Podcasts about editor's pick

With Jeff and Rebecca hither and yon, we asked our editors to drop in and talk about their favorite books of the year so far. Subscribe to the podcast via RSS, Apple Podcasts, and Spotify. For more industry news, sign up for our Today in Books daily newsletter! Check out the Book Riot Podcast Book Page on Thriftbooks! This content contains affiliate links. When you buy through these links, we may earn an affiliate commission. Discussed in this episode: Find Other Book Riot Fans (Social Media Handle Exchange) The Book Riot Podcast Patreon Moon of the Turning Leaves by Waubgeshig Rice Shift Happens by J Albert Mann Kill Her Twice by Stacey Lee A Suffragist's Guide to the Antarctic by Yi Shun Lai Here We Go Again by Alison Cochrun Cash Delgado Is Living the Dream by Tehlor Kay Mejia youthjuice by E.K. Sathue Magical/Realism by Vanessa Angelica Villareal A Ruse of Shadows by Sherry Thomas The Framed Women of Ardemore House by Brandy Schillace Hirayasumi, Vol. 1 by Keigo Shinzō, translated by Jan Mitsuko Cash Learn more about your ad choices. Visit megaphone.fm/adchoices

I cannot believe we have recorded 200 episodes of the Game on Girlfriend podcast. I am so happy to have been able to do this! We've gone in and dug through the top performing episodes between episode 100 and episode 200 to recap and bring you what we felt were the top hits. I really want to take a minute and thank you so much for the support. This is such a labor of love for me to help you come into the world of coaching and see what it's really like. Here is a preview of the seven episodes featured. Let's get to it! Episode 190: Can Coaches Really Make Money? BTS With MY Coach Kelsey Murphy https://sarahwalton.com/can-you-make-money-as-life-coach/ Kelsey really homes in on what we coaches -- those of us who really study the craft and the art and the skill behind coaching -- do because we really love other people, and we really love this planet. “So, you have all these wonderful, empathetic, big-hearted humans that are not successful out in the world. And I'm like, no F that. … That makes me feel like, no, something's not right in the world. Because these people, these communicators, are the ones that could stop wars. They could make people feel seen and heard.”  – Kelsey Murphy Teaching people the skills of being able to share emotions, ideas, and experiences in a way that expands rather than contracts the rest of the world is really special. Episode 187: Feel Like You're Pushing Water Uphill? This Will Help You Find Success https://sarahwalton.com/pushing-water-uphill/ This is a solo episode where it's me speaking to all of you directly. I've recorded them in cars, in closets. I basically have done these pretty much everywhere. So many people were reaching out to me, saying it just feels too hard right now. This episode was my response. “This idea that we have to show up and perform in a certain way, we have to show up and appear in a certain way. … We've got to be so aware of what we are here to deliver that we can't get distracted by what other people are doing. …  I want you to get really honest with you. Are you doing this to yourself? Are you showing up in the world the way you think the world wants you to be seen? Or are you showing up based on who you are? Because the moment you start to show up as who you really are is the moment your business will transform, your life will become a lot easier, and you'll probably start making more money.”  – Sarah Walton Self-trust is something that is just an absolute tenet of everything that I teach and everything that I do whenever I'm coaching. It's so important that we remember that we have so much power in how we talk to ourselves and how we decide to respond to the different pressures and stressors that come at us, as well as the joys. Other episodes mentioned: Our 100th Episode: Fan Favorites, Editors Pick, and The Best Clips and Highlights https://sarahwalton.com/100/  Episode 188: Social Media is NOT a Marketing Strategy with Ruthie Sterrett  https://sarahwalton.com/social-media-marketing-strategy/  Episode 186: The Art of Self-Control with Tracy Pleschourt https://sarahwalton.com/take-back-self-control/  Episode 193: Take Those Courses Off the Shelf: 4 Steps to Make Progress https://sarahwalton.com/make-progress/  Episode 192: Behind the Scenes with IVF and Fertility Specialist Tasha Blasi https://sarahwalton.com/tasha-blasi-fertility/  Episode 195: The Breakthrough I Didn't Know I Needed https://sarahwalton.com/breakthrough-in-business/  Thank you so much for listening. I'm so honored that you're here and would be so grateful if you could leave a quick review on Apple Podcasts by clicking here, scrolling to the bottom, and clicking "Write a review."Then, we'll get to inspire even more people! (If you're not sure how to leave a review, you can watch this quick tutorial.)  #BusinessSuccessStory #GameOnGirlfriendPodcast #PodcastMilestone #SarahWalton #SarahWaltonPodcast #MilestoneEpisode #entrepreneurship#IntuitiveBusinessCoach #SalesCoach

This week, co-hosts Steve Crowe and Mike Oitzman review the latest Boston Dynamics Atlas video and how Atlas is getting more agile through simulation. Mike Oitzman reviews his recent trip to CES 2023, and features interviews with Aeolus Robotics Head of Product, Dan Haddick. Next we talk to Robosen Chief Marketing Officer Tony Crisp about the capabilities of Optimus Prime toy robot, and what's next on their roadmap. Finally, Mike recaps the recent IAC @ CES autonomous car race and interviews IAC founder Paul Mitchell.

This week Ash + Avi met with the wonderfully talented and intelligent Bridget Cunningham. She is a conductor, harpsichordist and musicologist with a special focus on Handel. You can find her work in so many places including at Buckingham Palace performing for the Royal Family. Bridget shares what she is currently working on and a little bit more of an insight into the world of Handel and his music. With a new album coming out in June you definitely want to keep your eye out on her socials to see what's up next and where you can see Bridget and her London Early Opera family perform. “They are unashamedly intended to please the senses and, in the hands of stylistically informed players they never fail to do so. Bridget Cunningham is just such a player…her ability to entertain unassailable" ★★★★★ Handel's Eight Great Harpsichord Suites, BBC Music Magazine, January 2022 “Handel has never sounded better” ★★★★★Handel's Queens 5 Stars, BBC Music Magazine, 2019. "Handel in Italy....reaching for the heavens" Andrew McGregor, BBC Radio 3, Record Review and Editors Pick in Gramophone Magazine. Handel's Queens available from http://smarturl.it/handelsqueens “Superb album” Classic FM ⭐️⭐️⭐️⭐️⭐️ BBC Music Magazine This weeks 'Know it All' is brought to you by Ash, and is closely related to this weeks episode. Bridget's Links: Website | Twitter | Instagram London Early Music | LEO Instagram | LEO Twitter Help Ukraine

Techstination, your destination for gadgets and gear.   I'm Fred Fishkin.        So which books made the top of your list in 2021?   The editors at Amazon put together their top picks for the year…“It was interesting for us this year because fiction was king this year.  Last year it was more non-fiction...

How do you learn to fade your hitman? Reverend and Drag enthusiast Lysol Tony-Romeo moves to San Francisco in pursuit of the 3 Ps: legal pot, public transportation and punk rock music. But when a drunken brawl with a roommate lands him in a year long domestic violence class, he commits to 52 weeks of unlearning toxic masculinity. Can Lysol ditch old male role belief systems to become an open, vulnerable human being? And If you can't admit you're afraid, how can you ever feel safe? #Gender #LearnedBehavior #ArtisticGrowth #FightOrFlight #LeopardHeels #EmotionWheel   About this week's storyteller:    Lysol Tony – Romeo is the lead conceptual force behind the First Church of the Sacred Silversexual,  which has won a SF Best of the Bay's Editors Pick and puts on a yearly Bowie Birthday Bash at The Chapel in San Francisco each January.  He's mounted a conceptual political campaign as DJ Action President, in the form of a YouTube channel featuring satirical political ads and commentary on big donations in politics.  He is a founding member of Music For The Apocalypse (or MuFTA) a theatrical dance punk band is in no way to be held legally responsible for the current apocalypse. Learn more about David Bowie's Birthday Bash at https://www.facebook.com/bowielovesyou/   Song: ‘Now you're a Man' (DVDA) Episode Links: LikeAKitten: The holidays are coming up. Are you looking for the perfect erotic gift for you and your partner? Like A Kitten will light up your sex life with their Naughty or Nice box! Like A Kitten creates sexy, seasonal gift boxes with all your erotic essentials from tempting lubes to gold handcuffs. All shipped discreetly to your door in one amazing box.  Their Naughty or Nice Box is perfect for the couple looking to heat things up this winter. It comes with a Christmas cracker (a.k.a., a mini vibe & cock ring), smooth water-based lube, a Naughty or Nice game set, massage oil candles and matches, gold Handcuffs, a satin robe, kissable diamond dust, crystal breast pasties, toy cleanser and a Screaming O Panty Vibe!  Like A Kitten also has a Holiday Bestie Box designed for your best friend! How great would you feel if a friend thought about your pleasure and got you a sweet box, complete with a clit stimulator and tingly lip balm? (now *that's* a friend) Best of all: the boxes are a steal! The Naughty or Nice Box is $99 and comes with eleven amazing products. The Holiday Bestie Box is only $29.95! And right now, Like A Kitten is offering our listeners 20% off AND free shipping when you go to LikeAKitten.com/Dixie OR enter promo code DIXIE at checkout.  Patreon: SPECIAL OFFER for new Patreon supporters! If you join at the $10/month or higher level by December 31st, you'll receive:    • A playlist of all of our previous livestream replays • Collectible limited edition Bawdy stickers • Your own golden access key to the Bawdy community  • A personal piece of custom art from Dixie All the inspiration you'll need you to make 2022 the year that you make your own wildly adventurous dreams come true - but this special offer ends soon. Become a member of our Patreon community at https://www.patreon.com/Bawdy   You can also Support Bawdy by sending your one-time donation to: Venmo: https://venmo.com/u/bawdystorytelling Paypal: https://paypal.me/bawdystorytelling Buy Me a Coffee: http://buymeacoff.ee/bawdy CashApp: Cash.app/$DixieDeLaTour And THANK YOU for your generosity!   Bawdy Got Me Laid perfume, bawdy butter & more: Dixie has created her own fragrance: You'll love #BawdyGotMeLaid perfume, scented with amber, ylang ylang, warm vanilla and golden honey. There's also our (scented or unscented) creamy Bawdy Butter, Hair & Bawdy Oil, & more. Bawdy Merchandise means you can deliver your own great smelling Motorboats while supporting Dixie and Bawdy. Get yours today at https://bawdystorytelling.com/merchandise Cameo/Custom Dixie video: Need the perfect gift? Need some Applause Tiddies?  I've been having so much fun making customized videos, and they make such a great Holiday present. Send your friends and lovers a custom ‘Cameo' video from Dixie (with or without applause tiddies), it's a great way to send love from far away to a Bawdy fan… For just $69, you and I can have a short zoom call, you can tell me all about the recipient, and I'll make a custom video from you for their special day. Find out more by emailing dixie@BawdyStorytelling.com #CustomVideo #Gift   STORYTELLING WORKSHOP coming soon! My next storytelling workshop starts in January, and I'd love to have you in it! Join us on zoom from wherever you are. ProTip: Subscribe to our email list & you'll be notified of all upcoming workshops, Livestreams, Podcasts and Special Events first at https://bawdystorytelling.com/subscribe   I'm also offering Storytelling for Self-Discovery to help you customize your stories. Anxious about navigating what's next? Are you writing a book, or working on your brand storytelling for your business?  No matter what you're up against, I can help you communicate with calmness & clarity - and I'd love to help you find your story. Email me at dixie@BawdyStorytelling.com for more info - we can book a short discovery call, and I'm happy to answer any questions.   Check out our Bawdy Storytelling Fiends and Fans group on Facebook - it's a place to discuss the podcast's stories with the storytellers, share thoughts with your fellow listeners, & help Dixie make the podcast even better. Just answer 3 simple questions and you're IN! https://www.facebook.com/groups/360169851578316/   Thank you to the Team that makes this podcast possible! Team Bawdy is:   Podcast Producer: Marty Garcia Sound Engineer: David Grosof Archivist / Video: Joe Moore Bawdy Livestream pre-show video by Donal Mooney Storytelling support by Mosa Maxwell-Smith & Bawdy Creator & Podcast Host Dixie De La Tour & Thank you to Pleasure Podcasts. Bawdy Storytelling is proud to be part of your sex-positive podcast collective! 

It's a huge day over here at Team Sarah ... because today's the day we've created, produced, and published 100 episodes of the GAME ON GIRLFRIEND PODCAST! I had no idea that this ride was going to be this fulfilling and rewarding. The guests, the crying and laughing, the insights, the moments of learning. I mean, the women I've had on the show! What an honor. Scrolling back and listening to episode one and hearing the transformation is incredible. So much has changed since that first recording, but my message has stayed the same: The Game. Is. On. I truly believe that if you're reading this right now, it's because you're ready for more LIFE. I want you to know this podcast is a labor of love, and I love bringing this content to you. I hope it inspires you. I hope it lights you up. We decided to create episode 100 in true Girlfriend fashion, as we share clips from our favorite episodes in addition to fan favorites. We've had such a great time pulling these clips for you — so we can keep the excitement, inspiration, and personal development flowing to you. Full show notes: https://sarahwalton.com/100/ Instagram: https://www.instagram.com/thesarahwalton/

Join co-lead Coach, Jill Farmer as she sits down with the fascinating Dr. Lilit Garibyan, MD PhD. They discuss Dr. Garibyan's four keys to success that led a 12 year old immigrant to become one of the leaders and great innovators in her field of medicine at Harvard University: Trust that we can learn and explore when we are in difficult situations.  You don't have to know everything to be an expert. Every problem can be a possibility. Be a Trail Blazer. When you're on that journey to the unknown, commit to it and execute.  This is the hero's part of the journey where you have to stick with it and power through. Recognize that there will be ups and downs. There always are, even for the most successful people in the world. Tune in to get inspired and learn The Four Pillars that have served Dr. Garibyan throughout her life. Dr. Garibyan is a board certified dermatologist who specializes in medical, surgical and cosmetic/laser dermatology. She is also a lecturer in dermatology at Harvard Medical School where she conducts cutting-edge and innovative research in dermatology. She is the co-founder of the Magic Wand Initiative MagicWandInitiative.org info@magicwandinitiative.org  Find more info on Dr. Garibyan here: https://madermatology.com/team/lilit-garibyan-m-d/   Click Here Prepare For Your Board Exams & Get Your CME Quickly & Easily With Board Vitals! Save 10% on Question Banks with the promo code: DOCWORKING10   Our New DocWorking THRIVE Membership is coming in July!! You'll get ongoing Small Group Coaching with our Experienced Team, Ongoing Coaching Support in a Private Community that Fosters Peer Support and Mentorship, and superb virtual courses to include ‘STAT: Quick Wins to Get Your Life Back' with Gabriella Dennery MD and Master Certified Coach Jill Farmer, and ‘A New Era of Leadership,' with Lisa Kuzman, and so much more!    Join our community by clicking here.   At DocWorking, our specialty is Coaching Physicians. We bring an exceptional experienced team to Coach Physicians to achieve the best in life and medicine.    Doctors devote their lives to caring for others. But does that mean they must sacrifice their own health and wellbeing? Absolutely not!   At DocWorking, we have developed a unique way to embrace it all.   The caring for others that you do so selflessly AND the caring for YOURSELF AND YOUR FAMILY that you crave in order to bring it all into the perfect balance specific to YOU.   What if we told you that you CAN have it all? The career you dreamed of when you decided to become a doctor AND the life outside of medicine that you desire?   DocWorking empowers physicians to get back on the path to achieving their dreams.   At DocWorking, we understand the tug between life and medicine–a desire to make an impact through your specialized skills but a longing for more time to prioritize your own dreams and ambitions.   We understand because we are a team of physicians and experienced coaches who have been successfully coaching physicians for more than 10 years.   Professional coaching is transformational. Elite athletes, award-winning actors and top-performing executives all know this, which is why they embrace coaching to achieve such extraordinary success.  Smart leaders leverage the power of coaching to achieve outcomes that are meaningful, measurable, and attainable. Physicians definitively benefit from coaching, and we are here to provide the best of the best.   It's Time to Prioritize the Health and Wellness of Physicians! DocWorking is here for you.    Our Coaches Will Show You How!   To learn more about DocWorking, visit us here! Are you a physician who would like to tell your story? Please email Amanda, our producer, at Amanda@docworking.com to be considered. And if you like our podcast and would like to subscribe and leave us a 5 star review, we would be extremely grateful! We're everywhere you like to get your podcasts! Apple iTunes, Spotify, iHeart Radio, Google, Pandora, PlayerFM, ListenNotes, Amazon, YouTube, Podbean You can also find us on Instagram, Facebook, LinkedIn and Twitter.    Some links in our blogs and show notes are affiliate links, and purchases made via those links may result in small payments to DW. These help toward our production costs. Thank you for supporting DocWorking: The Whole Physician Podcast!  Occasionally, we discuss financial and legal topics. We are not financial or legal professionals. Please consult a licensed professional for financial or legal advice regarding your specific situation.   Podcast produced by: Amanda Taran

“I admit that I’m a recovering people pleaser. In that recovery process, I thought, ‘something is wrong, I feel irritated by what this person just said to me. But I can’t seem to stop it because I’m here to serve. Therefore it’s okay, I’ll just tolerate what is happening.’ And it could be any number of examples, whether it was patients, colleagues, or even at home.  I wasn’t terribly good at setting boundaries. And it became clear that it was exhausting, and really not a very self honoring situation to be in. So I had to learn how to to do it. It is not a skill I was born with. I don’t know if it’s a skill anyone is born with, and to be honest it is something you need to cultivate over time.” - Coach Gabriella Dennery MD   Join co-lead Coaches at DocWorking, Gabriella Dennery MD and Jill Farmer as they sit down to talk boundaries. We learn why boundaries are important and that they aren’t just important for us, but also for the people in our lives. We learn that having boundaries isn’t mean, it is actually helpful and the kind thing to do. Not having clear boundaries makes life and relationships messy but having clear boundaries cleans things up. Listen to find out how to implement boundaries in your life and live with the freedom it gives to you and those around you!   Get One-on-One Coaching with Coach Gabriella Dennery MD Get One-on-One Coaching with Master-Certified Coach Jill Farmer   Our New Virtual Courses ‘STAT: Quick Wins to Get Your Life Back’ and ‘A New Era of Leadership’ are Almost Here!  Learn More Now  DocWorking believes the time has come to prioritize the health and wellness of physicians. Professional coaching is transformational. Elite athletes, award-winning actors and top-performing executives all know this, which is why they embrace coaching to achieve such extraordinary success. Leading corporations also know this, which is why they encourage coaching for employees at every level. Smart leaders leverage the power of coaching to achieve outcomes that are meaningful, measurable, and attainable. Our Coaches Will Show You How! To learn more about DocWorking, visit docworking.com     We’re everywhere you like to get your podcasts! Apple iTunes, Spotify, iHeart Radio, Google, PlayerFM, ListenNotes, Amazon, YouTube, Podbean   Are you a physician who would like to tell your story? Reach out to Amanda at Amanda@docworking.com to apply. And if you like our podcast and would like to subscribe and leave us a 5 star review, we would be extremely grateful!   Some links in our blogs and show notes are affiliate links, and purchases made via those links may result in small payments to DW. These help toward our production costs. Thank you for supporting DocWorking: The Whole Physician Podcast! Occasionally, we discuss financial and legal topics. We are not financial or legal professionals. Please consult a licensed professional for financial or legal advice regarding your specific situation.   Podcast produced by: Amanda Taran

In this episode of The Creative and Ambitious Entrepreneur Podcast, we’re discussing how you can make more sales on Zazzle with Zazzle Editors’ Picks. If you’re not familiar with Zazzle Editors’ Picks, its products featured on the Zazzle platform with a gold star next to them and the words “Editors’ Pick” under the title. These products stand out to customers and let them know that Zazzle approves them and recommends these as good products to buy.  If your products are selected as Editors’ Picks, this can really help increase your sales! Today, we’ll share how the Editors’ Picks work, how you can get your product to receive one, and what the benefits are for you. Key points we discuss include: What an Editors’ Pick is How you can get your product to receive an Editors’ Pick The benefits of your product receiving an Editors’ Pick A little gold star can make a huge difference! The Editors’ Pick designation helps customers find and trust your products, AND it also helps increase your confidence as a designer! When you know that Zazzle likes your products, you know you’re headed in the right direction with your designs, and you can keep creating more and more products like that. All of this leads to you making the sales you deserve! To hear all the ways you can increase your sales with Zazzle Editors’ Picks, tune in to episode 41 of The Creative and Ambitious Entrepreneur Podcast! If you enjoyed this episode, take a screenshot of the episode to post in your stories and tag us! @msjenclarke and @elkeclarke Love it? Subscribe, rate, and review the podcast. We would love to hear your key takeaways. Share them with us! CONNECT WITH JEN & ELKE: Official Website Jen’s Instagram Elke’s Instagram Creative and Ambitious Entrepreneur Facebook Community The Profit by Design Academy™ The zSupercharger ™ 

On season 02 episode 054 we sit down with Dr. Cheryl Robinson. She has been a regular contributor for ForbesWomen. She focuses on women who have pivoted within their careers with an emphasis on their mindsets. Having interviewed over 300+ women and counting, she has had the fortunate opportunity to meet and engage with some of the most powerful, influential and inspiring women in the world including Suzanne Shank, Kathleen Kennedy, Bobbi Brown, Diane von Furstenberg, Susie Wolff, Claire Williams, Christie Pearce Rampone, Maria Sharapova, La La Anthony and Candace Cameron Bure. In addition, she has been featured in the ForbesWomen newsletter multiple times and has earned 20 Editors’ Pick recognitions. As an international speaker, Cheryl has spoken, moderated and conducted workshops and panels for over 20 years. Her speaking portfolio includes engagements at Columbia University, Penn State, Columbia University/Oxbridge, Girl Meets World, Lakewood BlueClaws, the Acronis Women in Tech & Motorsports in Abu Dhabi and the U.N.'s Girl Up Teen Advisory Board. This episode is sponsored by Anchor – the easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/laywill --- Send in a voice message: https://anchor.fm/laywill/message

Anita, an Ottawa resident, describes the difference between Canadian writers and those in the US, how she channeled her own grief experience into her main character, how she believes writing is rewriting, and how embracing bookstagrammers was her single best marketing decision.   Kushwaha's road to publication included a fulfilling career in academia, where she studied human geography at Carleton University and earned an M.A. and a Ph.D as a Tri-council funded scholar, collaborating with Indigenous communities in the eastern Canadian Arctic and Ottawa on socio-cultural and environmental issues. A graduate of the Humber School for Writers creative writing program, her work has appeared in Ms. Magazine, The Globe and Mail, Quill and Quire, The Literary Review of Canada, The 49th Shelf, Open Book, Word on the Street, The Ottawa Review of Books, Ottawa Life Magazine, Apt613, Girly Book Club, BookTrib, SavvyMom, CBC All in a Day, and Canadian Living among others. Her first novel, Side by Side, won an Independent Publisher Book Awards’ Silver Medal for Multicultural Fiction in 2019. She is also the author of a novella, The Escape Artist. Her novel, Secret Lives of Mothers & Daughters, was released in January 2020 by HarperCollins Canada and selected as a March Book of the Month by Word on the Street, highlighted as a “Books with Buzz” by Canadian Living, selected as an “Editors’ Pick” by The 49th Shelf, and included in the “Crazy for CanLit” reading list curated by the Giller Prize Foundation. Themes in her work include exploring the social and cultural pressures faced by South Asian girls and women, immigrant experiences, diaspora, intergenerational conflict, identity, belonging, place, and mental health explored through a cultural lens. She is a member of the Canadian Authors Association, the Women’s Fiction Writers Association, and is the recipient of an Ontario Arts Council Literary Creations Grant.  To learn more about Anita, click here.

Discover those Top10 market trends from a global perspective of Goldman Sachs after after 2020.

Discover the up-and-coming new fashion capital cities with VOGUE scoring from VOGUE Business China in Nov 2020.

Sara Collins talks to Hilary Mantel about her essay collection

Karen writes both fiction and creative nonfiction. Her memoir, Surrendered Child, won the AWP Award Series for Creative Nonfiction and was listed as a “notable book” by the National Book Critics Circle. She is also the author of Motel of the Stars, Editor's Pick from Oxford American, and a Lit Life Book of the Year. Strange Birds in the Tree of Heaven (University of Georgia Press), a novel that won the Lillie Chaffin Award for Appalachian Writing and, most recently, Walk Till the Dogs Get Mean, co-edited with Adrian Blevins, from Ohio University Press. Her essays have won the Annie Dillard Prize, the New Southerner Prize, the Orison Magazine Anthology Award and have several times been Notable in Best American Essays. A collection of her essays is forthcoming from Iris Books. Her newest book, a novel called Wanting Radiance, will be released in April 2020 from University Press of Kentucky. Karen has an MFA in Fiction Writing from the University of Virginia, an MA in Creative Writing from Hollins University, and a PhD from the University of Georgia, where she studied American Literature and Fiction Writing. Her work has received numerous awards, including grants from the National Endowment for the Arts, the North Carolina Arts Council, and the Kentucky Foundation for Women. She is frequently visiting writer and lecturer at a variety of programs and reading series. Karen is a lover of lakes, animals, sunlight, and her native Appalachian tongue.

Carli Goltowski, Founder and Neighbor-in-Chief at Good Neighbor sits down with our editor, Katie Kennedy, to talk about ethical and sustainable fashion.Follow EXP|DET on InstagramLike EXP|DET on Facebook

Every month our Editor-in-Chief selects one article from this publishing cycle to be featured in podcast format. This month we are featuring an article written by Staff Writer Lorenzo Béatrix. His article, "Are Contemporary Art Galleries Victims Of Globalization?", examines the effect globalisation has had on an effect on galleries and the art market artistically, economically, and conceptually.

118. Thompson Tee | Billy Thompson is the President of Thompson Tee. He is the inventor of the Thompson Tee with Hydro-Shield Sweatproof Technology, a patented undershirt guaranteed to block underarm sweat, preventing embarrassing wet marks and yellow stains. As seen on Shark Tank, "The Doctors" TV and Editor's Pick in SHAPE magazine. They are proudly serving customers in over 135 countries worldwide and their product is fully handcrafted in the USA. This Episode is Sponsored By:Mack Weldon is the most comfortable underwear, socks, shirts, undershirts, hoodies, or sweatpants that you will ever wear. They're even more comfortable when you get 20% Off... So to get the comfort you deserve go to: MackWeldon.com and enter promo code MILLIONAIRE at checkout.LinkedIn Jobs makes it easy to get matched with quality candidates who make the most sense for your role. Get $50 OFF your first job by using this link: millionaire-interviews.com/linkedin-jobs. Want to Support the Show? Our Kickoff Sale is

If you're lucky enough to not be back at work, you might be feeling like you need to quickly refresh your medical knowledge - and this podcast the BMJ's education editors take you on a whistlestop tour through the BMJ's education articles of 2019. Tom Nolan (GP in London) is joined by Navjoyt Ladher (GP in London), Anita Jain (GP in India) and Jenny Rasanathan (GP in Phnom Penh). Our reading list: Please don't call me mum https://www.bmj.com/content/367/bmj.l5373 Which emollients are effective and acceptable for eczema in children? https://www.bmj.com/content/367/bmj.l5882 Pre-eclampsia: pathophysiology and clinical implications https://www.bmj.com/content/366/bmj.l2381 A borderline HbA1c result https://www.bmj.com/content/365/bmj.l1361

This week we are rebroadcasting our interview with Pua Case, initially aired in December of 2017. In the past two and a half weeks we have seen the powerful swelling of protectors across the globe in reverence for Mauna a Wākea. On July 15, 2019 construction for the Thirty Meter Telescope (TMT) was scheduled to begin. In response, eight protectors chained themselves to a cattle guard in the early morning to prevent equipment vehicles from accessing the Mauna. No arrests were made until July 17, 2019, when DLNR officers arrested 38 people, most of whom were elders. Following the arrests, the Governor of Hawaii declared a state of emergency, allowing for the deployment of the National Guard. Since then, the National Guard has been called off and interisland police troops have been sent home, but Governor Ige and TMT International Observatory have both stated that they have no intent to halt the construction. What is taking place on Mauna a Wākea is about so much more than the construction of the TMT. It is in response to the 50 years of serious mismanagement of Mauna a Wākea by its occupiers. It is in response to the proposed two 5,000 gallon tanks of chemical and human waste that would be stored below ground, above waters aquifers and on ancestral burial grounds, should the TMT be built. It is about the ways in which colonial science condones the use of police force in the name of research and the grave impacts that research protocol and infrastructure have on communities. And most importantly, it is in response to decades of colonial rule where Kanaka ‘Ōiwi have been silenced while settler-colonists and U.S. interests have exploited people, culture, and resources for private profit. We do not need to “understand the advent of the universe” through an 18-foot story tall telescope. In fact, when it comes to the TMT, our personal opinions do not matter. We simply must recognize Indigenous sovereignty in action. This week we rebroadcast Pua Case’s interview in honor of the heart of a mountain and the rising of a Nation. ♫ Music by Hawane Rios & Mike Wall

Dr. Heidi and Yuan Wang, the Manifestation Architect, talk blockchain, distributed ledger technologies (DLT) and upleveling to Civilization 2.0. Yuan Wang is a futurist, technologist, manifestation architect, #1 best selling author and parallel entrepreneur who designs #DLT systems and transformational experiences that help humanity play its way to Abundance. For over two decades, Yuan designed, coded and operated some of the most popular 3D video games in history including Descent, Lucasarts’ Jedi Knight and World of Warcraft. He has built multiple startups, served as an executive at Blizzard Entertainment, Disney, and Midway Games and is currently building and advising decentralized technology and human performance organizations for Civilization 2.0. Yuan Wang’s 2018 book, The Abundance Prophecy.  website: theyuanwang.com Twitter ID: theyuanwang Instagram : theyuanwang       ******************************************************   This episode is brought to you by Rocketbook, Dr. Heidi’s favorite offline tech tool. Rocketbook is a brilliant concept that enables the use of pen and paper for recording, but easy transfer of that into digital means that is searchable and easy to organize and trace. Dr. Heidi has arranged a discount for you, her listeners, if you follow this link. http://www.getrocketbook.com?rfsn=1761454.14963a  

Billy Thompson is the President of Thompson Tee. He is the inventor of the Thompson Tee with Hydro-Shield Sweatproof Technology, a patented undershirt guaranteed to block underarm sweat, preventing embarrassing wet marks and yellow stains. As seen on Shark Tank, "The Doctors" TV and Editor's Pick in SHAPE magazine. They are proudly serving customers in over 135 countries worldwide and their product is fully handcrafted in the USA.  This Episode is Sponsored By: Mack Weldon is the most comfortable underwear, socks, shirts, undershirts, hoodies, or sweatpants that you will ever wear. They're even more comfortable when you get 20% Off... So to get the comfort you deserve go to: MackWeldon.com and enter promo code MILLIONAIRE at checkout. LinkedIn Jobs makes it easy to get matched with quality candidates who make the most sense for your role. Get $50 OFF your first job by using this link: millionaire-interviews.com/linkedin-jobs.   Want to Support the Show? Our Kickoff Sale is

It's 2019 and we're back in the studio! We had a bit of a staff shuffle and are introducing Ben So, our new content editor. In the garage are the Mercedes-AMG GLC 63 S, Genesis G70 2.0T Sport, and the Cadillac XT4. We also touch on our Editor's Pick award choices for 2018, and chat briefly about our Car of the Year recipient, the Genesis G70. Other notable test drives include the 2019 BMW X5 and the new Subaru Forester's ability to watch/monitor the driver's eyes and minimize distracted driving.

The Hawaiian Islands, like so many of our planetary coastal communities, are at the forefront of rising waters, diminishing trade winds, and climate chaos. We can choose to prepare and respond in ways that will sustain our communities and strengthen our families. This week we interview Reverend M. Kalani Souza, a gifted storyteller, singer, songwriter, musician, performer, poet, philosopher, priest, political satirist, and peacemaker. Kalani currently works as Community Outreach Specialist for the University of Hawaii’s National Disaster Preparedness Training Center and is the founding director of the Olohana Foundation, focused on community capacity and global response to climate adaptation. Music by Cover Story Doo Wop

This week we are honored to be in dialogue with Queen Quet, Chieftess and Head-of-State for the Gullah/Geechee Nation, who is striving for justice on the front lines of the most pressing Anthropocentric intersections: climate change, resource extraction, corrupt and negligent government bodies, land theft, encroaching development and exploitative tourism. The Gullah/Geechee are descendants of the first enslaved Central and West Africans who remained isolated along the inland, coastal area, and Sea Islands between present-day Jacksonville, North Carolina and Jacksonville, Florida. After the Civil War, these peoples were the first group of African descendants to own land in mass in the United States, allowing them to preserve their African cultural traditions and Indigenous practices. Queen Quet, Marquetta L. Goodwine is a published author, computer scientist, lecturer, mathematician, historian, columnist, preservationist, environmental justice advocate, film consultant, and “The Art-ivist.” Music by The Gullah Singers

Don’t miss this episode of WSFI 88.5FM Spotlight. Host John Morgan,  discusses the challenges and successes of Lake County PADS with its Executive Director Joel Williams, First Presbyterian Church, Libertyville PADS Site Manager, David Marsden and daughter Ella as well as  Michael Knight of St. Joseph Catholic Church in Libertyville who serves as Site Manager of PADS at the United Methodist Church.

1.  INTRO I’d be surprised to meet someone not familiar with HGTV in some way. HGTV has become quite a force in our American culture kicking off the DIY phenomenon, the urban farmhouse movement with Chip and Joanna Gaines, and the young, colorful, whimsical design aesthetic that HGTV is known for. Honestly, HGTV probably doesn’t have a lot of high end designer fans because of their not-so-realistic design transformations as it relates to the budget but we still appreciate HGTV for a lot of ways. We appreciate them VERY MUCH right now as we are finalists in the 2018 Faces of Design competition which we want to tell you all about. First up, a little bit of background and stories about K&K and HGTV. 2.  OUR FIRST PILOT IN 2012 - HOUSE ARREST WITH CINEFLIX A. Basis for the show B. Scope of work C. The best part – the host – Chris Lambton 3.  OUR SECOND PILOT IN 2013 - MOVE IN OR CASH OUT WITH DEPARTURE FILES A. Basis for the show i. working with Charles and Michael Holmes of List-4-Less Realty ii. Andrew Grein of Grein Productions B. Scope of work i. Weatherby Renovations ii. Kitchens by Caren Danneman iii. Ballard Designs iv. Donations to make it happen! 4. HGTV AS A RESOURCE A. Published twice always relating to our use of color – Joann porch/Jeanne Sellers B. HGTV.com i. What’s new in decorating ii. Craft Projects iii. The famous home giveaway C. HGTV Magazine 5. FACES OF DESIGN 2018 A. 8 Categories this year i. Waterside Retreats ii. Countryside Escapes iii. Big City Digs iv. Living large in small spaces v. Master Retreats vi. Color + Pattern vii. Kitchen & Dining viii. Dramatic Before & Afters B. We entered (5) categories and are finalists in (2) – Color & Pattern (Kelly’s house) and Kitchen & Dining (Wrigley) – There will be an Editors Pick and a People’s Pick for each category and (6) nominees for each category. Vote from August 23rd to September 27 2018. www.hgtv.com/facesofdesign

Dr. Kimmerer is a mother, scientist, writer, member of the Citizen Band Potawatomi, Distinguished Teaching Professor of Environmental Biology at the SUNY College of Environmental Science and Forestry in Syracuse, NY, and the founding Director of the Center for Native Peoples and the Environment. The Center’s mission is to create programs which draw on the wisdom of both indigenous and scientific knowledge for our shared goals of sustainability. Her research interests include the role of traditional ecological knowledge in ecological restoration and building resilience for climate change. In collaboration with tribal partners, she and her students have an active research program in the ecology and restoration of plants of cultural significance to Native people. She is active in efforts to broaden access to environmental science training for Native students, and to introduce the benefits of traditional ecological knowledge to the scientific community, in a way that respects and protects indigenous knowledge. Dr. Kimmerer has authored numerous literary essays and scientific papers on restoration and plant ecology, as well as the award-winning books Gathering Moss, and Braiding Sweetgrass, which interweave indigenous knowledge and scientific perspectives. She lives on an old farm in upstate New York, tending gardens both cultivated and wild.

Dan Kelley is no stranger to successful radio. Since his radio start during high school in suburban Chicago, Dan has been a station Program Director, Operations Director, Station Manager, Chief Engineer and on-air talent for such companies as CBS Radio, Clear Channel and Citadel Communications. Since 2007, he’s had a statewide perspective for the Michigan Association of Broadcasters.  There he servies as Director of Technical Services/Digital Communications Director/Engineering.  In addition to his work at the MAB, Dan also operates a successful listener-supported classic rock/adult alternative online radio station which has been featured as an "Editor's Pick" station multiple times in Microsoft Windows Media Guide.  We link to it in the show notes.    

Our first episode of 2018 involves us talking about our Editor's Pick awards of the past year. We also talk about Jerry's experience in Spain with the 2019 Volvo XC40, Adi driving a DIESEL-powered Honda Fit, and Louis hooning around Los Angeles in the Honda Civic Si. Relevant vehicles in the holiday garage include the Range Rover Velar, VW Golf R in TNT Orange, and the #HighMileClub Lexus LS400's first track day. Oh yeah, and Kevin the sports car and track day fanatic drives a Ram 1500.

Mohsin Hamid discusses his new book, Exit West and North Korean short stories

In the middle of the Christmas holiday season, we sit down and talk about shenanigans. Topics such as Lego Technic/Creator, the old Midtown Madness game series, and Chad's broken car are touched upon. We're driving the BMW X5 M-Performance, Infiniti Q60 Red Sport 400, Honda Civic Turbo Hatchback, and Cadillac CT6 Luxury. We also talk about our Editor's Pick awards being presented next week, and what cars individually captured each of our hearts. Tune in!

William Poundstone is the author of fourteen books, including Big Secrets, Prisoner's Dilemma, Fortune's Formula, and Are You Smart Enough to Work at Google? He has written for The New York Times, Harper’s, Harvard Business Review, and the Village Voice, among other publications, and has adapted several of his books for ABC television. He is on the board of advisors of the Center for Election Science. Poundstone was born in Morgantown, West Virginia, and studied physics at MIT. His writing often explores the social implications of scientific or philosophic ideas—from voting methods (Gaming the Vote) to competition and cooperation (Prisoner's Dilemma) to the gambling system known as the Kelly criterion (Fortune's Formula). Amazon rated Fortune's Formula the #1 Editor's Pick for nonfiction in 2005. Poundstone won the NYSSCPA's Excellence in Financial Journalism Award in 2011. Key Takeaways: [2:15] What the American public knows and what that says about us [4:40] Why some things are just worth knowing even though you could look them up [8:35] The correlation between vocabulary and your success in life [13:00] How many elected officials most people actually know [16:25] How little we're teaching kids about sex and what impact that's having [18:56] The theory of scientific betting and how to properly use it Website Mentioned: www.william-poundstone.com

[intro music]   Hello, and welcome to Episode Forty-Three of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. May Han, who discusses issues related to following patients with clinically isolated syndrome. But first, here are some new items on the MS Discovery Forum.   We recently posted an article on a surprisingly strong association between a certain gene variant and non-response to interferon beta in people with RRMS. The study is a meta-analysis of three independent cohorts in Italy, France, and the U.S., and it comes from the labs of Philip De Jager and Filippo Boneschi. You’ll find this article by clicking first on News & Future Directions and then on New Findings.   This past week we published the latest in our series of data visualizations. This month’s visualization is a series of word clouds illustrating how key terms in the MS clinical-trial literature have changed between 1993 and 2014. To find this visualization, first click on Research Resources, then on Data Visualizations, and then on Word Cloud.   According to our curated list of the latest scientific articles related to MS, 30 such articles were published last week. To see last week’s list, go to msdiscovery.org and click on Papers. We selected one of those papers as an Editors’ Pick. It’s study of the association between depressive symptoms and walking ability in people with RRMS.   Are you attending the annual meeting of the Consortium of Multiple Sclerosis Centers in Indianapolis this week? If so, please come visit us at the Accelerated Cure Project’s booth. We’ll be demonstrating some of our latest data visualizations along with other features of the MS Discovery Forum. You’ll find the booth in the hallway close to the main entrance to the exhibit hall, and we look forward to meeting you.   [transition music]   Now to the interview. Dr. May Han is an assistant professor in Neurology and Neurological Sciences at Stanford University. I spoke with her about following patients with clinically isolated syndrome, as well as her approach to patients with MS across the course of their disease. But first, she addressed some unmet needs in MS.   Interviewer – Dan Keller Dr. Han, you told me that we’re good at the diagnosis of MS in general, but still there’s a vast area that we don’t know about. What are some of those unmet needs?   Interviewee – May Han So it’s been over 150 years since Charcot first described multiple sclerosis, and I have to say that we have come a long way in understanding and treating this disease. But as you have mentioned, there are still areas where we have no idea, there are gaps in our understanding of this disease. One of these areas that is clinically very relevant and is very challenging is in the day and age where we have a dozen disease-modifying therapies for MS patients, and yet we don’t have a good way, a scientific way of selecting the most effective therapy for a particular patient is what I find quite challenging in the clinics.   MSDF What gives you clues or how do you approach this essentially algorithm of deciding where to begin and how to move on to other medications if the first one’s not working well?   Dr. Han Currently, of course, we follow the guidelines. So for any relapsing-remitting patients, our logic is to go for the safest medication that we think are going to be most effective, which means we go with the first-line therapies. So we have the convention ABC drugs such as beta-interferon family of therapies and glatiramer acetate, plus the newer oral medications such as Tecfidera and fingolimod or Gilenya that we use for the first-line therapy; not a whole lot of science in choosing these medications for a particular patient, but what we would do is initially we would educate the patient about these disease-modifying therapies and then select the medication together with the patient to see what would be most appropriate and the patient could be most compliant for a particular medication.   To give you an example, certain patients have aversion to needles, in which case we go with the oral medications. We also have in mind what the preference of the patient, such as whether they could be able to follow it through for years on end with a particular medication. Ideally, we would like to have zero relapses or MRI activity when a patient is on a disease-modifying therapy, but as we all know none of these medications are 100% foolproof, and they can still have some degree of MRI activity or infrequent relapses on this medication. However, if a patient is clearly not responding to a therapy either in terms of not being compliant, being intolerant to the mode of administration, or if they’re having worsening disease activity, we would decide to go on to stronger medications or second-line of therapy.   MSDF Do you initially discuss a plan of action, a stepwise pattern of medication prescribing, or do you wait until something needs to be changed to bring it up with patients?   Dr. Han That is a very good question. I’m sure it varies among clinicians, but, however, I would like to paint the picture to the patient the best that I can. So, let’s say for example, if a patient who is a newly-diagnosed MS patient who has very few MRI lesions, I would discuss with them what the most appropriate medication could be. We would decide a medication and we would also give them an outline of what the followup plan would be and when we would be deciding to switch to a different therapy, and if so, which medications would be most likely appropriate for them, and also how we would monitor them. So by doing this, it gives the patient a better picture of their path and what to watch out for, and in my experience we have a better outcome with these patients.   MSDF Do you find that once you achieve success in limiting relapses and lesions that the medication is fairly stable for a long time, or do you have to have an armamentarium that you keep moving through?   Dr. Han So my model if a patient is responding to a medication, unless they have other side effects or reasons to switch, I would like to get the most mileage out of the medication as much as I can for a particular patient. However, if a patient, for example, has JC virus positivity, in which case even if they’re responding to Tysabri really well, there is a cutoff time point where we have to sit down and consider whether this patient should be switched onto a different medication to prevent the development of opportunistic brain inflammation such as PML, in which case what the next medication would be. And so we would sit down and talk the pros and cons; this conversation was started even before the patient was started on medication, but that would be the checkpoint.   MSDF I suppose another aspect is do medications start to fail patients even after a long period of stability, or do they usually continue to be stable if the medication is working for some period of time?   Dr. Han This is also a very pertinent question. MS patients, as we know, is very heterogeneous. Some of the patients, if they are stable on a medication, they would continue to do well on a medication for several years up to decades. However, some patients would have an initial improvement or stabilization of their disease, however in the later stages they would have worsening disease. And it is really unclear whether because their disease per se is getting worse or whether their body is rejecting the medication secondary to the immune response. And that is also one area that we should do research on to better understand this condition.   MSDF When you say reject the medication, are you actually referring to an immune rejection such as with, say, interferon; I would think it would be less likely they would actually mount an immune response to a small molecule. Am I clear on that or not?   Dr. Han I think we have quite a lot of information in terms of beta interferon therapies, because we clearly know that patients do tend to develop antibodies against beta interferon, especially the therapy. However, even that we don’t really know if all those antibodies are attacking the drug or whether they are just there. So just by finding the antibody alone is not enough to say that the patient is not responding to it; I think we need to use it hand-in-hand with the clinical response as well as the MRI activity.   Getting to the second part of your question whether there’ll be less intolerance or rejection to the therapy if it were small molecules, but I don’t think we understand at the cellular or molecular level. For small molecules there could be receptor down-regulation, there could be availability or cellular sequestration, or even the prodrug being converted to an active drug, or how the breakdown process occurs. So when a patient does not respond anymore to a medication, we just know that the clinical response is worse, and we don’t really know whether it is because the disease activity has worsened or other aspects, pharmacodynamic or kinetic aspects of the system has changed in such a way that they no longer respond. So, again, we do need to do more research to have a better understanding.   MSDF You have called it MS comes in many different flavors. Have you found that any medications are particularly good for different constellations of symptoms, or is everything about equal no matter how they present?   Dr. Han Very good question as well. I think in the experimental models people know that MS, or central system autoimmunity, can have a bias towards one type of inflammation as opposed to the other. For example, some would say that certain medications are better to treat Th1 as opposed to the Th17 type of inflammation, however in human beings there’s no clear-cut Th1 MS or Th17 MS. I don’t think people have done enough studies to clearly decipher the immune profiles of patients. So the answer is we don’t know.   MSDF Finally, let’s talk about the need for biomarkers especially very early in the disease when someone’s presenting with CIS which may or may not become MS. Where does that stand and how acute is the need?   Dr. Han The need is there, especially if you look at it from a patient who just had an initial attack. If you tell them that we don’t really know whether this is a one-time thing or whether you’re going to develop MS, and we’ll have to wait and see for three-plus years. So for these three years, the patient’s life is very much consumed by the “is it going to be MS” kind of question. And it does affect their physical-mental wellbeing as well as their quality of life.   I think we’ve come a long way with the advancement of the MRI studies in such a way that if a patient has MRI lesions together with the first-time attack, we could almost clearly say that this is going to blossom into MS. However, for patients who are radiographically clean and who just had one episode, it would be very, very helpful to have some kind of blood biomarkers to predict whether this could be a single event or whether it could be a central nervous system inflammatory disorder.   MSDF You picked three years as a period of waiting, watching. Are they out of the woods after that, or how late can it blossom into full MS?   Dr. Han It’s always a bell-shaped curve. There are patients who would declare themselves sooner than three years, there are also patients who would take several years before they have the second attack. I have one patient who had an initial attack of optic neuritis and nine years later she had the second attack. During that period, she had had MRI scans for three years which were clean. So, I guess, one is never completely out of the woods, but at the same time it is also not prudent to perform unnecessary tests on a patient.   So I think we have to focus on what is the safety net and pick a period of time, but at the same time it is very important to educate a patient to symptoms to watch out for, how to get help, and to work very closely with the primary care physician or a neurologist so in case the symptoms show up they will not be ignored or delayed to receiving treatment.   MSDF Is there anything we’ve missed or is important to add? I’m sure it’s a gigantic field, but is there anything glaring that should be added?   Dr. Han I would like to encourage people in the field to also focus on the secondary-progressive stage of MS. We know that relapsing-remitting MS patients with or without therapy eventually would end up having secondary-progressive MS, so it’ll be really important to decipher whether during the secondary-progressive stage there is no inflammation but only the early neurodegeneration, or how the immune system and the central nervous system interact and how we can change it, or at least modulate it, to either delay or to prevent neurodegeneration. The third area that I think is very important is to try to understand the regenerative aspects of the central nervous system.   As I have given you the example, if we have two patients who have had similar lesion burden or even lesions that are approximately the same in similar areas, a patient can be severely devastated, neurologically devastated, whereas the other may have minimal neurologic deficits. And we would always say that it depends on the brain reserve, or neural reserve, but we don’t quite know what it is. Is it the stem cells, is it the nervous system being more resistant to insult and how the immune system interacts with it? And I think this is also a big area that we should focus on, of course, to prevent further damage, but also once the damage is done to limit the damage and perhaps to regenerate it. And I think that people always have within themselves the ability to heal.   MSDF Good, thank you.   Dr. Han Thank you.   [transition music]   Thank you for listening to Episode Forty-Three of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]

[intro music]   Hello, and welcome to Episode Forty-Two of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Lawrence Steinman, who discusses a surprising result involving amyloid, a molecule typically associated with destruction in Alzheimer’s disease, in an animal model of MS.   Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. During the past week we added 1 new trial and 16 other pieces of information. The drugs with important additions are dimethyl fumarate, daclizumab, glatiramer acetate, and natalizumab. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline.   According to our curated list of the latest scientific articles related to MS, 50 such articles were published last week. To see last week’s list, go to msdiscovery.org and click on Papers. We selected one of those papers as an Editors’ Pick. It’s a meta-analysis of epidemiological studies of neuromyelitis optica, also called NMO or Devic’s disease. The conclusion of the meta-analysis is that there’s a high level of heterogeneity among the 9 studies that met the inclusion criteria. The prevalence of NMO in the studies ranged from 0.51 per hundred thousand in Cuba to 4.4 per hundred thousand in southern Denmark.   Will you be attending the annual meeting of the Consortium of Multiple Sclerosis Centers in Indianapolis next week? If so, please come visit us at the Accelerated Cure Project’s booth. We’ll be demonstrating some of our latest data visualizations along with other features of the MS Discovery Forum. You’ll find the booth in the hallway close to the main entrance to the exhibit hall, and we look forward to meeting you.   [transition music]   Now to the interview. I spoke with Dr. Lawrence Steinman, professor of neurology and neurological sciences, pediatrics, and genetics at Stanford University, who has a new twist on amyloid, this time in MS.   Interviewer – Dan Keller Dr. Steinman, you have proposed that amyloid can be a protective molecule as well as what’s commonly viewed as a destructive molecule. How did you come upon this?   Interviewee – Lawrence Steinman We came about it serendipitously or by accident. I had a graduate student and I thought I would give that student some low-hanging fruit, and the low-hanging fruit was to take the conventional animal model that we use for multiple sclerosis called experimental autoimmune encephalomyelitis – EAE. And when she put in these long peptides from an infamous protein named amyloid beta – A-beta – she put it into the animals with EAE at the time they were paralyzed, and I thought well, these are molecules that cause even more inflammation in the central nervous system, so they should make the disease worse, or perhaps they’ll have no effect and then we’ll have to think of another project for her PhD. So the student, Jacqueline Grant, came back and said, “Well, I gave the A-beta peptides and the animals are all better, they’re walking around.” And I first reacted, no, you must have confused the cages, let’s do it again. And when we did it again there was the same result, so then we were off to the races.   There was a second reason besides the low-hanging fruit description. May Han, my colleague, and I had reported the proteomics of MS lesions; so we took well-defined MS lesions, May cut frozen sections and then removed the lesion area with a laser tool, and then we trypsinized, fragmented the proteins, and used a modern technique, mass spectroscopy, to get the proteome, a list of all the proteins in the lesions. So amyloid proteins such as amyloid precursor protein and cal protein are found in the lesions themselves, so I thought that that was a second opportunity, a second foundation for doing these experiments in EAE; let’s see what happens when we augment, if you will, a naturally occurring protein found in the lesion to see perhaps what it’s doing. But, again, my bias, based on the dominant theory in Alzheimer’s disease is that amyloid was going to cause harm in MS as well as Alzheimer’s.   MSDF In these experiments, the amyloid was injected IV so it seems to circulate, but does it get to the brain in these mouse EAE models?   Dr. Steinman Actually, it does not get to the brain. We’ve actually put it into the brain directly to see if it would spread throughout the brain, and in our hands the molecules we’re working with do not spread. Most of these experiments showing a prion-like spread of amyloid is done in animals that are overexpressing the amyloid proteins in the brain so that they’re sort of tilting the balance to enhance spread if it’s going to occur, but we don’t get these amyloid molecules into the brain when we inject them intravenously, nor do we spread them around when we injected them directly into the brain.   MSDF So if you’re injecting them peripherally, do you think that there is some direct effect, or do you think they’re acting through lymphocytes or other circulating cells?   Dr. Steinman Well, we now know that there are at least two mechanisms. One is that when we are injecting them peripherally, these amyloid-like molecules, they go to sites of inflammation and this could include sites of inflammation within the brain. But remember, they’re on the vascular side of the lesion. And they act in a way like molecular sponges. The amyloid molecule is very sticky; in fact, when you try to work with some of the amyloid molecules, they’re like bricks, they stick to the walls of test tubes, and more importantly, they stick to each other and form these long, brick-like fibrils.   So what they’re doing when we put them into the circulation is they’re sopping up many of the inflammatory mediators that appear in the circulation during inflammatory diseases, including inflammatory diseases of the brain. These inflammatory mediators include the complement proteins and some of the famous apolipoproteins that we’ve heard about in reference to Alzheimer’s, we’ve heard the most about apolipoprotein E. So these amyloid molecules, when they’re in the circulation, actually stick and take away, precipitate away these inflammatory mediators. So I call it a molecular sponge.   There’s another set of mechanisms that we’re learning about that we’re able to use these amyloid proteins to do a couple of things to lymphocytes. One, it sets up a type 1 interferon response in lymphocytes. So the amyloid fibrils are a known trigger for the production of type 1 interferon, and type 1 interferon is actually beneficial for neuroinflammation; we have approved drugs. It’s doing another thing that we’re on the verge of publishing, but I’ll sort of give the headline without too many details; it’s setting up a type of lymphocyte that has a more regulatory function. So these are all rather unexpected roles for amyloid proteins.   MSDF And you have done adoptive transfer of some of these lymphocytes and find similar effects?   Dr. Steinman Yes. And the adoptive transfer experiments are very interesting. When we set up the system to produce a lot of type 1 interferon after we give an amyloid fibril, if the type of disease is what’s called the Th17 disease, the increased beta interferon actually worsens that, and if we create a disease that is called T-helper 1 – Th1 – then the type 1 interferon is beneficial. So we’ve engineered some amyloid structures so that they trigger less type 1 interferon, and when they trigger less type 1 interferon, then they work in both the Th1 and Th17 models. We published on that in the Journal of Experimental Medicine. But, again, even here with the type 1 interferon, the effect is nuanced and we can engineer these amyloid structures to be really beneficial and to take away the harm.   I wanted to say one thing, that clinicians and working scientists generally understand amyloid very well. Amyloid-beta that’s well known. Other amyloid proteins that people are, of course, familiar with are tau, prion protein, alpha-synuclein. But an amyloid structure is a general description of a protein that forms beta sheet, so the beta strand structure allows through hydrogen bonds the formation of what you should think of as a venetian blind, these monotonously parallel sheets that actually intercalate dyes, like Congo red or thioflavin T, so that when you shine polarized light on them they refract it in a polarized way. So we can make these structures, if you will, they’re organized nano particulars, to be more or less water-soluble, to be greater or lesser inducers of type 1 interferon. So there’s a whole armamentarium of very interesting amyloid structures that we can engineer to provide benefit in different situations.   Now what does this all mean for the Alzheimer’s hypothesis? And we’re doing an audio interview, so I’m sort of smiling wryly. I don’t want to get into that because we haven’t done the experiment in the amyloid-beta overproducing transgenic mice that have served as the model system to test whether various amyloid-lowering procedures will provide benefit, we just haven’t done that. And we’ve tried our particular approach in a number of other conditions ranging from stroke to EAE, as I said, to experimental heart attacks. And in the systems that we’ve studied, we see benefit.   MSDF But as a further proof of concept of what you have found in the protective effect of amyloid, you’ve looked at amyloid precursor protein knockout mice. Is that right?   Dr. Steinman Yes. Well, that’s a whole interesting story, and thanks for reminding me. So in a series of experiments that we have done and others have done, we first noticed that amyloid precursor protein knockout mice, they had worse EAE. Another person in Australia, Colin Masters, who’s actually one of the leaders in the field of Alzheimer’s research, looked at experimental head trauma, and in the amyloid precursor protein knockout mouse, they had a worse condition after head trauma that was alleviated by giving amyloid precursor protein in its soluble form. And then other people have shown that experimental encephalomyelitis is worse in prion knockout animals and in tau knockout animals.   We had been working with a protein called alpha-B crystallin, which is also an amyloid-forming protein, and we noticed that EAE was worse in the absence of alpha-B crystallin. So there’s a long series of experiments that loss of function, loss of the parent protein of these amyloid-producing molecules, leads to worsened inflammation, whether it’s EAE, head trauma, or somebody else did it in experimental heart attack. And we also did it in experimental stroke, so under a variety of conditions.   So this makes the argument even stronger, suggesting that amyloid structures when augmented can provide benefit and reduce inflammation, and when absent can actually exacerbate inflammation; so gain of function better, loss of function worse. So you have to look at the amyloid molecule as something that is not always harmful and pathologic. Whether it is the main culprit in Alzheimer’s, whether Alzheimer’s is an example of neuroinflammation, I leave it to people in that field because I really don’t want to take them on headlong at this point in time when we have all these fascinating results elsewhere. But I let the listeners draw their own conclusion based on the published work that I’m talking about, not only from my own lab but from other investigators all over the world.   One might want to think a little bit differently the next time one thinks about the deleterious effects of amyloid in Alzheimer’s, but I’m not going to be the one that takes on that massive scientific opinion, we’ll just have to see how it works out. I hope everyone’s been right over all these years because we certainly need some answers in that field. And if they are right, then we’ll have to integrate the kinds of things that we’re understanding about the role of amyloid proteins in other types of inflammatory conditions with a positive result in Alzheimer’s when it’s taken into the clinic. If it turns out that the experiments do not succeed in Alzheimer’s, then it will be easier to reconcile these different outcomes. But I think we’ll have to be patient; science doesn’t move as fast as some of us would like to have it move.   MSDF What was the time course of seeing a result by injecting the amyloid in your EAE models?   Dr. Steinman It’s very fast. When you inject the amyloid, it’s within 48 hours. If you stop giving the amyloid – we like to give it every day – if you stop giving it for a few days, the inflammation recurs, and that suggests that these amyloid structures are acting like a pharmaceutical. It’s not one of these situations that you sometimes see in science; you give the molecule once or twice and the disease goes away forever. This seems to be suppressing ongoing inflammation while it circulates, and when you take it away the effect is gone and the disease recurs, so that’s very interesting.   MSDF The effect seems to be too quick for remyelination to be occurring as the answer, but when you give it chronically do you see remyelination?   Dr. Steinman So far, we haven’t looked for long enough periods of time or with sensitive enough techniques. Your question triggers an experiment and we should really take a look at that. I would imagine that if you can abrogate inflammation that you’ll allow for remyelination if there’s anything left in the oligodendrocyte precursor to remyelinate itself, or if you need a little augmentation, it would be good to do a stem cell type of therapy under the protection of this kind of antiinflammatory approach.   MSDF Are you planning any early human trials?   Dr. Steinman Ha! I chuckle because this is a tough one to bring into the clinic. I’ve been funded by people who first scolded me for saying don’t take this too fast into the clinic, because I like to translate results. In this one, we’ll have to be more cautious than we might for other types of therapies.   MSDF Is there anything important to add?   Dr. Steinman I thought the questions were very comprehensive. And as you can see from where our matters stand now, there’s a lot of positive leads to pursue. And I think we’ll have to be cautious about translating in the fields of multiple sclerosis or stroke because of the infamy of the molecule I’m working with, but we’ll get there. Thank you.   MSDF Thank you.   [transition music]   Thank you for listening to Episode Forty-two of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]

Hello AaA Fans and welcome to the latest episode of your Amps and Axes Podcast. This week the guys first bring up the new FAA guidelines for treating a guitar as a carry on. The conversation then continues with the Editors Pick by Guitar Player of the new Fishman Fluence pickups as well as the "Holy Grail" Les Paul auction. They then bring in this weeks guest, LA guitarist extraordinaire' as well as guitarist for Supertramp, please make welcome Mr Carl Verheyne. Enjoy and Thanks for Listening.

[intro music]   Hello, and welcome to Episode Twenty-Eight of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features part two of an interview with Dr. Brenda Banwell in which we discuss pediatric MS. But to begin, here’s a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Researchers recently put a simple measure of corpus callosum atrophy to the test in a 17-year-long study. The team measured the area of this inter-hemisphere highway in MS patients and found it correlated with their cognitive and physical disabilities over time. Corpus callosum area is faster, easier, and cheaper to measure than volume, since it requires no special equipment beyond the typical MRI machine. The researchers hope they will be able to demonstrate that this measurement can also predict disease course in future studies with larger cohorts.   Every Friday we curate research articles on all topics related to multiple sclerosis and highlight our favorites in the “Editors’ Pick.” Two weeks ago, the editors’ picks included a study on the HPV vaccine and MS and another about how cinnamon can ameliorate EAE. Last week we chose a study on heterogeneity among oligodendrocyte precursor cells and another on teasing out the causal variants in genetics association studies. You can see our weekly picks by going to our website, clicking on the “Papers” tab, and selecting “Editors’ Picks.” In addition to the Editors’ Picks, we link to every MS-related study found in PubMed.   Our senior science writer, Carol Morton, will be at the Keystone meeting on Neuroinflammation in Diseases of the Central Nervous System in Taos, New Mexico from January 25th through the 30th. She will be on the hunt for good stories and interviews for this podcast, so be sure to say “hi” and tell her all about your latest work.   [transition music]   Now to the interview. Dr. Brenda Banwell is Professor of Neurology and Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and chief of the Division of Neurology at The Children’s Hospital of Philadelphia. Last week, we talked about a new journal called Multiple Sclerosis and Related Disorders, of which she is one of the co-editors-in-chief. This week we turn to her particular subspecialty.   [Interview]   Interviewer – Dan Keller I’m here at The Children’s Hospital of Philadelphia with Dr. Banwell, and someone from the public affairs office is here with us. Dr. Banwell, let’s talk about pediatric MS. What are some of the clinical features that you see that may distinguish it from adult?   Interviewee – Brenda Banwell Maybe walk you through a little bit of the journey that the pediatric multiple sclerosis field has taken over the last 10-12 years. When pediatric multiple sclerosis clinics were first being created which was in the late 1990s, the literature on pediatric multiple sclerosis was extremely brief; it was a mixture of patients that we now recognize have multiple sclerosis, some have what we call acute disseminated encephalomyelitis – ADEM – and still others had different demyelinating disorders. And there were no consensus criteria for the diagnosis of multiple sclerosis in children and the criteria for the diagnosis in adults did not include pediatric-onset patients formally. All of that has changed. And in the process of making the diagnosis of multiple sclerosis more clearly, we obviously had to look at the clinical features.   So, first of all, I would say that multiple sclerosis onset during childhood and teenage years is relapsing-remitting in character, so clear relapses and periods of clear remission. We have not seen children with primary progressive multiple sclerosis. Worldwide there are a very, very small number of children who may have that diagnosis; it’s extremely unlikely that there are very many, so for all intents and purposes it’s a relapsing-remitting disease during the pediatric age group.   The clinical features of attacks are generally very similar to adults with a few caveats. In children who are under about 10, there’s a likelihood that the children will present a little more atypically than adults. The younger children present with an episode with multiple neurological deficits, confusion, even impairment in level of consciousness which can make that first episode very difficult to distinguish from the more traditional acute disseminated encephalomyelitis, the important difference between the two being acute disseminated encephalomyelitis is a monophasic disease, so one attack almost always without any MRI evidence of new disease over time and no further clinical relapses in the vast majority of those children. So it’s a very important diagnosis to distinguish from the lifelong disease, multiple sclerosis, and one can distinguish them obviously on the basis of time but also on certain MRI features. And specifically when one looks at the first presentation, looking for risk determinants for multiple sclerosis are also important.   So in that vein, we’ve looked at things that are associated with the likelihood that a first attack is really multiple sclerosis, and those include prior exposure to Epstein-Barr virus, which gives one about a sixfold increased likelihood of having MS; low vitamin D levels which is a problem because low vitamin D levels are quite common in the community now across the board in certain parts of the world, but children who have very low levels are more likely to have multiple sclerosis compared to children whose vitamin D levels were higher when they present with an acute event.   If the MRI scan in the brain shows areas of what we call “T1 hypointensity”, which are black holes or really are indications of focal prior brain injury, then those patients are much more likely to have multiple sclerosis. And the reason for that is that in multiple sclerosis, the first attack when you first have the deficits, there’s likely been a period of time behind the scenes where the immune system has begun to attack and has had focal areas of injury that the patient didn’t recognize but are clearly visible on MRI, so MRI is our extraordinarily helpful guide. So areas of abnormality in the brain that are in the what we call periventricular white matter, and then these dark areas on these what are called T1 sequences are strongly indicative that this is a first attack of multiple sclerosis.   Conversely, most children with transient illness either have a normal brain MRI and maybe have inflammation in the back of the eye, the optic nerve, or the spinal cord, or they have this ADEM – acute disseminated encephalomyelitis picture – which gives you these hazy, widespread, large, ill-defined changes in the brain MRI that are at least visually quite different from multiple sclerosis. The key subsequent to that is that in patients with multiple sclerosis, by definition there will be new disease over time both on serial MRI scans and clinically. And that is also the case in young adults with relapsing-remitting multiple sclerosis.   Genetically, pediatric MS patients do have – at least those from northern European heritage – a higher likelihood of having what we call the HLA-DRB*1501 locus, which is a gene that is important in immune system development or at least immune system recognition of self. And that relationship is true in adult-onset MS as well, and over the last few years the number of genes that have been linked to multiple sclerosis risk overall, and that panel of genes is similar in pediatric-onset MS.   So I think the overall message is that relapsing-remitting multiple sclerosis in children and adults is very likely to be the same disease. There are some subtle differences relating to the age of the patient, but if you follow people over time the relapsing-remitting character and the changes on imaging and these clinical feature of kids are really quite similar to relapsing-remitting MS in young adults.   MSDF When you mentioned exposure to Epstein-Barr virus as a risk factor, if you looked at adults about 90% of people have antibody. Do kids generally not have such a proportion of antibody and it’s more indicative there? Does it tell you more if they are positive than in an adult?   Dr. Banwell There’s a lot of evidence that suggests that your multiple sclerosis risk is determined by where you grow up in your childhood years. You may not manifest with the disease until you’re 20 or 30, but all sort of studies, particularly immigration studies, strongly suggest it’s where you grow up that determines your risk. Therefore, if something is a risk factor, one ought to have it if your onset is a 6-year-old or an 8-year-old or a 10-year-old, if it’s important in causing the disease. So when we looked at Epstein-Barr virus exposure in pediatric-onset MS patients, about 80-85% are positive, which compares to only about 35-40% of regional, age, and sex-matched healthy children. So our power to make the relationship is very high. What the Epstein-Barr virus means to the person may be very similar in kids and adults. Certainly in adult-onset MS patients, about 97-98% are positive, which compares to about 90% of the healthy population. So it’s still higher but, of course, you’re sampling the adult patients way past when the exposure may have occurred, and so there’s been time for people who don’t have the disease to also experience the exposure, it just doesn’t matter – presumably – to them; they’re not manifesting with MS.   In children, though, when we’re looking at patients who are presenting very, very close to when they presumably had the key risk exposure. So we think that’s biologically important. We’ve also looked at viral shedding. So Epstein-Barr virus is an interesting infection because once you acquire it, it lives in your B-cell population so you have EBV-infected B cells, and about 20% of the year you shed the virus in saliva, which is why it’s so easily spread, particularly in adolescence, which is when it’s particularly acquired. So we looked in our pediatric MS patients at how many times in the course of a year, so with a sample done with most swabs once a month, were they shedding the virus, and looked at Epstein-Barr virus-exposed healthy kids. Healthy children shed the virus 20% of the year, as has been previously reported; MS patients, it was 66-70% of the year.   So one of our hypotheses that we’re currently exploring further is whether maybe part of what Epstein-Barr virus might do in MS is, first of all, shed more often so you’re controlling it less well. Every time you shed the virus, your immune system has to turn itself back on and put the virus back into its latent state. If you don’t you can end up with all sorts of complications including lymphoma. And so if part of Epstein-Barr virus’ role in MS is turning the immune system on multiple months per year, that isn’t probably what you want when you have an autoimmune disease; you don’t want your immune system being turned on multiple times a year, particularly if unfortunately you turn on a component of the immune system that may then be directed at the brain. So that’s an interesting phenomenon that we’re currently doing further research on.   MSDF So it sounds like the EBV is something of a polyclonal activator of B cells which then cross-react in the brain, or do react in the brain?   Dr. Banwell Well, that’s the next stage is to see if you look at what immune cells are responding to the challenge of this reactivated EBV, is it that there are specific T-cell clones, and if so are those T-cells specifically looking at proteins expressed both by EBV and by proteins in the central nervous system, sort of a molecular mimicry model, which might be true? Or is it just unfortunate that you’ve turned the whole immune system on, or a large number of aspects of the immune system on, which is more of a general immune process? We don’t know the answer to that.   MSDF Considering these patients start out with relapsing-remitting MS earlier, do they progress to secondary-progressive earlier or at the same age as someone who gets it as an adult?   Dr. Banwell Good question. So the only really good paper on that question, keeping in mind that if we go from prospective studies that are really only started in 1999 to 2000, we don’t have a lot of prospectively rigorously studied pediatric patients. But Dr. Renaud in the New England Journal of Medicine published a paper from the French database where they looked at patients who reported pediatric-onset MS. And what they found was that from first attack until the point at which 50% of their pediatric-onset patients had started into secondary disease progression, that time interval was about 20 years, which is about 10 years longer than one would report on average in adult-onset MS. So if you look at adult-onset MS patients, 50% of them will have entered into secondary disease progression after 10 years from first attack. This is all untreated patients, which of course now is no longer really much the case in developed parts of the world.   So the patients with pediatric-onset take longer to start into secondary disease progression, but if you’re only 6 or 7 or 8 when you have your first attack, you’re 28 when you start to develop disability, which is about 10 years younger than most of the adult-onset patients. So the take-home message is it is certainly not more benign based on this particular data, the age at which patients are at-risk of becoming disabled is actually younger, but the time interval from the beginning of their disease until that time point is longer. And we hope that the current therapies and the new emerging therapies will change that outcome, but of course we only are just beginning to have a chance to see that.   MSDF What are some of the challenges in doing clinical trials with a pediatric population?   Dr. Banwell So in adult-onset MS patients, the clinical trial models have been very large; they’ve been randomized, double-blind, placebo-controlled, rigorously done studies that have often employed 200-400 individuals per study arm. And that is often quite feasible because the large MS programs around in North America and in many parts of Europe, an average adult MS clinic where MS is a common can have 3,000 patients alone. There are probably fewer than 3,000 pediatric-onset MS patients available for clinical trials worldwide total, and even that number may be inaccurate. So most pediatric MS programs in the world, of which there are still relatively few that have anything more than five or six patients, are really, really few and far between. So there just simply is a markedly reduced number of pediatric MS patients available for clinical trials.   Also challenging the current environment is that there are multiple trials all coming forward at the same time. So the FDA and the European’s Medicine Agency in particular require what they call “Pediatric Investigation Plans” – or PIPs – for all new drugs that are coming to market. In the MS field there are multiple new drugs coming to market. All of them have filed these Pediatric Investigation Plans. So even if we had the number of patients to power one study, we certainly don’t have enough patients to power five or six concurrently, therefore we run the risk of a given trial failing because it doesn’t reach its enrollment numbers.   We have families facing choices between multiple potential clinical trials at the same time and centers facing the challenge of launching multiple trials at the same time and the inherent difficulty with all of the work that goes into getting a study up and running at a given center. Pediatric MS patients have never previously been offered pediatric trial opportunities, so the culture of being in a trial is new so it’s a learning curve for everyone. And the medications that are being put forward have varying priorities. So some of the medications are oral, which may be quite appealing to children who are not, understandably, very keen on injections; some are given by infusion and that has varying challenges.   A clinical trial is not just an enormous time commitment on the behalf of the patient, in which our case is a child, but also their parents who have work and other commitments and other children. So being part of a clinical trial is an enormous commitment for a family, which is different than the commitment experienced by an individual who’s making that decision on their own behalf. And then adding to all of those challenges is the safety aspects of all these new medications, and of course our top priority amongst anything else is to make sure that our patients stay safe.   And so where there may be marked similarity in relapsing-remitting MS as a disease between children and adults, these therapies are being administered at a different time in terms of brain maturation, to a lesser worry but still important in terms of different levels of immune maturation, and certainly – very importantly – at a different stage of life in terms of acquisition of infection. And so many of the new medications that are coming online are more powerful than the medicines that are currently available, many are more capable of suppressing immune responses which puts a significant burden on making sure that everybody is fully vaccinated to the various things we can vaccinate against, but still kids are going to acquire their first infections during the window of time they may be on some of these medications. And so it’s really quite similar to some extent to some of the pediatric oncology care plans that we have to be very, very aware of.   MSDF It looks like the Canadian database of pediatric MS patients is one of the largest; I think when I talked to Amit Bar-Or, it was about 420 or 450. It sounds like there’s a real vying here for patients in terms of clinical trials, and is it even feasible; is it something that you should just discuss with the FDA and say how is this possible to do?   Dr. Banwell So I am one of four members of a clinical trials advisory group on behalf of the International Pediatric Multiple Sclerosis Study Group, which is an international group of about 150 physicians from 40 countries, so I do serve on an advisory to FDA and EMA under that umbrella. And the group of us have very much expressed this concern to FDA and EMA and have articulated our worry about underpowered trials. It’s a difficult environment, there’s a lot of discussion still to be had. The general statement from the regulatory authorities for each of the individual medications that are coming forward is that they are required to have a pediatric plan. And that was a hard-fought battle over many years to try to increase high-quality evidence for treatment of children, which all of us who treat children endorse.   So it’s not that we don’t want there to be good trials, it’s just, unfortunately, the reality is that it’s going to be very difficult to do traditional study designs with large arms and placebo-controlled, randomized, double-blinded models are not always going to be suited for all of the therapies. They’re not possible to do for every therapy that’s coming forward, and there’s going to need to be some discussion at a minimum on trial design and potentially on which trials are being done in what order, although that, of course, is certainly not my purview to decide, but it isn’t feasible to run multiple trials in this rare disease at the same time. So we’re going to need to look at rare disease models of therapy that have been put forward for perhaps some of the rare childhood cancers, for example, and other diseases, and we’re going to need the regulatory authorities to recognize we can’t use adult MS study designs for pediatric MS patients.   MSDF Very good, I appreciate it. Thank you.   Dr. Banwell Oh, you’re welcome.   [transition music]   Thank you for listening to Episode Twenty-Eight of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]  

In this episode, I have the immense pleasure of chatting with the very hilarious Jimmy Pardo. A comedian often described as a "comic's comic" and the host of the immensely popular podcast "Never Not Funny," Jimmy is a guy who never fails to make me laugh. His podcast is the #2 podcast on iTunes hosted by a comic, after Ricky Gervais'. His television credits include: “Conan,” “That 70’s Show,” “Last Comic Standing” “Becker,” “The Late Late Show With Craig Ferguson,” “Monk,” “The Tonight Show With Jay Leno” and his own half-hour special, "Comedy Central Presents Jimmy Pardo." You may have also seen him interviewing celebrities on Team Coco's web series, "The Pardo Patrol." We talk about everything from managing a record store in the 80's to writing bad jokes about tornados to his new web series "Write Now! with Jimmy Pardo," a joint production of Nerdist and Never Not Funny. It will come out on October 29 on the Nerdist YouTube channel. JIMMY PARDO'S BIO Jimmy Pardo is as funny talking to a stranger in an elevator as he is talking to a crowd from the comic stage. That's because everything he observes or thinks, he immediately scans to find the funny. And he always finds the funny. After Jimmy was told for like the thousandth time that he was even funnier offstage than he was onstage, he dropped most of the jokes from his act. Now he spends nearly his entire set interacting with, and making fun of, his audience. And they love it. Jimmy stands at the very center of the comedy world. That's not only because he's the ultimate "comic's comic," (as he's often called), but also because he represents where comedy is going, and everybody wants to come along. Jimmy's raucous-but-smart weekly podcast, "Never Not Funny," has revolutionized the way comedians use the internet to connect with their audiences. It's the No. 2 paid podcast hosted by a comedian, after Ricky Gervais's. His guest list reads like a Who's Who of comedy: Conan O'Brien, Adam Carolla, Kevin Pollack, and Sarah Silverman have all been guests. Actors Jon Hamm, Ty Burrell and Craig Bierko have appeared on several of the funniest episodes. "Never Not Funny" was voted by both iTunes and USA Today as one of the top podcasts of 2006 and 2007. It was an Editor's Pick in the September 2009 issue of Esquire magazine. In 2010, GQ magazine called the show "The Number 1 Relatively Obscure Thing You Need to Be Paying Attention To." The show, which started in Jimmy's dining room in 2006, now regularly hits the road with live tapings at festivals like SF Sketchfest, MaxFunCon, the Vancouver Comedy Festival and Bumbershoot. Twice, Jimmy and Co. have presented the "Pardcast-A-Thon," taping for up to 12 hours to raise money for The Smile Train. Besides the podcast, Jimmy continues to headline at some of America's top comedy clubs and currently works as Conan O'Brien's opening act on "Conan," getting the studio audience into a laughing mood before the show tapes (he did the same for Conan on "The Tonight Show"). A true multimedia talent, Jimmy has frequently appeared on television and in movies. He has performed on "The Tonight Show with Jay Leno" and "The Late Late Show with Craig Ferguson." He had his own half-hour special, "Comedy Central Presents Jimmy Pardo." He hosted "National Lampoon's Funny Money" on the Game Show Network, and was the co-host of AMC's "Movies at Our House" for four seasons. He has hosted episodes of VH1's "The Surreal Life" and "Love Lounge" and NBC's "Late Friday." He's appeared on popular shows such as "Monk," "That 70s Show," and "Becker." And he has acted in independent films such as "Relative Strangers" and "The Godfather of Green Bay." Jimmy was the co-writer and star of the critically-acclaimed one-man show subtly titled "Attention Must Be Paid: The Jimmy Pardo Story" and a live pilot presentation, "Jimmy Pardo's Dance Party." He hosts monthly shows at the famed Upright Citizen's Brigade Theatre in Los Angeles. He has recorded two comedy albums, "Uno" and "Pompous Clown."