Calling winds echo across the snow-covered reaches of the wild northwest. The Quaker Road Company, makers of Quaker Pop Wheat and Quaker Pop Rice, the delicious cereal shot from guns. In cooperation with the Mutual Broadcasting System, presents by special recording, Sergeant Preston of the Yukon. It's Yukon King, swift as his strongest lead dog of the northwest, breaking his trail for Sergeant Preston of the northwest, out at the link in his relentless pursuit of lawbreakers. On your knees! So, gold is covered in the Yukon, a stampede to the Klondike in the wild race for riches. Back to the days of the Gold Rush and the adventures of Sergeant Preston and his wondered-of Yukon King as they reap the challenge of the Yukon. Do you believe in people? Do you believe that a man living in a mud hut in some dark far-off corner of the world is still a man for all of that? If you do, this message is for you. It's the story of that man and his neighbors in a primitive village in the Orient, the Middle East, Africa, South America. There are thousands of such villages all seeking something better than they have had before. Enough food to go around, a clean well, a school for the children. These are the freedom villages of our world today, and they're coming into the 20th century primarily by their own bootstraps. They need just a little help. A contribution in any amount will help swell the fund, and village by village, the free world will be strengthened. Send your contribution today to Freedom Village Care, New York 16, to any local care office. This message is brought to you as a public service. Sergeant Preston and little Terry Wiggins were seated before a blazing campfire. They were just finishing their midday meals. Terry, an orphan, was on his way to live with an uncle who ran a general store in the town of Caribou Bend. Golly, but that was a good meal, Sergeant Preston. Glad you enjoyed it, Terry.   Food always tastes good on the open trail. How much farther is it to Caribou Bend? Oh, sure, I've learned about two more hours. You know my uncle Omar very well. Well, he well only runs a general store in Caribou Bend. Haven't you ever seen him before? No, sir, I've never seen him. I don't think he'll be very pleased to see me. What makes you say that? There was a lot of songs as though he didn't like the idea of me coming to live with him. But after mother and dad died, he was the only relative I had. But I suppose he couldn't very well refuse. Omar isn't a very friendly person. He has the reputation of being stingy. But don't be put off by his manners. Underneath it only has a good heart. I'm sure he'll take good care of you. You're supposed to let me keep sparking? It's hard to say, Terry. Doesn't he know you have it on? No, sir. I didn't let him know about sparking. So, sir, he'd make me get rid of him before I can. I thought if I just brought him along, Uncle Omar might like me to see them. Well, that's all for the best. In the meantime, we'd better be heading the trail. Omar Wiggins was an elderly, dried-up-looking man with a long, sharp nose and a fringe of gray hair encircling his bald dome. He was standing behind the counter, working on a customer. Sergeant Preston and Terry entered the store. All right, Mr. Here's your copy. Now, what else do you want? You better give me a pack of flowers who are ready. Well, well, it's Sergeant Preston. Hello, Omar. I thought it was Matthew. You know, I see. I see. So you're my Matthew Terry, eh? Yes, sir. You're not quite so big as I expected. I was counting on you to help me out with some of the hard work around the store. I'll be glad to help out, Uncle Omar. Don't worry, I'll see to it that you earn your keep, all right. Hey, what incarnation is that big black-and-white dog doing in here? I don't mind King being in the store, but get that other man out of here. For now, come on. Wait a minute. I belong to you. Yes, sir. You've been a sparky. Bye.  I suppose I should have let you know beforehand. If you had, you'd have saved yourself the trouble of bringing him all the way up here. Because I'll tell you right now, you're not going to keep him. But Uncle Omar, sparky is a good dog.  I don't like the cutters I never did. He's a well-mannered dog, Omar. I can vouch for that. He's powerfully built. He'd make you a fine watchdog. Yeah. He's big enough. That's what you mean? From the looks of him, he'd eat me out of house and home in time of a week. Sparky doesn't eat much. Honesty doesn't. At least give him a chance, Omar. That means a lot to Terry. Oh, no, no.  I might let him stay on for a few days till the boy gets settled. But after that, the dog will have to go. If you don't mind my button then, how about selling the rest of my order? What? Oh, yes. Yes, sir. I forgot about you. What else do I get you wanted? A sack of flowers. I'll get it for you right away.  I'll go with you, Sergeant. Oh, that's nice. I think I'm going to like you here very well. Always hard at first, Terry, moving into strange surroundings, but you'll get used to things after a while. Remember what I said about not being foot off while your uncle's running? I don't know what I'll do if he makes me get rid of Sparky. You'll have to have some changes, my son. Are you going to be like back to Dr. City? No, I have to go to Forty Mile, but I'll be back this way tomorrow. Stop getting there and see you. In the meantime, keep your chin up. The customer whom Omar had been waiting on was a tough-looking sourdough named Ben Hooper. After leaving the store, he put the supplies on his sled and went to a small cabin, which was located a short distance north of town. Ho! Ho! Ho! There, a man named Moose Farrell looked up as he entered the cabin. Well, if you don't surprise me, then... Yeah, I got him all right. I also got some bad news for you. What do you mean? The old guy's nephew has come to town to live with him. Young kid, about nine or ten. No, he brought him in while I was there. Well, what about it? The kid's got a dog. A dog? Yeah. He's got a big ring, he must, with a powerful set of choppers, too. Hey, that's not so good. Dog, all right, it's not so good. From the looks of him, as we try robbing the store tomorrow night, he's going to raise the roof. Holy mackerel, that happens. We'll have the whole town on us before we can make a getaway. Well, I know it. It's one thing in our favor, though. Old man Wheaton's don't like dogs. He told the kid that he could keep the dog for a couple of days, and then he'd have to get rid of them. Yeah, maybe well, maybe warm. We'll wait for that to happen. We may be twiddling our thumbs from now until next spring. Maybe we could hurry it up. Oh. But suppose we offered to buy them for a sled dog. You know what a miser the old guy is. Probably jump a chance to sell them if we offered a decent price. Yeah, that's an idea. Okay, we'll go into town tomorrow morning and buy the dog. We'll continue our adventure in just a moment. Today, July 1st, Canada, our good neighbor to the north, land strong alive, celebrates her 88th birthday. This is equal to our July 4th. And we send her our most hearty and sincere congratulations. Say, kids, which would you rather do? Read about your favorite baseball team in the papers. Or see a game on the screen. Or be right in the ballpark.  No, I'm not yelling. Nothing beats the fun in a ballpark. Come out to the game now as guests of a major or minor league team. Walk right through the gate without paying a cent. If you're 12 years or younger and bring mom or dad or another paying adult, you can now get a free baseball ticket right inside a package of Quaker Pop Wheat, or Quaker Pop Rice, or Muffet Shredded Wheat. Or buy Quaker Paco 10 and get two free baseball tickets. Names of teams and dates are on every ticket. Get in on the fun. Right away, get a free baseball ticket package Quaker Pop Wheat or Rice, Muffet Shredded Wheat, or Quaker Paco 10. If your store doesn't have the special packages yet, just send the box top from the regular packages of the same series. Send to baseball box 5205, Chicago 77, Illinois. To continue, the next day, Terry was busy dusting the shelves of the general store when Sparky, in the act of chasing a spider, accidentally knocked over a stack of canned food. Sparky, watch out! That comes the elephant down now. I'm sorry, Uncle Walmart, Sparky didn't mean to knock them over. I'll pick them all up right away. All right, Thunder, that's the last straw. First, he helps himself to a slab of smoked meat, and now he starts knocking my store down. That muck will have to go. Please, Uncle Walmart, give him another chance. Never mind, I'll do it right now. I've got to wait on these two customers. Yes, sir James, what can I do for you? Oh, you're the seller who was in here yesterday. Did you forget something on your order? No, but I remembered you saying that you might want to get rid of the dogs over there. You bet your boots I want to get rid of him. Well, sir, so happens that my partner and me need another dog for our team. We're pulling up stakes today, heading south. We might be willing to take the dog off your hand. And mister, you came along just at the right time. Bring the dog over here and let him look at him. I will, right away. Bring the dog over here, will you, Terry? No, no, please, Uncle Walmart! Bring that dog over here. Don't give any more of your back off. Come on, Sparky. Well, he looks healthy enough. Good size, too. I reckon we could use him as a wheeler. How's that, you what? We'll give you 75 bucks for it. Mister, you've just made yourself a deal. No, please, please, don't sell him. You have no right to sell him. Sparky's my pal. I bet him ever says he was a pot. I understand, there boy. If you don't hush up that nonsense, I will take my belt to you. Money in your pocket is better than a dog any day of the week. You'll find that out if you grow older. All right, here's your hundred bucks. Thanks, Mr. Duncan. He's all yours.  Looks like he's gonna act stubborn. Don't worry, we'll handle him. I'll tie this rope to his collar and we'll drag him out if necessary. No, no, I won't let you take Sparky away. I won't let you...  Hear what I'm telling you? Yes, sir. Yeah, that's better now.  Yes, sir. Go on. Go on, Sparky will help. Sparky was worried. He couldn't understand what was happening. He started after Terry, but a hand gripped his collar. Surely, pooch. Sparky gave an impatient growl and tried to pull free from his training hand. But Moose only jumped harder on his collar. Oh, you don't. All right, quick, then.  Right. But Sparky saw the bag descending over his head. He gave a smile of rage. But it was too late. He was trapped. Hold him, Moose! Don't worry, I got him. A few moments later, Moose had fastened the rope to Sparky's collar. Do you think it's a place to take off the bag now? Nothing's going. These two dogs are mad at each other. But a little later, we get back to the camera. Yeah, I reckon you're right. But in the meantime, I'll stuff the bag inside his collar. So, come on. Press, you won't read much. Now get moving. You're coming along with us!  As he entered the store, he found Terry huddled by the stove. His eyes red from sobbing. Omar was in the back room. Why, Terry, what's the matter? Uncle Omar told Sparky. He took him away. I'm sorry to hear that, Terry. I wish there was something I could do. There's nothing anyone can do. Perhaps your uncle will let you buy him back later on. I'll be glad to chip in on the price and sell all the console. It's no use. The men who bought him are leaving town. They're taking Sparky with them.  King Senterpries is with you. And so do I. Crying won't do any good. Every one of these days, I'll find you a puppy that you'll like just as well as Sparky. I don't want a puppy. I want Sparky. I'll never find another dog like him. And now I'll never see him again. It was nearing midnight when Ben Hooper and Moose Farrell prepared to leave their cabin and head for town to rob the general store. You got the teammates up, Moose? Yeah, they're all set. How about you? You get it here together. It's all packed up ready to load on the sled. How's that mutt we bought from old man Wiggins making out here? Don't worry about him. Now you got him tied up back in the cabin with a good stock rope. Who bad he's ordering?  Well, yeah, you got no time to break him in. It slows you up on the trail. Yeah, I suppose you're right. Okay, let's load this gear on the sled and get moving. A short time later, the two crooks arrived in town and halted their team in front of the general store. The rain street was dark and deserted, except where two lighted cafes located some distance away. Come in, Dan, and tie it on your face. All right. All set?  Now let's hope you'll open up for us. Don't worry. The old buzzard will open up any time of the night if it means a chance to make a fail. The repeated knocking may finally hurt Omar Wiggins approaching from inside the store. All right, all right, that's on. You don't have to bust down the door. What's the carnation you want out there? How about selling me some coal oil? Clamping that door, I'll let you have it. Very well. What do you want? Hand that lamp you're holding over to my part. Sure, sure. Here, take it, Mr. Get your hands up and start backing inside. Put the lamp down on the counter and go get the kid moosh. He's probably sleeping in the back room. All right. What are you going to do to it? Make you open up that safe. No, I won't do it. I don't keep money in there anyway. You'll open it all right. You better make it snappy before I start squeezing this trigger. Sparky have been chewing planically the ropes that held him ever since the two cooks had left the cabin. The rope was thick. Sparky's powerful fangs were more than equal to the job of gnawing through him. Finally, all but a few strands had been severed. Sparky stopped gnawing and strained against the rope by lunging repeatedly. Suddenly, the last strands parted. And with a joyous spark, the big dog laid himself through the night to return to his beloved young master.   I hope he doesn't strike our man out. Wouldn't you like to go to a real major or minor league game with your dad or mom? Well, come out to the ballpark now as guest of a major or minor league team. Admission is absolutely free if you're 12 years or younger and bring a paying adult. And your free baseball ticket is as close as your grocery store. It's right inside packages of Quaker Pop Wheat, Quaker Pop Rice, Muffet Shredded Wheat, and two tickets inside Quaker Paco 10. The tickets tell the name of the teams and dates of the game. So rush over to your store. Get a free baseball ticket package of Quaker Pop Wheat or Rice, Muffet Shredded Wheat, or Quaker Paco 10. Now, if these special packages are not yet in your store, just do this. Send a box top from the regular packages of these Quaker series to baseball box 5205 Chicago 77, Illinois. Go now, free. To continue, 20 minutes later, after cleaning out the safe, the two crooks had just finished tying and gagging Omar and Terry. You said we'll hold them. All right. Put out the lamp. Let's clear out of here. All right. If they opened the door, a snarling mass of puries playing out. But it was the movement. It was me. Hockey lay stunned by the brutal blows of the crooks' heavy six-shooter. And then gradually, he began to regain consciousness. The room was pitch dark, but his nostrils caught the scent of his young master. Getting up off the floor, he trotted over to the spot where Terry was lying bound and gagged.  Terry couldn't talk and tell the dog what to do. So instead, he rolled over and held out his wrist, which had been tied in back of him. For a few moments, Spocky was puzzled. And then finally, he realized what his master expected of him. With an eager growl, he began gnawing at the ropes around Terry's wrist. Sergeant Preston was spending the night at the cabin of Constable Dave Manley with the intention of starting back to Dawson the next morning. The two men were awakened by the noise of someone pounding at the door. We were in blazes and knocking at this time of night. I'll go see who it is, Dave. Okay. Now light the lamp. All right. Spocky, come on in. What's wrong, son? My uncle's fur was just globbed. Two men did it. The men who brought Spocky, they tied herself. He got away with all the gold, the money, and my uncle's fate. When did that happen? It was less than an hour ago. How'd you get loose, son? My dog came back just when they were making their getaway. One of the men knocked him out with a gun. But after he came to, he gnawed through the ropes on my wrist. What about your uncle? They had him knotted up so tight I couldn't untie the rope. So he told me to run and get you without wasting any more time. Come on, Dave. Get dressed and get over there as soon as possible. Back to him. When the two bodies arrived at the store, they found Omar Wiggins highly wrought up and nearly incoherent as he bewailed the loss of his money. After freeing him and calming him down, they questioned him for further details. As the robbers were wearing bandanas over their faces, what makes you so sure they were the men who bought Spocky? Well, I tell you, I recognize their voices. It's not only that. When Spocky jumped at them, one of them shouted, it's the kid's dog. The other said, he must have gotten loose. But you don't know what their names are or where they were. No, no, no. I've already chosen that. I've seen them around town a lot of times, but I never did know who they were. I suppose they've cleared up by now anyway. Knowing the dog gave away their identities. When they brought Spocky this morning, they said they were planning to leave town. Wait a minute. What's this piece of material lying on the floor? Spocky ripped that over one of the robbers' parkers. He had them by the arm. Oh, good work, Spocky. This might be the means of catching those two men. There it is. What do you mean, Spocky? I think this will give King of Sandy. Here, boy. What's this? You mean King will be able to try a little from that? I hope so. Bye. Send the rice.  How about it, King? Oh! That's the answer. Send it, all right. Come on, Dave. Let's see which way they headed. Right, Captain. Must they head it north? That's probably going to make it to the border. All right, Dave. Let's get our teams and start after them. Right, Captain. The two crooks traveled hard throughout the night. But as dawn began to pale the sky, they decided they would be safe to halt for several hours left. The spot they chose for making camp was located at the crest of a sharp rise, which commanded a good view of the trail they had just covered. They had just unhits the team, and then he's spreading out their bedrolls, and they heard the sound of approaching dog-team. Someone's coming. There you go. It is the same as you there. Let's take a look. See if we can make them out. There's two of them. After that, come and breeze with them. I know. For several moments the two men stared intently, trying to make out the nature of the two approaching travelers through the dim morning light. Suddenly they'd been exclaimed in alarm.  They must be coming after us. I'm finishing up the team. I'll drop down behind this boulder and hold them off with my right hook, or you're ready to go. All right. A few minutes later, the Mounties came within range. They were greeted by a shot from the top of the rise. Dave, Dave, Dave! The four teams to opposite sides of the trail, the two Mounties quickly took cover behind trees and began to return the fire. They'll never take them this way, Dave. What else can we do? We go charging up the trail. Let's follow it with a rifle of topic for sure.  What about you? I'm going to try to work my way up the slope among the trees and close in on them. Come on, King! Oh! Starting swiftly from point to point among the shadowy trees and underbrush, the sergeant quickly worked his way to the top of the rise. But as he closed in on the crooks, he realized that he would have to move more cautiously. Moose had just finished harnessing the teeth when he heard the rustle of underbrush and caught sight of sergeant Preston about 20 yards away. There he is! Get him! The sergeant fired first and Moose dropped to the ground, then swung around in panic. The bolder couldn't protect him now that he had been outflanked. He started from the nearest tree. But his attention was focused in the direction of the sergeant and he didn't realize that King was coming toward him through the underbrush from a different direction. When he did realize this day, he sure it was too late. The great dog shunned. In the yellow fight, he went down under King's attack, stopping his rifle as he did so. Don't get this dog away from me! Scold him off! I didn't know a boy like you could run. The moment later, the sergeant had picked up Moose's revolver and then came over to get Ben's rifle. Oh, my King, I have him.   You'll be a dead man by now. I still don't know.  You and your partner are under arrest in the name of the crown. After handcuffing Ben Hooper and attending to Moose Farrell's wounds, the two Motties started back to caribou Ben with their prisoners. Early that afternoon, the sergeant walked into Omar Wiggins' general store. The sergeant's back and he's from back. Five thunder so he has. Did you catch those crooks, sergeant? Did you get my money back? Yes, Omar. The crooks are in custody and your money and your gold are right here. Well, well... Better count it. Make sure it's all there. I sure do thank you, sergeant. If those crooks had gotten away, I'd have been ruined. No need to thank me. No need to thank me, Omar. But I'd say that Sparky deserves a great deal of gratitude. He set Tommy free and enabled him to notify us of the robbery. He ripped the piece off one crook's parka and that gave King the scent. Without that, we never would have been able to track them down. I realize all that, sergeant. I was a fool to ever sell Sparky in the first place. If I hadn't done that, those crooks probably never would have tried to rob me. They're right about that, Omar. I said so themselves. Then may I keep Sparky, Uncle Omar?  Why, Dad read it, Terry. You and Sparky rescued me from those crooks and saved my whole fortune. From now on, you're going to be my right-hand man. And if you need Sparky as a helper, you will have him. Oh, boy. Did you hear that, Sparky? You're gonna stay with him. You're her king. Well, thing, old boy, now that Terry has Sparky back, I'd say this case is closed. We'll return in just a moment about our next exciting adventure. The Adventures of Rin Tin Tin presented on mutual every Sunday over most of these stations is a listening treat especially designed for the whole family. Several generations have thrilled to the heroic exploits of Rin Tin Tin, the dog that's almost human. And now you can hear his further adventures every Sunday. The new series of Rin Tins' adventures are laid in the colorful and legend-filled era of the pioneer West. His young master is Corporal Rusty, who lives at Fort Apache. During the troublesome post-Civil War era, the Army cavalry finds plenty of action in keeping under control the renegade Indians who set fire to the early settlers' cabins. And as members of the Fort Apache cavalry unit, Corporal Rusty and Rin Tin Tin are engaged in many stirring escapades. Make sure your family enjoys the pleasurable listening on The Adventures of Rin Tin Tin presented by mutual every Sunday at the cost of these stations. Sergeant Preston. I'm personally reporting, sir. Sergeant, Bald Rock is out of your territory. But I wish you'd go there and investigate a mystery. Glad to, Inspector. Several people have come into Dawson from Bald Rock to sell their most treasured possessions. There must be some reason why they're so desperately in need of money. I want to know that reason. I'll start immediately, sir. Come on, King. Only some impelling force could make the people of Bald Rock lose their homes. Sergeant Preston may have to meet and fight that force. It could well be a battle to the death. Be sure to hear this exciting adventure, Monday. These Sergeant Preston of the Yukon Adventures are brought to you every Monday through Friday at this time by the Quaker Roads Company, makers of Quaker Pop Week and Quaker Pop Rice, the delicious cereal shot from guns. In cooperation with the Mutual Broadcasting System. They are a copyrighted feature of Sergeant Preston of the Yukon Incorporated, created by George W. Trendle, produced by Trendle Campbell Mule Incorporated and directed by Fred Flower Day. The part of Sergeant Preston is played by Paul Sutton. This is J. Michael wishing you goodbye, good luck and good health from Quaker Pop Week and Quaker Pop Rice. So long. This is Mutual, Radio Network for All America.


Okay, well thanks very much, Adam, and thanks to the organizers for the opportunity to be here today and speak with you. The topic that I was given was discovering variants conferring risk for common diseases. Certainly a central goal of genomics is to understand the genetic basis of human disease and use this knowledge to improve human health. I'd like to argue that serious advance toward this goal is a reasonable aim for the next five years. Common diseases obviously are important. Rod McInnes will be talking about these. They're of great importance in their own right, can be immensely instructive to understand the genetic basis of common diseases, and in a real sense Mendelian and Common are just two ends of a continuum. But my charge is to talk about common diseases, and it's certainly fair to say that common diseases are responsible for the large majority of human morbidity and mortality. I think now is also a good time to be talking about planning because we have substantial experience at this point with common variant GWAS, and with the results of large scale sequencing studies beginning to emerge we have some information for rare variant GWAS. So the questions posed to me by the organizers were, what are the big problems that can be solved? What will it take to solve these problems comprehensively? And what will happen if the NHGRI decides not to pursue this area? So what are the big problems that can be solved? This is really a proxy. This is a list of the 10 most common causes of death worldwide, and it's certainly not to imply that these are the diseases we should focus on or that we should do 10. And I absolutely would not favor road injury as one of the diseases on which to focus. But this is really to emphasize that there is a broad range of human, common, complex disease, really all of which deserve and in truth demand our attention. So what will it take to do this comprehensively? Well we really need to explore the full allelic spectrum of human variation, the frequency spectrum of human variation for all common human diseases to provide better understanding of human biology and disease ideology, to set targets for therapies and to allow better targeting of therapies and in some cases at least to improve risk prediction. It's easy to think about where we are right now and to forget where we've been. It's really quite interesting, quite amazing for someone who's been doing common diseases for a long time to think how far we've come in the last little bit of time. In 2006, the number of successes we've had in terms of identifying genetic variants associated with common diseases was remarkably few. This slide, a very exciting slide back in 2007 from my good friend David Altschuler is now a little quaint in the sense that we've come so much further and even this slide is a year and a half out of date but we're at the point now of having identified thousands of associations for hundreds of different diseases and traits. However, in terms of exploring the full allelic frequency spectrum, we've really only made a start and there's much more to be done in discovery genomics and then taking that information from discovery genomics further. Common variants explain only a portion of disease heritability. In terms of explained heritability, it tends to be quite small in terms of what we imagine it to be based on the data we have so far, typically of the order of 50% or less. And this talk is not meant to be about a charge for explaining the human heritability of disease but only to point out that with this information it's clear that other variants, less common and rare variants, also were important. Not a surprise but certainly clear. Low frequency and rare variants can help us understand many of these loci we've already identified through common variant association and GWAS and also help us to understand the impact of the remainder of the genome on human health and disease. The extent and effect size distribution of these less common variants is now beginning to be revealed, only beginning. But these certainly have the potential to suggest function to lead more directly to drugable targets and to clinical action. And so exploring this range of the allele frequency spectrum clearly is important. Okay, I'll be the next one to put up the slide. I actually have a point to make with it beyond just doing it for old time's sake. Certainly one of the reasons why we can talk about the kinds of studies we're talking about is this remarkable drop in sequencing costs. One of the things that's been a little sobering though is for the last few years this has been largely flat. I mean that's not flat because that is on a log scale, so there has been some decline and I think that last little blip up is probably just noise. But what is clear is with new technology coming along with these X-10 machines and I hope others as well, that curve is going to start going down again and how quickly it goes down and how much it goes down is actually quite important to us in terms of what is feasible. If we could encourage competition so there was more than one key vendor, that would be a good thing. So it's always worthwhile to think about what we've learned so far and as I say sort of 20 years of doing common human disease the key lesson from my perspective is sample size as in real estate it's location, location and location are the three most important things in real estate. Well sample size and sample size and sample size are really important when it comes to complex diseases. That's not to say you should do a terribly designed big study but that sample size is really important. As an example and I should say most of my examples for the talk are drawn from type 2 diabetes which reflects what I do a certain amount of parochialism and not wanting to spend too much time developing a talk. But here's an example from type 2 diabetes in terms of what we've done with GWAS. When about five of us were getting started on the first GWAS for type 2 diabetes our own fusion study that I lead had a GWAS with about 1200 cases, about 1200 controls. We then followed up in similar numbers some of the most interesting findings and if that had been the end of our study design we would have found exactly one locus for type 2 diabetes and in fact one that was well known. We had a little more foresight than that and already even before we got these data we had agreed our fusion group with David Alt Shuler's group with Mark McCarthy's group to combine primary data right from the start. A couple of years later we had a joint publication with our three studies now with 4,500 cases, 4,500 controls and follow up into more where we identified 17 total genome-wide significant loci. By adding more studies in 2010 we were up to 31 by adding more studies in 2012, 49 and at this point we're close to 100. That reflects at some level better methods, better technology and those were important advances but sample size was really important in making this happen and this is not in any way unique to type 2 diabetes. This is more generally true for over a lot of different disease and traits and one of the advantages of getting to larger numbers is more possible targets but also having more findings allows you to look for patterns and pathways that might be relevant. Okay so if a key lesson is sample size I just want to re-emphasize technology, analysis tools are also crucial in our case having informative low-cost genotyping arrays was incredibly important and genotype imputation made it possible to combine data across multiple studies when different arrays were used. At least as important to talk about and to be thinking about in terms of its implications for going forward is collaboration echoing something that Eric and Adam were talking about the importance of consortial efforts. Well that's certainly been true as we've been dealing with common diseases in the context of common variant GWAS. It's every bit and even more true as we're dealing with rare variants collaboration to allow joint and meta-analysis across multiple studies. It's worth thinking about what the implications of sample size are as we go to less common and rare variants because if you think about it the sample size required to detect association at some specific level of power if you keep everything else the same sample size increases with one over the minor allele frequency. So if we're going from something with a 30% allele frequency to 3 tenths of a percent as the allele frequency everything else being same requires a hundred times larger sample. Now what we hope is balancing that will be the possibility at least of somewhat larger effect sizes. With that we have a scaling in the opposite direction. A lot of our common variant findings have been with odds ratios of 1.2 or 1.1 or even less. If you go from 1.2 on the odds ratio scale to 3 you get a 36-fold advantage in the other direction. So some compensation. All right. So beyond sample size studies design matters as well. Most typically we talk about cohort studies in case control studies. Both of these have significant advantages depending on the trait and the question and in fact they're not even mutually exclusive. Case control studies are more powerful in general for genetic discovery for diseases and since we're not doing too many overpowered studies in this field thinking about what is most powerful is important. At the same time cohorts can be useful for estimating effect size, population impact. They can be particularly useful for discovery genomics for quantitative traits and also for very common diseases like type 2 diabetes where you can have substantial fraction of individuals who might be affected with particular disease for obesity as well. Cohorts are also useful for selecting extremes for quantitative traits and you can think of sort of extremes as being cases and controls when you're dealing with a dichotomous trait like disease. Beyond the general strategies there's the issue of sort of general preferences whatever study design you choose. I'd name three. I think deep phenotyping is extremely important. The more phenotyping information you have on the people you're going to sequence or do genetic studies on the better both to help us interpret associations for your primary trait of interest and also have more traits for which we might identify interesting associations. Also important particularly when we're spending large amounts of money on sequencing is broad consent to allow us to maximize the value of the samples we sequence not just for the primary purpose that we're undertaking but to make those data more generally useful. And something that becomes particularly important now is we're looking at the impact of rare variants is call back based on genotyping. So if we have samples that are appropriately consented and conveniently available in terms of the people for bringing people back in for more extensive phenotyping or to bring in their family members because if we're dealing with variants that are rare enough the only real way to get a decent number of people carrying those rare variances is by looking at their family members. Okay careful study design and analysis can weight the dice towards increased power. There's no silver bullet. There's not one thing you can say that's always going to make things better because there are different questions and there are different genetic architectures different situations but we can do a variety of things that can help. One of these is to assay multiple populations. We can do this for a variety of reasons most important at least one of the most important is that variants that are rare in some populations may be more common or even quite common in other populations. An example of that is variant in TBC1D4 and type 2 diabetes in Greenland where something that was quite uncommon was very common in the Greenland population. And then in our own T2D gene study where we sequence 13,000 individuals actually between T2D genes and go T2D two studies of the genetics of type 2 diabetes. We sequenced 5,000 Europeans, 2,000 East Asians, 2,000 South Asians, 2,000 African Americans and 2,000 Hispanics and we found that there is a variant in PAX4, R192H that was specifically associated with type 2 diabetes in East Asians. Frequency of about 8% in our 1,000 Koreans, about 13% in our Singapore Chinese meta-analysis of those two groups gave clear evidence for an association between that variant and type 2 diabetes. Interestingly enough, if we hadn't studied East Asians we wouldn't have found this at all because in the other roughly 10,000, almost 11,000 individuals that we included in our exome sequencing project there were only three copies present. I talked before about Greenland, well that's a special population founder effect likely. Here these are just large cosmopolitan populations and still quite different frequencies for these variants. Another thing we can do and must do is to group variants within functional units. In the example I'll use here is one that comes from Jason Flanek in David Altschuler's lab. This is looking at type 2 diabetes in SLC388. SLC388 was one of the original GWAS findings we had for type 2 diabetes, a common variant for SLC388. Altschuler's group decided let's take some individuals from Finland and Sweden, let's look at different regions that we have identified as being associated with type 2 diabetes, look at genes within those regions and look to see if we can find loss of function variants that might be of interest to us. When they did that they identified a nonsense variant in SLC388 that they then subsequently genotyped in a substantial number of individuals, 50,000, 54,000 Europeans, had some really interesting results but not in any way genome-wide significant, looked up the gene SLC388 in Iceland, looked it up in our T2D genes and go T2D sets to find other variants in that gene because there weren't that particular variant was not particularly common in those groups, identified other variants, other loss of function variants within that same gene, putting all of this information together ended up with an impressive p-value of 2 times 10 to the minus 6, a three-fold protection against type 2 diabetes, a potentially attractive drug target. Now to get there, that took the analysis of 12 different variants and 150,000 individuals across 22 studies. Really interesting result demonstrates the importance of being able to combine data across multiple variants to effectively increase allele frequency across multiple studies to increase sample size, enabled by analysis of data in multiple ancestries, but what a job. Jason Flanik's a really good guy and worked really hard, took a lot of time to put this together. It would be really great if data like this were in one place in an readily usable form. And so that brings me to my next point of the importance of data aggregation. I would claim that rapid data sharing, well, after the human genome sequence, is the most important legacy of the human genome project. I think that we want to do more than just deposit data as important as that is. And so aggregating data to maximize its utility, making it interoperable, harmonized, enabling more powerful and much more efficient, efficient in the sense of just being able to do it, science and inference. If we have broad consent, we can take this beyond just the realm of one particular disease area and do it more generally. And if we're wanting to go to the next step, we can take this information that we bring together and operate on in such a way that not just specialists but others can take advantage of the data being there to query the data, either with standard queries or queries from individuals, to allow us to provide results and information to a much broader audience than just the folks who are sitting here. Next question is, how large a sample is required? Well, large samples are required. Actual numbers are going to differ based on genetic architecture, which is largely unknown, not entirely. Lander's group, Zucadol and a PNAS paper earlier this year, went through a lot of interesting modeling to suggest the 25,000 cases and 25,000 controls per disease. If you're doing exome analysis as a reasonable starting point, we can argue about individual assumptions here and there, but certainly a reasonable starting point. Obvious question is, are these kinds of large samples available? And we have a happy fact of we're starting in a situation where a lot of GWAS has happened. And so this slide is courtesy of Eric Lander, bringing together across 18 different diseases. I guess this was in February, Eric said. Different numbers of genome-wide association study cases for cardiometabolic, cancer, psychiatric, neurologic and autoimmune diseases. So not all of those reach 25,000 cases, but a lot of them there are there or beyond. And particularly if one were to say, we want to do an effort where we're going to focus on a number of diseases with this kind of numbers. Some communities might be ready and some would have the impetus to do more to bring larger numbers together. So which diseases? I claim we ought to focus on some first, develop our strategies, develop our methods, cut our teeth, make our mistakes, and come to more clear choices in terms of how we want to go forward. Given many common diseases, I think we should be opportunistic and take advantage of diseases that have advantages already. In particular, diseases where we have large numbers of well phenotype, broadly consented, callback eligible samples. Situations where we have investigator groups that are well-organized, collegial and have a clear and strong record of data sharing. And ideally, and actually importantly, in speaking to something Eric said earlier, significant financial support from a categorical institute or some other funder. And there's no perfect predictors of success, but one of the predictors I think of success for choosing a disease, choosing a group, is to look at the success of the relevant GWAS consortium. How well did those groups work together? OK. We have some key strategic issues or choices. There's the issue of NHGRI versus the Categorical Institute, large centers versus distributed capacity, common versus Mendelian diseases, discovery versus translation, exome versus genomes. I don't like any of those. I think those are all false dichotomies. I don't think we can afford to deal with them as dichotomies. I think we have to recognize that on all of those issues we need both. We need NHGRI and the Categorical Institutes to work together. The role of the NHGRI is to advance paradigms, to develop and evaluate and harden methods and tools. Many, most of the methods and tools for this kind of work are general, and NHGRI is an established and logical leader. NHGRI should provide scale, infrastructure, and capacity. NHGRI is really good at imagining and developing foundational resources, from the human genome project to other genomes, to HapMap, to 1,000 genomes, and the list is very long. And exactly, in fact, I should have been looking at Eric's slide. I would have left some of the stuff out. But one of the critical things here to remember is the NHGRI's budget is small, and other ICs are much bigger. Large centers and distributed capacity, we need both of these things. Large centers set our standards, develop analysis paradigms, and infrastructure, industrialized genomics, and enable large studies. Small centers allow us increased opportunity, give competition, enable broader range of studies, and we want broader range of studies. Both sorts of centers are important for training, for innovation, and for expanding capacity. And we should be expanding capacity. Discovery and translation, genetic discovery for common diseases has really only begun. And for rare variants, it's barely started. So for translation for common diseases, to my mind requires much more discovery before it's totally practical at large scale. Translation now can take advantage of what we know now from endelian diseases, in some cases for common, and prepare us for when we know more. And we can build a virtuous circle here if we take what we have from discovery and translation, sorry, from discovery, use it in translation. And then what we do in translation in terms of gathering data, hypotheses, samples, take that back to discovery and go back and forth. Exomes and genomes. Exomes are great from the perspective of cost, relatively speaking. Sample size, interpretability, but they're inherently limited. Genomes cost more now, but I would predict that the cost for genomes will be coming down faster than the cost for exomes, making that comparison less unfavorable to genomes. It's surely the direction will be going eventually. It's time, I think, for more significant investments so we can learn what we can with genomes and prepare for when we're ready to do it at a larger scale. And genomes also provide better exomes. So I almost didn't bother with this slide because I suspect I'm right at about time. But what will happen if NHGRI decides not to pursue this area? It's hard for me to imagine that NHGRI would not pursue this area. But if NHGRI does not, for science and biomedicine, it would result in a more fragmented effort that will be slower, more costly, less efficient, and result in less interoperable data. And for NHGRI to be a huge lost opportunity. And so last two slides were asked to give a set of opportunities that I guess you and is then going to go over this afternoon. And so the ones I've put down here, two slides. First, we can focus on some exemplar diseases. Now, whether we should be selecting diseases as a group or I would prefer having groups propose their disease and how we go about it and what the advantages are and how they can make that happen, I would probably favor the latter. Samples. Despite my comment and Eric's nice slide in terms of samples available from GWAS, we really want to encourage identification and aggregation of large, well phenotype broadly consented samples because we will need more. And for many of those, the samples are not ideal in terms of all of those characteristics, in particular for callback. In terms of a resource, a set of recallable sequence genomes, for example, loss of function carriers for every human genome would be a cool gene, would be a cool thing to have. Technology, we cannot do anything but continue to focus on sequencing technology and statistical and computational methods and tools. That is what we are about at this institute. Whole genome sequencing, as I said a moment ago, I think it's time to do more. For information, more active data aggregation and sharing and knowledge sharing is important. Discovery and translation of virtual circle, if we take advantage. And the last three I really haven't spoken of, but functional characterization of variants right now is ad hoc, post hoc, slow, we need something that's more prospective and high throughput training. We need to invest more in genome science. I think it's great that we're investing in more training for translation, but more for genome science, statistical, computational science. This is really inexpensive investment, but a very important investment. And then because every speaker is allowed to put one thing at the end of a talk that they like, until genome sequencing becomes incredibly cheap, genotyping huge numbers of samples for genotyping arrays I think is a really good idea, not necessarily for this initiative or this institute, but something we shouldn't lose focus on, that there's a lot to be gained by doing that. And I think I will end there. I will thank the many people who gave me comments in preparation for this talk and look forward to hearing a discussion. Thank you. Thanks, Mike. I think we have time for about three questions, four questions. Yes, this is actually a technical question. On the issue of sample size, you made, brought up the point of 25,000 cases, 25,000 controls. And I think I saw that that was for exome sequencing. If you went ahead and thought about it for whole genome sequencing, do you need more? How does that affect it? So you do need more. And the Zook et al paper did a nice job of looking at that. And so you can view the genomes initially as your opportunity to do the exomes really well and think of the 25,000 and 25,000 as a good way to go and having the information to allow us to go further across the genome. But realistically, we will need more. Richard. Thanks, Mike. Can you make some high level comments, please, about family studies, very large family studies in, as we move ahead in design and different collection modes? Yeah. So, so as I mentioned briefly, family studies is one way to allow us to go for a really rare variance and find multiple people who are carrying them in a way that if we do case control or cohort, we're just not going to get very many people carrying those. Even so, you need really big families to get very many carriers. And so unless the effects are really strong, they have to be truly large families. I really believe in the importance of family studies. I mean, we still have Mendelian diseases we're working on and they're surely good there. But for rare variants, for common diseases, you really need very large families for it to work. And there was, please. So I don't want what I'm going to say to be misinterpreted. I think that NHGRI has to invest heavily in common diseases and the discovery of loci that influenced them. But I do think I'm missing and I have trouble seeing the especially midterm translation into the clinic. We wave our hands and we say drug discovery. And we all really know how hard drug discovery is and drug targets. So I guess I'm just saying this for two reasons. One is I think we have to remind ourselves that common diseases have many causes. Genetics is simply one minority cause. And we shouldn't kid ourselves about the, say, five year time horizon. And I guess the other question would be for the group as a whole is I think we need to think hard about what are the ways to translate these productively and realistically into the clinic. And the only two things, again, that we're used to hearing are drug targets and kind of this nebulous incentivizing of people who are at risk, which frankly is not much of a magic bullet. So I'm just interested in your. I'd agree with both comments. Is that time for one more? Hi, thanks. Carol Bult, Jackson Lab. So your comment about data aggregation and interoperability really resonated with me. And NHGRI has really also been a leader in developing sort of ontologies and semantic standards that make that possible. So I think that also needs to be part of the discussion over the next two days is how we support, what is the role of those projects that enable that kind of data integration and aggregation in an ongoing manner. No, I totally agree with that. And we're working hard on it in the context of type 2 diabetes and hoping to work on it also in the context of psychiatric disorders. I'm sorry to interrupt. I think we are going to have to move on to the next speaker. But please reserve some of those questions for the discussion following lunch.


Huntsman and Huntresses, the best and brightest warriors of remnant, ranking higher than kingdom police and even military in terms of strength and skill. The occupation was established alongside the Huntsman Academies after the Great War, with the hope of creating elite warriors whose sole purpose would be to combat the creatures of Grimm. The Beacon Academy was founded in Vale, Haven founded in Mistral, Shade founded in Vacuo, and Atlas founded in the now defunct Kingdom of Mantle. These institutions accepted graduates of primary combat schools who showed enough promise and tenacity to not only battle the world's deadliest creatures, but also protect their fellow man. For this reason, trainees are grouped into teams ensuring the continual development of communication, empathy and teamwork, traits that are vital to any guardian of peace. As an additional precaution to maintaining peace, the founders of the academies believe that their graduates should be kept separate from kingdom allegiance. Once finished with their training, Huntsman and Huntresses are free to choose who they work for as well as what kind of work they will do through the use of mission boards, allying with a particular kingdom or villages entirely up to the individual. However, Atlas Academy has come under increasing amount of scrutiny for the indoctrination of military lifestyle upon its students, pressuring them to enlist in the Atlas military's special operatives unit. Every academy has its own methods of teaching, but the end result is the same, Huntsman and Huntresses ready to make their own paths. Some will stay together as a team, some will move on to work alone, but all are expected to serve humanity and never succumb to the darkness.


We have all been looking for a magic pill in a bottle to sweep away those lousy waves of procrastination. Little did we know that Magic Mind has come up with a revolutionary match-up-based liquid formula that hosts the most potent tropics and adaptions to do the trick. But allow me to cut you the slack and get straight to the point. Does this notropic drink actually work? Now I've used it for an entire month and I have lots of secrets to unveil. Hello Inception Fam! My name is Greg Gostenkar, the founder of your Inception. If you're new to my channel, welcome! We talk about brain hacking and ways to boost your cognitive function in a safe and effective manner. Please like and subscribe to join our community. Today, the natropic taking away the lion might is Magic Mind. This is a match-up-based energy shot that contains lots of potent tropics. Now my first impression of this energy shot is that the packaging is so on point. It looks like a shot, it feels like a shot, and also has a fancy outlook to it. It's small, it's pocket-friendly bottle that you can carry around anywhere. But is it effective and how does it taste? As per the claims on their website, Magic Mind vouches to boost the effects of wakefulness without the jitters. It helps circulate energy for a prolonged time and also helps you time those spells of anxiety by inducing a serene state of mind. Now the adaptions help you unwind and stay calm, whereas the natropics work to sharpen your cognitive function. Much assails the deal by keeping your energy levels on the rise. Now people have come forth saying that Magic Mind helped enhance their productivity by several notches. This means you get to do more work, focus on what really matters in your life, and sideline spells of anxiety or stress.  Well I used Magic Mind for an entire month to experience its real effects. So what actually happened? First off, the taste. Now I wouldn't say it's the best, it might even be a tad bit hard to gallop for some. The rich and sharp matcha flavor boldly expresses itself on the palate. But I think it's drinkable, and don't forget this is just a shot so you can swallow it quite quickly. Now in terms of the effects, I started noticing results from day one, and they became progressively profound in the next days. I could definitely feel the natropics kicking in after 10 to 15 minutes, which is not what usually happens with capsules. Now the feeling was quite refreshing, I could feel this natropic formula doing its job. However this was like a regular shot of coffee or an energy drink. It was definitely more than that. The natropic effect was subtle, but tangible. I felt more productive, focused and more motivated. Now during my test period, there were days when I just didn't feel like waking up and getting worked on. Procrastination is very much real, and it can easily seep into anyone's life. Now on such days, Magic Mind didn't help as much as I wanted, and I will soon explain why is that. That being said, I'll advise my audience to remain grounded. The effect of Magic Mind is indeed noticeable, but it will not turn you into a Marvel superhero. This natropic drink is wholesome yet subtle. So for me personally, the effect lasted for about 2 hours. When I combined Magic Mind with a cup of coffee, I would say that the effect lasted for about 4 to 5 hours. But of course, then the price increases and you need to combine it with another drink or supplement. So is Magic Mind really worth its price as it's safe for long-term use? And can you compare this formula to my favorite natropic stack, Quality of Mind? Well, let's find out. By the way, are you searching for the best individual natropics for your needs? If yes, go for our free brain assessment, linked below, and get a personalized recommendation for the best natropics. Now Magic Mind is a mix of quite a lot of ingredients. This proprietary blend does list all the ingredients that go into the bottle, but it does not state the individual dosage of each component. So in my opinion, that's kind of a red flag, since full disclosure should be provided. Nevertheless, let's dive into the ingredients list and see which of them stand out. First, there is Matcha. The entire drink is stained bright green because of the Matcha component. This is a good substitute for caffeine and has antioxidant properties. Then, there is Lyon's main mushroom. Now, there's one natropic that took the internet by storm. It's this one. Everyone has been after it and it does deserve recognition because it truly is one of the big deadest in the natropic world. It enhances the BDNF, so the Brain Right Neurotropic Factor, and NGF, NeuroGrowth Factor, and therefore is sought as a potent cognitive stimulant. However, I'm afraid that the dosage of Lyon's main in this supplement is too low for any serious effects. Then, there is Rodiolaricea. This herb is also known as the golden root for its highly effective anti-inflammatory properties. Furthermore, a randomized controlled trial on eight depressed patients proved the efficacy of Rodiolaricea as an anxiolytic. It, therefore, clears brain fog and promotes a tranquil state of mind. Rodiolaricea is one of my favorite natropics, so I'm very happy it's in this stack. Now, let's talk about Ashwagandha, yet another hypnotropic. Now, people have been using this powerful herb for thousands of years. It is considered an adaption since it reduces stress and anxiety. Now, Ashwagandha is often referred to as the scripture of longevity because scientists have unveiled its neuroprotective effects as well. Now, some people love Ashwagandha and others hate it. I think it's a potentotropic, but not for everyone. Luckily, I think there's a relatively low dosage of Ashwagandha in this stack, since that's not really a problem. Okay, other natropics in this stack include Cyticholine, Phosphatylgelserine, Althianine, Organic Honey, Echinacea, Bacopa Monerii, and Cordyceps. Now, I'm a big fan of Cyticholine and Phosphatylgelserine. I find Althianine very potent and I think Cordyceps is great for long-term use. Bacopa Monerii is one great entropic as well, but I generally prefer to take it in the afternoon due to its potential negative effects on motivation. Now, to be honest, I see a lot of harmonious ingredients in this stack, which is a green flag for me. But I believe the dosages of those ingredients are very low, so I question its long-term efficacy. Now, for the best effects, you're supposed to take one bottle a day. Preferably along with your tea or coffee for enhanced longevity. Oh, and let me show you how Magic Mine looks like when it's shaked and when it isn't. It's quite a difference. I hope you can see it. Yeah, so definitely shake it before use. It is also recommended to religiously complete the course for at least 40 days to notice visible results. Now, the mushrooms and adeptions in this entropic drink take time to work their way in, so there is nothing wrong with that. Now, before I share my final verdict, let's talk about pros and cons of Magic Mine. By the way guys, if you like this video, please press the like button below and subscribe to my channel. So the biggest pros are it yields results within 10 to 15 minutes of usage. The results upscaled in intensity with regular usage. It is easy to carry in eco-friendly bottles. It's excellent for those looking to supplement their coffee or tea with a cognitive energy drink. It is probably a safe herbal drink, but we can't know for sure due to the lack of transparency from the brand. Now, how about the cons? It's quite expensive, so 30 bottles cost around $178, which is ridiculous in my opinion. And if you subscribe, you can get 30 bottles for around $97, which is way better. But this is still very expensive, especially if you compare it to quality on mind, which has double the amount of ingredients and those are way better dosed in my opinion. And they don't have a proprietary blend. The next con is the proprietary blend, which means that you cannot find the dosages of each individual ingredient. And this is quite a big problem for me. The next con is its taste. I think it's quite an okay taste, but I don't think everyone will like it. And the last con are its effects. I think the effects could be a bit more long lasting. Now, if you want to order Magic Mind, there's a link below. And if you use my link, you may get an even better deal. So, to my verdict, do I recommend Magic Mind? And who is it for? Well, Magic Mind is ideal for people who need a brain boost on the go. So, it's great for entrepreneurs and salespeople who have lots of meetings or for people who travel a lot. The drink is ready to use and is therefore perfect for those who have a hectic schedule. If you are someone who does not have time for meal, drink, preparation, this energy drink is for you. However, do not expect it to do unrealistic wonders for you. The effect is noticeable, but kind of a mild. So, would I repurchase it? Yes, I think so. And I will mainly use it while on the go. However, whenever I work from my office, I think Quality Mind is the better deal. And you can watch my full Quality Mind review up here. Thank you guys for watching and I hope to see you soon again. Stay well.


on everyone Sam here with late and sports guards we're up in 2022 pops triple threads baseball hobby nine box case break number 24 pick your team style going to read off a list of our names and teams a sham's royals allen c white socks andrew l athletics rockies oh and the rangers uh arcade sp with the Mets brandon s marlins chris m pirates christopher b with the cubs danney c angels darren b with the brewers eric r mariners evan m with the rays frank m dodgers gregg b reds guardians keila s redsox kevin p with the tigers kyle p with the orioles luke s cardinals nicholas h twins peter m yankees richard f diamondbacks rob l fillies rory w giants ryan m padres blue jays ryan d with the nationals steven s with the astros and steve f with the um braves so good luck here everybody les gets going on some triple threads bon what are some good basketball on tonight anything pistons pelicans yeah let's tear up the pistons we're a little bit bad pistons at kade right now it'd be a little more exciting nicks warriors yeah grizzlies nuggets that's good nicks warriors kind of lame i don't know why the nicks get prime time what yeah each year out of 199 and mike trout to 75 nice for the angels there derek jeter miguel cabrera jackie robinson there's a jazz chiseled jr that's nine out of 35 going to the marlins nice one there for the marlins and justin vertlander astros 16 out of 27 there you go sg nice jv yeah no curry either curry's out for a bit that's bad that's a that's a swing on this by the nba got shane boss the 125 chris bryant to 199 uh say asizuki a base rookie there's some base what's up keegan again there's mani machado 22 out of 27 and uh grand walkoffs nice one there for the padres and dodgers chris taylor 34 out of 50 jersey auto for the dodgers congrats la lad yes and it's a credit card information you get to some cards bulls he isn't a good game bulls is again they're seriously really interesting uh the tigers is and take a look for you right now uh kevin p kevin p has the tigers good 20 years it depends angela we have buy-ins ranging all the way from like two grand down to 20 a spot carl's career to 150 robin yon to 25 and it really it depends on the product how many usually do full cases but some we do some we don't face there's zander bogarts uh 17 out of 18 for the for the uh red sox and dylan cease 88 out of 99 for the white sox uh this is a pick your team so all the uh spots are a little bit different 299 cj abrams robin yon to 125 there's uh salvatore parez triple threads autograph rally card for the royals we'll get it right out to you mike estremski 25 out of 48 for the giants leases up in a couple months give me one too now go to um leighton sports cards dot com to uh buy into to buy into breaks leighton sports cards dot com link and buy a link in bio that's that's where you do everything do not send anything to this page it probably just won't get looked at chipper jones to 199 on the orange and honus wagner to 259 oh that's kind of nasty base base base we got a random this is a big random right here how about miguel cabrera carly estremski frank robinson wow holy cow seven out of nine this will be a random at the end of the break right here between the tigers the red sox and the oryals that's so cool man mag this one i think that's nasty that's nasty so yeah that doesn't fall i would say under a threshold of when we don't random cards we will random this at the end we got this into a mag for you guys as well good luck to all those three teams right there good luck good luck null and r and auto to 18 as well six triple right there christian yellich to 259 and corbin berns to 299 what is the connection between those three first they're not all first baseman are they estremski and uh and robinson what was robinson third am i thinking of somebody else i don't know what i i that's i was gonna ask you on that one this is spencer torkelson rookies i don't know what the connection is between those maybe they're where they're all from christian yellich to 36 that's true uh tricycle game used for the brew crew and going to yankees louise heal rookie auto 58 out of 199 top triple threads right here tops triple threads michael jordan yes he is okay you can't make that you're okay christian yellich to 50 and jose Ramirez to 299 yeah that's true greg yeah that's orals yankees and tigers let me just double check on that i don't know what the i don't know what the connection between those those three guys are they space nice one here for uh sg we've got triple astros patch bregman tucker and altuvay nice one there and going to the orals there you go kyle 29 out of 75 tray mancine tray mancine it's a ripping fire it's a ripping fire every time you're like lincoln bio people are like why are you promoting yourself you know that is the 125 a few the lines out of 199 mr brandon cooks there's uh spencer trokelson rookie Clayton kershaw and fernando tauti's nice one here sg how about the orange color match that is two out of 18 alex bregman 41 homerun homeruns 37 doubles and 119 walks there you go congrats on that game use let's go sg nice bregman and dj lemayu to 48 the inks the machine dj lemayu three even spencer i'll take that how many go dolphins are we at tonight not a ton spencer not because they blew it yesterday so i got called goldschmidt to 125 orange is bo jackson just the team on the card yeah just the team on the card greg unless it's like if it's like an unlicensed product then it'll usually it'll be a random to everybody or it'll be wherever they spent the majority of their career oh we just set you with a go purdy who said that who said that how dare you there's julio urias eight of nine 20 and three two color patch in the middle nice one they're dodgers how dare you and brandon marsh two out of 50 on the rookie jersey auto for the angels right on here what's up spencer spence spencer studies a regular around switch what's up you what's up spence donny baseball to 50 for the inks and many machado to 259 base base base going to the giants joey bart 24 out of 50 on card jersey auto what's up west virginia of rv from west virginia bobe chat for the blue jays 43 out of 48 and there he is on twitch there's spencer now on twitch that's awesome dude sand fran pretty nice that they walloped the dolphins let's say you got walloped those duffins but the truth will set you free you're surrounded by all girls everywhere true that's a good point uh chris bryant to 259 and rafael dubbers to 299 what's up main what's up a jay from main i'm gonna be up massachusetts next weekend let's hang base base there's auto Lopez that's 93 out of 99 a rookie jersey auto for the blue jays and sonny gregg to 36 for the twins game used a jay how cold is it in main we we just we sell them to customers on group breaks dude that's why we got zack from new hampshire not hampshire live free or die we'll be up there too they're jeter 259 and mariano revered at 299 base base wander franco rookie base rookie let's go dolphins and gladi jr nice one there that is uh tater trifecta 22 out of 27 for the blue jays get new england latin meetup incoming absolutely let's go south dakota ridge alex royalty from chile we've got how about delaware zack from delaware zack what's up i'm like checking in got four hands solar these dude four out of 25 that's brutal nice one therefore the marlins game used you know it's supposed to be that cold here this weekend okay now dude that texas repping california coup aj from new york sg also from new york illinois missouri sasca shawan that's pretty cool mississippi how come sasca's got your name texarkana texas what's up that's simp tulsa got eric checking in from iowa we've got tyler from tulsa got uh ryan from man as well origan mason mason checking in what's up from all the way up in origan hey it's got brandon from new york we've got wish go to Louisiana the boo boo minnesota minnesota revin carlos karat's in 99 that's from minnesota osan riley the 299 got missouri again minnesota put it on them boys this weekend they did that was an extra hit coming up here i believe we do it's gonna be randy johnson cj abrams rookie washington set and brian all the way out in uh wazoo michigan cliff don't worry christmas michigan adam jake uh cousins two out of 25 syphans cn dog in arizona what a dog arizona what up there's tyler stevensson to 48 nyc nyc's in the house and justin verlander for the astros there you go sg why wascansans in the house oh yeah it's cold as heck up there oh yeah sort of follow their gardener gardener every time i come in here man yeah i know every time i come in here tony gwin to 150 and ricky anderson to 199 not in my um not to my knowledge rv base base base there's brandon crawford for the giants 19 out of 36 depends on what you're talking about i think nice one there and also going to rory with the rory w is heliot ramos two out of 75 nice one there i don't think he signs for mlb products to be honest craig i don't i just i haven't seen it to be honest i've not seen it carl's craig deals on hold officially now oh my lord what is going on here man that wasn't a break uh talker i've got a redemption back uh backside redemption which is always good his own ill cruise to 259 for the pirates stop baseball there's uh to 299 is junk hose then crack out poland mark 2 12 a.m or 12 12 one of them yeah get one of them what the lock the door oh yeah later have a good night clayton kershaw 13 out of 27 for the dodgers to finish off is going to be going to greg there is a hunter green congrats on that on the redemption yeah we got soccer cards alex yes sir we do yes sir we do sitting right there man hunter green to 299 ohio in the house now wow virtual clonenta to 150 another redemption here space who's got this team gonna be steve f we got the triple ozzy albis ronald akunja and tripper chipper jones boom let's go baby nice one there relic combo sapphire perilla very nice we'll probably make this one right here very nice congrats on that one amsterdam netherlands netherlands in the house that's pretty cool good old holland appreciate that polar that'll be out of three nice from alaska ozzy albis to 48 from alaska who's that from alaska shon shon from alaska right there cousin yes sapphire out of three on that one that one's nasty dude absolutely nasty clements clements isn't a little bit more i think i know he's in panini stuff greg but no i have not seen a shilling in in years and i have not i've i haven't seen a bond since uh since upper deck top illegal legal uh we haven't done it yet jason we'll do the random at the end of the break before the recap you just won't be able to see it we only do it on um well you could see it if you switch over switch over to youtube or twitch exactly stream there 24 seven so we do basically yeah stan musul it's a 299 i appreciate that rv and christian yellich to 99 rv's a firefighter and paramedic watches us on his downtime thanks right on appreciate that man appreciate that beaver it was a j rod rookie uh ron lakuny thanks boston been watching for a while got on your first break what break uh boston boston it's not boston mike schmitt 12 out of 18 for the fills nice one there and luke voight that was 18 out of 99 for the padres nice one there all right last pack of the break good luck everybody origins py t nice nice nice nice good luck man thanks for jumping in appreciate that tony gwen to 99 and bo jackson for the royals to 259 what up ac ac that's true the red sox are bad don't say that says who said that who said the ac i take that back i can't tell you they are bad though it's not looking good jim tomat four years 190 homers 19 out of 27 for the fillies ah adam thought he was slick not going to get us to say that adam it's kind of funny but not gonna say that josh bell 14 out of 36 that'll do it right there i will set it i did too i saw for a second i'm not gonna do it me i don't read it first i just i know thank god you said something because i would have said it i know all day all right guys gonna do the random for this miguel cabrera carlia stremsky frank robinson numbered seven of nine one second guys touche very touche good i i you know what i appreciate the attempt on that one exactly i appreciate on that adam i would do that is pretty funny it's good that's something i would do if i'm on my burner account oh yeah very funny that is pretty good i almost said i did too you said that before i was right sox tigers royals touche all right guys let's go over to the random screen doing the random for this miguel cabrera uh carlia stremsky and frank robinson triple jersey auto seven of nine gonna roll the dice whatever team is on top after four times we'll get the card good luck guys one two three and four go into the tigers tigers picking that one up let's do a quick recap here guys good or uh not good luck but we'll do a quick recap we've got josh bell mike schmidt ozzy albis clayton kershaw brandon crawford tyler stevensson jesson berlander glad guru jr sonny gregg hulio urius that is bobeshet djelamehu uh triple for the astros christian the elix for the brewers nolyn aronato mike stremsky zander bogart jesson berlin and also a man named machado we've got jim tome filly uh luke voit padres hunter green reds heliott ramos giants jake cousins brew crew uh whore solar for the marlins that's auto lopez blue jays joey bart giants brandon march angels alex braggman for the astros trey mancini for the orioles louis heel yankies salvatore perez going to the um what's that gonna say royals uh dylan cease white socks that's chris taylor dodgers jazz chisel marlins we had the triple is miguel cabrera carlie stromsky frank robinson to nine and we had ozzy albis ronald acuña and chipper jones on the triple reduction that'll do it for the break thank you guys again for the fill next up is um uh full case tier


What's going on everyone? Sam here with late sports cards. Two boxes of 2021 Penina Mosaic football choice for Neil B. Let's go look, Neil. See what we got here, buddy. 2021 Mosaic choice, one autographed bird. Oh, he's just taking some time off for himself, quicks. Let's go jump and chat every now and then. Let's see in there. Peacock in there. It's gonna be Peyton Turner, rookie exclusive. Silver Jameson Crowder, that's Gary Brightwell, rookie Mosaic. You've got Otto, Marcus Stevenson. Nice one there. He is a Bill, Buffalo Bill. Rookie autographs, Marcus Stevenson. Got a Kenan Allen, 280. A David Johnson, 280. I appreciate that, quicks. Donald Driver, nice one there on the Peacock. That's awesome. For the Packers. And Javon Holland, that is seven of eight. Black gold, rookie for the Dolphins. Javon Holland. All right, Neil Fox too. Good luck, buddy. Let's see a teal auto. See a field's auto. See a chase auto. See all the autos. All the autos. Every single... Three autos in this. Another Peacock, very nice. Tobitrick Felton, Silver, Terrace Marshall, rookie. Deshaun Watson, auto is Dwayne Bow. Fantasy name legend, somewhere over Dwayne Bow. Fantasy team name legend, Dwayne Bow. He was actually super underrated too. Yeah. Nice one there. We've got an E.J. Brown, 280. Drew Brees, 280. Got a Peacock of Devin White, the Bucks. And Hunter Long, 78 of 88, rookie for the Dolphins. That'll do it for your box there, Neil. Thanks again for the support, as always, over here and with group breaks. Do appreciate it, my friend. Get them right out to you, buddy.