Podcasts about Selection

What is life, and where does it come from? These are two of the deepest, most vexing, and persistent questions in science, and their enduring mystery and allure is complicated by the fact that scientists approach them from a myriad of different angles, hard to reconcile. Whatever else one might identify as universal features of all living systems, most scholars would agree life is a physical phenomenon unfolding in time. And yet current physics is notorious for its inadequacy with respect to time. Life appears to hinge on information transfer — but, again, what do we mean by “information,” and what it is relationship to energy and matter? If humankind can't settle fundamental issues with these theoretical investigations, we might be missing other kinds of life (and mind) — not just in outer space, but here on Earth, right beneath our noses. But new models that suggest a vastly wider definition of life offer hope that we might — soon! — not only learn to recognize the biospheres and technospheres of other living worlds, but notice other “aliens” at home, and even find our place amidst a living cosmos.Welcome to COMPLEXITY, the official podcast of the Santa Fe Institute. I'm your host, Michael Garfield, and every other week we'll bring you with us for far-ranging conversations with our worldwide network of rigorous researchers developing new frameworks to explain the deepest mysteries of the universe.This week on the show, we speak with SFI External Professor Sara Walker (Twitter, Google Scholar), Deputy Director of The Beyond Center at ASU, where she acts as Associate Professor in half a dozen different programs. In this conversation, we discuss her pioneering research in the origins of life and the profound and diverse implications of Assembly Theory — a new kind of physics she's developing with chemist Leroy Cronin and a team of SFI and NASA scholars.  Sara likes to speculate out loud in public conversation, so strap in for an unusually enthusiastic, animated, and free-roaming conversation at the very bleeding edge of science. And be sure to check out our extensive show notes with links to all our references at complexity.simplecast.com.If you value our research and communication efforts, please subscribe, rate and review us at Apple Podcasts or Spotify, and consider making a donation — or finding other ways to engage with us — at santafe.edu/engage.Thank you for listening!Join our Facebook discussion group to meet like minds and talk about each episode.Podcast theme music by Mitch Mignano.Follow us on social media:Twitter • YouTube • Facebook • Instagram • LinkedInMentioned Papers:Intelligence as a planetary scale processby Adam Frank, David Grinspoon & Sara WalkerThe Algorithmic Origins of Lifeby Sara Imari Walker & Paul C. W. DaviesBeyond prebiotic chemistry: What dynamic network properties allow the emergence of life?by Leroy Cronin & Sara WalkerIdentifying molecules as biosignatures with assembly theory and mass spectrometryby Stuart Marshall, Cole Mathis, Emma Carrick, Graham Keenan, Geoffrey Cooper, Heather Graham, Matthew Craven, Piotr Gromski, Douglas Moore, Sara Walker & Leroy CroninAssembly Theory Explains and Quantifies the Emergence of Selection and Evolutionby Abhishek Sharma, Dániel Czégel, Michael Lachmann, Christopher Kempes, Sara Walker, Leroy CroninQuantum Non-Barking Dogsby Sara Imari Walker, Paul C. W. Davies, Prasant Samantray, Yakir AharonovThe Multiple Paths to Multiple Lifeby Christopher P. Kempes & David C. Krakauer Other Related Videos & Writing:SFI Seminar - Why Black Holes Eat Informationby Vijay BalasubramanianMajor Transitions in Planetary Evolutionby Hikaru Furukawa and Sara Imari Walker2022 Community Lecture: “Recognizing The Alien in Us”by Sara WalkerSara Walker and Lee Cronin: The Alien Debateon The Lex Fridman ShowIf Cancer Were Easy, Every Cell Would Do ItSFI Press Release on work by Michael LachmannThe Ministry for The Futureby Kim Stanley RobinsonRe: Wheeler's delayed choice experimentWikipediaOn the SFI “Exploring Life's Origins” Research ProjectComplexity Explorer's Origins of Life Free Open Online CourseChiara Marletto on Constructor TheorySimon Saunders, Philosopher of Physics at OxfordRelated SFI Podcast Episodes:Complexity 2 - The Origins of Life: David Krakauer, Sarah Maurer, and Chris Kempes at InterPlanetary Festival 2019Complexity 8 - Olivia Judson on Major Energy Transitions in Evolutionary HistoryComplexity 17 - Chris Kempes on The Physical Constraints on Life & EvolutionComplexity 40 - The Information Theory of Biology & Origins of Life with Sara Imari Walker (Big Biology Podcast Crossover)Complexity 41 - Natalie Grefenstette on Agnostic Biosignature DetectionComplexity 68 - W. Brian Arthur on Economics in Nouns & Verbs (Part 1)Complexity 80 - Mingzhen Lu on The Evolution of Root Systems & Biogeochemical CyclingAlien Crash Site 015 - Cole MathisAlien Crash Site 019 - Heather GrahamAlien Crash Site 020 - Chris KempesAlien Crash Site 021 - Natalie Grefenstette

2 Kings 20:1-22:2 Acts 21:18-36 Psalm 150 Proverbs 18:9-10 Selection from "Two Steps Forward" by Sharon Garlough Brown Song: Atch - Found You Music provided by Vlog No Copyright Music. Creative Commons - Attribution 3.0 Unported Video Link: https://youtu.be/G774NKvUm88#NoCopyrightMusic#VlogMusic#VlogNoCopyrightMusic

On January 1, 2015, physicist Max Tegmark gave up something most of us love to do: complain about things without ever trying to fix them. That "put up or shut up" New Year's resolution led to the first Puerto Rico conference and Open Letter on Artificial Intelligence - milestones for researchers taking the safe development of highly-capable AI systems seriously. Links to learn more, summary and full transcript. Max's primary work has been cosmology research at MIT, but his energetic and freewheeling nature has led him into so many other projects that you would be forgiven for forgetting it. In the 2010s he wrote two best-selling books, Our Mathematical Universe: My Quest for the Ultimate Nature of Reality, and Life 3.0: Being Human in the Age of Artificial Intelligence, and in 2014 founded a non-profit, the Future of Life Institute, which works to reduce all sorts of threats to humanity's future including nuclear war, synthetic biology, and AI. Max has complained about many other things over the years, from killer robots to the impact of social media algorithms on the news we consume. True to his 'put up or shut up' resolution, he and his team went on to produce a video on so-called 'Slaughterbots' which attracted millions of views, and develop a website called 'Improve The News' to help readers separate facts from spin. But given the stunning recent advances in capabilities - from OpenAI's DALL-E to DeepMind's Gato - AI itself remains top of his mind. You can now give an AI system like GPT-3 the text: "I'm going to go to this mountain with the faces on it. What is the capital of the state to the east of the state that that's in?" And it gives the correct answer (Saint Paul, Minnesota) - something most AI researchers would have said was impossible without fundamental breakthroughs just seven years ago. So back at MIT, he now leads a research group dedicated to what he calls "intelligible intelligence." At the moment, AI systems are basically giant black boxes that magically do wildly impressive things. But for us to trust these systems, we need to understand them. He says that training a black box that does something smart needs to just be stage one in a bigger process. Stage two is: "How do we get the knowledge out and put it in a safer system?" Today's conversation starts off giving a broad overview of the key questions about artificial intelligence: What's the potential? What are the threats? How might this story play out? What should we be doing to prepare? Rob and Max then move on to recent advances in capabilities and alignment, the mood we should have, and possible ways we might misunderstand the problem. They then spend roughly the last third talking about Max's current big passion: improving the news we consume - where Rob has a few reservations. They also cover: * Whether we could understand what superintelligent systems were doing * The value of encouraging people to think about the positive future they want * How to give machines goals * Whether 'Big Tech' is followin

2 Kings 18:13-19:37 Acts 21:1-17 Psalm 149 Proverbs 18:8 Selection from Blessings for the Morning by Susie Larson Song: Atch - Found You Music provided by Vlog No Copyright Music. Creative Commons - Attribution 3.0 Unported Video Link: https://youtu.be/G774NKvUm88#NoCopyrightMusic#VlogMusic#VlogNoCopyrightMusic

The Black Caps v England series is over and who could have predicted the past month of action? In this episode, Binksy, Baldy and Stu look back at the key moments and players. We discuss: Brendon McCullum, Ben Stokes and the England turnaround NZ's selection decisions The Ajaz Patel dilemma Whether the Black Caps should have a glass half-full or half-empty view of the series Runs from Jonny Bairstow, Ollie Pope, Daryl Mitchell and Tom Blundell NZ cricket depth Listener questions And much more as we deep-dive back into this fascinating series. June was a disrupted month for us with life and illness getting in the way, but we're expecting to be back on track in July. Please take the time to give us a like, follow, share or subscribe on all our channels (@toporderpod on https://twitter.com/Toporderpod (Twitter) and https://www.facebook.com/Toporderpod (Facebook), & @thetoporderpodcast on https://www.instagram.com/thetoporderpodcast/ (Instagram)) and a (5-Star!) review at your favourite podcast provider, or tell a friend to download. It really helps others find the show and is the best thing you can do to support us. You can also find all our written content, including our Hall of Fame series, at our https://www.thetoporderpodcast.com/ (website), and a few of our episodes are available on https://www.youtube.com/channel/UCo3GSknJELxxH4IDec2AjUA (YouTube) - we're slowly chipping away at populating this channel. You can also dip back into our guest episodes - including chats with Wasim Khan, Dion Nash, Mike Hussey, Finn Allen, Lesley Murdoch, Lockie Ferguson and many more fascinating people from all across the cricketing world. And if you'd like to reach out to us with feedback, questions or guest suggestions, get in touch at thetoporderpodcast@gmail.com. Thanks for listening.

Today's episode features a question and answer session with Joel Smith. On the show today, I answer questions related to “are there any bad exercises?”, sport speed concepts, jump training, “switching” sprint drills, and much more.  I love being able to highlight and integrate information from so many of the past guests on this podcast into my own training, coaching, and ultimately, the answers I provide on this show.  In many senses of the word, this is truly an “integration” episode of the podcast series. Today's episode is brought to you by SimpliFaster and Lost Empire Herbs. For 15% off your Lost Empire Herbs order, head to lostempireherbs.com/justfly. To try Pine Pollen for FREE (just pay for shipping), head to: justflypinepollen.com View more podcast episodes at the podcast homepage. Timestamps and Main Points: 3:16 –Is there any such thing as a bad exercise? 17:19 –How do we speed up soccer players? 30:25 –Do you find value in spending time on switching drills? 45:07 –Athletes who take too many steps in a start or acceleration. 53:19 –Does walking affect fast-twitch fibers? 54:45 –Setups for high jump off-season/yearly plyo program for high level jumpers? 1:01:36 –How to speed jump like elite high jumpers? About Joel Smith Joel Smith is the founder of Just Fly Sports and is a sports performance/track coach in Cincinnati, Ohio.  Joel hosts the Just Fly Performance Podcast, has authored several books on athletic performance, and in 2021, released the integrative training course, “Elastic Essentials”.  He currently trains clients in the in-person and online space. Joel was formerly a strength coach for 8 years at UC Berkeley, working with the Swim teams and professional swimmers, as well as tennis, water polo, and track and field.  A track coach of 15 years, Joel coached for the Diablo Valley Track and Field Club for 7 years, and also has 6 years of experience coaching sprints, jumps, hurdles, pole vault and multi-events on the collegiate level, working at Wilmington College, and the University of Wisconsin, LaCrosse, along with his current work with master's, high school and collegiate individuals. Joel has had the honor of working with a number of elite athletes, but also takes great joy in helping amateur athletes and individuals reach their training goals through an integrative training approach with a heavy emphasis on biomechanics, motor learning, mental preparation, and physiological adaptation.  His mission through Just Fly Sports is: “Empowering the Evolution of Sport and Human Movement”.  As a former NAIA All-American track athlete, Joel enjoys all aspects of human movement and performance, from rock climbing, to track events and weightlifting, to throwing the frisbee with his young children and playing in nature.

Today's episode introduces our latest series for brands, Influencer Drops. Understandably, if you follow us on social (and if you don't—you should) you may have some questions about it these drops, like, what are they? Why am I not on the list? How would one get on said lists?James also covers four things that impact influencer selection, how to play to your personal strengths, and treating your profile as a marketing site.

Live Recorded Set from VirtualDJ Radio Hypnotica

We speak with WBUR's education reporter and the executive director of the Massachusetts Association of School Committees on the 'systemic improvement plan' for Boston Public Schools and the upcoming vote for a new superintendent.

Featuring perspectives from Drs Javier Cortés, Matthew Goetz, Erika Hamilton, Ian Krop, Hope Rugo and Sara Tolaney, including the following topics: Introduction (0:00) Optimizing the Management of ER-Positive Localized Breast Cancer — Matthew P Goetz, MD (7:50) New and Novel Treatment Strategies for Localized Triple-Negative Breast Cancer (TNBC) — Erika Hamilton, MD (38:35) Considerations in the Care of Patients with Localized HER2-Positive Breast Cancer — Ian E Krop, MD, PhD (56:03) Evolving Clinical Decision-Making for Patients with HER2-Positive Metastatic Breast Cancer (mBC) — Javier Cortés, MD, PhD (1:18:47) Selection and Sequencing of Therapy for ER-Positive, HER2-Negative mBC — Hope S Rugo, MD (1:40:41) Recent Advances in the Care of Patients with Metastatic TNBC — Sara M Tolaney, MD, MPH (2:11:40) CME information and select publications

We discuss the hot topic of caliber selection. When people learn that I am shooting 6.5 Creedmoor it catches many people's attention in the precision rifle competition community. While the 6.5 Creed is a wildly popular cartridge, it has become less popular among PRS/NRL competitors in favor of lower recoiling cases like the 6 Dasher, 6 BR, and 6 BRA. I personally have shot the 6 Dasher for several years and love the round. It allowed competitors to shoot the same BC bullet the same speed as a 6.5 creed or 6.5x47L with significantly less recoil. With the advent of 153-156 class of bullets from Berger and Hornady, the extra BC has made the 6.5s look more and more appealing. The question is the bang worth the buck? We recorded this podcast on the drive home from the SAC Blue Ridge Rumble PRS match, that was held in Benge, Washington. We discuss the match and how we felt about it. It was a great match, with several unique stages that challenged everyone.

Catch up on all the Rugby League news from NRL360, Tuesday the 28th of June, with host Braith Anasta and of course, Paul Kent. The boys are joined by Dave Riccio and Paul Crawly to discuss the news of Cameron Ciraldo opting out of a deal with the Wests Tigers, and what that means for Brett Kimmorley.  For more of the show tune in on Fox League CH 502 or stream full episodes on KAYO. See omnystudio.com/listener for privacy information.

Join us as These Football Times senior writer and social media guru Josh Butler suggests who should be honoured on Manchester United's very own Mount Rushmore. With so many players to choose from, there's plenty of debate and opinion from across the panel.

CME credits: 0.25 Valid until: 28-06-2023 Claim your CME credit at https://reachmd.com/programs/cme/keeping-pace-in-hematologic-malignancies-optimizing-treatment-selection-in-relapsed-or-refractory-multiple-myeloma/13823/ Patients with multiple myeloma inevitably experience disease relapse, which is challenging. Rapid therapeutic advances have heralded an increasing number of efficacious targeted strategies and combination therapies for patients after a first relapse or in those with heavily pretreated disease. However, selecting the optimal regimen requires a individualized approach. Hear how Dr. Amrita Krishnan and Dr. Morie Gertz translate the evolving clinical data into their clinical practices and what factors influence their choices to improve durable responses and outcomes for patients with relapsed/refractory multiple myeloma.

Featuring perspectives from Drs Tanios Bekaii-Saab, Kristen Ciombor, Eileen O'Reilly, Philip Philip, John Strickler and Prof Eric Van Cutsem, including the following topics: Introduction (0:00) Integration of targeted therapy and immunotherapy into the management of metastatic colorectal cancer — Kristen K Ciombor, MD, MSCI (3:15) Other considerations in the management of early and advanced colorectal cancer — John Strickler, MD (33:15) Current and future treatment paradigm for gastroesophageal cancers — Eric Van Cutsem, MD, PhD (55:26) Selection and sequencing of therapy for advanced hepatocellular carcinoma — Philip A Philip, MD, PhD, FRCP (1:23:00) Novel treatment strategies for advanced biliary tract cancers — Tanios Bekaii-Saab, MD (1:50:31) CME information and select publications

À quelques jours du Tour de France, Maghalie s'entretient avec Antoine Duchesne pour entendre parler de sa sélection pour le Tour de France 2022. La sélection fut très émotive autant pour Antoine que pour sa femme Chloé. Le chemin pour s'y rendre n'aura pas été facile avec une mononucléose, une opération, et plusieurs autres obstacles, mais ils y sont arrivés ensemble! Cet épisode se veut une fenêtre sur l'envers du décor ainsi que sur la réalité pas toujours rose d'être un athlète de haut niveau, autant de la perspective de l'athlète que de la famille qui l'entoure.

“The most frustrating part I have found is the vast amount of information about schools, applications, and chances that is out there. It's been hard to sift through all the noise and really figure out what schools are good for you and what your actual chances are.” – Margaret, USA Feel the same way? Trust me, you're not alone. We've helped over 3,500 MBA applicants from 50 countries shortlist MBA programs, and hear comments like this all the time. What if you could figure out MBA programs you're excited about AND competitive at, that would be a great investment in your future? And do this with the least time and effort? I'm a former MBA Admissions Director who has thought about this problem – how to make school selection easier – for the past 10 years. I've also observed where applicants end up applying and attending. Why? So I could cut out any part of the research and selection process that has no utility. In other words, to save you time. I would like to share with you the 4-step method that I believe is most effective for shortlisting best-fit MBA programs. The best part of this method? It will give you the best chance of getting in, too. Topics Introduction (0:00) Rankings: The Good, The Bad and The Ugly (3:40) Step 1: Reflect on Your A, B, and C (9:25) Step 2: Determine Your "Must Haves" (12:10) Step 3: Evaluate Your Competitiveness (17:00) Step 4: Interact to Find Fit (22:00) Conclusion (24:45) Show Notes How to Choose the Right MBA Programs for You: Follow these Four Steps to Find the Right Business Schools Episode write-up and show notes: https://touchmba.com/business-school-selection-simplified Get free, personalized school selection help at Touch MBA: https://touchmba.com

Join Kenny Troiano and Frank Bradley, as they discuss Purity of Blood, and the Failures of the Modern-Day Breeder. Last week we talked about how long it can take to create a true strain. This time we're going to talk about why so many breeders fail to create a true strain. This topic can be controversial, and some say that breeding to create a pure strain is a myth. However, we will show you that not only is it not a myth, but it's very possible. This is a show you do not want to miss!   We specialize in gamefowl breeding, chicken breeding, and breeding related topics. This includes the use of proper breeding programs and proper selection practices. It is our mission to provide our followers and members a greater understanding of poultry genetics, poultry health care and disease prevention, and how to improve the production and performance ability of their fowl. If you are interested in creating a strain, or improving your established strain, you are going to enjoy this show. We also want to encourage you to join us at the Breeders Academy, where we will not only help you increase your knowledge of breeding, advance your skills as a breeder, but improve the quality and performance of your fowl.   If you would like to learn more, go to: https://www.breedersacademy.com   #breedinggamefowl #breedingchickens #gamefowlbreeders #chickenbreeders #gamefowlbreeding #chickenbreeding

On the Origin of Species By Means of Natural Selection by Charles Darwin This one should help you sleep, as it's so boring I lost track of what I was saying as I was reading this! I think it's mostly about people breeding domestic animals? I did live edit some pretty racist stuff out so be warned if you look it up to read forther. Story (07:04) SleepPhones, our exciting new partnership In our experience the best way to experience the bedtime stories of Sleepy Time Tales is with some type of headphone or earbud, but they can be cumbersome and uncomfortable. So we've partnered SleepPhones, manufacturers of headphones designed specifically to sleep in! They use a thin speaker fitted to a comfortable headband and have options from the cost effective wired headphones to the convenient Bluetooth model and will work with Sleepy Time Tales to improve your night's sleep. To check them out go to sleepphones.sleepytimetales.net to check them out and support Sleepy Time Tales. New Merch Store!! I've partnered with TeePublic to setup a new merch store. But because I'm no visual artist I'm taking advantage of a great TeePublic feature that allows me to share the works of other creators; expose them to my audience, allow their work to be purchased, and receive a small cut myself. Check out the storefront at https://www.teepublic.com/stores/sleepy-time-tales?ref_id=25247 or go directly to store.sleepytimetales.net or merch.sleepytimetales.net. I'd also like to issue a call. Any listeners with works up on TeePublic, please feel free to let me know and I'll look at adding your stuff to my store. No promises, but I do have a few thousand monthly listeners, so that may help give you a boost.   Find On the Origin of Species By Means of Natural Selection by Charles Darwin https://www.gutenberg.org/ebooks/1228 Supporting Sleepy Time Tales If you would like to support my work and help keep the podcast available and for free, there are several ways you can support the show. You can support the show as a supporter on Patreon and receive a host of bonuses including Patron only episodes and special edits https://www.patreon.com/sleepytimetales If you're enjoying Sleepy Time Tales and would like to make a financial contribution, but would rather not commit to a monthly payment then you can throw a tip in the jar at me/sleepytimetales Get yourself a set of SleepPhones, headphones designed specially for your needs as an insomniac who likes to listen to something to help you sleep, take a look at https://www.sleepphones.com/?aff=740 or sleepytimetales.net Or check out our new Merch store up at TeePublic where you can buy Sleepy Time Tales merch or even cool works from other creators. Go to sleepytimetales.net Treat yourself to a free audiobook to keep from Audible's significant range, and help Sleepy Time Tales to keep the lights on and grow. Go to com/sleepytime and sign up for a free 30-day trial. Patreon $5 Patrons ·         Jessica ·         Jennifer D ·         Sean O ·         Abby F ·         Felicity R ·         Chris & Moya ·         Michaela ·         Barcode ·         Adam ·         Tim ·         Joni ·         Callan ·         Mysti ·         Terri ·         Roberta   Please Share If you're enjoying the show, and finding it helps you sleep despite the stresses and strains of your life, the absolute best thing you can do is share it with your friends, families, acquaintances, cellmates etc. Anyone who needs a good night's sleep might benefit. So please share it with the people in your life, whether in person or on social media. Find The Show Website: sleepytimetales.net Patreon: https://www.patreon.com/sleepytimetales Twitter: https://twitter.com/sleepytimetales Facebook: https://www.facebook.com/sleepytimetalespodcast/ YouTube: https://www.youtube.com/channel/UC8gG5z50RjyiJ0_YXeQJpbg Merch: merch.sleepytimetales.net Music: http://loyaltyfreakmusic.com/ Music Patreon: https://tinyurl.com/loyaltyfreak Project Gutenberg Terms of Use https://www.gutenberg.org/wiki/Gutenberg:Terms_of_Use  

Join French Producer and DJ Laurent for the best in House, Funky House and Dance Music including exclusive remixes to get you kick started for your Saturday Night!

Today we hear the Combat Story of a long-time Green Beret, combat veteran, and retired Sergeant Major Josh Johnson. Josh spent multiple years downrange in Iraq and Afghanistan, many with 1st Special Forces Group, in combat where he led from the front but also spent years teaching other Green Berets and partner forces. [Support us on Patreon and get exclusive content and insights at www.patreon.com/combatstory]Josh was selected as an Exchange Officer to the Australian Special Air Services Regiment where he trained and fought alongside our very close Australian brethren. In his last two years of service, Josh focused specifically on leadership development and training.Since leaving the service, Josh has continued training and developing leaders, this time with Mike Sarraille's Talent War Group where Josh is a Partner and Senior VP of Leadership Development.I hope you enjoy this interesting and wide-ranging Combat Story as much as I did. Find Josh Online:-LinkedIN https://www.linkedin.com/in/joshuafhijohnson/Find Ryan Online: - Ryan's Linktree https://linktr.ee/combatstory- Merch https://www.bonfire.com/store/combatstory/- Instagram @combatstory https://www.instagram.com/combatstory- Facebook @combatstoryofficial https://fb.me/combatstoryofficial- Send us messages at https://m.me/combatstoryofficial- Email ryan@combatstory.com- Learn more about Ryan www.combatstory.com/aboutus- Intro Song: Sport Rock from Audio JungleShow Notes: 0:00 - Intro 0:41 - Guest Introduction (Josh Johnson) 1:36 - Interview begins 3:29 - His time fighting alongside the Aussies 8:11 - Growing up in small town in Utah and having a dad in military 18:41 - How he found himself on the SF track after National Guard and being an MP 30:24 - Funny story about robbing a Bosnian bathroom32:32 - Selection experience in 1999 and where he was when 9/11 happened 34:56 - Combat Story #1 - Operation Enduring Freedom – Philippines and his first time getting shot at 46:33 - Combat Story #2 -A multi-hour gun fight and getting hit with RPGs in Afghanistan 58:34 - Combat Story #3 - Stories of men getting shot next to him 1:09:35 - Experience as an ODA working with ranger battalion 1:19:18 - Transition to Talent War Group 1:25:42 - Benefits of vets in corporate America and unique challenges they face 1:31:24 - What did you carry into combat?1:35:20 - Would you do it again?1:39:20 - Listener comments and shout outs To learn more about a Green Beret In Combat, learn more at: https://www.combatstory.com/The video is all about a Green Beret In Combat but also covers the following subjects:- Green Berets Overcoming obstacles- Special Operations- Special Operations combat- Exchange programs with the Australian SASR and UK SAS- Multi-hour gun fightsSomething I noticed when I was looking for information on Green Berets In Combat was the lack of details._________________________Follow our video clips about Green Beret In Combat and various other similar topics on:Facebook: https://fb.me/combatstoryofficial Instagram: https://www.instagram.com/combatstory_________________________If you were searching for more information about living in Green Beret In Combat did this video help?Possibly you want to comment below and let me understand what else I can assist you with or Green Beret In Combat.

  Player: Garrett Wilson Team: New York Jets Selection: 10th Overall (Round 1 // Pick 10)   On the latest episode of the Razzball Fantasy Football Podcast, Bobby LaMarco and Donkey Teeth welcome in Sky Guasco to discuss former Ohio State wide receiver Garrett Wilson and what his potential fantasy value is as a rookie in New (Jersey) York. Please, blog, may I have some more?

Live Recorded Set from VirtualDJ Radio PowerBase

ESPN NBA Front Office Insider Bobby Marks joined OverDrive earlier today following yesterday's NBA Draft. He touched on the lack of suspense through the evening, the Raptors 33rd pick of Christian Koloko & how he sees the Kevin Durant saga playing out this offseason.

In Episode 1202, Sean Woodley talks about the Toronto Raptors selection of seven-foot Arizona center Christian Koloko with the 33rd-overall pick in the 2022 NBA Draft on Thursday night, before being joined by Mark Schindler (Basketball News, Tag the Roll) for a scouting report on the newest Raptor. Off the top, Sean details why the quiet overall night for the Raptors, which featured the Koloko selection and no OG Anunoby trade, was just about the ideal outcome Raptors fans should have been hoping for from the Draft, especially when you read the tea leaves on what it might suggest about the rest of the Raptors' off-season plans. Next, Sean replays a clip from Rafael Barlowe's recent appearance on the show breaking down Koloko and why his burgeoning three-point shot could be the swing skill that opens up a whole new world of upside for the Douala, Cameroon native. Lastly, Sean and Mark talk about why Koloko is a great fit in Toronto, the floor his defense will provide him, and what needs to happen for him on the offensive end for him to really tap into his potential as an all-around big man. Support Us By Supporting Our Sponsors! PrizePicks Check out PrizePicks.com and use promo code: “NBA” or go to your app store and download the app today. PrizePicks is daily fantasy made easy! Built Bar Built Bar is a protein bar that tastes like a candy bar. Go to builtbar.com and use promo code “LOCKED15,” and you'll get 15% off your next order. BetOnline BetOnline.net has you covered this season with more props, odds and lines than ever before. BetOnline – Where The Game Starts! Rock Auto Amazing selection. Reliably low prices. All the parts your car will ever need. Visit RockAuto.com and tell them Locked On sent you. Arcade1up Pre-order now from arcade1up.com - that's Arcade, the number 1, Up, dot com - for an estimated early September ship date! They are giving away a NBA JAM Shaq edition to a Locked On listener! Enter for a chance to win a game console for your man-cave at arcade1up.com/lockedon. Learn more about your ad choices. Visit podcastchoices.com/adchoices

O convidado mais do que especial do episódio #67 do Outliers é um dos maiores investidores da história moderna do mercado financeiro, Howard Marks - sócio-fundador da Oaktree Capital.Com mais de 50 anos de experiência, Howard montou, junto com Bruce Karsh, uma gestora que se destaca hoje entre as maiores casas focadas em crédito High Yield no mundo, com mais de 160 bilhões de dólares sob gestão.Na conversa, ele fala sobre as características mais importantes para se destacar no mercado, ciclos econômicos (e por que ele não acha que estamos em um ciclo comum), inflação e como acha melhor se posicionar hoje.Episódio simplesmente imperdível!O Outliers é apresentado por Samuel Ponsoni, gestor dos fundos da família Selection na XP, e Carol Oliveira, coordenadora de análise de fundos da XP.Acompanhe todos os conteúdos da XP em https://conteudos.xpi.com.br/Participe do canal do Telegram para estar sempre atualizado: https://t.me/xp_investimentosConfira mais conteúdos também através do nosso Instagram: https://www.instagram.com/xpexpert/ Assine o Expert Pass e tenha acesso a conteúdos exclusivos: https://bit.ly/ExpertPass.Deixe seu comentário, inscreva-se no canal e ative as notificações para receber todas as novidades: https://bit.ly/3lUQQWW.Investir com a XP Investimentos é fácil, basta criar o seu cadastro e em minutos você já pode começar a investir: https://t2m.io/0LmPbW4

O convidado mais do que especial do episódio #67 do Outliers é um dos maiores investidores da história moderna do mercado financeiro, Howard Marks - sócio-fundador da Oaktree Capital.Com mais de 50 anos de experiência, Howard montou, junto com Bruce Karsh, uma gestora que se destaca hoje entre as maiores casas focadas em crédito High Yield no mundo, com mais de 160 bilhões de dólares sob gestão.Na conversa, ele fala sobre as características mais importantes para se destacar no mercado, ciclos econômicos (e por que ele não acha que estamos em um ciclo comum), inflação e como acha melhor se posicionar hoje.Episódio simplesmente imperdível!O Outliers é apresentado por Samuel Ponsoni, gestor dos fundos da família Selection na XP, e Carol Oliveira, coordenadora de análise de fundos da XP.Acompanhe todos os conteúdos da XP em https://conteudos.xpi.com.br/Participe do canal do Telegram para estar sempre atualizado: https://t.me/xp_investimentosConfira mais conteúdos também através do nosso Instagram: https://www.instagram.com/xpexpert/ Assine o Expert Pass e tenha acesso a conteúdos exclusivos: https://bit.ly/ExpertPass.Deixe seu comentário, inscreva-se no canal e ative as notificações para receber todas as novidades: https://bit.ly/3lUQQWW.Investir com a XP Investimentos é fácil, basta criar o seu cadastro e em minutos você já pode começar a investir: https://t2m.io/0LmPbW4

Mike Mulligan and David Haugh were joined by NBC Sports Chicago analyst Will Perdue, who expressed a wait-and-see approach regarding the Bulls' selection of Arizona guard Dalen Terry with the No. 18 pick in the NBA Draft on Thursday evening. Perdue also explained why he isn't a fan of the Bulls potentially trading for Jazz center Rudy Gobert.

This week I go over some surprising recent Tour de France selection news and what it will mean for the race before (07:08) breaking down some key performances at the recent Tour de Suisse & Tour of Slovenia. Get daily in-depth pro cycling tactical analysis with the BTP newsletter Listen to Kristen Faulkner's appearance on the BTP podcast during his first pro season

As broadcast June 24, 2022 with plenty of hearts for your streaming lovefest.  Tonight we begin by paying tribute to a legend of the synthesizer and the studio in Patrick Adams, who passed away on Wednesday.  An inspiration to artists all over the spectrum, he left a massive mark for both those that were aware and even more so for those that were blissfully ignorant.  Rest In Power to a legend.  For the main event, Lizz Kalo is back in the studio with Danno to talk about her stellar video that debuted today to her latest single "Transition."  Our dear friend has also been spreading her wings on the events front, with her very successful Creative Social monthly going national to Seoul and Busan as well!#feelthegravityTracklisting:Part I (00:00)Marta Acuna – Dance Dance Dance (12” vers)Monique Bingham & Black Coffee – Deep In The Bottom – of AfricaThakzin feat Sun-el Musician & Thandazo – ICUSio feat Dunn – Reverse Flight Part II (35:16)Lizz Kalo – Shoot MeLizz Kalo – Tall GirlsRobert Glasper feat HER & Meshell Ndegeocello – Better Than I Imagined (DJ Tunez remix)Fela Kuti – Peace of Mind (Virgil Abloh remix)Keleketla feat Coldcut & Antibalas et al – International Love AffairTony Allen & Hugh Masekela – Robbers, Muggers, and Thieves Part III (65:32)Lizz Kalo – TransitionKendrick Lamar feat Blxst & Amanda Reifer – Die HardDoja Cat – WomanAUDREY NUNA – TimeBenson Boone – GHOST TOWNAsa – Show Me Off Part IV (98:38)Lizz Kalo – Treat Me BetterBurna Boy – Last LastLloyiso – SpeakCosta Titch feat C'Buda M, Alfa Kat, Banaba Des, Sdida, Man T – Big FlexaStefflon Don feat Ms Banks – DipAllen Stone – Consider Me 

When we take care of our leaders and their mental health, we're all able to show up as our best selves--at work and at home. As leaders in human resources, we can do this by unlocking potential by supporting them to growth their mental health skills - in empathy, leadership, and coping with challenges.This is important because organizations that are viewed as highly empathetic have employees that are more likely to positively talk about their company to friends, peers, and families. And organizations that truly focus on culture are twice as likely to retain their employees.We're in a world of change, with the great resignation and the lesser-talked about great retirement. Both are impacting the workplace in ways we couldn't have predicted.This week on the podcast, I'm happy to share this and more with you from Dr. Alexander Alonso, the Society for Human Resource Management's (SHRM) Chief Knowledge Cfficer. We're talking about unlocking leadership potential, the benefits of having taboo conversations, why we need to hold onto our talent, and so much more. Alex also shares more about the conversations he had at the recent SHRM conference and his newest book about making the most of polarizing conversations.About Alexander Alonso:Alexander Alonso, PhD, SHRM-SCP is the Society for Human Resource Management's (SHRM's) Chief Knowledge Officer leading operations for SHRM's Certified Professional and Senior Certified Professional certifications, research functions, and the SHRM Knowledge Advisor service.   He is responsible for all research activities, including the development of the SHRM Competency Model and SHRM credentials.  During his career, he has worked with numerous subject matter experts worldwide with the aim of identifying performance standards, developing competency models, designing organizational assessments, and conducting job analyses.   He was also responsible for working on contract task orders involving the development of measurement tools for content areas such as job knowledge (like teacher knowledge of instructional processes) and organizational climates (like organizational climate forecasting in military health care).Throughout his career, he has published works in peer-reviewed journals such as Industrial and Organizational Psychology: Perspectives on Science and Practice, Journal of Applied Psychology, International Journal of Selection and Assessment, People and Strategy, Personality and Individual Differences, Quality and Safety in Health Care, and Human Resources Management Review.  He has also authored several chapters on community-based change initiatives in workforce readiness, as well as co-authoring Defining HR Success: A Guide to the SHRM Competency Model in Practice.Dr. Alonso also served as a columnist analyzing major trends in the workforce for The Industrial Psychologist and HR Magazine. In addition, he has served on several professional society boards including the SIOP and the Personnel Testing Council of Metropolitan Washington. Mentioned in this Episode of Mental Health for Leaders:Talking Taboo: Making the Most of Polarizing Discussions at Work by Alexander AlonsoThink Again by Adam GrantWendi Safstrom: The Need to Prioritize Mental Health at WorkMental Health Skills TrainingJoin the monthly digital subscription

Gabe Ramirez opened his show by reacting to the Bulls' selection of Arizona guard Dalen Terry at No. 18 overall in the NBA Draft. He also listened to Bulls general manager Marc Eversley's press conference on what Terry will bring the team and what lies ahead in the offseason. Later, Ramirez took calls from listeners.

It's time for the finalists of the reality show Selection Project to take the stage! The winners will make their debut as idols, and the losers... Well. You'll see. (Also, is anyone getting a sense of deja vu?) ♡ Follow us on social media! Twitter | Instagram ♡ Join our Discord server!

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Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, highlight key advances in early phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting and also address toxicities, including immune checkpoint inhibitor-associated myocarditis. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. My name is Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology, specializing in melanoma and phase 1 therapeutics at the University of Pittsburgh's Hillman Cancer Center. I am the guest host of today's podcast. My guest today is Dr. Jason Luke, a colleague and the director of the Cancer Immunotherapeutics Center at the UPMC Hillman Cancer Center here.  Today, we'll be discussing advances in early-phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting.   You'll find our full disclosures in the show notes, and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Thanks so much for the invitation. It was a great ASCO, and I hope everyone had a good time.  Dr. Diwakar Davar: So, onto our abstracts. So, the first one that we'll be discussing, and Jason as you know we've done this before. We'll be rapidly transitioning between phase 1 therapeutics, melanoma, and advanced phase 2 and 3 trials, but you know this is something you do very well. So Abstract 2504, it's a phase 1 trial of TIM-3 inhibitor cobomilab immunotherapy and in combination with PD-1 inhibitors nivolumab and dostarlimab. The AMBER Trial that was presented recently, and in full disclosure, both you and I actually are on this abstract. So, what do you think of this abstract? What do you think of the data that is discussed, and how do we contextualize this in relation to what needs to be done in this space?  Dr. Jason Luke: So, I think this is an exciting abstract because it brings forward what may be the next high-priority immune checkpoint to try to target in clinical oncology. To level-set, I think everybody listening will know about PD-1 and CTLA-4 as immune checkpoints. In the last year, we've had LAG-3 come forward as now a standard of care element of armamentarium in melanoma, and we look forward to further studies of LAG-3 and other tumor types as we think it should be a good partner where PD-1 is otherwise approved.  So here now, we hear about TIM-3, which is another negative regulatory checkpoint on a number of different immune subsets. And in this abstract, the antibody targeting TIM-3 was cobolimab. So, TIM-3 is a very interesting molecule. It has, what you might call, pleiotropic effects in the immune system. So, while in the context of this abstract, it was being targeted as another immune checkpoint on T cells, it's important to point out that TIM-3 has other regulatory roles in other immune subsets such as myeloid cells and very particularly dendritic cells, and that's important because it might bring in another element of the innate immune system to try to drive anti-tumor responses. So, it's an exciting target because it might be able to expand the groups of patients who could benefit from immune checkpoint blockade.  So, in this abstract, we see initially the phase 1 data of combining cobolimab, anti-TIM-3 with anti-PD-1 of a couple of different flavors. And what you could take from this abstract is that in the phase 1 setting, the drug was well-tolerated and combined well, and had pharmacokinetic properties that would be consistent with what we'd expect for this kind of a monoclonal antibody. I think we have to marry this abstract, which is really the phase 1 data about safety in pharmacokinetic (PK) to another abstract presented in the melanoma session, which showed an expansion cohort of patients who got cobolimab plus nivolumab or dostarlimab.  And there we did see a 50% response rate, albeit that there was heterogeneity of patients being treatment naïve versus treatment-experienced. So, what I would say to this on a high level is that I think these data are preliminarily exciting, suggesting that further investigation into TIM-3 may be valuable in terms of expanding the population of patients initially in melanoma, but there will data coming soon in lung cancer and in other tumor types with another novel checkpoint. And I think if we think ahead into the future, the question is probably going to end up being, which combinations of checkpoints for which patients. That's pretty exciting to think about. We've seen a lot of data of PD-1 plus other molecules, and I think some future biomarker stratification really will be necessary to know which patient would benefit the most from which of these combos, but for the time being, this is exciting data to see where the field is going to go over the next couple of years.  Dr. Diwakar Davar: Great. And I guess, to your point, one important thing to highlight from the abstract is your point about the role of the different compartments. There was actually a very interesting dose-response relationship with the highest dose of the drug not necessarily being the most effective dose, suggesting that yes, as you escalate, you may have different effects in different compartments, and maybe therefore a broad selection of doses might be required to ensure that you have optimal engagement of the optimal target.  So, the next abstract is Abstract 3007. This is the tumor-agnostic efficacy and safety of erdafitinib. So, we now know that FGFR pathway aberrations are found from 77% of all malignancies, FGFR targets are now U.S. Food and Drug Administration (FDA) approved in cholangiocarcinoma with pemigatinib, infigratinib, and as well with erdafitinib metastatic urothelial cancer. We know that these agents are not necessarily effective tests in 1 tumor type because these alterations have risen in multiple tumor types. So, the RAGNAR trial, looking at this across multiple tumor types, what do you make of the interim analysis result presented by Dr. Loriot?  Dr. Jason Luke: So, I'd say that this is probably the future of targeted therapy. And so, I think that where we have activity in 1 disease, it's very likely we would have activity in others. So, the author has described this as the largest basket trial of a molecularly defined subset that's been pursued to date. There are upwards of more than 200 patients in the study. I think it's really important, as we think about the data, to realize, though, that all FGFR alterations are not exactly the same thing. And so, in this study, they gave erdafitinib to patients with solid tumors of any FGFR altered status. And so that's FGFR1, 2, 3, 4 mutations or gene fusions. And that's a lot of heterogeneity in there actually.  And in this study, there were two-thirds fusions and one-third mutations, mostly in FGFR2 and 3. That will become relevant as we start to think about the results. On a high level, I have to say that it is impressive in pan-cancer fashion, just selecting by FGFR alteration, there's about a 30% response rate observed. I think that no matter what, that's going to be valuable considering these were patients with refractory tumors with 3 lines of prior therapy on median. I think what we need to know more is the breakdown of which specific molecular alteration and FGFR in which tumor types drove most of the benefit.  So, for example, in bladder cancer where erdafitinib is already approved, that's almost entirely an FGFR3 fusion setting. So we know the drug is effective there. And so I think there will be a further breakdown of the data. As it matures more, you really start to tease out, is it really the case that any FGFR alteration can be treated or there are some that really ought to be the high priorities that we really ought to be going after. I think it would be remiss not to also note, however, that while there's excitement about this sort of pan-cancer approach, the current generation of FGFR inhibitors are not exactly the easiest drugs to take.  And so, the in-class, hypophosphatemia and stomatitis really does lead to dose reductions in a lot of the patients. And I think that that's probably really important to emphasize is that despite the pan-tumor activity, there's still a lot of potential in this field to refine further because it's almost certainly the case that if we had less off-target toxicity, so to say, we could improve the efficacy beyond that 30% that we saw here.  All the same, I think this is exciting for the concept of a pan-cancer tumor agnostic sort of approach, and we'll really look forward to more data to come from this study over the next, hopefully, few months.  Dr. Diwakar Davar: And I guess 1 corollary to that is that we now need to start looking for FGFR alterations in multiple tumor types. So, tests, tests, tests. All right, Abstract 3004, phase 1a/1b dose escalation and expansion study of the MDM2-p53 antagonist BI 907828 in patients with multiple solid tumors including advanced, metastatic, liposarcoma. So, we've recently had data of the previously undruggable KRAS, and now we've got previously undruggable p53, for which we now have targets. So, Jason, what do you make of the p53 targeting approach, in this case, using MDM2 and this particular drug from Boehringer Ingelheim?  Dr. Jason Luke: So, I think that this is an exciting abstract exactly for the reason that you mentioned, which is that p53 has been, and unfortunately, to some degree, still remains, one of those holy grails but undruggable targets in oncology. So MDM2, for those who are listening but might not be aware, is a negative regulator of p53. So, the concept here then is if you drug it, you might release p53 to reactivate activity in that pathway, and then p53 being the guardian of the genome, so to say, potentially leading to apoptosis of cancer cells.  And so, this drug binds MDM2 and MDM2 can be amplified as a resistance mechanism in p53 and several tumor types. And so here, they showed data for the early part of a clinical trial investigating the small molecule, BI 907828, but then they focus specifically in liposarcoma, which is a disease known to be an MDM2 amplified. And so, the results were pretty interesting. The toxicity of this kind of an approach, just to note, is really in class. It leads to some gastrointestinal (GI) toxicities as well as hematologic problems, and this goes again for most regulators of the cell cycle will have these effects, whether they're CDK inhibitors or MDM2 or p53 modulators.  But I think what was very interesting, this is a disease liposarcoma where chemotherapy, functionally speaking, has no role. We, unfortunately, give it to some patients sometimes, but it has almost no activity, and they observe that in poorly differentiated liposarcomas, the response rate was about 12%, but the stable disease was quite durable. And so, I think that really is potentially a big deal because this is an orphan disease. It really lacks any other treatment. But as you zoom out from that, if you start to think about targeting amplified MDM2 in other settings, I think the activity that we see here is intriguing, and potentially suggests that we may be coming to a future where we'll have multiple, sort of, orthogonal approaches after reactivating p53. There were actually other abstracts at ASCO Annual Meeting of other molecules that were less mature also along this line.  So, I think, very exciting to take away from this, one, a potential treatment for liposarcoma for all of those patients that anybody listening actually sees, but secondarily this concept of targeting p53, which I think we'll see a lot more of over the next couple of years.  Dr. Diwakar Davar: Excellent. Moving on to the Abstract 3002, this is a phase 1, two-part multicenter, first-in-human study of DS-6000a of an antibody-drug conjugate comprising the anti-CDH6 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload via a cleavable linker. And so basically, a way in which you can give topoisomerase: (1) TOP1 inhibitor, (2) CDH6-expressing cells. This was studied in advanced renal cell carcinoma (RCC) and advanced ovarian cancer in this abstract presented by Dr. Hamilton. Jason, what do you think of the results and what do you think of this approach in general, this antibody-drug conjugate (ADC) approach using novel targets as well as novel payloads?  Dr. Jason Luke: I think this is one of those that you can't help but be pretty excited about, and I think in the context of the data shown at the plenary session in breast cancer for antibody-drug conjugates (LBA3), I think this is really where the field is going to start to go. So, you mentioned that this is an antibody-drug conjugate that targets cadherin 6 or CDH6, which people will remember from biochemistry class and medical school, or something is a cell-cell adhesion molecule, really a basement membrane protein. So, the concept of targeting it really is just to go after a latch mechanism to get the molecule into the tumor where you want. And CDH expression is very high in renal cell carcinoma, upwards of 80% of samples, also high in ovarian cancer, which is why they chose those 2 tumors to go after.  So, the ADCC, and you described its structure just a little bit, but it's essentially the same backbone as trastuzumab deruxtecan, which we saw this outstanding activity for HER2 and breast cancer on the plenary, with these 8 chemotherapies moieties attached to it, but here now, targeting it instead to HER2, with this molecule now to CDH6. And I think, again, you can't help but be impressed. There were treatment responses on almost every dose level of the dose escalation in this study. There's in fact only 1 patient whose tumor was not, at least, stable disease or a PR, and I think that that just goes to show the power of truly bringing the chemotherapy in a targeted manner into the tumor microenvironment. Responses were heterogeneous. They were not super deep responses per se, but the stable disease was quite durable in the study, and the patients were going out more than 7 months. And again, realizing this is at the lower dose levels as we're increasing the dose and move this in their earlier lives of therapy is likely to be even more effective.  They did show a waterfall plot of the reduction in CA 125 for the patients with ovarian cancer that really looked quite impressive. And given that that's our clinical biomarker that we commonly follow, it may actually even more indicative of the benefit we would see as opposed to resist.  Now, again, there is some toxicity. It is a chemotherapy moiety that's conjugated to the ADCs. So, the most common toxicities were nausea, vomiting, and low platelet counts, but these are kind of toxicities that we're quite accustomed to with chemotherapy. Just to summarize, I think there's a lot of promise for this kind of antibody-drug conjugate targeting, and I think it can only be impressive that they had this amount of activity in the dose escalation of the study. [I] very much look forward to the expansion cohorts in renal and ovarian, which we'll presumably expect to see later this year, early in the next year.  Dr. Diwakar Davar: And as you alluded to, this really was parallel that ASCO, by the standing ovation given to Dr. Modi when she presented the DESTINY04 data of trastuzumab deruxtecan in HER2-low breast cancer, basically now redefining breast cancer from 4 camps, now we have to think of not just HER2 amplified or HER2-high, but also HER2-low. So yes, really have to now rethink how we classify these diseases (LBA3).  So Abstract 2509, the efficacy of anti-PD-1/PD-L1 immunotherapy in non–small cell lung cancer dependent based on CD8 and PD-L1 status. So really Dr. Galon taking us into what he has now described as the immunoscore—really a way of characterizing tumors. A way of thinking about tumors that you've also championed, Jason, in terms of this T cell-inflamed and uninflamed hypothesis. So, tell us a little bit about how these jives with your work and how you would think about lung cancer patients responding and not responding to immune checkpoint inhibitors (ICI) therapy in this context?  Dr. Jason Luke: Yeah. I think the focus quickly here on the immunoscore, so the people are aware of that, I think is really important for diving into these specific results. You have to realize our fundamental underlying predicate for immune checkpoint blockade inhibitor response is that patients have mounted an adaptive immune response. So, CD8 T-cells have gone into the tumor where they elaborate chemokines and cytokines like interferon gamma, which upregulates the expression of PD-L1 in the tumor but also in the surrounding immune cells.  So, you realize that even though antibodies are targeting PD-1, it's really that we're targeting that tumor microenvironment. So, the more robustly we can measure that, and we understand it, the more likely we are to know whether or not the patient is going to benefit. So, this is where the immunoscore comes in. The immunoscore is actually a fairly simple test. It's one slide, immunohistochemistry slide where they can stain jointly for CD8 and PD-L1 on the same slide. And that allows them to do a number of different things beyond just testing the total level of PD-L1. They can test the CD8 density, the PD-L1 expression, but then also the interaction between CD8 T-cells, their distance from each other, from PD-L1 expressing cells, and so on and so forth.  And so really [this] can give us a much more robust analysis of what all is going on in the tumor microenvironment again, off of a single slide. So here then, in this abstract, for patients with non–small cell lung cancer receiving anti-PD-1, they then compared the utility of only PD-L1 testing versus doing the immunoscore. And so, it was actually quite a large set. They had about 250 patients in their analytical set and then split about 150 or 180 or something into the training and validation sets, and they compared the immunoscore against 2 different standard PD-L1 antibodies, the 22C3 as well as the SP263. And what they saw was a high concordance for expression between PD-L1 and the immunoscore.  That's good, because, again, they're measuring PD-L1 in both of those. And so that was a good, sort of, level set. The immunoscore, however, allows them to look to 7 different parameters, again, beyond just PD-L1, as I mentioned. So, CD8 density, interaction, distance, and this kind of thing. Then in these test and training cohorts, they were able to actually split out patients who are PD-L1 positive into further groups, those that were immunoscore low and that were high. And in so doing, they were actually able to sort of dramatically predict the likely progression-free survival on PD-1 checkpoint blockade in those different non–small cell lung cancer groups.  So why is this important? Selection of patients by PD-1 has been very useful in the field of non–small cell lung cancer, but it's hardly a panacea. You're not at all assured your patient is going to do well just because they're PD-L1. And here comes a second assay that can be done in a standard of care setting. So, the immunoscore is a test. You could just order it, and that really does give you much more predictive power about who's likely to do well and who isn't. And I think this test and more broadly multi-spectral imaging is really going to become a core component to how we risk stratify and predict outcomes to checkpoint blockade and lung cancer, but broadly in other tumor types over the next couple of years.  Dr. Diwakar Davar: Okay. Now, moving on from a biomarker for PD-L1 and PD-1 to a setting in which PD-1 was just recently U.S. Food and Drug Administration (FDA)-approved, so I'll give a brief background to the trial that you've actually developed and led. And so, this is KEYNOTE-716, the abstract in question is LBA9500 (late-breaking abstract) 9500, but this is the distant metastasis-free survival (DMFS) data readout. The DMFS, distant metastasis-free survival with pembrolizumab versus placebo in the adjuvant setting for patients with stage IIB or IIC, that is high-risk node-negative melanoma and the data from the phase 3 KEYNOTE-716 study.  So, this data, at least the recurrence-free survival (RFS) data was actually earlier published, you had presented it earlier last year and also more recently this year, but it was published recently in Lancet. And we know that 716 is a study in which, for the first time ever, we have an immune checkpoint inhibitor PD-1 that was studied against placebo with the high-risk node-negative setting in stage IIB and C melanoma, demonstrated a significant RFS benefit in the setting against placebo. And now we have the DMFS readout.  Maybe you could tell us a little bit about both the RFS and the DMFS data, and why this is such an important advance for these patients.  Dr. Jason Luke: Thanks. And I agree this really is a sea change in how we thought about stratification of patients with melanoma, but I think this broadly has implications for other tumor types as well. So, in melanoma, we've historically thought of its involvement of the lymph nodes—stage III as being the high-risk disease, but we also, if you look at the outcomes from the AJCC, we see the patients with stage IIB and IIC, so deep primary lesions, actually have similar bad outcomes as those patients with stage IIIA and IIIB. And so anti-PD1 and adjuvant therapy and melanoma were originally proved for stage III, but having understood that about 5 years ago actually, started to think, well, why not also treat the patients with stage II if they're at similar risk.  And we pursued KEYNOTE-716 as you mentioned, and it read out last year as a positive trial for recurrence-free survival. And the abstract here then was to look at the impact on distant metastasis-free survival. So, while the regulatory consideration for approval, and it is approved and it's available for patients now, was based on relapse, what we really want to be preventing is the development of metastatic disease because presumably that would correlate with the eventual death of the patient from cancer.  So, in the abstract here, we see the first update for DMFS, which also was positive on its first analysis, the hazard ratio at 0.64. And so, again, very similar to the RFS benefit, showing about a 35-36% reduction in distant metastasis-free survival. And this is a theme that we've seen across adjuvant studies in melanoma, all the adjuvant studies in fact, is that the RFS improvement, the relapse-free survival hazard ratio mirrors very closely the distant metastasis-free survival ratio. We saw that again here. I think it just emphasizes that anti-PD-1 immunotherapy is highly effective in melanoma no matter what stage it's in, but rather related to the risk of death for melanoma.  And so this really has a practice changing in the field of melanoma oncology. Patients need to be referred to medical oncology early for discussion around risk stratification and consideration of adjuvant therapy—I think even at the same time that they're having resection of their primary lesion, and it even calls into  question of whether or not we should even fully be doing procedures like sentinel lymph node biopsies any longer, considering we can make the decision to give adjuvant therapy now based on the primary—albeit that's a controversial area of discussion.  And I would just love for this to start to penetrate into other disease settings. We've seen more recently, approval for neoadjuvant therapy in lung cancer and we see in kidney cancer, bladder cancer. We see adjuvant therapy in—I think we're going to see immunotherapy starting to become an important part of the armamentarium in these hard-to-treat cancers, even at the time that perioperatively before or after surgery.  So definitely a major change in the way we're thinking about stratifying patients and emphasizes that you need to get those patients with melanoma in to have that discussion around adjuvant therapy probably at the time of the primary lesion resection.  Dr. Diwakar Davar: And finally, Abstract 2507, single-cell profiling of human heart and blood in patients with checkpoint inhibitor-associated myocarditis. So, this is data from the NGH Group, Dr. Villani and colleagues are presented by Dr. Blum. We know that myocarditis is an uncommon but very serious immune related adverse event (irAE), and here in this particular dataset, this group which has done a lot of underlying work to really uncover the role of certain key phenotypes, cellular phenotypes, in the development of myocarditis it's presenting the data in the context of ICI-related myocarditis. So, what do you think of this data, what do you think of the use of checkpoint inhibitors are now, as you've said, migrated linear in the lifecycle of the patient, what do we need to be thinking about and how does this improve our understanding of both the use of the drug and what we need to be worried about?  Dr. Jason Luke: I think the toxicities of immunotherapy, while, less frequent than, say, chemotherapy, can actually be more disastrous. In the rare patients, we have extreme immune-related adverse events, there is an incidence of actually life-threatening and fatal events. And so, myocarditis, associated with checkpoint blockade, is one of those things that could be seen, and here at ASCO Annual Meeting, we saw a couple of abstracts summarizing the experience from the National Cancer Institute following myocarditis events, and then this abstract in a translational level trying to better understand what is actually going on in terms of the immune response in those myocarditis cases.  And so, I thought this was actually a very interesting abstract. There was only a small number of patients. They had 13 samples from patients who had had endomyocardial biopsies in the context of immune-related myocarditis, and you might say, well, only 13 samples, but fortunately, this is quite a rare event, less than 1% of patients who get immune checkpoint inhibitors. And what they saw was relatively unsurprising, which is that in patients who were having myocarditis, they saw an increase in T cells and in K-cells, as well as activated CD8 and CD4 T-cells.  I think what was very interesting was when they started to dig into what were the phenotypes of the cells and what were the pathways that were turned on. Again, it was not especially surprising to see that they saw increased levels of interferon signaling and immune-receptor signaling as well as motility and adhesion, but this really, I think emphasizes that there are potentially interventions beyond just the general immune-suppression approaches that we give. They could be more nuanced but perhaps more efficacious because sadly, patients do pass away when they develop this. And in their cohort of 13 patients, 3 of those patients died. And specifically, in looking in those 3 patients, they actually saw that all 3 patients had a shared T cell cluster. And they can't exactly say what it is exactly yet, but I think it's very interesting to see that because it suggests that there's probably something about the T cell response in those patients that disproportionately triggered a fatal event.  And if we can understand that better, we then may be able to really tailor our interventions in a way that is more useful. Because, frankly, the way these patients usually present is they show up in the emergency room (ER), and they're seen by an ER doctor who thinks they're having acute coronary. They ship them off to the catheterization (cath) lab. They open him up, and then they get in there, and there's nothing going on. There's no plaque. And so now, all of a sudden, everyone is quite confused. And so, if we had better ways to search for that ahead of time to be aware of it, we might have better interventions because usually what happens right at that moment is everybody gets very confused and starts calling the oncologist, and we start slapping on steroids and other immunomodulatory agents, but sometimes it's late.  So, I think this is a great abstract. It's really starting to preliminary give us an idea of what is the actual biology that underpins these terrible events, and we can hope that we can build off that over time hopefully to eventually come up with better predictors and then obviously better interventions to try to avoid these outcomes in a small but real number of patients.  Dr. Diwakar Davar: Excellent. One other point is you and I are both involved in drug development, and as we start thinking of side effects. Side effects are really on the flip side of responses in drug development. So really 1 point to make of this is that when people start developing side effects rather than, as you say, putting your hands up in the air and waving them around, 1 of the things that we should be doing in drug development is possibly biopsying these patients because we could get new PD insights into how these drugs work, why they work, and particularly which sub-populations themselves they work on, particularly in the early-drug development setting when you oftentimes don't have that many responses.  With that, thank you, Jason, for sharing your insights with us today.  Dr. Jason Luke: Thank you.  Dr. Diwakar Davar: And thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. So, thank you for your attention, and we will sign out.      Disclosures:  Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Vedanta Biosciences  Consulting or Advisory Role (Immediate family member): Shionogi  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences  Research Funding (Inst.): Zucero Therapeutics  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:   Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine  Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.     

Player: Zamir White Team: Las Vegas Raiders Selection: 113th Overall (Round 4 // Pick 17)   On the latest episode of the Razzball Fantasy Football Podcast, Bobby LaMarco welcomes in Sky Guasco to discuss former Georgia running back Zamir White and what his potential fantasy value is as a rookie in Las Vegas. Please, blog, may I have some more?

Agustin Lebron began his career as a trader and researcher at Jane Street Capital, one of the largest market-making firms in the world. He currently runs the consulting firm Essilen Research, where he is dedicated to helping clients integrate modern decision-making approaches in their business.Watch on YouTubeBuy The Laws of Trading: https://www.amazon.com/Laws-Trading-Traders-Decision-Making-Everyone/dp/1119574218Follow Agustin on Twitter: https://twitter.com/AgustinLebron3Follow me on Twitter: https://twitter.com/dwarkesh_spCheck out my blog: https://www.dwarkeshpatel.com/(00:00) - Introduction(04:18) - What happens in adverse selection?(09:22) - Why is having domain expertise in trading not important?(15:09) - How do you deal when you're on the other side of the adverse selection?(21:16) - Why you should invest in training your people?(25:37) - Is finance too big at 9% of GDP?(31:06) - Trading is very labor intensive(36:16) - Overlap of rationality community and trading(48:00) - The age of startup founders(50:43) - The role of market makers in crypto(57:31) - Three books that you recommend(58:47) - Life is long, not short(1:03:01) - Short history of Lunar Society This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.dwarkeshpatel.com

DwD 346:  Track Selection:  The Impact on Learning On this episode of Dominating with Dawson, we wanted to discuss an aspect of racing education that can often be overlooked.  The typical decision path to getting a racing license or going to an HPDE event or a track day is to find the closest track to you that has an event that fits within your schedule.  This is likely to be what you do as well.  However, one factor that is neglected in this methodology is the impact that the track design and layout can have on your learning and progression as a driver.  There are many tracks that have very little run off room or walls, trees, rocks, etc. that are very close to the track and can make a small off track event a potentially very large cost event.  It can also affect the comfortability of the driver towards pushing the car and their personal driving limits during the event.  We talk about a few examples of tracks that are very forgiving and a few that we have been to that have layouts that are not quite as friendly.  This is not to say that it is the tracks “fault” because in the end the responsibility always remains within the driver's seat and it is their responsibility to maintain control of the car and determine when/if they are going to push towards the limit.  We love every single track but wanted to point out something that should be taken into account, especially as you are in your middle stages of learning and progressing as a driver.  As a bonus, for the exact same price, we include a great story of an early HPDE event in Ben Dawson's HPDE history. If you have any favorite tracks to work on your skills or push your limits, please let us know.  Also, if we missed a few of the higher consequence tracks or turns, please let us know in a podcast review or on our social media, or send us an email at GarageHeroesInTraining@gmail.com and we can share it in an upcoming Dominating With Dawson. A link to the episode is: https://tinyurl.com/TrackChoice  If you would like to help grow our sport and this podcast: You can subscribe to our podcast on the podcast provider of your choice, including the Apple podcast app, Google music, Amazon, and YouTube etc.  Also, if you could give our podcast a (5-star?) rating, that we would appreciate that very much.  Even better, a podcast review, would help us to grow the passion and sport of high performance driving and we would appreciate it. For instance, leaving an Apple Podcast rating is amazingly easy.  If you go to your podcast library, look under shows.  Then click on this podcast.  Here you can leave a (5?) star rating and enter your review.  We hope you enjoy this episode! PS  If you are looking to stream or save your integrated telemetry/racing data with you video, Candelaria Racing Products Sentinel System may be the perfect solution for you.  We are during installing the system in two of our cars.  If this sounds like something that may help you and your team, please use our discount code "GHIT" for a 10% discount code to all our listeners during the checkout process. PS2  Please do not forget that if you are looking to add an Apex Pro to your driving telemetry system, do not forget to use our discount code for all Apex Pro systems you will receive a free Windshield Suction Cup Mount for the system, a savings of $40.  Just enter the code “ghitlikesapex!” when you order.  They are a great system and invaluable to safely increasing your speed on track and/or autocross, etc.  The recently released second generation systems and app increases the capability of the system. Best regards, Vicki, Jennifer, Ben, Alan, Jeremy, and Bill Hosts and Drivers for the Garage Heroes In Training team