Podcasts about MRC

MRC welcomes the legendary British penciller Mike Collins (who drew the first appearance of Gambit!) to discuss the books of November 1967, featuring Amazing Spider-Man 54, Daredevil 34, Thor 146, Tales to Astonish 97 with Namor and Hulk, and X-Men 38! Roomer has it! Too Dumb to Die! Volstagless-Thor! Swamp Men! Living Lightning! Blobby pupils! Check it out!

In today's MadTech Daily, we cover the IAB and MRC's release of draft guidelines for attention measurement, Frasers Group's launch of retail media network ELEVATE, and new research valuing the global podcast industry at USD$7.3bn, more than double previous estimates.

Entérate de lo que está cambiando el podcasting y el marketing digital:-Interpodcast 2025 arranca con una nueva edición internacional de intercambio podcastero.-IAB y MRC lanzan métricas de atención para audio y medios digitales.-Cómo mujeres afroamericanas están transformando su futuro financiero a través del podcasting.-El futuro de un auto sin radio inquieta a la industria.Patrocinios ¿Estás pensando en anunciar tu negocio, producto o pódcast en México? En RSS.com y RSS.media tenemos la solución. Contamos con un amplio catálogo de pódcast para conectar tu mensaje con millones de oyentes en México y LATAM. Escríbenos a ventas@rss.com y haz crecer tu idea con nosotros.Entérate, en solo cinco minutos, sobre las noticias, herramientas, tips y recursos que te ayudarán a crear un pódcast genial y exitoso. Subscríbete a la “newsletter“ de Via Podcast.

La menace spatiale! Shamelessplug Hackfest Swag Join Hackfest/La French Connection Discord Join Hackfest us on Mastodon Nouvelles La menace spatiale! Explosion d ‘emploi en cybersécurité, une vraie farce CVE will live on DOGE Whistle blower DOGE via NPR SSH exploit Deepfake et ingénierie sociale….seriez-vous différencier le vrai du faux avec vos proches SuperCard X Android Malware Enables Contactless ATM and PoS Fraud via NFC Relay Attacks Piratage et demande de rançon à la MRC de Maskinongé Dossier santé numérique: un conflit d'intérêts comme dans le fiasco SAAQclic? Publier une simple photo peut vous mettre en DANGER Crew Patrick Mathieu Steve Waterhouse Francis Coats Jacques Sauvé Richer Dinelle Crédits Montage audio par Hackfest Communication Music par Ecometric – TransPlants - Beatroots - Sailor (Ecometric Renavigation) Locaux virtuels par Streamyard

MRC finishes up October of 1967 with Fantastic Four 67, Strange Tales 161 with SHIELD and Dr. Strange, Tales of Suspense 94 with Iron Man and Captain America, and Avengers 45. The Creature in Lock 41! The Id-Paralyzer! All-Swipes! Titanium Miniskirts! MODOK vs. Beekeepers! Waffle-Pattern Eyes! Check it out!

Guest Bill D'Agostino, Research Analyst with MRC, joins to discuss low ratings and trust in the mainstream media. Discussion of negative coverage of the Trump administration, the changes of media coverage for ratings and profits, and the future of gathering content.  Update on Florida State Shooting and upcoming 2A debate on firearms.  REAL ID coming in May in order to travel? What is the purpose for another federal ID and who will be following the new rule? 

En 2009, une étude menée par le Conseil de Recherche Médicale d'Afrique du Sud (MRC) a révélé que plus d'un quart des hommes sud-africains interrogés ont admis avoir commis un viol. Cette enquête, dirigée par la professeure Rachel Jewkes, a porté sur un échantillon représentatif de 1 738 hommes des provinces du Cap-Oriental et du KwaZulu-Natal. Principaux résultats de l'étude :27,6 % des hommes interrogés ont reconnu avoir violé une femme ou une fille.Parmi eux, 23,2 % ont déclaré avoir violé deux ou trois femmes, 8,4 % entre quatre et cinq, 7,1 % entre six et dix, et 7,7 % plus de dix femmes ou filles. 46,5 % des auteurs de viols ont commis leur premier acte entre 15 et 19 ans, et 9,8 % avant l'âge de 10 ans.Ces chiffres alarmants mettent en lumière une culture de la violence sexuelle profondément enracinée en Afrique du Sud. Les raisons évoquées par les auteurs incluent la recherche de "plaisir", l'ennui, la pression des pairs et des notions de punition envers les femmes. Facteurs contribuant à cette situation :Normes culturelles et sociales : Des idées de masculinité basées sur la hiérarchie de genre et le sentiment d'un droit sexuel des hommes sont répandues. Inégalités socio-économiques : Les disparités économiques et le chômage élevé exacerbent les tensions et la violence.Héritage de l'apartheid : La période de l'apartheid a laissé une société fragmentée avec des structures familiales déstabilisées et une méfiance envers les institutions. Conséquences sur la santé publique :L'étude a également établi un lien entre la violence sexuelle et la prévalence du VIH. Les hommes violents envers leurs partenaires sont deux fois plus susceptibles d'être séropositifs. De plus, une femme violée par un homme de plus de 25 ans a une chance sur quatre que son agresseur soit porteur du VIH. Réactions et mesures prises :Face à ces révélations, des organisations locales et internationales ont intensifié leurs efforts pour lutter contre la violence sexuelle en Afrique du Sud. Des campagnes de sensibilisation ont été lancées pour remettre en question les normes de genre toxiques et promouvoir des relations égalitaires. Cependant, malgré des lois progressistes, leur application reste insuffisante, et la culture de l'impunité persiste. Conclusion :Les résultats de l'étude du MRC ont mis en évidence l'ampleur de la crise de la violence sexuelle en Afrique du Sud. Ils soulignent la nécessité d'une approche multidimensionnelle, combinant des réformes législatives, des programmes éducatifs et des initiatives communautaires pour transformer les attitudes et réduire la prévalence du viol dans le pays. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

MRC launches into October of 1967 with Amazing Spider-Man #53, Daredevil #33, Thor #145, Tales to Astonish #96 with Namor and Hulk, and X-Men #37! Seeds of the clone sagas! A laundry list of things not associated with beetles! T-Shirt Thor! Polar Serpents! The Beginning of the End of Human Evolution! Far Out Helmets! Check it out!

In today's podcast I talk about: Jumbo circus with Jithin, Rashmi, Riyaz and Seema. Reliving childhood memories. 31k run with MRC runners. Focusing on recovery.

Dan Schneider, Vice President for Free Speech at the Media Research Center, joins me to discuss Big Tech's censorship of conservative voices and the legacy media's unwillingness to reform in the wake of Trump's 2024 election victory. - - -  Today's Sponsor: Helix Sleep - Go to https://helixsleep.com/klavan to get an exclusive offer.

Jerry Giordano, author of Your 7 Words to a Happier You: Unlock the Story Sabotaging Your Relationships? With personal insights and a lot of humor, Jerry will talk about why we do what we do and how it's sabotaging our relationships and ourselves. Jerry has put his 7-word philosophy into practice by interviewing over 200 people from ages thirteen to ninety-four. He can share: How he tried every form of therapy, seminar, retreat, life coach, past-life regression, psychic and self-help book available, but still felt the same His realization that these were all left-brained approaches (logic) to a right-brained problem (emotion)Hitting rock bottom -- in the span of weeks, he lost his mother to cancer and his fiancée broke up with him How his newfound mindfulness practice and meditations helped him discover that his easygoing, people-pleasing persona was fake How he discovered the 7 words approach and how that's led to an in-depth understanding of the unconscious story that was affecting his life “As a psychotherapist, introducing a number of clients to their 7 Words has been an effective tool for uncovering their unconscious stories and circumventing their sabotaging lifelong patterns. The discovery of my own words was the breakthrough I was unknowingly in search of for decades! Jerry's writing exudes an uncommon vulnerability, clarity and authenticity, and this book takes self-help/self-discovery to a transcendent level.”— Melissa D. Borski, MRC, CFRC, LPCBecome a supporter of this podcast: https://www.spreaker.com/podcast/arroe-collins-unplugged-totally-uncut--994165/support.

MRC wraps up September 1967 with Fantastic Four #66, Strange Tales #160 with SHIELD and Dr. Strange, Tales of Suspense #93 with Iron Man and Captain America and Avengers #44! Electroni-Blades! Gravity-Nullifying Belts! The Lost Communion of Evil Intent! MODOK! Deadly belt buckles! Check it out!

Les recherches en génomique humaine effectuées en Afrique ont été le sujet principal du sommet de la Human Genome Organisation (HUGO) qui s'est tenu pour la première fois sur le continent en mars, dans la ville sud-africaine de Durban. Comme dans le cas de l'intelligence artificielle, le domaine de la génétique est aussi victime d'un biais dans la construction de son modèle de référence, avec très peu de données venues d'Afrique. Et cela peut avoir des conséquences pour le traitement des populations locales et pour la recherche mondiale. De notre envoyée spéciale à Durban,Faute d'infrastructures, de ressources ou de personnel, beaucoup de maladies génétiques restent non détectées sur le continent. En République démocratique du Congo (RDC), Aimé Lumaka, en est régulièrement témoin avec son équipe.« Nous avons, au début de notre carrière, rencontré une famille qui a perdu environ 14 garçons. Leur peau devenait très noire et ils mourraient. Nous avons pensé à une maladie génétique, et nous avons pu la confirmer, explique le chercheur de l'université de Kinshasa. Ce qui était choquant, c'est que c'était une maladie qu'on pouvait traiter facilement avec une supplémentation en cortisol. C'est dans ce genre de situation qu'on voit la force de la génomique : cela peut permettre d'éviter des décès inutiles, des décès évitables. »À lire aussiCes scientifiques qui tentent de faire progresser la recherche génomique en Afrique« La médecine de précision est très importante »Le manque de recherches sur les variations des génomes en Afrique complique aussi les diagnostics, car les bases de données proposent comme référence des séquençages liés à des populations d'origine européenne ou américaine.Segun Fatumo travaille sur la question de la diversité génétique pour l'université Queen Mary de Londres, et le Conseil pour la recherche médicale (MRC) d'Ouganda : « La médecine de précision est très importante. Un traitement qui fonctionne bien sur des personnes qui ont une ascendance spécifique, peut ne pas aussi bien marcher pour d'autres. C'est pour cela que l'on doit étudier les génomes de tout le monde. »Un médicament anti-cholestérol conçu grâce à des études génétiquesL'absence de données freine, de plus, le développement de traitements pour les maladies génétiques qui touchent particulièrement le continent, comme la drépanocytose. Sans compter que la recherche en Afrique et l'identification de mutations peuvent avoir un intérêt pour le reste du monde. La professeure de l'université du Witwatersrand Michèle Ramsay prend l'exemple un médicament anti-cholestérol conçu grâce à des études génétiques.« Cette découverte a été réalisée grâce à l'observation de mutations génétiques qui sont davantage répandues chez des populations d'origine africaine, et on savait que ces populations avaient un taux de cholestérol plus bas que la normale. Il y a encore beaucoup de choses que l'on ignore, sur le plan de la biologie, et la génétique peut nous apporter des indices. S'il y a des variants, en Afrique, qui ne sont pas sortis du continent, et qui ont pu être sélectionnés à cause de facteurs environnementaux, ces variants vont être associés à certaines spécificités. Et si on arrive à comprendre ce lien, cela peut créer des opportunités en termes d'intervention, pour n'importe qui dans le monde. »Mais si des découvertes sont faites à partir de données africaines, les chercheurs sont unanimes : il faut mettre des protocoles en place afin que les populations du continent puissent aussi bénéficier des résultats et des traitements.À lire aussiEn Afrique, développer les connaissances sur les variations du génome [1/3]

MRC goes guestless to tackle the first half of September, 1967, with Amazing Spider-Man 52, Daredevil 32, Thor 144, Tales to Astonish 95 with Namor and the Hulk, and X-Men 36! Penthouse Dungeons! Convenient antidotes! Asgaaard! The resource curse! Vacuum rays! The Quest for Gas Money! Check it out!

RECORDED LIVE from the MRC 2025 Vegas conference, Angela Borden, Fraud Specialist at Little Caesars, and Lisa Meyers, founder of Mastfiv Consulting, join the show recorded in the same room for a change! Angela is fresh off her first-ever speaking panel where she discussed the common "Build vs. Buy" scenario product people face. We discuss some key takeaways from our time so far at the show like the evolving role of AI in fraud management and the industry's future direction in areas like ad fraud, Visa and Mastercard network changes and of course Visa's VAMP program and recent changes We end with some practical advice for conference-goers: capturing actionable insights, justifying attendance costs, and planning follow-ups. Overall, the short episode highlights industry shifts, new fraud prevention trends, and insights into navigating professional growth and networking at major conferences.   Angela Borden: https://www.linkedin.com/in/angelamborden/ Lisa Meyers: https://www.linkedin.com/in/lisakmeyers/  

Buying a car is a big deal. Unless you live in a walkable area, your car is likely the primary method of transportation used to get around. If so, you'll want something reliable as well as affordable. Many factors affect the price of vehicles from inflation, chip shortages, supply chain interruptions, and even the possibility of looming tariffs. At the time of this recording the average new car price is around $48,000 and with a price tag like that, it may be wise to make sure the next car you choose is reliable. But with so many cars to choose from, how do you know which is the best for you? Keep listening to learn what cars should be your next ride.  Links: Check out the Consumer Report for the Most Reliable Cars for 2025 Shop for a new car with Triangle's AutoSmart tool Learn more about Mechanical Repair Coverage Check out TCU University for financial education tips and resources!  Follow us on Facebook, Instagram and Twitter!  Learn more about Triangle Credit Union Transcript: Welcome to Money Tip Tuesday from the Making Money Personal podcast.   A good place to start when looking for a reliable vehicle is Consumer Reports. Consumer Reports is a nonprofit organization that unbiasedly tests products with consumers in mind, to educate and inform potential buyers. For this particular report, they asked their members about the variety of car problems they encountered in the past 12 months. As a result, Consumer Reports gathered information on over 300,000 vehicles with model years ranging from 2000 to 2025.   They then looked at problem areas, from minor inconveniences such as squeaky brakes and broken interior trim to major problems like engine or transmission issues. Consumer Reports then used the results to score the reliability of vehicles in all the different areas, with the major problems being weighted more.  According to Consumer Reports' findings, the top 3 most reliable new car brands for 2025 are Subaru, Lexus, and Toyota. On the other side, the bottom 3 unreliable new car brands turned out to be GMC, Cadillac, and Rivian. For those looking to buy a used car, the top 3 most reliable brands are Lexus, Toyota, and Mazda. The bottom 3 unreliable brands are Dodge, Jeep, and Chrysler.   If you were considering getting an electric vehicle, Consumer Reports found that hybrids are the way to go. Results showed they are incredibly fuel efficient and just as reliable as gas powered cars. It was revealed that pure electric vehicles, on the other hand, have 42% more problems than gas-powered and hybrids and plug-in hybrids have 70% more problems than gas-powered and conventional hybrids. For those thinking of purchasing an electric vehicle it's important to consider how much driving you plan on doing. They don't have as far a range as gas-powered and hybrid vehicles, so make sure the infrastructure around you and wherever you plan to travel supports electric vehicles. Remember to check beforehand to see if there are any charging stations near you.  To explore more information and data on this particular report, visit consumerreports.org or check the link in the show notes.  Another great way to determine a car's reliability is to ask a trusted mechanic. They work constantly on cars and know which ones come in the most and what common issues are. Before buying a car, you can take it to a mechanic for an inspection. Similarly, ask friends and family what kind of car they drive, if they like it, and how dependable it is.  Okay, so what if you're considering a car that maybe wasn't on the Consumer Report's top reliable vehicle list. Maybe you've been eyeing that Jeep, Cadillac or Rivian for quite some time now? That's completely fine! Just do your research beforehand, talk to friends and mechanics to make sure you're fully aware of any long-term costs and maintenance associated with your vehicle. Another great way to make sure your car doesn't end up costing you more than you initially planned, is to consider getting Mechanical Repair Coverage, or MRC for short. MRC can help limit unexpected, covered repairs as your vehicle ages, potentially saving you thousands of dollars. Learn more about MRC and how to get it today at Triangle Credit Union. Visit trianglecu.org to check it out!  If there are any other tips or topics you'd like us to cover, let us know at tcupodcast@trianglecu.org. Also, remember to like and follow our Making Money Personal Facebook and Instagram to share your thoughts. Finally, remember to look for our sponsor, Triangle Credit Union, on Facebook and LinkedIn.         Thanks for listening to today's Money Tip Tuesday. Check out our other tips and episodes on the Making Money Personal podcast.    

Jerry Giordano, author of Your 7 Words to a Happier You: Unlock the Story Sabotaging Your Relationships? With personal insights and a lot of humor, Jerry will talk about why we do what we do and how it's sabotaging our relationships and ourselves. Jerry has put his 7-word philosophy into practice by interviewing over 200 people from ages thirteen to ninety-four. He can share: How he tried every form of therapy, seminar, retreat, life coach, past-life regression, psychic and self-help book available, but still felt the same His realization that these were all left-brained approaches (logic) to a right-brained problem (emotion)Hitting rock bottom -- in the span of weeks, he lost his mother to cancer and his fiancée broke up with him How his newfound mindfulness practice and meditations helped him discover that his easygoing, people-pleasing persona was fake How he discovered the 7 words approach and how that's led to an in-depth understanding of the unconscious story that was affecting his life “As a psychotherapist, introducing a number of clients to their 7 Words has been an effective tool for uncovering their unconscious stories and circumventing their sabotaging lifelong patterns. The discovery of my own words was the breakthrough I was unknowingly in search of for decades! Jerry's writing exudes an uncommon vulnerability, clarity and authenticity, and this book takes self-help/self-discovery to a transcendent level.”— Melissa D. Borski, MRC, CFRC, LPCBecome a supporter of this podcast: https://www.spreaker.com/podcast/arroe-collins-like-it-s-live--4113802/support.

George O'Connor returns to help MRC finish off August of 1967 with Fantastic Four 65, Strange Tales 159 with SHIELD and Dr. Strange, Tales of Suspense 92 with Iron Man and Captain America, and Avengers 43! Auras of Negativism! Contessa Valentina Allegra de Fontaine! La Leche Es Verde! 4/5ths Face! The Ultimate No-Prize! Convenient Homing-Beam Gizmos! Check it out!

Dr. John Sweetenham and Dr. James Foran discuss the evolving treatment landscape in acute myeloid leukemia, including new targeted therapies, advances in immunotherapy, and the current role for allogeneic transplantation. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. There has been steady progress in the therapies for acute myeloid leukemia (AML) in recent years, largely based on an increasing understanding of the molecular mechanisms which underlie the disease. On today's episode, we'll be discussing the evolving treatment landscape in AML. We'll explore risk group stratification, new targeted therapies, advances in immunotherapy for AML, and also a little about the current role for allogenic transplantation in this disease.  I'm delighted to welcome Dr. James Foran to this discussion. Dr. Foran is a professor of medicine and chair of the Myeloid Malignancies and Blood and Marrow Transplant Disease Group at the Mayo Clinic Comprehensive Cancer Center. He's based in Jacksonville, Florida.  Our full disclosures are available in the transcript of this episode.  James, it's great to have you join us on the podcast today, and thanks so much for being here. Dr. James Foran: I'm delighted and thank you for the invitation. Thank you very much. Dr. John Sweetenham: Sure, James, let's get right into it. So, our understanding of the molecular mechanisms underlying AML has resulted not only in new methods for risk stratification in this disease, which have added refinement to cytogenetics, but also has resulted in the development of many new targeted agents. Understanding that this is a complex area of investigation, and our time is somewhat limited, can you give us a high-level update on the current state of the art in terms of how risk factors are being used for treatment selection now? Dr. James Foran: Absolutely. I think in the past, you know, we had things broken down pretty simply into make a diagnosis based on morphology, do cytogenetics, break patients into the groups of those who were more likely to benefit from therapy – so-called favorable risk – those where the intensive therapies were less likely to work – so-called poor adverse risk, and then this large intermediate group that really had variable outcomes, some better, some worse. And for a long time, the progress was in just identifying new subtle cytogenetic risk groups. And then, late 1990s, we began to understand that FLT3 mutations or NRAS mutations may be more adverse than others that came along. In the first part of this millennium, in the, you know, 2000-2010 range, a lot of work was being done to understand better or worse risk factors with single genes. The ability to do multiplex PCR, and then more recently NGS platforms, have allowed us to really look at many genes and identify many mutations in patients. At the beginning that was used just to sort of refine – who did a little better, who did a little worse with intensive therapy – helped us decide who may benefit more from an allogeneic transplanter for whom that would not be necessary.  But the good news is that really, we're now starting to target those mutations. One of the first molecularly targeted treatments in leukemia was FLT3 mutations, where we knew they were adverse. Then along came targeted treatments. I was involved in some of those early studies looking at sunitinib, sorafenib, more recently midostaurin, now quizartinib, FDA approved, and gilteritinib in the relapse refractory setting.  So we're moving into a state where we're not just refining prognosis, we're identifying targets. You know, it's been slow progress, but definite incremental progress in terms of outcomes by looking for FLT3 mutations, then looking for IDH mutations, and more recently, mutations involving NPM1 or rearrangement of what we used to call the MLL gene, now the lysine methyltransferase 2A or KMT2A rearrangement, where we now have targets. And it's not just for refinement of prognosis, but now we're identifying therapeutic targets for patients and ways to even look for measurable residual disease which is impacting our care. Dr. John Sweetenham: That's great, James. And I'm going to expand on that theme just a little bit and perhaps ask you to elaborate a little bit more on how the introduction of these new therapies have specifically impacted frontline therapy. And a couple of ancillary questions maybe to go along with that: First of all, is ‘7+3' a standard therapy for anybody in 2025? And maybe secondly, you know, could you comment also maybe briefly on older patients with AML and how you think maybe the treatment landscape is changing for them compared with, say, 5 or 10 years ago? Dr. James Foran: I'll start with the therapy and then work my way back. So we've had ‘7+3' cytarabine daunorubicin or cytarabine anthracycline since 1976, and we're still using it as the backbone of our intensive therapy. There is still an important role for it, particularly in younger or fitter patients, and particularly for those with intermediate or favorable risk genetic groups or cytogenetic risk groups just because we achieve high rates of remission. Our 30-day induction mortality rates are lower now than they were 10 and 20 years ago. Our supportive care is better. And we still have a busy inpatient hospital service here at Mayo Florida and my colleagues in Rochester and Arizona as well giving intensive therapy. So that remains the backbone of curative therapy for younger adults. We are trying to be a little more discriminating about who we administer that to. We are trying to add targeted agents. We know from, now, two different randomized trials that the addition of a FLT3 inhibitor, either midostaurin or more recently quizartinib, has a survival advantage in patients with a FLT3 mutation, or for quizartinib, a FLT3/ITD mutation. And so yes, ‘7+3' remains important.  Off protocol for somebody who just comes in with acute leukemia in a 40-year-old or 30-year-old or even early 60s and fit, we would still be considering ‘7+3' therapy and then waiting for an expedited gene mutation panel and an expedited cytogenetics panel to come back to help us discriminate is that a patient for whom we should be giving a FLT3 inhibitor? I think there's a little more nuance about when we do a day 14 bone marrow, do they really matter as much anymore? I still do them. Some of my colleagues find them less important. But we're still giving intensive therapy. We're still giving high-dose ARA-C consolidation for younger patients who achieve complete remission.  In older adults, it's a different story. You know, it was only in the early part of the 2000s – 2004, 2007 range – where we really got buy-in from randomized studies that low-dose therapy was better than no therapy. There was a lot of nihilism before then about therapy for older adults, especially over age 75. We know that low-dose ARA-C is better than nothing. It looked like azacitidine was better than ARA-C or at least equivalent or slightly better. But with the advent of venetoclax it was a game changer. I ran a national randomized study of intensive therapy in AML. It was the last national randomized study of intensive therapy in older patients right before venetoclax got approved. And we were very excited about our results, and we thought we had some really interesting clinical results. And suddenly that's a little bit obsolete in patients over 70 and particularly over age 75 because of the high remission rates with azacytidine venetoclax or hypomethylating agents, so-called HMAs and venetoclax and the survival advantage. Now, it's not a home run for everybody. We quote 60% to 70% remission rates, but it's a little different based on your cytogenetics and your mutation profile. You have to continue on therapy so it's continuous treatment. It's not with curative intent, although there are some people with long-term remission in it. And the median survival went from 10 months to 15 months. So home run? No, but definitely improved remissions, meaningful for patients off transfusions and better survival. So right now it's hard to find an older adult who you wouldn't give azacitidine and venetoclax or something similar, decitabine, for instance, and venetoclax, unless somebody really was moribund or had very poor performance status or some reason not to. And so ‘7+3' is still relevant in younger adults. We're trying to get better results with ‘7+3' by adding targeted agents and azacitine and venetoclax in older adults.  I think the area of controversy, I guess there are two of them, is what to do in that overlap age between 60 and 75. Should people in that age still get intensive therapy, which we've used for years – the VIALE-A trial of aza-venetoclax was age 75 plus – or with cardiac comorbidities? And I think if you're 68 or 72, many of us are starting to bias towards aza-venetoclax as generally being better tolerated, generally being more outpatient, generally being slow and steady way to get a remission. And it doesn't stop you from going to transplant for somebody who might still be a candidate.  The other area of controversy is somebody under 60 who has adverse cytogenetics where we don't do very well with ‘7+3,' we still give it and we might do just as well with decitabine venetoclax. A lot of us feel that there's equipoise in the 60 to 75 group where we really can ask a question of a randomized study. Retrospective studies might suggest that intensive therapy is a little better, but there are now a couple of randomized studies happening saying, “Can we replace ‘7+3' in that intermediate age with aza-venetoclax?” And for younger adults similarly, we're looking to see how we apply that technology. Those are the areas where we're really trying to investigate what's optimal for patients and that's going to require randomized trials. Dr. John Sweetenham: Oh, that's great, thank you. And I'll just extend that question a little bit more, particularly with respect to the new targeted therapies. How much are they impacting the treatment of these patients in the relapse and refractory setting now? Dr. James Foran: Oh, they're definitely impacting it. When I trained and probably when you trained, AML was still a medical emergency. But that was the thing that you admitted to the hospital immediately, you started therapy immediately. The rule was always that's the one thing that brings the fellow and the consultant in at night to see that new patient on a Friday or Saturday. Now, we'll still admit a patient for monitoring, but we try not to start therapy for the first three or five or seven days if they're stable, until we get those genetics and those genomics back, because it helps us discriminate what therapy to pursue. And certainly, with FLT3 mutations, especially FLT3/ITD mutations, we're adding FLT3 inhibitors and we're seeing a survival advantage. Now, on the surface, that survival advantage is in the range of 7% or 10%. But if you then pursue an allogeneic transplant in first remission, you're taking disease where we used to see 30%, 40% long-term survival, maybe less, and you're pushing that to 60%, 70% in some studies. And so we're now taking a disease that– I don't want to get off topic and talk about Ph+ ALL. But that's a disease where we're actually a little excited. We have a target now, and it used to be something really adverse and now we can do a lot for it and a lot about it.  The other mutations, it's a little more subtle. Now, who knew until 2010 that a mutation in a sugar metabolism gene, in isocitrate dehydrogenase, or IDH was going to be so important, or even that it existed. We know that IDH1 and IDH2 mutations are still a minority of AML, certainly less than 10% to 15%, maybe overall. But we're able to target those with specific IDH1 and IDH2 inhibitors. We get single-agent responses. There are now two approved IDH1 inhibitors on the market. We don't yet have the randomized data that adding those to intensive therapy is better, but we're getting a very strong hint that it might be better in older adults who have an IDH mutation, maybe adding those is helpful and maybe adding those to low-intensity therapy is helpful. Those studies are ongoing, and we're also trying with low-intensity treatments to add these agents and get higher remission rates, deeper remissions, longer remissions. I think a lot of work has to be done to delineate the safety of that and the long-term efficacy. But we're getting hints it's better, so I think it is impacting.  The other area it's impacting is when you pick up adverse mutations and those have crept into our classification systems like an ASXL1 mutation or RUNX1 mutation for instance, or some of the secondary AML mutations like BCOR and others, where that's helping us discriminate intermediate-risk patients who we think aren't going to do as well and really helping us select a group who's more likely to get benefit from allogeneic transplant or for whom at least our cure rates without allo transplant are low. And so I think it's impacting a lot. Dr. John Sweetenham: Great. And I'm going to pick up now, if I may, on a couple of things that you've just mentioned and continue the theme of the relapsed and refractory setting. We've started to see some reports which have looked at the role of immune strategies for patients with AML, in particular CAR T or NK cells. Can you comment a little on this and let us know whether you think either these two strategies or other immune strategies are likely to have a significant role in AML in the future? Dr. James Foran: They are, but I think we're still a step behind finding the right target or the right way to do it. If you think of allogeneic transplantation as the definitive immune therapy, and we know for adverse AML we can improve survival rates and cure rates with an allotransplant, then we know inherently that immune therapy matters. And so how do we do what they've done in large cell lymphoma or in CD19 targeting for B cell malignancies? How do we bring that to acute myeloid leukemia? There have been a number of efforts. There have been at least 50 trials looking at different targets. CD33, CD123, CD7, others, CLL-1. So, there have been a number of different trials looking at how to bind a CAR T or a CAR T construct that can be active. And we have hints of efficacy. There was kind of a provocative paper in the New England Journal of Medicine a year ago in April of last year from a Chinese group that looked at a CD7-based CAR T and it was 10 patients, but they used CD7 positive acute leukemia, AML or ALL and had a CD7-targeted CAR T and they actually incorporated that with a haploidentical transplant and they had really high remission rates. People tolerated it quite well. It was provocative. It hasn't yet been reproduced on a larger scale, but the strong hints that the strategy is going to work.  Now, CD33 is a little tricky to have a CAR T when CD33 is expressed on normal hematopoietic cells. CD123 likewise. That's been something where there's, I think, still promise, but we've struggled to find the trials that make that work. Right now, there's a lot of interest in leveraging NK cells and looking, for a couple of reasons, but NK cells are attractive and NK cell markers might be attractive targets. NK cells might have similar degrees of immune efficacy. It's speculative, but they are likely to have less cytokine release syndrome and less neurotoxicity than you see with CAR T. And so it's kind of attractive to leverage that. We have had some ongoing trials looking at it with bispecifics and there certainly are trials looking at it with CAR NK-based strategies. One of the antigens that people looked at is the NK group 2D. NK group 2D or NKG2D is overexpressed in AML and its ligands overexpressed. And so that's a particular potential target. So, John, it's happening and we're looking for the hints of efficacy that could then drive a pivotal trial to get something approved.  One of the other areas is not restricting yourself just to a single antigen. For instance, there is a compound that's looking at a multi-tumor-associated antigen-specific T-cell therapy, looking at multiple antigens in AML that could be overexpressed. And there were some hints of activity and efficacy and actually a new trial looking at a so-called multi-tumor associated antigen-specific T cell therapy. So without getting into specific conflicts of interest or trials, I do think that's an exciting area and an evolving area, but still an investigational area. I'll stop there and say that we're excited about it. A lot of work's going there, but I'm not quite sure which direction the field's going to pivot to there. I think that's going to take us some time to sort out. Dr. John Sweetenham: Yeah, absolutely. But as you say, exciting area and I guess continue to watch this space for now.  So you've mentioned allogeneic stem cell transplants two or three times during this discussion. Recognizing that we don't have an imatinib for AML, which has kind of pushed transplant a long way further back in the treatment algorithm, can you comment a little on, you know, whether you think the role of stem cell transplantation is changing in AML or whether it remains pretty much as it was maybe 10 years ago? Dr. James Foran: By the way, I love that you use imatinib as an introduction because that was 6 TKIs ago, and it tells you the evolution in CML and you know, now we're looking at myristoyl pocket as a target, and so on. That's a great way to sort of show you the evolution of the field.  Allogeneic transplant, it remains a core treatment for AML, and I think we're getting much smarter and much better about learning how to use it. And I'm just going to introduce the topic of measurable residual disease to tell you about that. So I am a little bit of a believer. Part of my job is I support our allogeneic transplant program, although my focus is acute myeloid leukemia, and I've trained in transplant and done it for years and did a transplant fellowship and all that. I'm much more interested in finding people who don't need a transplant than people who do. So I'm sort of looking for where can we move away from it. But it still has a core role. I'll sidestep and tell you there was an MDS trial that looked at intermediate or high-risk MDS and the role of allogeneic transplant that shows that you about double your survival. It was a BMT CTN trial published several years ago that showed you about double your three-year survival if you can find a donor within three months and get to a transplant within six months. And so it just tells you the value of allotransplant and myeloid malignancy in general. In AML we continue to use it for adverse risk disease – TP53 is its own category, I can talk about that separately – but adverse risk AML otherwise, or for patients who don't achieve a really good remission. And I still teach our fellows that an allotransplant decreases your risk of relapse by about 50%. That's still true, but you have to have a group of patients who are at high enough risk of relapse to merit the non-relapse mortality and the chronic graft versus host disease that comes with it. Now, our outcomes with transplant are better because we're better at preventing graft versus host disease with the newer strategies such as post-transplant cyclophosphamide. There are now new FDA-approved drugs for acute and chronic graft versus host disease, ruxolitinib, belumosudil, axatilimab now. So we have better ways of treating it, but we still want to be discriminating about who should get it.  And it's not just a single-minded one-size-fits-all. We learned from the MORPHO study that was published in the JCO last year that if you have FLIT3-positive AML, FLIT3/IDT-positive AML, where we would have said from retrospective studies that your post-transplant survival is 60% give or take, as opposed to 15% or 20% without it, that we can discriminate who should or shouldn't get a transplant. Now that trial was a little bit nuanced because it did not meet its primary endpoint, but it had an embedded randomization based upon MRD status and they used a very sensitive test of measurable residual disease. They used a commercial assay by Invivoscribe that could look at the presence of a FLT3/ITD in the level of 10 to the minus 5th or 10 to the minus 6th. And if you were MRD-negative and you went through a transplant, you didn't seem to get an advantage versus not. That was of maintenance with gilteritinib, I'll just sort of put that on there. But it's telling us more about who should get a transplant and who shouldn't and who should get maintenance after transplant and who shouldn't.  A really compelling study a year ago from I don't know what to call the British group now, we used to call them the MRC and then the NCRI. I'm not quite sure what to call their studies at the moment. But Dr. Jad Othman did a retrospective study a year ago that looked at patients who had NPM1 mutation, the most common mutation AML, and looked to see if you were MRD positive or MRD negative, what the impact of a transplant was. And if you're MRD negative there was not an advantage of a transplant, whereas if you're MRD positive there was. And when they stratified that by having a FLT3 mutation that cracked. If you had a FLT3 mutation at diagnosis but your NPM1 was negative in remission, it was hard to show an advantage of a transplant. So I think we're getting much more discriminating about who should or should not get a transplant by MRD testing for NPM1 and that includes the patients who have a concomitant FLT3 mutation. And we're really trying to learn more and more. Do we really need to be doing transplants in those who are MRD-negative? If you have adverse risk genetics and you're MRD-negative, I'll really need good data to tell me not to do a transplant, but I suspect bit by bit, we'll get that data. And we're looking to see if that's really the case there, too. So measurable residual disease testing is helping us discriminate, but there is still a core role of allogeneic transplant. And to reassure you, compared to, I think your allotransplant days were some time ago if I'm right. Dr. John Sweetenham: Yes. Dr. James Foran: Yeah. Well, compared to when you were doing transplants, they're better now and better for patients now. And we get people through graft versus host disease better, and we prevent it better. Dr. John Sweetenham: That's a great answer, James. Thanks for that. It really does help to put it in context, and I think it also leads us on very nicely into what's going to be my final question for you today and perhaps the trickiest, in a way. I think that everything you've told us today really emphasizes the fact that the complexity of AML treatment has increased, primarily because of an improved understanding of the molecular landscape of the disease. And it's a complicated area now. So do you have any thoughts on what type of clinical environment patients with AML should be evaluated and treated in in 2025? Dr. James Foran: Yeah, I want to give you a kind of a cautious answer to that because, you know, I'm a leukemia doctor. I work at a leukemia center and it's what we focus on. And we really pride ourselves on our outcomes and our diagnostics and our clinical trials and so on. I am very aware that the very best oncologists in America work in private practice and work in community practice or in networks, not necessarily at an academic site. And I also know they have a much harder job than I have. They have to know lung cancer, which is molecularly as complicated now as leukemia, and they have to know about breast cancer and things that I don't even know how to spell anymore. So it's not a question of competence or knowledge. It's a question of infrastructure. I'll also put a little caveat saying that I have been taught by Rich Stone at Dana-Farber, where I did a fellowship a long time ago, and believe Rich is right, that I see different patients than the community oncologists see with AML, they're seeing different people. But with that caveat, I think the first thing is you really want to make sure you've got access to excellence, specialized hematopathology, that you can get expedited cytogenetics and NGS testing results back. There was a new drug, approved just a few months ago, actually, for relapsed AML with a KMT2A rearrangement, revumenib. We didn't talk about the menin inhibitors. I'll mention them in just a second. That's a huge area of expansion and growth for us. But they're not found on NGS platforms. And normal cytogenetics might miss a KMT2A-rearrangement. And we're actually going back to FISH panels, believe it or not, on AML, to try to identify who has a KMT2A-rearrangement. And so you really want to make sure you can access the diagnostic platforms for that.  I think the National Referral Labs do an excellent job. Not always a really fast job, but an excellent job. At my institution, I get NGS results back within three days or four days. We just have an expedited platform. Not everybody has that. So that's the key, is you have to be able to make the diagnosis, trust the pathologist, get expedited results. And then it's the question of trying to access the targeted medications because a lot of them are not carried in hospital on formulary or take time to go through an insurance approval process. So that's its own little headache, getting venetoclax, getting gilteritinib, getting an IDH1 inhibitor in first line, if that's what you're going for. And so I think that requires some infrastructure. We have case managers and nurses who really expedite that and help us with it, but that's a lot of work. The other piece of the puzzle is that we're still with AML in the first month and maybe even the second month. We make everybody worse before we make them better. And you have to have really good blood bank support. I can give an outpatient platelet transfusion or red cell transfusion seven days a week. We're just built for that. That's harder to do if you're in a community hospital and you have to be collaborating with a local blood bank. And that's not always dead easy for somebody in practice. So with those caveats, I do find that my colleagues in community practice do a really good job making the diagnosis, starting people on therapy, asking for help. I think the real thing is to be able to have a regional leukemia center that you can collaborate with, connect with, text, call to make sure that you're finding the right patients who need the next level of diagnostics, clinical trial, transplant consults, to really get the best results.  There was some data at ASH a couple of years ago that looked at – the American Society of Hematology and ASCOs had similar reports – that looked at how do we do in academic centers versus community practice for keeping people on therapy. And on average, people were more likely to get six cycles of therapy instead of three cycles of therapy with azacitidine venetoclax at an academic center. Now, maybe it's different patients and maybe they had different cytogenetics and so on, but I think you have to be patient, I think you have to collaborate. But you can treat those patients in the community as long as you've got the infrastructure in place. And we've learned with virtual medicine, with Zoom and other platforms that we can deliver virtual care more effectively with the pandemic and beyond. So I think we're trying to offer virtual consults or virtual support for patients so they can stay in their home, stay in their community, stay with their oncologists, but still get access to excellent diagnostics and supportive care and transplant consults, and so on. I hope that's a reasonable answer to that question. It's a bit of a nuanced answer, which is, I think there's an important role of a leukemia center, and I think there's a really fundamental role of keeping somebody in the community they live in, and how we collaborate is the key to that. And we've spent a lot of time and effort working with the oncologists in our community to try to accomplish that.  John, I want to say two other things. I didn't mention in the molecular platforms that NPM1 mutations, we can now target those on clinical trials with menin inhibitors. We know that NPM1 signals through the Hoxa9/Meis1 pathway. We know that similar pathways are important in KMT2A rearrangements. We know that there are some other rare leukemias like those with NUP98 rearrangement. We can target those with menin inhibitors. The first menin inhibitor, revuminib, was approved by the FDA for KMT2A. We have others going to the FDA later this year for NPM1. There are now pivotal trials and advanced expanded phase 1/2 studies that are showing 30% response rates. And we're looking to see can we add those into the first-line therapy. So, we're finding more targets.  I'll say one last thing about molecular medicine. I know I'm a little off topic here, but I always told patients that getting AML was kind of like being struck by lightning. It's not something you did. Now, obviously, there are risk factors for AML, smoking or obesity or certain farm environments, or radioactive exposures and so on. But bit by bit, we're starting to learn about who's predisposed to AML genetically. We've identified really just in the last five or eight years that DDX41 mutations can be germline half the time. And you always think germline mutations are going to cause AML in a younger patient, but the median age is 60 to 70 just like other AMLs. They actually might do pretty well once they get AML. We've reported that in several papers. And so we're trying to understand who that has a RUNX1 mutation needs germline testing, who with a DDX41 needs germline testing. And we're trying to actually come up with a cleaner pathway for germline testing in patients to really understand predisposition, to help with donor selection, to help with family counseling. So I think those are other areas where a leukemia center can contribute for somebody in who's community practice to understand genomic or genetic complexity in these patients. And we're starting to develop the databases that support that. Dr. John Sweetenham: Yeah, great. Thanks, James. I loved your answer about the clinical environment too. And I know from a patient-centric perspective that I know that patients would certainly appreciate the fact that we're in a situation now where the folks taking care of them will make every effort to keep them close to home if they possibly can.  I want to thank you, James, for an incredible review of a very complex subject and I think you did a great job. I think we all will have learned a lot. And thanks again for being willing to share your insights with us today on the ASCO Daily News Podcast. Dr. James Foran: John, it's my pleasure. And as you know, I'll do anything for a latte, so no problem at all. Dr. John Sweetenham: Okay. I owe you one, so thank you for that.  And thank you to our listeners for your time today. You'll find links to the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:  Dr. John Sweetenham  Dr. James Foran Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn  Disclosures:    Dr. John Sweetenham:    No relationships to disclose Dr. James Foran: Stock and Other Ownership Interests: Aurinia Pharmaceuticals Consulting or Advisory Role: Peerview, CTI BioPharma Corp, Remix Therapeutics, Cardinal Health, Medscape, Syndax, Autolus Therapeutics Research Funding (Inst.): Chordia Therapeutics, Abbvie, Actinium Pharmaceuticals, Kura Oncology, Sellas Life Sciences, Novartis, Roivant, Celgene/Bristol-Myers Squibb, Astellas Pharma, SERVIER Travel, Accommodations, Expenses: Peerview

Why are Australians feeling poorer despite their wages increasing? Shadow Finance Minister Jane Hume sat down with the MRC's Centre for Youth Policy Director Freya Leach to discuss why Gen Z in particular are feeling the pain of Australia's cost of living crisis.Senator Hume also shuts down misconceptions that the Coalition's Super for Housing policy will rob potential home buyers of their retirement funding and explains why lifting labour productivity is critical to lifting the standard of living. Sign up to the Menzies Research Centre's weekly newsletter: https://www.menziesrc.org/email

Au Cameroun, le parti d'opposition SDF, Social Democratic Front, qui s'est réuni en congrès extraordinaire, vient de désigner Joshua Osih comme son candidat à la présidentielle du mois d'octobre prochain. Le SDF a été longtemps la principale force d'opposition dans le pays. Depuis la dernière élection de 2018, il est moins en vue, mais cette année, il croit de nouveau en ses chances. En ligne de Yaoundé, le député Joshua Osih dévoile sa stratégie, qui pourrait bien s'inspirer de celle de Félix Tshisekedi en RDC. RFI : Dans votre programme, vous dîtes vouloir mettre fin aux violences dans les provinces du Nord-ouest et du Sud-ouest en seulement 100 jours. Comment vous allez vous y prendre ?Joshua Osih : Je pense qu'aucun autre parti politique ne connaît mieux le Nord-ouest et le Sud-ouest que nous. Nous savons ce qui se passe. Nous avons largement consulté sur la question. Nous avons parlé à toutes les parties en conflit et nous sommes sereins qu'en trois mois ou un peu plus, nous pouvons faire cesser la violence. Cela ne veut pas dire que la crise politique va s'arrêter. C'est pour cela que nous proposons en même temps de lancer un grand chantier qui devra aboutir au bout de trois ans sur un référendum constitutionnel. Cela va nous permettre de rétablir les équilibres politiques dans ce pays pour éviter des crises futures.Le président Biya, qui vient de fêter ses 92 ans, laisse entendre qu'il sera candidat à sa réélection en octobre prochain. Est-ce que vous pensez que son âge pourrait être un paramètre à prendre en compte dans la campagne ?Nous pensons que certainement l'âge du président de la République serait un handicap pour le pays si jamais il est élu. Vous savez, un président de la République à 100 ans, cela veut tout simplement dire que, si monsieur Biya devenait président de la République pour un autre mandat, le pays allait s'arrêter pour attendre la fin de son mandat. Sept années encore dans le noir, c'est quelque chose que la jeunesse camerounaise ne va pas accepter. C'est quelque chose que tous les Camerounais ne vont pas accepter. Nous sommes confiants que, qu'il soit candidat ou pas, son parti est dans l'impossibilité de gagner les élections de 2025.Dans vos discours, Joshua Osih, vous êtes moins véhément que Maurice Kamto. Est-ce à dire que face au RDPC au pouvoir, le SDF est dans une stratégie moins frontale que le MRC ?Ce n'est pas une question d'être moins véhément ou moins dans une stratégie frontale. C'est tout simplement parce que moi, j'ai appris à faire la politique auprès d'un très grand homme, John Fru Ndi et j'ai compris que, dans la politique, aucun adversaire n'est permanent. C'est déjà le premier point. Deuxièmement, il faut pouvoir se parler, même quand on est en désaccord. Donc, quand on fait la politique par les injures, et là je ne vise aucun parti politique, il y a malheureusement trop de personnes qui pensent qu'il faut passer la journée à insulter les uns et les autres. Nous sommes des adversaires politiques. La première des choses, c'est que nous devons nous respecter. Donc, je respecte le MRC, je respecte le RDPC, je respecte le PCRN, je respecte tous les partis politiques sur la place en attendant aussi d'eux un respect réciproque.En 2018, face à Joseph Kabila, Martin Fayulu et Félix Tshisekedi avaient deux stratégies différentes et à la fin, c'est Félix Tshisekedi qui est devenu président. Est-ce que vous avez ce scénario congolais dans la tête pour octobre prochain ?Bien sûr et je pense que nous sommes très proches de l'UDPS. Nous avons accompagné l'UDPS lors de ces élections-là. Et donc nous sommes plutôt dans cette logique-là que dans celle de Martin Fayulu. En 1992, nous avons gagné l'élection présidentielle. Tous nous donnent raison que nous avons gagné cette élection. Mais nous avions oublié qu'il faut gagner l'élection et aussi pouvoir prendre le pouvoir. Ce sont deux choses complètement différentes et nous n'avons pas réussi à prendre le pouvoir en 1992. Plus jamais nous n'allons faire cette erreur. Quand on est en politique, il faut avoir la capacité de construire des ponts et de parler avec ceux qui ont perdu le pouvoir pour qu'ensemble, on arrive à construire ce pays. Il ne s'agit pas pour le SDF d'arriver au pouvoir et de mettre tout le monde du RDPC en prison, de les jeter en pâture etc. Non, il s'agit de démontrer que, quand je vais gagner, il n'y aura pas de chasse aux sorcières parce qu'on aura besoin des 30 millions de Camerounais pour rattraper les 43 années que nous avons perdues.Face au candidat du pouvoir, vous serez beaucoup d'opposants. Maurice Kamto, Cabral Libii , Akere Muna, Madame Hermine Patricia Tomaïno Ndam Njoya et vous-même. Est-ce que par vos divisions, vous n'ouvrez pas un boulevard au candidat du RDPC au pouvoir ?Mutualiser nos forces dans les bureaux de vote, c'est une voie que nous pensons très importante. Que ceux qui sont dans les bureaux de vote où nous sommes absents nous représentent mutuellement. Et si tous ces autres partis que vous avez cités peuvent être présents dans les 30 000 bureaux de vote avec nous, cela fera que dans les bureaux de vote, il y aura une majorité de représentants de l'opposition par rapport au parti au pouvoir. Et dans ce cas-là, il n'y aurait aucune chance pour que le parti au pouvoir essaie de truquer les résultats. Nous sommes confiants que nous aurons les résultats que nous attendons. À lire aussiPrésidentielle au Cameroun: les prises de position contre une candidature de Paul Biya divisent des fidèles catholiquesÀ lire aussiPrésidentielle au Cameroun: les chefs traditionnels apportent leur «soutien» au président Paul Biya

MRC welcomes special guest George O'Connor to cover the books of August, 1967! A discussion of George's Asgardians graphic novels leads right into Thor 143, then Amazing Spider-Man 51, Daredevil 31, Tales to Astonish 94 with Namor and the Hulk, and X-Men 35! Lots of heroes pretending they don't know how money works! Pre-Puzo Puzo! Convenient fire-fighter nets! Lost weekends! Check it out!

Rare condition research is evolving, and patient communities are driving the breakthrough. In this special Rare Disease Day episode, we explore the challenges and opportunities shaping the future of rare condition therapies. From groundbreaking gene therapy trials to the power of patient-driven research, our guests discuss how collaboration between families, clinicians, researchers, and regulators is paving the way for faster diagnoses, equitable access to treatments, and innovative approaches like nucleic acid therapies and CRISPR gene editing. With insights from Myotubular Trust, we follow the journey of family-led patient communities and their impact on advancing gene therapy for myotubular myopathy - showcasing how lived experience is shaping the future of medicine. However, while patient-driven initiatives have led to incredible progress, not every family has the time, resources, or networks to lead these research efforts. Our guests discuss initiatives like the UK Platform for Nucleic Acid Therapies (UPNAT), which aims to streamline the development of innovative treatments and ensure equitable access for everyone impacted by rare conditions. Our host Dr Ana Lisa Tavares, Clinical lead for rare disease at Genomics England, is joined by Meriel McEntagart, Clinical lead for rare disease technologies at Genomics England, Anne Lennox, Founder and CEO of Myotubular Trust and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at University of Oxford. "My dream is in 5 to 10 years time, an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested. And at that exact time, the day of the diagnosis becomes also a day of hope, in a way, where immediately the researcher that sent the genetics lab flags that specific variant or specific mutations. We know exactly which is the best genetic therapy to go after." You can download the transcript, or read it below. Ana Lisa: Welcome to Behind the Genes.    [Music plays]  Anne: What we've understood is that the knowledge and experience of families and patients is even more vital than we've all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family, they would tell you, “Yes, my son has had the odd liver result.”  There were some very serious liver complications but everybody thought that was a minor issue, but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing.  [Music plays]  Ana Lisa: My name is Ana Lisa Tavares, I'm Clinical Lead for Rare Disease research at Genomics England and your host for this episode of Behind the Genes. Today I'm joined by Anne Lennox, Founder and CEO of the Myotubular Trust, Dr Meriel McEntagart, an NHS consultant and Clinical Lead for Rare Disease Technologies at Genomics England, and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at the University of Oxford.    Today we'll be hearing about the importance of involving the patient community, particularly as new rare therapies are developed, and discussing the forward-facing work that's happening that could have potential to unlock novel treatments for many rare conditions.  If you enjoy today's episode we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. Thank you so much for joining me today.  Please could you introduce yourselves.   Anne: I'm Anne Lennox, I'm one of the founders of the Myotubular Trust, a charity that raises research funds for and supports families affected by the rare genetic neuromuscular disorder myotubular myopathy.  Meriel: I'm Meriel McEntagart, I'm a consultant in clinical genetics in the NHS and I have a special interest in neurogenic and neuromuscular conditions.  Carlo: Hi, I'm Carlo Rinaldi, I'm Professor of Molecular and Translational Neuroscience at the University of Oxford. I'm a clinician scientist juggling my time between the clinic and the lab where we try to understand mechanisms of diseases to develop treatments for these conditions.  And I'm also here as a representative of the UK Platform for Nucleic Acid Therapies, UPNAT. Thanks for your invitation, I'm very pleased to be here.  Ana Lisa: Thank you. Meriel, I'd love you to tell us a bit about your work and how you met Anne, how did this story start?  Meriel: Thank you. Well prior to being a consultant in clinical genetics, I spent 2 years as a clinical research fellow in neuromuscular conditions, and as part of that training I worked on a project where the gene for myotubular myopathy had just been identified, and so there was a big international effort to try and come up with sort of a registry of all the genetic variants that had been found as well as all the clinical symptoms that the affected patients had, and then do kind of a correlation of the particular variant mutation with symptoms.   I worked when I was training to be a clinical geneticist because of my interest in neuromuscular conditions so when I eventually became a consultant at St George's Hospital I was actually interviewed by the Professor of Paediatrics and he knew Anne and her son, when Anne was looking for more information about the condition he suggested that perhaps I might be a good person for Anne to talk to.  Ana Lisa: Thank you. Interesting connections. Anne, can you tell us your story and how this led you to found the Myotubular Trust?  Anne: Yes, thanks Ana-Lisa.  Well, as many families will tell you when they're newly diagnosed with a rare disease, you go from knowing nothing about a condition to being one of the few deep experts in that condition because there are so few deep experts. So this happened to us in 2003 when our son, Tom, was born, and when he was born he was floppy and his Apgar scores, the scores they do on new-born babies, were pretty poor, and before long we knew that it was more than just momentary issues at birth.  And, cutting a very long story short, 5 weeks later he was diagnosed with this very rare neuromuscular genetic disorder that we didn't know we had in the family.  We were told that this was a very serious diagnosis.    At that time – more than 20 years ago – over 80% of those boys didn't make it to their first birthday and the stark statistic we had in our head a lot was that only 1% made it past the age of 10. And that has changed due to better ventilator and breathing equipment, etc, but at the time we expected that he might not make it to his first birthday.    We were very lucky, we had Tom longer than one year, we had him for nearly 4 years, 4 very lovely years where it was tough, but he was a really lovely member of our family.  Despite being really weak he managed to be incredibly cheeky and bossy, and he was a great little brother for his big sister. We were also very lucky that he was being looked after by Professor Francesco Muntoni, who is Head of the Paediatric Neuromuscular Service at Great Ormond Street. And, like Carlo, he is a clinical researcher and actually that I found to be amazing as a family member because you knew what was happening out there and Professor Muntoni, other than living with the reality day to day you want to know where things are going.    We began to realise that back then 20 years ago the more common rare neuromuscular diseases were finally beginning to get some fundamental research funds, like Duchenne, spinal muscular atrophy, and Professor Muntoni was very good at explaining to lay non-scientific parents like us that one day the technologies that would lead to a cure, that would re-engage proteins for other conditions and would translate down eventually into the possibility of replacing myotubularin, which is the protein not being produced or not being produced enough in myotubular myopathy. And then we began to understand actually what the barriers to that would be, that translating developments in more common, or let's say more prevalent conditions, would be hard to do without some translation research being done; you could not just not lag years behind, you could lag decades behind if you haven't done some other work.    So, I met Wendy Hughes, another mother, of a boy called Zak who was a few years older than Tom, and these were the days before social media, and it was amazing to be in contact with another family going through something similar and we had great conversations. But then they were also looked after by Professor Muntoni and we particularly began to develop the idea as 2 families that we might be able to raise some research funds towards this concept of keeping pace with the scientific developments.  And then we discovered there was no charity we could channel those funds through. Even the umbrella body for neuromuscular diseases who were covering 30 to 40 conditions, frankly, they just couldn't trickle their funding down into investing in every neuromuscular disease, and slowly but surely it dawned on us that if we did want to make that difference we were going to have to set up our own charity.   So that's what we eventually did and back in 2006, we founded what was actually the first charity in Europe dedicated to myotubular myopathy – luckily, more have come along since – and we were dedicated to raising research funding. In fact, it wasn't our goal to set up another charity but around that time, about a year in, we happened to go to a meeting where the Head of the MRC, the Medical Research Council, was giving a talk and he said that in the last few years the MRC had begun to really realise that they couldn't cure everything, that they couldn't cure the diseases that would be cured in the next millennium from a top down perspective. There had to be a trick, there had to be a bottom up as well, because that was the only way this was going to happen. And I have to say that that was a really reassuring moment in time for us to realise that we weren't just chasing pipe dreams and trying to do something impossible, that there was a role for us.    Ana Lisa: I think it would be really interesting for people to hear your story and the amazing set-up and fundraising that you've done, and at the same time it would be really good for us to reflect on how this isn't feasible for every patient and every family and how we're going to need to work cooperatively to move forwards with rare therapies.  Anne: When we explored the idea with Professor Muntoni and Meriel and others about setting up a charity one of the really reassuring things that Professor Muntoni got across to us was that this wasn't about raising the millions and millions it would take to fund clinical trials but the issue in the rare disease space was funding the proof of principle work, the work where you take a scientist's hypothesis and take it over the line, and the rarer the disease, the less places there are for a scientist to take those ideas. And the example he gave us was a piece of research like that might cost a hundred to a couple of hundred thousand, if you fund a piece of work like that and if it is successful, if the scientist's principle gets proven, then behind you it's much easier for the bigger muscle disease charities to also invest in it. It's harder for them to spread their money across all the very rare diseases hypothesis out there, but if you've helped a scientist get over the line they'll come in behind you and then they won't be the ones who fund the tens of millions that it takes to run a clinical trial.    If it's got potential, then that's where the commercial world comes in, and that's where the biotechs come in. So he'd given the example of if you spent £ten0,000 on a piece of research and it actually is proven, in behind you will come the bigger charities that would put in the million that takes it to the next phase, and in behind them will come the bio-checks that'll provide biotechs that'll provide the tens of millions.    And then, you know, a lot of what happens relies on serendipity as well, we know that, and you could easily run away with the idea that you made everything happen but you don't, you stand on the shoulders of others. And our very first grant application in our first grant round, which received extraordinary peer review for how excellent the application was, was a £100,000 project for a 3-year project that had gene therapy at the core of it by a researcher called Dr Ana Buj Bello at Généthon in Paris. This piece of research was so promising that 18 months in she and another researcher were able to raise $780,000 and, as Professor Muntoni predicted, from the French muscle disease charity AFM and the American muscle diseases charity MDA.  And 18 months into that 3 years it was so promising that a biotech company was started up with $30 million funding, literally just on her work.    So that doesn't always happen but, as Professor Muntoni explained, our job was not that $30 million, our job was that first £100,000, and our job was also to make ourselves known to the people in the neuromuscular field.  If you have lab time, if you have research time and you have a choice where you're putting it there is a place you can go to for a myotubular myopathy related grant application, so it's not just that this will come to us out of the blue, people will have done prior work, and our existence makes it worth their while, hopefully, to have done that prior work.  Ana Lisa: That's an amazing story how you've set up this charity and how successful that first application for gene therapy was. I'd love to hear more about that gene therapy and did it get to the clinic and to hear that story from you.  Because I think there are a lot of learnings and it's really important that the first patients who are treated, the first families that are involved, the researchers who start researching in this area, the first treatments lead the way and we learn for all the other treatments for all the other rare conditions that we hope and that together as a community we can share these learnings.  Anne: Yeah. I sometimes describe it a bit like going out into space. When you see a rocket going off look at how many people are behind and the amount of work that's been done, the degree of detail that's managed, and then you go out into space and there are a whole load of unknowns, and you can't account for all of them.  Who knows what's out there in this sphere.  But the amount of preparation, it feels similar to me now, looking back.  We were so idealistic at the beginning.  Our grant to Dr Buj Bello was 2008 and actually it is a really fast time in, the first child was dosed in the gene therapy trial in September 2017.  Ana Lisa: So, we're talking less than 1 years.  Anne: Yeah. And in the meantime obviously as a charity we're also funding other proof of principle research. One of the founding principles of the charity was to have a really excellent peer review process and scientific advisory board so that we wouldn't get carried away with excitement about one lab, one research team, that everything would always come back to peer review and would be looked at coldly, objectively. I don't know how many times I've sat in a scientific advisory board meeting with my fingers crossed hoping that a certain application would get through because it looked wonderful to me, and then the peer review comes back and there are things you just don't know as a patient organisation. So, yes, in those 9 years we were also funding other work.  Ana Lisa: You've just given an interesting perspective on sharing the learnings between the scientists, clinicians, the experts in a particular condition, if you like, and the families, and I'd be really interested to hear your views on what's been learnt about how families and the patient community can also teach the clinical and scientific community.  Anne: So, the first child was dosed in September 2017 and by the World Muscle Society Conference 2 years later in October 2019 the biotech had some fantastic results to show. Children who had been 24-hour ventilated were now ventilator-free, which, unless you know what it's like to have somebody in front of you who's ventilator-dependent, the idea that they could become ventilator-free is just extraordinary.    However, one of the things we've learnt about gene therapy is that we are going out into space so there are extraordinary things to be found, and extraordinary results are possible, as is evidenced here, but there is so much that we don't know once we are dealing with gene therapy. So unfortunately, in May, June and August of 2020, 3 little boys died on the clinical trial. So we have a clinical trial where the most extraordinary results are possible, and the worst results are possible, and both of those things are down to the gene…  What we discovered and what is still being uncovered and discovered is that myotubular myopathy is not just a neuromuscular disorder, it is a disorder of the liver too, and these children didn't die of an immune response, which is what everybody assumes is going to happen in these trials, they died of liver complications.    And one of the things that has come out of that, well, 2 sides to that. Number one is that it is extraordinary that we have found a treatment that makes every single muscle cell in the body pick up the protein that was missing and produce that protein, but also what we've understood is that the knowledge and experience of families and patients is even more vital than we've all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family they would tell you, “Yes, my son has had the odd liver result, yes.”    We could see something that looked like it was not that relevant because it was outside the big picture of the disease, which was about breathing and walking and muscles, but actually there was this thing going on at the same time where the children had liver complications. There were some very serious liver complications but everybody thought that was a minor issue but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing.  Ana Lisa: Yeah, thank you very much for sharing such a moving story and with such powerful lessons for the whole community about how we listen to the expertise that families have about their condition, and also I think the really important point about how we tackle the research funding so that we're including and sharing learnings from the conditions that are initially studied in greater depth, and we hope that many more conditions will be better understood and more treatments found and that actually the learnings from these first gene therapy trials will really help inform future trials, not just for gene therapies but also for many other novel therapies that are being developed.  [Music plays] If you're enjoying what you've heard today, and you'd like to hear some more great tales from the genomics coalface, why don't you join us on The Road to Genome podcast. Where our host Helen Bethel, chats to the professionals, experts and patients involved in genomics today. In our new series, Helen talks to a fantastic array of guests, including the rapping consultant, clinical geneticist, Professor Julian Barwell, about Fragile X syndrome, cancer genomics and a holistic approach to his practice - a genuine mic-drop of an interview. The Road to Genome is available wherever you get your podcasts. [Music plays] Ana Lisa: Carlo, I would really like to come to you about some of the initiatives that are happening in the UK, and particularly it would be really interesting to hear about the UK Platform for Nucleic Acid Therapies as a sort of shining example of trying to do something at a national scale across potentially many different rare conditions.    Carlo: Thanks, Ana-Lisa. Thanks very much, Anne, for sharing your fantastic story. I mean, I just want to iterate that as clinician scientists we do constantly learn from experiences and constantly learn from you, from the patient community, and this is absolutely valuable to push the boundary. And I really liked your vision of a rocket being launched in space and I would imagine that this is a similar situation here. So, we are facing a major challenge. So, there is over 7,000 rare diseases in the world and with improvements of genetic diagnosis this is only increasing. So, in a way rare diseases is the ultimate frontier of personalised medicine and this poses incredible challenges.   So, you mentioned the bottom-up approach and the top-down approach and in a way, both are absolutely necessary. So your story is a fantastic story but also makes me think of all the other families where they don't share perhaps the same spirit, you know, they are in areas of the world that are not as well connected or informed, where patient community simply cannot be ‘nucleated', let's say, around the family. So, there is definitely an issue of inclusivity and fair access.    So, what we're trying to do at UPNAT, which is the UK Platform for Nucleic Acid Therapy, is to try to streamline the development both at preclinical and clinical level of nucleic acid therapies. So, we'll start with antisense oligonucleotides just because those are the molecules of the class of drugs that are most ‘mature', let's say, in clinic. So, there are several antisense oligonucleotides already approved in the clinic, we know that they are reasonably safe, we understand them quite well, but of course the aspiration is to then progress into other forms of gene therapy, including gene editing approaches, for example.   And one of the activities that I'm involved, together with Professor Muntoni, is to try to streamline the regulatory process of such therapies and in particular curate a registry of, for example, side effects associated with nucleic acid therapy in the real world, and you would be surprised that this is something that is not yet available.  And the point is exactly that, it's trying to understand and learn from previous mistakes perhaps or previous experiences more in general.    And this is very much in synergy with other activities in the UK in the rare disease domain.  I'm thinking of the Rare Disease Therapy Launchpad, I'm thinking of the Oxford Harrington Centre, I am thinking of the recently funded MRC CoRE in Therapeutic Genomics. These are all very synergistic. Our point is we want to try to amplify the voice of the patient, the voice of the clinicians working on rare disease, and we want to systematise. Because of course one of the risks of rare disease therapies is the fragmentation that we do all these things in isolation. And I would argue that the UK at the moment leveraging on the relatively flexible and independent regulatory agencies, such as the MHRA, on the enormous amount of genetics data available through Genomics England, and of course the centralised healthcare system, such as the NHS, is really probably the best place in the world to do research in the rare disease area, and probably I'm allowed to say it because I'm a non-UK native.       Ana Lisa: Thank you, that's a brilliant perspective, Carlo, and across all the different therapeutic initiatives that you're involved with. And, Carlo, presumably - we're all hoping - these different initiatives will actually lead to ultimately a bigger scaling as more and more novel therapies that target both our RNA and DNA and actually are working, I guess further upstream in the pathway.    So classically in the past it's been necessary to work out all the underlying biology, find a druggable target somewhere in that pathway and then get a larger enough clinical trial, which can be nearly impossible with many of the rare and ultra-rare conditions or even, as you've said, the sub-setting down of more common condition into rarer subtypes that perhaps can be treated in different ways.  And with the many new different treatments on the horizon, ASO therapies, as you've said, is a place that's rapidly expanding, and also crisper gene editing. I'd be really interested to hear your reflections on how this might scale and also how it might extend to other new treatments.  Carlo: Yeah, that's exactly the right word, ‘scaling up'. I mean, there will be of course very unique challenges to every single rare disease but I would argue that with genetic therapies, such as ASOs or crisper gene editing, the amount of functional work that you need to do in a lab to prove yourself and the scientific community that this is the right approach to go for can be certainly very important but can be less just because you're addressing very directly because of the disease.    And then there are commonalities to all these approaches and possibly, you know, a platform approach type of regulatory approval might serve in that regard. You know, if you are using the same chemistry of these antisense oligonucleotides and, you know, similar doses, in a way the amount of work that you need to produce to again make sure that the approach is indeed a safe approach and an effective approach might be also reduced.    I would say that there are also challenges on other aspects of course, as you were saying, Ana-Lisa. Certainly the typical or standard randomised placebo control trial that is the standard and ultimate trial that we use in a clinical setting to prove that a molecule is better than a placebo is many times in the context of rare diseases simply not possible, so we need to think of other ways to prove that a drug is safe and is effective.   This is something that we all collectively as a scientific community are trying to address, and the alliance with the regulatory agencies, such as the MHRA, and you said that you have found your interaction with the MHRA very positive, and I can tell you exactly the same. So we are all trying to go for the same goal, effectively, so trying to find a way to systematise, platformise these sort of approaches. And I guess starting with antisense oligonucleotides is really the right place to go because it's a class of drugs that we have known for a long time, and we know it can work.  Ana Lisa: Meriel, can you tell us a little about the National Genomic Research Library at Genomics England and how this could link with initiatives to find many more patients as new treatments become available for rare and ultra-rare conditions?  Meriel: Yes, I think what's wonderful now is actually that what we're really trying to do is give everybody the opportunity to have their rare condition specifically diagnosed at the molecular level, and the way in which that is being done is by offering whole genome sequencing in the NHS currently in England but to all patients with rare diseases.    And so, it's about trying to establish their diagnosis. And as well as that, even if the diagnosis isn't definitely made at the first pass when the clinical scientists look at the data, because the whole genome has been sequenced, actually all that information about their genome, if they consent, can then be put into the National Genomics Research Library.  And that is a fantastic resource for national and international researchers who get approved to work in this trusted research environment to make new disease gene discoveries and identify these diagnoses for patients.  What's also offered by Genomics England as well is when the National Genomics Library data results in a new publication, the discovery of a new gene or perhaps a new molecular mechanism that causes a disease we already know about, that feeds back into the diagnostic discovery pathway within Genomics England back onto the diagnostic side of all the data.    So, patients who may have had genetic testing previously using whole genome sequencing where they've, if you like, had their sequencing done before the diagnosis was sort of known about, will also be picked up. And so, what this is really doing is trying to kind of give this really equal platform for everybody having testing to all have the same opportunity to have their diagnosis made, either on the diagnostic side or with research.  Ana Lisa: So, sort of on a cohort-wide scale as new discoveries are made and published you can go back and find those patients that may actually have that diagnosis and get it back to them, which is brilliant.  Meriel: Exactly. And this speeds up the whole process of getting these diagnoses back to people. So on a regular basis in the NHS, we will get feedback from the Diagnostic Discovery Pathway about “Here's some patients who you requested whole genome sequencing from a number of years ago and actually now we think we know what the particular molecular condition is.”  And so, it's key of course for our patients with rare conditions to make that molecular diagnosis because then we're able to have them identified for our colleagues who are doing this ground-breaking research trying to bring therapies for these rare conditions.  Ana Lisa: Thank you. And I hope that, as currently, if a novel genetic mechanism, as you've just described, is identified that could explain a rare condition that those patients can be found and they can receive that diagnosis, even many years later, and hopefully as novel treatments become available and say there's a chance to individualise ASO therapies, for example, to start with, that one could also go and look for patients with particular variants that could be amenable potentially to that treatment. And that's really sort of exciting that one could look for those patients across England, irrespective of which clinic they're under, which specialist they're under, and I think that could be really powerful as new treatments develop. I suppose, Meriel, if somebody comes to see you now in clinic are things different?  Meriel: Well, I think one of the things for me when patients come to clinic now is we might have an idea about what we think their condition is, maybe even we think it's a specific gene. And we can offer whole genome sequencing and so it's not just the way we used to do things before by looking just at the coding regions of the gene, we can find more unusual ways in which the gene can be perturbed using whole genome sequencing.  But let's say we don't make the diagnosis. I encourage my patients, if they're comfortable with it, to join the National Genomics Research Library, because really it's been incredibly productive seeing the new genetic discoveries that are coming out of that, but as well I say to them, even if we don't get the diagnosis the first time round when we look at the data, actually this is a constant cycle of relooking at their data, either if they're in the NGRL or as well on the Diagnostic Discovery Pathway side of the service that's run by Genomics England. So yeah, I feel like it's a very big difference; they don't have to keep coming every year and saying, “Is there a new test?” because actually they've had an excellent test, it's just developing our skills to really analyse it well.  Ana Lisa: Yes, and our knowledge, the technology and the skills keep evolving, certainly.  And I think one of the things that I'm sort of hearing from this conversation is that balance of hope and realism, Carlo we were talking about earlier how you need all the pieces of the puzzle to be lined up - so the regulatory agency, the clinicians, all the preclinical work has to have been done, monitoring afterwards for side effects - every piece of the puzzle has to be lined up for a new treatment to make it to a patient.    And, Anne, I'd like to come back to you because we've talked about this before, how one balances these messages of optimism and hope which are needed for bringing everybody together as a community to crack some of these very difficult challenges highlighted by treatments for rare and ultra-rare conditions and at the same time the need for realism, a balance conversation.  Anne: Yeah, that was one of our big learnings through the gene therapy trial and other trials we've had in the condition. As a rare disease charity, you do everything. You know, my title is CEO, but I tell people that's Chief Everything Officer because there's only a few of you and you do everything. So, you go and you lead the London Hope Walk and you also are a layperson on the Scientific Advisory Board and you also send out the emails about grants... And so, you could easily as a small rare disease charity conflate different communication messages because you're in a certain mode.  And so we have been from the early days in the mode of raising hope for people to say, “Look, we can make a difference as a patient community, we could raise funds, we might be able to move things forward, you've got the power to make a difference if you want to.” That's one set of hope.  And it's not dreamlike hope, we're linked to the reality of there are great breakthroughs.  So, you know, in the world of spinal muscular atrophy these clinical trials have led somewhere very quickly, so we're not selling false hope, we're talking about the difference we can make.    But then as soon as you flip into “There's a clinical trial being run” that's a completely different type of communication and you cannot conflate that message with the previous message.  And we always say to everybody, “We're your team, we're a family, we're a team, we all help each other.  When you are considering joining a clinical trial your team is the clinical trial team.    The other team does other things for you but the people you need to work with and ask hard questions of and listen hard to, that's your clinical trial team led by the principal investigator because then you're in that with them. And, you know, the reality of the fact that many, many clinical trials don't work as we wish they would be and the decision you make for your child, your baby, your little one, to join a clinical trial… because that's what it comes down to in our disease, has to be made with that team, not the team that's selling you a fundraising event. It's worth reminding rare disease patient organisations we're wearing different hats and the hope and the realism are different tracks you have to go down.    But at the same time as being realistic you also have to keep remembering that there is still grounds for hope, we are moving forward. And 21 years ago, when Tom was born the idea that you would be able to get all of the muscles in the body to switch back on – putting it in lay terms – seemed like a bit dream. Well, that is what has happened in the gene therapy clinical trial, we just have to now make it safer and understand more about what we're dealing with. So, the 2 things, the hope and the realism, do exist side by side.  Ana Lisa: I think that perfectly encapsulates a lot of the messages around rare disease therapies where there's such hope that novel treatments will really target directly the DNA or RNA to potentially correct the problem across many different rare conditions and therefore actually making treatments one day suddenly available to a much, much bigger population of people with rare conditions than we could've dreamt of 20 years ago or perhaps now, and at the same time this massive need to work cooperatively to all make this as fair, as equitable. Not everybody is going to have the opportunity to fundraise massively to be an expert about their condition, and the importance of sharing these learnings and also really, really listening to the patient community and really, as Carlo was saying, keeping track of side effects, having registries/databases to share these is going to be incredibly important.  [Music plays]  Ana Lisa:  Anne, can you tell us a little about your reflections on equity from the patient community perspective?  Anne: Well I mentioned serendipity early and one of the aspects of serendipity that played into our favour for setting up the Myotubular Trust was that by hook or by crook Wendy Hughes, who set up the charity with me, and I were both able to devote time at that period of our lives to setting up a charity. When my husband, Andrew, and I were told that Tom would more than likely die before his first birthday, one of the decisions we made as a family was that he would never not be with a parent, we would always have someone around, and that kind of meant someone had to give up a full-time job and that was me.  We thought, “If Tom has a few scarce months on the planet, we'll be with him.” And then when Tom lived to be nearly 4, as a family we got used to living on one salary and we were very lucky that we could pay the mortgage that way and run our family that way and eventually that meant I had the time to run the charity.    That doesn't happen that easily, that's a tall order, particularly when you have somebody in the family who has such high needs. And one of the things that I have often thought about is that in the rare disease space we could do with a different funding model for rare disease charities, we could, in an ideal world I have this nirvana that I imagine where there's a fund that you can apply to that is contributed to by the people who make profits out of finding rare disease cures - so the pharmaceutical companies and the biotechs - and there's a fund that they contribute to and that if you have a rare disease and you are willing to set up an organisation that supports families, that raises research funds, that provides a way of hearing the patient voice, then you could apply to that for running cost funds and then you'd be able to run this charity. And then you wouldn't have to rely on whether you live in an area where people will raise money for you or…  We were very lucky that we came across a few great benefactors who would give us money for running the charity, which is actually how we fund it.    All the research money we raise goes 100% into research, not a penny of it goes towards running costs because we have serendipitously found people who will be benefactors for the charity, but we're relying on a lot of good luck for that kind of model to work. And when you look at how much profit is made from developing rare disease treatments and cures – which is fine because that's what puts the passion and that gets people working on it – then why not have an advance fund to run rare disease charities? One of my nirvana dreams.  Ana Lisa: It's good to dream. Indeed, my hope is that there will be some amazing shining examples that lead the way that open doors, make things possible, prove that something can work and how and that then that will enable many other treatments for many additional rare conditions to be added in so that if you've learnt how this particular treatment modality works for this rare condition and there was funding behind it and everything else that's needed that then you can, the learning from that, I'm going to use the word ‘tweak', which sounds minor and could be very major but actually the concept that you can then tweak all those learnings and findings so that that same type of treatment modality could be adapted to treat somebody else with a different rare condition in a different location would be absolutely incredible and really powerful, given that if something like 85% of rare conditions affect less than one in a million people it's not going to be feasible to use the same strategies that have been used in the past for very common conditions.    One of the other big barriers is the cost of developing treatment for ultra-rare conditions.  Where it's a small number of patients that you have and therefore all the challenges that come with monitoring, checking for efficacy, monitoring safety and ultimately funding the challenges are much greater, however if some of these treatment modalities are also going to be used to treat common conditions it might be that actually there's a lot more cross-talk between the nano-rare, ultra-rare, rare and common conditions and that we can share a lot of that learning. I'd love to hear from each of you where you hope we will be for rare disease and rare therapies.  Carlo: Well my dream is that in 5 to 10 years' time an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested, and at that exact time the day of the diagnosis becomes also a day of hope in a way where immediately the researcher, the centre, genetics lab, flags that there are the specific mutations, we know exactly which is the best genetic therapy to go after, antisense oligonucleotides as opposed to CRISPR editing, and a path forward, both at the preclinical and clinical level, to demonstrate and to cure these patients eventually is already laid out in front of the patient.  So, transforming the day of their diagnosis as a day of hope, this is my dream with the next ten years.  Ana Lisa: Thank you, that's a wonderful dream. Meriel, can I come to you?  Meriel: Yes, I think I just want to echo Carlo.  We've had great developments and progress with getting whole genome sequencing into the NHS for testing but what we really need is for it to be fast and efficient and getting those diagnoses established quickly. And we have had that set up now and we're really getting there in terms of speed, but then what we need is exactly what's the next step and actually structure like UPNAT that are developing these processes that we can then say to the patient, “And from there, now that we've established your diagnosis, this is what we have options to offer.”  Ana Lisa: Brilliant. And presumably that if the diagnosis isn't achieved now there is a hope that it will be achieved in the future as well. Anne...  Anne: Well, stepping one hundred per cent into the patient's shoes rather than the scientific side that we don't so much influence....  stepping in the patient's shoes, in 5 years' time I would absolutely love it if we were in a situation where all the parties that have come to the table looking at a therapy or in the earlier research genuinely want to bring the patient voice into the room. As Carlo talked about, there's even going to be more and more and more of these rare diseases, then those voices, those few people who have experience of it, they may be able to shed light on something. Maybe even sometimes don't even know it's a fact that they know but that were brought to the table as passionately as everything else is brought to the table.  [Music plays]  Ana Lisa: We'll wrap up there. Thank you so much to our guests, Anne Lennox, Carlo Rinaldi and Meriel McEntagart, for joining me today as we discuss the collaborative power of working together and look to the future of rare therapies that could have the potential to unlock treatments for many rare conditions. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I've been your host, Ana-Lisa Tavares. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.  

Jijo Reed, recognized by LA WEEKLY and NEW YORK POST as "Top Trendsetter in 2023" is an Emmy Winning Producer, 16 time Telly Award Winner, and Executive Producer of over 80 feature films and/or series.Latest feature films include Crescent City starring Alec Baldwin and Terrence Howard, THE BLACKENING directed by Tim Story for MRC, Village Roadshow's CINNAMON, and MENDING THE LINE starring Brian Cox (Succession)... also, MACHINE GUN KELLY'S LIFE IN PINK 2022 documentary for Hulu/Disney and BACK ON THE STRIP with Kevin Hart and Tiffany Haddish.A high point in his career is when he deep dived to the wreck site of TITANIC in the Russian submersible, MIR 1, while directing and producing a documentary about the famed, ill-fated ship...during which he became one of the very few men in the entire world to dive the actual wreckage of TITANIC at 2.5 miles below sea level. More people have been to outer space than this depth of the ocean. His "ground breaking, cinematic" footage of Titanic is recognized globally. Reed states: "This was the most life changing project of my career."Also, Reed was Visual Effects Supervisor for THE AVENGERS S.T.A.T.I.O.N 3D interactive exhibit, the innovative and revolutionary experience which is currently a main attraction in Times Square, NY and Las Vegas.Jijo was Executive Producer of the 2013 OBAMA PRESIDENTIAL INAUGURATION Concert in Washington DC featuring WIL I AM and JOHN LEGEND. Additionally, he has produced screen media for live music concert tours, including EMINEM's MTV Awards performance and GUNS & ROSES.In 2004, Jijo created the hit VH1 show "CELEBRITY REHAB" which has won numerous awards and has helped people all over the world overcome addictionThroughout the 1990's, he worked as Post Supervisor on the audio/visual ad campaigns of studio films such as Martin Scorsese's CASINO, Jim Cameron's TRUE LIES, STAR TREK, DIE HARD, LETHAL WEAPON 4, THE UNFORGIVEN, and many others.Jijo Reed is a third generation Los Angeles native and the grandson of Alan Reed who was the voice of FRED FLINSTONE and acted in such movies as Breakfast At Tiffany's and Postman Always Rings Twice. Jijo is also the nephew of FRED ASTAIR'S choreographer, Hermes Pan.

In the 7 AM Hour: Larry O’Connor and Julie Gunlock discussed: WMAL GUEST: 7:05 AM - INTERVIEW - TIM GRAHAM - Executive Editor, Media Research Center's NewsBusters – Discussed MSNBC shakeup and MRC’s Defund PBS & NPR mobile billboard truck circling DC SOCIAL MEDIA: https://x.com/timjgraham Media Research Center has a digital billboard truck driving all around the Capital Tuesday through Thursday and will be saying to defund PBS and NPR. MSNBC axes THREE more stars' shows after Joy Reid in network bloodbath MSNBC host Rachel Maddow rips own network for axing Joy Reid’s show and other ‘non-white’ hosts’ programs Lester Holt is stepping down as anchor of 'NBC Nightly News' after a decade DeSantis announces Florida ‘DOGE task force’ WMAL GUEST: 7:35 AM -INTERVIEW - JIM HANSON - President of Security Studies Group and served in US Army Special Forces – discussed Ukraine talks Christopher F. Rufo ⚔️ on X: "EXCLUSIVE: @GrossmanHannah and I have obtained logs from the NSA’s secret transgender sex chatroom, in which NSA, CIA, and DIA employees discuss genital castration, artificial vaginas, piss fetishes, sex polycules, and gangbangs—all on government time. This is insane. Where to find more about WMAL's morning show: Follow the Show Podcasts on Apple podcasts, Audible and Spotify. Follow WMAL's "O'Connor and Company" on X: @WMALDC, @LarryOConnor, @Jgunlock, @patricepinkfile, and @heatherhunterdc. Facebook: WMALDC and Larry O'Connor Instagram: WMALDC Show Website: https://www.wmal.com/oconnor-company/ How to listen live weekdays from 5 to 9 AM: https://www.wmal.com/listenlive/ Episode: Tuesday, February 25, 2025 / 7 AM Hour See omnystudio.com/listener for privacy information.

WMAL GUEST: 7:05 AM - INTERVIEW - TIM GRAHAM - Executive Editor, Media Research Center's NewsBusters – Discussed MSNBC shakeup and MRC’s Defund PBS & NPR mobile billboard truck circling DC SOCIAL MEDIA: https://x.com/timjgraham Media Research Center has a digital billboard truck driving all around the Capital Tuesday through Thursday and will be saying to defund PBS and NPR. MSNBC axes THREE more stars' shows after Joy Reid in network bloodbath MSNBC host Rachel Maddow rips own network for axing Joy Reid’s show and other ‘non-white’ hosts’ programs Lester Holt is stepping down as anchor of 'NBC Nightly News' after a decade Where to find more about WMAL's morning show: Follow the Show Podcasts on Apple podcasts, Audible and Spotify. Follow WMAL's "O'Connor and Company" on X: @WMALDC, @LarryOConnor, @Jgunlock, @patricepinkfile, and @heatherhunterdc. Facebook: WMALDC and Larry O'Connor Instagram: WMALDC Show Website: https://www.wmal.com/oconnor-company/ How to listen live weekdays from 5 to 9 AM: https://www.wmal.com/listenlive/ Episode: Tuesday, February 25, 2025 / 7 AM Hour See omnystudio.com/listener for privacy information.

Willie is back talking about the latest media hypocrisy. Daniel Greenfiled from Front Page Mag joins the show. Isreal Ellis talks on Israel, the hostages and America's support for Israel. Steve Milloy debunks the climate change hysteria. Curtis Houck from MRC breaks apart the left-wing media, defunding PBS, NPR and more. Dr Suzanne Barchers on the state of education in America.

Willie is back talking about the latest media hypocrisy. Daniel Greenfiled from Front Page Mag joins the show. Isreal Ellis talks on Israel, the hostages and America's support for Israel. Steve Milloy debunks the climate change hysteria. Curtis Houck from MRC breaks apart the left-wing media, defunding PBS, NPR and more. Dr Suzanne Barchers on the state of education in America.

Willie is back talking about the latest media hypocrisy. Daniel Greenfiled from Front Page Mag joins the show. Isreal Ellis talks on Israel, the hostages and America's support for Israel. Steve Milloy debunks the climate change hysteria. Curtis Houck from MRC breaks apart the left-wing media, defunding PBS, NPR and more. Dr Suzanne Barchers on the state of education in America.

In this episode of the Pencil Pushers Podcast, host Mike Rosado interviews local designer and illustrator Lauren Griffin. Lauren shares her journey, from growing up in multiple cities to settling in Durham, North Carolina. With an impressive portfolio that includes work for Helms Workshop and Pabst Blue Ribbon, Lauren discusses her passion for creating playful yet sophisticated illustrations and brand identity design. She also talks about her newfound love for neon design, featuring pieces in the Museum of Neon Art in Los Angeles, as well as her preparations for her first solo show in Steamboat Springs, Colorado.Lauren reflects on her early influences, including her creative mother and a supportive teacher who nudged her toward an art and design career. She also shares her experiences working for agencies, freelancing, and even collaborating with Mike himself at his studio MRC in Raleigh, NC. The conversation explores the importance of knowing one's self-worth, the challenges of freelancing, and the evolving role of technology—including AI—in the world of design and art.

MRC finishes up July of 1967, with Fantastic Four 64, Daredevil 30, Thor 142, Tales of Suspense 91 with Iron Man and Captain America, and Avengers 42! Wonder of Wonders! Matt as Mike as DD as Thor! Anti-Force! Centrifugal Rays! Check it out!

"Jack Riccardi talked about Mexico and Canada blinking on tariff threats, joined by Gordon Chang, who also talked about China, tariffs and the Panama Canal, plus Chuck Schumer's party props, the grift of politicians writing books, and SA closing the MRC."

Fraudology is presented by Persona.Join Karisse Hendrick and special guest Tracy Brown as they dive deep into the world of e-commerce fraud prevention in this captivating episode of the Fraudology Podcast. Tracy, a veteran in the field and current VP at the Merchant Risk Council (MRC), shares her unique origin story in fraud prevention and how it led to the formation of the MRC. The duo discusses the latest fraud trends keeping merchants up at night, including the surprising rise of refund abuse and the challenges posed by alternative payment methods. Tracy provides an exclusive preview of the upcoming MRC Vegas conference, showcasing the event's diverse offerings from educational sessions to networking opportunities. Learn about the conference's innovative features, such as a behind-the-scenes look at issuing bank operations and a preparation course for the industry-recognized CPFPP certification.The episode also touches on the importance of building relationships within the fraud prevention community and leveraging events like the MRC conference to stay ahead of emerging threats. With insider tips on making the most of the conference experience and insights into the future of fraud prevention, this episode is a goldmine for anyone involved in e-commerce security. Don't wait - listen now and arm yourself with the latest intel from the frontlines of fraud prevention!To connect with Tracy Brown:https://www.linkedin.com/in/tracykobedabrown/To learn more about the MRC Vegas Conference:https://events.merchantriskcouncil.org/event/vegas2025/aboutFraudology is hosted by Karisse Hendrick, a fraud fighter with decades of experience advising hundreds of the biggest ecommerce companies in the world on fraud, chargebacks, and other forms of abuse impacting a company's bottom line. Connect with her on LinkedIn She brings her experience, expertise, and extensive network of experts to this podcast semi weekly, on Tuesdays and Thursdays.

While falling snow may look pretty, it can also be pretty dangerous for drivers. Winterizing your vehicle is a good precaution as it can save you money on car repairs and help you stay safe while on the road. If you own a car, here are some tips to get it winter-proof if you haven't already. Links: Visit our Auto page to explore current rates and learn more about GAP and MRC coverage for your vehicle Check out TCU University for financial education tips and resources!  Follow us on Facebook, Instagram and Twitter!  Learn more about Triangle Credit Union Transcript: Welcome to Money Tip Tuesday from the Making Money Personal podcast.   Roads often become slippery during the winter months. To counteract this, consider putting winter tires on your vehicle. You can use all-season tires during the winter, but when it gets cold, the rubber in these tires hardens, decreasing the grip on the road. Winter tires use a special compound that can resist the cold and won't harden. Winter tires also have better traction in snowy and icy road conditions, which means that they have better acceleration and are better at stopping than all-season tires. However, winter tires can be costly. Winter tires can cost over $600, plus you'll have to pay for the tire-swapping fees unless you do it yourself. A cheap alternative is putting chains on your tires to help with traction.  Regardless of what tires your car has, you'll want to check the tire pressure. Tire pressures drop 1 pound per square inch, or PSI for short, every 10 degrees Fahrenheit. You can check the correct tire pressure for your car in the manual or on the car door jamb. Another way to get your car winter-ready is to have the battery tested. Your car battery is essential for starting your car. Colder temperatures can affect the chemicals in the battery, which may result in a car having trouble starting or not starting at all. Consider buying a portable jump starter for your vehicle in case your car doesn't start due to low temperatures. Next, you'll want to make sure you have good visibility while driving. Check your windshield wipers to see if they are working properly, and don't leave smudge marks on your windshield. Fill up your windshield wiper fluid too. You can also get a hydrophobic repellant to add to your windshield, making scraping ice and snow off your car windows easier. Headlights are another thing to consider when winterizing your car. Snow can cause limited visibility when driving, but having a good set of headlights can help you see better, especially during the dark hours of winter. If you've noticed that your headlights aren't as bright as they used to be, you should get a headlight restoration kit or replace them altogether.  You should have a winter emergency kit in your car. If you get stranded with your vehicle, this kit will help you get back on your drive or at least keep you comfortable while waiting for help to arrive. In this kit, you should include a snow shovel, a snow broom, an ice scraper, a portable jump starter, warm clothing, including hats and gloves, blankets, a first-aid kit, a basic tool kit, traction mats, and flashlights.  If you're considering buying a car that's more suitable for winter, look for one that has 4-wheel drive or all-wheel drive instead of front-wheel drive. Vehicles with 4-wheel drive and all-wheel drive provide better traction on icy roads than front-wheel drive vehicles.  If you decide to buy a more winter-proof car, Triangle Credit Union offers auto loans tailored to fit your ride. If you get into an accident, Guaranteed Asset Coverage, or GAP coverage, is designed to reduce or eliminate the difference between the insurance settlement and the loan balance. This protects you from owing more than the vehicle is worth. Mechanical Repair Coverage, or MRC, can help limit unexpected, covered repairs as your vehicle ages, potentially saving you thousands of dollars.  If you're interested in either one of these coverages, contact the credit union or visit your local branch to learn more. If there are any other tips or topics you'd like us to cover, let us know at tcupodcast@trianglecu.org. Also, remember to like and follow our Making Money Personal Facebook and Instagram to share your thoughts. Finally, remember to look for our sponsor, Triangle Credit Union, on Facebook and LinkedIn.        Thanks for listening to today's Money Tip Tuesday. Check out our other tips and episodes on the Making Money Personal podcast.   

Analysts Don Kellogg and Roger Entner discuss Q4 earnings from the major players in telecom and cable, as well as key personnel updates for T-Mobile and the FCC.00:25 AT&T Q4 overview 03:06 Verizon Q4 overview 06:35 T-Mobile Q4 overview 08:04 Cable industry Q4 overview 08:53 T-Mobile to appoint Srinivasan Gopalan as COO 10:09 Telecom industry Q4 summary 10:25 FCC Chairman Carr appoints Scott Delacourt as Chief of StaffTags: telecom, telecommunications, wireless, prepaid, postpaid, cellular phone, Don Kellogg, Roger Entner, earnings, AT&T, net adds, churn, FWA, upgrades, Verizon, T-Mobile, MRC, ARPU, fiber, John Stanke, EBITDA, cable, Comcast, Black Friday, Charter, Sprint, Srinivasan Gopalan, FCC, Brendan Carr, Scott Delacourt

Happy Wednesday. Bob kicks off the show talking about the confirmation hearings of RFK and more. Bob then talks with Senator Bernie Moreno about the Columian president situation, ICE and illegals and the Trump agenda. Bob the talks with newly appointed senator Jon Husted. They talk about his plans and his support of President Trump. Bob then talks with Bill D'Agostino from MRC about the coverage of the pardons between Trump and Biden.. Bob takes calls to wrap up the show.See omnystudio.com/listener for privacy information.

MRC welcome super-special guest Dan McCoy, Emmy-winning writer and co-host of The Flophouse! We discuss four books from July 1967: Amazing Spider-Man 50, Strange Tales 158 with SHIELD and Dr Strange, Tales to Astonish 93 with Namor and Hulk, and X-Men 34! Spidey No More! Monocle upon eye patch upon monocle! An actual Pink Floyd Album cover! Shameless swipes! Check it out!

Analysts Don Kellogg and Roger Entner discuss current consumer perceptions surrounding big players in the telecom industry and if the perception matches reality.00:25 Where do current carriers stand? 1:10 Switching dictates perception 02:25 Verizon vs. T-Mobile on price and network 06:33 4G vs. 5G in reality 08:25 AT&T's perception 09:06 Carrier identity goals 10:00 Cable and Mint 12:12 Cable's transition and content challenges 15:00 Episode wrap-upTags: telecom, telecommunications, wireless, prepaid, postpaid, cellular phone, Don Kellogg, Roger Entner, Verizon, 4G, 5G, network, T-Mobile, AT&T, price, MRC, ARPU, Wi-Fi, data, FWA, slicing, net adds, gross adds, cable, Mint, churn, value, content, NFL, linear television, video, streaming

MRC finishes up June of 1967 with Fantastic Four #63, Strange Tales #157 with SHIELD and Dr. Strange, Tales of Suspense #90 with Iron Man and Captain America, and Avengers #41! The NYPD's Cement-Bazooka Squad! Hallucination Cubes! Neckless! 24-Hour Treason! Heckless! Check it out!

MRC unmasks June 1967, with Amazing Spider-Man 49, Daredevil #29, Thor 141, Tales to Astonish 92 with Namor and the Hulk, and X-Men 33. Bamboo TV! Dissociative identity disorder! Rasslin'! It! Wile E. Coyote Holes! Cyttorak Lollipops! Check it out!

CNN has been found guilty of defamation so MRC's Curtis Houck joins Jeff to give the latest update.

LA is on fire and the politicians are at fault. No thinning of the forest.....little to no water pressure in the fire hydrants and reservoirs are empty. Bill chats with Wayne Allyn Root on this and more. Dan Schnider from the MRC is on and we wrap up the show with Grover Norquist talking taxes and more.

In the 6 AM Hour: Larry O’Connor and Emily Domenech discussed: Trump’s reaction to the CA fires Biden mocked for tone-deaf ‘good news’ while Californians flee wildfires WMAL GUEST: 6:35 AM - INTERVIEW - NICHOLAS FONDACARO - Associate Editor for MRC and Newsbusters SOCIAL MEDIA: https://x.com/NickFondacaro CNN heads to court for high-stakes defamation trial about Afghanistan segment Jury set for CNN defamation trial after multiple candidates expressed disdain for network: 'Not a fan of CNN' Where to find more about WMAL's morning show: Follow the Show Podcasts on Apple podcasts, Audible and Spotify. Follow WMAL's "O'Connor and Company" on X: @WMALDC, @LarryOConnor, @Jgunlock, @patricepinkfile, and @heatherhunterdc. Facebook: WMALDC and Larry O'Connor Instagram: WMALDC Show Website: https://www.wmal.com/oconnor-company/ How to listen live weekdays from 5 to 9 AM: https://www.wmal.com/listenlive/ Episode: Thursday, January 09, 2025 / 6 AM Hour See omnystudio.com/listener for privacy information.

MRC finishes up May of 1967 with Fantastic Four #62, Strange Tales #156 featuring SHIELD and Dr. Strange, Tales of Suspense #89 featuring Iron Man and Captain America, and Avengers #40! Blastaar! Zip-a-Tone-Man! Zom! Bachelor Life! The Amalga-Beast! Check it out!

MRC steals the gimmick of May 1967, starting with Amazing Spider-Man #48, Daredevil #28, Thor #140, Tales to Astonish #91 with Namor and Hulk, and X-Men #32! Cruci-fiction! Blind/Freeze-Rays! Stimuloids! Democracy sucks! Infinite Weapons! Satan's Saints! Check it out!

Bill is back with you on Sunday night. NYC Subways are full of crime and crap. A homeless lady was set on fire this morning. The Governer of NY is telling Americans how she has made them safer? Willie talks to Julie Gunlock on the sham that is gender confirming surgery and the horrible things it does to kids. Bill Gagostino from MRC also joins the show. Willie wraps up the show talking to Brigette Gabriel gives us an update on the mid-east and much more.

MRC returns from hiatus to finish April 1967, going all out of order with Daredevil #27, Fantastic Four #61, Avengers #39, Tales of Suspense #88 with Captain America and Iron Man, and Thor #139! Rocking chair helicopters! Latverian headshop blacklight posters! Thunderboot! Pepper hooves! Kane tech! Colletta really messing this one up! Check it out!

The world is on fire and who is in charge? Biden? Harris? Or Barack Hussein Obama? Willie takes your calls on the election, what's ahead for this country and more. Linda Hansen talks to Willie about the death of DEI. Wayne Allyn Root, our "Nostradamus", tells us what may happen leading up to Trump taking office. Wrapping up the show with MRC's Curtis Houck.

Four years ago, news organizations and social media platforms deliberately suppressed or outright ignored the Hunter Biden laptop story—one of the biggest scandals of the 2020 election. This time around, those same media outlets are engaged in a different kind of censorship: hiding the radical policy ideas once advocated by Vice President Kamala Harris.  A new poll from Media Research Center confirms even Harris' most ardent supporters don't know her extreme positions on everything from defunding police and co-sponsoring the Green New Deal to legalizing drugs and supporting open borders. Brent Bozell, MRC's founder and president, spoke with The Daily Signal about the shocking findings. He also recounted the impact of burying the Biden laptop story. A postelection poll in 2020 found that if voters knew about the controversy, they would've backed then-President Donald Trump. "Trump would have won 317 electoral votes with ease. It would have been a massive landslide, but that's just the states we polled," Bozell said. "He would have won a landslide on the order of Ronald Reagan had they only known about the laptop." Bozell warned the media could have a similar impact on the 2024 presidential election by ignoring the most controversial aspects of Harris' policy positions. "The media delivered the victory to Joe Biden in 2020," Bozell said. "If she wins, it will be because they delivered the victory to her." Listen to the full interview with Bozell to learn more about the poll, his take on the presidential debates, and why Democrats are more likely to undermine the First Amendment.