Podcasts about Median

In this JCO Article Insights episode, Dr. Ece Cal interviews Dr. Martin Wermke, author of the JCO article, "Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas." TRANSCRIPT The disclosures for guests on this podcast can be found in the transcript. Dr. Ece Cali: Welcome to this episode of JCO Article Insights. This is Dr. Ece Cali, JCO editorial fellow, and today I am joined by Dr. Martin Wermke, Professor for Experimental Cancer Therapy at Dresden University of Technology, to discuss the manuscript “Phase 1 Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-like T-Cell Engager Obrixtamig in Patients with DLL3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas.” Obrixtamig is a bispecific T-cell engager that binds to DLL3 on tumor cells and CD3 on T-cells. This manuscript presents the phase 1A dose escalation results of Obrixtamig in patients with DLL3+ small cell lung cancer and neuroendocrine carcinomas. In this study, 168 patients were treated with Obrixtamig across four different dosing regimens. 49% of the patients had small cell lung cancer, 42% had extrapulmonary neuroendocrine carcinoma, and 8% had large cell neuroendocrine carcinoma of the lung. Patients received a median of two prior lines of therapy. 33% of the patients had brain metastases at baseline. Of note, this trial did not mandate baseline brain imaging. Maximum tolerated dose was not reached. 88% of the patients experienced a treatment-related adverse event, however, only 3.6% of the patients had to discontinue treatment due to treatment-related AEs, and dose reduction due to treatment-related AEs was documented in 2.4% of the patient population. Similar to the other DLL3-targeted bi-therapies, the most common adverse events included CRS in 57%, dysgeusia in 23%, and pyrexia in 21% of the patients. CRS events were mostly mild. They occurred more frequently in the first two to three doses. 9% of the patients experienced ICANS, of which 3% were graded as Grade 3 or higher. And let's review the efficacy results. Responses were only seen in patients who received 90 microgram per kg or more once weekly or once every three weeks dosing. The objective response rate in patients who received an effective dose was 28%. If we review by tumor type, 21% of the small cell lung cancer patients, 27% of the extrapulmonary neuroendocrine carcinoma patients, and 70% of the large cell neuroendocrine carcinoma patients had objective response. Median duration of response was 8.5 months, though this data is immature due to short follow-up. Dr. Wermke, DLL3-targeted bispecific T-cell engagers are reshaping the treatment landscape of small cell lung cancer. This trial investigates Obrixtamig in other high-grade neuroendocrine tumors as well. Can you put this trial into context for us and explain why it may represent an important step forward? Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to discuss our data today. I think the data with Obrixtamig in small cell lung cancer are largely similar to what has been observed with other bispecific T-cell engagers such as tarlatamab with respect to the response rate and duration. It has, however, been to be mentioned that BI 1438001 had a bit more liberal inclusion criteria than other trials around. You already mentioned the fact that we allowed the inclusion of patients without mandatory brain imaging, which led to some patients having their brain mets been diagnosed during the treatment with obrixtamig and then adding to the progressive disease patients. That is something which was not the case with the tarlatamab trials where you really had to have a brain imaging before, and in the Phase 1 trial you were even required to treat the brain mets before you included the patient. So it is a bit different, more poorest patient population. I think the trial adds on existing data by being the first trial to also include non-SCLC neuroendocrine carcinoma of other origin, for example from the gastrointestinal tract, and also by including large cell neuroendocrine carcinoma of the lung, which is a really hard to treat pulmonary neoplasm which currently lacks any standardized treatment. So that is really a step forward which we will build on in the future. Dr. Ece Cali: And one thing I would note in this trial, only patients with tumor expressing DLL3 were enrolled. Can you tell us a little bit more about this target, DLL3 in the context of neuroendocrine tumors, and does DLL3 expression predict clinical outcomes after treatment with DLL3 BiTEs, or do we actually need other predictive biomarkers for these novel agents? Dr. Martin Wermke: Yeah, thank you. That's a pretty interesting question. First of all, DLL3 is an atypical notch ligand, which is expressed by the majority of neuroendocrine carcinomas, virtually absent on healthy adult tissues. Therefore, turning it really into a bona fide target for T-cell engaging therapies, pretty low risk for on-target off-tumor side effects. We found that in all the patients we screened, we had an expression rate of about 94% in small cell lung cancer, 80% of large cell neuroendocrine carcinoma of the lung were positive, and also about 80% of the extrapulmonary neuroendocrine carcinoma. So it's really a high prevalence. So the fact that we only included DLL3+ tumors still means we included most of the patients that presented with these diseases. I think at the moment there are no data suggesting a clear-cut association between DLL3 expression levels and outcome on DLL3 CD3 T-cell engagers. There's also not a lot published. If you want to find this out for tarlatamab, you have to look into their patent to really see the data, but it's not clear-cut and I'm sure we need other markers to complement that. And I think what probably plays a major role is intrinsic T-cell fitness. So the question how really diseased your T-cells are, how old you are, because age also correlates with the fitness of the immune system, and other patient characteristics such as tumor burden, we've seen all across the board that the higher the tumor burden, the lower the rate of prolonged response is in such trials. And I also think we need to focus on other components of the tumor microenvironment. So see how high the T-cell infiltration with obrixtamig is and how abundant suppressive elements like regulatory T-cells or myeloid-derived suppressive cells are. That is work which is currently being done. Data are emerging, but I don't think that at the moment we have any clear biomarker helping us to select who should not receive DLL3 T-cell engagers. Dr. Ece Cali: Those are great points and there is a lot we need to learn about how to use these novel agents in the future. I'd like to highlight the results in large cell neuroendocrine carcinoma of the lung. The response rate in this group was remarkably high at 70%. Though we should note the small sample size of only 14 patients in this trial. After first line chemoimmunotherapy, current approved options for this population have very modest clinical activity. Given these trial results, how do you envision the field moving forward for patients with large cell neuroendocrine carcinoma? Dr. Martin Wermke: Yeah, I think LCNEC is really an area which urgently needs further improvement of therapeutic standards. At the moment, as I said, there is no real standard. We are usually extrapolating from results we have in small cell lung cancer or non-small cell lung cancer, but I don't think we have too many prospective trials really informing this. Of course, 14 patients is a small sample size, but I think it's still fair to say that we can claim that DLL3 T-cell engagers are not doing worse in LCNEC than they do in SCLC. And that's why I think we really need to move forward clinical trials that are specifically targeting this population. Although I fear a bit that, given the rareness of this disease and the aggressiveness of its phenotype, that this is probably not the main focus of the pharmaceutical industry. So I think it's up to us academic investigators to really come up with investigator-initiated trials trying to fill the knowledge gaps we have here. Dr. Ece Cali: And one more thing that I want to talk about is the accessibility for these drugs. These novel agents are showing real promise in improving outcomes for patients with high-grade neuroendocrine tumors, an area where progress has been limited until very recently. However, as DLL3 BiTEs become more widely used, issues of logistics and access come into sharper focus. With unique toxicities and the specialized monitoring, their use is restricted to certain centers. Looking ahead, what kinds of strategies could help mitigate some of these adverse events or make these treatments more broadly available? Dr. Martin Wermke: Yeah, I think if you look at countries like the United States where tarlatamab has already been approved, we can see how the management strategies are evolving. I've heard about a colleague equipping their patients with thermometers and a pill of Dexamethasone, alongside with a temperature control protocol and clearly instructing them, "If you measure a temperature above a certain level then start taking the Dexamethasone and come back to our office and we're going to take care of you." I think that's one way to move forward. I think we are lucky in a way that CRS usually manifests within the first 24 hours. This was the same in our study, like in the tarlatamab studies. So we really know when the time of trouble is for our patients. And in this time, I think we need to instruct the patients to stay close to the hospital. I don't think we need to hospitalize all of them, but we probably need them to stay in a nearby hotel to be able to reach the emergency room if needed in a short period of time. And I think we can also learn in this strategy how to manage bispecific antibodies from the experience our colleagues in hematology had because they have been using bispecific T-cell engagers for quite some years right now and they developed strategies and networks that were able to successfully treat these patients also on an outpatient basis. And I think that is clearly an experience we need to follow, acknowledging that we are talking about diseases which are much more frequent than the standard hematology indications. Dr. Ece Cali: Thank you so much, Dr. Wermke, for this informative discussion and for sharing your perspective on this evolving field. Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to talk about data. It was really great being able to share that, and I really think that we are just at the beginning of a new exciting area for the treatment of neuroendocrine carcinomas, and I think much improvement is yet to come for our patients. Dr. Ece Cali: Yes, that's really exciting. And thank you everyone 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 this 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. Dr. Martin Wermke's Disclosures Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer,  BMS GmbH & Co. KG, Regeneron, MJH/PER, Takeda Consulting or Advisory Role: Bristol-Myers Squib, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, immatics, Bayer, ImCheck therapeutics, AstraZeneca, Tacalyx, Regeneron, Daiichi Sankyo Europe GmbH, Zymeworks, PharmaMar, Iovance Biotherapeutics, T-Knife, Genentech Research Funding: Roche Patents, Royalties, Other Intellectual Property Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb, AstraZeneca,  Amgen,  GEMoaB, Sanofi/Aventis, immatics,  Merck Serono, Janssen Oncology, Iovance Biotherapeutics, Daiichi Sankyo Europe GmbH"

As new data shows mortgage payments are soaring over $1,100 more than rent each month, and 88% of renters are priced out of the market, renting isn’t just a choice—it’s becoming a necessity. Paul Smith, Executive Director with The Rental Housing Association of Utah joins the show to discuss renting in Utah.

The median Seattle couple with kids makes $250,000 // Mackenzie Scott donates $70 million to UNCF // AGREE TO DISAGREE: Is America dealing with shared national trauma? // WE HEAR YOU! and WORDS TO LIVE BY

Vasemmistosumutus | Sammallahti Rostila | #neuvottelija 352. Oikeistokansanedustajat Tere Sammallahti ja Onni Rostila arvioivat miksi vasemmiston annetaan sumuttaa enemmän ja väkivaltaisemmin kuin oikeiston mm. Charles Kirkin murhan tapauksessa ja Tampereen maahanmuuttajien luksumajoituksessa. Hyväksyikö Suomi kuitenkin Teemu Keskisarjan keskustelunavauksen tavallista helpommin?(00:00) Vaellusta Norjassa ja uimataitoja lapsille(01:00) Eriarvoistava Etelänmatkan uimakoulu vs valtio hoitaa(01:13) Charlie Kirkin murha(01:44) Jimmy Kimmelin sumutus ja Trumpin cancelointi(02:52) Kaasuvalottaminen, sumutus ja yhteiskunnan propaganda(03:53) Late Night -koomikota USA:ssa ahtaalla(04:20) Hesarikin kirjoitti kaasuvalottamisesta(06:03) Alaikäisten turvapaikanhakijoiden luksusmajoitus Tampereella(08:15) Kaasuvalotus, Gaslight-elokuva ja sumutus(09:43) Typerä tamperelaiskilpailustun puolustus vasemmalta(11:42) Charlie Kirk vs. 20 Liberals(12:07) Median valikoiva kohujen hyödyntäminen(15:56) Vasemmiston ja oikeiston väkivalta ja siihen suhtautuminen(18:01) Cancel-kulttuurin laineet molemmille puolille(19:58) Media valitsee mitä sinä näet(21:41) Poliittisen väkivallan sietämäinen työyhteisöissä(23:51) Atte Korhola tulkitsee vasemmistoa suopeasti(25:32) Vasemmiston hyväksyntä poliittiselle väkivallalle(27:43) Taisteluvallasta ja politiikan luonteesta(29:23) Overtonin ikkuna ja Teemu Keskisarja siirtämässä maalitolppia(31:14) Suhtautuminen ulkomaalaisten etuihin Euroopassa(33:22) Median sumutus ja tilastojen kääntäminen(35:22) Kansalaisuus ja ulkomaalaisten ongelmat(37:10) Julkisten palveluiden kohdistaminen maahanmuuttajille(39:17) Ongelmien ratkaisemisen siirtäminen eteenpäin(41:30) Terveydenhuolto ja yksityinen maksaminen(42:52) Työllistämisen vaikeudet ja markkinatalous(43:13) Demarit estäneet talouden tasapainottamisen(47:30) Talouskasvun illuusio ja säästöjen tarve(49:15) Poliittiset lupaukset ilman säästötoimia(51:07) Kotitalousvähennys ja poliitikkojen vastaukset(51:24) Valtionvarainministeri ja euroanalyysit(53:13) Vieraina Tere Sammanlahti ja Onni RostilaSisäpiirissä visioidaan Rinteen eiku Lindtmanin vasemmistohallituksen SuomeaKatso Sisäpirijaksot ja tue Samiahttps://www.youtube.com/channel/UCRI34L9OtDJuZpaWicbNXzg/join#neuvottelija Sami Miettinen

Our CIO Mike Wilson joins U.S. Equity strategist Andrew Pauker to answer frequently asked questions about their latest economic outlook, including how U.S. equities are transitioning to a new bull market. Read more insights from Morgan Stanley.----- Transcript ----- Mike Wilson: Welcome to Thoughts on the Market. I'm Mike Wilson. Morgan Stanley's CIO and Chief U.S. Equity Strategist. Today we're going to try something a little different. I have my colleague, Andrew Pauker from the U.S. Equity Strategy Team here to discuss some of the client questions and feedback to our views. It's Monday, September 22nd at 11:30am in New York. So, let's get after it. Andrew, we constantly deal with client questions on our views. More recently, the questions have been focused on our view that we've transitioned from a rolling recession to a rolling recovery in a new bull market. Secondarily, it's about the tension between the equity market's need for speed and how fast the Fed will actually cut rates. Finally, why is accelerating inflation potentially good for equities? Where do you want to start? Andrew Pauker: Mike, in my conversations with clients, the main debate seems to be around whether the labor cycle and earnings recession are behind us or in front of us. Walk us through our take here and why we think the rolling recession ended with Liberation Day and that we're now transitioning to an early cycle backdrop. Mike Wilson: So, just to kind of level set, you know, we've had this view that – and starting in 2022 with the payback and the COVID demand. And from the pull forward – that began, what we call, a rolling recession. It started with the technology sector and consumer goods, where the demand was most extreme during the lockdowns. And then of course we've had recessions in housing, manufacturing, and other areas in commodities. Transportation. It's been very anemic growth, if any growth at all, as the economy has been sort of languishing. And what's been strong has been AI CapEx, consumer services, and government. And what we noticed in the first quarter, and we actually called for this almost a year ago. We said now what we need is a government recession as part of the finishing move. And in fact, Doge was the catalyst for that. We highlighted that back in January, but we didn't know exactly how many jobs were lost from Doge's efforts in the first quarter. But we got that data recently. And we saw an extreme spike, and it actually sort of finished the rolling recession. Even AI CapEx had a deceleration starting in the summer of 2024. Something else that we've been highlighting and now we're seeing pockets of weakness even in consumer services. So, we feel like the rolling recession has rolled through effectively the entire economy. In addition to the labor data that now is confirming – that we've had a pretty extreme reduction in jobs, and of course the revisions are furthering that. But what we saw in the private sector is also confirming our suspicions that the rolling recession's over. The number one being earnings revision breath, something we've written about extensively. And we've rarely seen this kind of a V-shaped recovery coming out of Liberation Day, which of course was the final blow to the earnings revisions lower because that made companies very negative and that fed through to earnings revisions. The other things that have happened, of course, is that Doge, you know, did not continue laying people off. And also, we saw the weaker dollar and the AI CapEx cycle bottom in April. And those have also affected kind of a more positive backdrop for earnings growth. And like I said before, this is a very rare occurrence to see this kind of a V-shape recovery and earnings revision breaths. The private economy, in fact, is finally coming out of its earnings recession, which has been in now for three years. Andrew Pauker: And I would just add a couple of other variables as well in terms of evidence that we're seeing the rolling recovery take hold, and that Liberation Day was kind of the punctuation or the culmination of the rolling recession, and we're now transitioning to an early cycle backdrop. So, number one, positive operating leverage is causing our earnings models to inflect sharply higher here. Median stock EPS growth, which had been negative for a lot of the 2022 to 2024 period is now actually turning positive. It's currently positive 6 percent now. The rolling correlation between equity returns and inflation break evens is also now significantly positive. That's classic early cycle. That's something we saw, you know, post COVID, post GFC And then lastly, just in terms of the market internals and kind of what, you know, under the surface, the equity market is telling us. So, the cyclical defensive ratio was down about 50 percent into the April lows. That's now up 50 percent from Liberation Day and is kind of breaking the downtrend that began in April of 2024. So, in addition to the earnings revisions V-shaped recovery that you mentioned, Mike. Those are a couple of other variables as well that are confirming that we're moving towards an early cycle backdrop and that the ruling recovery is commencing. Okay. So, we had the FOMC meeting. As expected the Fed delivered a 25 basis point cut. Mike, what's your read on the meeting as it relates to equities and the reaction function? Mike Wilson: Yeah, I mean this is really what we expected along with the consensus. We didn't have a different view that the Fed would give us 50. They gave us 25, and some people have characterized this as sort of a hawkish cut and very different than what we saw a year ago when the Fed kicked off that part of the rate cutting cycle with 50 basis points because they probably were worried a bit more about the labor market than they were about inflation. But you know, ultimately we think the labor data is going to get worse or the payroll data will prove to be worse because of the delay between the Doge layoffs and when those folks can file for unemployment insurance, which should be in October. And it's that delayed data that will then get the Fed cutting in earnest, which is what's necessary for the full rotation to kind of the lower quality parts of the market. So, while you're right that we've seen cyclicals perform, they haven't performed in the same way that we've seen prior cycles, like in 2020 or [20]08-[20]09, because the Fed hasn't cut. They're very far behind the curve. If you buy into our thesis that, you know, we had a rolling recession, we had an employment cycle, and they should be much more generous here. So that tension between the Fed's delay to get ahead of the curve and the market's need for speed to get there sooner and more deliberately – is where we think that, you know, we have to wait for that to occur to get the full rotation to the lower quality, kind of really cyclical parts of the market. Andrew Pauker: Okay, so let's talk about the back end of the yield curve a little bit and why that's important for stocks. In my dialogue with investors, there's a lot of focus here, just given what happened last fall when the Fed cut at the front end and the back end of the yield curve move higher. How should market participants think about this dynamic? Mike Wilson: Yeah, I mean, I think this is an unknown known, if you will, because we saw this last fall. Where the Fed cut 100 basis points and the back end of the 10-year and 30-year Treasury market sold off. That's the first time we've ever seen that in history, where the Fed cuts that aggressively and the backend moves out. And this is a function of just all the fiscal imbalances and the debt issues that we face. And this is not a new issue. So, I think it remains to be seen if the bond market is going to be comfortable with the Fed not ignoring the 2 percent target – but you know, letting it run hot. As we've said, we think ultimately, they will have to let it run hot and they will, because that's what we need to have a chance at getting out of the debt problem. And so that sort of risk is still out in the future. I have less concern about that more recently because of the way the backend of the bond market has traded. But it's something that we need to keep in the back of our mind. If yields were to go back to 4.50, which is our key level, then that would be a problem as long as we're below, you know, sort of 4.50 and we're well below that now we're close to 4, I don't think this is a problem at all. Andrew Pauker: Yeah. One of the points that our colleague in rate strategy Matt Hornbach has highlighted is that the difference between now and the fourth quarter of last year when we saw that dynamic play out was that, you know, the bond market was very focused on the uncertainty around the fiscal situation. You know, we were going into an election, there was a fair amount of uncertainty around what Trump would do from a fiscal standpoint.And now, that is a known known, you know. We have the One Big Beautiful Bill signed into law. We know what the deficit impact is, so there is more clarity for the bond market on that front. So that is one key difference now versus last fall and why we may not see the same kind of reaction in the rates market. Mike, you brought up, kind of, run it hot, which was the title of our note from a couple of weeks ago. I just wanted to get your take on why some inflation coming back is actually a positive for equities and why actually the deceleration that we've seen in inflation over the last couple years is one reason why earnings for small cap indices, for instance, have deteriorated so much. And so, for in this environment where the Fed is perhaps a bit more tolerant of inflation in 2026, why that's actually a positive for equities. Mike Wilson: This is just an underappreciated sort of factoid that we actually identified back in 2020 and [20]21 as well. That when inflation is accelerating, that's a sign that pricing power is pretty good. And we actually see broader earnings. In fact, the best year for earnings, not just small caps, but the – call it the equal weighted S&P 500 was 2021. And that was the year where obviously inflation was really getting out of control. That was just pure profit for a lot of these businesses. And so – earnings will be better. Our call over the next 12 months is not about multiples or the Fed so much, but that we think earnings are going to end up being better than people expect because (a) we've been through this three-year earnings recession. There's a ton of pent-up demand. Okay? And now inflation is reaccelerating as demand comes back. And that is actually going to fall to the bottom line. So not only is that good for stocks, okay, but it's actually, it's also why the equity risk premium can be lower. Because if you want to hedge that risk of inflation moving higher, well then you should be willing to accept a lower equity risk premium relative to what is actually a pretty good base rate for 10-year yields, close to 2 percent on a real basis. So, you know, that's why the equity risk premium can stay low and why stocks can accrue at a, you know, pretty high PE multiple as these earnings come through better than expected. And one of the reasons is that inflation actually is accelerating in some of these areas where it's been deflationary. Andrew Pauker: Lastly, Mike, you know, you brought this up briefly. I want to address rotations under the surface of the market. We took off our large cap buys a few weeks ago, and as you mentioned, kind of signaled our intention – to get more constructive on small caps later this year in the fourth quarter. Can you specifically kind of walk through the signpost that we're waiting for before pressing the long, small cap trade here? Mike Wilson: Yeah, I mean, we've probably… This is probably one of the areas we've done a really good job of just, you know, staying away from the fray. Meaning that, you know, we've been underweight small caps for really four years, and they've underperformed that entire time. I think the thing that we've been really patient about is just waiting for the Fed to lower rates to a level that's more conducive for these businesses that (a) need to obviously recap themselves, but then the cost of capital is just too high. So that's number one. But , at the end of the day, I mean, that should translate into better earnings revisions and that also has lagged. So, it's a combination of the two. The Fed getting ahead of the curve, which I would define as fed funds at least equal to two-year Treasury yields, but hopefully below two-year Treasury yields. Right now, we're about 60-65 basis points still above two-year yields . And then the second one is this ‘earnings your vision breadth on a relative basis. Small over large. It is trying to turn up now. It's been in a straight downtrend really for the last, you know, four years. And so those two together will affect a more robust relative outperformance. And just to be clear, small caps have done really well since Liberation Day, okay. So, in absolute terms, it's been great. It's just the relative trade has not really worked yet. That's where we're going to leave this conversation. Thanks for speaking with me, Andrew, to explain some of the thinking behind our calls. To our listeners, thanks for tuning in. I hope you found it informative and useful, and let us know what you think by leaving us a review. If you think Thoughts on the Market is worthwhile, tell a friend or colleague to try it out.

Do sněmovních voleb v Česku zbývají méně než dva týdny. Záříjový průzkum agentury Median pro Radiožurnál a iRozhlas.cz ukázal, že nejpřijatelnější vládou by byl pro Čechy a Češky jednobarevný kabinet hnutí ANO, pro což se vyslovilo více než čtyřicet procent lidí. Na druhém místě skončila s podporou sedmatřeceti procent koaliční vláda ANO a SPD s tím, že na třetím se umístila někdejší pětikoalice Spolu, STAN a Pirátů. Jaké scénáře Českou republiku od října čekají? Jaká je pravděpodobnost, že by se ČR vydala stejným směrem, jako Slovensko po zvolení současné vlády Roberta Fica? A v čem má společnost v těchto turbulentních časech hledat sílu? Nejen o tom mluví v další epizodě Československého podcastu šéfredaktor Respektu Erik Tabery, novinář a spisovatel Martin M. Šimečka a novinářka slovenského Denníku N Monika Tódová. Moderuje Zuzana Machálková.

Vládneme, nerušit #27: Ať už vzejde z říjnových voleb jakákoliv vládní koalice, většině Čechů se zřejmě nebude příliš zamlouvat. Z průzkumu agentury Median pro Český rozhlas totiž vychází, že největší podporu by měla menšinová vláda hnutí ANO, kterou by podporovalo 41 procent Čechů, tedy ani nejideálnější varianta nemá podporu většiny obyvatel. Co to může znamenat pro skládání příští vlády? A jak jsme se dostali do tohoto stavu? O tom v novém díle podcastu Vládneme, nerušit diskutují redaktoři František Trojan a Filip Zelenka společně s šéfredaktorem Erikem Taberym. 

This episode explores Americans' financial well-being in 2025, using a Yahoo Finance/Marist survey as the springboard. Don and Tom discuss how their audience differs from the average American listener, how perceptions of financial health can be misleading, and what to actually do if your finances—or your feelings about them—are getting worse. They debate the usefulness of net worth tracking, stress the importance of financial literacy, and suggest automating savings. Listener questions cover indexed annuities, bond substitutes, tax implications, and long-term care sales pitches. They also read a letter defending Rick Edelman and challenging their dismissal of crypto, which leads to a lively discussion about evidence-based investing, Eugene Fama's critique of Bitcoin, and the dangers of sensationalized advice. They end with a reflection on public criticism and the value of having one's views challenged. 0:29 Comparing TRM listeners to Ramsey and Kiyosaki audiences 1:37 Median savings for over-65 Americans and why $200k still isn't enough 2:42 Yahoo/Marist survey results: affordability, debt, emergency savings 3:50 One in three say finances worsened; generational breakdown 4:51 Explaining net worth, what to include and exclude 7:01 Tracking net worth annually as a financial benchmark 8:00 Divorce, net worth, and the joke about “kill them off” 9:50 Income gap, gender differences, and perception vs. reality 10:34 How uncertainty and fear shape financial outlooks 11:41 Producer note joke about being “sexist but not leftist” 11:50 Dissatisfaction with savings and personal spending habits 13:06 Fixing bad finances: literacy, automation, benchmarking 17:20 Don argues perception matters more than reality for many 18:20 Listener question: fixed index annuity as bond substitute 19:46 Caps, participation rates, and underperformance vs. markets 21:10 Tax treatment of annuities vs. ETFs 22:55 Importance of advice near retirement (decumulation phase) 23:44 Listener shares bad LTC/annuity sales pitch experience 24:54 Fixed annuity guarantees vs. CDs and government bonds 25:39 Listener defends Rick Edelman, suggests an open dialogue 26:52 Don's critique of Edelman's shift toward sensationalism 29:29 Eugene Fama's comments on Bitcoin, clash with Edelman's stance 31:23 Public criticism is fair game—reading recent Apple Podcast reviews 32:48 Bitcoin adoption debate and institutional incentives Learn more about your ad choices. Visit megaphone.fm/adchoices

A Tulsa ordinance to crack down on homelessness gets the mayor's signature.Oklahoma wants to jam cellphones in its jails and prisons.A new non-profit is working to fill OKC's Crossroads Mall with services for the community.You can find the KOSU Daily wherever you get your podcasts, you can also subscribe, rate us and leave a comment.You can keep up to date on all the latest news throughout the day at KOSU.org and make sure to follow us on Facebook, Tik Tok and Instagram at KOSU Radio.This is The KOSU Daily, Oklahoma news, every weekday.

Hnutí Stačilo! podle posledního průzkum agentury Median stoupá voličská podpora. Zatímco preference vedoucího hnutí ANO podle stejné agentury klesají a preference SPD, Starostů a koalice Spolu stagnují, Stačilo! posílilo na 9 procent. „Jde o data z poloviny srpna. Novější průzkumy ukazují, že by se do Sněmovny dostalo, ale s o hodně nižším ziskem,“ uvádí politický analytik Deníku N Jan Tvrdoň.

Hnutí Stačilo! by podle srpnového volebního modelu agentury Median získalo 9 procent hlasů. Podle bývalého místopředsedy KSČM Jiřího Dolejše ale levice v těchto volbách propásla svou šanci. „Hnutí Stačilo! nepovažuji za levici. Je to takový podivný slepenec s krajní pravicí, který je v podstatě zaměřený destruktivně,“ rozebírá Dolejš.

Hnutí Stačilo! podle posledního průzkum agentury Median stoupá voličská podpora. Zatímco preference vedoucího hnutí ANO podle stejné agentury klesají a preference SPD, Starostů a koalice Spolu stagnují, Stačilo! posílilo na 9 procent. „Jde o data z poloviny srpna. Novější průzkumy ukazují, že by se do Sněmovny dostalo, ale s o hodně nižším ziskem,“ uvádí politický analytik Deníku N Jan Tvrdoň.Všechny díly podcastu Interview Plus můžete pohodlně poslouchat v mobilní aplikaci mujRozhlas pro Android a iOS nebo na webu mujRozhlas.cz.

Hnutí Stačilo! by podle srpnového volebního modelu agentury Median získalo 9 procent hlasů. Podle bývalého místopředsedy KSČM Jiřího Dolejše ale levice v těchto volbách propásla svou šanci. „Hnutí Stačilo! nepovažuji za levici. Je to takový podivný slepenec s krajní pravicí, který je v podstatě zaměřený destruktivně,“ rozebírá Dolejš.Všechny díly podcastu Osobnost Plus můžete pohodlně poslouchat v mobilní aplikaci mujRozhlas pro Android a iOS nebo na webu mujRozhlas.cz.

The FOMC cut interest rates by 25bps, which was widely expected by markets. Additionally, median projections for a path forward indicate 50bps worth of cuts coming later in 2025. Kevin Hincks helps investors digest the market reactions and explains what the initial report means heading into Fed chair Jerome Powell's press conference.======== Schwab Network ========Empowering every investor and trader, every market day. Subscribe to the Market Minute newsletter - https://schwabnetwork.com/subscribeDownload the iOS app - https://apps.apple.com/us/app/schwab-network/id1460719185Download the Amazon Fire Tv App - https://www.amazon.com/TD-Ameritrade-Network/dp/B07KRD76C7Watch on Sling - https://watch.sling.com/1/asset/191928615bd8d47686f94682aefaa007/watchWatch on Vizio - https://www.vizio.com/en/watchfreeplus-exploreWatch on DistroTV - https://www.distro.tv/live/schwab-network/Follow us on X – https://twitter.com/schwabnetworkFollow us on Facebook – https://www.facebook.com/schwabnetworkFollow us on LinkedIn - https://www.linkedin.com/company/schwab-network/ About Schwab Network - https://schwabnetwork.com/about

M

Elul is the 12th and final month of the Jewish calendar year. Elul Unbound is a Judaism Unbound initiative all about making Elul meaningful, through creative digital modalities. In this episode, Lex Rofeberg and Wendie Bernstein Lash explore the notion of chiasm (for "what is a 'chiasm' -- which is a great question -- click here), along with what it has to do with the month of Elul and the broader 7-year Shmita cycle. This Elul podcast is the third in a mini-series of four that are being released as part of Elul Unbound 2025 (our 26th-29th Elul episodes overall).--------------------------------------To check out all our Elul bonus episodes from previous years, which can still be relevant to your experience of Elul this time around, click here. Join our bi-weekly journey through Elul Unbound 2025 by signing up at this link, and sign up for our Elul Unbound Shabbat gatherings here, where we will be forging our kavanot (intentions) for the new year in real time with fellow Unbounders.If you're enjoying Judaism Unbound, please help us keep things going with a one-time or monthly tax-deductible donation -- support Judaism Unbound by clicking here!

Opening Reflections and California Concerns The AgNet News Hour began with hosts Nick Papagni and Lorrie Boyer sharing lighthearted Friday greetings before shifting to California's serious agricultural challenges. Papagni noted worsening Central Valley air quality caused by wildfires, likening the smoke to winter fog. He warned that tensions between state and federal governments over forest management may intensify as fall approaches. Boyer added that federal intervention could even extend to California's 2028 Olympic preparations. Policy Spotlight: Mexican Wolf Debate Boyer reported on a House Natural Resources Subcommittee hearing on the Enhancing Safety for Animals Act of 2025. The legislation would delist the Mexican wolf from the Endangered Species Act, a move supported by the National Cattlemen's Beef Association, the Arizona and New Mexico Cattle Growers Associations, and the Public Lands Council. Tom Patterson, President-elect of the New Mexico Cattle Growers Association, testified that wolf populations have shifted from a livestock concern to a community safety threat, citing attacks on pets, horses, and even children. In regulatory news, the EPA declined stricter wastewater rules for meat and poultry processors, concluding that current Clean Water Act requirements suffice. The National Chicken Council applauded this decision as a balanced approach to water quality regulation. Immigration Reform and the Dignity Act The program's central feature was an interview with Manuel Cunha, President of the Nisei Farmers League, who addressed farm labor shortages and immigration policy. He highlighted the bipartisan Dignity Act (H.R. 4393), introduced by Rep. María Elvira Salazar (R-FL) and Rep. Veronica Escobar (D-TX), as the most promising reform since the early 2000s. The Act includes a three-pronged approach: Long-Term Residents – renewable work authorization cards with penalties for undocumented status. Legal Pathways for New Workers – stronger background checks and legal entry channels. Criminal Entrants – removal of individuals linked to crime or gang activity. Cunha emphasized that the Act also provides protections for Dreamers and addresses Social Security benefits for long-term contributors who have paid into the system for decades. Coyotes, Fear, and Fake Documents Cunha warned about coyotes—human smugglers who charge up to $15,000 per person and often supply migrants with fraudulent documents. Workers fall into debt while employers unknowingly hire with false credentials. He called the system a “disaster” and urged growers to pressure congressional leaders like David Valadao, Jim Costa, Jimmy Panetta, and Vince Fong to support the Dignity Act. Despite federal assurances, many farmworkers still live in daily fear of deportation. Some alter their appearance to avoid suspicion, while enforcement remains concentrated in large metropolitan sanctuary cities. Farm Labor: Hard Work Few Will Do Papagni stressed that farm labor is not unskilled work, pointing to strawberry, lettuce, melon, and table grape harvesting as examples requiring years of expertise. Cunha agreed, noting that domestic welfare recipients are unlikely to take on such demanding jobs—something proven during the 1996–1998 Welfare to Work Program. With many long-time workers nearing retirement and fewer young people entering agriculture, Cunha pressed for a comprehensive guest worker program. A Call to Action Cunha's message to farmers and ag communities was clear: contact your congressional representatives and urge support for the Dignity Act. He highlighted Vince Fong as a key California lawmaker yet to sign on. If passed, the bill would initiate a five- to six-month rule-writing process, during which workers would receive documentation verifying employment, providing immediate protection while regulations are finalized. Farm Income and Market Updates According to the U.S. Economic Research Service (ERS): Net farm income in 2025 is projected at $179.5 billion, up 40.7% from 2024—the second-highest on record. Median farm household income, however, is projected to decline by $1,189 in 2025, reflecting weaker off-farm earnings. Government payments are forecast at $40.5 billion, the highest since 2020. The dairy sector is also strengthening, with exports reaching 18.7% of domestic production in June—the highest since 2022. Domestic yogurt consumption rose 12.2%, while overall use of milk solids grew 3%. Competitiveness and Global Pressures Papagni noted the difficulty of competing with countries paying $10–20 per day compared to California's $16 per hour wages, combined with stricter U.S. regulations. Boyer emphasized that despite higher costs, U.S. agriculture provides the world's safest and most affordable food supply, thanks largely to immigrant labor. Citrus Greening and Global Potato Trends Rick Dantzler of the Citrus Research and Development Foundation reported promising progress in the fight against citrus greening disease. Oxytetracycline trunk injections are showing strong results, with healthier canopies and improved fruit quality, though production costs rose 7%. Meanwhile, the global frozen potato market has shifted dramatically. Between 2019 and 2024, China and India moved from net importers to exporters of frozen fries and processed potato products, expanding markets into Asia and the Middle East. Criminal Provisions in the Dignity Act The legislation also strengthens criminal enforcement, including: Tougher penalties for illegal re-entry after multiple deportations. DNA testing to confirm family ties. Stricter penalties for voting by non-citizens. Increased minimum penalties for child sex trafficking. Boyer linked these provisions directly to combating coyote networks and broader exploitation. Wrapping Up The episode closed with Papagni and Boyer urging farmers to engage in the policy debate, follow updates at AgNetWest.com, and recognize that immigration reform is essential to keeping U.S. agriculture competitive and sustainable.

City Manager Brian Johnson joins host Rico Figliolini on Peachtree Corners Life for a practical update on projects shaping the city's next few years. He walks through the newly developed Simpsonwood Park master plan—designed to keep the park passive and natural while adding ADA-friendly access, renovated bathrooms, an updated chapel, selective forestry management, and a modest river overlook. Johnson also explains why the city is outsourcing maintenance of the Peachtree Parkway median so residents finally see consistent, five-day-a-week care despite legacy design constraints.The episode dives into traffic and road fixes at East Jones Bridge and 141 (longer turn lanes, better alignment, and a right-turn slip lane), the ESPLOST renewal on the ballot, and the last phase of the Waterside development—now tracking at roughly half the density initially allowed and focused on equity (for-sale) housing. With candid context on what's been approved or denied since cityhood, plus how extended-stay conversions and the Housing Authority factor in, this conversation is a clear, chart-backed look at how Peachtree Corners balances growth with character.Key takeawaysSimpsonwood Park will remain a passive park—no ballfields, pickleball, mountain biking, or major programming.Plan includes ADA-accessible paved paths, renovated bathrooms (including one closer to the river), resurfaced parking, and a chapel renovation.Selective forestry and wildlife/erosion work will improve long-term health of the park.City is outsourcing median maintenance on Peachtree Parkway; crews will be dedicated five days a week for mowing, edging, litter removal, and plant adjustments.Median design differs from Johns Creek (at-grade vs. raised), which has made upkeep harder; outsourcing addresses consistency and appearance.East Jones Bridge & 141: entrance realignment, longer left-turn stacking, and a right-turn slip lane to move traffic more safely and quickly.No municipal election this cycle for three council seats (no challengers qualified), but ESPLOST renewal is on the county ballot.Waterside final phase moves forward with for-sale (equity) units; overall buildout drops from up to 916 approved units to ~450.Post-2012 housing approvals show a measured approach—some apartment proposals approved, many reduced to townhomes or denied.Extended-stay hotel issues are being addressed, including a supervised conversion to efficiency units via the Housing Authority.Timestamp:(00:03:29) Simpsonwood Park master plan details and community input.(00:09:55) Renovation of chapel, bathrooms, and forestry management plans.(00:15:27) Outsourcing median maintenance on Peachtree Parkway.(00:24:27) Election update and ESPLOST renewal.(00:27:03) Waterside development's final phase and reduced density.(00:30:12) East Jones Bridge road improvements and traffic flow changes.(00:36:37) Housing trends, multifamily approvals, and denials over time.(00:42:41) Extended stay hotel conversions and housing authority oversight.(00:45:47) Balancing growth, community resistance, and long-term city planning.

Wall St closed lower on Tuesday to kick off the September trading month in the red as investors took profits from the summer bull rally and hold concerns over tariff uncertainty after a federal appeals court on Friday ruled that most of Trump's global tariffs are illegal. The Nasdaq lost 0.82%, the S&P500 dropped 0.7% and the Dow Jones ended the day down 0.55%.In Europe overnight, markets tumbled amid a rise in bond yields and the prospect of further tariff uncertainty out of the US. The STOXX 600 fell 1.5%, Germany's DAX fell 2.2%, the French CAC lost 0.7% and, in the UK, the FTSE100 ended the day down 0.9%.Across the Asia region on Tuesday, market sentiment was hit by tariff uncertainty leading to a mixed session in the region. Japan's Nikkei rose 0.3%, India's Nifty 50 gained 0.3%, South Korea's Kospi Index rose 0.94%, and Hong Kong's Hang Seng ended the day down 0.5%.The local market started the new trading month lower with a 0.3% decline on Tuesday as investors digested the August reporting season showing a weaker outcome than expected for FY25 and repositioned portfolios for the tailwinds expected in FY26. Australia's August reporting season delivered weaker-than-expected results, with only 20-30 % of companies beating earnings expectations compared with more than 80% in the US. Median earnings downgrades of 3.6% outpaced upgrades of 2% locally.With some heavyweight market stocks trading ex-dividend yesterday and Wall St closed on Monday, investor moves were buoyed yesterday by strength among the banks and a rally among key commodity prices yesterday however this wasn't enough to boost the ASX to a green finish.Gold rose 1.4% to $3,496.24 per ounce, and silver surpassed $40 for the first time since 2011, driven by expectations the US Federal Reserve will cut interest rates in September, according to ANZ.Collin's Food (ASX:CKF) soared over 7% yesterday after posting a 6.7% rise in total sales for the first 18-weeks of FY26 and the KFC Australia operator also reaffirmed guidance for FY26 targeting underlying NPAT of low-mid teens.What to watch today:On the commodities front this morning, oil is trading 1.33% higher at US$65.49/barrel, gold is up 1.5% at US$3528/ounce and iron ore is up 0.71% at US$102.53/tonne.The Aussie dollar has weakened against the greenback to buy 65.13 US cents, 96.70 Japanese Yen, 46.82 British Pence, and 1 New Zealand dollar and 11 cents.Ahead of the midweek trading session the SPI futures are anticipating the ASX will open the day down a sharp 0.42% tracking global market uncertainty overnight.Trading ideas:Bell Potter has maintained a buy rating on Harvey Norman (ASX:HVN) and have increased the 12-month price target on the homewares retailer from $6.00 to $8.30 following the release of FY25 results beating expectations and a strong start to FY26 especially from within the Australian business.And Trading Central has identified a bearish signal on Supply Network (ASX:SNL) following the formation of a pattern over a period of 268-days which is roughly the same amount of time the share price may fall from the close of $36.02 to the range of $27.50 to $29.00 according to standard principles of technical analysis.

El modo de vida de Haces, Monreal, Gutiérrez Luna, Noroña, López Hernández y etcéteras que los acompañan, como que no encaja con la filosofía de la que habla la secretaria de Gobernación, Rosa Icela Rodríguez

Friends, there isn't much to say here other than we at the show always mourn the loss of loved ones, including a truck load of meat. Rest In Sauce. And if you spot a thing that shouldn't be, send it in to janesays@civicmedia.us and we might use it on the show! So join us Monday through Friday at 11:51 a.m. for “This Shouldn't Be A Thing!” or search for it on Spotify, Apple or wherever you get your podcasts. And thanks for listening!!

Series - An Exposition of Exodus Text - Exodus 2:15-22  by Nick Neves, pastor | Midweek Service | 08.20.25   Pastor Nick continues to show parallels between Moses and Jesus, who is the better Mediator that Moses' ministry anticipates. Jesus sojourned with us by taking upon Himself a human nature. Though Moses' time in Median was a humbling experience, God expertly used it to train him and ready him to serve as a godly leader over the covenant people. 

Filmwax Radio is proud to welcome 3 female documentary filmmakers to the podcast for their first time. First up is the filmmaker Wendy Lobel. "Anxiety Club" provides an intimate and humorous look at anxiety through the eyes and minds of some of the most brilliant comedians working today. Marc Maron, Tiffany Jenkins, Baron Vaughn, Aparna Nancherla, Mark Normand, Eva Victor and Joe List offer candid reflections on their relationship with anxiety through exclusive interviews, standup performances, sketch videos, therapy sessions, and everyday life. With rare access to private therapy sessions, the film follows comedian Tiffany Jenkins (a content creator with over 9 million followers) as she undergoes behavioral therapy, capturing the profound changes her treatment brings about. Others find support from alternative sources, such as world-renowned meditation expert Tara Brach, PhD, or the psychologist-in-residence at The Laugh Factory, or simply from mentors in the comedy community. All of the comedians in "Anxiety Club" have created standup or sketch material about their mental health that is not only funny but uniquely relatable and disarming to audiences. With comedy, vulnerability, and honesty, these comedians provide remarkable insight into anxiety - the most prevalent mental health disorder affecting an estimated 300 million people worldwide. Then filmmakers Steph Ching and Ellen Martinez with their PBS documentary "Slumlord Millionaire". Winner of the Audience Award at the 2024 DOC NYC Film Festival, “Slumlord Millionaire” explores the rapid gentrification of New York City neighborhoods and the housing crisis sweeping not only New York but the nation. Median rents nationwide are higher than ever, and in Manhattan, the average rent is now almost $5,000 per month. As rents increase, some landlords have become aggressive in getting long-term tenants to leave: ignoring repairs, turning off heat and gas, and doing nothing to eliminate mold and vermin infestations. The landlord's goal is to make the apartment so uninhabitable that residents are forced out, allowing them to deregulate the apartment and turn it over to market rate for a high profit. These actions drive up costs in the already unaffordable housing market and displace families who make up the fabric of these neighborhoods, changing communities forever. “Slumlord Millionaire,”  premieres on the PBS series VOCES on Monday, July 28, 2025, 10:00-11:30 p.m. ET (check local listings) on PBS, PBS.org and the PBS app.  

Wondering where the real estate market is heading? In this July 2025 update, we break down the latest housing trends in the Greater Philadelphia area — including Chester, Bucks, Delaware, Montgomery, South Jersey, and northern Delaware.

Wes and Scott talk about the 2025 State of Devs survey, diving into trends in salaries, job titles, remote work, health, hobbies, and more. Show Notes 00:00 Welcome to Syntax! 01:44 Brought to you by Sentry.io 02:08 Years of experience vs yearly income 11:48 Layoffs 18:07 Job title 19:55 Remote work 24:40 Job happiness 25:40 Work hours 26:24 Workplace perks 26:53 What phones devs use 27:46 Desktop OS 28:44 Programming languages 29:29 Productivity apps 30:54 Social media 32:13 Median age of RSS feed users 33:41 Community contributions 35:37 Health and fitness 37:01 Health issues 39:11 Scott's health update 42:28 Hobbies 45:54 Favorite music 47:10 Favorite video games 47:37 Favorite movies 49:35 Metadata Hit us up on Socials! Syntax: X Instagram Tiktok LinkedIn Threads Wes: X Instagram Tiktok LinkedIn Threads Scott: X Instagram Tiktok LinkedIn Threads Randy: X Instagram YouTube Threads

The 401k was never designed to be your soleretirement plan—it was meant to supplement pensions, not replace them.Median 401k balance for people in their 60s?Around $112,000.-Companies love 401ks because they offload all responsibility onto the employee

A new report shows that housing costs are higher than at any other point in history ... which has many people wondering if it's time to reevaluate the American dream. On Deadline is hosted and produced by Lauren Barry and produced by Christy Strawser.

A new report shows that housing costs are higher than at any other point in history ... which has many people wondering if it's time to reevaluate the American dream. On Deadline is hosted and produced by Lauren Barry and produced by Christy Strawser.

A new report shows that housing costs are higher than at any other point in history ... which has many people wondering if it's time to reevaluate the American dream. On Deadline is hosted and produced by Lauren Barry and produced by Christy Strawser.

A new report shows that housing costs are higher than at any other point in history ... which has many people wondering if it's time to reevaluate the American dream. On Deadline is hosted and produced by Lauren Barry and produced by Christy Strawser.

A new report shows that housing costs are higher than at any other point in history ... which has many people wondering if it's time to reevaluate the American dream. On Deadline is hosted and produced by Lauren Barry and produced by Christy Strawser.

The D50 is a value that represents the median particle diameter in a sand. I calculated the D50 for 302 sands from around the world, and 15% of them are finer than the limit defined by the USGA Recommendations for a Method of Putting Green Construction.Read about this at https://www.asianturfgrass.com/post/d50-median-sand-diameter/Read more about all kinds of turfgrass topics at https://www.asianturfgrass.com/Find a suite of decision-making tools at https://www.paceturf.org/Get free ATC newsletters at https://www.asianturfgrass.com/newsletter/ Turf Without Borders show page: https://turfwb.asianturfgrass.com/International Turfgrass Society: https://turfsociety.com/

Derek Moore and Mike Snyder get into why anyone was short Opendoor and how the options market is flashing crazy implied volatility. Plus, how volatility and price movement may cause market makers to buy shares known as a “Gamma Squeeze”. Later, they get into how the signs are there that this bull market might have more to run (or not). Oh, and let's not forget to look at what the options market is forecasting for expected moves on Microsoft, Amazon, and Apple earnings next week. All this plus some recommendations this week.    Short Interest on Opendoor Implied volatility in the options for Opendoor What is a gamma squeeze? Why market makers might be forced to buy more shares to hedge when people buy calls How implied volatility, price, and time impact how many shares market makers buy Looking at a monthly breakdown of when all-time highs are reached by month Analysts are forecasting the most dissents by FOMC members at a meeting in 30 years Looking at market breadth widening Comparing the RSP equal weight ETF vs the SPY ETF performance lately Median single family home prices are holding up Why Are Stocks Up? Nobody Knows WSJ article Median S&P 500 Index Performance after 60 days above the 20-day moving average   Mentioned in this Episode   WSJ Article Why are Stocks Up? Nobody Knows https://www.wsj.com/finance/stocks/why-are-stocks-up-nobody-knows-e40e5f42?gaa_at=eafs&gaa_n=ASWzDAgNaz0DDWFH6gDHn6aERrjSRwPmYAW_gghkSG_vodoYjhptA0P1MDkxjbWf_I8%3D&gaa_ts=6884571e&gaa_sig=yozSyPX1hqhHz6UAZ2l-hgP3YdDvVJAHPTMiUXl-RbQszZ0B_F6nf5MoO9DjUl2uwotmVVavxIG3wmp2BPUwOg%3D%3D   Derek Moore's book Broken Pie Chart https://amzn.to/3S8ADNT   Jay Pestrichelli's book Buy and Hedge https://amzn.to/3jQYgMt   Derek's book on public speaking Effortless Public Speaking https://amzn.to/3hL1Mag   Contact Derek derek.moore@zegainvestments.com       

Today's poem is Sunflowers in the Median by Natalie Homer.The Slowdown is currently taking a break. We'll be back soon with new episodes from a new host. This week, we're going back into the archive to revisit Ada Limón's time as host. Today's episode was originally released on March 4, 2022. In this episode, former host Ada Limón writes… “What is it about noticing beauty that brings you out of yourself and returns you to yourself? I love rooting for beauty, for awe, for those unexpected visions that make life a little easier to manage. In today's vibrant poem, we see how the image of sunflowers can allow for a sort of grace. I love this poem for its appreciation of unexpected beauty.” Celebrate the power of poems with a gift to The Slowdown today. Every donation makes a difference: https://tinyurl.com/rjm4synp

The median home value across the state rose by two thirds in the last 4 years. Montana Free Press' Eric Dietrich crunched the numbers and joined MTPR's Elinor Smith to break them down.

A 3.73 GPA isn't the same as a 3.2—schools care about more than medians, and every point counts in the index. The solution for below-median GPAs? Crush the LSAT.Read more on our website. Email daily@lsatdemon.com with questions or comments. Watch this episode on YouTube!

Rising supply and falling demand is pushing down rents. New Cotality analysis of MBIE data shows the national median rent dropped 0.3% in the year to May. That's the first time the rent has dropped in more than 15 years. Aspire Property Management's Managing Director Mike Atkinson told Mike Hosking housing supply is increasing at the same time incomes are falling in real terms. He says there's also been a huge drop-off in net migration, with fewer people coming into the country. However, there could be some good news on the way for landlords. Atkinson says things should pick up over summer, when migration typically increases. LISTEN ABOVE See omnystudio.com/listener for privacy information.

Median home pricing at $400,000? We need answers! So we talked to Andy Babula who is a professor of Real Estate and Finance with the Opus College of Business at the University of St. Thomas about why the housing market is so high - in fact the first time it has hit $400,000 ever! Then we discuss the latest addition to your Minnesota Twins uniforms! Also, in DeRush Hour News Headlines we honor the closing of Edina Grill after three decades, high paying jobs where you can make a haul of cash and much more!

Podle agentury Median u nás letos klesl historicky na nejnižší úroveň zájem o volby. Ještě před dvěma lety chtělo jít k volbám skoro 80 procent dotázaných. Počátkem letošního roku jenom něco málo přes 60 procent, v dubnu 54, v květnu už jen 53 procent. Trend je zřetelně klesající.

Big O talks Crypto 062725

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. 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. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

Don tackles a stack of listener questions in this rapid-fire Friday Q&A, covering what a financial plan should cost, how tipping might work in a cashless future, and how to fine-tune a retirement portfolio with Avantis funds. He also addresses important estate planning steps after a death, how to use QCDs with inherited IRAs, and whether AUM fees are worth it compared to hourly planners. Along the way, he reflects on why he still manages his own money—and maybe shouldn't. 0:04 Intro to Friday Q&A and how listener questions are selected 2:12 What should a detailed retirement plan cost? Median price range explained 4:33 How will we tip in a cashless society? From bellboys to Bitcoin to Apple Pay 7:39 Listener portfolio check: 85% AVGE, 10% AVUV, 5% AVDV—too tilted? 11:36 Credit after death: Should an executor notify the credit bureaus? Yes—and how 13:45 Inherited IRA RMD workaround: Can QCDs help avoid taxes before age 70½? 17:02 AUM fees vs. flat-fee advisors: Is paying more for more assets fair? 25:51 Why Don still manages his own money (for now)—inertia, taxes, and habits Learn more about your ad choices. Visit megaphone.fm/adchoices

최근 실시된 글로벌 조사에서 호주가 성인 1인당 중간 재산(Median wealt) 기준 세계 2위를 기록했습니다.

Mathias ist Vorstandsvorsitzender von Axel Springer, Medienmanager, Autor und Journalist. Und vor allem ist er laut ChatGPT auf Platz 2 der mächtigsten Medienmänner weltweit. Ich wollte von ihm wissen, wie seine Biografie ihn geprägt hat, welche Werte er mit Freiheit verbindet und wie sich das eigene Verhältnis zu Geld verändert, wenn man Milliardär ist. Außerdem habe ich mich gefragt, was seine heutige Sicht auf den Fall Julian Reichelt ist. Wir sprechen über Macht, Vertrauen, Zweckpessimismus, es geht um Widerstand, Mut, Risiko, Diskussionskultur und familiäre Werte. WERBEPARTNER & RABATTE: https://linktr.ee/hotelmatze MEIN GAST: https://ullstein.de/urheberinnen/mathias-doepfner DINGE: Nile Rodgers - Le Freak: https://thalia.de/shop/home/artikeldetails/A1020984635 Benjamin von Stuckrad-Barre - Noch wach?: https://thalia.de/shop/home/artikeldetails/A1064678458 Maximilian Frisch - Produktion Torben Becker - Redaktion Lena Rocholl - Redaktion Mit Vergnügen - Vermarktung und Distribution MEIN ZEUG: Mein neues Fragenset: https://beherzt.net/liebe Mein neues Buch: https://bit.ly/3cDyQ18 Die Hotel Matze Suite bei Apple: https://apple.co/43V3hGq Die Hotel Matze Suite bei Spotify: https://spoti.fi/3U3ZySC Wunschgäste bitte in die Kommentare: https://apple.co/2RgJVH6 Mein Newsletter: https://matzehielscher.substack.com/ TikTok: https://tiktok.com/@matzehielscher Instagram: https://instagram.com/matzehielscher LinkedIn: https://linkedin.com/in/matzehielscher/ YouTube: https://bit.ly/2MXRILN Twitter: https://twitter.com/hotelmatze1 Mein erstes Buch: https://bit.ly/39FtHQy Mein erstes Fragenset: https://beherzt.net/matze

MDJ Script/ Top Stories for June 6th Publish Date:  June 6th    Commercial: From the BG AD Group Studio, Welcome to the Marietta Daily Journal Podcast.    Today is Friday, June 6th and Happy Birthday to Tommie Smith I’m Keith Ippolito and here are the stories Cobb is talking about, presented by Times Journal New $50,000 Median to Drive Safety on Fairground Street Attempted Carjacking Suspect Held at Gunpoint by Civilian, Arrested in Marietta Kennesaw’s Salute to America is July 3 Plus, Leah McGrath from Ingles Markets on controlling your sweet tooth All of this and more is coming up on the Marietta Daily Journal Podcast, and if you are looking for community news, we encourage you to listen and subscribe!  BREAK: TOP TECH MECHANICAL STORY 1: New $50,000 Median to Drive Safety on Fairground Street Marietta is enhancing road safety with a new median on Fairground Street near Haley Street. The $50,000 project, set to finish next week, aims to prevent U-turns that have caused accidents and traffic issues. The median will allow only left turns off Fairground Street, with 200 feet of median and 115 feet of curb being installed. Signage will alert drivers to the changes, ensuring smoother and safer traffic flow. STORY 2: Attempted Carjacking Suspect Held at Gunpoint by Civilian, Arrested in Marietta A carjacking suspect, Rico Riley, was arrested in Marietta after a witness, Gary Edwards, intervened and held him at gunpoint. Riley allegedly attempted to steal two cars at a Chevron gas station on Franklin Gateway. He first fought a woman for her car keys, then tried to carjack a second vehicle with a family inside. Edwards intervened both times, ultimately detaining Riley until police arrived. Riley faces multiple felony charges, including attempted armed robbery and child cruelty, and is held without bond. Marietta Police commend Edwards but urge witnesses to prioritize safety and call 911 in such situations. STORY 3: Kennesaw’s Salute to America is July 3 Kennesaw's annual Independence Day celebration, **Salute to America**, takes place July 3 from 6–10 p.m. in downtown Kennesaw. The free event features live music, food vendors, family activities, and a fireworks finale at 9:30 p.m. Performances include Tripp’n at 6 p.m., Girls Night Out at 7 p.m., and Guardians of the Jukebox at 8 p.m. Kids can enjoy ticketed inflatables, and food and drinks will be available for purchase. Reserved seating is $20, with reservations at kennesawjuly3.com. Tobacco and e-cigarettes are prohibited, and the event may be rescheduled for bad weather. We have opportunities for sponsors to get great engagement on these shows. Call 770.799.6810 for more info.  Break: Ingles Markets 2 STORY 4: Update: Asylum Seeker Married to Alpharetta Man Released on Bond Colombian asylum seeker Daniela Landin, 24, was released on a $10,000 bond after nearly a month in ICE custody. Married to Alpharetta resident Richard Landin, she fled gang violence in Colombia and sought asylum last year, though her initial request was denied and is under appeal. ICE detained her in May, citing an issue with her ankle monitor, despite it functioning properly. Her bond was granted after a delayed hearing, with the judge convinced of her sincerity and low flight risk. The couple, unable to fly due to her lack of ID, is driving back to Georgia, relieved to reunite. STORY 5: OUT AND ABOUT: 5 Things to Do This Weekend in Cobb County — June 6 - 8 This weekend in Cobb County offers a variety of events: Marietta Square hosts its free Art Walk Friday from 5-9 p.m., showcasing local art alongside shopping and dining. The BLADE Show at Cobb Galleria Centre runs Friday-Sunday, featuring unique blades and collectibles, with tickets starting at $30. The Kennesaw Grand Prix 5K kicks off Saturday at 8 a.m., followed by a post-race party. The Strand Theatre presents "Grease" with showtimes through June 22, and Swift-Cantrell Park in Kennesaw screens "Moana 2" Saturday at 8:15 p.m., with pre-movie activities starting at 6 p.m. Break: And now here is Leah McGrath from Ingles Markets on controlling your sweet tooth We’ll have closing comments after this. Break: TIDWELL TREES Signoff-   Thanks again for hanging out with us on today’s Marietta Daily Journal Podcast. If you enjoy these shows, we encourage you to check out our other offerings, like the Cherokee Tribune Ledger Podcast, the Marietta Daily Journal, or the Community Podcast for Rockdale Newton and Morgan Counties. Read more about all our stories and get other great content at mdjonline.com Did you know over 50% of Americans listen to podcasts weekly? Giving you important news about our community and telling great stories are what we do. Make sure you join us for our next episode and be sure to share this podcast on social media with your friends and family. Add us to your Alexa Flash Briefing or your Google Home Briefing and be sure to like, follow, and subscribe wherever you get your podcasts. Produced by the BG Podcast Network Show Sponsors: www.ingles-markets.com tidwelltrees.com toptechmech.com #NewsPodcast #CurrentEvents #TopHeadlines #BreakingNews #PodcastDiscussion #PodcastNews #InDepthAnalysis #NewsAnalysis #PodcastTrending #WorldNews #LocalNews #GlobalNews #PodcastInsights #NewsBrief #PodcastUpdate #NewsRoundup #WeeklyNews #DailyNews #PodcastInterviews #HotTopics #PodcastOpinions #InvestigativeJournalism #BehindTheHeadlines #PodcastMedia #NewsStories #PodcastReports #JournalismMatters #PodcastPerspectives #NewsCommentary #PodcastListeners #NewsPodcastCommunity #NewsSource #PodcastCuration #WorldAffairs #PodcastUpdates #AudioNews #PodcastJournalism #EmergingStories #NewsFlash #PodcastConversations See omnystudio.com/listener for privacy information.

Welcome to the "Saturday Morning Golf Stat" from the Hack it Out Golf Podcast. You've missed the green in the rough, but you're still hoping to get up and down and save a score. How far are you likely to end up from the hole when you're 35 yards away and in the rough? In this episode, Lou quizzes Mark and Greg on median distance by handicap. Afterwards, they reiterate why you need to be aware of what a good shot really is—and how expectation management can increase your performance on the course. Each of these will be a mini-episode (10-15 minutes long) about an interesting golf stat. We will discuss what you can learn, and most importantly, how you can apply this on the golf course to lower your scores and lower your handicap. Listen on your drive to the golf course or over your Saturday morning coffee! Data is sourced from Arccos Golf. They have over 1 BILLION shots in their database.  Check them out at: https://www.arccosgolf.com/  Use code DATALOU15 for 15% off! Learn more about your ad choices. Visit megaphone.fm/adchoices

Home prices are falling fast in some prime real estate markets across the country while others remain stubbornly stuck. What's the defining factor between a stable housing market and one where sellers are actively cutting prices? Housing inventory! This metric defined the 2020 - 2022 run-up in home prices, but the rubber band of demand is snapping back as buyer power grows, housing inventory rises, and investors get even better buying opportunities. Remember when people said, “I'll buy when prices drop”? Well, now might be the time. ResiClub's Lance Lambert joins us to provide a holistic view of housing inventory, prices, demand, and emerging opportunities. Lance walks through the most up-to-date data on where housing inventory is rising fast, where prices are quickly declining, and which markets are holding on as sellers remain in control. We'll also talk about why homebuilding costs are about to JUMP and the reason Warren Buffett sold his homebuilding stocks shortly after buying them. Will construction slow down, limiting new inventory and leading us back into ultra-low supply? If so, this could push home prices higher, creating a prime opportunity for real estate investors. In This Episode We Cover: Is spiking inventory a worrying sign for the housing market, or are we merely normalizing? What to look at in your housing market to forecast whether prices will rise or fall  Why are homebuilding costs about to JUMP, and could this lead to even more inventory problems? The new housing trend: Older renters, but could this mean more demand for rentals? And So Much More! Links from the Show Join BiggerPockets for FREE Let Us Know What You Thought of the Show! Ask Your Question on the BiggerPockets Forums BiggerPockets YouTube Apply to Be a BiggerPockets Real Estate Guest ResiClub: The cost breakdown for constructing a single-family home in 2024 ResiClub: Did Warren Buffett see this coming? Homebuilder margins face pressure in 2025 ResiClub: The vanishing young homebuyer: Median first-time homebuyer age jumps from 28 in 1991 to 38 in 2024 Invest in Private Market Real Estate with the Fundrise Flagship Fund Grab Dave's Book, “Real Estate by the Numbers” Sign Up for the BiggerPockets Real Estate Newsletter Find an Investor-Friendly Agent in Your Area Inventory Is Key to a Stable Real Estate Market—Will It Recover? Join Lance's Newsletter Connect with Dave Check out more resources from this show on BiggerPockets.com and https://www.biggerpockets.com/blog/real-estate-1101 Interested in learning more about today's sponsors or becoming a BiggerPockets partner yourself? Email advertise@biggerpockets.com. Learn more about your ad choices. Visit megaphone.fm/adchoices