Going on everyone say I'm here with late sports cards. I've been 23 24 Bowman Chrome University Basketball hobby and delayed summer box fiction number six random team style Here is a look again at your random results As always you can find these all on the website under the results tab as well as the link in chat I'm gonna do you guess the Super Fracture 30 seconds to guess a player on the Checklist you pull a super of that player you will win $330.  Good luck. What happened there that he put his hand on it. Oh, yeah Make sense then four three two one guesses closed There you go, let's get started 76 really This is a snoozer I guess they really are funny my good Again three to go three two to go two to go Chuck F picking up Miami St. John FAU combo. Thank you buddy Michigan State, Maryland Michigan State and Maryland left That is it. That is it Michigan State and Maryland So Michigan State have four guys or has four guys on the checklist Which is a pretty solid? Very good chance of hitting something especially in a case of delight with 36 autos usually more usually it's up toward 40 When you get extras and such So definitely a good school and then Maryland's got two guys Jameer Young the in the main one and then the Sean Harris Smith is your other one So a couple of good possibilities there Go on any bebop rides As we kept saying you were going on all the city I didn't go on any bebop right don't win all the big boy, right? Sure. I did it's a small world is not a big That song is fired come on Get into it, especially when you're stuck on it. I Think Sean might lose his mind Is Katelyn Clark for Iowa I say both I'm like I'm calm Ronnie James base and Justin Edwards Jared McCain Hey, Aliyah Edwards two three fifty whoa Rassache went down Johnny broom two two fifty on the refractor auto nice one there at Auburn The angle No, right cool. Excuse me play Akavitch and Middleton a Tyrese proctor God season number 50 Paige Beckers 399 Rikia Jackson kind of see Base auto Ashton hardaway Penny Sun going to Memphis. That's on that Memphis very nice Rassache that'll be a random two all at the end We'll do a random for all the bait the non numbered cards Jadon at Akins to 99 for Michigan State one of the teams still left Zaden high Dusty Strowmer Two to go on the next one everybody Chris Johnson Michigan State and Maryland on the next one Brandon Karrison to 99 for Ohio's or Oklahoma State Hey, I'm the Mari Burnett Mookie Cook Purple Solomon ball. Oh, yeah. Yeah, there is a little bit of damage on the Rikia Jackson You can see it under the first. We'll send an empty box to wrap a good catch on that red shimmer Aiden holiday, uh, Holloway to 10 for Auburn. That's on that Auburn. Very nice X Fractor L Ellis a Stefan Castle Rikia Jackson and Rijon or Rijon Ellis Play B-Bop So it's switched from it's channel twos a bot lobby to now you're playing B-Bop We should have sound bite Yeah, I know I'm playing B-Bop Pretty much exactly a fissian auto exactly And just two left Maryland, Michigan State everybody Jake G underscore. Oh, yeah That guy's that guy's late Xavier Booker Ronnie James first Kwame Evans Purple Isaiah Collier to 399 USC That is Jamari McDowell X Fractor a Versace again, that'll be random to all First refractor Elijah Martin a Matt's Buzellis Purple shimmy of Kwame Evans Oregon Purple Mini diamonds to 399 Justin Edwards for Kentucky X Fractor Katelyn Clark for Iowa a El Marco Jackson 299 on the Bowman throwback auto congrats on that good stuff Kansas I'll play Jordan Kane First about Freddie Delione Delion castle Sharp shooters Justin Edwards to 1 299 Mackenzie and Bako for Indiana That is a Cormac Ryan for Unk Unk Wilde a nice one there. You know, UNC 75. Let's go punk. Unk Is DJ Wagner Like Henson a Trevon Brazil a Sean Stewart An orange shimmer Darren Green jr. To 25 get them some church pants a Spencer Jones for Stanford nice one there too To 1 99 on the lava Tyrese proctor Tray Norman and more base probably number three now Everybody just Michigan State in Maryland in the next one Eric M with Auburn, Florida State Baylor number eight and Daniel L With Michigan State in Maryland. We're sold out of the next one Daniel. Thank you, brother Let's go Eric. Thank you as well. Thank you as well Eric So we are down to number seven is what we got to fill up next. So next one is done One two three four five six six to go on number seven everybody. All right, everybody You got six to go on the light case in number seven Teams are all marked down again in that one. Thank you. We've our price match pretty much everything Available So you got Duke still available in that one there way down on sale now That's You Yeah, I pulled a bunch of good stuff out of this so far shorts orange brawny James is my best on release day It's a 99 Milan mom mom's a little bitch Extractor of Edie It's brawny James seven to go in number eight now. Thank you. Well first brawny James refractor Hell, yeah, let's go snowball. Good luck, man. Angel Reese Purple shimmer El Marco Jackson Auburn FSU Baylor is not bad a pretty good spot actually 399 to Mari Burnett Extractor first Devin Williams. That is a Santiago Vascovi Got orange big kahuna Simeon Wilshire 225 for st. John's congrats on that one the SJU Shepherd and Ashland Hardaway Versace To 299 Hannah Hidalgo Green Tyrese proctor first for Duke the 99 congrats blue Devils very nice one there on the auto a Ron Holland Omaha bill you Bradshaw X factor Tyrese proctor and Sean Stewart Omaha bill you Cameron break the Kayla Williams to 299 Orange true orange Jackson shell stat for Oregon congrats on that Oregon to 25 Justin Edwards First refractor to Sean Harris Smith Haley van lith and Jeff S with Illinois Memphis K state and 8 Joseph I with Oregon and 7 so we're down to 5 to go in number 7 now everybody Thank you both Duke, Michigan State Kansas Maryland Miami St. John's FAU the go Edie. That's your guy con man I know that that's your boy. All right, first delight box. Good luck everybody Oh, can we get the get get out out mods get them out, please Love sab get them out, please. Oh sab is welcome. No not after that comment Sab is as unwelcome as I could possibly make you Hi, Sam 299 my real little to 399 Aaron Bradshaw You can stay 99 Zaden I The UNC to 299 El Marco Jackson for Kansas the 399 Simeon Wilcher St. John's and to uh 75 yellow Deshaun Harris Smith from Maryland Jeremy fears rice hopkins Aaron Shannon jr. Isaac Collier for USC to 150 on the sharpshooters raywave Got Xavier Booker throwback auto 299 Go USC brawny james First base auto going to sloppy joe. Congrats, buddy Brawny James good stuff, man. First base auto Sloppy j and Stefan Castle so 199 for a Yukon. Very nice. Yeah, Edwards to 150 To 299 Raquia Jackson for Tennessee to 399 Dylan Jones. Weaver state to 199 dusty stromer and to 299 is Tyson Chapman My real little DJ Hoggard Quinton post DJ Wagner to 199 Good lord. Isaiah Collier to 199 for USC now. Congrats USC Good stuff another nice one base auto of Santiago Vascovi And green Xavier Booker color match for Michigan State. Congrats MSU. Very nice That's awesome. That's freaking awesome con man. Yeah, he was like the hottest guy him and Clark and Wenby obviously And scoot I suppose but yeah, he was uh, he was a big one with his first last year Uh, AJ Hoggard uh Coleman Hawkins to 199 no to 100 excuse me to 199 Milan Momsilovic Devin Royal to 299 and to 399 Amari Burnett First refractor Sean Stewart Jaden Aikens Rob Dillingham Jared McCain sharpshooters Got Kevin McCuller Jr. First base auto for Kansas That's KU refractor to 250 Santiago Vascovi for Tennessee Uh, Jamir Young first base auto for Maryland. Nice one there. Congrats Maryland and to 75 Haley Van Liff Congrats on that one at their LSU. Very nice. Haley Van Liff Got the rainbow beside the super. Hell yeah, do you know if the super has been polled? Have you seen it con man or no? Jordan Dingle to 320 uh, 399 Oh 1500. Yeah, it's a lot to 199 Reed Shepard RJ Jones to 399 Wooga poplar Wooga 299 and Brandon Garrison to 399 Justin Edwards first refractor those RJ Jones Kyle Philippowski and Simeon Wilcher We've got Tyrese Proctor first base auto for Duke got a first refractor out of Baba Miller to 250 You got to get him that guy from church pants, too. Nice one there 250 and first base auto ashen hardaway for Memphis Saber you still in here? No, did you dip? I have a question for you if you aren't still in here, so Um, I feel quick recap here everybody again. We've got just uh, six to go. I believe No, five to go on number seven five to go on number seven Uh, there was a ray wave. I believe math uh, Matthew a green shimmer Milan, uh, mom Salovich Brandon Garrison Zaden high jaden akins to 75 to john harris smith To 25 Simeon Wilcher darren green jr. To 10 aid in hallowed Uh, not that I don't think there was any turn Shannon Tyrese proctor kevin mccullough jamiri young sanctiago viscovi ashton hardaway twice To 250 bava miller sanctiago viscovi johnny broom is a collier to 199 as well as spencer jones and stephen castle To 150 Xavier booker el marco jackson to 99 Xavier booker tyrese proctor 75 hailey ben litt cormack ryan 25 is jackson shellstad And then abrony james on the first base auto congrats on that usc. That'll do it for the break everybody Thanks again for the fill up next is the first


It is an honor to present to the court the applicants to take the oath of allegiance today, representing 56 different nationalities. Equador, Somalia. What makes us Americans? China. And what makes people from all over the world want to become U.S. citizens? Senegal. The U.S. Constitution, a four-page document written more than 200 years ago, is part of the reason. We the people. These are the first three words of the United States Constitution, a document that defines the structure of the U.S. government, and is the foundation for the freedoms and responsibilities of U.S. citizens. In the United States, a country with people of many different backgrounds, the principles of our Constitution unite all of us as a nation. 300 years ago, the early 1700s. Although Native Americans had lived in this land for centuries, the European settlers who came here called this the New World. These early settlers were drawn here for many of the same reasons that immigrants come here today. These people formed 13 colonies, ruled by Great Britain. At first, Britain allowed these colonists to govern themselves in many ways. Later, Britain made many demands on the colonists, including taxing them without their consent. As the colonists established their lives and built communities here, it became more and more important to them to be able to govern themselves. In 1776, representatives from the colonies issued a Declaration of Independence. Thomas Jefferson was the primary author of this document, and later became the third President of the United States. The Declaration of Independence announced that the colonies were free and independent states, no longer under British rule. It stated that all men are created equal and are born with the natural right to life, liberty, and the pursuit of happiness. Over time, the idea of equal rights included all people in the United States. Of the 56 men who signed their names to the Declaration of Independence, eight were foreign-born. They were immigrants, like many people in the United States today. The colonists pledged everything they owned. They pledged their honor and even their lives in order to win independence from Britain. To free themselves from British rule, colonists had to fight the most powerful army in the world. The American Revolutionary War was a hard, brutal struggle with ongoing battles for eight violent years. George Washington commanded the colonists' army, later becoming the first President of the United States. Out of this hard-fought war, a young country was born. But there were problems. The Revolution had produced 13 independent states held together by a treaty called the Articles of Confederation. The 13 states were not a unified country yet. They needed a stronger agreement to tie them together and to ensure the survival of this country. To find a solution to this problem, a convention was called in 1787 and delegates from the new independent American states met in Philadelphia. The delegates were passionate about protecting the idea that here no one is born a ruler. They felt power must come from the people. The challenge facing the delegates was complex. They wanted to create a government strong enough to hold the entire country together, but limited enough that the rights of the states and the individual freedoms of the citizens could be protected. After three and a half months of intense debate, the delegates created a plan, a constitution that defined a completely new kind of government. First, they put aside the idea that there would be a single final authority, a king or an emperor, for example. Instead, they divided power between the states and a new national government, whose powers would be specific and limited. Then, within the national government, the delegates further divided power into three branches, Congress, the presidency, and the judiciary. Each of these would have its own role, but none would have total control. This is what no country had ever done, control power by dividing it, putting it under the limits of a written constitution, and then placing the final authority with the people who govern themselves through elected representatives. The power and responsibility for freedom belong to us, the citizens of the United States, we the people. The constitution is a document as relevant today as the day it was signed. Over the years, the constitution has changed through what are called amendments. The first ten amendments to the constitution are called the Bill of Rights. Those amendments establish some very basic rights of citizens, freedom of religion, freedom of speech, right to a fair trial, right to bare arms, and other important liberties. For more than 200 years, the U.S. Constitution has had daily impact on the lives of citizens, and over time, its promise of freedom has included more and more people. Many groups of people were denied certain freedoms in the past, but have gained equality through amendments to the U.S. Constitution. It took 75 years and a civil war to end slavery, and it was another 100 years until laws were passed to make it illegal to discriminate against people based on race, color, religion, sex, or national origin. In 1965, the Voting Rights Act made sure that every U.S. citizen would be allowed to vote. At the same time, the United States removed many unfair restrictions on immigration. This allowed legal immigrants from all over the world to come to America and make this country their home. From early settlers to today's immigrants, the freedoms guaranteed by the U.S. Constitution have drawn many people to this country. With each person who joins the nation, we the people become stronger. Together, we have built a free nation. We have been able to imagine, invent, and live our lives as we choose. We've been free to dream and make those dreams become real. All the while, we continue to debate, as the delegates did, the challenges that face a free nation. The Constitution protects our many freedoms. It also allows each person to decide how to use these freedoms.  Freedoms and rights come with important responsibilities. Make a commitment to be part of your community. Get to know and help your neighbors. Discuss the issues that affect your community. Learn English. Learn about U.S. history and government. And respect the law. If you become a U.S. citizen, serve on a jury, if you're called to do so, and vote. The right to vote allows each citizen to help the nation remain strong and grow. Voting allows all of us to have a voice in how our lives and communities are built and how they change over time. Voting is an important part of U.S. citizens responsibilities. What makes us U.S. citizens? What makes us a nation? Why did you come to this land? Each of these questions reaches far into our shared history, to the birth of the United States, and to the document that protects and ensures our freedoms, the U.S. Constitution. And it begins with three words. 56 countries that are here to become citizens today. This is a serious time in your life. Through these words and the guarantees of the Constitution, we are a nation of free men and women, men and women united by a shared history and the common civic values that make us all Americans. Now it is your decision. What will you do with freedom? I say thank you. Our country now is better off a few minutes ago. Colleges today representing 56 different nationalities. Ecuador. What makes us Americans? And what makes people from all over the world want to become U.S. citizens? The U.S. Constitution, a four-page document written more than 200 years ago is part of the reason. We the people. These are the first three words of the United States Constitution, a document that defines the structure of the U.S. government and is the foundation for the freedoms and responsibilities of U.S. citizens. In the United States, a country with people of many different backgrounds, the principles of our Constitution unite all of us as a nation. 300 years ago, the early 1700s. Although Native Americans had lived in this land for centuries, the European settlers who came here called this the New World. These early settlers were drawn here for many of the same reasons that immigrants come here today. These people formed 13 colonies, ruled by Great Britain. At first, Britain allowed these colonists to govern themselves in many ways. Later, Britain made many demands on the colonists, including taxing them without their consent. As the colonists established their lives and built communities here, it became more and more important to them to be able to govern themselves. In 1776, representatives from the colonies issued a Declaration of Independence. Thomas Jefferson was the primary author of this document and later became the third president of the United States. The Declaration of Independence announced that the colonies were free and independent states, no longer under British rule. It stated that all men are created equal and are born with the natural right to life, liberty and the pursuit of happiness. Over time, the idea of equal rights included all people in the United States. Of the 56 men who signed their names to the Declaration of Independence, eight were foreign born. They were immigrants, like many people in the United States today. The colonists pledged everything they owned. They pledged their honor and even their lives in order to win independence from Britain. To free themselves from British rule, colonists had to fight the most powerful army in the world. The American Revolutionary War was a hard, brutal struggle with ongoing battles for eight violent years. George Washington commanded the colonists' army, later becoming the first president of the United States. Out of this hard-fought war, a young country was born. But there were problems. The Revolution had produced 13 independent states held together by a treaty called the Articles of Confederation. The 13 states were not a unified country yet. They needed a stronger agreement to tie them together and to ensure the survival of this country. To find a solution to this problem, a convention was called in 1787, and delegates from the new independent American states met in Philadelphia. The delegates were passionate about protecting the idea that here no one is born a ruler. They felt power must come from the people. The challenge facing the delegates was complex. They wanted to create a government strong enough to hold the entire country together, but limited enough that the rights of the states and the individual freedoms of the citizens could be protected. After three and a half months of intense debate, the delegates created a plan, a constitution that defined a completely new kind of government. First, they put aside the idea that there would be a single final authority, a king or an emperor, for example. Instead, they divided power between the states and a new national government, whose powers would be specific and limited. Then, within the national government, the delegates further divided power into three branches, Congress, the presidency, and the judiciary. Each of these would have its own role, but none would have total control. This is what no country had ever done, control power by dividing it, putting it under the limits of a written constitution, and then placing the final authority with the people who govern themselves through elected representatives. The power and responsibility for freedom belong to us. The citizens of the United States, we the people. The Constitution is a document as relevant today as the day it was signed. Over the years, the Constitution has changed through what are called amendments. The first ten amendments to the Constitution are called the Bill of Rights. Those amendments establish some very basic rights of citizens, freedom of religion, freedom of speech, right to a fair trial, right to bare arms, and other important liberties. For more than 200 years, the U.S. Constitution has had daily impact on the lives of citizens, and over time, its promise of freedom has included more and more people. Many groups of people were denied certain freedoms in the past, but have gained equality through amendments to the U.S. Constitution. It took 75 years and a civil war to end slavery. And it was another 100 years until laws were passed to make it illegal to discriminate against people based on race, color, religion, sex, or national origin. In 1965, the Voting Rights Act made sure that every U.S. citizen would be allowed to vote. At the same time, the United States removed many unfair restrictions on immigration. This allowed legal immigrants from all over the world to come to America and make this country their home. From early settlers to today's immigrants, the freedoms guaranteed by the U.S. Constitution have drawn many people to this country. With each person who joins the nation, we the people become stronger. Together, we have built a free nation. We have been able to imagine, invent, and live our lives as we choose. We've been free to dream and make those dreams become real. Over the while, we continue to debate, as the delegates did, the challenges that face a free nation. The Constitution protects our many freedoms. It also allows each person to decide how to use these freedoms. Whether you are a new immigrant or ready to apply for citizenship, freedoms and rights come with important responsibilities. Make a commitment to be part of your community. Get to know and help your neighbors. Discuss the issues that affect your community. Learn English. Learn about U.S. history and government. And respect the law. If you become a U.S. citizen, serve on a jury if you're called to do so. And vote. The right to vote allows each citizen to help the nation remain strong and grow. Voting allows all of us to have a voice in how our lives and communities are built and how they change over time. Voting is an important part of U.S. citizens' responsibilities. What makes us U.S. citizens? What makes us a nation? Why did you come to this land? Each of these questions reaches far into our shared history to the birth of the United States and to the document that protects and ensures our freedoms, the U.S. Constitution. And it begins with three words. 56 countries that are here to become citizens today. Thank you, the old religion. This is a serious path in your life. Through these words and the guarantees of the Constitution, we are a nation of free men and women, men and women united by a shared history and the common civic values that make us all Americans. Now it is your decision. What will you do with freedom? I say thank you. Our country now is better off than our country was a few minutes ago.


Stocks of Kinzhal, caliber missiles at critical level, but large stock of S-300. In the Russian Federation, the stocks of Kinzhal and caliber missiles are at a critical level. There is no possibility of a rapid increase in the production of new high-precision missile weapons, said Andrey Yusov, a representative of the main intelligence agency of the Ministry of Defense of Ukraine. There is no possibility of a rapid increase in the production of new high-precision missile weapons. Russians are constantly looking for circumvention of sanctions, Yusov said on the air of the National Telethon. He stressed that Ukraine and the International Pro-Ukrainian Coalition are constantly working to strengthen the sanctions policy, which creates production difficulties for the Russian Federation. But there is a certain production. We can talk about dozens a month. Even if they pause for months, say until the fall, they will not be able to cover what they have already spent on the war in Ukraine, Yusov added. At the same time, the intelligence service noted that the Russian Federation still has a large supply of certain missile weapons, especially the S-300, but about high-precision weapons. Those very Kinzles, calibers, they are really already at a critical level, Yusov said.


This is Think Tech Hawaii. Community matters here. Good afternoon and thanks for joining us here on likeable science on Think Tech Hawaii. It's another Friday afternoon and we're glad you're with us. Likeable science is all about how science is in all of our lives, a vital part of all of our lives, interesting, current and relevant to everyone. So we shouldn't be scared of it. We shouldn't try to relegate it to the ivory tower. We should embrace it and enjoy it. Today to help me explore that is Susan Scott. Welcome Susan. Thank you. Good to have you back here. Nice to be back. Susan is a naturalist, biologist, author, speaker, all kinds of things and she has a new book out called the Kolea. A beautiful, beautiful book.  It won an award from the Hawaii Publishers Association for her Best Natural History Book for the last two years. Congratulations. I'm really proud of it and happy for our Kolea and I'm the co-author of this. Right. Your other author is currently in Montana. Yeah, the my co-author is in Montana and he's the one who did all the research that got and all the pictures that got in there. Yes, beautiful pictures, all kinds of stuff, great things on the history of it of the stones they used to use to help catch them, how the Hawaiians caught them. Amazing, great information this book and so well presented. Well, thank you, thank you. Wally Johnson is the name of the researcher and he has been studying these birds most of his adult life and writing research papers on them that were kind of hard to find and for the public to get to and so I started writing about the birds in my column and. This is the Ocean Watch column. In my Ocean Watch column, I write a weekly column for the Starvertiser and someone years ago sent it to Wally in Bozeman, Montana and he sent me some of his papers knowing that I was interested. So we did that for some years and then a couple years ago said you know we need to get together on this and write a popular science book for the public so they have a place to look up the birds because people love their birds and one of the reasons they love the birds is because they are so adaptable to human beings. Right and maybe on that note we should show you got you gave us a series of pictures here. So can you get the first one of those up? So that's the book and that's Wally. The great thing about the references in this book is the references are Johnson Johnson Johnson Johnson. Wally is the only one who's done research on these for years and published a lot of papers and so the research was easy because they were all one person so if I asked Wally and he didn't know no one knows and so there were a few things you know we'd still like to know and he is actually still doing some research. So the birds are really popular in Hawaii because they're so adaptable and they have really taken advantage of our buildings our golf courses are mowing the lawns introducing alien insects and they they've just taken taken over so they're they're really quite tame they're wild birds but but they become accustomed enough to people and come to the same place every year each individual has its own foraging area because that's its survival that's its food and so every year if you have a bird in your yard you'll see that bird year after year and they live up to 20 years that that's really old for a bird mostly there they're eight to ten but but they have that they will do live up to 20 and so you get to know the birds and the birds get to know the people in the house and so I get lots of stories really fun stories from my column from people who say oh my bird I have one that said my bird won't go out of the backyard unless I open the gate and these birds can fly and so he said if he opens the gate the bird will walk through the gate and then it'll close it and then it forges around the front yard and then he opens the gate and it goes in the back I don't know if it's knocking and another reader said my neighbor put out a broken television set on the curb for pickup and his plover went out there and sat in front of the tv seeing its reflection obviously but looked like it was watching television and he said it was hilarious all the neighbors were watching the bird like this in the tv so so they're they're really charming birds and they're very that picture I showed is was my plover who comes up to the the lani and knows when the the screen was shut now lucy is a pretty old mellow dog and she didn't ever lunch after it but it knew if the screen was open it didn't come up there and if the screen was shut it would come up there and then I would give it some scrambled eggs which is what walley says we can feed them the birds that get to know us if you can get the bird away from the miners and the other ones because they all like scrambled eggs sure but it's protein and fat and that's that's really good food for them excellent so so maybe we'll get the next picture here and because this will help get people familiar with them in case you don't recognize them already and I think people have written to me it's like I had this beautiful bird in my yard this collared in my yard all winter and it looks like this and then come February March I had a different bird so this is the winter colors of these birds they change colors so the next picture this is the spring colors and both of them you can see look quite different all of them look like the former picture the males turn in this beautiful black black feathers on their face and breast and the females have more of a model color but it's still quite a change and so the bird was the same bird that the person had in their yard but people people don't know that you know it was hard they mold this is a these are breeding colors and so they're getting ready in these at this time to go to Alaska and that's where our birds go right and it's amazing and these birds fly obviously non-stop uh from here to Alaska right and that's many thousands of miles they leave around April 26 27th the date's pretty fixed because they go by light by the amount of light and they fly 3 000 miles non-stop right there's four ounce birds by that but in the spring they're about seven ounces but it's just an astonishing feat of nature to be able to fly over the Pacific Ocean they don't stop they get up to 100 miles an hour in the jet stream I mean you think their little feathers would just go flying off the 100 miles an hour I don't know if we how long we could stand it on but they're one of the reasons Wally wanted to make the subtitle of the book the amazing life of the Pacific goldblowers is because they are amazing yeah that that's really I mean I was going to say you know you talked about how they live considerably longer than similar sized birds this is the benefits of exercise right exactly and then they go there because they're going to raise chicks right and so no one knows if they form pair bonds here in Hawaii there's there's another population outside of Hawaii but our books mostly about the Kalea in Hawaii that's because Kalea is a Hawaiian word but there's another population in Asia so anyway the the birds go our Hawaii birds go to a certain area in Alaska that Wally has identified by by tracking the birds and and they mate the male makes a lovely little nest on the ground and the female chooses whichever male and nest she likes and they have four eggs she lays four eggs and that weighs four chicks the chicks are like chickens and that when they're hatched they immediately start eating as soon as they're dry they're walking around eating and they're in Alaska because there's 24 hours of light so they can eat 24 hours and the insects are just swarming right so I don't know if you've been there but no but I would barely breathe yeah and it's it's it's a it seems like such a crazy idea they would fly 3000 miles but what they're flying to is this banquet which is the only way they can have enough food so the chicks can eat and they have to grow up really fast and so yeah they can't delay their turn either no no and so so that's the reason and they've you know they've evolved to fly those distances there's other shore birds that do the same thing so yeah it really makes you appreciate nature yes I mean lots of birds migrate most of them much shorter than that most of them over land but these amazing sea over sea migration where you realize that there is no stopping right there's no there's no let's do this in two bounds instead of one the plover the pacifical and plovers that spend winters in Samoa Tahiti Palau the South Pacific Islands and I've seen them there and think I can't believe he's fool because it's even far for me to fly from here to Palau but they they stop over in Japan and eat insects in rice fields and other areas because they can't carry enough fat to make that long of a migration so that's one stop yeah a road will be short stop it's like a rice field stop yeah yeah so they'll stop and refuel yeah exactly and then going up and that's the wall he calls it a refueling stop yeah and so if they if they carried enough fat to make the trip they couldn't fly right so yeah no it's again a beautiful example of biological sort of mechanism how do you balance off that exactly yeah how much fat you can afford to carry and then and then the chicks mature fairly fast um they're flying in them they have their wings developed in a month i'm not sure they're actually flying but in august the females leave first exhausted from laying eggs if they lose their four eggs they can relay four more yeah i was reading that in just a matter of like a week yeah amazing total weight of the four eggs is the same weight as the female so it's an enormous uh energy expenditure right and so it's not no wonder the females get back to Hawaii and yeah and then the males stay with their chicks they don't they don't stay right with them because they're out all foraging for themselves but if it's cold or predators are nearby the males and the females both protect them so they show some parental care and they show parental care up until then when the males leave so we see the females in early august and every year people say wow they're back really early they're always back in early august it's just that there aren't that many we don't really not everyone sees them in august and then the males come next and this is in general and then the chicks stay as long as they can find food right and it's not snowing i mean once the weather changes and the insects are gone they eat berries so they can still eat berries but they get as much weight on them as they can before they take off again you think about the interesting biological pressures you have to be a very good at sort of sensing just just how long can you stay here eating exactly because you don't want to be caught by the first snow you're going to be losing right losing weight well the bad news is only about 20 percent of the chicks survive their first year in Hawaii so they've got to get here on their own they don't have any adult guidance that's just an instinct and then once they get here they've got to find their own territory and birds that already have staked out their territory will fight and and these birds are really skinny there's a picture in there of a nude first year bird that just looks emaciated so uh the good news is the 20 percent that make it through their first year live long lives yeah so i see empty spaces sometimes you know in my travels in my life that i think this would be a perfect spot for a kalea you could come over here because they don't really need that much space right no because no as long as there's a diversity of insects and i live near kailua beach park and there's there's four and right next not right next to each other but you can kind of see where the edges of their territories are and they're always the same ones and i know that because we tried to rescue one's got a broken leg i think i have a picture of the one with the broken leg uh one another reader called me and said there's a kalea who's just returned this was in uh september or no it was actually in um still in august she's returned and her leg's broken so we i went over and took this picture and we decided um my husband's a doctor and said it's dislocated that that's the ankle they have really long ankle bones uh it seems dislocated and if we could catch it we might be able to pop it back because you can do that in people right so we went to uh the bird was actually looking not bad and she's hopping around and walley said they live fine with one leg if we could have to even remove it that would be okay so the next picture was um i called uh one of walley's former colleagues who's here in hawai and this is called a net gun and these birds are very wary but if you just walk by and you act like you're not really paying attention you can you know you get get pretty close and so josh brought over the the net gun and we um tried to act very casual next picture and that's the net so when you fire the gun it's a co2 cartridge it throws the net out it's got little weights on those corners and then you know doesn't hurt the bird but catches it so next picture we tried josh shot once and he's done quite a few but he overshot because normally the birds when the pop goes it's a loud bang goes the bird flies forward and and storm we named this one storm flew sideways and so the net went over it and that bird really we were there for a couple good couple hours afterwards just saying oh i'm not trying to catch you and i said you know and so this is josh and that's storm and she was watching every thing he did and so he said i i can see her looking at me there's no way i'm going to get close as soon as he would try to he's loaded the gun again as soon as he got around she would take off you know and we didn't want to want to make her fly because she's already damaged so um i was there the next picture this is yesterday uh i sent you this picture earlier but but i was there yesterday and got an identical picture and she's still got the leg but she's fat yeah yeah so all we think she'll do better if we can catch her so we might try again but they're brilliant so and we're going to continue this conversation i've been told we need to take a short break here okay and uh susan scott is here with me here on likable science i'm your host ethan alan and we'll be back in just a minute this is think tech hawaii raising public awareness aloha i'm carol mon lee think tech hawaii is volunteer chief operating officer an occasional host and this is minky for the first time think tech hawaii is participating in an online web based fundraising campaign to raise 40 000 dollars your thanks think tech will run only during the month of november and you can help please donate what you can so think tech hawaii can continue to raise public awareness and promote civic engagement through free programming i've already made my donation and look forward to yours please send in your tax deductible contribution by going to this website www.thanksforthinktech.causevox.com on behalf of the community enriched by think tech hawaii's 30 plus weekly shows thank you mahalo and shisha for your generosity and you're back here on likable science here on think tech hawaii i'm your host ethan alan with me today in think tech studios is susan scott naturalist biologist author and we are talking about her new book uh the collia the hawaiian golden plover and we're going she was actually just telling us this amazing bird locally i guess over and you say collia uh the beach park right storm right uh with apparently a dislocated leg right and uh trying to catch it so you can help it uh although it sounds like you doesn't need that much help if it's able to avoid you so right well you don't want to hurt it right in the process of helping it right but um i think with what we might try again yeah i don't think she can migrate with that legs it kind of stands out sideways so so uh interesting okay and um and let's see was this the end of our pictures or okay okay great um um so these birds they they do this migration to alaska uh in this in the spring basically april end of april and then come back here in august basically and uh while they're here they're basically go out of breeding condition and are just relaxing and enjoying hawaii right right exactly and and bulking up from those 3000 mile flights as they do that twice a year right yeah and getting ready for the next double job is to get fat right for the migration both ways yeah and it's intriguing they're they're i mean their life it sounds like rolls around this whole holes are eating binge right they're here eating to fuel up for their journeys right there so their chicks can get enough food because their chicks couldn't survive on the small plots they have here basically right but the good news is we have enough we have imported a lot of uh alien insects and spiders and things that they can eat and so that's good for us they eat a lot of those things right right so these are these birds are good to have around yeah and we've we've opened up a lot of space by mowing the lawns they like the flat right there are some pictures in here of their preferred kind of habitat which is very much sort of more or less our preferred habitat punch pole cemetery right it's a great place for you so there's must be yeah goodly numbers of them there yes i think i think well i said there's about 100 and 100 acres and speaking of these birds oh you were just telling me when you came in about an amazing one you just well yeah i got an email yesterday that said uh from a reader who i don't know yet but i probably will he said i found a leucistic plover a leucistic and leucistic i looked up i i knew it had something to do with white but uh it's not albino but it's it's got a melanin disorder that makes it mostly white so this one has all white feathers it's got a few dark spots on its back but its eyes are dark so it probably does not have the vision problems that albinos have and um so i sent that to walley who's our worldwide plover expert and he said oh i have never heard of one really exciting so i drove out there this morning with my new camera and the reader is his name is bill kulk cok he said um it was right near the entrance where you drive in well these birds are so territorial they're so they're so accommodating to us they were there he was the she was there i named her blanche just so we don't say the bird with the leucistic bird which no no one else will know but uh blanche was right on the curb right on the edge there and i got in my car and she let me take a bunch of pictures she's mostly all white feathers just a few dark spots on her back and seems to be really healthy interesting because that again as with the albinos is somewhat of a disadvantage in the wild right they become their obvious target basically yes and the big target the big predators are cats feral cats and so at hey boat harbor next door is hey a estate park and people feed cats there i counted 35 in the parking lot uh about a year ago when i was there and i'm looking for a picture for a white turn book i'm writing of a feral cat and i thought well i'm in feral cat i have in here so i pulled in there there were 15 just all lying around and um that's her gonna be her biggest problem because it's really close and cats and that's you know they they seem pretty tame and there are four food dishes out so people are clearly feeding them so maybe she'll be okay but plovers are really alert to predators super alert so walley said i've not been to alaska with him when he's doing his his tag gps tagging but um he can't get anywhere near the same birds that you can walk pretty much up to here yeah it's very intriguing again it's just the birds intelligence that they have a sense of sort of context they know that when they're here people moving near them are of no concern but in alaska and there when they have chicks anything moving as a predator and they're very very wary and they have a bunch of strategies to uh i mean they one they can freeze and blend in quite well yeah but they can also they'll do a broken wing kind of strategy they pretend their wings broken and leave the predator away yeah yeah and then manage recover nicely that's right and then recover yeah um and they can't i mean i guess they can put up a good struggle to uh when push comes to shove right if they get yeah and there yeah there's picture of them uh fighting here in hawaii over territory and i had a couple readers have emailed me that their plover can beat up a mina their plover wins when they're fighting with a mina over food or sticks and the food thing a lot of people say don't feel wild birds and almost everybody does it's just one of those things it's our touch with wildlife it's our it's it's the thing that we as humans need i think to to see wildlife and to be connected exactly and so walley said if you if if you do decide to feed your bird uh because it does feel like your bird too there's just one to give them healthy food and mealworms are another thing besides the scrambled eggs but he has a picture of a guy who tamed his bird well enough to land on his hand and eat mealworms out of his hand and the bird lived i think 17 maybe 15 years and so clearly did find by by feeding it yeah yeah that's uh just want to be careful not to feed it with their cats around right or mongooses yeah i want to want to be sure that although i can't imagine any of those animals getting predators getting close to these birds because they're so wary of something like that you know a small animal like that would just totally scare them away right interesting that they can again they make that distinction and understand that people are no real threat to them here right exactly that's a very it's a contextual dependent but also discriminating right right the one thing they haven't learned is uh about barn owls so they sleep on flat roofs and at night they're up high they're usually fine but we have imported the state of hawai imported barn owls to control rodents now i didn't i didn't know that till i read that in this book actually in the 1950s and there's a lot of barn owls uh in hawaii and they are nocturnal predators so they just pick them off i've seen dead plovers out at flat island off kawaii beach park probably from the owls but they should presumably continue to do reasonably well with further development in some sense is just giving them more territory right right as we clear off what were agricultural fields that are not so useful to them basically exactly turn them into suburban yards that works for them yeah yeah unlike most wildlife it works for birds these birds in particular but yeah there's no official count but i think walley believes that they're doing just fine yeah that makes sense yeah that's uh there they are truly uh amazing creatures uh and it's so wonderful to have this this absolutely gorgeous uh guide to them that so it's thorough it's it's authoritative it's it's accessible which is which is you know i as you were saying earlier that's what you want to when you're doing a popular science book you can't you don't want to stick in a lot of scientific names you don't want to stick in a lot of jargon a lot of technical information but you've got nice beautiful diagrams and pictures uh very uh easy to understand but but a great deal of information it's it's truly a beautiful book um where are you off to next you because you're just back right yeah i'm just back from australia where craig and i have our sailboat in townsville and we had some great times on the great barrier reef i read about the ocean watch column and i'm off to midway and craig's going to go with me we are going to be counting albatrosses at midway at all and then after that pull out pull out i'll get it busy busy what are you doing in pullout i'm i'm leading a i'm the naturalist on a snorkeling trip for oceanic society okay so it's a job yeah i know life's tough it's a job and after that it's so busy here for us uh we're going to bangladesh to uh work in a clinic craig and i started in 1997 that's still going and doing well we had to skip last year there was some violence there but it seems to have been stopped and the uh state department thinks it's safe again so excellent well susan it was great having you on the show here again and uh susan scott co-author uh with walley johnson of hawai's colea a wonderful book highly encourage everyone to read it thank you very nice to have you here aloha thanks for inviting me again and join us next week for another episode of likable science


Your Coca-Cola bottler presents Claudia based on the play and novels by Rose Franken Brought to you transcribed Monday through Friday by your friendly neighbor who bottles Coca-Cola Relax and while you're listening, refresh yourself Have a Coke and now Claudia Well, here you are Hello, dear When did you get in? I didn't hear you just now. I didn't know you were home. Oh, I just got in too Why are you hiding in the bedroom? Aren't you glad to see me? Of course. I am delighted.  That's wishy-washy glad Oh That's better you were You were the home late and I was out all day, too I was at dr. Rowland's and what did dr. Rowland have to say the baby's fine. What do you think he'd say the baby's fine What about you? Oh, I'm fine, too. This is not and he said you are fine fine Now tell me what are you hiding in the bedroom hiding?  I mean besides the chair. I don't see anything besides it David What dear don't what dear me.  I must be a contortionist if you don't tell me I'll tickle you. Oh, no, no, no, no, no, not that That's there you are bluffs confessed for me. So that's it David.  Oh, I just thought I'd glance through it waiting for you to come home And that's why you hid in the bedroom. Is it? Well, it's getting late. Just give me the catalog And while you shower, I'll just glance through it. Oh, I've got plenty of time. It's still early It's not as early as you think David then maybe you'd better go and start getting done already. Oh, it is not that late I've just timed it too What's so funny you me Me both I'll tell you why We'll sit down together and read the mail order catalog together. How's that? Oh, that's perfect I love reading something at the same time with you. I was afraid of that That's the way I like reading best and come on. We'll go in the living room You know, I hardly had a chance to look at it this morning But it looks fascinating this mail order catalog darling is This for many people the only way to shop you mean many people who never get to a store Many people who live hundreds of miles from the nearest store David. That's awful. Oh, it's not so terrible I died just wait until you read this catalog You'll never want to go to a store again. Well, I do love getting mail and Everything in this book is a bargain. Really? Come on quick get sit down here. I never saw you so anxious to read something. I'll turn on the standing lamp There All ready now. Let me see. I was reading page 623 now farm equipment farm equipment I don't want to look at farm equipment. Just look at that tractor Isn't that the most beautiful thing you ever saw stunning? You'd never think to look at it. Would you that that this tractor can pull a double plow fancy that And look at this look at this side delivery rate. What do you think you're not gonna buy one of those things? Are you of course? I am some day soon. You'll realize how handy it is to be able to buy my mail For instance now all of this farm equipment No reason why I should spend my time in stores. I'm going to order it by mail. Well, that's up to you Well, I'm certainly not going to Maybe I maybe I ought to buy one of these incubators. What's an incubator for hatching chicks? I thought the hand did that well hens can Once the chicks are hatched you keep them warm and a brooder like What's the matter? You look as if you didn't like the idea. I don't think I do Why? David how many chicks are in a brooder? Different sizes some to 70 some 350 or 450. No Here you are. Here's the picture right in front of you. Well, they must get all mixed up. What? Chicks how do the hens know what is theirs? Darling it it doesn't matter to the hand. How do you know? Well It's always done this way and doesn't convince me a hand is a mother, isn't she? Well, so I've always thought and I certainly wouldn't want my child in a brooder with darling Are you comparing yourself to a hen? Well, I think I know a little more the way she feels than you do There you hear here Here's a pasteurizer. You'll have to get one of those to David you changed the subject dinner And here's a separator only 3450 What's the separator separates the cream from the milk? Oh, then we don't want one of those why I like my milk creamy I think it's a gypsy serve milk with the cream skimmed off the top. Oh David look we don't want all this farm stuff. It'll only complicate things such as oh Taking chicks away from hens and cream away from milk Next thing you know, we'll be taking our nice crow away away from the field. We will we will Absolutely, I'm sorry. I brought it up. Well Now, let's see what they have in the line. Hey David. It's my turn. We've been looking at farm stuff Let's look at the rest what clothes and I knew this would happen. What? Darling, I'm getting starved. Don't you want to get dinner ready? Don't you want to take a shower? All right, all right, you win. What else do you want to look at? Well, there's a big section on household furnishings. You want to look at that? Oh, David that's a lot of fun stoves and refrigerators and Look look here's one. It's got six top burners and Insulated oven and two non-tip oven racks, whatever they are. I think I'll write in for it darling You don't want to write in for things. Why not? What's the fun of shopping this way, but David?  No, let's see. Let's see what else there is I want just make a wish and then look it up in the indexed and it's yours. I wish for I Wish for Just look at this index a moment. It's the story of your life My life Yours mine everybody's This catalog begins at your birth and ends at the end Here here you have everything you need to get born baby powder thermometers cribs toys The next big step Graduation David that's a stunning graduation dress marriage See Right here. I could buy you a thousand dollar engagement ring a perfect blue white diamond and wedding bands Nine to thirty dollars Why it's certainly a lot cheaper to get married and engaged many lad has been trapped that way Then after marriage your first home The furniture for it the tiling and the linoleum for the floor wall paper for the wall Book clubs to help fill those library shelves all sorts of clothing Livestock to fill the barn seats to flower the gardens lightning rods to protect the house You need one of those cute little pinafores for your daughter Rompers for your son sleds and tennis racket fishing lines for vacation Now, let me see. Where are we? Oh, yes, then the man in the family starts to make a little money He buys a car by mail Well, you can get all the upholstery tires and replaceable parts. They'd be a big help without the car and and mind you he can get a Garage door. I think we could use a garage door.  Well, then what do we buy that? Well, now let's see By now we've gotten a little older So it's a cold stove to keep the living room a little warmer. See we put the cold stove over in the left hand Oh, yes, I'm gonna be right underneath it. A rocking chair to rock it knitting needles yarn You can keep the yarn Corn plasters. I'll keep the corn plasters a Magnifying glass to read the evening paper with yes woolen underwear That's scratchers maybe some paints and brushes to catch that last sunset and then Then a wheelchair and finally on page 1172 a nice marble monument They think of everything don't they everything It's the seven ages of man and beast in a mail-order catalog. Oh, David Makes me feel so married. I mean now we've got a mail-order catalog between us sort of Telling us all about our lives You know come to think it's really almost all you need to get married in Almost but not quite not quite You know, I I think I'll get myself a pencil and paper And then I'm going right straight from front to back in this catalog And I'm going to make a list of every single one of the things that I want now. Let me see a tractor tractor Separator one separator how much was that 34? Oh, that's terribly spent a wheelbarrow.  I expect to wear the pants in this family Wait a minute. Wait a minute wheelbar Where the wheel? David listen, we can't do it this way. It's like pulling numbers out of the hat We have got to have a system a system. I see That you and your system not now just what would you suggest? Well, let me see I Think we ought to begin at the beginning and then go through it page by page page by page Yes, let's see certainly. Well, how else are we going to know everything that's in here? Oh, looky here What there is a pair of pants just exactly like I had when I was a little boy. Oh Dave look at those corduroy's. I think you Everything's wonderful. It's going to be a wonderful night. Look this catalog has how many? 1196 pages. Let's see what's on the last page. We'll buy something on the last page One thousand one hundred and see if we bought it. Here it is a halter for a horse I can get one of those for you and let's see Darling you underestimate yourself. It's going to be a wonderful week. Come on. Let's start at the beginning page one page You don't need to go in for extravagant Entertainment if your object is simply to give your guests a gracious welcome and make them feel at home Actually a bottle of ice-cold Coca-Cola will do that to everybody's satisfaction at the mere expenditure of five cents Have you plenty of coke on ice by the way? No telling when that doorbell a ring, you know Well David, you know we had quite a session there listening to you get through that whole catalog Yes, we did page by page every last single one now a list of things to order It's practically as long as the catalog. You sure you haven't forgotten anything I promise Claudia that we haven't all we need now is a house to move into and a mailbox to stand by the gate Oh, why didn't you buy the mailbox by mail that it really be logical, you know Well, Claudia has a feeling about mailboxes yo, I suppose I'll find out about that tomorrow You will and I have a feeling that when Claudia has a feeling. Well, I'll see you tomorrow see what you mean. Goodbye David Every day Monday through Friday Claudia comes to you transcribed with the best wishes of your friendly neighbor who bottles Coca-Cola So listen again tomorrow at the same time And now this is Joe King saying olive wire and remember Whoever you are whatever you do wherever you may be and you think of refreshment think of Coca-Cola or Coca-Cola makes any pause the pause that refreshes and Ice-cold Coca-Cola is everywhere And now here's a word from your friendly neighbor who bottles Coca-Cola


Oh Mr. President, great to see you. You're looking good at all of this. I was sitting on the table yesterday. There you go. You bet. You're good. Oh yes. And you know you sit and look at it and it's just got such a melancholy to it. And he told me that the man who did it, did it from a painting. There was a painting and that's a trail boss looking down and burying the cowboy who was trapped in a stampede and he's looking down at the grave there. But you sit and look over there. That's very attractive. Juries, officers, warm, you know, friendly. How are you? I gotta tell you one quick story. You see him at the pleasure of seeing your sister. Thank you.


All right guys, Sierra 1000 here. I got these teeth in and we'll get to that in a minute but today we're going to put this muffler on to that 1973 Bergen Stratton Edgerton. Stay tuned. I'm going to wear these teeth because Monkey and I made a bet whether she was going to sell that that little knob. It was going to be a clown nose but the clown nose wasn't any good so we got these teeth so that was the bet. She sold the knob today to a guy named Steve. Steve. Thanks Steve. So we told him the story. Oh he had to buy it so he's going to watch this video just to see me wear these teeth so again thanks Steve. I love a nice guy though but anyhow so let's get this put on to the the edger okay hang tight and I'll be right with you. All right guys, here's the old muffler. There's not much left of it. A lot of that heat will come over here to the carburetor and it'll want to loop or lock but let's go ahead and start it up so we can hear the difference. I never did it adjust that carburetor. So let's go ahead and take this old muffler off. Now it's nice and hot. So there's these little tabs right here. Let me zoom in. Little tabs right here. Just going to want to get on one of them and give it a quick tap but not real hard. This is aluminum and this is steel so you got to be careful especially when they've been in here this long. There it is. Okay so now we can unscrew this out but this one was pretty easy and the one I took out of the other motor over there it was actually pretty easy too. It was a little harder than this one but it wasn't bad. So let me get you back out here so you can get the idea. Well now we'll put the air cleaner see if it needs adjusted again. Sometimes you got to readjust them after you put the air cleaner on but we'll just have to see. We're going to screw this back on here. We're just going to take these and tap it the other way and that's good enough. It don't have to be super done or walking tight. Okay so let's put this on. So that's why I got the teeth in. I lost the bat but actually I'm going to kind of told the story to help monkey up but I didn't think the guy would buy it but Steve bought it so my dad is paid. Anyway thanks for watching guys. Remember say bear, the myth, the man, the legend. I'm gone for now. Bye bye guys. Take care.


Well, I guess right now the floor is open for general discussion So if you have any questions for any of the speakers in this session, this is a time To ask I know there are some people want to ask questions I have a question for Mike about the you have to show the slide in the About the OCCUP, OCCUP and ZEMPIN Since because the structure is similar to COZEMPIN So people are always thinking about where the genetic link is to the BFINAL2 Have a similar reaction similar link and my question is Because by clinical observation the instance even in Asian countries instant quite low Although the drop structure is similar and also the severity is also low So I consider the genetic test that the COZE effect is how I would like to know how the FDA consider that That is whether Could you I'm sorry, how FDA considers what? To label if I know the BFINAL2 have been labeled for OCCUP and PIN in Europe You've been coming also in Taiwan, but I don't know whether how the FDA to Think it how it's possible to label BFINAL2 for OCCUP and PIN is like like I Will ask Sally to comment, but I would just say that we can't really speak about a sort of specific labeling considerations necessarily, but you know the principle would apply that if you have sufficient suspicion that You know one drug in class causes an event and you can predict it and identify patients who are likely to have toxic response that You would use any available information to help inform other similarly Compounds that have similar viabilities that we can't necessarily label or restrict use based on theoretical concerns So, you know, there does have to be some obvious risk that's that's been detected You mentioned at the conclusion of your talk about the FDA having some desire to potentially you utilize clinical decisions support to help with The avoidance of these severe adverse events This may be an unfair question because I suspect it's in another portion of this large agency that you don't necessarily touch But FDA has expressed the Opinion that they have the ability to regulate clinical decision support as a device Because a concern about safety and so my question is is Do you see that as inherently in conflict or is this a way that we could potentially move forward to try and Get through this potential Mindfield of problems relating to the device Perception of the FDA Yeah, I think the so that is managed by the Center for Devices and I will I'm from the Center for Drugs so So, you know, I the spirit of that that comment was more that You know FDA labeling as a communication tool to inform prescribing is not the most agile And and I think that there probably is some value in having dynamic clinical decision support systems that would able be able to Inform prescribing in a real-time basis based on accumulating evidence even if imperfect Because they're the other systems aren't necessarily going to to be able to react so quickly That was the nature of that comment I we work with devices a lot If I may actually just follow up to that point I mean there had there has been interest with all the next generation sequencing talk as as Evidence in previous workshops that there is an intense amount of interest in trying to figure out other ways to Communicate clinical validity and have that be established that's outside of FDA walls There's been very little said about African Americans or Africans and the risk for these complications But my as far as in liver disease African Americans are over represented when it comes to liver injury from allopurinol and the aromatic anti-convulsants do we have any idea of the rates of Stevens-Johnson syndrome and in blacks Yeah, this is an issue we looked at many years ago One of the problems in the literature was that cases kept being re-reported and accumulated So when somebody said, oh, there were so many thousand cases. It was you know, the same cases kept being reported over and over again so we looked at it in Toronto with the people that we were studying and We looked at it and compared it to the census data Which was about a year old at the time And there did not appear To be a strong Signal it might be for the anti-epileptics. It looked like it might be twice as high as In the white population But then there was a paper around the same time to say that said that epilepsy was probably twice as prevalent in a black population So I don't know what that means. However, I would say that when blacks have had Stevens-Johnson TN They would have perhaps more severe disease and worse outcomes and part of that might well be the recognition of the rash early on People have maybe tender skin, itchy skin, the rash isn't picked up That's my concern and that extra delay of even three days or four days Whether it's access to health care or good diagnosis could result in worse outcomes From higher mortality rates and higher morbidity For sure, so I think it's a it's a very important but potentially a loaded question and trying to figure out exactly all that's going on But there's others are going to comment on it as well So it goes to the issue of FDA labeling if you say for Asians that It's worthwhile screening for this The problem is this this whole problem. We don't have data. It's not like the data is negative. We don't know How do we deal with them? I mean we we try to communicate that uncertainty the best of our ability. I mean it was a little Unsettling to hear that there's a genetic predictor in Italians and not the rest of Europe And I shuddered to think how you could write something around that you know, so There's uncertainty and I think for a lot of adverse reactions and For micro genetic biomarkers that you know if there is a absence of an effect that's often stated if There's uncertainty about what the implications of it are that will also be communicated Well, we certainly know the rates of these HLA types and African-Americans are they overrepresented Well, I mean some of it some of them are 58 oh one is is pretty much represented across races, although it's most prevalent in Southeast Asians it is represented in blacks and And Caucasians and the same with 1502 but 5701 obviously is much lower in blacks And you know when you look at African-Americans, obviously you're looking at admixture So you have to take into account admixtures. So the Prevalence the carriage rate is going to be somewhat intermediate and we saw that obviously was 5701 where it's less than 1% in Africans continental Africans, but two to three percent in African-Americans and You know, unfortunately the actual true Prevalence rates haven't been worked out in terms of actually there's continuing admixture. So it's it's a bit of a moving target I mean clearly there's admixture continuing in the United States. So some of these things I think need to be re-evaluated over time It's the same with what we call Hispanics, which is a diverse Racial mixed, you know the Mexican-Americans are different than like Cuban-Americans and like more represent Native peoples Gene the genes of Native people. So these types of things would be very I think very important to look at the rates of these these alleles in different populations and can you say for sure that the risk of these severe adverse reactions is different in Different races independent of the The clue that we should be looking if you see actually I mean the initial clues That actually led to looking for HLA associations with drugs to begin with actually were that there was an over Representation in specific racial groups So it goes both ways if there's actual epidemiological evidence that there's a clear clue that there's a racial preponderance and that is actually an important clue to actually look first for an HLA Association and the other issue that Manier was talking about yesterday with never a pin and C401 That is an allele that's well represented across races. Although there still may be other metabolic factors In certain racial groups like blacks Where there is actually a heightened risk because of that for instance, so there's complex effects and the phenitone Sip to C9 star 3 issue In Southeast Asians is another example where you're not just looking at an HLA association There's complex effects, but when you see a strong independent Epidemiological effect, I would say that's that's actually a strong indication in an immunologically mediated drug reaction That it is almost going to be a pure HLA effect So obviously as niceties are very important issue in this. So can we have Maya to comment on this? Actually my point was what what Neil said what they observed in the black population and what you asked when we did a study or We part of our epidemiological study in Europe was to look for certain exposures And when we compared the people with SJS TN exposed to never a pain It turned out that most of them were of African ancestry in in different countries, but mainly in France and So when we compared this group of of never a pain induced SJS TN patients to all other Patients the severity of the disease was about the same the outcome was about the same So this is not black and white comparison But it is among the eight these never a pain HIV infected patients the majority were Africans so what I was saying is we couldn't see that the severity of the disease was higher and we didn't see a higher death rate But the HIV infected patients are usually younger than the other ones We have and we know that age is one of the factors for Higher death rate. So just to put this a little bit into perspective I just want to ask a question on the drug induced liver injury We also collecting samples for the entity be drug induced liver injury and Because it's a cocktail and when I asked the doctors, you know, what do you do when you actually found a liver injury? The answer is never the same because the causative agent can be any of the you know form Main items in the cocktail all this while you thought it was I said nice it and then I think Thailand reported that is more or is it was it Rika in Indonesia that said that is probably more it than but all So, you know, I was wondering with all these uncertainties That would actually prolong the treatment that is required and for for For the entity be part. So perhaps I like a comment from you Because I think that what we are trying to do this Southeast Asian group is actually get all our Cases together and do it as a project at the moment. It's actually individual I I'm sorry, I didn't understand the question Perhaps you could talk about it during lunch because we do have to move on. We have a couple of more questions Yeah, sorry Did you switch me off? Comment first of all I was involved in the working party that Changed the label with the European medicine agency for carb may spin in 1502 And the longest time of discussion that we had was well, how do you define an Asian? How do you find a Southeast Asian and and obviously we're coming to how do you define occasion? Etc. And I think that is a big challenge as we go deeper into genomics That is facing all of us and the regulators in particular I think that needs to be some harmonization Across the different regulatory agency in terms of how that is done And how that's defined because you'll see that the European label in terms of how it defines with 1502 is completely different from the From the FDA label. So I think it is important That maybe the international conference harmonization might be an avenue where people need to sit down and talk about Well, how they're going to I should start defining this within drug labels That's a comment question for Mike. So Let me just put in disclaimer first as a senior author on the new general medicine 31 or one paper and and you compared and contrasted the 1502 and 30 one or one And 30 one one does lead to is I completely agree that the effect size is less than with 1502 and it does lead to a wide variety of Adversive X some which are mild but some which are also very serious including dress, you know Where it's been replicated in many different ethnic populations in in the I'm gonna use the terms again Caucasians Asians Chinese hand Chinese etc so With so much replication What evidence do you need to be able to make them label more sort of mandatory rather than Information only do you need a prospective study? Do you need a prospective trial? What would you need to be able to change the label from what it is to be consistent with what's seen with the 1502 Yeah, I mean it's it's complicated to answer. I mean there's probably no I mean the evidence is there the it's the effect size is smaller and the the efficiency of screening in terms of True positives that you're going to get in terms of positive predictive value negative predictive value We're likely going to shift quite a bit You know whether there's some odds ratio threshold that you cross that you make some More affirmative recommendation That's not been defined So it's hard to say I don't if you have suggestions and I agree it is difficult to say but but you know and Matt may want to comment on this and Matt did some power calculation But you would need a huge prospective study to be able to and get the same precision of estimates that can be seen with the case control studies that are already available and And my worry is that sometimes we have a different level of evidence needs for genetic markers compared to other markers So if you had let's say serum rhubarb, which said that they predisposes to carbamase been hypersensitivity because serum rhubarb might be easily measured in a laboratory and Everybody knows about that test. It might be easy. It might be easier to get that into the label than to get a genetic test marker and That is a worry and then that you can see that genetic exceptionalism Everywhere within within medicine. Yeah, I mean there is that exceptionalism and I'm not sure why it exists I think if you can make some assessment risk assessment for an individual patient based on age and race You should do just the same for genetics, but the reality is right now We don't necessarily have all that information and there's a societal burden of imposing testing on costs and all the other things and We also don't necessarily dictate medical practice absent contra indications and indications so The professional societies may have a say in this as well. I see pick I'm not sure So any questions not for mark Leave leave for Mike alone Yeah, I'll just answer I do not know question for Mary Harrington because What's the best technology now and cheapest to just do the HLA type for um, you know an individual because It we if we can just do it once and then the patient knows it for alipurinol and and carbamase apine and You know at the back of here and and then all the other risks that you mentioned for disease Maybe that's the most efficient use of our health care dollars The big problem is it it's actually in our lab we can do ABC DRD QDP for $80 The problem is is that when we do that we're doing nearly 400 people at a time so the real issue here is trying to Come up with an inexpensive way of typing one individual very quickly and that's what you need and I would say You see so what I'm saying is it's much more cost effective to do a whole lot of people at once Then it is one person every day for five months or something and So there are kits that can be purchased and I and you know, they are meant for typing And I think they're from Dino They can be purchased and they are meant for typing a single individual at a time And I think a lot of transplant labs use those They're not they're not hugely inexpensive, but I don't think they're outrageous I actually don't know how much they they cost But um, but they're quick and they'll do one person at a time They might not be huge resolution, but it doesn't sound to me like that's really what you need Maybe I could I could follow up if you don't mind with with Mary on that on that question I think Alan raised a very insightful question about how about looking at all of the the variation I mean it's variable of region as that is it's hard to imagine that all of the types that are known Possibly encompass all of the variation that that could be there So so is there working on to identify more serotypes or is it that that humans are a young population? And so really we don't have all of the of the variants there You know there somebody mentioned this I Maybe it was Elizabeth that at the be low because there are over five thousand alleles Okay, so and there there will be more leels Most of those the vast majority of those are hugely rare The problem is is that all of the techniques that we've used historically They keep the rare ones rare because they make the assumption. Oh This I've got this sequence I don't have sequence from Exxon 4 and the most common one is you know 1502 so it must be a 1502 and that keeps the rare ones really rare so but now Deep sequencing is used routinely for HLA typing You know there is like the junior the ABI junior could be used to sequence a single individual and I don't really know the cost I could look into what those kind of costs are maybe you know Elizabeth but And that gives really high resolution data and But but I think right now what I would do is look at what the transplant labs are doing They're getting high enough resolution that you know, they can go ahead and do a transplant and they're using You know techniques that are the least expensive And you know, there are a lot of techniques, you know, we used to use Sequence specific primers and it was a really inexpensive way to do it You need a good bit of DNA, but I don't think that would be a problem here It's inexpensive. You do one person at a time. There are things so and that's basically what that dinoc it is as well so If it was useful, I could try to generate Identify information on that in the cost for doing different types, which you know a lot of people I don't know if there's somebody here from a transplant lab that could comment Is it is one of our clinical center colleagues here who does the transplant typing or maybe I Might just make a comment that research labs that have high throughput and our lab for instance has both research and clinical accreditation But as Mary said, it's the high throughput nature of it It gets it down to reagents costs and with reagent costs You can get things down to 50 to 70 dollars a sample for sure But but at the end of the day even if you have all the alleles available with you to you You're still left with the decision support aspect of things and getting a report The other caveat is that it really is important to have quality labs doing this and labs that actually have quality assurance programs I mean we saw this early in the back of your story that once the clinical a story and The association had been worked out that all the safety issues moved to the lab And there were episodes of false positives and false negatives for 5701 There were blacks in the UK being called as 5701 Positive when they were negative and there's there were smattering of cases That were safety issues where they were false negative for 5701 in the early days So it really is important to get the lab technology right and that the final sort of point I'll make is really There's other sort of innovative techniques flow cytometry should not be overlooked There's actually a lab in San Francisco. I think Alan Wu is doing HLA B 57 by B 17 Using a B 17. I think it's the one lambda antibody But because B 58 is part of that same serotype He could actually effectively if he had Q8 it for this screen for both alipur and a baccadir with that B 17 Antibody so there are other innovative ways of doing this But I would still at the end of the day say if you ended up with information on 5,000, you know, you know Across the population on different HLA Leels, how would what information would you provide to patients? That's the problem So to a final comments It's actually done in my laboratory at the NIH clinical center Department of Transfusion Medicine and We looked into that very carefully and with the format genomics for for HLA in the clinical center program It's not that cheap and one has to do it at a Clinical approved Level to make a clinical decision that's different from Simply doing research and doing screening that can be done relatively inexpensively But once you actually want to make a clinical decision, it does cost some money in particularly in the United States And one has to consider that big issue and perhaps one could contribute something to that is Forwarding the information, you know, you have to do it only once in a lifetime if the documentation is properly Maintained and that can be used Decades from now and I we would be perceived a lack of Infrastructure to have this documentation in place and perhaps a cost-efficient Aspect would be to get a good documentation of what is done on can be done today typically One would probably look for sequencing results at this time, which is expensive. That's not $80 But it's worthwhile along a term to do it at the sequence level and also identify rare Leals, which otherwise would be missed if you do it inexpensively Thank you last comment give you an actual cost For immune the immunology lab at the hospital. I work to do MHC one MHC two is four hundred dollars I can also tell you this you need to be very careful about discussing cost because often people are discussing your agent costs So it's costing him $40 to for the reagents But then it may be costing another two hundred dollars for the manpower or person power So to say it the test only cost $40 isn't a real reflection of the economics of the test Okay, I think we just got here and This is a great session I would like to send all the speakers and all the comments and questions and next time We should have more time for question. I think The way we get more time for questions is the speakers stay to their times So so that was a challenge, but yeah, so thank you and thank you Mike So now we have a brief break for lunch We we only have 20 minutes to be able to run down get our lunch and bring it back So we're gonna be eating lunch while Lauren is speaking and and Lauren is going to start at 12 45 because we want to Have time for discussion, so we'll see you in 20 minutes