Podcasts about N2

Springvale is booming with record sales, a R14 million home sold in two weeks, and new developments like the N2 off-ramp and Seaton House school adding value. Beyond this growth, the estate offers security, space, and a welcoming community, making it a top choice for families and investors. Radio Life & Style on Facebook · The Morning Show Sponsor: Excellerate Security

In today's BizNews Briefing, Ninety One CEO Hendrik du Toit defies the political consensus with a rare public critique, while Ramaphosa's land reform praise stirs growing unease. Cape Town ramps up policing to combat N2 violence, and BizNews prepares to launch the Ricardo Portfolio at the end of September. Also in focus: AI's disruption of Hollywood, Elon Musk's trillionaire trajectory, Altvest's bold Bitcoin bet, and key updates from AVI and Metrofile.

Cape Town's safety chief, Alderman JP Smith, tells Alec Hogg how the city is deploying hundreds of new law enforcement officers, drones, cameras, and even bait cars to confront the surge of violent incidents on the N2 and R300. With pressure mounting on the national government to devolve policing powers, Smith warns that Cape Town is no longer waiting for Pretoria to act.

durée : 00:02:48 - Retour sur le match de N2 du Stade Poitevin Foot Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

Bonjour à toutes et tous, Footballeuses, footballeurs et tous les coaches, pour lancer cette SAISON 4 , j'accueille Nicolas Puydebois qui est l'entraineur des gardiens N2 du Goal FC. Aujourd'hui nous partons à la rencontre d'un ancien professionnel de football au poste de gardien. Nicolas nous raconte son parcours pro et la bascule dans le monde amateur. Il oppose et met en relief ses deux mondes sans langue de bois. On prend le temps d'échanger sur la causerie qu'il fait avec les gardiens de son club avant et pendant les matchs. N'hésitez pas à brancher vos écouteurs pour écouter le parcours le parcours de Nicolas et sa vision sur le monde amateur. Podcast comme d'habitude à ne pas  manquer. Une fois de plus nous n'avons pas vu le temps passé. Un GRAND MERCI à Nicolas pour le temps accordé et d'avoir joué le jeu de l'interview.Bonne écoute à tous et merci encore pour votre soutien !!!N'hésitez pas  à échanger sur nos RS et AUTOUR DE VOUS. Si vous souhaitez avoir des précisions ou si vous souhaitez m'aider à améliorer le contenu vous pouvez me contacter directement à lacdc69@gmail.com .Vous pouvez rejoindre l'association LaCDC69 en adhérant. Différents packs  sont à votre dispositions pour nous soutenir et ainsi faire durer le podcast. ✴️ Pour adhérer c'est ici : https://bourdelon.wixsite.com/lacdc69/nous-soutenir  ✴️Podcast : https://podcast.ausha.co/lacdc69 Site web : https://bourdelon.wixsite.com/lacdc69 Instagram : https://www.instagram.com/lacdc69 Facebook : https://Facebook.com/ lacdc69 Twitter : https://twitter.com/LaCDC69Youtube : https://www.youtube.com/channel/UCzr8REkRNLGlUh98H78UAUAHébergé par Ausha. Visitez ausha.co/politique-de-confidentialite pour plus d'informations.

In today's BizNews Briefing, we honour Neil de Beer, a true patriot and a national treasure. Also on the agenda: Cape Town's deadly N2 gauntlet, shocking revelations about the perks and pay of South African MPs, Nvidia's results shaking global markets, Cell C's high-stakes restructure, Bidvest's steady but pressured numbers, and CA Sales' strong growth despite currency headwinds.

durée : 00:02:45 - Foot : retour sur la 3ème journée de N2 et les résultats de Poitiers et Chauray Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

Wayne Coetzer and anti-crime activist Paul Treleven share chilling first-hand accounts of deadly attacks along the N2 highway near Cape Town International Airport. With boulders hurled at cars, tourists targeted, and law enforcement absent, they warn Alec Hogg that without urgent action the Western Cape's booming tourism and wine industries could face devastating consequences.

In this JCO Article Insights episode, Dr. Joseph Matthew interviews authors Dr. Yang Zhang and Dr. Haiquan Chen about their recently published JCO article, "Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity–Dominant Lung Adenocarcinoma" TRANSCRIPT Joseph Mathew: Welcome to the Journal of Clinical Oncology Article Insights episode for the August issue of the JCO. This is Joseph Mathew, editorial fellow for JCO, and today, it is my pleasure to have with us Dr. Haiquan Chen and Dr. Yang Zhang, authors of the recently published manuscript, "Phase 3 Study of Mediastinal Lymph Node Dissection for Ground-Glass Opacity-Dominant Lung Adenocarcinoma," which we will be discussing today. Dr. Chen is the Director of the Institute of Thoracic Oncology at Fudan University and the Chief of Thoracic Surgery at Fudan University Shanghai Cancer Center, where he is also the Head of Thoracic Oncology MDT and the Director of the Lung Cancer Center. Dr. Chen is a surgeon-scientist and a pioneer in developing individualized surgical strategies for early-stage non-small cell lung cancer. Dr. Zhang is a surgical oncologist and a member of the team which Dr. Chen leads at the Fudan University Shanghai Cancer Center. Welcome Dr. Chen and Dr. Zhang. Thank you very much for accepting our invitation and joining us today as part of this podcast episode. To summarize the salient points, this study presented the interim analysis of a multi-center, open-label, non-inferiority, randomized controlled trial investigating the necessity of systematic mediastinal lymph node dissection at the time of segmentectomy or lobectomy in patients with clinical stage T1N0M0 ground-glass opacity-dominant invasive lung adenocarcinoma, as defined by a consolidation-to-tumor ratio of 0.5 or less on thin-section computed tomography and a maximum tumor diameter of 3 cm or less. Eligible participants with intraoperatively confirmed invasive adenocarcinoma on frozen section analysis were randomized to either the systematic mediastinal lymph node dissection arm or to no mediastinal lymph node dissection. In the latter experimental group, mediastinal lymph nodes comprising the N2 nodal stations were not dissected, and the hilar nodes were variably addressed at the discretion of the operating surgeon. The primary endpoint of the trial was disease-free survival at 3 years. Secondary endpoints included perioperative outcomes, the status of lymph node metastasis in the systemic lymph node dissection arm, and 3-year overall survival. Before the trial reached its accrual target, a pre-planned interim safety analysis set for the time point when enrollment reached 300 patients was performed. It was noted that while none of the patients in either arm had nodal metastasis on postoperative pathological evaluation, lymph node dissection-related intraoperative and postoperative complications were more commonly observed in the systematic lymph node dissection arm, including one life-threatening episode of massive bleeding. Since this met the predefined criteria for trial termination, and in accordance with the principle of non-maleficence, further recruitment was stopped and the trial terminated. Although the 3-year disease-free survival and the overall survival for the enrolled patients were comparable, operative outcomes, including the duration of surgery, blood loss, chest tube duration, length of postoperative stay, and the rate of clinically significant complications, were significantly lower in the experimental arm compared with the systematic lymph node dissection group. The authors concluded that for well-selected patients, mediastinal nodal dissection could be omitted without adversely affecting oncological outcomes, representing a significant shift in current surgical practice, given that guidelines the world over recommend systematic lymph node dissection or sampling for all invasive lung cancers. In summary, this study addressed a clinically relevant question with regard to the extent of nodal dissection, especially in the light of recent evidence recommending less extensive parenchymal dissections for early-stage non-small cell lung cancer, with the findings suggesting that invasive lung adenocarcinoma associated with ground-glass opacities of consolidation-to-tumor ratio up to 0.5 was an excellent predictor of tumor biology, and in clinical T1N0M0 lesions, a reliable predictor of negative mediastinal lymph node involvement. So Dr. Chen and Dr. Zhang, could you tell us some more about what led you to do this research and the challenges which you faced while recruiting patients for this trial? Dr. Yang Zhang: Dr. Mathew, thank you for your summary. The current clinical guidelines recommend systematic lymph node dissection or sampling for every patient with early-stage lung cancer, regardless of their lymph node status. And in our clinical practice, we observe that this procedure causes a lot of surgical complications including chylothorax and recurrent laryngeal nerve injury. Furthermore, dissecting the tumor-draining lymph nodes actually may potentially damage the body's anti-tumor immunity. So, Dr. Chen proposed the concept of selective lymph node dissection, which we aimed to dissect the metastatic lymph nodes, while at the same time we try to preserve as many uninvolved lymph nodes as possible. So previously, we have conducted a series of retrospective studies to identify reliable predictors of nodal negative status in certain mediastinal zones, and we have performed a prospective observational phase 2 clinical trial to validate that the six criteria we proposed are 100% in predicting node-negative status. And this forms the basis for our phase 3 clinical trial. Dr. Haiquan Chen: This trial is only one of the series of trials. The meaning of this trial you already said. And for a long time, from the surgeon's point of view, we considered minimally invasive surgery. It minimizes the size of the incision and minimizes the number of the holes we made. So, the true and the high-impact of minimally invasive, we make a concept of minimal dissection, that means organ-level minimally invasive. So we proposed the concept of minimally invasive 3.0, that means minimal incision, minimal dissection (that means organ-level minimal), and systemic minimally invasive. So at first, we judged from the point of minimally invasive surgery. As long as immunotherapy is widely used in the clinical practice, we know immunotherapy, that means you use drugs to stimulate and activate the lymph node site. If we dissect all the metastatic lymph nodes, cut them out, how can we restimulate that lymph node site? So, from minimally invasive trauma and second, from the functional aspect, to try to save as many uninvolved lymph nodes as possible. Joseph Mathew: Thank you, Dr. Chen. That's a very interesting concept that you alluded to even in the discussion of this paper, as to the potential role of the non-metastatic lymph nodes as immune reservoirs. So, coming back to this paper, were there any challenges which you faced while recruiting patients for this trial? Dr. Haiquan Chen: The criteria is very clear. That means invasive adenocarcinoma, that means most of the centimeter is 3.0 centimeter and also CTR ratio less than 0.5. And we can see that, you know, we did study about that. Even the invasive component of the subsolid nodule, it's bigger than the solid part. That means even the pure GGO, we can find out that there's still some invasive component. From this point of view, pure GGO and subsolid GGO, from this part of invasive carcinoma, that means it's a special clinical subtype that we, from retrospective study and also prospective study, we find out this group of patients, there are no mediastinal lymph node metastasis. So I think it's very important for this kind of group that we can avoid doing the mediastinal lymph node dissection. And we can do organ-level minimally invasive surgery. And also, we try to keep the patient's immune function as normal as possible. Dr. Yang Zhang: Well, Dr. Mathew, we believe that the biggest challenge when we are enrolling these patients is that there needs to be a paradigm shift in the mind because systematic lymph node dissection has long been the standard of care. And some patients may misunderstand. Before the enrollment, we have to give them informed consent, but if the patient hears that they may be enrolled in the no-lymph-node-dissection group, they may feel that they do not receive radical, curative-intent surgery. So we believe, as Dr. Chen has said, after the release of our results, the no-lymph-node dissection may be incorporated in the future guideline for those patients without lymph node involvement, we can just omit the lymph node dissection. Joseph Mathew: The study described two pre-planned interim points during the course of subject enrollment when the data was analyzed. So Dr. Chen and Dr. Zhang, could you please explain a little more about these two interim points of analysis that were planned and the rationale behind it? Dr. Yang Zhang: When conducting this trial, we have two concerns. One is if there is any lymph node metastasis, there may be omission of metastatic lymph nodes not dissected in the no-lymph-node-dissection group. And there is another concern is that if all these lymph nodes are uninvolved, then dissecting these lymph nodes may cause life-threatening complications. So, we set the 150 interim analysis to ensure that there is no lymph node involvement in this group. And the other early termination criteria is set because if there is no lymph node involvement found in both groups, then a severe complication which is life-threatening is unacceptable because it threatens the patient's safety. Joseph Mathew: So, although you did briefly allude to in the paper, what was the basis for selecting DFS as the primary endpoint when the objective of this trial was to assess nodal involvement in this subset of tumors? Dr. Yang Zhang: Well, previously, we have done a series of retrospective studies and one prospective phase 2 trial. And in these studies, we have identified that GGO-dominant lung adenocarcinoma, even if it's invasive, it has no lymph node involvement. So this phase 3 trial was primarily designed to compare the survival outcomes. But as the trial went on, as Dr. Chen has concerns that if the patients have no lymph node metastasis at all, it may be unfair to dissect the lymph nodes for patients enrolled in the systematic lymph node dissection group. So there is one life-threatening complication that happens due to dissecting the lymph nodes and injury to the superior vena cava, which leads to massive bleeding. It is at this point that we decided to terminate this trial for patient safety concerns. Joseph Mathew: Yeah, that's a very fair point. So you made sure that the ethical considerations were kept intact. So another point was, there was a mention in the study of the historical data from your institution suggesting a 3-year disease-free survival of 96.6% for patients with clinical T1N0M0 ground-glass opacity-dominant invasive lung adenocarcinoma. So could you please elaborate on the patterns of recurrence which you noted for this group of patients who had developed a recurrence? Dr. Haiquan Chen: Yeah, I think over 90% 3-year DFS, that's the least. From our retrospective data for this kind of group of patients, their DFS is so good. To the best of my knowledge, almost 100%. So this is very conservative, 94, 90% is very conservative. I think the trial eventually would have been positive. It's a special clinical subtype, even for invasive adenocarcinoma, their prognosis is much better than the other type of invasive adenocarcinoma. Joseph Mathew: So this question may be slightly outside the purview of this study, but in your clinical practice, would you advocate either segmentectomy or lobectomy for all patients meeting the trial criteria, that is, lesions measuring 3 cm or less with a CTR of up to 0.5? Or is there a subgroup of patients you would recommend a wedge dissection for? Dr. Haiquan Chen: I think CTR ratio is one parameter and also the location is another very important parameter. So we put it together to make a decision, the patient should do a lobectomy or segmentectomy. Even for an ongoing trial, for even the patient, invasive adenocarcinoma, we can do in the right location, even wedge, it can achieve enough negative margin in the ongoing trial to verify the comparable result for the patient, we can do the wedge dissection. So not just the CTR ratio, that's not the only parameter to make a decision on what kind of procedure we'll do. Joseph Mathew: Yeah, great point, Dr. Chen. So from my perspective, this study was a well-designed, randomized control trial based on a relevant and clinically valid research question. So what, in your opinion, are the main strong points of this study? Dr. Yang Zhang: We believe that this study represents the first randomized clinical trial published, yet, regarding the topic of selective lymph node dissection. It basically offers the highest level of evidence. We believe our results should be incorporated in the future clinical guideline. Joseph Mathew: Given the increasing incidence of these lesions, I think it was- a randomized control trial in this arena was much awaited. And the other point is that GGO-dominant lung adenocarcinomas, the specific clinical guidelines are not very clear. So I think your study brought out that lymph node dissection for these tumors which satisfy the eligibility criteria could be omitted safely. Important consideration here is that the conclusions of the trial were based on an interim analysis, and this analysis was not planned for an early assessment of the primary endpoint. In other words, the study was not adequately powered to detect a significant difference in DFS at 3 years. So Dr. Chen and Dr. Zhang, what do you perceive are the most important limitations of this study which you feel should be addressed in future research? Dr. Haiquan Chen: So the surgery now is more individualized. I think the surgery from the last two decades, from the maximum tolerable intervention to minimum effective treatment, there's a big shift. So I think that the consensus, we can preserve normal lung parenchyma as much as possible. For the lymph nodes, I think that the big shift, we should shift it to keep as many as uninvolved lymph nodes as possible. So that's very important, not just to reduce the intraoperative trauma, but also to keep the immune environment as normal as possible. Joseph Mathew: Another point was the limited long-term follow-up data to determine the actual impact of omitting lymph node dissection on local-regional disease control. So is any future follow-up planned to assess the long-term survival outcomes for the 302 patients which were enrolled in this trial? Dr. Haiquan Chen: Yeah, I think that's very important for us. This trial we terminated just because if we keep the trial going, it's unfair for the mediastinal lymph node dissection group. We tried to just stop here, and we shifted to the single-arm trial. So, 2 or 3 years, this trial and another trial, they will give our final result to demonstrate more if selective mediastinal lymph nodes have a better result than ever before. And we will support the mediastinal lymph node dissection. That's one way. And the American College just asked me, how can we put this policy into clinical practice in the United States? Because most of the patients they meet have solid tumors. So we have another trial, try to figure out how we can make sure before and intraoperative the lymph node status is negative or positive, and then we can solve that problem and put this policy into clinical practice in the Western society. Joseph Mathew: Great. So that would be something we should all be looking forward to. So, this brings me to the final point of discussion on future research in this field. Dr. Chen, you commented in the paper that future studies should focus on improving the reproducibility of CTR evaluation. What are your thoughts on this subject? Dr. Haiquan Chen: The CTR ratio, the concept from the JCOG 0201, just a concept from that prospective study, the phase 2 study, only subgroup analysis they give the concept of CTR ratio and the diameter. How can we reproduce? In our group and also I believe in Japan and in China, in Korea, and in our daily practice, I think CTR ratio is not a big issue. There are two very important things. One, you make sure the CTR ratio, not in a common CAT scan, but in a high-resolution CAT scan. So the imaging, that's the first thing. And the second, not from the single section and a two or three section, you make sure that your calculation is accurate. That's not just the single section, you make sure that you got the conclusion, the CTR ratio is the same number. We make sure that totally we, from the top to the bottom of the whole lesion, we make sure that the CTR ratio is accurate. Joseph Mathew: Thank you, Dr. Chen. I think that would involve training our radiologists also to be aware of the CTR ratio and how it should be interpreted. So another very interesting concept which you had alluded to in the discussion was the potential role of non-metastatic lymph nodes as immune reservoirs. So how do you think we could preserve these nodes and do you think sentinel node biopsies would play a role in future? Dr. Yang Zhang: Actually, Dr. Chen has also led some basic research on this topic. We are investigating the immunological role of the tumor-draining lymph nodes. And our preliminary results have already shown that the tumor-draining lymph nodes of lung cancer, especially those uninvolved lymph nodes, have a vital role in the anti-tumor immunity and also effective response to the current anti-PD-1 immunotherapy. In the future, we believe that by incorporating our clinical evidence and those findings from our basic research, we will be able to provide very strong rationale to support selective lymph node dissection. Joseph Mathew: So lastly, what are the questions that still remain to be answered and what do you perceive as the next step in this field? Dr. Haiquan Chen: I think for the lung cancer surgery, especially for the cT1N0M0, they are more individualized. We can, based on the patient, the location, the CTR ratio, we can do wedge dissection, or segmentectomy, or lobectomy. For the lymph node dissection, we can do no mediastinal lymph node dissection or selective, only to dissect the positive one, or we have to do the systemic mediastinal lymph node dissection. So we can see there are too many combinations. So in the near future, for the surgery perspective, we have it more individualized. In the future, we just try to make sure we do not cut as many as possible. We just make sure that we can avoid over-diagnosis or overtreatment or over-dissected. I think that in the near future, that goal will come true. Joseph Mathew: That's a great point, Dr. Chen. So that would be something also for the thoracic oncology community to work towards. This wraps up today's episode of JCO Article Insights. Dr. Chen and Dr. Zhang, thank you very much for taking the time to join us today in what has been a very insightful session. Dr. Haiquan Chen: Thank you. Dr. Yang Zhang: Thanks. Joseph Mathew: To our audience, thank you for listening. Please stay tuned for more interviews and articles, summaries, and be sure to leave us your comments and ratings. 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.

Disciples! Nate and I are back to ‘the usual’, playing catchup and hangin’ out. Oh, and we’ve brought friends: Witch Hound from Poland and The Incantus from Australia. Let’s do this.m/ What’s Nate been listening to?Artist: Allman Brothers BandAlbum: Idlewild SouthSong: Revival ——————————————————-CURRENT EVENTS——————————————————-G1: ERIC BRITTINGHAM And FRED COURY Are ‘Open’ To CINDERELLA Reunion For One-Off Concerthttp://blabbermouth.net/news/eric-brittingham-and-fred-coury-are-open-to-cinderella-reunion-for-one-off-concert N2: … Continue reading (373) DotW Featuring ‘Witch Hound’ and ‘The Incantus ‘ →

Send us a textChuck shares his eye-opening experience at BICSI Beyond 2025 in Las Vegas, revealing industry shifts and technological developments that will impact ICT professionals. The conference highlighted alarming workforce demographics and showcased emerging technologies that could transform how cable installation is performed.• Introduction to Challenge Coins as special recognition tokens for major contributors to the podcast• Recording of interviews with John Daniels (BICSI CEO), Chuck Wilson, and Matt Affel from the JATC• Participation in multiple committee meetings including the new ICT Lifecycle Management Training Committee• Updates on industry standards including revisions to the N1, N2, and N3 documents• Insights from Matthew Griffin's keynote about AI's impact on ICT, including cable-pulling robots• Industry statistics showing 67% of low voltage workers are over 40 and only 13% under 30• Revelation of 9.9 million job vacancies in the low voltage industry• Exhibit hall highlights including new cable testing technology from Trend NetworksIf you enjoy this content, please consider becoming a Patreon member to support the podcast. Your contributions help me represent your interests at industry events and committees while creating valuable content for the ICT community.Support the showKnowledge is power! Make sure to stop by the webpage to buy me a cup of coffee or support the show at https://linktr.ee/letstalkcabling . Also if you would like to be a guest on the show or have a topic for discussion send me an email at chuck@letstalkcabling.com Chuck Bowser RCDD TECH#CBRCDD #RCDD

Kuukausipalaveri 23 agenda: ⁠Opiskelijoiden siirtyminen asumislisään Rahoituksen saatavuus Kuluttajahinnat Pankkien luotonannon seurantakysely Suomen tulokset N2/2025 Euro area bank lending survey Rakennuskustannusideksi Kiitos Ostan Asuntoja -sisällön mahdollistavalle sponsorille:   Asuntopehtoori on suomalainen perheyritys, joka tarjoaa asiakkailleen vuokravälitystä, sijoitusasuntojen hallinnointia ja asuntomyyntiä sekä isännöintiä ympäri Suomen. Huolenpitopalvelullaulkoistat vuokrasuhteen hoidon Asuntopehtoorille, joka hoitaa asuntoon ja vuokrasuhteeseen liittyvät käytännön asiat puolestasi ja takaa vuokrat koko vuokrasuhteen ajan.. VuokravälityksenAsuntopehtoori hoitaa kilpailukykyisin kiintein hinnoin vuoden vuokratakuulla. AsuntopehtooriIsännöintitarjoaa nykyaikaista proaktiivista isännöintiä, jonka avulla pystytään parantamaan taloyhtiöiden arvoa. Lisätietoaasuntopehtoori.fi Kiitos Ostan Asuntoja -sisällön mahdollistavalle sponsorille: Sijoitusasunnot.com ostaa huolellisesti tutkimiaan kokonaisia kerrostaloja ja myy niistä valmiiksi vuokrattuja sijoitusasuntoja alle markkinahinnan. Mikäli etsit kassavirtapositiivista sijoitusasuntoa, liity sijoitusasunnot.comin sijoittajalistalle. Saat uusista kohteista kattavat myyntimateriaalit, joissa on asuntosijoittajan keskeisimmät tunnusluvut ja taloyhtiöiden tiedot selkeässä muodossa. Tarjolla on myös monimuotoista opastusta asuntosijoittamisen saloihin ja sisältöä Instassa, Facebookissa ja YouTubessa. Tutustu maksuttomaan Asuntosijoituskouluun Lue Sijoitusasunnot.com Blogista: Täydellinen vuokrailmoitus Kiitos Ostan Asuntoja -sisällön mahdollistavalle sponsorille: On kuulopuheita ja luulopuheita – ja sitten on oikeaa tietoa. Tätä tietoa ja tukea tarjoaa yli 34 000 jäsenen Suomen Vuokranantajat. Jäsenenä saat pääsyn muun muassa vuokranantajan työkaluihin, markkinatietoon, kattavaan tietopankkiin ja maksuttomaan lakineuvontaan. Luotettavaa osaamista. Liity jäseneksi ja suosittele kaverillesi: vuokranantajat.fi/liity Työpaikalle on kiva mennä Eemeli Karlsson Osa 1 – Ostan Asuntoja Podcast #310 Karlsson, Grahn, Parviainen, Huru – Kuukausipalaveri 21 – Ostan Asuntoja Podcast #364   Naapurikodit ostaa kokonaisia kiinteistöjä, jalostaa niistä viihtyisiä koteja ja jää omistajaksi nostamaan taloyhtiön arvoa. Osa asunnoista tarjotaan ostettavaksi. Haluatko asuntosijoittajana mukaan? Lue lisää naapurikodit .fi   Naapurikoteja Anniina ja Jesse Parviainen Osa 1 – Ostan Asuntoja Podcast #283 Taloyhtiösäästö etsii säästö- ja lisätulokohteita taloyhtiöllesi. Palvelulla on tulostakuu. Maksat vain toteutuneesta taloudellisesta tuloksesta. Katso lisää taloyhtiosaasto.fi Syövätkö korkeat vastikkeet vuokratuottoa? Leikkaa taloyhtiön kustannuksia Valvean energiasäästöpalvelunavulla. Palvelu ei vaadi alkuinvestointeja. Se sisältää koevuoden ja säästötakuun. Palvelumaksu on energiakustannussäästöä pienempi. Pyydä taloyhtiölle maksuton säästölaskelma. Valvea.fi Uudistunut Vuokraovi on entistä houkuttelevampi vuokra-asuntojen markkinapaikka, jossa hyvää vuokrakotia etsivät vuokralaiset ja niitä tarjoavat vuokranantajat onnistuvat löytämään toisensa vieläkin helpommin. Vuokraovi.com Vastuu palovaroittimista siirtyy taloyhtiöille vuoden -25 loppuun mennessä. Onko taloyhtiösi valmis? Valvo on pilvipalvelu, joka tarjoaa modernit etäluentapalvelut sisältäen huoneistojen palovaroittimien, vedenkulutuksen, vuotojen ja sisäilmaparametrien valvonnan. Saatavilla myös laitteistot avaimet käteen periaatteella. Oletko ostamassa sijoitusasuntoa ja haluaisit markkinahinta-arvion ostettavasta asunnosta? Pankkiarvio.fi on edullinen ja helppo palvelu tähän tarpeeseen. Täytät vain omat tietosi ja lähetät sinulla olevat dokumentit. Markkinahinta-arvion avulla saat näkemystä siihen, ettet maksa asunnosta liikaa. Pankkiarvio.fi. Asuntosijoittamisen lumipalloefekti -kirjan tilauspaikka on asuntosijoituskirja.fi. Koodilla TAVOITE -25 %. Kirja on vuokratuloista verovähennyskelpoinen kulu. E-kirjan saa luettavaksi heti. Isyysblogin muistiinpanot Asuntosijoittamisen lumipalloefekti -kirjasta – Tiistaiaudio #314 Marko Kaarton esikoiskirja "Sijoita Asuntoihin! Aloita, kehity, vaurastu" löytyy samalta sivustolta. Koodilla ALOITA saat lisäalennuksen. Asuntosijoittajan ABC -verkkokurssin tilauspaikka on rahamedia.fi/verkkokurssit.  ostanasuntoja@NostrVerified.com, Ostan Asuntoja X, Ostan Asuntoja Insta, Ostan Asuntoja FB, Ostan Asuntoja TikTok

durée : 00:02:03 - Le 2' chrono, ici Poitou Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

開會卡卡、思緒不清？別再怪自己！其實是身體在抗議。美鳳姐真心推薦的－娘家大紅麴，唯一有3健字號的紅麴品牌，不傷肝腎成分：有助於調節血脂、血糖，還能延緩衰老，顧健康又顧狀態！立即點擊領取優惠

Via libera del Ministero dell’Ambiente al decreto attuativo che regola gli incentivi per l’acquisto di veicoli elettrici. A disposizione ci sono 597 milioni di euro, risorse che arrivano dal Pnrr. La misura riguarda anche i veicoli elettrici commerciali che appartengono alle categoria N1 e N2, quindi furgoni e autocarri fino a 12 tonnellate. Era attesa da mesi dalle imprese di autotrasporto in un tempo caratterizzato dal calo costante delle immatricolazioni dei veicoli commerciali e degli autocarri ma anche degli industriali, come sottolineano gli ultimi dati diffusi da Anfia. Ne parliamo con Gianmarco Giorda, direttore generale di Anfia.Al porto di Napoli sospesa la serrata dei tir impegnati nei trasporti dei container. Ricostruiamo la vicenda con Attilio Musella, Cna Fita Campania.

Most of us know the feeling: the alarm rings and you either spring out of bed ready to face the day, or you groggily fumble for the snooze button. But why does waking up feel so different from day to day? New research published in the journal Current Biology has revealed what's happening inside the brain during those first few seconds of waking up. Using high-density EEG (electroencephalography) to record over 1,000 awakenings, they discovered a consistent pattern of brain activity that helps explain why we feel alert or not after sleep. The researchers found that waking up is not like flipping a switch. Instead, it's more like a wave rippling through the brain, with certain regions turning on before others. The found that: The front of your brain (prefrontal cortex) wakes up first. This area is responsible for decision-making and attention. The back of your brain (visual and sensory areas) lags behind by a few seconds. If you're waking from deep (NREM) sleep, your brain shows a brief burst of slow brain waves (delta waves), a kind of transition signal before ramping up to faster, more alert-like activity. Waking from REM sleep, by contrast, skips the slow-wave burst and jumps straight into high-frequency activity. The team also found that this order was consistent across different types of awakenings, whether spontaneous or caused by an alarm. Participants who had a strong slow-wave signal (linked to a type of brain wave called a K-complex) just before waking were less sleepy once awake. It seems that a little bit of “sleep-like” brain activity right before you wake up might help you feel more alert. These waves seem to act like a “reset” signal that prepares your brain for the shift into wakefulness. But too much of another type of slow brain activity (called “type II” slow waves) right before or after waking? That was linked to feeling groggier. In short: Helpful slow waves (type I): Lead to more alert wake-ups. Unhelpful slow waves (type II): Make you feel sluggish. So, how can you apply these findings to your own mornings? Here is what the research found: 1. Wake Up at the Right Sleep Stage Use a sleep tracker or app that wakes you up during light sleep (N2 stage) if possible. Waking during REM or deep sleep increases the chance of grogginess. 2. Use Gradual Alarm Sounds Loud, jarring alarms can skip over the natural slow-wave transition, especially in REM sleep. Try gentle sounds or wake-up lights that simulate sunrise to help your brain transition naturally. 3. Consistency is Key Stick to a regular sleep schedule. The more your brain is in sync with your circadian rhythm, the more likely it will initiate a healthy wake-up sequence. 4. Get Moving Quickly Since your brain finishes “waking up” from front to back, physical movement (even just sitting up or stretching) can help speed up the rest of the brain's activation. 5. Don't Snooze Too Much Snoozing might send your brain back into deeper sleep stages, increasing the odds of waking up groggy when the alarm rings again. One solid wake-up is better than several mini ones. See omnystudio.com/listener for privacy information.

For many real estate agents, marketing and advertising are murky must-do activities we don't understand. We know we need to “get out there” and stay in front of our target market. We've been told to build a brand, show up in more places, put money behind our efforts, and wait for the ROI to show up.  But what does that actually mean, and does it even work?  With so many options and so much noise, it's no wonder agents feel stuck, scattered, or skeptical. Add to that the pressure to show instant results, and most agents end up measuring the wrong thing, too soon, and in all the wrong ways.  The truth? ROI isn't about what happens in the first 30 days. It's about what happens after consistent visibility and long-term trust compound. In this episode, I sit down with JP Hamel, the newly appointed President and CEO of The N2 Company.  With 16 years of experience in hyper-local advertising and a background as a franchisee himself, JP offers a clear-eyed perspective on what it really takes to grow your visibility, reputation, and referrals in real estate.   There are many places to advertise, but businesses generally don't get a great education on where to spend their money. -JP Hamel   Things You'll Learn In This Episode  ROI isn't broken, your timeline is Why do most businesses misunderstand ROI entirely? What crucial variable are they leaving out that changes everything about how you should measure success? Omnipresence beats one-time hits What does Verizon's marketing have in common with the average small business advertiser, and how can you become unignorable in your niche? Most no's are just not yets Your ideal client wants to hire you, but they're just not ready yet. How do we unlock the power of long-term brand saturation in buying cycles? Spray-and-pray is for Doritos How do you know if you're advertising in the wrong places entirely? Guest Bio JP Hamel is the President and CEO of The N2 Company. He has the privilege of leading a team of over 800 of the most talented, top-earning, and inspiring salespeople in the nation. This team has taken N2 to revenues of over $125M and to over 850 publications nationwide. JP is incredibly passionate about his job and believes in faith over fear when it comes to sales and selling. Find JP Hamel on LinkedIn.   About Your Host Remington Ramsey is a speaker, author, entrepreneur, and visionary in the world of real estate. As the creator of "Real Producers", a widely acclaimed magazine connecting top agents and industry leaders, Remington has built an impressive platform dedicated to celebrating and elevating the real estate community. Remington is also the author of Agent Allies: Building Your Business With Strategic Real Estate Partnerships. With a passion for motivating and mentoring, he's shared stages with some of the biggest names in business, helping professionals break through barriers and reach new heights. When he's not busy being a real estate guru, Remington is known for his contagious energy, practical wisdom, and a good dose of humor—because let's face it, navigating life and business requires both grit and a sense of humor. With multiple successful ventures under his belt and a reputation for engaging storytelling, he has the rare ability to make even the driest industry stats sound exciting.    Follow the show on our website, Apple Podcasts or Spotify so you don't miss a single inspiring episode! Start a Real Producers Magazine in YOUR Market! Learn more about franchise opportunities at realproducersmag.com

A groundbreaking experiment in reproductive biology has resulted in mice being born from two biological fathers. By fusing sperm and putting them into an emptied egg cell, researchers in China have produced healthy and fertile offspring from two male mice. While it's early days and the technique requires hundreds of embryos to get results, it opens up the possibility of same-sex reproduction in mammals, including humans, in the future. New insights into the power of sleep reveal how short naps can boost creativity. A study found that reaching a certain stage of sleep, known as N2, significantly increased people's chances of having an “aha!” moment. It's more evidence of how deeply intertwined sleep is with problem-solving and innovation, and why naps might be more productive than we thought. One ancient lizard family managed to survive the asteroid that killed the dinosaurs, and they're still around today! Scientists have traced the lineage of night lizards back to over 90 million years ago. Their ability to shelter underground and survive on little energy may have helped them live through one of Earth's biggest disasters. Chapters: (00:38) Same-sex reproduction breakthrough (12:09) Power naps and creativity (22:37) Ancient lizard survives dinosaur-killing asteroid Hosted by Rowan Hooper, Penny Sarchet, and Michael Le Page. To read more about these stories, visit https://www.newscientist.com Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, 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. More on 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   ASCO on BlueSky   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 

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

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

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.

'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:

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。

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

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.  

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.

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

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.      

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

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

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