Podcasts about N2

Walter Sisulu University's Mthatha campus has been rocked by fresh student protests following the release of residence manager Manelisi Mampane on R10,000 bail yesterday. The situation is still tense on the N2 road near Walter Sisulu University in Mthatha in the Eastern Cape. This as students are in confrontation with the police who are trying to maintain order. Mampane is facing charges of murder, attempted murder and possession of unlicensed firearm. This after he allegedly fatally shot a 24-year-old student, Sisonke Mbolekwa, during a protest at the institution in April. Sakina Kamwendo spoke to SABC Reporter, Fundiswa Mhlekude

Neurovedec Tomáš Hromádka, ktorý je členom predsedníctva SAV, rozpráva ako vníma momentálne dianie v politike, z ktorého vyplynulo prešetrovanie pandémie, hlasovanie o pandemickej dohode či analýza mRNA vakcín, ktorou je SAV poverená. "Aj keď niektoré názory počuť viac, neznamená to, že sú silnejšie. No a rozhodne nie sú správnejšie, pretože jednoducho nie sú ničím podložené. Sú vymyslené a je na to aj technický termín. Sú to somariny. To je všetko," hovorí Hromádka o diskusiách, či je očkovanie nebezpečné. *Vedecký podcast N2 mení od júna názov na Zvedavosť. Nájdete ho každé dva týždne na tomto mieste, ktoré takisto mení názov z Denník N Podcasty na Zvedavosť.*

JCO Editorial Fellow Dr. Ece Cali Daylan and JCO Associate Editor Dr. Thomas Stinchcombe discuss the ASCO 2025 Simultaneous Publication paper "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small-Cell Lung Cancer." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Ece Cali: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Ece Cali, JCO Editorial Fellow, and I am joined by JCO Associate Editor, Dr. Tom Stinchcombe. In this episode, we will discuss the Journal of Clinical Oncology article and abstract presentation "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer.” NeoADAURA is a randomized global phase III study investigating the efficacy of neoadjuvant osimertinib-containing regimens in patients with resectable EGFR-mutated stage II to IIIB non–small-cell lung cancer. 358 patients were randomized 1:1:1 to receive osimertinib plus chemotherapy, osimertinib monotherapy, or placebo plus chemotherapy in the neoadjuvant setting. The primary endpoint was major pathological response. Osimertinib plus chemotherapy and osimertinib alone demonstrated MPR rates of 26% and 25%, respectively, compared to 2% in the chemotherapy plus placebo arm with a p-value of less than 0.001. Tom, can you please explain to our listeners how you interpret this data? Dr. Thomas Stinchcombe: Great question. Yeah, I think to give a little context, obviously, chemotherapy and immunotherapies preoperatively is becoming the standard of care. However, patients with EGFR-mutant lung cancer generally have not responded to immunotherapy, and many of the trials excluded patients with known EGFR mutation. There have been smaller phase II trials that had looked at EGFR TKIs preoperatively, but none of these were definitive. So I think that this trial is a big trial, and I think some of the strengths are that it has osimertinib alone and chemotherapy with osimertinib arms as compared to the standard of chemotherapy. I think it's going to be really interesting at the meeting to see how this is discussed by the discussant and also what the reaction is to its public presentation. And I think that's largely because there's an alternative paradigm now, surgical resection adjuvant osimertinib, that's available to patients. So I think this will be interesting to see what the reaction is to the induction therapy. For patients with known N2 disease, I've generally given some form of induction therapy prior to surgical resection. So I think that's the subgroup of patients that I'm most likely to employ this approach with based on the results. Dr. Ece Cali: So, in this trial, more than 90% of the patients on the osimertinib-containing regimens underwent curative-intent surgery. So, this speaks to the feasibility of the approach, and the higher MPR rate with osimertinib-containing regimens is encouraging. Event-free survival data is currently immature. You have already touched upon some of the strengths of the trial, but what are the weaknesses and the strengths of this trial? Dr. Thomas Stinchcombe: So, I mean, I think there are some weaknesses. A major pathological response was chosen as an endpoint, and there could be an argument that path CR is more of a prognostic marker. However, the rates of path CR are relatively low, so it would have been very hard to design a trial such as that. And then I think the trial started off as a preoperative trial but effectively became a perioperative trial with preoperative EGFR-TKI, postoperative osimertinib. And so I think it's going to be very hard to determine what the contribution of the components are. And then you've hit on another part that I think is very important when we interpret the data that the maturity on the event-free survival is only 15%, and most people are still on therapy. So the event-free survival, which is an important endpoint, is very immature right now. Dr. Ece Cali: And this trial was designed to compare the neoadjuvant approaches, hence the comparator arm here is neoadjuvant chemotherapy followed by surgery. So, considering the ADAURA trial results with upfront surgery followed by osimertinib as adjuvant, so how do you see this trial's impact on the current clinical practice? Dr. Thomas Stinchcombe: Well, very good question, I think one that we're still struggling with as we kind of look at this data. I think, for me, stage II patients will most likely go to surgery and then get adjuvant osimertinib, and then maybe the N2 patients will get an osimertinib-containing regimen as an induction therapy. I think one of the questions is does it really matter when you get the osimertinib as long as you get it at some point? And I think that's going to be the critical interpretation of some of the data at this point. Dr. Ece Cali: And how do you think this trial shapes the future research for patients with resectable EGFR-mutated lung cancer? Dr. Thomas Stinchcombe: Well, I mean, I think it shows that chemotherapy was really modestly active with an MPR rate of 2%, no pathological responses. And then I think you're going to have to look at an osimertinib plus another targeted therapy component. I think, you know, when I looked at the osimertinib versus the chemo-osimertinib arm, I also was sort of surprised that the MPR rate and the path CR rate were very, very similar. So I think that the question is would a double targeted therapy approach or some other approach matter? And I think it also sets a safety standard. And you touched on this in your comments, that there was not a disparity in terms of the rate of going to surgery or R0/R1 resections. So patients were not having progressive disease events or toxicities that prevented surgery. So I think it does give us good safety data. Dr. Ece Cali: Tom, thank you so much for sharing your insights on the JCO article, "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting, and please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

Formation Metals CEO Deepak Varshney joined Steve Darling from Proactive to announce plans for a 20,000-metre multi-phase drill program at the company's flagship N2 Gold Project in Quebec. The N2 Project hosts a historic global resource of approximately 870,000 ounces of gold, including 18 million tonnes grading 1.4 g/t Au across four zones, and 243,000 tonnes grading 7.82 g/t Au in the high-grade RJ zone. The N2 project was acquired from Walbridge Mining in January. Varshney said the project attracted them because of a historical resource and a clear pathway to expanding this to over 3 million ounces.. Varshney confirmed that the first 5,000 metres of drilling is fully funded and set to begin this summer. The program will focus on discovery drilling at new high-potential targets along the mineralized trends in the “A,” “RJ,” and “Central” zones in the northern part of the property. The goal is to uncover new gold-bearing trends and expand existing mineralization. Additionally, the program will include targeted infill and expansion drilling to significantly enhance the project's resource base, supported by a recently secured exploration permit. #proactiveinvestors #formationmetalsinc #cse #fomo #otc #fomtf #GoldExploration #N2Project #QuebecMining #JuniorMining #GoldDrilling #MiningInvesting #ResourceExpansion #ExplorationDrilling #ProactiveInvestors

The Service Level Plan between the City of Cape Town and the Passenger Rail Agency of SA (PRASA), which is the first step in moving the management of passenger rail to the City, has still not been finalised; the thorny truth of Lesotho’s rosehip industry; people living along the N2 near Mfuleni want the City of Cape Town to include them in its budget; learners with disabilities steal the show at Shakespeare festival. Lester Kiewit speaks to Barbara October of GroundUp News. Good Morning Cape Town with Lester Kiewit is a podcast of the CapeTalk breakfast show. This programme is your authentic Cape Town wake-up call. Good Morning Cape Town with Lester Kiewit is informative, enlightening and accessible. The team’s ability to spot & share relevant and unusual stories make the programme inclusive and thought-provoking. Don’t miss the popular World View feature at 7:45am daily. Listen out for #LesterInYourLounge which is an outside broadcast – from the home of a listener in a different part of Cape Town - on the first Wednesday of every month. This show introduces you to interesting Capetonians as well as their favourite communities, habits, local personalities and neighbourhood news. Thank you for listening to a podcast from Good Morning Cape Town with Lester Kiewit. Listen live on Primedia+ weekdays between 06:00 and 09:00 (SA Time) to Good Morning CapeTalk with Lester Kiewit broadcast on CapeTalk https://buff.ly/NnFM3Nk For more from the show go to https://buff.ly/xGkqLbT or find all the catch-up podcasts here https://buff.ly/f9Eeb7i Subscribe to the CapeTalk Daily and Weekly Newsletters https://buff.ly/sbvVZD5 Follow us on social media CapeTalk on Facebook: https://www.facebook.com/CapeTalk CapeTalk on TikTok: https://www.tiktok.com/@capetalk CapeTalk on Instagram: https://www.instagram.com/ CapeTalk on X: https://x.com/CapeTalk CapeTalk on YouTube: https://www.youtube.com/@CapeTalk567 See omnystudio.com/listener for privacy information.

durée : 00:03:23 - Basket - Longueau devrait maintenir son entraîneur en N2 la saison prochaine - Entretien avec le pdt Serge TRISTRAM

'n Transitorooftog in Umlazi, suid van Durban is dramaties gefnuik, nadat 'n bestuurder die gewapende rowers ontduik het deur by die Mega City-winkelsentrum in te ry. Die voertuig is op die N2-snelweg in 'n lokval gelei. 'n Woordvoerder van A-L-S Paramedici, Garrith Jamieson, sê die bestuurder het vinnig gereageer en by die winkelsentrum se parkeerarea ingery, waarna sekuriteit die hekke gesluit en die aanvallers gedwing het om te vlug terwyl skote afgevuur is:

Cada semana en Onda Cero junto a Agustín Bravo, Sergio Alberto Gama y Sofía Menéndez analizamos la seguridad vial. El pasado día 2 de marzo nevó en la Sierra de Guadarrama y afectó a la A6 y a la A1 y a la N2. El problema no está en ATGC, y tampoco en el Ministerio de Transportes, el problema estuvo en la falta de formación o la desidia de los conductores, de muchos conductores… 1 De casa se sale con el coche revisado 2 Con cadenas en el maletero 3 Cuando empieza a nevar, si no tienes neumáticos de invierno y no tienes cadenas, para en la primera estación de servicio y quédate ahí. 4 Si tienes neumáticos de invierno o cadenas, repostas el tanque a tope, compras agua y comida y puedes continuar, si no eres un cafre al volante. Como la gente hace lo que la da la gana y piensa que papá estado le tiene que resolver todo se meten en carretera y ponen el riesgo si vida y la del resto de usuarios de la vía. Cuando está nevando y llega el primer repecho la gente se para, y si con nieve te paras… ya no arrancas si no tienes cadenas Si está parado en carretera, con o sin nieve, hay que dejar libre del todo un carril para los equipos de emergencia y/o para la quitanieves Hasta aquí el programa de hoy del podcast de seguridad vial y educación vial. ¿Quieres escuchar episodios anteriores sobre seguridad en moto? • P138 100 tramos más peligrosos para motoristas https://go.ivoox.com/rf/72292314 • P154 Hugo de 14 años muere en el campeonato Europeo de motociclismo. https://go.ivoox.com/rf/73574655 • P176 Motos sin ITV https://go.ivoox.com/rf/75543112 • P262 Seguridad Vial en moto No me llames paquete https://go.ivoox.com/rf/93733543 • P289 Caídas en quad o moto y la importancia de la equipación adecuada. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101146657 • P300 Seguridad vial en moto en el Dakar https://go.ivoox.com/rf/101515123 • P327 Seguridad vial en moto, formación conducción, compra de equitación y exigir la retirada de guardarraíles asesinos https://go.ivoox.com/rf/105221622 • P376 seguridad vial en moto, episodio 5 del verano de seguridad en Onda Cero https://go.ivoox.com/rf/114152759 • P470 La seguridad vial en moto a debate https://go.ivoox.com/rf/126752010 • P566 chaleco airbag moto para la atgc https://go.ivoox.com/rf/135729959 • P557 4000 motos en la manifestación motera por la seguridad vial https://go.ivoox.com/rf/134812092 ¿Quieres escuchar episodios anteriores sobre seguridad en Euro NCAP? • P22 Seguridad infantil en Euro NCAP 2020 https://go.ivoox.com/rf/60410726 • P31 La seguridad infantil de los 7 coches ensayados en Euro NCAP 2020 https://go.ivoox.com/rf/63999896 • P119 En AutoFM hablamos del origen de lo que hoy es Euro NCAP https://go.ivoox.com/rf/70766776 • P192 Hyundai Ioniq 5 en Euro NCAP https://go.ivoox.com/rf/77624794 • P200 El coche más seguro para niños según Euro NCAP https://go.ivoox.com/rf/79810679 • P278 ¿Qué es EuroNCAP? https://go.ivoox.com/rf/97118681 • P320 Seguridad EuroNCAP en el Lexus RX https://go.ivoox.com/rf/104093361 • P325 Cupra en Euro NCAP seguridad made in Spain https://go.ivoox.com/rf/104841125 • P353 Euro NCAP y la seguridad de nuestros vehículos https://go.ivoox.com/rf/111970962 • P413 Etiquetas de seguridad en EuroNCAP https://go.ivoox.com/rf/121984964 • P426 BMW Serie 5 en EuroNCAP https://go.ivoox.com/rf/121989858 ¿Quieres escuchar episodios anteriores sobre patinetes eléctricos (VMP) y su influencia en la educación vial y seguridad vial? • VMP o los patinetes eléctricos (13-11-2020) https://go.ivoox.com/rf/58970634 • P29 200€ de multa a los patinetes que circulen por la acera (19-1-2021) https://go.ivoox.com/rf/63999858 • P39 El 80% de los accidentados en patinete eléctrico iban sin casco. https://go.ivoox.com/rf/64652023 • P88. En la sección de RiveKids dentro de AutoFM hablamos de atropellos de niños con patinete eléctrico VMP https://go.ivoox.com/rf/68488690 • P134 Tráfico dice que se va a poner duro con patinetes y bicicletas https://go.ivoox.com/rf/71998645 • P205 certificado para VMP y manual de características del patinete eléctrico https://go.ivoox.com/rf/81250012 ¿Quieres escuchar episodios anteriores sobre cómo la DGT afronta la educación vial y seguridad vial? • P47. La DGT recauda más de un millón de euros al día en multas https://go.ivoox.com/rf/65042824 • P68 2.880 conductores fueron denunciados dos o más veces en un mismo año por no llevar el cinturón de seguridad. https://go.ivoox.com/rf/66793732 • P72 La otra cara del rescate en carretera. DGT https://go.ivoox.com/rf/67030950 • P78 ¿Por qué nos denuncia la DGT en España? https://go.ivoox.com/rf/67470851 • P85 los tribunales anulan la mitad de las multas que pone la DGT. https://go.ivoox.com/rf/68027004 • P189 Cómo adelantar con seguridad https://go.ivoox.com/rf/76818386 • 6 puntos por usar el móvil al volante y más cambios de la DGT. https://go.ivoox.com/rf/60394281 • P383 ¿Hay que abrochar el cinturón de seguridad incluso sin ocupantes en las plazas traseras? https://go.ivoox.com/rf/115775880 • P444 Ocurrencias de la DGT en 2024 https://go.ivoox.com/rf/124103189 • P559 estrategia de país en la seguridad vial https://go.ivoox.com/rf/134812303 • P447 Propuestas de la DGT para bajar fallecidos en carretera https://go.ivoox.com/rf/124482117 ¿Quieres escuchar episodios anteriores del podcast de educación vial y seguridad vial? • P6 Coronavirus y Seguridad Vial https://go.ivoox.com/rf/49513283 • P169 Seguridad vial en Onda Cero https://go.ivoox.com/rf/74292123 • P125 ¿Isofix en un SsangYong Rodius? Y mucha más seguridad vial https://go.ivoox.com/rf/71289331 • P196 Seguridad vial para bebés prematuros y CIPSEVI https://go.ivoox.com/rf/78652365 • P168 Sin ruedas no hay seguridad vial https://go.ivoox.com/rf/74292023 • P182 La educación vial en El Enfoque, Onda Madrid https://go.ivoox.com/rf/76018355 • P7 Mascarillas y guantes son al coronavirus lo que el cinturón de seguridad y los SRI a la violencia vial https://go.ivoox.com/rf/50038459 • P197 Estudio sobre la inseguridad vial en el contenido de las series en Capital Radio https://go.ivoox.com/rf/78897119 • P565 la mayoría de gente no usa el cinturón de seguridad https://go.ivoox.com/rf/135729932 • P561 4 de cada 10 conductores dan positivo en drogas https://go.ivoox.com/rf/134812530 • P541 La DGT no sabe dónde hay más de 650 millones de euros https://go.ivoox.com/rf/133580231 ¿Quieres escuchar episodios anteriores del podcast de seguridad vial en el Dakar? • P290 Lluvia torrencial, helicópteros que no pueden volar y buggies en medio de riadas. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101146767 • P291. Señalización de accidentes en la carrera más dura del mundo. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101146815 • P295 Exceso de velocidad, radar, sanción y distancia de frenado. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101147162 • P297 Muere atropellado por conseguir la mejor foto. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101514720 • P302 El Dakar 2023 da una lección de seguridad vial. La velocidad no mata, matan otras cosas. Seguridad vial Dakar https://go.ivoox.com/rf/101515334 • P301 Seguridad Vial con Manolo Plaza en el Dakar y en la vida. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101515325 • P300 La seguridad vial en moto en el Dakar y en las carreteras españolas. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101515123 • P294 Cansancio y fatiga extrema en competición. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101147100 • P296 ¿Es más seguro un chasis tubular? Biomecánica del impacto y aceleraciones en la seguridad vial Dakar 2023 https://go.ivoox.com/rf/101514635 • P288 Arco antivuelco o jaula de seguridad. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/100776113 • P293 Hans. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101146904 • P292. Pos seguridad después de un vuelco o un accidente ¿qué hacer?. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/101146866 • P287 Arnés vs cinturón de seguridad. Seguridad vial Dakar 2023 https://go.ivoox.com/rf/100775999 • P299 Conducir sin luna en la seguridad vial Dakar 2023 https://go.ivoox.com/rf/101515049 • P298 Fallece atropellado un aficionado que estaba viendo el Dakar 2023. Seguridad vial dentro y fuera de la competición https://go.ivoox.com/rf/101514818 • P430 Prologo Dakar 2024, seguridad vial https://go.ivoox.com/rf/122182887 • P438 Etapa 10 Dakar 2024 competición vs vida real en la señalización https://go.ivoox.com/rf/123338733 • P435 Etapa 5 Dakar 2024, la fatiga https://go.ivoox.com/rf/122440640 • P440 Etapa de descanso Dakar 2024 los twit de la DGT https://go.ivoox.com/rf/123339096 • P439 Etapa 11 Dakar 2024 adelantamientos extremos https://go.ivoox.com/rf/123338820 • P436 Atropello de un espectador en el Dakar 2024 https://go.ivoox.com/rf/122440725 • P434 Etapa 4 seguridad jurídica y excesos de velocidad en el Dakar 2024 https://go.ivoox.com/rf/122440464 • P431 Etapa 1 Dakar 2024, espectador atropellado https://go.ivoox.com/rf/122229047 • P432 Etapa 2 Dakar 2024, jaula de seguridad y Carles Falcón https://go.ivoox.com/rf/122229139 • P433 Etapa 3 Dakar 2024, los 3 impactos de un accidente https://go.ivoox.com/rf/122440325 “El verdadero viaje es el que termina como comenzó, con felicidad e inocencia” Feliz viaje hasta el próximo programa. _______________________________________

欢迎收听雪球出品的财经有深度，雪球，国内领先的集投资交流交易一体的综合财富管理平台，聪明的投资者都在这里。今天分享的内容叫行业探讨｜机器人马拉松，是危机还是机会？，来自围棋投研。周末最受关注也是最有趣的新闻，就是在北京亦庄举行的全球首个人形机器人半程马拉松，20支人形机器人赛队参赛，引来群众强势围观，连官媒都给到了全程直播。人形机器人现在是完全搬到了真正赛道，俗话说“是骡子是马，拉出来溜溜”，站在投研人视角，正好能阶段性做个验证。首先，看看参赛选手们的情况。在参赛队伍里，有正经机器人企业、有科研院校、还有科技发烧友等，很遗憾，最终完赛者并不多，就稍微记录几支队伍的情况。冠军是天工队，来自于北京人形机器人创新中心的天工Ultra，身高180cm，体重52kg。这家企业来头不小，由优必选作为发起单位，京城机电、小米机器人、亦庄机器人等10家行业领军企事业单位共同出资，集万千技术于一身。不像其他比赛只认冠军，机器人马拉松的每位选手都备受瞩目，亚军选手是来自于小顽童队的松延动力N2，身高120cm，体重30kg。全程基本都是自己在跑，陪跑员介入得相对比较少。此外，另个队伍旋风小子队也是用的松延动力N2，第三个冲线，可惜比赛途中换过几次机器人被罚了时间，最终错失季军。不过在“小顽童”到达终点后，出现了惊人的一幕，他毅然转身往终点走去，等待着迎接好兄弟“旋风小子”，虽然是由人为控制，但也是爱意满满。季军是行者二号队，使用卓益得机器人，身高170cm，体重不到30kg，和刚才那位120cm小个子一样重，特点是双腿非常纤细。腿细就跑不快，然而他们的策略就是龟兔赛跑，主打个坚持到底就是胜利。如果有了解机器人领域的朋友，就要疑惑了，怎么都是些名不见经传的机器人厂商，除了优必选，那些当红公司怎么都没来？尤其是宇树机器人，跳舞、爬山和武术，跑马拉松应该是小菜一碟啊。其实赛道上是有宇树机器人的，但表现不咋地，一会躺在地上不肯走、一会像喝醉了跌跌撞撞、一会竖起大拇指自我鼓励，反正就是不好好比赛，最终放弃。事后宇树发文称，官方并没有参赛，是有客户买了宇树产品并配上了自己的算法前来参加，原文里还有句是“机器人和其他电子产品类似，表现性能和使用者息息相关”，言下之意就是，这并不是宇树真正实力。这个原因算能够接受，但至于为什么这么多头部厂商都不来，我自己还有个不成熟的想法：真的是不敢来，怕翻车、也怕影响品牌力和融资节奏。有企业甚至明说“我们就是跑不下来，一开始想报名的，后来就退缩了。”说到这里，就要看看机器人的表现到底是不是符合预期。简单一句话点评，相比之前各家机器人厂商视频里的“卖家秀”，这场机器人马拉松就是真正的“买家秀”：有摔了一跤就再也爬不起来的，有跑着跑着头掉下来，掉了竟还能继续跑的，有刚出发就罢工，坐地上赖着不肯动的，甚至有些连起跑线都过不了，当场就被工作人员提走维修的。有趣的事情还有呢，大赛结束后，有几台机器人是被推着轮椅离场，不禁让我想起曾毓群董事长在宁德股东大会所说：出门时候是机器人，回来时候是机器爹。很明显，相比于大赛前的期盼，投资者都想象着机器人相互竞技的场面，到真正比赛里却是状况百出，低于预期。有个朋友持有了不少概念股，和我说边看直播边擦汗，觉得下周大跌是逃不掉了。实际上，之前多篇文章里都有提到，人形机器人离产业化有不小的距离，调研主机厂时说得更直白：还没有找到适合的场景。因此，对于这场马拉松的展示结果，我并不算特别意外，算是符合预期吧。最后，落地到投资维度，想想有什么启发。猜测短期涨跌，并不是能力圈范围所及，而且不会有太大意义，但作为投研人，需要从这项活动里看到更多的产业趋势。第一，当前仍有不少技术有待完善。上面聊到的都是现象，像是摔跤啊踉跄啊，其背后都是技术问题。平时在实验室里或者室内都是环境安逸，而马拉松是户外场景，对于机器人综合性能提出很大挑战，是对关节结构设计、热管理、电池续航、控制算法、通信干扰、软硬件耦合等方面的综合性考验。比如散热，跑着跑着关节处摩擦严重，就要有陪跑员给膝盖喷散热剂；比如续航，跑着跑着要换电池或者换个机器人，就说明电池能量密度不给力；比如平衡，有人看小个子跑得稳，就觉得这家厂商技术高超，实际不然，机器人每高出10cm，对平衡能力的要求就指数级增长。这些暴露出来的种种缺陷，很可能就是后面技术发展的重点方向。第二，落地场景依然要继续开发。最近是年报和一季报披露期，很多产业链企业的业绩都还不错，当然这里是指主营业务，或机械或汽零等等。有时在业绩会聊到人形机器人业务，管理层都说在做试验线或者少量供货，几十台或几百台。这些货都供到哪里呢？要么是科研院所做研究，要么是企业放在那里做展示，要么被竞争对手买去拆解……这些场景都有个共同特征：市场空间有限。有朋友说，原来还担心要失业，看完比赛彻底放心了，人形机器人不会造成社会失业，反而促进就业，毕竟1个人形机器人至少需要2-3个人看护。玩笑归玩笑，人形机器人的应用场景排序，依然是科研院所、消防等特色场景、工业领域、养老、家庭。这里面最重要的一个环节，就是工业领域的规模化，说起来还有点悖论。一方面，双足机器人技术不够成熟、成本有点高，要想快速迭代以及降低成本，唯有大批量用在工厂里才能实现；另一方面，现在工厂里用机械臂和轮式机器人就很有效率了，用双足机器人反而是又贵又磨叽。没有前期的付出和贡献，就没有后期的高效，道理都懂，那么谁来当第一个吃螃蟹的人呢？恕我直言，除非有补贴，否则国内企业都难当重任。所能想到的第一人，就是马斯克。他有梦想，要用人形机器人帮助人类去开拓火星，他有基础，特斯拉机器人能用在特斯拉汽车工厂，内部消化对利润影响就小很多。因此，排除对等关税这种特殊因素，特斯拉产业链还是值得重视。第三，远期空间依然是星辰大海。这场比赛虽然叫机器人马拉松，但人类参与度还是挺高的，主办方允许使用“遥控”和“跟跑”模式，甚至有机器人身后还牵着根绳子，整场比赛都像极了刚学会走路的小朋友，出门时身边家长都贴身保护。从咿呀学语到蹒跚学步，从临池学书到长大成人，人类如此，机器人亦是如此。市场机构预计，2024-2026年，机器人行业将呈现100倍的增长速度，行业规模从2024年的不到10亿，增长至2026年的接近1000亿，这是总盘子。其中，人形机器人是机器人远期最大的应用场景，但从阶段性来看，正如上文提到，工业机器人、特种机器人等领域预计将率先实现落地，并为相关上市公司带来规模化的收入和利润。以风险偏好从高到低排序：技术缺陷弥补，特斯拉产业链，工业机器人。总的来说，尽管赛事里“糗事”不少，但我依然非常敬佩能前来参赛的每一支队伍，能迈出第一步就已经足够有勇气。明年如果还有机器人马拉松，相信惊喜就会多于惊吓。想起来，1894年6月11日，巴黎第一次汽车大奖赛，100多公里路程，21辆车只有17辆完成了比赛，第一名用时11个小时，跑的比马车还慢。当时的报刊和观众，就都是充满了嘲笑和讥讽。如今这场机器人马拉松，绝不是黑历史，而是来时路。

Kunstgjødsel inneholder nitrogen i en form som plantene trenger og er helt nødvendig for å fø 8 milliarder mennesker. En bieffekt fra denne tilførselen av nitrogen er utslipp av lystgass (N2O) fra jordene. Lystgass er en kraftig klimagass, og disse utslippene står for omtrent 5% av menneskenes klimautslipp.  Forskningsgruppen til dagens gjest har funnet en bakterie som potensielt kan løse dette problemet. Den lever i jorda og konverterer lystgass til klimamessig ufarlig nitrogengass (N2.)

Dr. Ko Un “Clara” Park and Dr. Mylin Torres present the latest evidence-based changes to the SLNB in early-stage breast cancer guideline. They discuss the practice-changing trials that led to the updated recommendations and topics such as when SLNB can be omitted, when ALND is indicated, radiation and systemic treatment decisions after SLNB omission, and the role of SLNB in special circumstances. We discuss the importance of shared decision-making and other ongoing and future de-escalation trials that will expand knowledge in this space. Read the full guideline update, “Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update” at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-00099       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'm interviewing Dr. Ko Un "Clara" Park from Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Dr. Mylin Torres from Glenn Family Breast Center at Winship Cancer Institute of Emory University, co-chairs on “Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update.” Thank you for being here today, Dr. Park and Dr. Torres. Dr. Mylin Torres: Thank you, it's a pleasure to be here. Brittany Harvey: And 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. Torres and Dr. Park, who have 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. To start us off, Dr. Torres, what is the scope and purpose of this guideline update on the use of sentinel lymph node biopsy in early-stage breast cancer? Dr. Mylin Torres: The update includes recommendations incorporating findings from trials released since our last published guideline in 2017. It includes data from nine randomized trials comparing sentinel lymph node biopsy alone versus sentinel lymph node biopsy with a completion axillary lymph node dissection. And notably, and probably the primary reason for motivating this update, are two trials comparing sentinel lymph node biopsy with no axillary surgery, all of which were published from 2016 to 2024. We believe these latter two trials are practice changing and are important for our community to know about so that it can be implemented and essentially represent a change in treatment paradigms. Brittany Harvey: It's great to hear about these practice changing trials and how that will impact these recommendation updates. So Dr. Park, I'd like to start by reviewing the key recommendations across all of these six overarching clinical questions that the guideline addressed. So first, are there patients where sentinel lymph node biopsy can be omitted? Dr. Ko Un "Clara" Park: Yes. The key change in the current management of early-stage breast cancer is the inclusion of omission of sentinel lymph node biopsy in patients with small, less than 2 cm breast cancer and a negative finding on preoperative axillary ultrasound. The patients who are eligible for omission of sentinel lymph node biopsy according to the SOUND and INSEMA trial are patients with invasive ductal carcinoma that is size smaller than 2 cm, Nottingham grades 1 and 2, hormone receptor-positive, HER2-negative in patients intending to receive adjuvant endocrine therapy, and no suspicious lymph nodes on axillary ultrasound or if they have only one suspicious lymph node, then the biopsy of that lymph node is benign and concordant according to the axillary ultrasound findings. The patients who are eligible for sentinel lymph node biopsy omission according to the SOUND and INSEMA trials were patients who are undergoing lumpectomy followed by whole breast radiation, especially in patients who are younger than 65 years of age. For patients who are 65 years or older, they also qualify for omission of sentinel lymph node biopsy in addition to consideration for radiation therapy omission according to the PRIME II and CALGB 9343 clinical trials. And so in those patients, a more shared decision-making approach with the radiation oncologist is encouraged. Brittany Harvey: Understood. I appreciate you outlining that criteria for when sentinel lymph node biopsy can be omitted and when shared decision making is appropriate as well. So then, Dr. Torres, in those patients where sentinel lymph node biopsy is omitted, how are radiation and systemic treatment decisions impacted? Dr. Mylin Torres: Thank you for that question. I think there will be a lot of consternation brought up as far as sentinel lymph node biopsy and the value it could provide in terms of knowing whether that lymph node is involved or not. But as stated, sentinel lymph node biopsy actually can be safely omitted in patients with low risk disease and therefore the reason we state this is that in both SOUND and INSEMA trial, 85% of patients who had a preoperative axillary ultrasound that did not show any signs of a suspicious lymph node also had no lymph nodes involved at the time of sentinel node biopsy. So 85% of the time the preoperative ultrasound is correct. So given the number of patients where preoperative ultrasound predicts for no sentinel node involvement, we have stated within the guideline that radiation and systemic treatment decisions should not be altered in the select patients with low risk disease where sentinel lymph node biopsy can be omitted. Those are the patients who are postmenopausal and age 50 or older who have negative findings on preoperative ultrasound with grade 1 or 2 disease, small tumors less than or equal to 2 cm, hormone receptor-positive, HER2-negative breast cancer who undergo breast conserving therapy. Now, it's important to note in both the INSEMA and SOUND trials, the vast majority of patients received whole breast radiation. In fact, within the INSEMA trial, partial breast irradiation was not allowed. The SOUND trial did allow partial breast irradiation, but in that study, 80% of patients still received whole breast treatment. Therefore, the preponderance of data does support whole breast irradiation when you go strictly by the way the SOUND and INSEMA trials were conducted. Notably, however, most of the patients in these studies had node-negative disease and had low risk features to their primary tumors and would have been eligible for partial breast irradiation by the ASTRO Guidelines for partial breast treatment. So, given the fact that 85% of patients will have node-negative disease after a preoperative ultrasound, essentially what we're saying is that partial breast irradiation may be offered in these patients where omission of sentinel node biopsy is felt to be safe, which is in these low risk patients. Additionally, regional nodal irradiation is something that is not indicated in the vast majority of patients where omission of sentinel lymph node biopsy is prescribed and recommended, and that is because very few of these patients will actually end up having pathologic N2 disease, which is four or more positive lymph nodes. If you look at the numbers from both the INSEMA and the SOUND trial, the number of patients with pathologic N2 disease who did have their axilla surgically staged, it was less than 1% in both trials. So, in these patients, regional nodal irradiation, there would be no clear indication for that more aggressive and more extensive radiation treatment. The same principles apply to systemic therapy. As the vast majority of these patients are going to have node-negative disease with a low risk primary tumor, we know that postmenopausal women, even if they're found to have one to three positive lymph nodes, a lot of the systemic cytotoxic chemotherapy decisions are driven by genomic assay score which is taken from the primary tumor. And therefore nodal information in patients who have N1 disease may not be gained in patients where omission of sentinel lymph node biopsy is indicated in these low risk patients. 14% of patients have 1 to 3 positive lymph nodes in the SOUND trial and that number is about 15% in the INSEMA trial. Really only the clinically actionable information to be gained is if a patient has four or more lymph nodes or N2 disease in this low risk patient population. So, essentially when that occurs it's less than 1% of the time in these patients with very favorable primary tumors. And therefore we thought it was acceptable to stand by a recommendation of not altering systemic therapy or radiation recommendations based on omission of sentinel nodes because the likelihood of having four more lymph nodes is so low. Dr. Ko Un "Clara" Park: I think one thing to add is the use of CDK4/6 inhibitors to that and when we look at the NATALEE criteria for ribociclib in particular, where node-negative patients were included, the bulk majority of the patients who were actually represented in the NATALEE study were stage III disease. And for stage I disease to upstage into anatomic stage III, that patient would need to have pathologic N2 disease. And as Dr. Torres stated, the rate of having pathologic N2 disease in both SOUND and INSEMA studies were less than 1%. And therefore it would be highly unlikely that these patients would be eligible just based on tumor size and characteristics for ribociclib. So we think that it is still safe to omit sentinel lymph node biopsy and they would not miss out, if you will, on the opportunity for CDK4/6 inhibitors. Brittany Harvey: Absolutely. I appreciate you describing those recommendations and then also the nuances of the evidence that's underpinning those recommendations, I think that's important for listeners. So Dr. Park, the next clinical question addresses patients with clinically node negative early stage breast cancer who have 1 or 2 sentinel lymph node metastases and who will receive breast conserving surgery with whole breast radiation therapy. For these patients, is axillary lymph node dissection needed? Dr. Ko Un "Clara" Park: No. And this is confirmed based on the ACOSOG Z0011 study that demonstrated in patients with 1 to 3 positive sentinel lymph node biopsy when the study compared completion axillary lymph node dissection to no completion axillary lymph node dissection, there was no difference. And actually, the 10-year overall survival as reported out in 2017 and at a median follow up of 9.3 years, the overall survival again for patients treated with sentinel lymph node biopsy alone versus those who were treated with axillary lymph node dissection was no different. It was 86.3% in sentinel lymph node biopsy versus 83.6% and the p-value was non-inferior at 0.02. And so we believe that it is safe for the select patients who are early stage with 1 to 2 positive lymph nodes on sentinel lymph node biopsy, undergoing whole breast radiation therapy to omit completion of axillary lymph node dissection. Brittany Harvey: Great, I appreciate you detailing what's recommended there as well. So then, to continue our discussion of axillary lymph node dissection, Dr. Torres, for patients with nodal metastases who will undergo mastectomy, is axillary lymph node dissection indicated? Dr. Mylin Torres: It's actually not and this is confirmed by two trials, the AMAROS study as well as the SENOMAC trial. And in both studies, they compared a full lymph node dissection versus sentinel lymph node biopsy alone in patients who are found to have 1 to 2 positive lymph nodes and confirmed that there was no difference in axillary recurrence rates, overall survival or disease-free survival. What was shown is that with more aggressive surgery completion axillary lymph node dissection, there were higher rates of morbidity including lymphedema, shoulder pain and paresthesias and arm numbness, decreased functioning of the arm and so there was only downside to doing a full lymph node dissection. Importantly, in both trials, if a full lymph node dissection was not done in the arm that where sentinel lymph node biopsy was done alone, all patients were prescribed post mastectomy radiation and regional nodal treatment and therefore both studies currently support the use of post mastectomy radiation and regional nodal treatment when a full lymph node dissection is not performed in these patients who are found to have N1 disease after a sentinel node biopsy. Brittany Harvey: Thank you. And then Dr. Park, for patients with early-stage breast cancer who do not have nodal metastases, can completion axillary lymph node dissection be omitted? Dr. Ko Un "Clara" Park: Yes, and this is an unchanged recommendation from the earlier ASCO Guidelines from 2017 as well as the 2021 joint guideline with Ontario Health, wherein patients with clinically node-negative early stage breast cancer, the staging of the axilla can be performed through sentinel lymph nodal biopsy and not completion axillary lymph node dissection. Brittany Harvey: Understood. So then, to wrap us up on the clinical questions here, Dr. Park, what is recommended regarding sentinel lymph node biopsy in special circumstances in populations? Dr. Ko Un "Clara" Park: One key highlight of the special populations is the use of sentinel lymph node biopsy for evaluation of the axilla in clinically node negative multicentric tumors. While there are no randomized clinical trials evaluating specifically the role of sentinel lymph nodal biopsy in multicentric tumors, in the guideline, we highlight this as one of the safe options for staging of the axilla and also for pregnant patients, these special circumstances, it is safe to perform sentinel lymph node biopsy in pregnant patients with the use of technetium - blue dye should be avoided in this population. In particular, I want to highlight where sentinel lymph node biopsy should not be used for staging of the axilla and that is in the population with inflammatory breast cancer. There are currently no studies demonstrating that sentinel lymph node biopsy is oncologically safe or accurate in patients with inflammatory breast cancer. And so, unfortunately, in this population, even after neoadjuvant systemic therapy, if they have a great response, the current guideline recommends mastectomy with axillary lymph node dissection. Brittany Harvey: Absolutely. I appreciate your viewing both where sentinel lymph node can be offered in these special circumstances in populations and where it really should not be used. So then, Dr. Torres, you talked at the beginning about how there's been these new practice changing trials that really impacted these recommendations. So in your view, what is the importance of this guideline update and how does it impact both clinicians and patients? Dr. Mylin Torres: Thank you for that question. This update and these trials that inform the update represent a significant shift in the treatment paradigm and standard of care for breast cancer patients with early-stage breast cancer. When you think about it, it seems almost counterintuitive that physicians and patients would not want to know if a lymph node is involved with cancer or not through sentinel lymph node biopsy procedure. But what these studies show is that preoperative axillary ultrasound, 85% of the time when it's negative, will correctly predict whether a sentinel lymph node is involved with cancer or not and will also be negative. So if you have imaging that's negative, your surgery is likely going to be negative. Some people might ask, what's the harm in doing a sentinel lymph node biopsy? It's important to recognize that upwards of 10% of patients, even after sentinel lymph node biopsy will develop lymphedema, chronic arm pain, shoulder immobility and arm immobility. And these can have a profound impact on quality of life. And if there is not a significant benefit to assessing lymph nodes, particularly in someone who has a preoperative axillary ultrasound that's negative, then why put a patient at risk for these morbidities that can impact them lifelong? Ideally, the adoption of omission of sentinel lymph node biopsy will lead to more multidisciplinary discussion and collaboration in the preoperative setting especially with our diagnostic physicians, radiology to assure that these patients are getting an axillary ultrasound and determine how omission of sentinel lymph node biopsy may impact the downstream treatments after surgery, particularly radiation and systemic therapy decisions, and will be adopted in real world patients, and how clinically we can develop a workflow where together we can make the best decisions for our patients in collaboration with them through shared decision making. Brittany Harvey: Absolutely. It's great to have these evidence-based updates for clinicians and patients to review and refer back to. So then finally, Dr. Park, looking to the future, what are the outstanding questions and ongoing trials regarding sentinel lymph node biopsy in early-stage breast cancer? Dr. Ko Un "Clara" Park: I think to toggle on Dr. Torres's comment about shared decision making, the emphasis on that I think will become even more evident in the future as we incorporate different types of de-escalation clinical studies. In particular, because as you saw in the SOUND and INSEMA studies, when we de-escalate one modality of the multimodality therapy, i.e., surgery, the other modalities such as radiation therapy and systemic therapy were “controlled” where we were not de-escalating multiple different modalities. However, as the audience may be familiar with, there are other types of de-escalation studies in particular radiation therapy, partial breast irradiation or omission of radiation therapy, and in those studies, the surgery is now controlled where oftentimes the patients are undergoing surgical axillary staging. And conversely when we're looking at endocrine therapy versus radiation therapy clinical trials, in those studies also the majority of the patients are undergoing surgical axillary staging. And so now as those studies demonstrate the oncologic safety of omission of a particular therapy, we will be in a position of more balancing of the data of trying to select which patients are the safe patients for omission of certain types of modality, and how do we balance whether it's surgery, radiation therapy, systemic therapy, endocrine therapy. And that's where as Dr. Torres stated, the shared decision making will become critically important. I'm a surgeon and so as a surgeon, I get to see the patients oftentimes first, especially when they have early-stage breast cancer. And so I could I guess be “selfish” and just do whatever I think is correct. But whatever the surgeon does, the decision does have consequences in the downstream decision making. And so the field really needs to, as Dr. Torres stated earlier, rethink the workflow of how early-stage breast cancer patients are brought forth and managed as a multidisciplinary team. I also think in future studies the expansion of the data to larger tumors, T3, in particular,reater than 5 cm and also how do we incorporate omission in that population will become more evident as we learn more about the oncologic safety of omitting sentinel lymph node biopsy. Dr. Mylin Torres: In addition, there are other outstanding ongoing clinical trials that are accruing patients right now. They include the BOOG 2013-08 study, SOAPET, NAUTILUS and the VENUS trials, all looking at patients with clinical T1, T2N0 disease and whether omission of sentinel lymph node biopsy is safe with various endpoints including regional recurrence, invasive disease-free survival and distant disease-free survival. I expect in addition to these studies there will be more studies ongoing even looking at the omission of sentinel lymph node biopsy in the post-neoadjuvant chemotherapy setting. And as our imaging improves in the future, there will be more studies improving other imaging modalities, probably in addition to axillary ultrasound in an attempt to accurately characterize whether lymph nodes within axilla contain cancer or not, and in that context whether omission of sentinel lymph node biopsy even in patients with larger tumors post-neoadjuvant chemotherapy may be done safely and could eventually become another shift in our treatment paradigm. Brittany Harvey: Yes. The shared decision making is key as we think about these updates to improve quality of life and we'll await data from these ongoing trials to inform future updates to this guideline. So I want to thank you both so much for your extensive work to update this guideline and thank you for your time today. Dr. Park and Dr. Torres. Dr. Mylin Torres: Thank you. Dr. Ko Un "Clara" Park: Thank you. 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/breast-cancer-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.  

  Bill and Loren Armstrong, the husband and wife team behind NEVERSECOND - the cutting edge nutrition brand that in only a couple years has become very popular among trail runners, establishing itself as a leader in the category. Of course, Freetrail has officially been in partnership with NEVERSECOND since the beginning of the year, and in that time we've loved getting to know Bill and Loren and have developed a huge admiration for how they conduct themselves and their business – a quality and professionalism that 100% shows up in their products, which are exquisite. I'm excited to share a bit more of their story here.     Topics discuss:     Their previous business Whipsmart which they owned and operated for 20 years The founding story of N2 and building a business on their own terms We talk about branding, timing, differentiation and other practical business considerations The systems based approach to fueling and recovery The NEVERSECOND product line and what sets it apart Doing things that don't scale Working with some of the best athletes in the sport including Katie Schide and a funny story about connecting with Jim Walmsley The future of the brand The flavorless C30 gel that hit the market this week! A lot more       Sponsors: Use code freetrail10 for 10% off Speedland Footwear Grab a trail running pack from Osprey Use code FREETRAIL25 for 25% off your first order of NEVERSECOND nutrition at never2.com Go to ketone.com/freetrail30 for 30% off a subscription of Ketone IQ Freetrail Links: Website | Freetrail Pro | Patreon | Instagram | YouTube | Freetrail Experts   Dylan Links: Instagram | Twitter | LinkedIn | Strava

《N2文法30天必考攻略》博客來，金石堂，誠品書店 --- 教學內容 想對編輯說的話：提問箱 來IG學更多：EZJapan IG -- Hosting provided by SoundOn

durée : 00:02:33 - Le Stade Poitevin Foot reçot Saint-Brieuc en N2

durée : 00:02:21 - Retour sur le match de foot de N2 du Stade Poitevin à Saint-Malo

UPDATE: afirmei neste episódio de que iria realizar a N2 para a semana que vem, já não vai acontecer. Adiei para outra altura do ano. Budda Guedes, The Shaggs e outras coisas que tais.

At least eight people have tragically lost their lives in a devastating accident in KwaZulu-Natal. 80 of the victims were church members traveling from Richards Bay to Shakaskraal when their bus suffered a tyre burst on the N2 between Mandeni and Stanger. The driver lost control, causing the vehicle to roll down an embankment. For more on this Elvis Presslin spoke to IPSS Security Operations Manager Phumlani Vezi

durée : 00:02:16 - Retour sur le match de foot de N2 de Poitiers contre Saint-Pryvé

Individualized medicine means that your set of symptoms are your own personal collection and we misunderstand symptoms when we consider them accidental and/or a set of predetermined generalized syndromes or diseases that everyone experiences.  Symptoms are not accidental and they are signs and responses to different things happening to the individual.  Trying to collect them into syndromes means you are treating something that does not exist. Narratives that can provide more insight into better understanding this episode are 23, 30, 34, 35, 49 and 119.  For those with no prior knowledge of homeopathy, listening to N2-5 may help you reach a basic understanding of homeopathy, its principles and how remedies work. All views presented are based on credible sources, but they are explained through the individual's viewpoint.  Doing your own research while integrating new information is always important when forming your own viewpoint. The information in this podcast is not meant to address individual health needs, it is general in nature and should not be used as medical information for your health unless used in combination with your health practitioner.  

In this JCO Article Insights episode, Peter Li summarizes “Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years,” by Dr. Jianwei Zhang et al. published on December 13, 2024. TRANSCRIPT Peter Li: Hello and welcome to the JCO Article Insights. I'm your host Peter Li and today we will be discussing the Journal of Clinical Oncology article, “Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years,” by Dr. Jianwei Zhang et al.  For a reminder to the audience, the FOWARC study is a Chinese-based study that looked into the treatment of locally advanced rectal cancers with neoadjuvant chemotherapy based regimens with or without radiation. This study was first published back in 2019 where the three-year data showed no difference in three-year disease-free survival over survival between the three study arms. As a reminder of what those arms were, there were one historical control and two interventional arms. The control arm used 5-FU with radiation therapy with five cycles of 5-fluorouracil with radiation during cycles two to four followed by surgery and then seven cycles adjuvantly. Their first interventional arm was the same as the control arm with the addition of oxaliplatin on day 1of each cycle. And lastly, the third arm was FOLFOX only for four to six cycles followed by surgery and then six to eight cycles adjuvantly completing about a total of 12 weeks of chemotherapy.  They recruited about 495 patients with 165 patients randomized to each arm. They were relatively well balanced by age, clinical staging and distance from the anal verge. Median age was about mid-50s with a slight male predominance and patients were primarily stage 3 with 20% to 30% being stage 2. About 30% had clinical T4 disease and about 25% had clinical N2 disease. Median follow up time was 122.5 months or 10 years and their follow up endpoints were disease-free survival, overall survival and local recurrence, and they also performed subgroup analyses based on post surgical pathological staging. Survival was analyzed using Kaplan-Meier method with a significant threshold of p being less than 0.05. About 451 patients actually underwent surgery, which is about 91% of patients. The main reason for not going through surgery was due to refusal but one was due to toxicity and two were due to disease progression in the control arm. Follow up loss rate was about 10% in each group. Now looking at their primary endpoints in their initial study, local recurrence was about 8.8% in the control arm versus 7.9% in the FOLFOX radiation group versus 9.2% in the FOLFOX only group. Distant metastasis was about 30% in each arm and the sites of metastases were primarily in the lung and liver.   Now, following up with 10 years, there were only three new events in the chemoradiation group with local recurrence happening at 10.8% in the control arm versus 8% in the FOLFOX RT group versus 9.6% in the chemo only group. These findings were not statistically significant. In their subgroup analysis by pathological staging, they found that pathological CR or complete response had a lower rate of local recurrence compared to those with increasing pathological staging coming in at 3% versus 4.3% versus 11.6% versus 15.8% in pCR versus Stage 1, 2, 3 respectively. And they found no difference in each stage with each interventional arm. Looking at long term survival their 10-year disease free survival showed 52.5% in the 5-FU radiation group versus 62.6% in the FOLFOX RT group versus 60.5% in the chemotherapy only group with no statistically significant difference between three groups. By pathological staging, they found improved 10-year disease survival in those who achieved pathological complete response versus those who did not with 84.3% in the pCR group versus 78.7% versus 56.8% versus 27.7% in the stage 1 versus 2 versus 3 group. And again they found no statistical significance difference between each arm.   Now looking at the 10-year overall survival rates between the three arms, in the control arm the 10-year overall survival was 65.9% versus 72.3% in the FOLFOX RT group versus 73.4% in the chemo only group. By pathological stage, again, they showed a statistically significant difference in those who achieved pCR versus those who had pathological stage 1 to 3 disease with overall survival being 92.4% in those who achieved pCR versus 84.9% versus 68.6% versus 48.8% in stage 1, 2, 3 respectively. Now in the discussion, authors mentioned that with a median follow up of 10 years, FOLFOX alone had similar disease-free survival, local recurrence and distant metastasis and overall survival compared to those who received neoadjuvant chemoradiation, justifying the omission of radiation without compromising results or outcomes for each patient. There were no differences in subgroup analysis for disease free survival local recurrence or overall survival based on pathological staging. There were only three new events compared to the last follow up, with local recurrence happening only in the chemo radiation groups. Local recurrence rates at 10 years was about 10%. Compared to other clinical trials such as CAO, ARO or AIO-94, the rate of local recurrence was similar to those historical trials.  The authors also compared their findings to the PROSPECT study which looks at the use of total neoadjuvant chemo radiation versus chemotherapy alone, which boasted only about a 2% local recurrence rate. But as a reminder, high risk locally advanced rectal cancers were excluded, mainly those with T4 or N2 disease, which may explain the difference in terms of local recurrence in the PROSPECT versus this study. Another finding is that pathological complete responses are also an important prognostic marker with lower 10-year local recurrence rate, disease-free survival and overall survival with worse outcomes with increased pathological staging. Distant metastasis rates were still at 30%, with the most common site being lung then liver then lymph nodes consistent with other historical studies. Chemotherapy seemed to be better at reducing liver mets than lung metastasis per their findings. In their post hoc analysis of their own study, chemo radiation was also associated with higher incidence of low anterior resection syndrome and persistent ostomy compared to chemotherapy alone, meaning that they had better quality of life with the chemotherapy only approach.  In conclusion, a chemotherapy only approach can be safe and a feasible treatment for locally advanced rectal cancer without compromising outcomes. Omission of radiation may reduce the risk of overtreatment and improve quality of life for some of these patients. However, this does not necessarily exclude the role of radiation as it may still play a role in a response escalation approach for those who do not respond to chemotherapy alone.   This wraps up today's episode. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts.   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.  

durée : 00:02:12 - Le Stade Poitevin Foot affrontait Blois en N2

Disclaimer: This podcast does not provide medical advice. The content of this podcast is provided for informational or educational purposes only. It is not intended to be a substitute for informed medical advice or care. You should not use this information to diagnose or treat any health issue without consulting your doctor. Always seek medical advice before making any lifestyle changes. Diane's Story: I had no idea I was sick, never mind having lung cancer. There were times when I did feel something was not right with my health, but the doctors thought it was all in my head. So, I just continued living life. On December 9th , 2012, I started to get pains in my chest and felt sick to my stomach. My family thought I was having a heart attack and called 911. I was taken to the emergency room, and it was there after all the tests showing I wasn't having a heart attack; the doctor informed me that I had a mass in my chest. I cannot find the words to describe how I felt after the ER doctor so nonchalantly gave me the results of the chest x-ray. He then proceeded to give me morphine for the pain and medicine for the nausea. So that was the start of my surreal relationship with lung cancer. After having a PET scan and a CT Guided Biopsy, I was diagnosed with Primary, Thorax Small Cell Lung Cancer Stage, IIIA (T3, N2, M0, G2) Lymph-Vascular Invasion in my upper left lung and given the news on January 15, 2013. On January 31, 2013, I had surgery (Lobectomy) to remove the tumor from my upper left lung. Now the treatments begin to lessen the possibility of cancer recurring in my lungs and keep it from spreading to other parts of my body. My first round of chemotherapy in March 2013 almost killed me. The day after my first treatment I had to be admitted into the hospital because, I was allergic to the chemo drug, cisplatin. I was unable to eat for a week. I was so sick, and my potassium and magnesium level were extremely low. I thought I was going to die. After this incident, I was told there was nothing else they could do for me, so I opted for a second opinion.

durée : 00:02:24 - Retour sur le match de foot de N2 entre Poitiers et Avranches

durée : 00:02:35 - Le 2' chrono, ici Poitou

Viele Mannheimer haben den Kopf geschüttelt, als das Stadthaus am Paradeplatz im Sommer 2021 unter Denkmalschutz gestellt wurde. Ähnlich waren die Reaktionen jetzt, als das Parkhaus in N2 diesen Status bekam. Bei „Mensch Mannheim“ erklärt Martin Hahn vom Landesamt für Denkmalpflege, wie solche Entscheidungen zustande kommen, warum sie wichtig und in gewisser Weise auch nachhaltig sind. Er verrät außerdem, was sein Lieblingsdenkmal in Mannheim ist – und wie ein Denkmalschützer eigentlich privat wohnt.

Radio 4 Brainport expands its DAB+ broadcasting coverage. The international radio signal in the Brainport region will now also reach large parts of the Kempen area. A powerful new transmitter will feed four antennas located in the radio tower at de Croy, along the A2 and N2 highways in western Eindhoven. This tower will provide a strong radio signal throughout Eindhoven and its surrounding communities. With its height of 90 meters, it has a direct line of sight with almost all of the Kempen. Radio presenter Jean-Paul Linnartz visited the installation team from Radio Network Nederland and spoke with project manager Peter Oonk. The DAB transmitter is capable of carrying up to 18 radio stations simultaneously, including Studio040, GlowFM, and Rivierenland Radio.

De radio wordt digitaal en dat geldt nu ook voor de lokale radio. Vier lokale stations breiden hun DAB+ uitzendbereik flink uit. Vanaf deze week bereikt een digitaal radiosignaal van Rivierenland Radio, Studio040, GlowFM en Radio 4 Brainport ook grote delen van de zuidoost Brabant. Een krachtige nieuwe zender zal vier antennes voeden die zich in de zendmast op de Croy bevinden, langs de snelwegen A2 en N2 in West-Eindhoven. Deze 90 meter hoge toren zal zorgen voor een sterk radiosignaal in heel Eindhoven en de omliggende gemeenten, vanaf een plek waar ook de hele Kempen is te overzien. Radio 4 Brainport presentator Jean-Paul Linnartz bezocht het installatieteam van Radio Netwerk Nederland en sprak met projectmanager Peter Oonk. De DAB-zender kan tzt maximaal 18 radiostations tegelijk verzenden.

KZN woke up to a huge traffic jam on the N2 caused by a cash-in-transit heist that turned deadly. The crime scene delayed KZN drivers, causing frustration and fear. We spoke to various people on the ground who gave updates on the situation. Webpage

KwaZulu Natal police are currently on the lookout for an unknown number of suspects. This comes after the N2 freeway in the south of Durban was this morning closed during peak traffic following a cash-in-transit (CIT) heist, where one person was killed one and 10 injured. The attack took place between the M7 and the M1 Higginson Highway. All suspects reported to have fled the scene. For an update we are joined on the line by Colonel Robert Netshiunda

A 30 ans, elle dirige l'une des plus belles scale-up de la French Tech.Laetitia s'installe dans le fauteuil de tech 45' cette semaine

A 30 ans, elle dirige l'une des plus belles scale-up de la French Tech.Entrée comme Chief of staff en 2022, Laetitia est désormais la N2 de Greenly, c'est notamment elle qui a mené leur dernière levée de fonds de près de 50M€. Qui a dit que la tech

Justin Bruce welcomes first-time guest Brendon Holland to recap the January 10 & 11, 2025 shows at Tree House Brewing Company in Deerfield, Massachusetts.Brendon is a professional videographer and recorded full videos of both shows and uploaded them to YouTube! N1 delivers a near-40 minute Figure It Out jam for the ages, and N2 garnered attention as the band infused a jammed-out Waiting Game with Phish's First Tube and elements of DWD and Chalkdust Torture.Thanks to Al W. for the crispy audience recordings used in the numerous jam clips scattered throughout this episode. Listen to his AUDs of N1 and N2 and peruse his catalogue of recordings on his Archive.org profile page.Vice or Virtue is a proud part of Osiris Media.Follow Vice or Virtue on InstagramFollow Justin Bruce on MastodonFollow Vice or Virtue on BlueskyEmail viceorvirtueaneggypod at gmail dot com Hosted on Acast. See acast.com/privacy for more information.

HPQ Silicon Inc. (TSX-V: HPQ)HPQ Silica Polvere has reached a major milestone with the commencement of operations at its Fumed Silica Reactor pilot plant. This breakthrough positions HPQ as a leader in green engineering and advanced materials, targeting industries like cosmetics and electronics. The reactor is set to deliver high-purity fumed silica with a projected capacity of 50 metric tons annually. HPQ is also collaborating with global partners, including Evonik, for product validation, further solidifying its industry position. Draganfly Inc. (NASDAQ: DPRO)Draganfly is partnering with Volatus Aerospace to revolutionize oil and gas exploration with advanced Bathymetric LiDAR technology and its Heavy Lift Drone. This innovative solution is set to enhance underwater mapping and operational efficiency in the $104 billion offshore energy market, showcasing the transformative potential of drone and LiDAR applications. BrandPilot AI (CSE: BPAI)BrandPilot AI is leading the adtech revolution by integrating cryptocurrency payments through Coinbase Commerce. By accepting Bitcoin, Ethereum, and USD Coin, the company simplifies global transactions and aligns with the growing demand for blockchain solutions in digital marketing. This bold move positions BrandPilot AI as a forward-thinking leader in adtech and blockchain innovation. Formation Metals (CSE: FOMO)Formation Metals has acquired the N2 property in Quebec's Casa Berardi Gold Trend, securing 87 mineral claims with a historical estimate of 810,000 ounces of gold. Located in one of North America's most productive gold districts, this acquisition represents a strategic step in bolstering the company's presence in the mining sector, with significant exploration potential for long-term value creation. Galway Metals (TSX-V: GWM)Galway Metals announced high-grade drill results at its Clarence Stream Gold Project in New Brunswick, including 26.9 g/t gold over 8.6m and 368.0 g/t over 0.5m. With 2.25 million ounces of gold resources and critical antimony deposits, Galway is advancing exploration and economic studies, positioning itself as a standout player in Canada's resource economy. GoGold Resources (TSX: GGD; OTCQX: GLGDF)GoGold has released a Feasibility Study for its Los Ricos South Project in Mexico. Key highlights include: After-Tax NPV: $355M with a 28% IRR. Mine Life: 15 years, targeting 80M silver-equivalent ounces. Sustainability: Incorporates environmentally friendly dry-stack tailings. GoGold aims to secure permits by March 2025, moving closer to construction and solidifying its position as a leader in silver and gold mining. Follow AGORACOM for more breaking small-cap news and updates.

Na estante desta semana, temos uma memória familiar que resultou num filme de sucesso: “Ainda Estou Aqui”, de Marcelo Rubens Paiva, que deu origem à película com que Fernanda Torres ganhou o Globo de Ouro de melhor actriz; há também um livro que percorre a Nacional 2 em fotografias a preto e branco: “N2, O Signo e a Paisagem”; e recomenda-se ainda o romance que conquistou o prémio Booker Internacional: “Kairos”, de Jenny Erpenbeck.See omnystudio.com/listener for privacy information.

Justin Bruce welcomes Ryan Storm and Al W. back to the pod to discuss the band's late November co-headlining run at the Capitol Theatre in Port Chester, New York with Dogs in a Pile. Ryan wrote great reviews of N1 and N2 on his Substack page. This episode utilizes Al's audience recordings. Thank a taper! You can find all of his AUDs on his Archive.org profile page. Al's conversation begins around the 50 minute mark of this episode.Follow Vice or Virtue on InstagramFollow Justin Bruce on MastodonFollow Justin Bruce on BlueskyEmail viceorvirtueaneggypod at gmail dot com Hosted on Acast. See acast.com/privacy for more information.

Have you ever snapped someone's head off simply because you are a sleepy head?  Our fuses can get pretty short when we're sleep deprived.  We need dream time therapy to hit reset on our emotions. And without it, look out. Sleep is so much more than rest. You and those around you can appreciate the benefits of good sleep on emotions and mood. Sleep is so much more than rest. You and those around you can appreciate the benefits of good sleep on emotions and mood. I'm Dr. Vickie Petz Kasper, I help you make changes that make a difference. Healthy Looks Great On You podcast takes you to mini medical school so you can learn the power of lifestyle medicine. Sleep is hard work. And I don't mean getting to sleep and staying asleep is hard work, though it often is. I mean, there's a lot of work that goes on while you sleep.  Sleep rebuilds your mental landscape. What happens when you sleep affects your emotions while you're awake. The brain undergoes active processing and healing while you're getting your Z's. You need sleep for emotional maintenance. The physiology is absolutely fascinating. So let's start right off the bat by going to mini medical school and learning about how sleep affects mood. Now, don't worry. I'll make it fun so you don't sleep through class.  Let's start with sleep cycle basics. There are two primary types of sleep that alternate in cycles throughout the night. And those are REM and non REM. That probably already sounds familiar. REM stands for rapid eye movement  and  they each have different functions. Non REM does the work of physical restoration and recovery, while REM does the emotional processing and cognitive maintenance. It's divided into three stages. Now this is going to be super easy to remember because the stages are called N1, N2, and N3. But let's peek under the covers and explore each of them a little more. Stage N1 is light sleep. And this is a transition between being asleep and being awake, and it only lasts about 5 or 10 minutes. In this stage, your muscle activity slows down, though you might twitch occasionally, and you can be easily awakened and even somewhat aware of your surroundings. You're actually asleep, but you're just in that lightest stage of sleep.  Stage N2 is moderate sleep, and this accounts for about 50 percent of total sleep time. During stage N2 sleep, your body cools down. The temperature actually gets lower, and your heart rate slows, and your brain waves slow down, and this is so important for memory consolidation. In fact, stage N2 sleep has a huge impact on your ability to learn, remember, and retain new information. The cognitive impact also includes decision making skills. Without adequate stage in to sleep, Memories don't get consolidated, and processing speed is slowed down, and so this causes increased difficulty with complex cognitive tasks. Lack of adequate sleep doesn't just affect your cognitive ability, though. It also affects mood. It makes us more susceptible to the effects of stress, both physically and emotionally. And emotionally.  Poor sleep disrupts emotional regulation, so we're more reactive.  The next time someone's voice goes up a couple of octaves in response to something you said, maybe, just maybe, They didn't sleep well last night.  I don't recommend mentioning it.  Even more serious than becoming a soprano during a conversation, without good sleep, people have an increased risk of mood disorders like depression and anxiety. And at the very least, the symptoms of anxiety are heightened without adequate shut eye. And listen, everyone reacts to having their buttons pushed, but when the work of sleep is on strike, our emotional resilience is kaput.   And the fruit of the spirit just goes right out the window. No peace, no patience, no kindness, no goodness, and definitely no gentleness.  Now, emotional reactions can be dangerous, but the physical health consequences of poor sleep can be deadly. Without good quality sleep, the immune system is weaker, metabolism is wrecked, Inflammation skyrockets and even hormones get out of whack. We need sleep for healing and recovery every single time the earth revolves around the sun. Think of your brain as a computer. You know, it has to be charged in order to function. Without recharging through sleep, there are several neurologic effects on your brain. Those grouchy neurons in your head quit communicating effectively. This leads to impaired synaptic plasticity. The dampening of the pathways in the brain to adapt and rewire themselves. It causes the brain to filter and organize information much less effectively. This leads to decreased productivity, more errors, and accidents. This process is crucial for emotional learning, adaptation, and developing resilience to emotional challenges. And don't we all have emotional challenges?  Stage N2 sleep is critical for overall cognitive and physical restoration. Chronic deficiency can lead to cumulative negative effects on mental and physical well being. Now before you put your head down on your desk for a little nap, Now, let's move on to the deepest subject, stage N3, or deep sleep. This one is essential for feeling refreshed. And here's the deal, you can't really skip over stage N1 and stage 2 to get there.  You can probably guess that this stage of deep sleep is the most restorative. It's harder to wake up during N3. It's so critical for physical recovery,  strengthening the immune system and promoting growth and repair of tissues.  You know how they always do road work at night? Well, your brain kind of does the same thing. And just like highway repair, it's never ending. Now, let's shift gears a little bit and talk about REM sleep. The brain undergoes a sophisticated process of emotional memory integration. And this just isn't passive storage, but it's an active recalibration of all of your emotional experiences.  And as implied by its name rapid eye movement. The eyes move rapidly beneath the eyelids and the brain is actually highly active, but the body is temporarily paralyzed.   This part of the sleep cycle is critical for cognitive functions like memory consolidation, emotional regulation, learning, and creative problem solving. I mean, have you ever woken up in the morning and just had a better perspective on things?   I certainly have. But while your eyes are dancing, your brain is sorting and processing emotional experiences. And this is what leads us to be more clear headed and in control of our emotions during the day. And without it, you're probably going to wind up on Santa's naughty list.  So, how does all this work? Well, that little maintenance crew in your brain goes to work in your prefrontal cortex. When the work of sleep is disrupted, emotional processing is impaired, which causes heightened emotional reactivity  and the reduced ability to manage stress.  No wonder we get irritable when we're sleep deprived.  Even more serious, during this phase of sleep, traumatic or intensely emotional memories are processed, and they're gradually detached from their immediate emotional intensity. So think about that. If they don't get detached, you just keep reliving it over and over with all of the emotional intensity attached.  That's miserable.  The brain essentially sorts out these emotional experiences and helps reduce their psychological impact. And that prevents us from being overwhelmed and it keeps us resilient.  Now that you understand how this neurochemical rebalancing of sleep has a direct impact on mood, Let's step into the lab for a sec and just look at a little bit of sleep chemistry. You see, sleep keeps neurotransmitters and hormones in balance to stabilize mood. Everybody's always worried about their hormones being out of balance. Well, how about trying a good night's sleep? Things like serotonin, the happy hormone, cortisol, the stress hormone, and dopamine, the motivating and pleasure hormone. All get regulated during sleep. What happens is, sleep replenishes the serotonin and dopamine while clearing out the excess cortisol.  When these neurochemicals are out of balance, due to poor sleep, there's more inflammation in the brain.   And that can increase anxiety and depressive symptoms. In fact, studies show that chronic sleepyheads are ten times more likely to experience symptoms of depression.  So, there's this little cleanup crew in the brain that's supposed to haul all of those inflammatory proteins to the dump. We call that the glymphatic system. But without good sleep at night,  they  don't get an opportunity to come in and clean up all those messes created during the day. As a result, there are more mood swings and more mood disorders. And here's the deal. It doesn't take a lot of sleep deprivation to cause a pile up. Even mild sleep deprivation can affect emotions. Just one night of poor sleep can increase negative emotional reactivity by up to 60%.    The bottom line is that sleep is so much more than rest. It's actually hard work. It's an active and very complex process coordinated by the amygdala. which is the brain's emotional processing center, as well as the prefrontal cortex, and that's where we make rational decisions. Or if we're sleep deprived, it's where we make irrational decisions.  The brain's nightly housekeeping crew, which occurs most effectively during deep sleep, helps maintain and restore emotional control. It's necessary to reset communication patterns, and reduce impulsive outbursts.    Think of it as a nightly emotional tune up for your brain, helping you process, adapt, and maintain psychological balance. And we all need balance, don't we? But like everything in life, this is no quick fix. Adults go through four to five complete sleep cycles every night, and each one of them lasts about 90 to 120 minutes. In other words, it takes some time to get there.  REM sleep tends to be shorter early on in the night and gets longer as the night goes on. It can last up to an hour. So, if you're feeling big feels that are out of proportion to the situation, take a look at your sleep quantity and quality.  Maybe your crankiness is a result of imbalance caused by lack of good sleep,  or depression, anxiety, or plain old stress that impacts sleep which interferes with that critical maintenance that goes on during shut eye.  Are you struggling with this area of your health?  If you have trouble with spinning thoughts that keep you from lying down in perfect peace, then grab a sleep freebie from my website.  This cheat sheet will help get you started turning off your mind so you can turn on restorative sleep. There's a link in the show notes or you can just head on over to my website www. healthylooksgreatonyou.com and look for the sleep freebie. If you want to feel rested, restored, and refreshed during the day, you need a good night's sleep.   It will help you feel in control of your emotions instead of them tricking you into making mountains out of molehills. Getting enough shut eye is crucial for your health, and healthy looks great on you.       RESOURCES: Cheat sheet to TURN OFF YOUR MIND AND TURN ON RESTORATIVE SLEEP Healthy Looks Great on You  Good food for good mood Move for better mood How alcohol, sugar and caffeine affect mood Navigating connections during the holidays From loneliness to belonging    

Hoy te traigo la herramienta más importante de un creador de contenido:El calendario de publicaciones.Vas a aprender exactamente cómo planificar los contenidos que debes publicar en las próximas semanas y meses y lo vamos a hacer, en menos de 15 minutos. Gracias a herramientas de IA y Notion.¿Estás suscrito ya?Hay un mensaje muy repetido en redes por diferentes creadores y divulgadores: “Consistencia > Talento”Es una frase que me encanta y estoy muy de acuerdo con ella.Pero, lo que no te explica esta frase es que la consistencia es muy muy complicada de conseguir y mantener.Como creadores de contenido, la consistencia hace referencia a ser capaz de mantener una frecuencia y calidad en tus creaciones.Si consigues esto en tu proyecto, ganas la partida.Es así de simple.Así de complejo.Por eso quería dedicar un episodio completo a explicarte cómo crear un calendario de publicaciones que de consistencia a nuestro proyecto.Vamos a ello.1- Temática y público objetivoLo primero que necesitamos es tener definida nuestra temática y público objetivo.Esto es algo básico e indispensable.No puedes pasar al siguiente punto si no sabes de qué vas a hablar y a quién quieres llegar.Para ponerte un ejemplo, con FailAgain mi temática es “creación de contenido” y mi público son “otros creadores que están empezando o están estancados y necesitan inspiración y nuevas ideas”.Yo lo tengo muy claro y ya puedes ver cómo este contenido está 100% dirigido a este público.Tómate unos minutos para definir este punto y seguimos con el siguiente que es uno de los más claves.2- Pilares de contenidoDentro de tu temática, tienes que encontrar los diferentes pilares de contenido que la construyen.Este es el primer paso para clasificar las publicaciones que vas a crear y te va a permitir ser organizado y obtener ideas de forma mucho más rápida.Estos pilares son categorías de tus contenidos.Te voy a poner el ejemplo de 4 pilares que tengo en FailAgain para que entiendas el punto:* Creatividad* Crecimiento de audiencias* Monetización* Estrategia y planificaciónPara obtener estos pilares, puedes hacerlo de varias formas:* Sentarte con un folio en blanco y pensar* Revisar tus contenidos y los de tus competidores y encontrar dichos pilares.* Utilizar herramientas de IA que te lo hagan más fácil.Si te decantas por esta última opción, te dejo un prompt que puedes copiar y utilizar en ChatGPT o Claude donde solo tienes que indicar tu temática principal y público objetivo para que la herramienta te dé tus pilares.# Prompt para identificar pilares de contenido Eres un estratega experto en content marketing. Tu tarea es identificar 4-6 pilares de contenido principales que sirvan como base para estructurar un proyecto de creación de contenido. Necesito que me ayudes a identificar los pilares de contenido para mi proyecto. Te comparto: 1. Temática principal: [¿Sobre qué tema creas contenido?] 2. Público objetivo: [¿Para quién creas este contenido?] Por favor, proporciona: - 4-6 pilares principales de contenido - Una breve descripción de cada pilar (máximo 2 líneas) - Los pilares deben ser lo suficientemente amplios para generar contenido regular pero específicos para mantener el foco - Evita solapamientos entre pilares Ejemplo de respuesta esperada: PILAR 1: [Nombre del pilar] Descripción: [Breve explicación de qué trata este pilar y por qué es relevante para tu audiencia] [Repetir formato para cada pilar]3- Canal, tipos y frecuenciaEstamos a nada de obtener las primeras ideas de contenido para nuestro calendario de publicaciones, pero antes, necesitamos seleccionar el canal y frecuencia de publicación.A partir de este punto estaremos creando una estrategia adaptada a uno de los canales con los que quieres trabajar y podrás posteriormente realizar más estrategias de publicación para el resto de los canales que gestiones.Es decir, si quieres crear contenido en una newsletter y en YouTube, tendrás que venir a este punto con cada uno de los canales que quieras trabajar y realizar todo el proceso de forma adaptada.No te preocupes porque te voy a poner varios ejemplos.Supongamos que quiero establecer mi estrategia de publicaciones para YouTube.¿Cómo puedo saber la frecuencia que necesito para mi canal?Tremenda pregunta.Aquí vamos a juntar varios factores que son clave para responderla:* Tipo de contenido: nuestra tipología de vídeos van a marcar mucho la frecuencia con la que publicamos, ya sea por la profundidad con la que abordamos los temas o la calidad con la que generemos el contenido. No es lo mismo crear una píldora de 5 minutos con un consejo grabada con el móvil que una guía completa de una hora grabada con 2 planos y cientos de cortes de edición.* Capacidad y tiempo disponible: cuánto contenido eres capaz de generar en tu tiempo disponible para este canal. Necesitas saber lo que te cuesta crear una pieza y publicarla y entender que la clave de la consistencia es que puedas mantener esta frecuencia a lo largo del tiempo sin fallo.* Competencia y sector: revisa tus competidores y encuentra patrones de frecuencia. ¿Sacan contenido cada día? ¿Cada semana? ¿Cada mes? No tiene por qué ser determinante, pero sí te ayudará a entender el nivel de trabajo que requiere tener un canal en tu sector de forma exitosa.Con esto anterior en mente… ¿cuántos contenidos vas a ser capaz de publicar este mes?Haz tus cálculos y vamos a pasar a la fase final de creación del calendario.4- Creando el calendarioComienza la acción. Te cuento el plan para que estés preparado.* Vamos a generar un listado de ideas. ¿Cuántas? Muchas, no te preocupes.* Clasificaremos y ordenaremos esas ideas* Relacionaremos unas ideas con otras para fomentar que nuestro público siga consumiendo nuestros contenidos hasta el infinito.1- Obtener ideasLas ideas llegan a nosotros de dos formas: aparecen ingeniosamente sin buscarlas o nos ponemos a currar y las terminamos encontrándolas.Hoy nos centramos en esta segunda vía.Para buscar ideas puedes hacer esto:* Volver a ponerte delante del folio en blanco y estrujarte el cerebro.* Revisar contenido de competidores* Revisar comentarios de otras publicaciones tuyas o de competencia* O puedes usar un prompt que te dejo para extraer nuevas ideas desde ChatGPT y ClaudeEste prompt necesita que le coloques toda la información que hemos trabajado previamente:* Temática* Público objetivo* Pilares de contenido* Canal de publicación# Prompt para generar ideas de contenido por pilar Eres un estratega de contenido experto. Tu objetivo es generar ideas de contenido específicas y accionables para cada pilar proporcionado, adaptadas al canal de publicación indicado. Para ayudarme a generar ideas de contenido, te proporciono: 1. Temática principal: [¿Sobre qué tema creas contenido?] 2. Público objetivo: [¿Para quién creas este contenido?] 3. Pilares de contenido: [Lista tus 4-6 pilares principales] 4. Canal de publicación: [¿Dónde se publicará este contenido?] Por favor, genera: - 10 ideas de contenido concretas para cada pilar - Cada idea debe ser un titular o concepto específico, no genérico - Las ideas deben adaptarse al formato del canal especificado - Cada idea debe resolver un problema o aportar valor concreto - Evita solapamientos entre ideas de diferentes pilares Ejemplo de formato de respuesta esperado: PILAR 1: [Nombre del pilar] 1. [Título/Concepto específico de la idea 1] 2. [Título/Concepto específico de la idea 2] [...] 10. [Título/Concepto específico de la idea 10] [Repetir para cada pilar] Asegúrate de que: - Los títulos sean llamativos y específicos - Las ideas sean accionables - El contenido sea relevante para el público objetivo - Las ideas aprovechen las fortalezas del canal elegidoEstos prompts son solo el inicio de la conversación, tú puedes seguir pidiendo ajustes y mejoras sobre el contenido que te va generando la IA y eso te llevará a ideas mucho más refinadas para tu calendario.Antes de continuar yo dedicaría un rato descartar y transformar aquellas ideas que no encajan en lo que tú quieres publicar. Esto es 100% necesario si no quieres que tu contenido sea simplemente un listado de ideas regurgitadas por ChatGPT.2- Clasificar y ordenarCon todas las ideas que has ido obteniendo la cosa va tomando forma.Ahora vamos a poner en una lista todas las ideas que se han generado y clasificarlas y ordenarlas.Las agruparemos evidentemente por los pilares de contenido que hemos definido al inicio y las ordenaremos de forma inteligente, siendo los conceptos más básicos los primeros y subiendo el nivel progresivamente.Para esta tarea también podemos usar IA así que te dejo el Prompt para que puedas usarlo en la misma conversación de ChatGPT o Claude donde estés trabajando.# Prompt para organizar y clasificar ideas de contenido Eres un experto en arquitectura de información y desarrollo de audiencias. Tu objetivo es organizar un listado de ideas de contenido por pilares y niveles de complejidad para crear una progresión lógica de aprendizaje. Por favor, analiza las siguientes ideas de contenido y organízalas según estos criterios: 1. Lista de ideas de contenido: [Pegar aquí tu listado de ideas] 2. Pilares de contenido: [Lista tus pilares] Organiza el contenido en tres niveles por cada pilar: - Nivel 1 (Fundamentos): Conceptos básicos y primeros pasos - Nivel 2 (Intermedio): Aplicación práctica y estrategias - Nivel 3 (Avanzado): Optimización y conceptos complejos Formato de respuesta: PILAR [Nombre]: Nivel 1 - Fundamentos: - [Idea 1] → Por qué este es contenido básico - [Idea 2] → Por qué este es contenido básico [...] Nivel 2 - Intermedio: - [Idea 1] → Por qué este es contenido intermedio [...] Nivel 3 - Avanzado: - [Idea 1] → Por qué este es contenido avanzado [...] [Repetir para cada pilar] Consideraciones para la clasificación: - El contenido básico debe ser accesible para principiantes absolutos - El contenido intermedio requiere conocimiento de conceptos básicos - El contenido avanzado debe construir sobre conceptos intermedios - La progresión debe ser lógica y permitir un aprendizaje escalonado Ya tenemos la lista completa, clasificada y ordenada.Vamos con un último ajuste que puede marcar la diferencia.3- Interrelación de contenidosEstamos generando un listado de contenidos que va a tener muchísimas conexiones entre sí.No aprovechar este punto sería un fallo tremendo por nuestra parte, así que vamos a conectar las ideas y generar una red de conocimiento entre nuestras publicaciones.Todo ello en esta fase de planificación, no me digáis que no es una pasada.Para esta tarea, vamos a ir directamente a la herramienta de IA que estemos utilizando y le vamos a incorporar el resultado obtenido con el trabajo previo.Como en los anteriores pasos, te dejo el prompt con todo lo necesario y el resultado que vas a obtener es una tabla ya lista para que nos la podamos llevar a Notion.# Prompt para Crear Tabla de Contenido Relacionado Eres un experto en gestión de contenido editorial. Tu objetivo es crear una tabla detallada en formato Markdown que organice el contenido y establezca relaciones entre las diferentes piezas. Por favor, genera una tabla organizada con el siguiente contenido: 1. Lista de ideas de contenido: [Pegar aquí tu listado de ideas organizadas por pilares y niveles] Crea una tabla con las siguientes columnas: - ID: Número único para cada publicación (formato numérico: 00001) - Título: Título de la publicación - Pilar: Pilar de contenido al que pertenece - Nivel: Básico (N1), Intermedio (N2), Avanzado (N3) - Contenido Relacionado: IDs de publicaciones previas relacionadas Formato de la tabla en MD: ```markdown | ID | Título | Pilar | Nivel | Contenido Relacionado | |----|--------|-------|-------|---------------------| | 00001 | [Título] | [Pilar] | [Nivel] | [IDs relacionados] | ``` Criterios para relacionar contenido: - Contenido del mismo pilar que sea prerrequisito - Contenido de otros pilares que complemente la información - Máximo 3 contenidos relacionados por publicación - Priorizar relaciones con contenido de nivel inferior Ejemplo de relación: - Una publicación N2 debería referenciar contenido N1 relevante - Una publicación N3 debería referenciar contenido N2 y posiblemente N1 - Las publicaciones N1 pueden no tener contenido relacionado si son muy básicas Ordenamiento: 1. Primero por pilar 2. Dentro de cada pilar, por nivel 3. Dentro de cada nivel, por complejidad del temaYa lo tienes.5- Panel de control¿Qué nos falta?Pues muy poquito. El trabajo duro ya está hecho.Lo que hay que hacer ahora es llevarse esta información a un entorno más controlable, como puede ser un Excel o Notion, que es la herramienta que yo utilizo.Te dejo una plantilla de gestión de contenido que se adapta exactamente al resultado que hemos generado en el último paso. Copiar plantilla de NotionTodo listo y preparado para que comiences a crear contenido y asignes fechas de publicación a cada una de tus creaciones.Recuerda que debes poner en práctica este proceso por cada canal que quieras trabajar y puedes juntarlo todo dentro del mismo Notion que te he compartido.Si necesitas más información o tienes más dudas del proceso, responde a este contenido y te ayudaré.Te recomiendoVamos con recomendaciones megatop para esta semana:* Ramón Maiden: lo de este artista es impresionante. Estuve en una charla el viernes con él aprendiendo de su proceso creativo y trayectoria. Un tatuador que no tatúa. Te dejo enlace a sus redes para que flipes.* Queso Viejo Tostado: producto de Mercadona con los que quedas bien incluso en una cena pija.* IA de Notion: estoy empezando a usar el asistente integrado de Notion para la creación de contenidos y me está gustando bastante. Creo que podré hacer un tutorial si os interesa.Qué estoy creandoSemanita cargada de curro en la preparación del contenido para YouTube. He estado (sigo ahí) en varias conversaciones con editores de vídeo para que me ayuden a dar un mejor formato al tema, y encontrar a alguien está siendo complejo.Estoy aprendiendo mucho de este sector que desconocía: formas de trabajar, tarifas, condiciones… poco a poco voy entendiendo.Espero que el próximo vídeo que salga ya en YouTube cuente con mano experta en la edición.P.D.El contenido de hoy me ha tomado 8 horas y 50 minutos en estar listo para publicar.Tu feedback honesto me vendría de perlas.¿Qué te ha parecido esta entrega?Un abrazote :) This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.guitermo.com

A bonanza on the semiconductor industry and hardware scaling to AGI by the end of the decade.Dylan Patel runs Semianalysis, the leading publication and research firm on AI hardware. Jon Y runs Asianometry, the world's best YouTube channel on semiconductors and business history.* What Xi would do if he became scaling pilled* $ 1T+ in datacenter buildout by end of decadeWatch on YouTube. Listen on Apple Podcasts, Spotify, or any other podcast platform. Read the full transcript here. Follow me on Twitter for updates on future episodes.Sponsors:* Jane Street is looking to hire their next generation of leaders. Their deep learning team is looking for FPGA programmers, CUDA programmers, and ML researchers. To learn more about their full time roles, internship, tech podcast, and upcoming Kaggle competition, go here.* This episode is brought to you by Stripe, financial infrastructure for the internet. Millions of companies from Anthropic to Amazon use Stripe to accept payments, automate financial processes and grow their revenue.If you're interested in advertising on the podcast, check out this page.Timestamps00:00:00 – Xi's path to AGI00:04:20 – Liang Mong Song00:08:25 – How semiconductors get better00:11:16 – China can centralize compute00:18:50 – Export controls & sanctions00:32:51 – Huawei's intense culture00:38:51 – Why the semiconductor industry is so stratified00:40:58 – N2 should not exist00:45:53 – Taiwan invasion hypothetical00:49:21 – Mind-boggling complexity of semiconductors00:59:13 – Chip architecture design01:04:36 – Architectures lead to different AI models? China vs. US01:10:12 – Being head of compute at an AI lab01:16:24 – Scaling costs and power demand01:37:05 – Are we financing an AI bubble?01:50:20 – Starting Asianometry and SemiAnalysis02:06:10 – Opportunities in the semiconductor stack Get full access to Dwarkesh Podcast at www.dwarkeshpatel.com/subscribe

This week Russ and Clint talk with Sam Katacic VP of Sales for Rapidshape.  Rapidshape is a 3d printer company out of Germany that has focused more on the lab side of the dentistry than the clinician side right now in the US.  We talk at length about the changes in the market for 3d resins and how automation is driving a lot of changes.  Rapidshape has validated over 200 resins on their platform and has processes to ensure that each print is routine and predictable.  This is really nice especially if you have staff turnover, it is easy to train new employees to your resin. Also Russ gets pretty excited to hear about their curing unit which doesn't need N2 to cure but rather uses a vacuum.  He will be looking into that product for sure.   If you want to learn more about Rapidshape, go to Rapidshape.de.

Dr. Megan Daly presents the latest rapid recommendation update to the ASCO management of stage III NSCLC guideline, based on data from the phase III randomized LAURA trial, presented at the 2024 ASCO Annual Meeting, and subsequently published. She discusses the results of the trial, shares the updated recommendation from the expert panel, and the impact for both clinicians and patients. We also discuss future research in the area and exciting new developments to watch out for in the field. Read the full rapid update, “Management of Stage III Non-Small Cell Lung Cancer: ASCO Rapid Guideline Update” at www.asco.org/thoracic-cancer-guidelines. TRANSCRIPT   This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-01324. 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'm interviewing Dr. Megan Daly from the University of California Davis Comprehensive Cancer Center, lead author on, “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Rapid Guideline Update.” Thank you for being here today, Dr. Daly. Dr. Megan Daly: Thanks for having me, Brittany. Brittany Harvey: Great. Then 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. Daly, 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 start us off on the content of this update, first, this guideline was updated based off new evidence presented at the 2024 ASCO Annual Meeting. Dr. Daly, could you describe the trial that prompted this rapid update to the management of stage III non-small cell lung cancer guideline? Dr. Megan Daly: The trial that prompted this update is the LAURA trial. The LAURA trial was a phase III randomized trial conducted in patients with unresectable stage III non-small cell lung cancer harboring EGFR mutations, either exon 19 deletions or L858R insertions. Patients in this trial were randomized 2:1 between the third generation EGFR tyrosine kinase inhibitor osimertinib or placebo, and osimertinib or placebo were continued until progression or other reasons for discontinuation. Osimertinib was found to provide a considerable benefit in progression free survival, with a hazard ratio of 0.16. The median progression free survival for patients randomized to osimertinib was 39.1 months, and for patients on the placebo arm, it was 5.6 months. We did not yet have overall survival data from the LAURA trial. The data is not mature, but the considerable progression free survival benefit noted with osimertinib has drawn a lot of interest to this trial. Brittany Harvey: Absolutely. Thank you for describing the results of those trials and the endpoints. So then, based on this new evidence, what is the updated recommendation from the guideline expert panel? Dr. Megan Daly: The updated recommendation from the panel is that patients with unresectable stage III non-small cell lung cancer with an EGFR exon 19 deletion or exon 21 L858R mutation may be offered consolidation osimertinib after definitive chemoradiotherapy, which can be either platinum-based chemotherapy and thoracic radiation given either concurrently or sequentially. Our evidence quality is moderate and the strength of the recommendation is strong. Brittany Harvey: Great. And thank you for reviewing both the strength of the recommendation there as well as the evidence quality rating. So it's great to have this new option for patients. So what should clinicians know as they implement this new recommendation? Dr. Megan Daly: I think it's important for clinicians to know when they're counseling patients about considering osimertinib to understand that first, the LAURA trial enrolled patients who had common EGFR mutations. So exon 19 deletions or L858R mutations. Patients with other uncommon EGFR mutations were not included in the trial. It's important to know that overall survival data is not yet mature. We do not know yet whether the use of consolidation osimertinib leads to a survival benefit at this time. We only know that it leads to a progression-free survival benefit as compared to placebo. I think it's also important to know that there was increased toxicity noted on the experimental arm. Grade 3 or higher adverse events was significantly higher with the use of osimertinib. So these are all important considerations when counseling patients and considering the use of osimertinib. Brittany Harvey: Absolutely. Those are definitely key points, as you mentioned, to consider. And you've already touched on this a little bit. But how does this change impact patients living with stage III non-small cell lung cancer? Dr. Megan Daly: We do see in the LAURA trial a rather remarkable benefit for progression-free survival. The progression-free survival, as I already mentioned, increased from 5.6 months median on the control arm to 39.1 months on the experimental arm with consolidation osimertinib. So this is an exciting new option for patients with unresectable stage III non-small cell lung cancer who have one of these mutations to extend their progression-free survival by almost three years. And we hope that this progression-free survival benefit will end up translating into a considerable overall survival benefit as well. So, certainly, the overall survival data is eagerly awaited. Brittany Harvey: Definitely, this is a promising option for patients, and we look forward to future readouts of long-term data on this trial. So that's one of the outstanding questions here. But what other outstanding questions are there regarding the management of stage III non-small cell lung cancer? Dr. Megan Daly: I think what many of us question when we look at this data is whether we could extrapolate to the use of other targeted agents with other less common oncogenic driver mutations. Unfortunately, the answer is we simply don't know yet. We hope to see some ongoing data in the resectable setting. Doing randomized trials with rare oncogenic drivers in unresectable stage III lung cancer is very difficult, unfortunately, and there's always a degree of extrapolation for clinicians when trying to figure out how to best manage our patients. But for me, that's one of the biggest outstanding questions I think specifically ties into interpreting the LAURA trial and other related trials in patients with oncogenic driver mutations. I think there's still many outstanding questions about how we continue to improve outcomes for our patients with unresectable stage III non-small cell lung cancer, questions about how we optimize our radiation regimens to have the best possible local control while reducing toxicity. We still need to continue to have randomized trials looking at questions on optimizing radiation, optimizing concurrent chemotherapy, whether there are any settings where we might be able to reduce or omit chemotherapy in place of some of these newer agents. These are all outstanding questions that hopefully will be answered over the next several years. We also continue to have open questions about when patients are more appropriate for surgery and more appropriate for non-surgical options, those borderline patients with N2 nodes who may technically be surgical candidates or could potentially be downstaged with neoadjuvant therapy. So, I think there's a lot of exciting work going on in stage III right now. Brittany Harvey: Absolutely. We'll look forward to that more data that you mentioned for more optimal individualized options for these patients with stage III non-small cell lung cancer. And I want to thank you so much for your time to rapidly update this guideline based off new evidence presented and then published. And thank you for your time today, Dr. Daly. Dr. Megan Daly: Thank you, Brittany. It's great to be on here. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline update, go to www.asco.org/thoracic-cancer-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.      

Taylor Swift ist in Deutschland und selbst Internetstar anredo wird zum Swiftie. BastiMasti versteht den Hype nicht und will nachvollziehen, wieso die Tour des Mega-Stars das ganze Land in den Ausnahmezustand treibt. Sie hat's schon drauf. Taylor Swift hilft anredo wieder zum Internetstar-Titel. Ein virales Video seines engelsgleichen Gesangs macht den Ex-X-Star endlich wieder zum TikTok-Millionär. Jetzt ist er endgültig Swiftie. Und das, obwohl er vorher gar nicht so großer Fan war. In dieser Folge #rundfunk17 berichtet er BastiMasti von seinem Konzerterlebnis in Reihe 28. Wie so oft ist er mal wieder derbe unseriös in den Ticketverkauf gerutscht und hat irgendeinem großen Swiftie aus Klasse 7c die Eintrittskarte weggekauft. Was man nicht alles tut für "The Eras" - was auch immer das genau ist. Neu-Swiftie @anredo hat sich vorab weder über die Musik, noch über das korrekte Outfit informiert und blamierte sich bereits auf dem Parkplatz in Gelsenkirchen mit seinem nicht vorhandenen Taylor-Wissen. Wie gut, dass die Podcast-Community ihm ein umfangreiches Onboarding bereitgestellt hat. Was dann folgt, ist ein wunderbarer Podcast-Erlebnisbericht zum Konzert in der sogenannten N2, der den Hype um Taylor Swift bis ins kleinste Detail beleuchtet. Schließlich wusste Basti nicht einmal, dass Taylor und Lana Del Rey nicht dieselbe Person sind. In feinstem Feedback-Sandwich erörtert anredo, was ihm gut gefiel und wo noch Luft nach oben ist: Wie bewertet Deutschlands ehrlichster Konzert-Kritiker die Stimmung in Swiftkirchen, die Soundqualität, Essen & Trinken und Taylors Style? Besonders angetan sind BastiMasti und anredo von den vielen unterstützenden Eltern und Boyfriends der meist jungen Frauen auf Schalke. Einzig der Bauer im pinken Shirt fällt aus dem Raster. Das war jedoch (neben der veganen Currywurst) fast der einzige Fauxpas in der Arena. Basti nutzte N3, um abends durch die leeren Gassen von Darmstadt zu flanieren. Er berichtet von einer unangenehmen Situation an der Tür des berühmt-berüchtigten "Schlosskellers". Hier fand die langweilige Party der Bundesrepublik statt, für die "Marc, das Wunderkind" beinah 40 D-Mark hingeblättert hätte. Die beiden Star-Moderatoren des Erfolgs-Podcasts rundfunk 17 sind sich einig, dass frühere Feierei inkl. Daydrinking unbedingt wieder salonfähig gemacht werden müssen. anredo geht mit gutem Beispiel voran und erzählt nächste Woche vom CSD in Köln. Werbung: Das Erfolgs-Kartenspiel "Trash TV - Promis, Pannen, Peinlichkeiten" könnt ihr hier kaufen.* *) Dieser Link ist ein sogenannter Ref-ID-Links. Wenn man über diesen Link etwas kauft, verdienen wir daran eine kleine Provision, ohne dass für euch Mehrkosten entstehen.

The key quality traits of successful individuals in any industry are not merely talent or luck. It's a powerful combination of discipline, resilience, and a growth mindset.   The truth is, success is a result of consistent actions and the right mindset. However, despite having potential, many individuals fail to cultivate these traits effectively.   What does it take to be the best of the best? What methodologies do highly successful people use and what mindset do they have?   In this episode, CRO of The N2 Company, JP Hamel, joins me to talk about the different traits of successful individuals, how they're not always successful at first and why it's important to keep pushing through.   If I had stayed where I was, just complacently accepting, I would never have made the jump to where I am today. -JP Hamel   Three Things You'll Learn In This Episode    -Starting from the bottom Everyone starts at ground level but not everyone stays there. What are some of the thought processes we experience at ground level?   -Start with the end When it comes to public speaking and relaying a message, where do we start?   -Is success the end goal? It's the little moments that make up success. The small details make up the success that we're looking for.   Guest Bio JP Hamel is the CRO of The N2 Company. He has the privilege of leading a team of over 800 of the most talented, top-earning and inspiring sales people in the nation. This team has taken N2 to revenues of over $125M and to over 850 publications nationwide. He's incredibly passionate about his job, and believes in faith over fear when it comes to sales and selling. Find JP Hamel on LinkedIn @JP Hamel Visit https://n2co.com/

TWiV reviews measles in Kenya, a trial for a intranasal COVID vaccine, dengue in the Florida Keys and in Central/South America, Spain connecting government with scientists, T cell activation and viral RNA fragments persist for up to 2 years after SARS-CoV-2 infection, and durable cross-reactive and protective antibodies against avian N2 neuraminidases elicited by A(H2N2) and A(H3N2) influenza pandemics. Hosts: Vincent Racaniello and Alan Dove Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode MicrobeTV Discord Server Measles in Kenya (WHO) Intranasal COVID vaccine trial (NIH) Dengue in Florida Keys (Florida Health) Dengue rising in Central/South America (NPR) Spain to connect scientists with government (Science) Persistence of T cells and viral RNA after SARS-CoV-2 infection (Sci Transl Med) Influenza pandemics induce cross-reactive antibodies against avian N2 (Nat Comm) Letters read on TWiV 1129 Timestamps by Jolene. Thanks! Weekly Picks Alan – The first few minutes of this video by Roger Barnes Vincent – Billy & Molly: An Otter Love Story Listener Picks Fernando – A City on Mars Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv

Dr. Shaalan Beg highlights practice-changing studies in GI cancers featured at the 2024 ASCO Annual Meeting, including the ESOPEC trial in esophageal adenocarcinoma and durable responses to PD-1 blockade alone in mismatch repair-deficient locally advanced rectal cancer. TRANSCRIPT Geraldine Carroll: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Shaalan Beg, an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center. Dr. Beg will be discussing practice- changing abstracts and other key advances in GI oncology that were presented at the 2024 ASCO Annual Meeting. His full disclosures are available in the transcript of this episode.  Dr. Beg, thanks for being on the podcast today.  Dr. Shaalan Beg: Thank you for having me. Geraldine Carroll: Let's begin with LBA1, the ESOPEC trial. This was featured in the Plenary Session, and this study compared two treatment strategies for locally advanced esophageal adenocarcinoma that could be treated with surgery. The strategies include the CROSS protocol, which consisted of chemoradiotherapy before surgery, and the FLOT protocol of chemotherapy before and after surgery. Can you tell us about this practice-changing study, Dr. Beg? Dr. Shaalan Beg: Yes. According to this study, perioperative chemotherapy with FLOT was better than neoadjuvant therapy with chemoradiation and carbo-taxol for people with adenocarcinoma of the esophagus. There were 438 patients enrolled on this phase 3 study. R0 resection rates were fairly similar across both groups. The PCR rates were a little higher on the FLOT group. But when you look at the median overall survival difference, 66 months in the FLOT group versus 37 months in the CROSS group, 3-year survival was 57% versus 50% favoring FLOT therapy as well.  So a couple of caveats on this clinical trial, because the first thing to note is that the standard treatment for this disease has evolved because we now don't only give CROSS chemoradiation, we also give immunotherapy after the completion of chemoradiation for this group of patients. And in this study, since it predated that standard of care, patients did not receive immunotherapy. But having said that, the take home for me here is that chemotherapy is better than chemoradiation for this group of patients, recognizing the fact that 1) they only enrolled adenocarcinoma patients, and 2) patients with high T stage were not included. So the folks with high T stage would be those who we would expect would benefit from the radiation aspect. So my take home here is that more chemotherapy is better in the perioperative space. Radiation should be considered for individuals who need more local control. But in general, I think we're going to see us moving more towards chemotherapy-based regimens with FLOT for this group of patients. Geraldine Carroll: Great. So moving on to rectal cancer, in LBA3512, investigators reported durable, complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. Can you tell us more about the promising durable responses that occurred in this trial?  Dr. Shaalan Beg: On first glance, seeing that immunotherapy has good activity in patients with mismatched repair deficient rectal cancer isn't really headline breaking news anymore. We've known about this activity for this group of patients for many years. Earlier at ASCO, the investigators presented early results of this compound for people receiving six months of dostarlimab therapy for people with mismatched repair deficient, locally advanced rectal cancer, and showed that they had a very high complete response rate. At that time, it generated a lot of interest and there was a lot of curiosity on whether these outcomes will be sustained. We don't know other characteristics of their biologic status and whether this was some sort of reflection of the patients who are selected or not.   So here in this presentation at ASCO 2024, they did come back to present follow-up data for people with mismatch repair deficient colorectal cancer, having received 6 months of dostarlimab. Forty-seven patients had been enrolled, and the 41 patients who had achieved a clinical complete response continued to have disease control with no distant metastases. So that's very compelling information. There were no additional serious adverse events greater than grade 2 that they saw, and they did follow circulating tumor DNA, and those did normalize even before they had their colonoscopy to examine their tumors.  So, again, we're continuing to see very encouraging data of immunotherapy, and the response rate with dostarlimab seems to be very interesting for this disease, and it will be interesting to see how this pans out in larger studies and how this translates into the use of dostarlimab across other diseases where other checkpoint inhibitors are currently being used. Geraldine Carroll: Absolutely. So, moving on to LBA3501. The COLLISION trial looked at surgery versus thermal ablation for small cell colorectal liver metastases. This was an international, multicenter, phase 3, randomized, controlled trial. How will this study change clinical practice?  Dr. Shaalan Beg: Kudos to the investigators here. They looked to understand the difference in outcome in treating people with colorectal cancer with liver only metastases. These clinical trials are extremely difficult to design. They're very difficult to enroll on because of the multidisciplinary aspect of the interventions and patient and provider biases as well. So on this clinical trial, the investigators enrolled people with resectable colorectal cancer, liver metastases so they did not have any metastases outside the liver. Patients were required to have 10 or less known metastases that were less than 3 cm in size. There were other allowances for larger tumors as well. And after an expert panel review, patients were randomized to either resection or ablation. It was up to the physicians whether they performed these laparoscopically or openly or percutaneously, depending on the biology of the patient and the anatomical presentation.  There was a predefined stopping rule at the half-time for this clinical trial, which showed a benefit in the experimental arm of ablation compared to standard of care. The overall survival was not compromised. Progression-free survival was not compromised with local therapy. But there were differences in morbidity and mortality, as we would expect, one being a surgical procedure and the other being ablation, where, according to this study, of the 140 or so patients who received either treatment, 2.1% of people who underwent resection died within 90 days of surgery. The AE rate was 56% in the resection sample compared to 19% in ablation, and the 90-day mortality for ablation was 0.7%. So less morbidity, improved mortality, reduced adverse events with ablation versus surgical resection without compromising local control and overall survival.   And I think for practice here in the United States, this does provide very interesting data for us to take back to the clinic for lesions that are relatively small and could generally be addressed by both surgery and ablation. Historically, there are various non biologic factors that could go into deciding whether someone should have surgery or ablation, and it could be based on who the physician is, who's seeing the patient, what the practice patterns in a specific organization are, and where their expertise lie. But here we're seeing that ablation for the small lesions is a very effective tool with very good local control rates, and again, in this selected group of patients with liver only metastases. And I think it is going to make tumor board discussions very interesting with data backing ablation for these lesions. Geraldine Carroll: Well, let's move onto the MOUNTAINER study. This study created some buzz in the colorectal cancer space. That's Abstract 3509. Can you tell us about the final results of this phase 2 study of tucatinib and trastuzumab in HER2-positive metastatic CRC? What are your thoughts on this treatment option, which seems to be well tolerated? Dr. Shaalan Beg: So, HER2 overexpression or amplification occurs in about 3 to 5% of patients with metastatic colorectal cancer and up to 10% of people who have a RAS/RAF wild type disease. On the previous episodes of the podcast we have covered precision targeted therapy in colorectal cancer, focusing on c-MET, focusing on BRAF, and here we have updated results targeting HER2 for colorectal cancer. And the results of the MOUNTAINEER study have been out for a while. This is a phase 2 study looking at combining tucatinib which is a highly selective HER2 directed TKI with trastuzumab, the monoclonal antibody for HER2 targeting. And what they found on this study is the confirmed overall response rate was 38%. Duration of response was 12 months, overall survival was 24 months and these are the results that have been already released and now we have an additional 16 months of follow up and these results continue to hold on. PFS and overall survival gains were held, which makes it a very interesting option for people with colorectal cancer. You mentioned the tolerability aspect and side effects. I think it's important to know the spectrum of side effects for this disease may be a little different than other TKIs. There's hypertension, but there's also the risk of diarrhea, back pain and pyrexia, with the most common grade 3 treatment related adverse event was an increase in AST level seen in 10% of people of grade 3 and above.  So where does that really leave us? There is a confirmatory randomized first-line trial of tucatinib and trastuzumab in the first line setting, which is currently ongoing. So we'll stay tuned to see where that leads us. And with the HER2 space right now for colorectal cancer with the development of antibody drug conjugates, we may have more than one option for this group of patients once those trials read out. Geraldine Carroll: Excellent. Well, moving on to LBA4008, that's the CheckMate-9DW trial. This trial reported first results looking at nivolumab plus ipilimumab versus sorafenib or lenvatinib as first-line treatment for advanced hepatocellular carcinoma. Can you tell us about this trial? Will there be a potential new standard of care in advanced HCC? Dr. Shaalan Beg: When we think about patients with advanced HCC, the only treatment option that they had for about a decade and a half were just oral track tyrosine kinase inhibitors that had modest to moderate clinical activity. Since then, we've seen that combination therapy is better than TKI therapy, and the combination therapy has taken two different forms. One is a combination of checkpoint inhibitor and antiangiogenic therapy, such as in the combination of atezolizumab and bevacizumab. The other is a combination of dual checkpoint inhibitor therapy. Here we are talking about the results of nivolumab and ipilimumab. Previously, we've talked about the combination of durva and tremi for the treatment of patients with HCC.   So in this study, nivo was given for the first 4 cycles, nivo and ipi were given together, nivo 1 mg per kg, and IPI 3 mgs per kg every 3 weeks for 4 cycles. And then the CTLA-4 inhibitor ipilimumab was stopped. And this was followed by monotherapy nivolumab every 4 weeks until disease progression or up to 2 years. And it was compared to dealers' choice, lenvatinib or sorafenib. The median overall survival of nivo-ipi was 23 months versus 20 months with lenvatinib-sorafenib. The 24-month overall survival was 49% with ipi-nivo versus 39%. And the overall response rate with nivo-ipi was 36% compared to 13%. So again, significantly improved clinical activity.   And when we talk about immunotherapy combinations, the question that comes to mind is how well is this tolerated? There's a lot of work and iteration that took place in figuring out what the right combination strategy of ipi and nivo should be, because some of the earlier studies did demonstrate fairly high adverse events in this group of patients. So on this study, we saw that grade 3 or 4 treatment related adverse events were seen in 41% of people who received nivo-ipi and 42% if they received lenvatinib or sorafenib. So, certainly a high proportion of treatment related adverse events, but probably also reflective of the disease population, which is being tested, because those numbers were fairly similar in the control arm as well.  So we've known that nivo-ipi is active in HCC. There is an approval in the second-line space, so it remains to be seen if this data helps propel nivo-ipi to the first-line space so we end up with another combination regimen for patients with advanced hepatocellular carcinoma.  Geraldine Carroll: Excellent. Well, before we wrap up the podcast, I'd like to ask you about LBA3511. In this study, investigators looked at total neoadjuvant treatment with long course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors. So this was a multicenter, randomized, open label, phase 3 trial. What are your key takeaways here? Dr. Shaalan Beg: Key takeaway here is that total neoadjuvant therapy was better than the conventional chemoradiation followed by chemo. So this clinical trial enrolled people with T4a/b resectable disease with clinical N2 stage, and they were randomized, as you mentioned, to receiving chemoradiation with radiation capecitabine followed by surgery, and then CAPOX or capecitabine versus chemo, short-course radiation, and additional chemotherapy followed by surgery.  And when we compare both arms, the total neoadjuvant therapy led to improved disease-free survival, improved PCR rates compared to standard concurrent neoadjuvant chemo radiotherapy in this group of patients. The two arms were fairly well-balanced. The number of T4 lesions was a little higher in the chemoradiation group. There were 49% in the chemo radiation group versus 46% had clinically T4 disease, but the nodal status was fairly similar. We should keep in mind that the other baseline characteristics were fairly well balanced.  And when we look at the outcomes, the disease-free survival probability at 36 months was 76% in the total neoadjuvant group compared to 67% with chemoradiation. And the metastasis free survival in total neoadjuvant therapy was 81% versus 73%. So a fairly compelling difference between the two arms, which did translate into an overall survival of 89% versus 88% in the two groups. So definitely higher disease-free survival and metastasis free survival, no difference on the overall survival with these groups. And it talks about the importance of intensifying chemotherapy upfront in this group of patients who can have a fairly high burden of disease and may struggle with receiving chemotherapy postoperatively. Geraldine Carroll: Excellent. Well, thank you, Dr. Beg, for sharing your fantastic insights with us on these key studies from the 2024 ASCO Annual Meeting. It's certainly a very exciting time in GI oncology. Dr. Shaalan Beg: Absolutely. Thank you for bringing these studies out, because I think a lot of these are practice-changing and can start impacting the clinical care that we're giving our patients right now. Geraldine Carroll: Thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Shaalan Beg   @ShaalanBeg     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:  Dr. Shaalan Beg:   Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen   Speakers' Bureau: Sirtex   Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics   Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune  

Our short and to the point PRESSURISED version of episode 47. If you don't have time for the full episode and want to get right to the science without any of our waffle, this is the place to be! Read the show notes and find the full episode here: https://www.armatusoceanic.com/podcast/047-baikal   Located in southern Siberia and covered in thick ice for almost half of the year, the colossal Lake Baikal reaches depths of 1600m making it the oldest, and deepest lake in the world. With hydrothermal vents, methane seeps and vast swathes of endemic species, this ancient lake was too tempting not to talk about.   We speak with Professor Marianne Moore, a Limnologist who has been working on the lake for over 2 decades. She guides us through its incredible ecosystems and species such as the world's only freshwater seal, deep water insects and foot-long flatworms!   We're really trying to make this project self-sustaining so we have started looking for ways to support the podcast. Here's a link to our page on how to support us, from the free options to becoming a patron of the show. We want to say a huge thank you to those patrons who have already pledged to support us!   Thanks again for tuning in, we'll deep-see you next time!   Check out our podcast merch here! Which now includes Alan's beloved apron and a much anticipated new design...    Feel free to get in touch with us with questions or your own tales from the high seas on: podcast@armatusoceanic.com We'd love to actually play your voice so feel free to record a short audio note!   We are also on  Twitter: @DeepSeaPod, @ArmatusO Facebook: DeepSeaPodcast, ArmatusOceanic  Instagram: @deepsea_podcast, @armatusoceanic   Keep up with the team on social media Twitter:  Alan - @Hadalbloke (https://twitter.com/Hadalbloke) Thom - @ThomLinley (https://twitter.com/ThomLinley)  Georgia - @geeinthesea (https://twitter.com/geeinthesea)    Instagram:  Georgia - @geeinthesea Thom - @thom.linley    Read the show notes and find out more about us at: www.armatusoceanic.com FURTHER RESOURCES LAKE BAIKAL READING Intro to Lake Baikal and lakes: Mogolov, L.S. 2017. The Soul of Siberia at Risk. Wellesley Magazine. p.16-22. Moore, M.V., S.E. Hampton, L.R. Izmest'eva, E.A. Silow, E.V. Peshkova, and B. Pavlov. 2009. Climate change and the world's ‘Sacred Sea' – Lake Baikal, Siberia. BioScience 59:405-417 Thomson, P. 2007. Sacred Sea: A Journey to Lake Baikal, Oxford University Press. 320 p. Vincent, W.F. 2018. Lakes. A Very Short Introduction, Oxford University Press. 146 p. Vents and seeps: Crane, K., Hecker, B. and Golubev, V., 1991. Hydrothermal vents in Lake Baikal. Nature, 350(6316), pp.281-281. Zemskaya, T.I., Sitnikova, T.Y., Kiyashko, S.I., Kalmychkov, G.V., Pogodaeva, T.V., Mekhanikova, I.V., Naumova, T.V., Shubenkova, O.V., Chernitsina, S.M., Kotsar, O.V. and Chernyaev, E.S., 2012. Faunal communities at sites of gas-and oil- bearing fluids in Lake Baikal. Geo-Marine Letters, 32, pp.437-451. Fish: Sideleva, V.G. 2003. The Endemic Fishes of Lake Baikal. Backhuys Publishers. Sideleva, V.G. 2004. Mysterious Fish of Lake Baikal. Science First Hand 3:N2. (Note: ‘black umber' and ‘white umber', mentioned in this article, are two endemic varieties of the Siberian grayling Thymallus arcticus.) Sideleva, V.G., 2016. Communities of the cottoid fish (Cottoidei) in the areas of hydrothermal vents and cold seeps of the abyssal zone of Baikal Lake. Journal of Ichthyology, 56, pp.694-701. Seal: Nomokonova, T., Losey, R.J., Iakunaeva, V.N., Emelianova, I.A., Baginova, E.A. and Pastukhov, M.V., 2013. People and seals at Siberia's Lake Baikal. Journal of Ethnobiology, 33(2), pp.259-280. Watanabe, Y.Y., Baranov, E.A. and Miyazaki, N., 2020. Ultrahigh foraging rates of Baikal seals make tiny endemic amphipods profitable in Lake Baikal. Proceedings of the National Academy of Sciences, 117(49), pp.31242-31248. Environmental threats: Moore, M.V., S.E. Hampton, L.R. Izmest'eva, E.A. Silow, E.V. Peshkova, and B. Pavlov. 2009. Climate change and the world's ‘Sacred Sea' – Lake Baikal, Siberia. BioScience 59:405-417. Timoshkin, O.A. 2015. Ecological Crisis on Lake Baikal: Diagnosed by Scientists. Science First Hand 41:N2. Timoshkin, O.A., D.P. Samsonov, M. Yamamuro, M.V. Moore, O.I. Belykh, V.V. Malnik, M.V. Sakirko, A.A. Shirokaya, N.A. Bondarenko, V.M. Domysheva, G.A. Fedorova, A.I. Kochetkov, et al. 2016. Rapid ecological change in the coastal zone of Lake Baikal (East Siberia): Is the site of the world's greatest freshwater biodiversity in danger? Journal of Great Lakes Research 42:487-497. doi: 10.1016/j.jglr.2016.02.011   PEOPLE MENTIONED Professor Marianne Moore & Marianne's excellent paper on interdisciplinary work   CREDITS Theme – Hadal Zone Express by Märvel Edited by - Georgia Wells

In this mind-blowing episode, we explore how one man's quest to create artificial fertilizer transformed the trajectory of human history. Inspired by listener Martin from Frankfurt, we dive into the story of Fritz Haber, whose discovery of the Haber-Bosch process for synthesizing ammonia not only revolutionized agriculture and saved billions from starvation but also fueled the rise of chemical weapons in World War I. From explosive bat guano to the delicate balance of ding-dongs and Twinkies, we unravel the complex web connecting fertilizer, food production, and the very bombs that shaped the 20th century. Brace yourself for a wild ride through the unintended consequences of scientific breakthroughs! —

Here's Martin's email to us which includes lots more information and links to learn more about his intriguing IF! From: Martin Subject: A world without NH3 (a What The If idea) I had another idea for a potential IF, or - to give credit where credit is due - my colleague Thomas has it. He read that BASF in Germany has sold an NH3 (ammonia) plant in Ludwigshafen (their main production site) after having produced NH3 there since 1913 It was the first industrial plant that realized the -then- completely new Haber-Bosch process. So Thomas asked: what (the if) would a world without NH3 look like? Then we started discussing :-) It's sort of chemist's lore that Haber and Bosch tested many, many catalysts before they found a good one to combine N2 and H2 to NH3. Some sources put the number of tested catalyst formulations to as many as 2500 (https://www.sciencedirect.com/topics/chemistry/haber-bosch-process#:~:text=In%20order%20to%20find%20a,Germany%2C%20now%20part%20of%20Ludwigshafen). What if they lost interest after test #1000 (and never found the iron-based catalyst that was ultimately the one)? Probably this (hypothetical) failed attempt on large scale would deter other groups of scientists at that time to even start their own catalyst developments? Anyhow, let's assume there has never been an industrial NH3 synthesis process in our "What the If" world. It's quite obvious that agriculture would have been very different. Our World in Data has the key answer here: https://ourworldindata.org/grapher/world-population-with-and-without-fertilizer — without ammonia as fertilizer we would be able to feed max 4 bn people (instead 8). So many more famines? Or slower population growth? Certainly a different diet, less feed for animals, and more plants that can fixate N2 from the atmosphere. Our World in Data has a little fun with that: (https://ourworldindata.org/how-many-people-does-synthetic-fertilizer-feed#could-we-have-achieved-the-same-without-synthetic-nitrogen) more peas and beans (and some others — https://en.wikipedia.org/wiki/Category:Nitrogen-fixing_crops — including lupines — https://en.wikipedia.org/wiki/Lupinus#Uses — which leads -of course- directly to one of my favorite Monty Python sketches "Dennis Moore"). Not nice. I wouldn't survive the season, that's for sure (no / less fruits and other vegetables) Side note: I was surprised that per capita for many decades (https://ourworldindata.org/grapher/fertilizer-per-capita?tab=chart&country=OWID_WRL~OWID_EUR~CHN~IND~EGY~NLD~DEU~USA) the Western world had significantly higher values than Africa, India, Egypt. So without NH3 Europe / USA would have suffered more), probably more focus has to be put on bringing food on the table for everyone and less activities in new technologies etc. (basically staying longer at the bottom levels of Maslow's pyramid of needs) And then there is war. NH3 was an important ingredient to make TNT - some folks estimate that TNT has killed 100-150 million people in all wars combined. TNT Is Still With Us | Science | AAAS https://www.science.org/content/blog-post/tnt-still-us
Despite being an older explosive, TNT remains relevant due to its stability and relative safety compared to newer, more volatile alternatives. All the best, Martin

Located in southern Siberia and covered in thick ice for almost half of the year, the colossal Lake Baikal reaches depths of 1600m making it the oldest, and deepest lake in the world. With hydrothermal vents, methane seeps and vast swathes of endemic species, this ancient lake was too tempting not to talk about.   We speak with Professor Marianne Moore, a Limnologist who has been working on the lake for over 2 decades. She guides us through its incredible ecosystems and species such as the world's only freshwater seal, deep water insects and foot-long flatworms! Plus, we hear about the myths and mysteries of the lake: from scientifically testing whether the mafia can use amphipods to effectively dispose of bodies, to whether there really is 1600 tonnes of gold hiding at the bottom of the lake.    The Professor is back on land after a succession of crazy adventures which includes writing a paper on backwards swimming in deep sea fish, finding the worlds deepest nudibranch (possibly) plus discovering his friends live in the most metal place ever.  There's no Coffee with Andrew segment this month as he is taking a well deserved break (and is possibly touring the country looking for the strangest milks he can find), but we do hear from Kakani Kajita about the recent release of FathomVerse - the mobile game helping to contribute to deep sea citizen science. Kakani tells us about how it's doing in its first month of release, and how it's already making an impact in training deep sea AI models.   We're really trying to make this project self-sustaining so we have started looking for ways to support the podcast. Here's a link to our page on how to support us, from the free options to becoming a patron of the show. We want to say a huge thank you to those patrons who have already pledged to support us: Elinor Wahl | Andrew Stewart | KJ Quintanilla | Thomas Brattheim Thanks again for tuning in, we'll deep-see you next time!   Check out our podcast merch here! Which now includes Alan's beloved apron and a much anticipated new design...    Feel free to get in touch with us with questions or your own tales from the high seas on: podcast@armatusoceanic.com We'd love to actually play your voice so feel free to record a short audio note!   We are also on  Twitter: @DeepSeaPod, @ArmatusO Facebook: DeepSeaPodcast, ArmatusOceanic  Instagram: @deepsea_podcast, @armatusoceanic   Keep up with the team on social media Twitter:  Alan - @Hadalbloke (https://twitter.com/Hadalbloke) Thom - @ThomLinley (https://twitter.com/ThomLinley)  Georgia - @geeinthesea (https://twitter.com/geeinthesea)    Instagram:  Georgia - @geeinthesea Thom - @thom.linley    Read the show notes and find out more about us at: www.armatusoceanic.com FURTHER RESOURCES Triton submarines are building a new submarine to visit the Titanic to show that deep sea exploration is safe Robotic Explorers Uncover Unexpected Ancient Origins of Strange Seafloor Formations  Deep-sea sponge's 'zero-energy' flow control could inspire new energy efficient designs    LAKE BAIKAL READING Intro to Lake Baikal and lakes: Mogolov, L.S. 2017. The Soul of Siberia at Risk. Wellesley Magazine. p.16-22. Moore, M.V., S.E. Hampton, L.R. Izmest'eva, E.A. Silow, E.V. Peshkova, and B. Pavlov. 2009. Climate change and the world's ‘Sacred Sea' – Lake Baikal, Siberia. BioScience 59:405-417 Thomson, P. 2007. Sacred Sea: A Journey to Lake Baikal, Oxford University Press. 320 p. Vincent, W.F. 2018. Lakes. A Very Short Introduction, Oxford University Press. 146 p. Vents and seeps: Crane, K., Hecker, B. and Golubev, V., 1991. Hydrothermal vents in Lake Baikal. Nature, 350(6316), pp.281-281. Zemskaya, T.I., Sitnikova, T.Y., Kiyashko, S.I., Kalmychkov, G.V., Pogodaeva, T.V., Mekhanikova, I.V., Naumova, T.V., Shubenkova, O.V., Chernitsina, S.M., Kotsar, O.V. and Chernyaev, E.S., 2012. Faunal communities at sites of gas-and oil- bearing fluids in Lake Baikal. Geo-Marine Letters, 32, pp.437-451. Fish: Sideleva, V.G. 2003. The Endemic Fishes of Lake Baikal. Backhuys Publishers. Sideleva, V.G. 2004. Mysterious Fish of Lake Baikal. Science First Hand 3:N2. (Note: ‘black umber' and ‘white umber', mentioned in this article, are two endemic varieties of the Siberian grayling Thymallus arcticus.) Sideleva, V.G., 2016. Communities of the cottoid fish (Cottoidei) in the areas of hydrothermal vents and cold seeps of the abyssal zone of Baikal Lake. Journal of Ichthyology, 56, pp.694-701. Seal: Nomokonova, T., Losey, R.J., Iakunaeva, V.N., Emelianova, I.A., Baginova, E.A. and Pastukhov, M.V., 2013. People and seals at Siberia's Lake Baikal. Journal of Ethnobiology, 33(2), pp.259-280. Watanabe, Y.Y., Baranov, E.A. and Miyazaki, N., 2020. Ultrahigh foraging rates of Baikal seals make tiny endemic amphipods profitable in Lake Baikal. Proceedings of the National Academy of Sciences, 117(49), pp.31242-31248. Environmental threats: Moore, M.V., S.E. Hampton, L.R. Izmest'eva, E.A. Silow, E.V. Peshkova, and B. Pavlov. 2009. Climate change and the world's ‘Sacred Sea' – Lake Baikal, Siberia. BioScience 59:405-417. Timoshkin, O.A. 2015. Ecological Crisis on Lake Baikal: Diagnosed by Scientists. Science First Hand 41:N2. Timoshkin, O.A., D.P. Samsonov, M. Yamamuro, M.V. Moore, O.I. Belykh, V.V. Malnik, M.V. Sakirko, A.A. Shirokaya, N.A. Bondarenko, V.M. Domysheva, G.A. Fedorova, A.I. Kochetkov, et al. 2016. Rapid ecological change in the coastal zone of Lake Baikal (East Siberia): Is the site of the world's greatest freshwater biodiversity in danger? Journal of Great Lakes Research 42:487-497. doi: 10.1016/j.jglr.2016.02.011   PEOPLE MENTIONED Professor Marianne Moore & Marianne's excellent paper on interdisciplinary work Kakani Kajita   SOUNDTRACK OF THE MONTH Frightening Fishes CREDITS Theme – Hadal Zone Express by Märvel Logo image - Vereshchagina et al (2021), Sitnikova et al (2018), Teterina et al (2010) Edited by - Georgia Wells  

Drs. Vamsi Velcheti and Nathan Pennell discuss key lung cancer abstracts from the 2024 ASCO Annual Meeting, including data from LUMINOSITY and ADAURA, novel therapies in KRASG12C-mutant advanced NSCLC, and the need for effective adjuvant therapies for patients with rare mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at Perlmutter Cancer Center at NYU Langone Health. Today, I'm delighted to welcome Dr. Nathan Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research at the Taussig Cancer Center. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Dr. Pennell is sharing his valuable insights today on key abstracts in lung cancer that will be presented at the 2024 ASCO Annual Meeting. You'll find our full disclosures in the transcript of the episode.  Nate, it's great to have you here on the podcast. Thank you for being here. Dr. Nathan Pennell: Thanks, Vamsi, for inviting me. I'm always excited for the ASCO Annual Meeting, and we have a tremendous amount of exciting lung cancer abstracts. I know we're not going to discuss all of them on this podcast, but even exciting Plenary presentations coming up.  Dr. Vamsi Velcheti: So, one of the abstracts that caught my attention was Abstract 103, the LUMINOSITY trial, which will be presenting the primary analysis at the meeting. So, there's a lot of buzz and excitement around ADCs. Can you comment on this abstract, Nate, and what are your thoughts on key takeaways from this abstract?  Dr. Nathan Pennell: Absolutely, I agree. This is really an exciting new potential target for lung cancer. So historically, when we think about MET and lung cancer, we think about the MET exon 14 skipping mutations which are present in 3% or 4% of adenocarcinoma patients. And we have approved tyrosine kinase inhibitors, small molecule inhibitors that can be very effective for those. What we're talking about here is actually an antibody drug conjugate or ADC telisotuzumab vedotin, which is targeting the MET protein over expression in non-squamous EGFR wild type advanced non-small cell lung cancer. The LUMINOSITY was a single arm, phase 2 study of teliso, and first of all, I think we have to define the patient population. So, these were MET over expressing non-small cell lung cancer by immunohistochemical staining. So, it included both what they considered MET high expression and MET intermediate expression, both of which had to be 3+ IHC positive on 25% to 50% of cells in the intermediate and 50% or higher in the high expressing group. They were treated with the ADC and had pretty promising results, a response rate of 35% in the MET high group and 23% in the intermediate group. Duration of response at nine months and 7.2 months in those two groups, and the PFS was five and a half and six months. So I would say in a previously treated population, this was relatively promising and potentially defines a completely new and unique subgroup of biomarker defined patients. So, Vamsi, I'm curious, though, if this ends up moving forward to further development, what your thoughts are on adding yet another biomarker in non-small cell lung cancer? Dr. Vamsi Velcheti: Yeah, I think it's certainly exciting. I think for this population, we really don't have a lot of options beyond the second line, and even in the second line, docetaxels are low bar. So,I think having more options for our patients is certainly outcome development. And I think MET IHC is relatively easy to deploy in a clinical setting. I think we already test for MET PD-L1 IHC routinely, and now recently, as you know, HER2 IHC given approval for ADCs, HER2 ADCs there in that space. So, I think from a technical standpoint, I don't see a big barrier in terms of adding an additional IHC marker. And usually, the IHC testing is pretty quick. And I think if you have a therapeutic approval based on IHC positivity, I think certainly from an operational standpoint, it shouldn't be a very complicated issue. Dr. Nathan Pennell: Yeah, I agree. This is cheap. It's something that can be done everywhere in the world. And as you said, in addition to diagnostic IHC, we're already looking at PD-L1, and probably moving towards doing that for HER2. This is really wonderful that we're moving into kind of the era of the ADCs, which is opening up a whole new therapeutic group of options for patients. Dr. Vamsi Velcheti: So, the other abstract that caught my attention was like, the Abstract 8005. This is the molecular residual disease MRD analysis from the ADAURA trial. The ADAURA trial, as you all know, is the trial that led to the FDA approval of adjuvant use of osimertinib in patients with EGFR mutant stage 1B through 3A non-small cell lung cancer. And in this trial, osimertinib demonstrated significant improvements in DFS and OS. And in this particular study, Abstract 8005, the authors looked at the role of MRD in predicting DFS in the study. And after 682 patients who were randomized, 36% of the patients had samples to look at MRD post- surgery. And in the trial the MRD status predicted DFS or event free survival at 36 months with a hazard ratio of 0.23. And the MRD status had a median lead time of 4.7 months across both the arms, both osimertinib and the placebo arm. So, suggesting that MRD could potentially identify high risk subgroups of patients post-surgery to tailor personalized approaches potentially in this population. So, Nate, in your practice, of course, we don't have a clinically validated approach yet to kind of use MRD in this setting, but if we have an option to use an MRD based assay, do you think that would potentially be an opportunity to perhaps escalate or de-escalate adjuvant strategies with TKIs in the adjuvant setting? Do you see value in using MRI assays post- surgery? Dr. Nathan Pennell: Yeah, I think this is a really important study because this is such an important topic around adjuvant targeted treatment. So, of course, ADAURA really changed how we treated people with EGFR mutant lung cancer who underwent surgical resection, because we know that the three years of osimertinib significantly improved disease-free survival and overall survival. But there's still a lot of questions being asked about, is that affordable? Obviously, we're putting a lot of resources into three years of treatment, and not everyone necessarily needs it. There may well be people who are cured with surgery alone and adjuvant chemotherapy. And then what about duration? Is three years enough? Do we need even longer treatment, or do we need shorter treatment? And up to date, we haven't really been able to tell people at risk of recurrence other than the pure odds-based risk based on their stage.   And the assay that was used in the ADAURA study was a personalized tumor informed assay based on the resected tumor. It's unclear to me whether this was just a subgroup of people that had this done or whether they tried to do it in all 600 patients and only, it looks like they were successful in about 32% of people. Maybe about a third were able to successfully have a tumor informed assay. So, the first question is, “Can you use this to help guide who needs treatment or not?” And I think what they showed was only about 4% of people in osimertinib arm in 12% had MRD positive at baseline after surgery. So probably, upfront testing is not really going to be all that helpful at determining who's at high risk and needs to be treated.   Interestingly, of those who were positive, though, most of them, or 80% of them, did go MRD negative on osimertinib. And what I found really interesting is that of those who did have a recurrence, 65% of them did have the MRD test turn positive. And as you mentioned, that was about five months prior to being picked up radiographically, and so you can pick them up sooner. And it also looks like about two thirds of recurrences can be identified with the blood test. So that potentially could identify people who are recurring earlier that might be eligible for a more intensive treatment. The other thing that was really interesting is of those who recurred in the osimertinib arm, 68% of them happened after stopping the osimertinib, suggesting that for the majority of patients, even those not necessarily cured, they seem to have disease control while on the osimertinib, suggesting that maybe a longer duration of treatment for those patients could be helpful. The problem is it still isn't necessarily helpful at identifying who those people are who need the longer duration of treatment. So, definitely an important study. I think it could be useful in practice if this was available clinically, especially at monitoring those after completion of treatment. I think as the sensitivity of these MRD assays gets better, these will become more and more important. Dr. Vamsi Velcheti: I think it's a little bit of a challenge in terms of standardizing these assays, and they're like multiple assays, which are currently commercially available. And I think the field is getting really complicated in terms of how you incorporate different assays and different therapeutics in the adjuvant space, especially if you're kind of looking at de-escalating immunotherapeutic strategies at the adjuvant setting, I think, makes it even more challenging. I think exciting times. We definitely need more thoughtful and better studies to really define the role of MRD in the adjuvant space. So, I guess more to come in this space. Dr. Nathan Pennell: Vamsi, I wanted to ask you about another really interesting Abstract 8011. This is a subgroup of the AEGEAN perioperative study for early-stage resected non-small cell lung cancer. This abstract is specifically looking at baseline N2 lymph node involvement in stage 2A-3B with N2 positive patients in an exploratory subgroup analysis. What are your key takeaways from the study?   Dr. Vamsi Velcheti: I felt this was a very interesting abstract for a couple of reasons. As you know, this is the AEGEAN trial, the phase 3 trial that was reported earlier last year. This is a perioperative study of durvalumab plus new adjuvant chemotherapy versus new adjuvant chemotherapy alone and adjuvant durvalumab plus placebo. The study obviously met its primary endpoint, as we all saw, like the event-free survival. And here in this abstract, the authors present an exploratory subgroup analysis of patients who had N2 lymph node involvement prior to study enrollment. So, in this study, they were focusing on perioperative outcomes. And one of the issues that has come up multiple times, as you know, in a lot of these preoperative studies, is the impact of neoadjuvant chemo immunotherapy on surgery or surgical outcomes. And consistently, across a lot of these trials, including the CheckMate 816, about 20% of patients don't end up making it to surgery. So in that light, I think this study and the findings are very interesting. In this study, they looked at patients who had N2 nodal involvement and of the patients with N2 nodal involvement, the surgical operability or the number of patients who completed surgery was similar in both the groups. So, there was no significant difference between patients who received durva versus chemotherapy and also among patients who had N2 subgroup who had surgery, similar proportions of durvalumab and placebo arms had open versus minimally invasive versus pneumonectomy. So durvalumab didn't have a negative impact on the type of surgery that the patients had at the time of surgery. So overall, the findings were consistent with other trials, perioperative trials that we have seen. So, the surgical outcomes were not negatively impacted by adding immunotherapy in the neoadjuvant perioperative space. So, this is consistent with other trials that we have seen. And also, the other issue, Nate, I'd like to get your opinion on is, across the board, in all the perioperative trials we have seen that about 20% of the patients actually don't end up making it a surgery. And of course, most of these perioperative trials, a lot of these patients are stage 3 patients. And my take on this was that there's probably a little bit of a patient selection issue. We generally tend to err on the side of operability when we have a stage 3 patient discussed in the tumor board, sometimes feel like the patient may downstage and could potentially go to surgery. But even in the real world, in stage 3 operable patients, what proportion of patients do you think don't end up going to surgery? Dr. Nathan Pennell: That is such an important question that I don't think we have the best answer to. You're right. All of these perioperative studies have a relatively high- sort of 20% to 30% of people who enroll on the studies don't necessarily go to surgery. And I don't think that they've done as great a job as they could in all of these trials describing exactly what happens to these patients. So in the real world, obviously not everyone would be fit enough to go to surgery or might progress in the time between when they were diagnosed and the time as planned for surgery. But probably more of them would go to surgery if they weren't getting neoadjuvant treatment, because that would be their initial treatment. The question is, of course, is that the right choice? If someone gets 12 weeks or nine weeks of neoadjuvant treatment and then a restaging scan shows that they've had progression with metastatic disease, are those really the people that would have been optimally treated with surgery upfront, or would they just have had recurrence on their first postoperative scan? So, it's really an important question to answer. I think the bigger one is, is the treatment preventing them through toxicity from going to treatment? And I think the studies have generally felt that few patients are missing out on the option of surgery because of toxicity being caused by the IO. And in the AEGEAN study, for example, in this subgroup, a slightly numerically higher percentage of patients in the durvalumab arm actually underwent surgery compared to those who got neoadjuvant chemo. So, it doesn't seem like we're necessarily harming people with the neoadjuvant treatment. But I know that this is a concern for patients and doctors who are undergoing this approach. Dr. Vamsi Velcheti: Definitely, I think having multiple data sets from perioperative trials, looking at the relative impact of IO on the safety and the nature of the surgery is going to be important, and this is a very important study for that reason. Dr. Nathan Pennell: Can I ask you another thing that I thought really interesting about this particular one is they looked at the difference between those with single station N2 and multi station N2. And I know this is one of those, should we be operating on people who have multi station N2 disease? And the AEGEAN study did include people who had multiple N2 stations where perhaps in the pre-IO era, these would have been treated with definitive chemoradiation and not surgery at all. But the disease-free survival hazard ratio was essentially the same for multi station N2 as it was in the overall population. So, has that changed the way we're approaching these patients in these multidisciplinary discussions? Dr. Vamsi Velcheti: Absolutely, Nate. I think surgical operability is in the eye of the beholder. I think it depends on which surgeon sees the patient or how the discussion goes in the tumor boards, as you know. Certainly, I think with this optionality of having a chemo IO option and potential for downstaging, kind of pushes, at least in our practice, more of these patients who are multistation, who would have otherwise gone down the chemoradiation route are now actually going through neo adjuvant chemo IO and with the hope that they would make it to surgery. So, I think it's an interesting change in paradigm in managing our locally advanced patients. So, I think it's certainly interesting, but I guess to your point, there clearly are some patients who probably should just have chemoradiation upfront, and we may be kind of like delaying that definitive chemoradiation approach for at least a subset of patients. So, at the end of the day, I think it's a lot of clinical decision-making and I think there's going to be a little bit of art to managing these patients and it's going to be really hard to define that population for a clinical trial.  Dr. Nathan Pennell: Yeah, clearly, multidisciplinary discussion, still very important for earliest age non-small cell lung cancer patients. If we move back to metastatic lung cancer, let's talk about Abstract 8510 looking at one of our newer, exciting biomarkers, which are the KRASG12Cmutant non-small cell lung cancer. So this is a study of a second generation KRASG12Cinhibitor, olomorasib, which was combined with pembrolizumab, the anti PD-1 antibody, in patients with advanced KRASG12C mutant non-small cell lung cancer. This is something that has been tried before with first generation G12C inhibitors, with some concerns about how safe it was to do that. So, Vamsi, what did you learn from this abstract? Dr. Vamsi Velcheti: Definitely, I think one of the concerns that we've had in other trials is like the cumulative toxicity of adding checkpoint inhibition to G12C inhibitors, especially the sotorasib CodeBreaK trial, where we see increased rates of grade 3, 4 transaminitis. So, it is encouraging to see that some of the newer agents have less of those issues when it comes to combining the checkpoint inhibition. So especially with KRASG12C, as you know, these are patients who are smokers, and often these are patients who have high PDL-1 could potentially also benefit from immunotherapy. In order for these KRASG12C inhibitors, in order to move these targeted therapy options for these patients to the front line, I do think we need to have substantial comfort in combining the checkpoint inhibitors, which is a standard treatment approach for patients in the frontline setting. I think this is exciting, and I think they're also like, as you know, there are other KRASG12C inhibitors also looking to combine with checkpoint inhibition in the frontline settings. So, we'll have to kind of wait and see how the other agents will perform in the setting. Dr. Nathan Pennell: Yeah, I completely agree. I think this is such an important area to explore specifically because unlike our other targeted oncogenes like EGFR and ALK, we have multiple options for these patients, both immunotherapy and targeted treatments. And if we could think about sequencing them or even combining them and if it could be done safely, I think that would be well worth investigating. There still was significant toxicity in this trial; 30% of people had diarrhea, even at the reduced dose, and there was transaminitis at sort of about 20% or so, although probably at a manageable level. But the response rate was really quite promising. And these are all previously IO and mostly G12C TKI pre-treated patients still had a response rate of 63%. And in those who were naive to IO and TKIs, it was 78% response rate. So, if it could be done safely, I think it's definitely worth pursuing this in further trials. Dr. Vamsi Velcheti: And also, there's some data, preclinical data, like looking at G12C inhibition. And also we have known with MET inhibition for a long time that it could potentially augment immune responses and could be having some synergistic effect with IO. So, we'll have to wait and see, I think. But safety is really the top in mind when it comes to combining these agents with checkpoint inhibitors. So, it's really encouraging to see that some of the newer agents may be more combinable IO. Now moving on to the next abstract, and moving on to, again, the early-stage setting. So, Abstract 8052 from our colleagues in Princess Margaret reported outcomes in early-stage non- small cell lung cancer in patients with rare targetable mutation. This is actually becoming increasingly more relevant because we are seeing at least, like with the ALINA data, with the ALK and EGFR, now with ADAURA, we know that these patients don't benefit with adjuvant immunotherapy, especially some of these rare oncogene living mutations, other than like G12C. So I always struggle with this. When you have early-stage patients, with, let's say, a ROS or a RET, where we just don't have data, and we know that those are poor actors because biologically these are aggressive tumors. So, there's a really odd clinical question to ask in terms of, what is the role of adjuvant immunotherapy? Of course, this trial and this abstract are not really addressing that. But what is your take on this abstract? If you could just summarize the abstract for us. Dr. Nathan Pennell: Sure. Well, I think this is incredibly important, and this is an area near and dear to my own heart. And that is, of course, the whole landscape of how we manage early-stage patients has changed with both ADAURA, because we now have effective treatment in the adjuvant setting for EGFR mutant patients, and now more recently with the ALINA trial for adjuvant alectinib for ALK positive patients now being FDA-approved. So, what that means is we actually have to be testing people at diagnosis even before they would be getting adjuvant treatment, and potentially before even surgery to look for these targets. We need the PD-L1 status, we need EGFR and ALK. And if you're going to be looking at these biomarkers, I think there is a reasonable argument to be made that you should be doing broad testing for all of the targetable oncogenes in these patients. There are some studies suggesting that there's value to this and identifying them for treatment at the time of recurrence. But we also know that these patients are at high risk of recurrence and probably need to be investigated, at least in trials for the adjuvant setting. So, this particular study looked at 201 resected, mostly adenocarcinoma patients, and then they basically sequenced them for all of the targeted oncogenes. And they were quite common, perhaps even more common than you might expect in an advanced population. So, 43% of them had KRASG12C mutations, 13% had EGFR Exon 20 mutation, ERBB2 or HER2 mutations found in 11%, MET mutations in 10%, ALK in 7%, ROS1 in 6%, BRAF in 5%, and RET in 2%. So quite common to find these targetable oncogenes in this particular population, perhaps a somewhat biased population at Princess Margaret Hospital, but very common. And then they looked at the outcomes of these patients without targeted adjuvant treatment. And what they found was there was a very high rate of recurrence. So, relapse-free survival was pretty high in these patients across different stages, and generally their prognosis was worse than the more common KRASG12C patients. Most of these, in particular the HER2 mutant patients, seem to have a significantly worse relapse free survival. Interestingly enough, though, that did not carry over to overall survival. Overall survival was better in those who had targetable oncogenes. And my guess is that that probably had to do with the availability of targeted treatments at the time of recurrence that may have impacted overall survival. But I do think that this particularly highlights the need, the unmet need for effective adjuvant treatment in these patients. And most of them, with the exception of KRAS and perhaps BRAF, perhaps MET unlikely to benefit from adjuvant immunotherapy, as you mentioned. And so, I think we really need to be investing in trials of adjuvant targeted treatments in these populations.  Dr. Vamsi Velcheti: Yeah, this is an area that we really don't have a lot of data. But Nate, a question for you. So tomorrow you have a patient with RET fusion, stage 2, N1 disease. What would you do? Would you offer them an adjuvant RET inhibitor? Dr. Nathan Pennell: I think I would search really hard for a trial to give them access. But if you really want to know what I think, and I'm usually willing to tell people what I think, I think the proof of concept is there. I think we know that in the setting of highly effective and very tolerable adjuvant targeted treatment in the EGFR space with osimertinib, in the ALK space with alectinib, if anything, drugs like selpercatinib and pralsetinib in RET fusion positive lung cancer in the advanced setting are just as well tolerated and easily as effective and long lasting. And so, I think if you did a trial and they are doing trials looking at these drugs in the adjuvant space, almost certainly you're going to see the same really dramatic disease-free survival benefit from these treatments, which, at least in the EGFR space, seems to have translated into an improvement in overall survival. And so if I had a stage II or a resected stage 3, especially a RET fusion positive patient today, I would definitely talk to them about off-label use of a RET inhibitor if I could not find a trial. Now, I understand that there are going to be reimbursement issues and whatnot associated with that, but I think the extrapolation is worth discussing. Dr. Vamsi Velcheti: Yeah, I think it's really challenging because some of these fusions are so rare and it's hard to really do large adjuvant trials for some of these rarer subgroups. Nate, fascinating insights. Our listeners will find links to the abstracts we discussed today in the transcript of the episode. And Nate, I look forward to catching up with you at the Annual Meeting, and again after the meeting for our wrap up podcast to discuss the practice-changing lung cancer abstracts and highlights from the Plenary Session. Thank you so much for joining us and sharing your insights today. Dr. Nathan Pennell: Thanks for inviting me. Vamsi. I look forward to touching base after we get to see all the late-breaking abstracts. Like I said, this is, I think, a year for lung cancer with a lot of exciting data, and I know we'll have a lot to talk about. Dr. Vamsi Velcheti And thank you so much to all our listeners for your time. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate and review and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Vamsi Velcheti @VamsiVelcheti   Dr. Nathan Pennell @n8pennell   Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures: Dr. Vamsi Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Laurens is a vibe. His Live Slow, Ride Fast mantra is a media company and it's a way of life! He has very big plans for 2024, so listen in as we talk the Portugal N2 trip, his target of Tour Divide, how he stays fit at 43, and what it takes to compete at the pointy end of World Tour bike races in this modern age. N2 trip in summary: https://www.youtube.com/watch?v=M7I4RBIlp9c Follow Laurens at: @laurens_ten_dam And why don't you buy yourself some AG1 at: www.drinkAG1.com/tedking

Are you getting the sleep you need? Do you wish you could improve your sleep, but you're not sure how? Dr. Gina Poe is an accomplished researcher and trained neuroscientist with a PhD in basic sleep. Currently a professor at UCLA, Dr. Poe has been researching the functions of sleep for over 30 years and has authored nearly 200 publications on the topic. Today, Dr. Poe is here to answer your questions like, Why do you sleep? What is your brain doing as you sleep? What is REM sleep? What are sleep cycles? What are circadian rhythms? And perhaps most importantly, you'll get 5 research-backed recommendations from Dr. Poe on how anyone, including you, can not only improve their sleep but also get a “perfect” night's sleep, as defined by a neuroscientist. In this conversation, Dr. Poe discusses topics such as:What is the “perfect night's sleep”?How long are you supposed to sleep every night?What is a sleep cycle, and why should you care?What is N1 sleep?What is N2 sleep?What is N3 sleep?What is paradoxical sleep and how can you tell someone's in that state?What REM sleep really is and how often we must be in it.The physiological and neurological difference between being awake and asleep.What a neurotransmitter is and how it changes composition when asleep.What the functions of our brain's two hemispheres are.How sleep cleans the brain.The connection between sleep and neuroplasticity.The link between sleep and brain health.The scientific reason why they call it “falling” asleep.How sleep directly affects longevity and vitality.Why you don't remember your dreams.How sleep impacts how we learn during the day.What happens to your body and brain when you close your eyes at night.The one phase of sleep you cannot miss.A neuroscientist's top 5 recommendations for better sleep.What the purpose of vasodilation is.Which hours of sleep are absolutely critical for memory processing.How many hours of sleep you really need for optimal functioning.Why a consistent bedtime is the start of the best sleep of your life.  Follow Dr. Poe: Instagram: instagram.com/poe.gina Webpage: bri.ucla.edu/people/gina-poe-ph-d/Watch the episodes on YouTube: https://bit.ly/45OWCNrMy book! ‘High 5 Habit', here: https://a.co/d/g1DQ8Pt Follow me: Instagram: https://bit.ly/3QfG8bbThe Mel Robbins Podcast Instagram: https://bit.ly/49bg4GPLinkedin: https://bit.ly/46Mh0QBTikTok:  https://bit.ly/46Kpw2v Sign up for my newsletter:  https://bit.ly/46PVnPs  Want more resources? Go to my podcast page at melrobbins.com/podcast. Disclaimer