Podcasts about Exon

Premier producteur mondial de noix de cajou avec 1,2 million de tonnes en 2024, la Côte d'Ivoire transforme 30 % de sa récolte et veut porter ce pourcentage à 50 % d'ici à 2030. Des stratégies sont mises en œuvre pour atteindre cet objectif, mais le défi est de taille, face à la concurrence des acheteurs asiatiques, au manque de main-d'œuvre qualifiée et aux difficultés d'accès au financement. De notre correspondant à Abidjan,Dans l'usine Cilagri Cajou, à Vridy, en Côte d'Ivoire, les machines tournent à plein régime. Ici, la noix de cajou arrive brute avant d'être décortiquée, pelée, triée et conditionnée. En 2024, l'usine a produit 17 000 tonnes d'amandes de cajou. Mais derrière cette performance, un défi persistant subsiste : le coût de production. « Le secteur de la noix de cajou a connu des turbulences en 2022 qui ont fait que le coût de production ne permettait pas de faire face au coût des amandes sur le marché, regrette Cynthia Namoutié, directrice générale de l'usine. Donc une restructuration des équipements pour permettre de réduire le coût de production était le seul moyen de continuer à survivre. »Modernisation et formationMais moderniser les outils ne suffit pas. Il faut aussi former les travailleurs pour piloter ces machines. « On a une main-d'œuvre disponible, mais elle manque encore de compétences, reconnaît-elle. Il y a un vrai besoin de formation pour que nos employés puissent piloter ces machines sans qu'on ait recours à des expatriés. »Autre enjeu de taille : les usines ivoiriennes sont en concurrence avec leurs puissantes rivales d'Asie du Sud, prêts à acheter la noix brute à des prix élevés. Malgré ces défis, la transformation locale progresse. L'an dernier, le pays a exporté pas moins de 72 000 tonnes d'amandes et compte une quarantaine d'usines actives.Pâte et lait de cajouLa transformation ne s'arrête pas aux amandes brutes. Un nouveau marché émerge : les produits dérivés. « On a la transformation des noix qui donne des amandes de cajou blanches qui sont réutilisés par les acteurs de la deuxième transformation qui vont maintenant produire des pâtes de cajou, du lait de cajou, détaille Marcel Ouattara, secrétaire exécutif du groupement des industriels du cajou en Côte d'Ivoire. On peut même en faire de la farine. Aujourd'hui, on espère qu'on aura un changement dans les habitudes de consommation qui va permettre de pouvoir distribuer tous ces produits dérivés localement. »Exonérations fiscalesPour accélérer la transformation, le gouvernement multiplie les incitations. Cette année, il va donner la priorité aux transformateurs locaux pour l'approvisionnement en noix brutes. « La faveur sera donnée aux transformateurs locaux de disposer de la noix de cajou, a annoncé le ministre de l'Agriculture Kobenan Kouassi Adjoumani. C'est après que nous allons ouvrir la possibilité d'acheter des noix de cajou en vue de l'exportation dans les autres pays. »Autre coup de pouce : l'exonération des taxes sur les amandes transformées localement et les équipements importés. Avec ces mesures, la Côte d'Ivoire espère franchir un cap : ne plus être seulement le premier producteur mondial, mais aussi un acteur clé de la transformation du cajou.À lire aussiAu Sénégal, la transformation de la noix de cajou en difficulté

Il réagissait à la réponse du Premier ministre hier au parlement concernant sa question sur les Smart Cities. Le député du Parti Travailliste voulait savoir le montant des exemptions fiscales obtenues par les promoteurs pour les Smart Cities. Le Premier ministre a ainsi révélé que 19 certificats de Smart City Scheme ont été émis par l'Economic Development Board (EDB) depuis 2015 et ce pour 6 332 arpents de terrains. Cependant, aucun de ces projets n'est prêt même si 16 d'entre eux ont débuté les travaux. Navin Ramgoolam a souligné que ces promoteurs ont déjà bénéficié d'exemptions fiscales totalisant Rs 6,61 milliards. À savoir que ces exemptions avaient été votées par l'ancien gouvernement pour encourager ce genre de projets. Raviraj Beechook trouve les chiffres révélés par le Premier ministre ahurissants.

Christophe Bordet présente les nouvelles mesures gouvernementales visant à faciliter la transmission du patrimoine, encourager la rénovation énergétique et soutenir l'accession à la propriété. Il détaille notamment les exonérations fiscales sur les dons familiaux jusqu'à 300 000 euros pour l'achat ou la rénovation d'un logement. Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.

In this episode of Conversations in Lung Cancer Research, A/Prof Mel Moore, along with thoracic oncologists Dr. Malinda Itchins and A/Prof Surein Arulananda, delve into the characteristics, detection, and treatment of EGFR exon 20 insertion mutant non-small cell lung cancer. The podcast discusses recent advances, the efficacy of various treatments including small molecule tyrosine kinase inhibitors and monoclonal antibodies, and the potential future of targeted therapies. Special focus is given to the Phase 3 Papillon study and the drug Amivantamab, highlighting the need for next generation sequencing in clinical settings. Key challenges and questions in the field are also addressed, including the impact of co-mutations and optimal therapy sequencing.This episode is sponsored by: Johnson & Johnson(00:00) Introduction and Acknowledgements(00:48) Introducing the Experts(01:29) Understanding EGFR Exon 20 Insertion Mutations(05:04) Challenges with Current Treatments(06:30) Emerging Therapies and Clinical Trials(11:03) Papillon Study Insights(21:27) Future Directions and Unanswered Questions(29:34) Conclusion and Final Thoughts

Le secteur de l'IA en Bourse, l'émission «Qui veut être mon associé» sur M6… Rattrapez l'actualité économique du jour avec notre podcast 120 secondes. Hébergé par Audion. Visitez https://www.audion.fm/fr/privacy-policy pour plus d'informations.

Year in Review: Clinical Investigator Perspectives on the Most Relevant New Datasets and Advances in EGFR-Mutant Non-Small Cell Lung Cancer | Faculty Presentation 2: Other Relevant Topics in EGFR Mutation-Positive NSCLC, Such as Nonmetastatic Disease, Exon 20 Insertion Mutations and Novel Agents — Helena Yu, MD CME information and select publications

Join Dr. Paloma Giangrande, Editor-in-Chief of Molecular Therapy Nucleic Acids, as she discusses RNA exon editing with Ascidian Therapeutics' leadership: CSO Dr. Robert Bell and CEO Dr. Michael Ehlers. Their conversation explores Dr. Bell's recent MTNA publication "RNA Exon Editing: Splicing the Way to Treat Human Diseases." Last Call: Submit your abstracts for ASGCT's 2025 Annual Meeting in New Orleans by January 31st, 11:59 PM ET. Present at cell and gene therapy's premier event and get published in Molecular Therapy. Details at annualmeeting.asgct.org/abstracts. In This Episode Paloma Giangrande, PhDEditor-in-Chief, Molecular Therapy Nucleic Acids and Chief Technology Officer at Eleven Therapeutics Robert Bell, PhDChief Scientific Officer at Ascidian Therapeutics Michael Ehlers, MD, PhDPresident and Chief Executive Officer at Ascidian Therapeutics 'Electric Dreams' by Scott Buckley - released under CC-BY 4.0.www.scottbuckley.com.auShow your support for ASGCT!: https://asgct.org/membership/donateSee omnystudio.com/listener for privacy information.

Un cessez-le-feu a commencé cette nuit entre Israël et le Hezbollah, une première dans ce conflit qui dure depuis deux mois. Les Belges épargnent de plus en plus, les banques privées du royaume gèrent plus de 500 milliards d'euros. Uniformiser les exonérations sur les dividendes, ce sont les nouvelles propositions de loi déposées par l'Open Vld et la N-VA.  Le Brief, le podcast matinal de L'Echo  Ce que vous devez savoir avant de démarrer la journée, on vous le sert au creux de l'oreille, chaque matin, en 7 infos, dès 7h. Le Brief, un podcast éclairant, avec l'essentiel de l'info business, entreprendre, investir et politique. Signé L'Echo. Abonnez-vous sur votre plateforme d'écoute favorite Apple Podcast | Spotify | Podcast Addict l Castbox | Deezer | Google Podcasts  See omnystudio.com/listener for privacy information.

Ecoutez Le débat du jour avec Amandine Bégot et Thomas Sotto du 19 novembre 2024.

Ecoutez Le débat du jour avec Amandine Bégot et Thomas Sotto du 19 novembre 2024.

Ecoutez Le débat du jour avec Amandine Bégot et Thomas Sotto du 19 novembre 2024.

Ecoutez Le débat du jour avec Amandine Bégot et Thomas Sotto du 19 novembre 2024.

Comment bénéficier d'une exonération de CFE pour enfin ne plus avoir à payer la cotisation foncière des entreprises ?C'est possible mais comme toujours, sous certaines conditions. Et les motifs d'exonération de CFE ne sont pas toujours ce que l'on croit :Peut-on être exonéré de CFE quand on travaille de son domicile ou chez ses clients, sans local professionnel ?Et l'exonération des artisans ?Est-ce que ça dépend du chiffre d'affaires ? Doit-il être inférieur à 5000 € pour obtenir une exonération de CFE ?Y a-t-il d'autres moyens d'éviter la CFE ?Les réponses dans cet épisode de podcast !La transcription est disponible sur le blog J'aime la paperasse : https://www.jaimelapaperasse.com/157------Télécharge le livre blanc : Kit de lancement spécial micro-entreprise conçu avec

Aujourd'hui, je vais te montrer comment réduire ou même éviter complètement ta taxe foncière en fonction de ta situation personnelle. Si tu es propriétaire d'un bien immobilier, que ce soit ta résidence principale ou une construction neuve, il existe des solutions pour alléger cette charge. Je vais passer en revue les exonérations, dégrèvements, et plafonnements auxquels tu pourrais avoir droit. Alors si tu te demandes comment payer moins cher ta taxe foncière, cet épisode est pour toi !Voici ce dont on va parler :Exonération pour les revenus modestes : Qui peut en bénéficier et comment cela fonctionne.Dégrèvement de 100 € pour les plus de 65 ans : Une réduction simple, mais efficace.Plafonnement de la taxe foncière : En fonction de tes revenus, tu pourrais réduire significativement le montant.Exonération temporaire pour les constructions neuves : Découvre comment économiser pendant 2 ans.Exonération pour les logements économes en énergie : Si tu as fait des travaux, tu pourrais bénéficier d'une exonération pendant 3 ans.Pourquoi payer ta taxe même si tu fais une réclamation : Pour éviter les pénalités et les majorations.Cet épisode est un guide complet pour comprendre les opportunités d'exonération et alléger ta facture de taxe foncière. Si tu remplis certaines conditions, tu pourrais vraiment économiser !Si tu veux apprendre à mieux gérer ton argent, j'ai écrit un e-book 100% gratuit dans lequel j'enseigne aux femmes comment épargner et investir, tout en comprenant la relation qu'elles entretiennent avec l'argent.Lien pour télécharger mon guide : https://www.vanessamoneyetmindset.com/guideultimeLien pour rejoindre mon groupe whatsapp : https://chat.whatsapp.com/J5obhvDBStkFGzZTiw9VovHébergé par Ausha. Visitez ausha.co/politique-de-confidentialite pour plus d'informations.

La taxe foncière, payée par les propriétaires de logements comme par les entreprises, ne cesse de s'alourdir. En 2024, elle devrait progresser, au minimum, de 3,9 %, certaines villes prévoyant une augmentation pouvant aller jusqu'à plus de 20 %.Elle devient donc une véritable charge pour certains contribuables. Il est cependant possible d'en être exempté. Et d'abord pour des raisons liées à l'âge. Ainsi, les contribuables âgés de 75 ans et plus, au 1er janvier 2024, profitent d'une exonération totale de la taxe foncière.De leur côté, les propriétaires âgés de 65 ans et plus ont droit à un dégrèvement, pour peu qu'ils justifient d'un certain niveau de ressources.En effet, la modestie des revenus permet aussi de profiter de l'exonération de la taxe foncière. Si le propriétaire d'une résidence principale respecte les conditions de ressources, elle est accordée automatiquement, alors qu'il faut en faire la demande pour une résidence secondaire.Pour en bénéficier, il ne faut pas dépasser certains seuils, fixés à 12 455 euros par an pour une part fiscale ou à 19 107 euros pour 2 parts.Les ressources des titulaires de certaines allocations correspondent à ces limites. C'est notamment le cas des bénéficiaires de l'Allocation de solidarité pour les personnes âgées (ASPA), de l'Allocation adulte handicapé (AAH) ou de l'Allocation supplémentaire d'invalidité (ASI).Il est également à noter que les résidents d'une maison de retraite ou d'un Établissement d'hébergement pour personnes âgées dépendantes (EHPAD) peuvent être dispensés de taxe foncière. À condition, toutefois, qu'ils satisfassent aux conditions de ressources prévues et que leur résidence principale soit inoccupée.Enfin, le logement lui-même peut permettre de bénéficier d'une exonération de la taxe foncière. C'est notamment le cas si le propriétaire d'un appartement ou d'une maison a entrepris des travaux de rénovation énergétique.Mais l'exonération n'est consentie que pour cinq ans, au maximum. Elle peut être partielle ou totale et dépend de l'ampleur des travaux réalisés.Par ailleurs, les propriétaires de logements neufs profitent d'une exonération limitée à deux ans. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Dr Salgia discusses how he chooses between tepotinib and capmatinib in patients with stage IV NSCLC harboring MET exon 14 skipping mutations.

"BFM STORY" du lundi au jeudi de 17h à 19h avec Olivier Truchot & Alain Marshall. Deux heures pour faire un tour complet de l'actualité en présence d'invités pour expliquer et débattre sur les grands sujets qui ont marqué la journée.

"Poursuivre dans l'hémicycle un moment d'unité nationale". Voici l'objectif du député Les Républicains Olivier Marleix. L'ancien patron des députés de droite souhaite déposer une proposition de loi visant à exonérer d'impôts, les primes reçues, à chaque médaille, par les champions olympiques français. "Exonérons nos médaillés aux JO et Jeux paralympiques d'impôt sur leurs primes", a-t-il écrit sur X. Dans un document diffusé par Le HuffPost, Olivier Marleix explique vouloir compenser le manque à gagner par une surtaxe sur le tabac.

Ce mercredi 3 juillet, la promesse de Jordan Bardella, le chef du Rassemblement national, d'exonérer de cotisations pendant 5 ans les entreprises qui accorderaient des augmentations de salaires, ainsi que le caractère coûteux de cette mesure pour les finances publiques, ont été abordés par Laurent Vronski, DG d'Ervor, Patrick Bertrand, DG d'opérations d'Holnest, Christian Saint-Etienne, professeur au CNAM et membre du Cercle des Économistes, et Stéphane Carcillo, responsable de la division revenu/travail de l'OCDE et professeur à Sciences Po, dans l'émission Les Experts, présentée par Nicolas Doze sur BFM Business. Retrouvez l'émission du lundi au vendredi et réécoutez la en podcast.

Aujourd'hui Barbara Lefebvre, Bruno Pomart et Mourad Boudjellal débattent de l'actualité autour d'Alain Marschall et Olivier Truchot.

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Featuring perspectives from Dr Justin F Gainor and Dr Karen Reckamp, including the following topics: Introduction: Bringing Research into Practice (0:00) EGFR Activating Mutations (14:01) Exon 20 Insertion Mutations (38:06) MET Exon 14 Alterations (41:49) HER2 Mutations and Overexpression (50:27) CME information and select publications

Dr Paik discusses key findings from the phase 2 VISION trial investigating frontline tepotinib in patients with NSCLC harboring MET exon 14 skipping alterations, real-world data from the TOGETHER pooled analysis of tepotinib vs other frontline treatment options in this patient population, and insights regarding treatment sequencing with tepotinib in pretreated patients in this population.

Viele Verschwörungstheorien sind nicht belegbarer Blödsinn. Aber es gibt tatsächlich nachgewiesene Verschwörungen mit dem Ziel, die Wahrheit zu manipulieren. Einige Konzerne haben immer wieder Studien und die Öffentlichkeit beeinflusst, um ihre Produkte zu verkaufen. // Alle Quellen und weiteren Spezials findest Du hier: https://www.quarks.de/daily-quarks-spezial/ Von Sartori / Sonntag.

Amivantamab Approved by FDA today, March 1! In this episode of Lung Cancer Considered, host Dr. Stephen Liu leads a discussion on the FDA approval of first-line amivantamab plus chemotherapy for NSCLC with an EGFR exon 20 insertion, based on the phase III PAPILLON trial. These data were first shared at ESMO 2023 in Madrid with a simultaneous publication in the New England Journal of Medicine.

Today, on this mid-week special, Oncology for the Inquisitive Mind is delighted to welcome Dr. Jeff Jones, a haematologist, oncologist and the Chief Medical Officer of Cullinan Oncology. Biotech companies are at the forefront of novel drug development, and it is fascinating to take a look behind the curtain and glimpse a small part of how targets are chosen and developed. This includes areas of unmet need, including Exon 20 EGFR mutant lung cancer treatment.Cullinan Oncology conducts research focused on immuno-oncology and translational cancer medicine, specifically focusing on small molecules and biologics to identify unique targets and develop transformative therapeutics across cancer indications.Many thanks to Dr Jones and the team at Cullinan for taking the time to appear on our show.For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

HOST: Hildy Grossman, Co-Host: Jordan Rich GUESTS: Pasi Janne, MD, Ph.D., Director, Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, and the Scientific Director of the Belfer Center for Applied Cancer Research Gabrielle Goodman, HER2 patient Bill Brand, HER2 patient Caren Suesserman, Exon 20 Group Virtual Meeting Leader and Patient Advocate Most people are … Continue reading HER2 BIOMARKER ISN'T JUST ABOUT HER Not Just a Breast biomarker! →

CME credits: 0.25 Valid until: 11-12-2024 Claim your CME credit at https://reachmd.com/programs/cme/keeping-pace-in-lung-cancer-breaking-barriers-advances-in-treating-egfr-exon-20-insertions-in-nsclc/16082/ We now have FDA approved targeted therapies to treat NSCLC with EGFR exon 20 insertion mutations. Drs. Wakelee and Bazhenova discuss the most current data on both approved therapies and drugs in development.=

Minneapolis Fed President Neel Kashkari says policymakers have yet to win the fight against inflation, and that they will consider more tightening if needed. Neil Dutta, Renaissance Macro Research US Economic Research Head, says a rebalanced labor market could led to a rate cut. Katy Kaminski, AlphaSimplex Chief Research Strategist, expects more potential buying for treasuries in the short-term. Mohamed Younis, Gallup Editor-In-Chief, previews the off-year elections happening across several US states. Nadia Martin Wiggen, Svelland Capital Director, discusses the global oil market as prices fall to over two-month lows. Get the Bloomberg Surveillance newsletter, delivered every weekday. Sign up now: https://www.bloomberg.com/account/newsletters/surveillance    Full transcript: This is the Bloomberg Surveillance Podcast. I'm Lisa A. Bromoids, along with Tom Keen and Jonathan Ferrow, join us each day for insight from the best in economics, geopolitics, finance and investment. Subscribe to Bloomberg Surveillance on demand on Apple, Spotify and anywhere you get your podcasts, and always on Bloomberg dot Com, the Bloomberg Terminal, and the Bloomberg Business app. This morning, Mike McKay Drumrow, fantastic guests the random type with us to talk about Fed policy. Yes, and thank you very much, John, because we are pleased to welcome Neil Kashkari, the President of the Federal Reserve Bank of Minneapolis, to the table today. Thank you for coming in making the trip all the way to New York only for us. I'm sure nothing else There would be nothing else this morning, and except for Bloomberg Surveillance. You're kind of known as the guy who is the most hawkish. I don't want to characterize you exactly now, given how things have changed over the last couple of months, but you have left open the possibility of doing more. How much more would you think the economy might need? Are we talking about just that one leftover move from the dot plot in September, or if you have to start raising again, do you have to go farther. Probably. Well, first of all, it's great to see you, Thanks for having me. People are looking for certainty, and I wish I could give that certainty provided there's been so much, so much it's unusual about the reopening of the economy and the dynamics that led to the high inflation, and how long it has taken, and the dynamics as the disinflation process has taken hold. I wish I knew. We have to let the inflation data guide US, the labor market data guide US, just to point out the obvious. Our forecasts have not been great over the past couple of years, and so we just need to We're all committed. Everybody on the FORMC has committed that two percent is our inflation target. We have to get inflation back down to two percent over a reasonable period of time. Ultimately, the economy will tell us how much is needed to get there, And I just don't know. Well, at what point do you think you would believe you have tightened enough or not tightened enough? What is it that you're looking for. Well, I'll give you some good news is that core PC on a three month basis is running about two point five percent, and it's lower than the six month data. It's lower than the one year data. So that suggests that the disinflation is real. If we continue to see inflation numbers of that range two point five percent or lower on a go forward basis, that would tell me, Okay, we are now on a path back to two percent inflation. But three months data is still only three months data, and if we see that start to tick back up again, that would tell me our job is not yet done. Tick back up means what? In other words, we get another couple of CPI reports in a PCE report before your next meeting, a couple of tents higher. The chairman and others say it's going to be lumpy or does it have to be a significant move? In other words, what are you thinking about for December? Well, I think we could look at, as the chairman always says, we look at all of the data. So what surprises Over the past few months, We've been surprised by how strong American consumers have been. Consumer spending is held up remarkably well, we've been surprised by GDP growth. When activity continues to run this hot, that makes me question is policy as tight as we assume that it currently is. So if you saw inflation tick back up and you saw continued very strong economic activity on the real side of the economy, that would tell me, okay, we might need to do more. So it's hard for me to say this one data point needs to be here. I would be looking at the suite of data. Did we outsource doing more to financial markets? In the arts week? Have we outsourced doing more to financial markets? You know, this is a very complicated question on what has been driving the long end of the Yeld curve. Some people point to term premium, and I always joke the term premium is the economist version of dark matter. It's the residual of all the stuff we can't explain. It's not that our models are wrong, it's the dark matter is out there. So that's the term premium. And some people say, well, that's driven by fiscal If it was fiscal driving the term premium, I would have expected to see a week dollar. Usually when investors are worried about a country's fiscal position, their currency weekends our currency has been quite strong. It makes me wonder is it really fiscal driving the term premium. Another possibility is the path of policy over the next few years. That could explain both the stronger dollar and the weaker stock market going into the last meeting. Another one is that maybe the neutral rate is higher, or maybe it's a combination of all three of these. And so these are things that we're spending a lot of time trying to understand what the markets are doing. But just speaking for myself, I'm not comfortable saying which of those three it is, because which of those three it is determines what it means for policy. If it is the term premium, then it is doing some work for the FED. But if it's the neutral rate, or if it's the forward guidance of the path of policy, then we would actually have to follow through to preserve those rates. So how did this line end up in the statement? And I'll share it with that audience. The kind of financial and credit conditions for households and businesses are likely to wound economic activity, hiring, an inflation. Where's that coming from? Oh, that's been there for a long time. I mean, that's been in there since the Silicon Valley bank episode and the banking stresses leading to some tightening of credit conditions across the economy. So I think that that's right. I, for one, don't say that that means the recent moves in the old curve. How fluid is that assessment? Can that change from month to month, meeting to mating, because some of those comments around that has inspired quite a move in this market over the last week. Well, you know, one of the things about the statements, we always have to be careful about putting things into the statement because they tend to be long lived and it's hard to pull them out of the statement because as soon as you take something out, then all of a sudden, people say, oh my gosh, they're declaring that all the banking stresses are over, as an example, and so, you know, I would look at all of the range of commentary that you get, look at what the chairman says, look at his press conference to get a read of the thought of the committee. You said that people want certainty that you can't give it to them, and I understand that, but people don't just want certainty, they also want some sort of guiding philosophy. Do you think that Fed Shir Powell has outlined some sort of guiding philosophy and where the bar is to cut rates and where the bar is to raise them further. Well, I think he's articulated very clearly that we're committed to getting back to two percent inflation. Right. There's been some chatter amongst economists that maybe we should raise the inflation target. I think he's done a great job saying that is not on the table. We're not going to do that. We're going to get inflation back to two percent, and we're going to let the data guide us. We've moved very aggressively. We've made a lot of progress on inflation. We're not done yet, meaning inflation is not back to our target, and if we need to do more, we will. There seem to be a feeling in markets that the bar to cut rates has been lowered over the past week or two weeks. Suddenly not only are we reaching a pause and have we seen a peek in the FED funds rate, but that also the Fed will cut next year, maybe surgically. Neil Dada is talking about that and he's coming up next. Do you want to push back against that? Do you think that the bar to cut is still just as high as it was. I have no idea where market participants are getting that. There's no discussion amongst me and any of my colleagues about when we're going to start preparing to cut rates. The only thing that's been talked about at all is that at some point, when inflation is well on its way back down, if we didn't back off a little bit, then real rates would be getting tighter and tighter and tighter. And that's real, but that's math. But is there enough weakness currently in the market in the economy, I should say to give you that sense at this point, look at the last GDP print. I mean, does anybody look at that and think, oh, my gosh. The economy we for the last twelve months GDP has been very strong. The labor market continues to be quite robust. Yes, the unemployment rate is ticked up to three point nine percent, but we've also seen a huge surge of labor supply, which is really positive come online. So I'm looking at this, I'm seeing consumers that are strong. My air by the way, my airplane that I came here on was one hundred percent full yesterday. It's going to be one hundred percent full today, I'm not seeing a lot of evidence that the economy is weaken Well, whether you go higher or not, you are on board for longer. And so you must have modeled out some idea of how long you would need to leave rates unchanged before you could get down to a level low enough that you could take your foot off the break a little bit. How long do you think you'll be at five point five into twenty twenty four. Well, I think it's going to depend if we continue to see inflation prints similar to the ones we've seen the last few months, you know, and we end up with a year of a year at two point five percent core inflation and it continues to trend down, that constellation would give me evidence to say, hey, we ought to look at should we start backing off just so the real policy isn't getting tighter and tighter and tighter, because we're clearly on our way back down to two percent. But again, I don't want to just point to one data series. We will be looking at the suite of data to try to get a read of where the economy is headed. Well, not just data. You talk to businesses in your district, all the time, What are they telling you now about their view of growth and hiring and pricing going forward. It's moderating. So the labor market is still tight in my district, people especially in the Dakotas, really have a hard time finding workers. But in Minnesota, it's still a tight labor market, but it's not as tight as it was six months ago. It's not as tight as it was a year ago. So that kind of maps to the national data that we're seeing of a gently cooling labor market but one that's still very very warm. Same thing with economic activity. Depending on the sector, they're saying, Hey, we feel pretty good about things. We're a little cautious about the future. Obviously, they watch the news, they read the news. There's a lot of economic anxiety that is reported on that people, you know, factor that into their own thinking and their own business planning. So I think the outlooks are still optimistic, but it's cautious optimists. Well are they still raising prices or think they need to? So it's funny there Still they still buy and large have some pricing power more than they had before pandemic, but not as much pricing power as they had six months or a year ago. Can we finish on housic sure in the space of three years, we've had record low interest rates in the highest rates in several decades. Is this housing market broken? Well? I think since the pandemic, we have structurally underbuilt the number of units that we need to meet our growing population. And that's the factor. And that's really about regulation at the local level that are creating barriers to more supply coming in. The raid environment will settle out over time, but structurally we have to actually bring a lot more supply online to meet America at the time, but it could be like twenty thirty years. I think this is the issue here. The legacy of this FMC could well be a generation of people look down to the housing market. Why do you say that there could be a generation of people with two three percent mortgages that never sound their home. Yeah, I don't know. People end up needing to move. It's funny when people don't tell their home because they're locked into a low mortgage. That's less supply, but that's also one less buyer. Most people who buy homes are leaving another home, and so that affects both the supply side and the and the demand side of That's why I set a generation look down because I'm renting and count by, so I'm not sounding anything, and that's the generation. I'm talking about that generation specifically, you concern that could be the legacy at the FORMC. Now. I think the legacy of this FMC is that we've dealt with the pandemic very aggressively. Then we were surprised by very high inflation, but then we move very aggressively to bring the inflation back down. I want to ask you about a story on the Bloomberg terminal today about all the financial CEOs from the US over in Hong Kong sounding very doer and down about the prospects for the economy. They suggest that things are pretty fragile right now, both in the economy and the markets, given everything that's going on around the world and in the shadow banking system as well as theirs. How worried are you, well, I mean, we're always worried about things that can happen all around the world. We've got teams of people looking at different scenarios around the world. Ultimately, we have to focus on what we can control, you know, geopolitics. When Hamas attacked Israel, the first thing we thought of is what's it going to do to the oil market, what's it going to do to commodity prices. Remarkably, the response so far has been muted. But that's something we're obviously paying close attention to. But the broader geopolitical issues are just so far outside of our bounds of forecasting. You know, we have a hard enough time forecasting inflation trying to forecast where geopolitics is going. We just have to focus what we can control. Oil price is dropped. I mean, that's the crazy thing about the last month. Physically, it doesn't make any sense. And this is the reason why trying to get it right is just impossible. And then trying to get the idea of a FED put and whether they're going to respond. I'm just saying people are talking about that now, so yeah, talking about it in the last few hours. Yes, it's on this program. No, always a pleasure, Thank you, Sirving Neil, Cash County, the Minneapolis FED price Alongstide Plympecks, Mi M chab No Tatsa, the head of US economic research at Renaissance Macron. Nil, good morning to you. Good morning. Let's go straight there because my IB was lighting up with messages from you. We're not thinking about tapering. Two months later, we're a long way from neutral cutting a month later. What do you think is going on within the FBC. Where do you think this is going? Well? I think I agree that it doesn't pay much to forecasts right now. It's important just to look at the data as it's coming to you, and so I do sympathize with that. But at the end of the day, I mean, the unemployment rate is up above the fed's forecast for this year, and that's the first time that's happened since March of twenty twenty two. Now you know we're in. When you're in the thick of it, it's hard to know whether that represents the start of something much more onerous or whether it's just the normalization of the labor market. But I think for the FED, I think the doves on the FMC, and remember you know President Kashkari, he tends to lean on the hawkish side of the consensus at the FED. I think for the doves, they have all the ammunition they need to basically put the hawks in a casket. Okay, I mean, I think that's the way I would think about it. I mean, you can point to the pickup in productivity and what that's done to unit labor costs. You can point to what Powell has said, right, I mean, when when central bankers use proceed carefully risk management, that's code for doing nothing. And you know, finally, I mean the employment report was probably understating payroll growth. That's my view. I mean, there's a lot of strike activity and so far, but at the end of the day, average hourly earnings are running just over three percent at an annual rate over the last several months. So I don't think the hawks on the committee frankly, can use the labor markets as a rationale to be hawkish anymore. So that is over and so I think the doves can basically say that the labor markets have been rebalanced. And if they can say that just implicitly, it means that the door is a little bit cracked open for a cut. And you know, the point I'm making to you is, you know J Powell, it wouldn't be the first time he basically, you know, flipped on a dime. I mean, we're a long way from neutral. I mean a few months later he's cutting rates, We're not even thinking about thinking about tapering or hiking, and then we're hiking and tapering basically in the same month. So you know, to me, the fact that they're not talking about it is irrelevant. It's also in their sep for next year. The question is whether these surgical cuts, what are surgical cuts? Basically a few cuts to stabilize the economy. I mean, I think the issue is is the extent to which cutting quickly translates into rapid economic stable So I mean, for as an example, I mean, let's see what happens with mortgage purchase demand. Over the next couple of weeks. We've seen mortgage rates basically come down to what like seven percent. Okay, I'm trying to wrap my head around this. Six months ago, you were talking about way more economic strength in the US economy than people had expected. Now you're talking about strategic or surgical cuts by the Federal Reserve to stabilize the economy. Are you saying that they are warranted because the economy No, I don't think that they are. Part of the tention, Lisa, is that my job isn't to tell people what I think the Fed should do. My job is to try to get into their head and figure out what they will do. I mean, if I was there, would I be I would probably be more hawkish than the consensus on the FMC. But I'm not there. Well, but does this mean that you think the consequence of surgical cuts to fortify the economy will be prolonged inflation? Yes? Okay, So then how do you sort of arrange around that sort of what is the inflation rate? How do you sort of lean into the rally that we've seen in the bond market and say, wait a second, you guys have gotten ahead of your skis based on the game theory that the FED is playing and the way that they're likely to do Searga, I don't know that the bond market's getting ahead of itself. I think the bond market is sniffing out that the distribution of risks have changed. I don't know what the FED may do next. I mean, that's what I think the bond market is doing, and I think bond market investors are right to do that, because, as I say, you know, you think about it basically three prongs, right, the labor market, inflation, and then financial conditions. If the FED can look at the labor market and say the labor markets are rebalanced. Okay, that's check done. You can't use that anymore as a reason to be hawkish. So, if anything, if the unemployment rate's not going up a little bit, the distribution of risks are that they would cut because the labor markets. And right, if the labor markets are thawing, that's going to give them increased confidence that inflation will thaw and so and then finally, if that's the case, they're not going to be particularly concerned about the easing and financial conditions that you've seen since the last in the last week, which is what we've been talking about through this morning, whether they are going to tolerate the easing we've seen over the last week. And it feels like perhaps they will help me work with me here. It feels like to me that you believe the world might have changed post pandemic versus pre pandemic. Do you sense that they still believe were still in the same old world pre pandemic? I do. I mean, I mean, if you listen to someone like New York Fed President John Williams, even Chair Powell, I mean, there's not much there's quite a bit of reluctance to just say that, you know, neutral rates are higher. I mean, why do you think that, is, Neil? You know, I don't know. I mean I think that maybe in their minds things haven't changed. I mean all, I mean, you saw Powell talk about this at at the press conference last week. I mean, oh, well, if we get to pick up in potential growth, it's a temporary pick up and potential growth, then we'll go back down. So if you don't think that the world has fundamentally changed, then you're going to be more sort of cognizant of overtightening risk. Right Like, So if the unemployment rate is starting to go up, you may have thought, well, maybe you overdid it, so you might be more willing to cut sooner as a result. So are you more bullish on the US economy but also expect inflation to remain higher and the FED When people look back, this will be considered a policy air that they weren't hawkish enough. Yeah, I mean I think that that would be Yeah, I mean that would be something I could be saying in twenty twenty five. What would you point to if you had this conversation right now? And I would love to get you around the table next time I have a FED official to work through somebody's issues. But what would you it sounds dangerous as the number one thing that indicates to you that the world has changed, versus pandemic that ultimately they don't believe it. What would you point to, Well, I mean the first is just look at let's look at the obvious. I mean, you've done a lot, and yet the economy is still kind of hanging in there. I would say that things like household formation rates are running twice the rate they did after the Financial crisis. I mean, to me, I think it's much easier to tell the story about why the post financial crisis period was actually the anomaly than not. So I think we're actually going back to the old normal more so than anything else. Obviously, you think about all those people during the financial crisis period or the years after that, we're saving up for retirement. A lot of them have now since retired and they're now dissaving, which is you know, implies higher neutral rates. You think about income inequality, it was something that we were talking about all throughout the twenty tens. Well, it's coming down now. People at the lower end of the wage spectrum. We're seeing more rapid growth in their wages. You see more increased sort of union activity and unions getting big wins for blue collar workers. I mean, these are not things. I mean, and those folks have a much higher propensity to spend. And so I think it's it's not right in my view to say that things haven't changed. But if that's what the FED believes, then you have to be recognizing what that implies for what they might do later. And so I think just because they're not talking about cuts now does not mean they won't be talking about cuts in three six months. That should be in the realm of possibility, and I think the market's Frankly, I'm not willing to fight the move yet. I mean, okay, no a clinic as always. You know you're one of my favors. I think everyone knows that. No data, every nice loose Macro, No, thank you joining guess now. Katy Kaminski, chief research strategist over Alpha Simplex. Katie, it's the number one question for us. Are you still short treasuries? Yes? Why? Well, this is because for trend falling, it's not just about a couple of days, It's really about persistent trends in the market, and I just want to point out, and this is something interesting, trend falling signals have been net short for nine quarters. This is the first time in many decades that this has been the case. And so the reason I'm pausing right now is because we've been saying short, short, short all year, and for the first time, it's starting to feel like we already got that short come through. What's next? What does the market do now? Buy are coming in because yields are at interesting levels. They're probably thinking, maybe we've finally hit that point. Do you think something changed fundamentally to lead to that in the last few weeks. I do, And then I think that the data has come out to support the narrative for investors. But I also think a narrative that has made sense to me is that investors have woken up to the idea that five percent yields at some point there's a buying point where you think, well, there's a chance this could actually go down. And now you start to see this equilibrium occur where you're seeing the disinverted curve, which is something we've been looking for since the beginning of the year. So Katie just to put a bow on this, are you now not short treasuries and actually starting to see value, particularly if yields get up to that five percent level in the tenure. So we're still short in terms of the overall frequency that we see signals, but we are seeing consolidation in those signals, so there's a reduction in that particular conviction. But what I will say is that I'm seeing more and more positive signals on higher frequency, and so I think on the shorter term you're going to see more and more potential buying for treasuries. But I do want to remind everyone inflation is still an issue. Rates could be higher for longer, so there's still really a good chance that we're going to see a lot of volatility instead of a new trend per se that starts to emerge. Yet this raises this question of which particular data points are going to be the real action drivers, like what we saw over the past ten days. Is it going to be basically every inflation read that we get, or do you really buy into this idea that it's treasury supply that's been dictating a lot of the volumes and a lot of the angst that we felt over the past month. It's really interesting that you bring this up, Lisa, because we've been talking about the supply issue. I mean, how often do people actually talk about supply. They're only talking about it because I think people are trying to understand the equilibrium of where people sit and what yield should cost, I mean, what should be the right yield. And I think from our side on the technical side, what we're looking for is potential breakouts so that we're seeing a steeper curve at some point. Our view is it's going to depend on really what happens with the economic data of whether we end up with tighter conditions or if we actually see something very extreme where we actually saw higher yields. Again, that to me seems very unlikely right now, but I think it's really a point to start watching every data point to see which direction the yield market is going to go or which direction the yields go, because it's definitely an inflection point than Katie, were going to catch up with Nil Kashgari in about twenty minutes time. I think we're all looking forward to this conversation. There is this second paragraph in the statement that they put out last week on kind of financial conditions it reaches follows. I'm sure you're familiar with it. Time of financial and credit conditions for households and businesses are likely to weigh on economic activity, hiring, and inflation. Could you still write that same sentence today? After the move we've seen in the last week, what's that on the movement we've seen in the last month, for the the last six months, what do you think it is? Well? I think the challenge is that these numbers come in at different frequencies. Last week we had a massive buying but this could also be somewhat of a relief rally given how much movement we've seen downward, especially in equities. And let's just be honest, like I said, at a five percent yield started to get exciting, people said, oh I better get in there. So I think there's really still This could just be the tip of the beginning of understanding how serious financial conditions have changed, and if it's enough to actually warrant a point where we might actually have cuts at some point earlier than some would would have thought, like myself, who's been very pessimistic about rate cuts. Hey, Ketty, do you have a decent understanding of the conditions that would lead to those cuts. Well, usually in terms of this, I think we'd have to see pretty severe deterioration in financial conditions to see rate cuts, given the mandate of the FED and the fact that the other factors that are really focused on have not come down to their target level. So the fact that inflation is sticky, and the fact that we have a strong workforce and that we have all of these conditions putting us in a good place. They have been pretty clear that they're going to keep us higher for longer until we can sort that out. On the other hand, if we had some sort of very severe draw down or deterioration and credit that was clear, I think that they would have to act. So that to me would be the situation where we would see those rate cuts. Is if you saw something in the credits markets or something in terms of consumers really struggling that would cause them to actually react. So the FED put still exists, just at a much higher pain point, I would say probably yes. I mean, I think it always exists somewhere, but it's definitely moved a lot compared to what we liked in twenty nineteen and before. Kelly Let's finish what we started. Given the uncertainty you now have about your position, why maintain the shot? That's what I'm going to walk away from this conversation scratching my head about why maintain the short when it can be as expensive as it was on weeks last week. So this is the point of trend falling. Systematic trading is about not double sort of using your emotion in the moment. And I think what works with trend falling is following the data, and we just need more data to know the answer, and over longer periods of time, it turns out the market is actually quite good at giving us indications of where things are moving, and it's particularly short term movements where they disagree. Where you want to lean on your own gut, but you shouldn't, because that's what systematic trading is really about. It's about measuring and falling the markets and allowing the markets to tell you what the market where we're going, as opposed to sort of my own personal view. Unfortunately, Katie, thanks for the clarity on that point. I appreciate it. Katie commenced you that of aphasimplex, two major political parties remain unpopular in the United States, fifty six percent of Americans viewing the Republican Party unfavorably, fifty eight percent saying the same thing of the Democratic Party. Mohammed Junis, the editor in chief at Gallop, joined us now, Muhammad, help us out. I've been rinting through this piece. Neither party is well liked. You guys have pointed out that the GP has an edge on certain issues. Can we just talk about the likability of both parties right now, Muhammed? How unusual is this? Unfortunately, you know at harkens to your Amtrak conversation earlier. We're at a state right now in the United States when both parties are really not doing that great in terms of their favorability. It's nothing new, Unfortunately, It's been quite a while since Americans had a favorable view of either party in the majority. We're also at a time where there's a record high of Americans saying that they'd like to see a third party in American politics. Of course, easy to say I want more. It doesn't necessarily mean that that party would exist or actually be powerful. But we're also at a time, John and Lisa where there's a high of people that identify as independents, and that is important not only in the current moment, but also in our analysis over generations. What we find is that younger Americans today are actually sticking with that independent id much further along their lifespan than previous generations young folks. So, certainly America is highly dissatisfied with national government. We've talked about that a lot. They're really, in some ways most dissatisfied with both parties. That being said, today is a local election. It's really, I know, it's so tempting for us to jump to twenty twenty four. Americans line up today to vote on local issues, and there's a huge difference in the way people perceive local government versus the national government here in the United States. SOMEHOWMA just explain that a little bit more. What is the big difference between the two currently? Basically and coetence. Americans have very low trust and competence in the national government and national institutions. Perceptions of corruption are astronomically high. When you come to local government, though, people have a much more positive perspective on local government, whether it's the efficacy, transparency of local government and corruption, but also how they feel about their local governing officials. So Americans light up at the ballot box today, they're hearing a lot of echo chamber on the national what this means, we're twenty twenty four, but really what they're going to be focusing on our local issues, and the national conversation certainly will inform that. That's why things like abortion, things that implicate attitudes about big and small government, for example, they're on the ballot box. They will be discussed. They're going to be they have been a focus of the campaign. We know in Ohio there's a really big push on abortion. It'll be a really important weather vane in terms of whether or not Roe v. Wades overturning has sort of faded, The impact of that has faded or is still with us. I have to say, as you're talking about local elections and how different they are than the nationals, I think, well, they're probably not on TikTok, the local elections, they're probably not on Facebook. How much is it the social media echo chamber that polarizes people and gives them a worse and expected view of national politics in a way that local politics might be slightly immune. I think that's a great point. Lisa it's much easier to sort of check the bs if you will. On a topic or an issue. When it's about where you live, you know that reality. You have direct information from people you know where you live. You can talk to your neighbors, you can talk to your local religious leaders or community leaders. With national politics, it's a very different thing. It really tends to have now become sort of a war of the propaganda's if you owe both parties where truth is very hard to identify, but both sides are absolutely out there to religiously convict you excuse me, to religiously convert you to their worldview. So that's certainly a factor. But look, when it comes to twenty twenty four, and it's important for us to keep our eye on that mark. Everything that we've done with regards to national elections really comes down to one thing. Americans focus on the economy. The economy is king. It's not only king, it's king, queen and bishop when it comes to picking a president here in the United States. And that's going to be a huge factor in where people place their votes in November twenty twenty four. But as you all know, we are light years ahead from where that is in terms of assessing where the economy is going to be then, and that's going to be the major factor when it comes to party advantages. The Republicans definitely have maintained their historic advantage in terms of Americans viewing them as more competent in keeping the country prosperous, keeping the economy booming, and keeping the country safe. That's said, how much are you looking to Glenn Youngkin today? And maybe there is going to be very much local issues that are decided, but the local issues have implications for their glens might be the Republican con candidate for presidency. Do you think that's a stretch. I think looking at the polls right now, that is a stretch. It's hard to argue that President Trump is not the front runner of the Republican Party. You know, every poll you do, every poll, what we've done. We don't do too many political polls anymore, but there are good polls out there. It's really hard to see somebody sort of astronomically jump ahead of him. Now that being said, we haven't had a president in modern time that's facing the legal challenges that he's facing, and that's a whole other sort of curveball that's being thrown here. It's not clear exactly what his situation will be come real. Kind of rubber meets the road in terms of November twenty twenty four. But you know there are still we heard from David Axelrod this week about the Democratic side. There's still a lot of movement in this race, and I wouldn't rule out any surprises or sudden departures on either side up against the clol kid. Just to squeeze it in and finished where we started. You do mention in the piece of the GP holds advantages on certain issues. Can we just bring some life into that, Mohammad? Which issue specifically? There are really three issues In specific one is keeping the country prosperous. Republicans have a pretty sizable advantage to Democrats in terms of perceptions of keeping the country prosperous. The other one is keeping the country safe. As you know, we're now very focused on too pretty significant conflicts across the world. Hopefully that doesn't become a reality for us here in the United States, but as Americans focus more on security issues, Republicans do have that advantage in our polls. The final one is who's most competent to handle the most important problem facing the country. And what's fascinating about that question is that the most important problem facing the country, as I have said on this show many times right now, is actually poor leadership and government. So Americans identify the quality, the low quality of national le as the most important problem facing the country. So it's the most of our problem. The economy and keeping America safe fascinates in gright. To catch out Mohammed azoh Wis, He's going to say, Mohammed unus of gallop. Everyone's been pointing to oil prices. Why have they not caught up given that there is a sort of existential risk and threat that seems to be escalating every single day in the Middle East? Joining us now to help us understand what exactly to look for. Nadia Martin Wiggan, Director ats fell in Capital, Nadia, I just want to start there. What do you make of the fact that we're seeing crude traded on the NMEX blow eighty dollars a barrel again today despite what's going on in Israel and in Gaza. Hello, great to be on. I think what we saw last week is that Hezbollah and Iran for right now, they're on the sidelines, right, They don't actually want to show an escalation of the war going on in Gaza right now. So that has taken off some of the risk premium. For the last ten days, we actually see the implied volatility in the options market come down. So it's not even something that's happened just today, it's been for the last ten days that trend. I think. In addition, when that premium, that initial shock goes away, as we saw was the case with the war in Ukraine by Russia, eventually you know, the market starts to think about how to work around that. And for example, we've seen that freight rates have gone much higher, and part of that is when you look at it, it's almost like a risk balancing that, Okay, if we can't flow through the Suez and we have to go around, then let's de risk ourselves if things were to take longer. And we see that the freight market has actually priced that in as if they have to avoid the Suez, which they haven't had to do. So as a result, things have come down also in the oil market. Okay, so let's take a step back for a second. Nadia. If you're looking at freight producers, that already come up with alternate roots that avoid the suz Canal to avoid potential or the straits of our moves to avoid potential blowback from Iran. Does this mean that oil prices are actually higher than where they would be at this point if there weren't this geopolitical overhang, because it's actually being priced into the market in a material way. Yeah. If we look at what was happening to the market in oil before the October seventh attack, we could see that prices were coming off right. We had a lot of pressure on refinery margins. We had physical creed trading poorly. You know, we've had the largest overhang in the West African market that we've had in years. We had more than twenty twenty five million barrels unsold out of the November loading program. So we saw that kind of weakening and then this is where the market would like to rebalance. We saw the physical premiums come down for those grades, but the futures market has remained quite strong, and this is where we have to see that kind of reb ballancy. When we look at kind of the momentum and what is happening to pure speculative traders, you know, the CTAs and so forth. That short term momentum has been downwards, right, and that is put pressure bringing us down to where we are now in WTI, you know, just above the two hundred day moving average. If we look at that long term momentum, it's still intact for a strong market, right. So there are still those longs in the market that we've had in since before all of this started. But again, the market is preparing in case something were to happen, because you know, things had been taking along well in the Middle East and we were about to have a deal between Saudi Arabia, the US and Israel recognizing Israel, which would take off potentially a premium right, and instead we've moved in the opposite direction. How much is the US becoming the swing producer at a time where there is consolidation in the shale patch and you are seeing companies try to realize the value from their stores, basically pump the oil while it's still valued in the world. The deal of Exon, for example, buying Pioneer right, that really shows that they are focusing on the Permian right. And what interestingly Exon announced in their earnings call is that they believe that with their equipment and knowledge, they're able to bring in a total of one billion barrels of oil more out of those same assets that Pioneer was able to. So, when we think about the terminal regular production rate in the US, that goes from around fourteen and a half million barrels per day to maybe fifteen and a half million barrels per day, and the question is when do we reach that. Right August production was thirteen point one million barrels per day. It will probably take two years, but of course that depends on the short term oil price and the signals short term meaning monthly, quarterly, and the signals that that yields to shale producers in terms of activity. Right, a weaker oil price will slow that down. A strong oil price we'll speed that up. So right now, given more prices are do you expect more consolidation to be expedited currently or do you think that people are going to wait until prices go up a bit further. Well, prices are reasonably strong, right, the whole oil complex is in a good situation and making money. So when what we saw at the start of October is that demand was starting to get hit, right, we had producers selling crewed for more than one hundred dollars a barrel, and then we saw, for example, companies like India really complaining. Part of that is because Russian crudis continued to flow and we had price caps breached, right, so you were paying more than sixty dollars a barrel, maybe you were paying seventy dollars a barrel, and then on average, facing more than one hundred dollars a barrel was becoming difficult. So I think we've been in a pretty comfortable space, you know, in the eighty dollars range for everyone to make money, so it makes it ripe for consolidation and valuable resources. We don't really need things to move much higher. Do you think that all things being a well, this is going to be the range for the foreseeable future, just because of the pushes and the pulls that seem to be working in equilibrium from a technical level, yes, But of course things can suddenly change very quickly, both in the Middle East, you know, towards the negative towards a positive, so that can really shift things. And the number one thing to keep track of is that inventories were expected to draw quite steeply in the fourth quarter, and so far in October they only drew on land around three hundred thousand barrels per day. So the market is waiting for evidence that actually we have tightness led by these supply cuts and demand isn't waning, Whereas you know, on the other hand, if it continues waiting, then we could see for the falls and price. Nadie Martin Wigan of Spell and Capital, thank you so much for being with us. Subscribe to the Bloomberg Surveillance podcast on Apple, Spotify, and anywhere else you get your podcasts. Listen live every weekday starting at seven am Eastern on Blueberk dot com, the iHeartRadio app tune In, and the Bloomberg Business app. You can watch us live on Bloomberg Television and always on the Bloomberg terminal. Thanks for listening. I'm Lisa Abramowitz, and this is Bloomberg.See 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Bonne nouvelle pour les personnels travaillant dans le secteur de l'hôtellerie-restauration : leurs pourboires continueront à être exonérés d'impôt sur le revenu et de prélèvements sociaux.La mesure, en effet, n'est pas nouvelle, puisqu'elle date du 1er janvier 2022. Elle a donc été reconduite pour 2024, pour soutenir un secteur durement touché par les conséquences de l'épidémie de Covid.Les pourboires en question sont les gratifications données directement par les clients, mais aussi celles qui sont incluses dans l'addition, au titre du service. Les pourboires en espèces ne sont pas les seuls concernés. Ils sont aussi inclus dans la mesure s'ils sont versés au moyen de la carte bancaire.Une limite est tout de même apportée à cet avantage fiscal. En effet, les pourboires qui y donnent droit ne peuvent dépasser 20 % du salaire annuel brut du salarié. Ceci pour éviter que ces pourboires ne finissent par prendre la place, du moins en partie, de son salaire.Une mesure reconduite en fonction de son efficacitéCette reconduction de la défiscalisation des pourboires a été bien accueillie dans les milieux concernés, qui la jugent toujours nécessaire. En effet, si le secteur de l'hôtellerie-restauration a pu surmonter en parie les effets de la crise sanitaire, elle se trouve aujourd'hui menacée, comme d'autres d'ailleurs, par la reprise de l'inflation.Toutefois, les professionnels relativisent la portée de cette mesure. En effet, même si le pourboire est toujours considéré comme l'un des avantages du métier, son usage est moins courant.De fait, la plupart des clients réglant leur note par carte bancaire, ils n'ont pas toujours des pièces de monnaie à laisser en pourboire. D'où cette demande, faite par la profession, de pouvoir inclure le pourboire dans l'addition.La reconduite de la mesure au-delà de 2024 est pour l'instant incertaine. Elle dépend du contenu du rapport qui doit être remis au Parlement avant le 1er octobre 2024.Il doit en effet apprécier l'efficacité de la mesure. Elle ne sera pas jugée telle, notamment, si les pourboires se raréfient ou si, au contraire, ils tendent à se substituer en partie aux salaires. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Bonne nouvelle pour les personnels travaillant dans le secteur de l'hôtellerie-restauration : leurs pourboires continueront à être exonérés d'impôt sur le revenu et de prélèvements sociaux. La mesure, en effet, n'est pas nouvelle, puisqu'elle date du 1er janvier 2022. Elle a donc été reconduite pour 2024, pour soutenir un secteur durement touché par les conséquences de l'épidémie de Covid. Les pourboires en question sont les gratifications données directement par les clients, mais aussi celles qui sont incluses dans l'addition, au titre du service. Les pourboires en espèces ne sont pas les seuls concernés. Ils sont aussi inclus dans la mesure s'ils sont versés au moyen de la carte bancaire. Une limite est tout de même apportée à cet avantage fiscal. En effet, les pourboires qui y donnent droit ne peuvent dépasser 20 % du salaire annuel brut du salarié. Ceci pour éviter que ces pourboires ne finissent par prendre la place, du moins en partie, de son salaire. Une mesure reconduite en fonction de son efficacité Cette reconduction de la défiscalisation des pourboires a été bien accueillie dans les milieux concernés, qui la jugent toujours nécessaire. En effet, si le secteur de l'hôtellerie-restauration a pu surmonter en parie les effets de la crise sanitaire, elle se trouve aujourd'hui menacée, comme d'autres d'ailleurs, par la reprise de l'inflation. Toutefois, les professionnels relativisent la portée de cette mesure. En effet, même si le pourboire est toujours considéré comme l'un des avantages du métier, son usage est moins courant. De fait, la plupart des clients réglant leur note par carte bancaire, ils n'ont pas toujours des pièces de monnaie à laisser en pourboire. D'où cette demande, faite par la profession, de pouvoir inclure le pourboire dans l'addition. La reconduite de la mesure au-delà de 2024 est pour l'instant incertaine. Elle dépend du contenu du rapport qui doit être remis au Parlement avant le 1er octobre 2024. Il doit en effet apprécier l'efficacité de la mesure. Elle ne sera pas jugée telle, notamment, si les pourboires se raréfient ou si, au contraire, ils tendent à se substituer en partie aux salaires. Learn more about your ad choices. Visit megaphone.fm/adchoices

References Molecular Neurobiology 2022. volume 59, pages 4223–4241 Hum Genet. 1994 Jan;93(1):67-73 Mol Cell Biol. 2012 Jan;32(1):126-38 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Ce mercredi 4 octobre, la fin proche de l'exonération fiscale pour les retraités européens résidant au Portugal a été abordée par Benaouda Abdeddaïm dans sa chronique, dans l'émission Good Morning Business, présentée par Laure Closier et Christophe Jakubyszyn, sur BFM Business. Retrouvez l'émission du lundi au vendredi et réécoutez la en podcast.

Depuis le 1er janvier 2023, la taxe d'habitation touchant la résidence principale est supprimée pour tous les contribuables. De ce fait, la taxe foncière devient une des principales ressources des municipalités. Dès lors, on peut comprendre que, d'après l'Association des maires de France, près de 20 % des villes de plus de 40.000 habitants songent à l'augmenter en 2023. Titulaires de minima sociaux et personnes âgées Certaines personnes, cependant, peuvent se voir exonérer de taxe foncière. Il s'agit d'abord des titulaires de certaines prestations sociales. C'est notamment le cas des personnes recevant l'Allocation de solidarité aux personnes âgées (ASPA) ou l'Allocation supplémentaire d'invalidité (ASI). Dans ces deux cas, l'exonération est accordée sans condition de ressources. En revanche, les revenus des titulaires de l'Allocation aux adultes handicapés (AAH), qui ont également droit à cette exonération, sont pris en compte. L'âge est également un facteur pris en considération. Ainsi, les contribuables âgés de plus de 75 ans peuvent être exonérés de taxe foncière. À condition, toutefois, que leurs revenus ne dépassent pas un certain plafond. Il est plus élevé pour la première part que pour chaque demi part supplémentaire. Même si ce plafond est dépassé, l'exonération peut être encore accordée pour deux ans. Il est à noter que, dans un couple, l'âge ou le handicap d'un seul des deux conjoints suffisent à donner droit à cet avantage. Les autres cas d'exonération D'autres personnes encore peuvent bénéficier d'une exonération de la taxe foncière. En effet, les propriétaires de logements neufs ont droit à une exonération durant les deux ans qui suivent l'achèvement des travaux. L'exonération est accordée aussi bien aux personnes ayant acheté un logement neuf qu'à celles ayant eu recours à la vente en l'état futur d'achèvement (VEFA). Sont aussi éligibles les logements ayant fait l'objet de gros travaux de rénovation. Certaines villes, assez peu nombreuses pour l'instant, exonèrent également de taxe foncière les propriétaires entreprenant d'importants travaux de rénovation énergétique. Dans ce cas, l'exonération peut être accordée pour une durée de trois ans. Learn more about your ad choices. Visit megaphone.fm/adchoices

Depuis le 1er janvier 2023, la taxe d'habitation touchant la résidence principale est supprimée pour tous les contribuables. De ce fait, la taxe foncière devient une des principales ressources des municipalités.Dès lors, on peut comprendre que, d'après l'Association des maires de France, près de 20 % des villes de plus de 40.000 habitants songent à l'augmenter en 2023.Titulaires de minima sociaux et personnes âgéesCertaines personnes, cependant, peuvent se voir exonérer de taxe foncière. Il s'agit d'abord des titulaires de certaines prestations sociales.C'est notamment le cas des personnes recevant l'Allocation de solidarité aux personnes âgées (ASPA) ou l'Allocation supplémentaire d'invalidité (ASI). Dans ces deux cas, l'exonération est accordée sans condition de ressources.En revanche, les revenus des titulaires de l'Allocation aux adultes handicapés (AAH), qui ont également droit à cette exonération, sont pris en compte.L'âge est également un facteur pris en considération. Ainsi, les contribuables âgés de plus de 75 ans peuvent être exonérés de taxe foncière. À condition, toutefois, que leurs revenus ne dépassent pas un certain plafond. Il est plus élevé pour la première part que pour chaque demi part supplémentaire.Même si ce plafond est dépassé, l'exonération peut être encore accordée pour deux ans. Il est à noter que, dans un couple, l'âge ou le handicap d'un seul des deux conjoints suffisent à donner droit à cet avantage.Les autres cas d'exonérationD'autres personnes encore peuvent bénéficier d'une exonération de la taxe foncière. En effet, les propriétaires de logements neufs ont droit à une exonération durant les deux ans qui suivent l'achèvement des travaux.L'exonération est accordée aussi bien aux personnes ayant acheté un logement neuf qu'à celles ayant eu recours à la vente en l'état futur d'achèvement (VEFA). Sont aussi éligibles les logements ayant fait l'objet de gros travaux de rénovation.Certaines villes, assez peu nombreuses pour l'instant, exonèrent également de taxe foncière les propriétaires entreprenant d'importants travaux de rénovation énergétique. Dans ce cas, l'exonération peut être accordée pour une durée de trois ans. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

A new editorial paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Latest updates on MET targeted therapy for EXON 14 mutations in lung cancer.” In their new editorial, researchers Mira Al Jaberi, Wolfgang Clough and Samir Dalia from Mercy Hospital discuss the MET gene. Several alterations in the MET gene were identified as targetable oncogenic changes leading to non-small cell lung cancer (NSCLC). These include genomic amplifications, exon 14 skipping mutations and fusion. Capmatinib has been considered as a first-line treatment for patients with NSCLC carrying a MET exon 14 skipping mutation since May 2020 by the USFDA. A study newly published in early 2023 showed that Crizotinib, a tyrosine kinase inhibitor, was also effective for MET fusions, which occur rarely in 0.2–0.3% of patients with lung cancer. A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance. “A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance [4, 5].” Several structurally different MET tyrosine kinase inhibitors (TKIs) have been developed or are under clinical evaluation. TKIs are categorized into type I TKIs (type Ia: crizotinib; type Ib: savolitinib, capmatinib) and type II TKIs (cabozantinib, glesatinib, merestinib). Combination therapy reduces resistance and enhances clinical outcomes. “These clinical trials along with others will show us if other MET inhibitors or combination therapy may be better than the current standard of care.” DOI - https://doi.org/10.18632/oncotarget.28419 Correspondence to - Samir Dalia - samir.dalia@mercy.net Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28419 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, non small cell lung cancer, MET mutation, targeted therapy, precision medicine About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Go online to PeerView.com/AYJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this engaging and animated activity, an expert on EGFR exon 20 insertion–positive NSCLC discusses the role of biomarker testing and examines the evidence for new and emerging therapies to offer patient-centered guidance on individualizing care and improving outcomes. Upon completion of this activity, participants should be better able to: Discuss the heterogeneity of EGFR mutations in NSCLC, frequency and characteristics of EGFR exon 20 insertion mutations, latest evidence and guidelines on targeted therapies in this setting, and importance of biomarker testing to identify patients for these therapies in clinical practice; Apply multidisciplinary strategies for biomarker testing and targeted treatment selection and sequencing to optimize therapeutic outcomes in patients with NSCLC harboring EGFR exon 20 insertion mutations; and Engage patients with EGFR exon 20 insertion–positive NSCLC in shared decision-making regarding available targeted therapy options to ensure individualized treatment selection that aligns with their needs, values, and preferences

Go online to PeerView.com/AYJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this engaging and animated activity, an expert on EGFR exon 20 insertion–positive NSCLC discusses the role of biomarker testing and examines the evidence for new and emerging therapies to offer patient-centered guidance on individualizing care and improving outcomes. Upon completion of this activity, participants should be better able to: Discuss the heterogeneity of EGFR mutations in NSCLC, frequency and characteristics of EGFR exon 20 insertion mutations, latest evidence and guidelines on targeted therapies in this setting, and importance of biomarker testing to identify patients for these therapies in clinical practice; Apply multidisciplinary strategies for biomarker testing and targeted treatment selection and sequencing to optimize therapeutic outcomes in patients with NSCLC harboring EGFR exon 20 insertion mutations; and Engage patients with EGFR exon 20 insertion–positive NSCLC in shared decision-making regarding available targeted therapy options to ensure individualized treatment selection that aligns with their needs, values, and preferences

Go online to PeerView.com/AYJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this engaging and animated activity, an expert on EGFR exon 20 insertion–positive NSCLC discusses the role of biomarker testing and examines the evidence for new and emerging therapies to offer patient-centered guidance on individualizing care and improving outcomes. Upon completion of this activity, participants should be better able to: Discuss the heterogeneity of EGFR mutations in NSCLC, frequency and characteristics of EGFR exon 20 insertion mutations, latest evidence and guidelines on targeted therapies in this setting, and importance of biomarker testing to identify patients for these therapies in clinical practice; Apply multidisciplinary strategies for biomarker testing and targeted treatment selection and sequencing to optimize therapeutic outcomes in patients with NSCLC harboring EGFR exon 20 insertion mutations; and Engage patients with EGFR exon 20 insertion–positive NSCLC in shared decision-making regarding available targeted therapy options to ensure individualized treatment selection that aligns with their needs, values, and preferences

Go online to PeerView.com/AYJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this engaging and animated activity, an expert on EGFR exon 20 insertion–positive NSCLC discusses the role of biomarker testing and examines the evidence for new and emerging therapies to offer patient-centered guidance on individualizing care and improving outcomes. Upon completion of this activity, participants should be better able to: Discuss the heterogeneity of EGFR mutations in NSCLC, frequency and characteristics of EGFR exon 20 insertion mutations, latest evidence and guidelines on targeted therapies in this setting, and importance of biomarker testing to identify patients for these therapies in clinical practice; Apply multidisciplinary strategies for biomarker testing and targeted treatment selection and sequencing to optimize therapeutic outcomes in patients with NSCLC harboring EGFR exon 20 insertion mutations; and Engage patients with EGFR exon 20 insertion–positive NSCLC in shared decision-making regarding available targeted therapy options to ensure individualized treatment selection that aligns with their needs, values, and preferences

Go online to PeerView.com/AYJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this engaging and animated activity, an expert on EGFR exon 20 insertion–positive NSCLC discusses the role of biomarker testing and examines the evidence for new and emerging therapies to offer patient-centered guidance on individualizing care and improving outcomes. Upon completion of this activity, participants should be better able to: Discuss the heterogeneity of EGFR mutations in NSCLC, frequency and characteristics of EGFR exon 20 insertion mutations, latest evidence and guidelines on targeted therapies in this setting, and importance of biomarker testing to identify patients for these therapies in clinical practice; Apply multidisciplinary strategies for biomarker testing and targeted treatment selection and sequencing to optimize therapeutic outcomes in patients with NSCLC harboring EGFR exon 20 insertion mutations; and Engage patients with EGFR exon 20 insertion–positive NSCLC in shared decision-making regarding available targeted therapy options to ensure individualized treatment selection that aligns with their needs, values, and preferences

Go online to PeerView.com/AYJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this engaging and animated activity, an expert on EGFR exon 20 insertion–positive NSCLC discusses the role of biomarker testing and examines the evidence for new and emerging therapies to offer patient-centered guidance on individualizing care and improving outcomes. Upon completion of this activity, participants should be better able to: Discuss the heterogeneity of EGFR mutations in NSCLC, frequency and characteristics of EGFR exon 20 insertion mutations, latest evidence and guidelines on targeted therapies in this setting, and importance of biomarker testing to identify patients for these therapies in clinical practice; Apply multidisciplinary strategies for biomarker testing and targeted treatment selection and sequencing to optimize therapeutic outcomes in patients with NSCLC harboring EGFR exon 20 insertion mutations; and Engage patients with EGFR exon 20 insertion–positive NSCLC in shared decision-making regarding available targeted therapy options to ensure individualized treatment selection that aligns with their needs, values, and preferences

Dr. Navneet Singh highlights the latest evidence-based recommendation updates from the ASCO living guideline on stage IV non-small cell lung cancer with driver alterations. This update focuses on new second-line options for patients with advanced NSCLC and an EGFR exon 20 insertion, including amivantamab and mobocertinib. Dr. Singh also discusses updated results from CodeBreaK 200 and the option of second-line therapy with sotorasib for patients with advanced NSCLC and a KRAS-G12C mutation. Read the update, “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.2” and view all recommendations at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.01055  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.   My name is Brittany Harvey, and today I am joined by Dr. Navneet Singh from the Postgraduate Institute of Medical Education and Research in Chandigarh, India, co-chair on “Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2023.2.” Thank you for being here, Dr. Singh.  Dr. Navneet Singh: Thank you for having me, Brittany. Brittany Harvey: Before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the Guideline panel, including Dr. Singh, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into this living clinical practice guideline, Dr. Singh, this living guideline for systemic therapy for stage IV non-small cell lung cancer with driver alterations is being routinely updated. What new studies were reviewed by the panel to prompt an update to the recommendations in this version? Dr. Navneet Singh: So for this 2023 version 2 update, three trials were included. These include two studies which involved patients with exon 20 insertion mutations, who had received prior platinum-based chemotherapy and subsequently were treated with either amivantamab in the CHRYSALIS trial or with mobocertinib in the EXCLAIM trial. The third trial which formed the basis for this update was one which involved patients with KRAS G12C mutation who had previously received systemic therapy and subsequently were treated with sotorasib. And this was the CodeBreaK 200 trial. Brittany Harvey: Understood. So then, based on these three new trials that you've just mentioned, what are the updated recommendations from the expert panel for patients with advanced non-small cell lung cancer? Dr. Navneet Singh: For patients with advanced NSCLC with an EGFR exon 20 insertion mutation and an ECOG performance status of 0 to 2 who have received prior platinum-based chemotherapy, clinicians may offer amivantamab or mobocertinib as monotherapy. It is important to mention here that in the absence of head-to-head comparison of amivantamab or mobocertinib with each other or with other standard second-line therapies, no recommendation for sequencing can be made and therefore treatment should be individualized. Now, use of either of the two drugs is based on low-quality evidence and has a weak strength of recommendation. And the updates for treating KRAS G12C-mutated NSCLC is largely similar; that patients who have received prior systemic therapy may be offered sotorasib.  Brittany Harvey: Thank you for reviewing those updated recommendations. So what should clinicians know as they implement these new recommendations and how do they interface with the existing recommendations? Dr. Navneet Singh: It is important for clinicians involved in the management of EGFR mutant lung cancer to realize that exon 20 insertions are the third most common group of EGFR mutations and comprise approximately 5% of all EGFR mutations. Now, historically, the EGFR targeted drugs which have been the first, second, or third generation tyrosine kinase inhibitors have largely shown efficacy for the two common types of EGFR mutations, namely the exon 19 deletions and the exon 21 L858R point mutation. Exon 20 insertion mutations thus did not have any effective targeted therapy so far. But now, both of these drugs, amivantamab and mobocertinib, have shown very promising results for pretreated patients with this molecular aberration and therefore may be used in view of standard second line therapy. Similarly, in the case of KRAS G12C mutation, before this, there was no effective targeted therapy, but now sotorasib, based on the CodeBreaK 200 trial, appears to be a very valid option in view of standard second-line therapy.  Brittany Harvey: Excellent. So then, what do these new treatment options mean for patients with stage IV non-small cell lung cancer and an exon 20 insertion or a KRAS G12C mutation?  Dr. Navneet Singh: For patients with stage IV NSCLC and harboring an EGFR exon 20 insertion, the availability of two specific targeted drugs will improve the treatment options available following standard first-line therapy. Furthermore, ongoing trials for these agents in the treatment-naive setting may eventually lead to a scenario wherein such patients may be treated upfront with targeted therapy rather than chemotherapy or chemoimmunotherapy, analogous to how patients with the common EGFR mutations are treated. The ultimate aim of precision medicine is to offer the most effective treatment based on biomarker expression and targeted therapies in comparison to chemotherapy because these lead to better treatment outcomes and lesser side effects. Brittany Harvey: Absolutely. The goal of better outcomes with less side effects is what we're looking to achieve here. So then, finally, as this is a living guideline, what emerging therapies or targets is the panel monitoring for future guideline updates? Dr. Navneet Singh: As was already said, the expert panel eagerly awaits data from ongoing trials which are assessing the efficacy of drugs targeting the EGFR exon 20 insertion mutations, namely amivantamab and mobocertinib as first-line therapy, as also the drugs which target the KRAS G12C mutations which is sotorasib and adagrasib in the treatment-naïve setting. Ultimately, the optimal sequencing of therapies needs to be established in advanced and metastatic non-small cell lung cancer for several of the oncogenic driver alterations other than classical EGFR mutations and ALK and ROS-1 rearrangements. These include the EGFR exon 20 insertions and other uncommon EGFR mutations, the BRAF V600E, KRAS G12C, the HER2, and the MET exon 14 skipping mutations as well as the RET and NTRK fusions.  Brittany Harvey: It sounds like the living guideline expert panel will be busy moving forward then. So I want to thank you so much for your work to update this living guideline and thank you for your time today, Dr. Singh.  Dr. Navneet Singh:  Thank you so much, it was a pleasure being here. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.  

Cell & Gene: The Podcast Host, Erin Harris, welcomes Romesh Subramanian, Ph.D., CEO of Ascidian Therapeutics, a Boston-based biotech focused on rewriting RNA to the pod. During the episode, Subramanian defines RNA exon editing, and they discuss the differences between RNA exon editing and gene editing. With current programs in ophthalmology, neurological and neuromuscular disorders, as well as rare diseases, Subramanian explains the overwhelming potential of RNA exon editing. 

In this episode of Lung Cancer Considered, host Dr. Stephen Liu leads a discussion on a specific subset of lung cancer: EGFR exon 20 insertion NSCLC. Joining the podcast are distinguished panel of clinicians and lung cancer advocates: Dr. Rosario Garcia Campelo, the Head of Medical Oncology and the Thoracic Tumor Unit Chair at the University Hospital A Coruna, Spain. Marcia Horn, executive director of the Exon 20 Group and CEO of ICAN, the International Cancer Advocacy Network. Yonsei University College of Medicine, Professor Byoung-Chul Cho, Director of the Lung Cancer Center at Yonsei Cancer Hospital in Seoul, South Korea.

Dr. Shannon Westin and her guests, Dr. Paul Frankel, Dr. Judith Karp, and Dr. Robert Maki discuss how to better inform patients of the risks involved in phase 1 clinical trials. TRANSCRIPT Dr. Shannon Westin: Hello, everyone, and welcome to another episode of the Journal of Clinical Oncology After Hours podcast, where we do a deep dive on manuscripts that are published in the Journal of Clinical Oncology. We're so excited to have you all here today. I am your host, Shannon Westin, GYN Oncologist at MD Anderson Cancer Center, and it's my great pleasure to serve as the social media editor of the JCO and the host of this podcast. Today we are going to be discussing a very important manuscript titled “Ethics and Clinical Research: Improving Transparency and Informed Consent in Phase 1 Oncology Trials”. And I'm joined today by several of the authors, as well as one of our editors that helped to review this paper. But before I start, I'll note that none of our authors have any conflicts of interest to disclose. And with that, I'd like to introduce our guests. First is Dr. Paul Frankel. He's a research professor at the Division of Biostatistics, Department of Computational and Quantitative Medicine, at the City of Hope National Medical Center. Welcome. Dr. Paul Frankel: Hello and thank you. It's a great honor to be here today. Dr. Shannon Westin: Also with Dr. Frankel is Dr. Judith Karp, who is Professor Emerita of Oncology and Medicine at the Johns Hopkins University School of Medicine in Baltimore, Maryland. Welcome. Dr. Judith Karp: Thank you. And I echo exactly what Paul said. Thank you for having me. Dr. Shannon Westin: And then finally, our esteemed Associate Editor of the JCO, Dr. Robert Maki. He's a professor of hematology and medical oncology, a physician leader in developmental therapeutics, clinical leader of the Sarcoma program at the University of Pennsylvania. Dr. Robert Maki: Hi, Shannon. Thanks for having me on the program. Dr. Shannon Westin: Well, it's awesome to have this star-studded group of guests. We are going to try to cover as much details about this important paper as we can in a short period of time. But I encourage you also to check out the JCO to read the paper in full. So first, let's level set. As we start this discussion around phase 1 trials and ethics, maybe, Dr. Mackie, can you start by giving the basics of just phase 1 trials just to make sure everyone's on the same page? Dr. Robert Maki: Sure, absolutely. Since we have people who are listening from different walks of life, that's for sure. Clinical trials in cancer run anywhere from phase 1, 2 to 3. There are also such things as phase 0 and phase 4 trials. But the primary ones we'll discuss today are phase 1 trials. These are the initial tests, be there a brand-new drug never tested before in people, or it might be testing a new combination of treatments, or it might be looking at an already approved drug or an experimental drug in a new population of patients. Let's say you wanted to take a look at a drug in an elderly population. There aren't any data about that in people who are, let's say, 80 or older, and that would constitute a phase 1 trial. The idea of the trial is to start with low doses of a medication and increase the doses in a systematic way, tracking the side-effects that occur with treatment, and then come to an answer as to how you should move forward with the medication in future trials to determine whether the drug is actually active or not and in which setting. The important point, I guess, in that sense is that a phase 1 trial isn't necessarily looking at whether a drug is useful or not, really just looking at the toxicity of the agent or new combination or new setting overall. Dr. Judith Karp: If I could add one thing to that, and I think this is something that has evolved—well, it's evolved over the last 30 years, but in terms of practicality and application, it's really over the last 10 years, roughly speaking. It's also, I think, the opportunity to identify potentially informative biomarkers through a series of pharmacodynamic studies. I'm an old leukemia doctor, and so I've had that capability, if you will, with our diseases because they're so accessible. But I think there's been a new emphasis on that over the last decade. And it's an important one because it becomes a tool for stratifying in phase 2 and ultimately for identifying, hopefully, in a prognostic fashion, who is potentially likely to respond versus not. And if it's a versus not, then you go in a different direction once you got a bunch of—or if you're lucky enough to have a bunch of different directions. Dr. Robert Maki: It's a really important point about looking at so called pharmacokinetic and pharmodynamic markers. How long is the drug staying in the body? What is the body doing to the drug? What is the drug doing to the body? Judith is right on the mark. You can get leukemia cells right out of the body, oftentimes take a look at them directly, whether you're actually hitting the target you think you're hitting. This is a really great place to—and it's often mandatory to get pre- and post-treatment biopsies, even in solid tumor patients, to know if you're actually hitting your target of interest. So, yeah, if you're not achieving that much, then you shouldn't really be moving the drug forward. Dr. Shannon Westin: I agree. And it's so critical because, as we've seen, you know, to your point, Dr. Maki, about the true goals of a phase 1 trial, I think we've done a lot better job of trying to ensure there is efficacy or trying to clarify for whom we are getting efficacy. And I think we all are aware of several drugs that have gotten approvals from an extended so-called phase 1, right? An appropriately selected population. And certainly that's something new over the last five, six, seven years that we've been able to do that. But things like PARP inhibitors in BRCA-mutant populations and TRK fusion inhibitors like Larotrectinib and others in those with NTRK fusions just come to mind kind of quickly. And even more so, we're seeing these focus drugs, right, that are focused on abnormalities in a specific—Exon, like the G12C inhibitors and things like that. So it is interesting to see how drug development is kind of changing in the phase 1 space where we're trying to move that efficacy potentially up earlier and earlier, just to Dr. Karp's point about that biomarker development. So I think it's a really exciting time. Okay, so the next piece I wanted to just make sure, again, to ensure that we're all on the same page, is these are very common trials, I'd say, and certainly the foundation of drug development. Do one of you want to give an estimate of approximately how many phase 1 trials are ongoing currently and maybe how that's changed over time? Are we seeing more phase 1? Less phase 1? About the same? Dr. Paul Frankel: Yeah, I can take a look at that. The number of phase 1 studies that are currently accruing patients today in oncology is around 4500, something like that. I think there's 4451 open clinical trials and phase 1 clinical trials in oncology today. If you look at, let's say, in May of this year, there was 4263. So you're seeing it's increasing. But if you want to look at really the increase, you can look at between 2000 and 2010. There were a little bit over 5000 phase 1 clinical trials that had started in that period, that 10-year period. If you look at the next 10-year period, 2010 to 2020, it's over 10,000 that started. So the number of phase 1 clinical trials is very large, and it's increasing at a rapid rate. And these do set, as you mentioned, the foundation for all the studies that subsequently follow. Dr. Judith Karp: It's very interesting to me that Paul has these numbers in his head. I am not as quantitative as Paul, but we have these increasing numbers of trials, and yet the percentage of patients who go on those trials has not increased at the same rate. There's still that gap where now for children with leukemia—actually, for children with cancers, it's 90%. 90% of those children go on clinical trials. But for adults, it's still around 8 or 10%. It's unfortunate. Dr. Robert Maki: It's a really good point. There really should be more adults being put on clinical trials. But by the same token, not every adult is appropriate for a clinical trial. Let's say you have—there are things you can do that are clinical trials that aren't treatment either. And if it's data collection or patient-reported outcomes, something that we really don't have a lot of information of in a broad manner, there certainly are clinical trials, even if you're getting standards of care in which patients can be enrolled. So you're certainly speaking to a group of people who espouse and promote clinical research wherever it can be done. Dr. Paul Frankel: These clinical trials, I think, are often the best opportunity that patients have. And even though we're going to be talking about issues with consent and other issues with regard to phase 1 clinical trials, they still remain the best option for patients in almost every situation, if you can get on them. Dr. Judith Karp: Yeah. I just think of them as… Dr. Shannon Westin: Yeah, and I think we could have a whole ‘nother podcast of how to expand an exclusion criteria to allow for those patients, but maybe we'll bookmark that for another episode. Paul, you kind of started mentioning, I think, the last place to level set before we get into a little bit more detail from the paper that you all wrote is from regards to informed consent. Can one of you, or more than one, review the importance and challenges of this process for our listeners? Dr. Judith Karp: I'll take a stab at that one. I think the importance of informing a patient, however well we can do it, of what we expect to happen and what we know and what we know we don't know is a very important part of the contract between the physician and the patient. And it's really a partnership, especially for phase 1 trials, where we really know so little. And what we do know is that the patient—these are for treatment trials. We know that there is no therapy widely available for that patient that's going to do that patient any good. So we have to enter into a partnership with the patient to say, “We're going to try something. We know this little bit. We don't know this huge amount.” And so I think that that's really the importance, just ethically, to have the patient be informed. In terms of the challenges, I think that—this is certainly not politically correct, but were I on the receiving end, on the patient end, and somebody gave me a 35-page document to read, I would not for many reasons. In some ways, it's too much information. Most patients are not, by definition, medically sophisticated. That's one. Two, they don't want to read 30 pages. They're either going to sign it, or they're not. And it's confusing. And, yes, you can say to a patient, “Look, take this home, read it, come back in a week, call me in a week,” whatever. There are many instances, certainly in the leukemia field, where you can't do that. You don't have that luxury. So I think that that is a real challenge that we really haven't addressed. And in the good ol' days when all of us physicians really sat down and talked to the patient, then I think that the challenges were much less. And I think that that's key. Dr. Robert Maki: Yeah. I mean, Judith, AML over age 65. You're not going to get most people into remission, and you've got a captive audience because there they are with low counts. And what are you going to do next? We all, in our research, want to follow the Belmont report. We want to respect people. We're looking for studies that offer beneficence, that do no harm. We can't really do no harm a lot of the time, but we can at least minimize harm. And I think it's where the consent process kicks in. And justice, the third tenet of the Belmont report, being sure that we're using well-considered procedures as part of the research. All those are part of those beautiful words that you used, “partnership” and “contract,” that I think are really important in developing that bond with the individual patient who you're going to treat is super critical. Dr. Judith Karp: Yeah, absolutely. And in some senses, the only real informed consent is if the patient has been through it before. Dr. Shannon Westin: Right. Dr. Paul Frankel: So one of the things making it even more challenging, all these challenges exist throughout. And one of the focuses of our paper is that there's been an increasing trend to use designs that specifically target toxicity rather than limit toxicity during the dose finding of the phase 1 study. And so that introduces a whole ‘nother aspect to the consent process. So if you look at those studies, the most common toxicity target, as noted by others, is a 25% DLT rate. And if interpreted directly, that means that these risk-targeting designs, they claim to aim to find the dose where one in four patients are expected to experience a severe or a life-threatening adverse event in the first cycle of therapy, which is usually 28 days. And that's despite dose modifications. And further, most of these designs consider it a positive feature if a large percent of the enrolled patients are treated near the target. Now, whether this is really what the physicians want or not is separate. But one way or the other, what we have noted in our paper is that our collective experience that the actual toxicity target, the targeted risk, whether it's 20%, 25%, or even 33%, is not disclosed to the patient in the initially submitted consent forms that we see. That is a fundamental change in the way we've designed studies, but it requires that we adapt the consent process to this very challenging problem. Dr. Judith Karp: Along those lines, you're talking about toxicity. Any treatment that targets a non-itchy skin rash has got to be a lot less toxic than a drug that is targeting refractory ovarian cancer or leukemia or what have you. And the disease itself is toxic. So I think there has to be a way to approximate and weigh those toxicities, the toxicity of the treatment versus the toxicity of the disease, because the disease is not benign. Dr. Shannon Westin: One of my mentors, Dr. Razelle Kurzrock, used to always say, “The worst toxicity is progression of cancer.” And I completely—that's a very wise woman. But I think it's a really good point. And I think, just to kind of summarize what you all were saying, if we're targeting a certain toxicity level, we just need to make sure that patients are aware of that. And many of them might be willing and would probably be willing to take that for that potential benefit and things they might get out of it, but we need to be more transparent on that kind of individual protocol level. Would you say that's…? Dr. Paul Frankel: That's the critical thing is to be transparent about these things. And certainly certain different treatments which have maybe more curative potential, certain types of diseases, they're going to be more amenable to a higher toxicity threshold. But it depends on the intent of the therapy, and these need to factor into the decision of what's being used, what kind of target and kind of design is being used. That's kind of part of the issue of transparency is once you get that in front of the patient and the physician and they discuss it, you're likely to get people to agree if it's at least a reasonable target. Dr. Robert Maki: The toxicity targets up from some of these Bayesian designs, oftentimes they're kind of guardrails to ensure there's not too little or too much toxicity on a trial. I think people are using more of the rules-based designs, this risk-targeting design, than the classic three plus three simply from the inability to come up with an adequate dose-escalation scheme using three plus three simply from the fact that you're just looking at the prior three patients. If you look at a lot of the kinase inhibitors that have been approved over time, even when they're FDA approved, drugs like lenvatinib or cabozantinib, even in the phase 3 trials, patients had to have their dose reduced two times out of three. And it really speaks to something went awry in the development of these agents if they really were looking for a 16% DLT rate in a classical sense, which is what you get from that three-plus-three design, one out of six people. It's pretty crazy that two thirds of people in a larger population need that dose reduction. So perhaps by putting better guardrails with one of these rule-based designs, we'll actually end up with a schema for treatment of a patient that ends up being more appropriate. Dr. Judith Karp: It would be very interesting, actually, to examine how often we're wrong. It might be very easy. 100% of the time, I would imagine. But how often the so-called RP2D turns out not to be that. And even with phase 3 trials, you never really know a drug until it's out on the street and thousands and thousands and thousands have been treated with that drug or combination. Paul, maybe that's our next study. What do you think? Nah, I can tell you don't like it. Dr. Shannon Westin: This is kind of getting at what Project Optimus is trying to do, right, is getting away from that idea that we have to get to the max dose and instead look at long-term tolerability. And yeah, Robert, I've given quite a bit of lenvatinib and pembrolizumab in my clinic to patients with recurrent endometrial cancer. You can see that that max dose is not the ideal dose for a lot of patients. Now, there are some patients that tolerate just fine, but 70% grade 3/4 toxicity is legitimate, and making sure we're protecting patients from that is really critical. And I want to cover a few more things before we wrap up. I guess we've talked a little bit about what to do on an individual protocol level. Do you all have some recommendations about what can be done at the research/enterprise level to kind of address the issues that we've been discussing today? Dr. Paul Frankel: One of the issues is, if you look at, let's say, clinicaltrials.gov, you'll see that there's very few studies that have both a model consent form or the protocol on clinicaltrials.gov. And I think if you look at all the clinical trials, the number that have both, you can count on one hand. So the question is whether or not there's a way to systematically evaluate whether the consent form is appropriate, whether the target is reasonable, that kind of thing. And it's very hard to do when you don't have a way to assess that information in a systematic way. So one thing that can happen is that the registries could require a model consent form where they could ask for it, encourage it, one way or the other. It's just a simple document. The other thing that they can do is make sure that the protocol summaries, if the design uses a DLT targeting method to at least state what the target is in the protocol summary, that would help quite a bit. And then you can go through and see if this is reasonable or if this has been communicated in the consent form in particular. And so that's one thing that can happen on the enterprise level that would help considerably. Dr. Judith Karp: The only thing I would add to that is that I think a model consent form, a template, is it's surprising that it hasn't been done yet, although, as you say, it's not easy with all of these studies being done by government and pharma and other enterprises. But that has to be modulated for the disease that's being targeted and for the drug. You can't have the same thing for cell cycle cytotoxic agents and immunotherapy because they're totally disparate. And you can't have the same thing for leukemia and breast cancer. The pathogenesis may be the same, but the phenotyping is not. So that's the only thing I would add. Dr. Robert Maki: The patient population involved as well can certainly impact that. Greater or poorer performance status, susceptibility to complications, all that figures into that consent form. So it's not an easy thing to prepare, at least in a coherent way that a patient is going to understand, especially, as you were saying there, with a 40-page tome that reads at somewhere between grade levels 11 and 14. How do you expect a patient with, let's say, an 8th or 9th grade reading level to fight their way through that if they really wanted to understand the side-effects. It's kind of like the teacher in the Charlie Brown cartoons: “Wah wah wah wah, wah, wah, wah, sign here.” So there are many challenges. Dr. Paul Frankel: There's no question that this is a minimum requirement. Having a written consent form is just an absolute minimum. But the conversation that needs to take place, the communication, that's a whole ‘nother level that I think the physicians are better able to address. But it's just the minimum requirement to have something in the document, and it doesn't make the document longer to communicate the targeted risk in some of these studies. There's really no extra effort that's being asked. I mean, the model consents exists. The DLT targeting is stated in the protocol. It's all fairly simple. Dr. Robert Maki: Yeah, it'd be another line or two, wouldn't it? It's just saying here's what our expected rate of toxicity is. And uploading, whether you're a cooperative group, whether you're an industry, whether it's an investigator-initiated trial, some sort of redacted consent form makes a lot of sense. You may not have to have the grid of activities, which oftentimes is now included in one of these cumbersome documents, but at least the description of the treatment and the toxicity would be at least something everybody could agree to. Dr. Judith Karp: Yeah, some kind of a precede or a FAQs, frequently asked questions. What is this? Why are we doing this? Very simple. Dr. Robert Maki: And that's now mandated, I think. They said at NCI, they insist that we have a summary of the trial, and one page or page and a half at the beginning of that long document. That, to me, has been incredibly effective, as have been things like a little drawing of patient and going one randomization and things like that. Simple means can really be powerful, especially on those first two pages before the eyes glaze over. Dr. Judith Karp: Exactly, yeah, a little CONSORT diagram or something like that, very nice, schema. Dr. Shannon Westin: This has been a really awesome discussion, and I think the bottom line is we need to increase our transparency. And it seems—I don't know, after this discussion, I feel like it's a pretty straightforward ask. Are there any downsides to being transparent? I know we've already talked a little bit about patient burden and how we don't think that would add much to that piece. Dr. Judith Karp: The fear that might exist, that, “Oh, my God, if we really tell them what we're going to do, they're not going to do it. They're going to say no.” I don't think that's realistic. I think patients, especially for phase 1, we're dealing with a population of people for whom there is not a reliable, effective therapy available. These patients know that. Many times they've been through rounds and rounds of chemotherapy or immunotherapy or surgery already. So many patients say, “Just give it to me, and I'll sign it.” And you say, “No, no, no, you must read it.” So they say, “Okay, I'll read it. Where do I sign?” Dr. Robert Maki: Done. Exactly. But it's a really important point that I'd also like to highlight, that phase 1 trials aren't just for the patients with performance status 3, very sick. You can certainly impose those earlier in a patient's course, especially in situations where there is not a randomized trial, for example, showing evidence of survival benefit. Short of that, I tend to be more aggressive about putting patients in earlier lines on phase 1 trials simply because it provides more options for them. Dr. Judith Karp: Yes, and I think a good example, as you had brought up, Robert, earlier, the older patient with AML, maybe a myelodysplasia-related AML. There are lots of things you can do, but none of them work. And so is it an opportunity to look at improving the hypomethylating agents where you get a 25% response rate, not much in terms of complete remission, and a year survival, maybe a year and a half survival. Can you improve on that if you add a drug that interrupts the survival pathway targeting BCL? Can you do that? The answer has been yes, but the only way to get there is to do the phase 1 trial initially and then move up the trial schema. Dr. Robert Maki: To your question, Shannon, though, the administrative burden is a small one. It's uploading a document, adding a little bit more to a consent form. It should not be a deal breaker, I would think. Dr. Paul Frankel: There's plenty of burdens on the research team. We certainly don't want to increase that at all, and I don't think this does. One of the questions you mentioned are the downsides of transparency, but some of the upsides also: by having the physicians have more discussion with the patient on some of these issues in a more transparent and lay language, I think, increases the understanding between the physician and the patient. And the physician can take that back to the statistician who's designing the study with the physician and say, “Hey, maybe we need to reconsider this.” There's some upsides in a variety of ways. Transparency and discussion are only going to be improving the ultimate product. And we certainly don't want to find drug doses that end up being a program drug death or unnecessarily hurting patients. Either one are totally unnecessary and unacceptable. Dr. Shannon Westin: Well, great. I think you've made a very clear call to action. I think the last question is how do we get this done besides raising awareness and just kind of setting the bar, right? Because I know, coming from my standpoint as a clinical trialist, it's not something we think to put into the informed consent as we've transitioned to this more risk-targeting type of trial, which I think, as you mentioned, is becoming much more common and over, like, the three plus three and things like that. How do we implement this? Too big of a question? You're like, “You tell me.” Dr. Judith Karp: We, as physicians, have removed ourselves from patients in so many ways. And how do you get it done? You sit down with the patient. And listen, I'm no saint, and none of us are saints, and we all have other things that we have to do, and there are—you know, we're pressed for time and this and that the other. But much of this, yes, full transparency, you have a 20%, a 25% chance of having a dire consequence. That doesn't mean that you will. If you do, it's 100% in you, right? But there's got to be a communication part that goes with it. That's personal. You can't just do it on paper. You need to do it on paper, but you gotta do it with people, too. Dr. Robert Maki: And the discussion point around potential toxicity, all of the visits, extra visits you might have to make, what extra work you might have to go through, versus, let's say, supportive care only if you are at that point. That is an incredibly important point to make to patients, that you really have exhausted many therapies. Is it best just to go with supportive care for whatever time is left? Because this certainly is rolling the dice. You're going to have some side-effects. And what's the chance of benefit in a phase 1 trial? I think that it's higher now these days, simply from the ability of immunotherapy to intervene on so many different diseases. For example, our success rate is higher than the 5% that's quoted previously, but it's not a home run in any case. And we don't want to take away hope, but we also don't want to give false hope. And I think with Paul's paper and your paper have really pointed out how important it is to have that discussion around the degree of toxicity you might have to expect. Dr. Judith Karp: Absolutely. Absolutely. Dr. Shannon Westin: Well, great. I just want to thank you all for such a lively discussion. I learned a ton, and I hope that our listeners did, too. I do want to remind our listeners to check out this paper, “Ethics and Clinical Research: Improving Transparency and Informed Consent in Phase 1 Oncology Trials,” published in the JCO. And also check out other episodes of the JCO After Hours podcast to learn more. So thank you all again and have a wonderful day. 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.  

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we continue our discussion on metastatic non-small cell lung cancer, focusing on NSCLC with driver mutations. * The approach to treatment of a patient with widespread metastatic NSCLC (mNSCLC) is very different than a patient without distant disease, which highlights why we do what we do:- Important to complete staging (discussed in prior episodes) to determine the extent of disease- Important to check molecular testing (looking for mutations in the cancer cells) and IHC for tumor proportion score (TPS) helps determine treatment options - If your molecular testing is identified in a driver mutation gene, there are targeted options for this! *Driver mutations are predictive of response to an oral therapy and a LACK of response to immune therapy (particularly in EGFR and ALK mutated patients) * EGFR Mutation:- Pay attention to the types of mutation in EGFR (not all are the same):-- Exon 19 deletion -- Exon 19 L858R-- Exon 21 T790M-- Exon 20 Insertion (Osimertinib [see below] cannot be used for this mutation)- Osimertinib is first-line standard of care for patients with EGFR-- Used to be a second-line agent. Many patients with EGFR mutations receiving earlier generation TKIs would develop resistance and when these tumors were sequenced, they would have Exon 21 T790M mutations. Osimertinib was effective even with this mutation and had superior overall survival data compared to chemotherapy (AURA3 Trial)--Now it is used in first-line setting for patients with EGFR mutation based on the FLAURA trial --- In this study, patients received osimertinib as first line vs. older generation EGFR-targeting TKIs (erlotinib or gefitib) and Osimertinib had better outcomes: ---- Showed that the median OS was 38.6 months with Osi vs. 31.8 months; also improved brain penetration! ---- Also effective in patients with metastatic disease to the brain: ----- Only 6% of patients had CNS progression with Osi vs. 15% with others- What if a patient is on Osi and later develops new brain mets?-- If there is progression within just the brain (and good control in other sites of the body) you can refer patient to Radiation Oncology for SRS-- Remember, based on discussion with Dr. Osmundson in our RadOnc lectures (Episode 028), it is important to HOLD Osimertinib if patient is going to get radiation to minimize the side effects- What is patient had progression of disease in several sites throughout the body?-- Management is less straightforward. -- In many of these cases, you can consider:--- Consolidative radiation - If small amounts of disease--- Changing therapy - If there has been widespread progression; likely would change to chemotherapy (without IO, since lower predictive response to IO with EGFR mutation)---- No clear guidelines if you should continue the TKI---- Remember that IO + TKIs can cause increased risk of side effects, such as pneumonitis and hepatitis. DO NOT DO THIS!* ALK Mutation:- There are many options for ALK mutations-- The first generation drug is crizotinib--- Lots of side effects —> “It is crazy to start with crizotinib”--- Studies for later generation TKIs were compared to crizotinib -- Many people today will use third generation ALK-inhibitor alectinib (Important trials: ALEX Trial and J-ALEX Trial)--- With alectinib, PFS 34.8 months, RR 83%, less CNS progression (12% vs 45%)--- 5 year OS rate 62.5%- What to do with disease progression while on ALK inhibitor?-- In ALK, you can actually switch to another ALK inhibitor and many will respond well--- Of course, with each change, you may expect not as great of a response * Lots of other mutations!- TFOC recommends just looking these up!-- Link to NCCN Guidelines on NSCLC; Page 41 has full list!- Another way to think about this, when do we NOT do TKIs as first line: -- KRAS G12C-- EGFR Exon 20 Insertion-- HER2- How do you counsel a patient when considering/starting a TKI? -- Patients with highest chance of having a targeted mutation are younger non-smokers with adenocarcinoma-- Set expectations: great outcomes overall, but still not a cure. -- Remembering the drugs: All TKIs usually end in “-nib” -- In general, the way we recommend remembering this: “Fatigue, GI, Derm (skin/nail changes)”; rarely pneumonitis References:* AURA3 Trial - https://www.nejm.org/doi/full/10.1056/NEJMoa1612674Established osimertinib was better than chemo for patients with EGFR mutation and acquired Exon 21 T790M resistance mutation* FLAURA Trial - https://www.nejm.org/doi/full/10.1056/nejmoa1713137 Established osimertinib as first-line agent for patients with EGFR mutation * ALEX Trial - https://www.nejm.org/doi/full/10.1056/nejmoa1704795Helped establish alectinib as superior for ALK mutations compared to crizotinib * J-ALEX Trial - https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltextHelped establish alectinib as superior for ALK mutations compared to crizotinib * NCCN Guidelines on NSCLC - https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450 Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google PodcastLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!

Dr Elamin discusses results from a phase 2 study of poziotinib efficacy in EGFR exon 20–mutant non–small cell lung cancer and highlights the agent's sensitivity in relation to insertion location.

Welcome to the NeurologyLive® Mind Moments® podcast. Tune in to hear leaders in neurology sound off on topics that impact your clinical practice. In this episode, we spoke with Christopher Elder, MD, clinical assistant professor of neurology, Comprehensive Epilepsy Center, NYU Langone Health. He joined the show to talk about the latest updates in the care of patients with epilepsy, the clinical therapeutic pipeline developments on the horizon, and the need to continue stressing conversations around sudden unexpected death in epilepsy (SUDEP). Episode Breakdown: 1:15 – The rise of neurostimulation in epilepsy care 4:00 – Increasing implantation of minimally invasive options 5:15 – Patient reception to nontherapeutic approaches 7:45 – The impact of cenobamate (Xcopri; SK Life Science) on the paradigm 10:35 – Managing refractory epilepsy 12:00 – Upcoming options for those with generalized epilepsy 13:50 – Neurology News Minute 18:30 – Path forward for gene and cell therapies in epilepsy 21:00 – The need to improve early recognition of epilepsy 25:20 – Standardizing questionnaires and information for epilepsy 27:00 – The need to continue discussing SUDEP This episode is brought to you by the Medical World News streaming service. Check out new content and shows every day, only at medicalworldnews.com The stories featured in this week's Neurology News Minute, which will give you quick updates on the following developments in neurology, are further detailed here: FDA Approves Midazolam Autoinjector for Status Epilepticus Sirolimus Topical Gel Available for Facial Angiofibroma Associated With Tuberous Sclerosis Complex FDA Lifts Hold on Phase 2 Trial of SRP-5051 in DMD Amenable to Exon 51 Skipping Philips Respironics Recalls Masks for BPAP and CPAP Machines After Safety Concerns FDA Advisory Committee Votes to Recommend AMX0035 for Treatment of ALS Thanks for listening to the NeurologyLive® Mind Moments® podcast. To support the show, be sure to rate, review, and subscribe wherever you listen to podcasts. For more neurology news and expert-driven content, visit neurologylive.com.

We're back! We apologize for the pause in new episodes for #QualityMatters, but we're back! Today we're diving into a topic that Kyle is very passionate about, the role of small business in Oil & Gas here in America. The simple fact is, the super majors like Chevron and Exon do not play near the role in Oil & Gas extraction for the average American as small business does. https://sbecouncil.org/2020/04/17/reminder-during-the-covid-19-crisis-the-oil-and-natural-gas-industry-is-dominated-by-small-businesses/ Drilling Oil and Gas Wells Size of Firms by Number of Employees Percent of Total Employer Firms in the Drilling Oil and Gas Wells Sector Less than 10         70.5% Less than 20         80.5% Less than 100         93.4% Less than 500         97.4% Support Activities for Oil and Gas Operations Size of Firms by Number of Employees Percent of Total Employer Firms in the Support Activities for Oil and Gas Operations Sector Less than 10      71.4% Less than 20      82.9% Less than 100      95.4% Less than 500      98.4% The role of newly evolving ESG "Environmental - Social - Governance" requirements is placing additional requirements on small business.  But this is not all bad news.  The small businesses and teams that are prepared to implement, and quickly and more efficiently than the larger or otherwise slower counterparts are in a great position to dominate their space and stay competitive.  Special thanks to our friend Mark LaCour of OGGN the "Oil & Gas Global Network" for joining us again today.  Be sure to follow OGGN (as if you have not already) where ever podcast can be found.   #QualityMatters podcast is streaming on:iTunes | Spotify | Google | Audible | Stitcher | TuneIn Learn more about #QualityMatters & Texas Quality Assurance :LinkedIn | Facebook | Twitter  | Instagram  | YouTube | Rumblewww.qmcast.com | Texas Quality Assurance