a boy. Oh, good luck. Thank you. We sure there was like, hey, love to call Tyna. That was my fault. I thought about that later. All right, you guys have a good one. Let's go. And just like that, it is the end of the video. I hope you guys enjoyed the content. Guess what? We made 203.82. What it do? Look at the time. Wow. 111, baby, with the Mac 11. Thank God for his blessings that we done today, baby. Honestly, today we're very, very smooth. One of the best days ever. We're earlier, at least. Like around 11 is just started to slow down a little bit, but we still got to do it. And it's only 111, baby. So I hope you guys enjoyed the video. Make sure you lock in tomorrow because going back down, I'm about to drop off Snow White to go get this oil change, man, because we got to get this oil change. We, it seems like we get oil change like every month. If you want their dashing, or whatever you may be doing as far as gig work, comment below and let me know how often you get oil change. It may be like every month or every month and a half, but we drive a lot of miles. We bought this car with 63,000 miles. It now has 78. And we bought it in, it almost has 79,000. We bought it in, I think it was like in December, January, February, March. Three months, that's the three months. We need to put all these miles on it. But I hope you guys enjoyed the video. Make sure you lock in tomorrow because it's going back down. We ain't playing around. 2022 is back season. I'll see you on the next one. Be going, be going, be flowing. You already know it. It's DDK and I'm on my way.


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We are here again to face one of the rare events that can unfortunately occur more frequently in the sports arena than in the general world, which we usually hear from the newspaper for the general communication media after a major catastrophe, but this time we want to talk about a good story, a story where some fear and tribulation was originated from screening, but eventually a correct, complete evaluation could finally conclude that there is a hope for clarifying the prognosis and optimize the prevention that is the proper way to treat this event of sudden death in athletes. We can now do effective prevention by routine, accurate screening, and this is what we have done for the last three years, prospectively at the Texas Art Institute, and it was very gratifying to conclude a short, but very intense and in-depth evaluation with very good news. Thank you. My name is Jose Naranjo. I am the team doctor of a professional soccer team in Spain, Sevilla Football Club. We are here because in routine examination we found a problem in a soccer player. It consists of an anomaly of coronary arteries. This is associated in some cases with sudden death in sports people. So it was very, very important to determine what kind of anomaly it was and what was the prognosis for the practice, professional practice. So we came to the Texas Hurt Institute because looking for the opinion of the doctor Angelini and his team, we know this center is the top level in the world in the Hurt pathology. And fortunately, all examinations have demonstrated that the variety of anomaly in this case is benign anomaly and we are very, very happy and very lucky because the player will continue his professional activity. Hello. My name is Edviras Maduro. I'm a soccer player of Sevilla Football Club in Spain. And I'm really happy that I came here to Texas, in Texas, Houston because they found something in my hardware that I was born with and I think it was really important to study that because it's the hardest, I think the most important part in our body. And we took a decision to come here because I think the best doctors of the world are here in Texas, Houston to help me with this problem and finally we did this and the result was really, really good so now I'm really happy that I can play soccer again and I look forward to play with my teammates in Spain. I'm really happy and thankful to all the doctors who helped me and other nurses also so it was really a great experience. So Real Madrid, be ready. Real Madrid, be ready because now I'm coming with more power now.