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Welcome to a RealTalk MS special series on MS clinical trials. This special series is made possible through a generous grant from Sanofi. In today's episode, you'll meet two participants from the TEAMS Study, a research study at the University of Illinois Chicago's UI Health, in conjunction with the University of Alabama Birmingham School of Public Health. TEAAMS is an acronym for Targeted Exercise for African-Americans with Multiple Sclerosis. And the study's research team analyzed the effects of a remotely delivered, racially tailored exercise training program among African Americans with MS living in low-income areas of the Southeastern United States, including Alabama, Georgia, Mississippi, North Carolina, South Carolina, Louisiana, Arkansas, and Tennessee. This is a part of the country that doesn't have many primary care or MS clinics that provide full exercise and rehabilitation services for patients with MS. The TEAMMS study consists of two 16-week exercise programs, completed 3 days per week at home. One exercise program combines aerobic and resistance training, while the other focuses on stretching and flexibility. Study participants were randomly assigned to one of the two programs, and all of the materials to complete each program, like yoga mats, resistance bands, and training manuals, were provided. And every study participant receives a $90 gift card in compensation for completing the program. The study's research team hypothesizes that completing the TEAAMS program would improve walking, reduce symptoms of fatigue, anxiety, depression, and pain, and enhance quality of life. This special episode of RealTalk MS is made possible by a generous grant from Sanofi. Sanofi has two ongoing Phase 3 clinical trials in MS studying Frexalimab, an investigational second-generation anti-CD40 ligand monoclonal antibody. If you are interested in learning more about these clinical trials, please visit SanofiStudies.com SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/ct3 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! Privacy Policy

Dr. Linda Duska and Dr. Kathleen Moore discuss key studies in the evolving controversy over radical upfront surgery versus neoadjuvant chemotherapy in advanced ovarian cancer. TRANSCRIPT Dr. Linda Duska: Hello, and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Linda Duska. I am a professor of obstetrics and gynecology at the University of Virginia School of Medicine.  On today's episode, we will explore the management of advanced ovarian cancer, specifically with respect to a question that has really stirred some controversy over time, going all the way back more than 20 years: Should we be doing radical upfront surgery in advanced ovarian cancer, or should we be doing neoadjuvant chemotherapy? So, there was a lot of hype about the TRUST study, also called ENGOT ov33/AGO-OVAR OP7, a Phase 3 randomized study that compares upfront surgery with neoadjuvant chemotherapy followed by interval surgery. So, I want to talk about that study today. And joining me for the discussion is Dr. Kathleen Moore, a professor also of obstetrics and gynecology at the University of Oklahoma and the deputy director of the Stephenson Cancer Center, also at the University of Oklahoma Health Sciences.  Dr. Moore, it is so great to be speaking with you today. Thanks for doing this. Dr. Kathleen Moore: Yeah, it's fun to be here. This is going to be fun. Dr. Linda Duska: FYI for our listeners, both of our full disclosures are available in the transcript of this episode.  So let's just jump right in. We already alluded to the fact that the TRUST study addresses a question we have been grappling with in our field. Here's the thing, we have four prior randomized trials on this exact same topic. So, share with me why we needed another one and what maybe was different about this one? Dr. Kathleen Moore: That is, I think, the key question. So we have to level-set kind of our history. Let's start with, why is this even a question? Like, why are we even talking about this today? When we are taking care of a patient with newly diagnosed ovarian cancer, the aim of surgery in advanced ovarian cancer ideally is to prolong a patient's likelihood of disease-free survival, or if you want to use the term "remission," you can use the term "remission." And I think we can all agree that our objective is to improve overall survival in a way that also does not compromise her quality of life through surgical complications, which can have a big effect. The standard for many decades, certainly my entire career, which is now over 20 years, has been to pursue what we call primary cytoreductive surgery, meaning you get a diagnosis and we go right to the operating room with a goal of achieving what we call "no gross residual." That is very different – in the olden days, you would say "optimal" and get down to some predefined small amount of tumor. Now, the goal is you remove everything you can see.  The alternative strategy to that is neoadjuvant chemotherapy followed by interval cytoreductive surgery, and that has been the, quote-unquote, "safer" route because you chemically cytoreduce the cancer, and so, the resulting surgery, I will tell you, is not necessarily easy at all. It can still be very radical surgeries, but they tend to be less radical, less need for bowel resections, splenectomy, radical procedures, and in a short-term look, would be considered safer from a postoperative consideration. Dr. Linda Duska: Well, and also maybe more likely to be successful, right? Because there's less disease, maybe, theoretically. Dr. Kathleen Moore: More likely to be successful in getting to no gross residual. Dr. Linda Duska: Right. Yeah, exactly. Dr. Kathleen Moore: I agree with that. And so, so if the end game, regardless of timing, is you get to no gross residual and you help a patient and there's no difference in overall survival, then it's a no-brainer. We would not be having this conversation. But there remains a question around, while it may be more likely to get to no gross residual, it may be, and I think we can all agree, a less radical, safer surgery, do you lose survival in the long term by this approach? This has become an increasing concern because of the increase in rates of use of neoadjuvant, not only in this country, but abroad. And so, you mentioned the four prior studies. We will not be able to go through them completely. Dr. Linda Duska: Let's talk about the two modern ones, the two from 2020 because neither one of them showed a difference in overall survival, which I think we can agree is, at the end of the day, yes, PFS would be great, but OS is what we're looking for. Dr. Kathleen Moore: OS is definitely what we're looking for. I do think a marked improvement in PFS, like a real prolongation in disease-free survival, for me would be also enough. A modest improvement does not really cut it, but if you are really, really prolonging PFS, you should see that-  Dr. Linda Duska: -manifest in OS. Dr. Kathleen Moore: Yeah, yeah. Okay. So let's talk about the two modern ones. The older ones are EORTC and CHORUS, which I think we've talked about. The two more modern ones are SCORPION and JCOG0602. So, SCORPION was interesting. SCORPION was a very small study, though. So one could say it's underpowered. 170 patients. And they looked at only patients that were incredibly high risk. So, they had to have a Fagotti score, I believe, of over 9, but they were not looking at just low volume disease. Like, those patients were not enrolled in SCORPION. It was patients where you really were questioning, "Should I go to the OR or should I do neoadjuvant? Like, what's the better thing?" It is easy when it's low volume. You're like, "We're going." These were the patients who were like, "Hm, you know, what should I do?" High volume. Patients were young, about 55. The criticism of the older studies, there are many criticisms, but one of them is that, the criticism that is lobbied is that they did not really try. Whatever surgery you got, they did not really try with median operative times of 180 minutes for primary cytoreduction, 120 for neoadjuvant. Like, you and I both know, if you're in a big primary debulking, you're there all day. It's 6 hours. Dr. Linda Duska: Right, and there was no quality control for those studies, either. Dr. Kathleen Moore: No quality control. So, SCORPION, they went 451-minute median for surgery. Like, they really went for it versus four hours and then 253 for the interval, 4 hours. They really went for it on both arms. Complete gross resection was achieved in 50% of the primary cytoreduced. So even though they went for it with these very long surgeries, they only got to the goal half the time. It was almost 80% in the interval group. So they were more successful there. And there was absolutely no difference in PFS or OS. They were right about 15 months PFS, right about 40 months OS.  JCOG0602, of course, done in Japan, a big study, 300 patients, a little bit older population. Surprisingly more stage IV disease in this study than were in SCORPION. SCORPION did not have a lot of stage IV, despite being very bulky tumors. So a third of patients were stage IV. They also had relatively shorter operative times, I would say, 240 minutes for primary, 302 for interval. So still kind of short. Complete gross resection was not achieved very often. 30% of primary cytoreduction. That is not acceptable. Dr. Linda Duska: Well, so let's talk about TRUST. What was different about TRUST? Why was this an important study for us to see? Dr. Kathleen Moore: So the criticism of all of these, and I am not trying to throw shade at anyone, but the criticism of all of these is if you are putting surgery to the test, you are putting the surgeon to the test. And you are assuming that all surgeons are trained equally and are willing to do what it takes to get someone to no gross residual. Dr. Linda Duska: And are in a center that can support the post-op care for those patients. Dr. Kathleen Moore: Which can be ICU care, prolonged time. Absolutely. So when you just open these broadly, you're assuming everyone has the surgical skills and is comfortable doing that and has backup. Everybody has an ICU. Everyone has a blood bank, and you are willing to do that. And that assumption could be wrong. And so what TRUST said is, "Okay, we are only going to open this at centers that have shown they can achieve a certain level of primary cytoreduction to no gross residual disease." And so there was quality criteria. It was based on – it was mostly a European study – so ESGO criteria were used to only allow certified centers to participate. They had to have a surgical volume of over 36 cytoreductive surgeries per year. So you could not be a low volume surgeon. Your complete resection rates that were reported had to be greater than 50% in the upfront setting. I told you on the JCOG, it was 30%. Dr. Linda Duska: Right. So these were the best of the best. This was the best possible surgical situation you could put these patients in, right? Dr. Kathleen Moore: Absolutely. And you support all the things so you could mitigate postoperative complications as well. Dr. Linda Duska: So we are asking the question now again in the ideal situation, right? Dr. Kathleen Moore: Right. Dr. Linda Duska: Which, we can talk about, may or may not be generalizable to real life, but that's a separate issue because we certainly don't have those conditions everywhere where people get cared for with ovarian cancer. But how would you interpret the results of this study? Did it show us anything different? Dr. Kathleen Moore: I am going to say how we should interpret it and then what I am thinking about. It is a negative study. It was designed to show improvement in overall survival in these ideal settings in patients with FIGO stage IIIB and C, they excluded A, these low volume tumors that should absolutely be getting surgery. So FIGO stage IIIB and C and IVA and B that were fit enough to undergo radical surgery randomized to primary cytoreduction or neoadjuvant with interval, and were all given the correct chemo. Dr. Linda Duska: And they were allowed bevacizumab and PARP, also. They could have bevacizumab and PARP. Dr. Kathleen Moore: They were allowed bevacizumab and PARP. Not many of them got PARP, but it was distributed equally, so that would not be a confounder. And so that was important. Overall survival is the endpoint. It was a big study. You know, it was almost 600 patients. So appropriately powered. So let's look at what they reported. When they looked at the patients who were enrolled, this is a large study, almost 600 patients, 345 in the primary cytoreductive arm and 343 in the neoadjuvant arm. Complete resection in these patients was 70% in the primary cytoreductive arm and 85% in the neoadjuvant arm. So in both arms, it was very high. So your selection of site and surgeon worked. You got people to their optimal outcome. So that is very different than any other study that has been reported to date. But what we saw when we looked at overall survival was no statistical difference. The median was, and I know we do not like to talk about medians, but the median in the primary cytoreductive arm was 54 months versus 48 months in the neoadjuvant arm with a hazard ratio of 0.89 and, of course, the confidence interval crossed one. So this is not statistically significant. And that was the primary endpoint. Dr. Linda Duska: I know you are getting to this. They did look at PFS, and that was statistically significant, but to your point about what are we looking for for a reasonable PFS difference? It was about two months difference. When I think about this study, and I know you are coming to this, what I thought was most interesting about this trial, besides the fact that the OS, the primary endpoint was negative, was the subgroup analyses that they did. And, of course, these are hypothesis-generating only. But if you look at, for example, specifically only the stage III group, that group did seem to potentially, again, hypothesis generating, but they did seem to benefit from upfront surgery.  And then one other thing that I want to touch on before we run out of time is, do we think it matters if the patient is BRCA germline positive? Do we think it matters if there is something in particular about that patient from a biomarker standpoint that is different? I am hopeful that more data will be coming out of this study that will help inform this. Of course, unpowered, hypothesis-generating only, but it's just really interesting. What do you think of their subset analysis? Dr. Kathleen Moore: Yeah, I think the subsets are what we are going to be talking about, but we have to emphasize that this was a negative trial as designed. Dr. Linda Duska: Absolutely. Yes. Dr. Kathleen Moore: So we cannot be apologists and be like, "But this or that." It was a negative trial as designed. Now, I am a human and a clinician, and I want what is best for my patients. So I am going to, like, go down the path of subset analyses. So if you look at the stage III tumors that got complete cytoreduction, which was 70% of the cases, your PFS was almost 28 months versus 21.8 months. Dr. Linda Duska: Yes, it becomes more significant. Dr. Kathleen Moore: Yeah, that hazard ratio is 0.69. Again, it is a subset. So even though the P value here is statistically significant, it actually should not have a P value because it is an exploratory analysis. So we have to be very careful. But the hazard ratio is 0.69. So the hypothesis is in this setting, if you're stage III and you go for it and you get someone to no gross residual versus an interval cytoreduction, you could potentially have a 31% reduction in the rate of progression for that patient who got primary cytoreduction. And you see a similar trend in the stage III patients, if you look at overall survival, although the post-progression survival is so long, it's a little bit narrow of a margin.  But I do think there are some nuggets here that, one of our colleagues who is really one of the experts in surgical studies, Dr. Mario Leitao, posted this on X, and I think it really resonated after this because we were all saying, "But what about the subsets?" He is like, "It's a negative study." But at the end of the day, you are going to sit with your patient. The patient should be seen by a GYN oncologist or surgical oncologist with specialty in cytoreduction and a medical oncologist, you know, if that person does not give chemo, and the decision should be made about what to do for that individual patient in that setting. Dr. Linda Duska: Agreed. And along those lines, if you look carefully at their data, the patients who had an upfront cytoreduction had almost twice the risk of having a stoma than the patients who had an interval cytoreduction. And they also had a higher risk of needing to have a bowel resection. The numbers were small, but still, when you look at the surgical complications, as you've already said, they're higher in the upfront group than they are in the interval group. That needs to be taken into account as well when counseling a patient, right? When you have a patient in front of you who says to you, "Dr. Moore, you can take out whatever you want, but whatever you do, don't make me a bag." As long as the patient understands what that means and what they're asking us to do, I think that we need to think about that. Dr. Kathleen Moore: I think that is a great point. And I have definitely seen in our practice, patients who say, "I absolutely would not want an ostomy. It's a nonstarter for me." And we do make different decisions. And you have to just say, "That's the decision we've made," and you kind of move on, and you can't look back and say, "Well, I wish I would have, could have, should have done something else." That is what the patient wants. Ultimately, that patient, her family, autonomous beings, they need to be fully counseled, and you need to counsel that patient as to the site that you are in, her volume of disease, and what you think you can achieve. In my opinion, a patient with stage III cancer who you have the site and the capabilities to get to no gross residual should go to the OR first. That is what I believe. I do not anymore think that for stage IV. I think that this is pretty convincing to me that that is probably a harmful thing. However, I want you to react to this. I think I am going to be a little unpopular in saying this, but for me, one of the biggest take-homes from TRUST was that whether or not, and we can talk about the subsets and the stage III looked better, and I think it did, but both groups did really well. Like, really well. And these were patients with large volume disease. This was not cherry-picked small volume stage IIIs that you could have done an optimal just by doing a hysterectomy. You know, these were patients that needed radical surgery. And both did well. And so what it speaks to me is that anytime you are going to operate on someone with ovary, whether it be frontline, whether it be a primary or interval, you need a high-volume surgeon. That is what I think this means to me. Like, I would want high volume surgeon at a center that could do these surgeries, getting that patient, my family member, me, to no gross residual. That is important. And you and I are both in training centers. I think we ought to take a really strong look at, are we preparing people to do the surgeries that are necessary to get someone to no gross residual 70% and 85% of the time? Dr. Linda Duska: We are going to run out of time, but I want to address that and ask you a provocative question. So, I completely agree with what you said, that surgery is important. But I also think one of the reasons these patients in this study did so well is because all of the incredible new therapies that we have for patients. Because OS is not just about surgery. It is about surgery, but it is also about all of the amazing new therapies we have that you and others have helped us to get through clinical research. And so, how much of that do you think, like, for example, if you look at the PFS and OS rates from CHORUS and EORTC, I get it that they're, that they're not the same. It's different patients, different populations, can't do cross-trial comparisons. But the OS, as you said, in this study was 54 months and 48 months, which is, compared to 2010, we're doing much, much better. It is not just the surgery, it is also all the amazing treatment options we have for these patients, including PARP, including MIRV, including lots of other new therapies. How do you fit that into thinking about all of this? Dr. Kathleen Moore: I do think we are seeing, and we know this just from epidemiologic data that the prevalence of ovarian cancer in many of the countries where the study was done is increasing, despite a decrease in incidence. And why is that? Because people are living longer. Dr. Linda Duska: People are living longer, yeah. Dr. Kathleen Moore: Which is phenomenal. That is what we want. And we do have, I think, better supportive care now. PARP inhibitors in the frontline, which not many of these patients had. Now some of them, this is mainly in Europe, will have gotten them in the first maintenance setting, and I do think that impacts outcome. We do not have that data yet, you know, to kind of see what, I would be really interested to see. We do not do this well because in ovarian cancer, post-progression survival can be so long, we do not do well of tracking what people get when they come off a clinical trial to see how that could impact – you know, how many of them got another surgery? How many of them got a PARP? I think this group probably missed the ADC wave for the most part, because this, mirvetuximab is just very recently available in Europe. Dr. Linda Duska: Unless they were on trial. Dr. Kathleen Moore: Unless they were on trial. But I mean, I think we will have to see. 600 patients, I would bet a lot of them missed the ADC wave. So, I do not know that we can say we know what drove these phenomenal – these are some of the best curves we've seen outside of BRCA. And then coming back to your point about the BRCA population here, that is a really critical question that I do not know that we're ever going to answer. There have been hypotheses around a tumor that is driven by BRCA, if you surgically cytoreduced it, and then chemically cytoreduced it with chemo, and so you're starting PARP with nothing visible and likely still homogeneous clones. Is that the group we cured? And then if you give chemo first before surgery, it allows more rapid development of heterogeneity and more clonal evolution that those are patients who are less likely to be cured, even if they do get cytoreduced to nothing at interval with use of PARP inhibitor in the front line. That is a question that many have brought up as something we would like to understand better. Like, if you are BRCA, should you always just go for it or not? I do not know that we're ever going to really get to that. We are trying to look at some of the other studies and just see if you got neoadjuvant and you had BRCA, was anyone cured? I think that is a question on SOLO1 I would like to know the answer to, and I don't yet, that may help us get to that. But that's sort of something we do think about. You should have a fair number of them in TRUST. It wasn't a stratification factor, as I remember. Dr. Linda Duska: No, it wasn't. They stratified by center, age, and ECOG status Dr. Kathleen Moore: So you would hope with randomization that you would have an equal number in each arm. And they may be able to pull that out and do a very exploratory look. But I would be interested to see just completely hypothesis-generating what this looks like for the patients with BRCA, and I hope that they will present that. I know they're busy at work. They have translational work. They have a lot pending with TRUST. It's an incredibly rich resource that I think is going to teach us a lot, and I am excited to see what they do next. Dr. Linda Duska: So, outside of TRUST, we are out of time. I just want to give you a moment if there were any other messages that you want to share with our listeners before we wrap up. Dr. Kathleen Moore: It's an exciting time to be in GYN oncology. For so long, it was just chemo, and then the PARP inhibitors nudged us along quite a bit. We did move more patients, I believe, to the cure fraction. When we ultimately see OS, I think we'll be able to say that definitively, and that is exciting. But, you know, that is the minority of our patients. And while HRD positive benefits tremendously from PARP, I am not as sure we've moved as many to the cure fraction. Time will tell. But 50% of our patients have these tumors that are less HRD. They have a worse prognosis. I think we can say that and recur more quickly. And so the advent of these antibody-drug conjugates, and we could name 20 of them in development in GYN right now, targeting tumor-associated antigens because we're not really driven by mutations other than BRCA. We do not have a lot of things to come after. We're not lung cancer. We are not breast cancer. But we do have a lot of proteins on the surface of our cancers, and we are finally able to leverage that with some very active regimens. And we're in the early phases, I would say, of really understanding how best to use those, how best to position them, and which one to select for whom in a setting where there is going to be obvious overlap of the targets. So we're going to be really working this problem. It is a good problem. A lot of drugs that work pretty well. How do you individualize for a patient, the patient in front of you with three different markers? How do you optimize it? Where do you put them to really prolong survival? And then we finally have cell surface. We saw at ASCO, CDK2 come into play here for the first time, we've got a cell cycle inhibitor. We've been working on WEE1 and ATR for a long time. CDK2s may hit. Response rates were respectable in a resistant population that was cyclin E overexpressing. We've been working on that biomarker for a long time with a toxicity profile that was surprisingly clean, which I like to see for our patients. So that is a different platform. I think we have got bispecifics on the rise. So there is a pipeline of things behind the ADCs, which is important because we need more than one thing, that makes me feel like in the future, I am probably not going to be using doxil ever for platinum-resistant disease. So, I am going to be excited to retire some of those things. We will say, "Remember when we used to use doxil for platinum-resistant disease?" Dr. Linda Duska: I will be retired by then, but thanks for that thought. Dr. Kathleen Moore: I will remind you. Dr. Linda Duska: You are right. It is such an incredibly exciting time to be taking care of ovarian cancer patients with all the opportunities.  And I want to thank you for sharing your valuable insights with us on this podcast today and for your great work to advance care for patients with GYN cancers. Dr. Kathleen Moore: Likewise. Thanks for having me. Dr. Linda Duska: And thank you to our listeners for your time today. You will find links to the TRUST study and other studies discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Linda Duska  @Lduska Dr. Kathleen Moore Follow ASCO on social media:     @ASCO on X (formerly Twitter) ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures of Potential Conflicts of Interest:    Dr. Linda Duska:   Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma  Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics  Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn  Dr. Kathleen Moore: Leadership: GOG Partners, NRG Ovarian Committee Chair Honoraria: Astellas Medivation, Clearity Foundation, IDEOlogy Health, Medscape, Great Debates and Updates, OncLive/MJH Life Sciences, MD Outlook, Curio Science, Plexus, University of Florida, University of Arkansas for Medical Sciences, Congress Chanel, BIOPHARM, CEA/CCO, Physician Education Resource (PER), Research to Practice, Med Learning Group, Peerview, Peerview, PeerVoice, CME Outfitters, Virtual Incision Consulting/Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Merck, Eisai, Verastem/Pharmacyclics, AADi, Caris Life Sciences, Iovance Biotherapeutics, Janssen Oncology, Regeneron, zentalis, Daiichi Sankyo Europe GmbH, BioNTech SE, Immunocore, Seagen, Takeda Science Foundation, Zymeworks, Profound Bio, ADC Therapeutics, Third Arc, Loxo/Lilly, Bristol Myers Squibb Foundation, Tango Therapeutics, Abbvie, T Knife, F Hoffman La Roche, Tubulis GmbH, Clovis Oncology, Kivu, Genmab/Seagen, Kivu, Genmab/Seagen, Whitehawk, OnCusp Therapeutics, Natera, BeiGene, Karyopharm Therapeutics, Day One Biopharmaceuticals, Debiopharm Group, Foundation Medicine, Novocure Research Funding (Inst.): Mersana, GSK/Tesaro, Duality Biologics, Mersana, GSK/Tesaro, Duality Biologics, Merck, Regeneron, Verasatem, AstraZeneca, Immunogen, Daiichi Sankyo/Lilly, Immunocore, Torl Biotherapeutics, Allarity Therapeutics, IDEAYA Biosciences, Zymeworks, Schrodinger Other Relationship (Inst.): GOG Partners

Defense technology has shifted from a social liability in Silicon Valley to commanding 35-40% of venture capital allocation—up from a historical 10%. This isn't just trend-following; it reflects fundamental market dynamics as SaaS becomes hypercompetitive and AI lowers barriers to entry, pushing capital toward deep tech where moats still exist. Blacklake, a defense holdco based in Austin, helps emerging defense companies navigate government procurement and expand into Europe, Asia-Pacific, and allied markets. In this episode, Jeff Crusey, EVP of Technology & Acquisition at Blacklake, reveals the emerging defense tech playbook, explains why lobbying ROI dwarfs traditional GTM spending, and details what actually matters when hardware meets government procurement. Topics Discussed: Why VC capital is rotating from SaaS to deep tech and defense The defense tech go-to-market playbook versus enterprise SaaS mechanics SBIR grant programs as non-dilutive capital for hardware development Lobbying and appropriations as core revenue drivers, not nice-to-haves Field deployment and operator feedback as the only viable iteration strategy Investor evaluation criteria for hardware-intensive defense businesses Emerging threat vectors in Arctic defense and orbital domain awareness GTM Lessons For B2B Founders: Launch lobbying concurrent with SBIR Phase 1 applications: Companies initiating lobbying and appropriations work at the moment they apply for SBIR grants hit revenue milestones materially faster than those treating government affairs as a later-stage function. This means seed-stage companies maintain Capitol Hill presence—a pattern that didn't exist five years ago. The talent profile matters: government affairs hires need proven relationships within specific congressional committees and appropriations staff. Initial engagements typically involve external lobbying advisors with established networks, transitioning in-house at Series A when contract pipeline justifies dedicated headcount. This is consistently the highest-ROI channel in defense GTM. Optimize for deployment speed over system perfection: Modern conflict operates as continuous technological adaptation where capabilities become obsolete within weeks, not years. Companies achieving persistent field presence with operators—not laboratory perfection—win iterative cycles. The tactical approach: deploy minimum viable hardware to operational environments, capture real-world performance data and failure modes, then rapidly incorporate feedback into next iterations. This contradicts traditional defense procurement assumptions about "exquisite systems" and requires founders to resist over-engineering before battlefield validation. Solve the prototype funding problem through non-dilutive capital: Defense investors require working prototypes before capital deployment due to hardware risk profiles—fundamentally different from software's low marginal cost of iteration. This creates a chicken-and-egg problem: prototypes require capital, but capital requires prototypes. The solution path combines bootstrapping to early proof-of-concept, then leveraging SBIR Phase 1 grants (tens of thousands) to reach demonstrable prototype stage. Phase 2 awards (single-digit millions) fund production validation. Strategic founders pursue direct-to-Phase-2 pathways when possible, compressing the timeline from concept to validated demand signal. Strip technical complexity from investor communications: Defense founders with deep domain expertise consistently over-index on technical sophistication during fundraising conversations, losing investor attention before reaching commercial traction narratives. VCs evaluate market timing, defensibility, and path to scale—not engineering elegance. The correction: communicate technology at middle-school comprehension levels. This isn't condescension; it's recognizing that capital allocators optimize for portfolio construction, not technical peer review. Founders often feel they're "dumbing down" their innovations, but clarity on problem-solution fit and market size matters infinitely more than technical specifications during early fundraising stages. Treat SBIR phases as progressive demand validation, not just funding: The phased SBIR structure functions as government-backed demand signaling: Phase 1 validates concept feasibility, Phase 2 confirms development viability, Phase 3 demonstrates production readiness for potential program of record status. Investors decode these phases as risk reduction milestones. Phase 1 awards indicate government interest; Phase 2 awards (especially direct-to-Phase-2 or enhanced Phase 2) signal validated customer pull; Phase 3 contracts position companies for program of record awards worth hundreds of millions annually. Beyond capital, SBIR progression provides founder-market fit evidence and customer commitment that traditional LOIs cannot match in defense contexts. // Sponsors: Front Lines — We help B2B tech companies launch, manage, and grow podcasts that drive demand, awareness, and thought leadership. www.FrontLines.io The Global Talent Co. — We help tech startups find, vet, hire, pay, and retain amazing marketing talent that costs 50-70% less than the US & Europe. www.GlobalTalent.co // Don't Miss: New Podcast Series — How I Hire Senior GTM leaders share the tactical hiring frameworks they use to build winning revenue teams. Hosted by Andy Mowat, who scaled 4 unicorns from $10M to $100M+ ARR and launched Whispered to help executives find their next role. Subscribe here: https://open.spotify.com/show/53yCHlPfLSMFimtv0riPyM

Brian, Blake, and Richard are back for Episode 592 of the Chasing Tone Podcast - What's happening to the price of US guitars, the rise of the robots, and Brian's goth phase  Blake has a wallet bursting conundrum as not one but two of his favorite bands are on the same bill and he needs help which Brian and Richard are more than happy to not give. Richard bores Brian to near death with Pink Floyd related updates and then talks about his new old music discoveries. Richard has AI based concerns and he expresses them via the medium of terrible analogies. Brian is not convinced that he is right but there is a business idea and a possible confession. The horrors persist for Richard as he discusses a brand new release from Gibson and Brian taunts him with emojis. There are some language barriers that need to be broken down and there is much confusion. Marshall have released an amp in conjunction with Spinal Tap and Brian ponders the possibilities of an infinitely loud amplifier. Fishing, The Great British Bake off, Ticket Touts, The nuttercut, Lorries...it's all in this week's Chasing Tone!We are on Patreon now too!Support the show (https://www.patreon.com/chasingtonepodcast)Awesome Courses and DIY mods:https://www.guitarpedalcourse.com/https://www.wamplerdiy.com/Youtube:https://www.youtube.com/@chasingtonepodcastFind us at:https://www.wamplerpedals.com/https://www.instagram.com/WamplerPedals/https://www.facebook.com/groups/wamplerfanpage/Contact us at: podcast@wamplerpedals.comSupport the show

This episode kicks off a four-part series exploring each stage of the path to mastery—Startup, Stability, Success, and Mastery. Today, we're diving into how to not just survive the startup phase but step up and own your role as a true business owner.We'll talk about the roadblocks to expect, how to avoid the “shiny object syndrome,” and the value of getting guidance from someone who understands your goals and journey.So listen to real client stories, take in the insights, and let's get you winning through your startup phase!Learn more in The Coaching Equation - Path to Mastery: How to Survive the Startup Phase and Avoid the Fatal Mistakes That Kill 90% of New Coaching BusinessesEnjoy the podcast? Subscribe and leave a 5-star review!Brook Bishop spent over two decades immersed in Personal Development and Business Consulting, driven by a passion for unlocking the potential of coaches and coaching organizations. As the co-founder of EMPIRE Partners, his journey is defined by transformative roles: leading sales at Buffini and Company, the world's largest real estate coaching company, and serving as Tony Robbins' Executive of Business Solutions for 15 impactful years.Connect with Brook Bishop!Website: https://brookbishop.com/ Instagram: https://www.instagram.com/brookthebishop1/ LinkedIn: https://www.linkedin.com/in/brookbishop/ Facebook: https://www.facebook.com/brookthebishop Ryan Lang is the CEO of EMPIRE Partners and a highly sought-after performance coach and consultant. He helps establish business owners, coaches, and thought leaders transform from elite practitioners to transformational leaders by building businesses on five critical pillars instead of one wobbly leg. Over 20 years, he has guided 1000+ professionals to predictable, profitable growth using his Whole Performance Coaching methodology—combining sales mastery, strategic marketing, and human optimization principles that create lasting stability.Connect with Ryan Lang!Website: https://www.ryanrlang.com/ Instagram: https://www.instagram.com/realryanlang/ LinkedIn: https://www.linkedin.com/in/ryan-lang-b46a545b/ Facebook: https://www.facebook.com/ryan.lang.984 Learn more about Empire Partners: Website: https://empirepartners.net/ LinkedIn: https://www.linkedin.com/company/empire-partners/Facebook: https://www.facebook.com/profile.php?id=100093312203714 #PathToMastery #StartupSuccess #BusinessGrowth 

Most service business owners make the same hiring mistake: they either clone themselves or swing too far in the opposite direction. Dave MacDonald, founder of The MacDonald Group, has cracked the code on bringing in leadership that elevates your business without losing what makes it profitable. In this episode, Dave shares his battle-tested approach to hiring leaders who bring proven systems from larger operations—without the disconnect that kills profitability. If you've ever wondered how to scale past $10M, $20M, or beyond without chaos, this conversation is your roadmap. The "Descending Ladder" Hiring Strategy That Changes Everything Dave's counterintuitive approach: hire leaders from companies roughly double your size. Not too small (they won't bring new systems), not too large (they'll lose touch with the hands-on work that drives profit). The sweet spot: If you're running a $20M service business, target leaders from $40M firms. They've seen the systems that work at scale, but they're still close enough to remember the grind. The danger zone: Hiring someone from a $100M operation for your $20M business. They'll design systems for problems you don't have yet—and profitability vanishes while they build their empire. "Throw Them in the Pool" - The Onboarding System That Reveals Everything Forget the standard two-week onboarding playbook. Dave's approach tests what really matters: can they swim when unexpected challenges hit? Phase 1 - The Pool Phase 2 - The Brick Phase 3 - Juggling The Three I's: Building a Culture That Repels the Wrong People Dave's non-negotiable cultural framework filters out mismatches before they become expensive problems: Integrity - Takes a full year to truly assess. You can't shortcut this one. Intensity - Either they match your pace or they don't. Create an environment where low intensity feels awkward. Intentionality - Can be taught, but natural focus is gold. Look for people who think three steps ahead. Systems That Actually Improve (Instead of Just Existing) The Annual Rewrite: Every Standard Operating Procedure gets completely rewritten yearly. Yes, completely. This forces evolution and prevents "we've always done it this way" from killing your growth. The Weekly Rhythm Feedback loops that matter The People-First AI Strategy for Service Businesses Dave's refreshingly practical take on AI: "Old-world values with today's most robust technology." What they're actually using AI for: Writing and presentation creation Back-office automation (invoicing, payroll) Initial candidate screening What they're NOT doing: Chasing bleeding-edge tools that aren't proven Replacing the human connection in recruiting Top-down AI mandates Why This Matters for Your Service Business If you're stuck between $5M and $20M, you're probably missing one thing: leaders who've already solved the problems you're facing. The systems you need exist—you just need someone who's lived them. Dave's approach removes the guesswork. Hire people who've already built what you're trying to build. Test them hard and fast. Build a culture so strong that mediocrity feels uncomfortable. Most importantly: don't let your systems gather dust. Annual rewrites might sound exhausting, but it's the difference between a business that scales and one that plateaus. Want to transform your hiring and onboarding systems? These aren't just recruitment tactics—they're the foundation for scalable growth. The question isn't whether you can afford to implement these systems. It's whether you can afford not to.

If you've ever wondered what it actually takes to generate consistent, predictable, and sustainable $10K–$50K months as a personal trainer, health coach, nutritionist, or registered dietitian… this episode lays out the entire blueprint step by step.Inside this episode, Beverley pulls back the curtain on the exact systems, structure, and strategy required to build a coaching business that produces dependable revenue month after month — without relying on trends, hacks, freebies, or burnout hustle.Whether you're scaling past your first 10K month or setting your sights on 50K+ months, this is your complete roadmap.⭐ In This Episode, You'll Discover:

Brazil's environment minister Marina Silva is calling on nations to commit to a voluntary and "self-determined" fossil-fuel phaseout roadmap at COP30. Debate continues over how aggressive nations should be and how such a roadmap should be enforced. Source: https://www.theguardian.com/environment/2025/nov/16/have-courage-to-create-fossil-fuel-phaseout-roadmap-at-cop30-brazilian-minister-urges Sodium-Ion Batteries That Work at -100°C Researchers at Purdue University have demonstrated a sodium-ion battery capable of operating reliably in extreme cold. The pouch cell was tested with real wind and solar inputs, raising possibilities for remote, polar, and space applications. Lightning Round At COP30 there are 50 fossil-fuel lobbyists for every delegate from the Philippines. The IEA's latest oil-demand forecast assumes no EV growth outside China and Europe—an assumption that defies basic economics and was influenced by Trump-era pressure. Sky debuts a silent, zero-emission hydrogen + sodium battery power system for film and TV sets. Story: https://fcw.sh/RgGKB0 Contact Us cleanenergyshow@gmail.com or leave us an online voicemail: http://speakpipe.com/clean Support The Clean Energy Show Join the Clean Club on our Patreon Page. Our PayPal Donate Page offers one-time or regular donations. Store Visit The Clean Energy Show Store      

In this episode, I talk honestly about the struggles we all face as child-centered play therapists — not as problems to be avoided, but as essential parts of our own therapeutic journey. After two meaningful conversations this week, and in the context of my own recent grief, I've been reflecting on how CCPT doesn't just grow our clients; it grows us. I share how every CCPT clinician eventually hits a wall of resistance, self-doubt, and frustration, and why that moment is actually the turning point toward mastery if we stay the course. I draw parallels between the phases children move through in the playroom and the phases we go through as clinicians — initiation, resistance, work, and ultimately a long, steady season of competence and grounded confidence. This episode is a reminder that resistance is not a sign you're doing something wrong. It's a sign that you're becoming who you're meant to be as a CCPT therapist. When we trust the process for ourselves the same way we trust it for our kids, we emerge stronger, clearer, and more connected to the work than ever. PlayTherapyNow.com is my HUB for everything I do! playtherapynow.com. Sign up for my email newsletter, stay ahead with the latest CCPT CEU courses, personalized coaching opportunities and other opportunities you need to thrive in your CCPT practice. If you click one link in these show notes, this is the one to click! Topical Playlists! All of the podcasts are now grouped into topical playlists on YouTube. Please go to https://www.youtube.com/kidcounselorbrenna/playlists to view them. If you would like to ask me questions directly, check out www.ccptcollective.com, where I host two weekly Zoom calls filled with advanced CCPT case studies and session reviews, as well as member Q&A. You can take advantage of the two-week free trial to see if the CCPT Collective is right for you. Ask Me Questions: Call ‪(813) 812-5525‬, or email: brenna@thekidcounselor.com Brenna's CCPT Hub: https://www.playtherapynow.com CCPT Collective (online community exclusively for CCPTs): https://www.ccptcollective.com Podcast HQ: https://www.playtherapypodcast.com APT Approved Play Therapy CE courses: https://childcenteredtraining.com Facebook: https://facebook.com/playtherapypodcast Common References: Cochran, N., Nordling, W., & Cochran, J. (2010). Child-Centered Play Therapy (1st ed.). Wiley. VanFleet, R., Sywulak, A. E., & Sniscak, C. C. (2010). Child-centered play therapy. Guilford Press. Landreth, G.L. (2023). Play Therapy: The Art of the Relationship (4th ed.). Routledge. Landreth, G.L., & Bratton, S.C. (2019). Child-Parent Relationship Therapy (CPRT): An Evidence-Based 10-Session Filial Therapy Model (2nd ed.). Routledge. https://doi.org/10.4324/9781315537948 Benedict, Helen. Themes in Play Therapy. Used with permission to Heartland Play Therapy Institute.

Fühlst du dich auch manchmal wie in einer Engstelle, wo alles um dich herum chaotisch ist und gleichzeitig deine tiefsten inneren Wunden an die Oberfläche kommen? In dieser Folge teile ich mit dir, warum wir gerade durch eine Zeit der Bedrängnis gehen und wie wir sie als Chance zur Erneuerung nutzen können, statt uns davon überwältigen zu lassen. Ich erkläre, warum diese herausfordernde Phase ein Geschenk sein kann, das uns auf etwas Neues vorbereitet – wenn wir bereit sind, uns darauf einzulassen. Lass uns gemeinsam entdecken, wie wir in dieser Zeit der Bedrängnis nicht nur überleben, sondern innerlich wachsen können.

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a host of transformative events reshaping the landscape, from strategic acquisitions and funding infusions to regulatory maneuvers and scientific breakthroughs.Johnson & Johnson has taken a decisive step in its oncology strategy with the $3 billion acquisition of Halda's cell death technology. This acquisition, focusing on the "hold and kill" bifunctional small molecule platform, is poised to enhance J&J's prostate cancer pipeline significantly. It underscores J&J's commitment to expanding its oncology portfolio through innovative platforms designed to improve therapeutic outcomes. The move highlights a broader industry trend toward personalized medicine and targeted cancer therapies, which are becoming pivotal in improving patient care.In another domain of cancer treatment, Nuvalent has unveiled promising Phase 1/2 data for its candidate neladalkib, which could position the company as a formidable competitor to Pfizer's established lung cancer drug, Lorbrena. The promising data might expedite regulatory discussions with the FDA, potentially leading to an accelerated approval process. This development illustrates the competitive landscape in oncology, where firms strive to introduce novel therapies with improved efficacy and safety profiles.The field of antibody-drug conjugates (ADCs) is also experiencing significant advancements. A San Diego-based biotech has secured $120 million in funding to develop a best-in-class ADC formula, with support from Merck & Co. This initiative aims to refine the precision and efficacy of ADCs by delivering cytotoxic agents directly to cancer cells while minimizing collateral damage to healthy tissues. Such innovations are crucial as they represent a new frontier in targeted cancer therapy.In terms of financial activities, Artios Pharma's successful $115 million Series D funding round is set to bolster its clinical efforts in exploring DNA damage response inhibitors for cancer treatment. These inhibitors target cancer cells' ability to repair DNA damage, holding potential for more effective therapies against resistant cancer types. Meanwhile, Sofinnova Partners' €650 million raise for biotech and medtech investments amid a volatile economic environment underscores continued investor confidence in life sciences despite market uncertainties.Bayer is making strategic moves in China by opening an incubator in Beijing. This facility will host local biopharma companies such as Suzhou Puhe Biopharma and Beijing Youngen Technology, fostering innovation and collaboration within China's burgeoning biotech landscape. Such initiatives reflect global efforts to leverage regional strengths and foster cross-border collaborations.On the operational side, Nxera Pharma is restructuring its workforce by laying off 15% of its staff as part of a strategic pivot towards profitability. This decision mirrors broader industry trends where companies refocus resources on core projects to streamline operations and enhance financial stability.A recent study has highlighted the impact of NIH grant cuts on clinical trials across the United States. Over 383 trials involving more than 74,000 patients have been disrupted due to funding terminations under the current administration. This situation raises concerns about the sustainability of clinical research funding and its implications for ongoing medical advancements.Jazz Pharmaceuticals has reported practice-changing Phase 3 results for its HER2-targeted drug Ziihera for gastroesophageal adenocarcinoma. These findings reaffirm Jazz's confidence in positioning Ziihera as a preferred first-line treatment option for HER2-positive cancers, poSupport the show

Turn online alignment into an offline community — join us at TheWayFwrd.com to connect with like-minded people near you. Have you ever wondered if your phone is quietly rewiring your brain? In this episode, I sit down with Tristan Scott, an electrical engineer turned health researcher who's helping build healthier technology at Daylight Computer. He bridges two worlds that rarely meet: the precision of electrical engineering and the intuition of human biology. And what he's discovered is that our digital tools might be draining more than just our attention. We explore why grounding and sunlight matter more than most people realize, what really happens when EMFs meet the body's own electrical system, and why "energy efficiency" might be costing us our health. Tristan is designing tech that respects human circadian biology instead of hijacking it at Daylight Computer. Because our bodies are already electrical systems, the question is whether we're working with that power or against it. You'll Learn: [00:00] Introduction [00:10:56] The surprising link between Bitcoin, health, and personal sovereignty [00:23:04] Why grounding into your power outlet may be harming you more than helping [00:45:20] The shocking truth about electromagnetic "mind control" experiments [01:03:43] How energy-efficient design quietly removed healing infrared light from our lives [01:09:52] Why working outdoors can literally recharge your biology [01:11:43] The hidden power of cold exposure and mitochondrial uncoupling [01:13:38] Why modern environments are breaking down the body's fourth phase water [01:48:41] When sensitivity returns, your body finally knows what's real [01:55:13] The real reason children lose themselves to screens, and how to fix it Resources Mentioned: Bitcoin and Beef by Tristan Scott | Book or AudiobookThe Way Forward episode on Tuning the Zodiac & Balancing Through Sound featuring Eileen McKusick | Listen NowThe Way Forward episode on The 4th Phase of Water: The Blueprint for Biological Energy with Dr. Gerald Pollack | Listen NowThe Invisible Rainbow by Arthur Firstenberg | Book or AudiobookDanny Hamilton's SunSense | WebsiteCross Currents by Robert Becker | BookThe Body Electric by Robert Becker & Gary Selden | BookThe Anxious Generation by Jonathan Haidt | Book or AudiobookPollock's Paper on Oxygen is an Electron Donor | TelegramThe Brain That Changes Itself by Norman Doidge M.D. | Book or AudiobookJoe Rogan Experience #1235 - Ben Greenfield | Spotify or AppleThe Creature from Jekyll Island by G. Edward Griffin | BookDecentralized Radio Podcast with Tristan Scott and Ryan Brown | Spotify or AppleAires Tech – EMF Protection Devices | WebsiteBio Geometry | Website Visit daylightcomputer.com and use the Code TWF50 for $50 Off. Become a Member of TWF, receive $75 off. Find more from Tristan: Daylight Computer | Website Daylight Computer | InstagramDaylight Computer Kids | WebsiteDaylight Computer Kids | InstagramTristan Scott | XTristan Scott | InstagramTristan Scott | Substack Find more from Alec: Alec Zeck | InstagramAlec Zeck | XThe Way Forward | Instagram   The Way Forward is Sponsored By: RMDY Academy & Collective: Homeopathy Made Accessible High-quality remedies and training to support natural healing.  Enroll here Explore here   New Biology Clinic: Redefine Health from the Ground Up Experience tailored terrain-based health services with consults, livestreams, movement classes, and more. Visit www.NewBiologyClinic.com and use code TheWayForward for $50 off activation. The Way Forward members get the $150 fee waived

This episode includes: #RateMyMeal, teacher makes club gains, oatmeal, nutrition while at theme parks, forearm training and new releases!Join The SwoleFam https://swolenormousx.com/membershipsDownload The Swolenormous App https://swolenormousx.com/swolenormousappMERCH - https://papaswolio.com/Watch the full episodes here: https://rumble.com/thedailyswoleSubmit A Question⁠ For The Show: https://swolenormousx.com/apsGet On Papa Swolio's Email List: https://swolenormousx.com/emailDownload The 7 Pillars Ebook: https://swolenormousx.com/7-Pillars-EbookTry A Swolega Class From Inside Swolenormous X: https://www.swolenormousx.com/swolegaGet Your Free $10 In Bitcoin: https://www.swanbitcoin.com/papaswolio/   Questions? Email Us: Support@Swolenormous.com

Being a caregiver for a loved one with MS isn't an easy job. And, while it may consume hours of your time, often, it's not your only job. Many caregivers are the only family members bringing in an income. So, in addition to their caregiving responsibilities, they may also be facing the responsibilities that go along with holding down a full-time job.  This week, Diana Grazio joins me to discuss how she balances her roles and responsibilities as her partner's caregiver while holding down a full-time job.  You have online opportunities tomorrow! Participate in the National MS Society's Hispanic LatinX MS Experience Summit, or catch the International Progressive MS Alliance's global webcast, How Existing Drugs Could Transform MS Treatment. We have all the info for you to register for either or both!   If you purchase your health insurance through the ACA Healthcare Marketplace, you've probably already been notified that your premiums will skyrocket in 2026. MS Activist, Sarah Quezada, shares how those premium increases will affect her family. Roche has announced the outcomes of Phase 3 clinical trials for Fenebrutinib and Relapsing MS, and Primary Progressive MS. It's positive news, and we have the details! Could nanoparticles penetrate the blood-brain barrier and deliver anti-inflammatory medication directly to the central nervous system?  University of Illinois researchers say yes! We're sharing the details. We have a lot to talk about! Are you ready for RealTalk MS??! This Week: It's National Family Caregiver Month  :22 The MS Care Partner Connection  :34 The National MS Society is hosting the Hispanic LatinX MS Experience Summit TOMORROW!  2:20 The International Progressive MS Alliance Global Webcast is TOMORROW!  2:51 Sarah Quezada shares how astronomical increases in ACA health insurance premiums will affect her family  3:46 Roche announces outcomes for Phase 3 clinical trials for Fenebrutinib and Relapsing MS, and Primary Progressive MS  11:59 Could nanoparticles penetrate the blood-brain barrier and deliver anti-inflammatory medication directly to the central nervous system?  13:43 Diana Grazio discusses how she manages her role as a caregiver while holding down a full-time job  16:07 Share this episode  29:10 Next week's episode  29:30 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/429 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com PARTICIPATE: Take the Shaping Tomorrow Together Online Survey https://s.alchemer.com/s3/Perspectives-on-MS SIGN UP: Become an MS Activist https://nationalmssociety.org/advocacy REGISTER: The Hispanic LatinX MS Experience Summit https://nationalmssociety.org/resources/get-support/education-programs-and-library/hispanic-latinx-ms-experience REGISTER: International Progressive MS Alliance Global Webcast https://msif.org/news/2025/11/03/alliance-webcast VISIT: The MS Care Partner Connection https://mscarepartnerconnection.com STUDY: Nanoparticle-Boosted Myeloid-Derived Suppressor Cell Therapy for Immune Reprogramming in Multiple Sclerosis https://www.science.org/doi/10.1126/sciadv.ady4135 JOIN: The RealTalk MS Facebook Group https://facebook.com/groups/realtalkms REVIEW: Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 429 Guests: Sarah Quezada, Diana Grazio Privacy Policy

In this conversation, we discuss the challenges and strategies involved in navigating the first building phase of muscle growth. We explore the psychological side of body image, the importance of mindset, and how nutrition supports long-term progress. We highlight the need for self-acceptance, the importance of managing expectations during physical changes, and the value of community support throughout the journey of personal growth and strength training. Find us on Instagram here: Level Up: https://www.instagram.com/levelup_podcast_/ Sharelle: https://www.instagram.com/sharellegrant/ Dani: https://www.instagram.com/daniantonellos/

The orexin receptor agonists are coming. After years of managing narcolepsy with stimulants, sodium oxybate, and wake-promoting agents, we soon will have medications that target the root cause of the disorder: the loss of orexin signaling. These new drugs—developed by Takeda, Alkermes, and Centessa—aren't just incremental improvements. They represent a genuine shift in how we understand and treat hypersomnolence disorders. In this episode, we will:Define what orexin is and why losing it destabilizes wakefulness, REM boundaries, muscle tone, and cognitionLearn how orexin agonists work—not as stimulants, but as replacement therapy for a missing neurotransmitterFind out why OX2R is the key receptor, and how selective agonists restore stable wakefulness, reduce cataplexy, and normalize attentionReview the available clinical data from the new wave of programs: oveporexton (Takeda), alixorexton (Alkermes), and ORX750 (Centessa)See what makes these drugs different from modafinil, amphetamines, solriamfetol, and oxybate therapiesLearn why Phase 1, Phase 2, and Phase 3 trials matter—with quick insights on how these drugs reached such strong resultsConsider safety and side effects, including what Hy's Law means and why regulators watch liver signals so closelyLook ahead to what these medications may mean for NT1, NT2, IH, and other hypersomnolence disorders in the coming yearsSpeculate why this class represents one of the most exciting moments in modern sleep medicineProduced by: Maeve WinterMore Twitter: @drchriswinter IG: @drchriwinter Threads: @drchriswinter Bluesky: @drchriswinter The Sleep Solution and The Rested Child Thanks for listening and sleep well!

This is the morning All Local update for November 17, 2025.

Recording date: 14th November 2025The precious metals sector is experiencing a convergence of favorable conditions that veteran investors describe as one of the best commodity setups in decades. At the recent Precious Metals Summit in Zurich, industry leaders including Pierre Lassonde, Frank Giustra, and Marc Faber highlighted observable market fundamentals supporting this outlook: global liquidity at record highs, structural demand emerging from technological infrastructure, and mining companies generating unprecedented cash flows while trading at reasonable valuations.Global liquidity continues expanding despite recent volatility. The People's Bank of China maintains liquidity injections, while the New York Fed has announced plans for substantial liquidity injection into US markets during Q1 2026. The recent government shutdown ending will release capital trapped in the treasury system for over a month. This liquidity expansion creates sustained support for precious metals as fiat currency purchasing power deteriorates.A less obvious but transformative demand driver emerges from artificial intelligence infrastructure development. The US needs to build at least 350 gigawatts of power dedicated to AI infrastructure—equivalent to 50 nuclear power plants—representing a trillion-dollar investment cycle for power generation alone. This excludes electrical grids, transmission infrastructure, and computing hardware. Recent government partnerships with Brookfield, Cameco, and Westinghouse for nuclear facility development signal the beginning of infrastructure spending requiring massive copper, steel, and concrete quantities while necessitating continued government liquidity injection supportive of gold prices.Third quarter 2025 results demonstrated the financial leverage inherent in gold mining operations. AngloGold Ashanti increased quarterly operating cash flow from $300 million to $1.4 billion—more than quadrupling while gold prices doubled. Even accounting for the Centamin acquisition contributing 20% of production, cash flow expansion significantly exceeds gold price appreciation. The company now operates with zero net debt, increased dividends, and strategic flexibility for acquisitions or capital returns while trading at roughly half the valuation of Agnico Eagle Mines despite comparable cash generation.K92 Mining offers equally compelling value, posting six consecutive quarters of free cash flow while organically funding construction of a complete new mill, twin declines, and associated infrastructure. The Phase 3 expansion completing commissioning in Q4 2025 will drive significant cash flow growth as throughput increases with minimal incremental operating costs. Operating costs scale favorably—an 800 tonne per day mill requires similar oversight as a 3,000 tonne per day mill. Market valuations have not yet reflected this coming cash flow expansion, creating opportunity for investors who understand the timeline and trust management execution.The M&A cycle is accelerating as producers with pristine balance sheets deploy capital. Recent examples include B2 Gold taking a 19.9% stake in Prospector Generator (now funded with $40 million for 2026 exploration), Probe Gold's acquisition, New Gold's pending takeover, and Gold Fields committing $50 million to junior investments. The competition for quality assets remains in early stages despite this activity.Investment opportunities span the market capitalization spectrum: established producers generating record profits at reasonable valuations, funded developers approaching major cash flow inflections, and well-backed exploration companies positioned for discoveries. Current Q4 volatility represents tactical entry opportunities before typical Q1 seasonal strength, with multiple fundamental drivers supporting sustained outperformance of real assets over the coming decade.Learn more: https://cruxinvestor.comSign up for Crux Investor: https://cruxinvestor.com

Matt is joined by Bloomberg's Lucas Shaw to investigate a historically bad fall season at the box office by highlighting which issues are actually real and which are insignificant. They look at larger industry-wide trends, like the shortening of theatrical windows and the rise of streaming, as well as smaller, more recent developments like releasing independent movies wide rather than platforming them. They discuss whether the "movie-star problem" excuse is overblown or legitimate, as well as if this could simply be explained by judging the actual quality of the films themselves (02:33). Matt finishes the show with an Academy Awards prediction after attending the premiere of Netflix's ‘Jay Kelly' (25:54). For a 20 percent discount on Matt's Hollywood insider newsletter, ‘What I'm Hearing ...,' ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠click here⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠. Email us your thoughts! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠thetown@spotify.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Host: Matt Belloni Guest: Lucas Shaw Producers: Craig Horlbeck and Jessie Lopez Theme Song: Devon Renaldo Learn more about your ad choices. Visit podcastchoices.com/adchoices

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a myriad of pivotal changes and advancements that have been shaping our industry.The competitive nature of acquisitions within the biopharma sector has been exemplified by recent strategic buyouts. Lundbeck's decision to outbid Alkermes for Avadel Pharmaceuticals highlights how companies are leveraging acquisitions to expand their capabilities and portfolios. Similarly, Pfizer's finalized acquisition of Metsera after a fierce bidding war with Novo Nordisk underscores the importance of securing valuable assets to strengthen positioning in critical therapeutic areas, such as obesity treatment, where demand continues to rise.Regulatory milestones remain at the heart of industry progress. Organon and Henlius's Poherdy recently received FDA approval as a biosimilar to Roche's Perjeta, offering a new treatment avenue for HER2-positive breast cancer patients. This approval is noteworthy as biosimilars play an essential role in oncology by providing similar efficacy to original biologics but at reduced costs, thereby enhancing healthcare affordability and accessibility. In Europe, the EMA's Committee for Medicinal Products for Human Use has endorsed several innovative drugs, including Otsuka's Dawnzera for hereditary angioedema and Lilly's Inluriyo for certain cancer types. These endorsements reflect the growing pipeline of treatments addressing both rare genetic disorders and widespread diseases.Merck & Co.'s acquisition of Cidara Therapeutics for $9.2 billion underscores a strategic pivot towards bolstering its antiviral portfolio. This deal is particularly significant given Cidara's promising influenza antiviral candidate, initially abandoned by Johnson & Johnson. In an era where infectious diseases pose ever-evolving challenges, Merck's investment in antivirals reflects a commitment to advancing therapeutic solutions in this crucial area.However, drug development's inherent uncertainties were highlighted by Bristol Myers Squibb and Johnson & Johnson's joint anticoagulant venture, which faced termination due to a Phase 3 trial failure. This setback emphasizes the challenges and risks entailed in developing novel therapeutics, particularly within high-stakes areas like cardiovascular health.Leadership changes can significantly impact corporate strategy, as seen with Bavarian Nordic following an unsuccessful private equity takeover attempt. Such shifts can influence investor confidence and reshape strategic directions.Investment trends also paint an optimistic picture for innovation within the sector. European life sciences investor Medicxi's successful raising of €500 million signifies robust financial support for biotech ventures. This influx of capital is vital for propelling early-stage research and development efforts across Europe, fostering breakthroughs in chronic and rare disease treatments.In terms of scientific innovation, advancements in bispecific antibody production through AI/ML-driven molecular design promise higher yields and enhanced quality. These technological innovations could revolutionize complex biologics manufacturing, potentially accelerating timelines and expanding therapeutic possibilities.The regulatory landscape is seeing significant activity as well. Notably, FDA officials introduced a novel pathway aimed at accelerating gene editing therapies' development and approval. By facilitating faster market entry for personalized medicines, this regulatory innovation could pave the way for treatments tailored to individual genetic profiles.Kyowa Kirin's collaboration with Kura Oncology reached a milestone with FDA approval for an oral medication targeting acute myeloidSupport the show

Right now, TSMC Arizona's completed Fab 21 Phase 1 consumes about 18,000 cubic meters of water every day. That's about 4.75 million gallons of water, each day. And there are two more phases coming up. Semiconductor manufacturing is water intensive and that has made some people anxious about TSMC's arrival to the Arizona desert. More than a few people have asked, "Don't these fabs use a ton of water? Why are we building them in the desert?" The answer of course is that Phoenix offers TSMC certain things that are not easily found elsewhere. Water is scarce there, sure. But it is not impossible to find, the amounts are manageable, and it can be recycled. Some claim the facility is stealing water from farmers. Saying, “You can't eat chips!” (Technically you can) The implication being we can only have one or the other. I don't think that's true. Farms use way more water than TSMC. In today's video, I want to revisit the fab in the desert and take a dip into the water situation.

Right now, TSMC Arizona's completed Fab 21 Phase 1 consumes about 18,000 cubic meters of water every day. That's about 4.75 million gallons of water, each day. And there are two more phases coming up. Semiconductor manufacturing is water intensive and that has made some people anxious about TSMC's arrival to the Arizona desert. More than a few people have asked, "Don't these fabs use a ton of water? Why are we building them in the desert?" The answer of course is that Phoenix offers TSMC certain things that are not easily found elsewhere. Water is scarce there, sure. But it is not impossible to find, the amounts are manageable, and it can be recycled. Some claim the facility is stealing water from farmers. Saying, “You can't eat chips!” (Technically you can) The implication being we can only have one or the other. I don't think that's true. Farms use way more water than TSMC. In today's video, I want to revisit the fab in the desert and take a dip into the water situation.

Sind steigende Löhne wirklich ein Gewinn für alle? Die Befürworter des Mindestlohns und seiner weiteren Steigerung verweisen auf den bisherigen Erfolg des Instruments. Und in der Tat hatte der deutliche Anstieg des Mindestlohnes seit seiner Einführung 2015 von 8,50 Euro je Stunde auf heute 12,82 Euro keinen messbaren negativen Effekt auf die Beschäftigung. Trotz einer durchschnittlichen Lohnsteigerung von 5 Prozent pro Jahr, die nach Inflation zu real rund 15 Prozent höheren Mindestlöhnen geführt hat. In den kommenden zwei Jahren soll der Mindestlohn um weitere 14 Prozent bis auf 14,60 Euro (2027) steigen. Die Optimisten erwarten auch künftig keine negative Beschäftigungswirkung, schließlich sei es doch nur gerechtfertigt, dass man von seinem Einkommen leben können muss. Wer könnte da schon widersprechen? Nur ist die Zeit der progressiven Entwicklung des Mindestlohns eine besonders gute Phase in der deutschen Wirtschaftsgeschichte gewesen. Daraus zu schließen, man könne einfach so weitermachen wie bisher, könnte sich als naiv erweisen.Besonders spannend: Daniel Stelters Gespräch mit Dr. Effrosyni (Efi) Adamopoulou, stellvertretende Leiterin des Forschungsbereichs „Ungleichheit und Verteilungspolitik“ am ZEW Mannheim. Sie erklärt, wie Mindestlöhne innerhalb von Unternehmen wirken, warum sie Produktivitätsschocks ungleich verteilen und weshalb Kurzarbeit eine bessere Antwort auf Krisen sein kann als Entlassungen. Eine Episode über die feine Balance zwischen sozialer Gerechtigkeit, Wettbewerbsfähigkeit und ökonomischer Vernunft.HörerserviceStudie Minimum Wages, Productivity, and Reallocation des IZA - Institute of Labor Economics finden Sie hier: https://is.gd/bnkMpCEconomist-Artikel What harm do minimum wages do? - Three decades of research have led to a rethink: https://is.gd/xM8vADStudie Minimum Wages and Insurance within the Firm des ZEW zum Mindestlohn: https://is.gd/pFndEo beyond the obviousNeue Analysen, Kommentare und Einschätzungen zur Wirtschafts- und Finanzlage finden Sie unter think-bto.com.NewsletterDen monatlichen bto-Newsletter abonnieren Sie hier.RedaktionskontaktWir freuen uns über Ihre Meinungen, Anregungen und Kritik unter podcast@think-bto.com.ShownotesHandelsblatt-Aktion vom 14. November bis 8. Dezember 2025 – Für alle, die schon länger mit einem Handelsblatt-Abo liebäugeln: Das gibt es jetzt für 12 Monate mit 50 % Rabatt – gedruckt oder digital. Mit fundierten Recherchen, starken Meinungen und exklusiven Hintergründen behalten Sie den Überblick über die wichtigsten Wirtschaftsthemen. Das Aktionsangebot finden Sie unter handelsblatt.com/podcast50. WerbepartnerInformationen zu den Angeboten unserer aktuellen Werbepartner finden Sie hier. Hosted on Acast. See acast.com/privacy for more information.

LSD shows promise for anxiety treatment. A Phase 2b clinical trial found that 100 micrograms of MM120 (pharmaceutical LSD) reduced anxiety significantly with lasting effects Study results were encouraging. Researchers noted that 65% of participants experienced clinical response at optimal dosing, with 47.5% achieving remission that sustained through 12 weeks of follow-up Safety profile was manageable. Most side effects occurred during dosing sessions and resolved quickly, with visual changes and nausea being most common under medical supervision Note that LSD remains illegal. It is currently classified as Schedule I controlled substance, accessible only through approved clinical trials, with results of Phase 3 trials expected by 2026 In the meantime, natural anxiety alternatives exist. Breathing techniques like nasal breathing, horizontal breathing patterns, and controlled breathing practices can help manage anxiety symptoms without medication

durée : 00:19:08 - L'invité de 8h20 - Benjamin Stora, historien, professeur émérite des universités, président de la partie française de la commission mixte des historiens algériens et français, dernier ouvrage avec Thomas Snegaroff “France, Algérie. Anatomie d'une déchirure” (Les Arènes) est l'invité de 8h20. Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

For the second time in 4 weeks, Jim "Smitty" Smith joins Joe for an "off the cuff" podcast conversation! Specific topics discussed include: Behind-the-scenes insight into Phase 2 of Built Different; A nuanced approach to training variability (and programming in 4-week blocks); 3 things that the "happiest people in the world" always have; Valuable gym lessons from high achievers; How to get your weaker limb stronger in record time; Remembering Mike Mentzer; The difference between "science-based coaches" & "science-based KIDS"; How to blow up your biceps in ONE iNsAnE set...And so much more! *For a full list of Show Notes + Timestamps visit www.IndustrialStrengthShow.com. IMPORTANT LINKS Team Forever Strong [FREE Trial] Iron Business Blueprint [Apply Now] Smitty's Instagram Joe D's Instagram Manukora Honey

Carl Rivera is the Chief Design Officer at Shopify, where he previously led both Merchant Services and the Shop App as VP of Product. Before joining Shopify through its acquisition of Tictail, Carl was the co-founder and CEO of Tictail, the "Tumblr for e-commerce," where he built one of the most beloved design-forward commerce platforms of its era. AGENDA: 05:05 Biggest Lessons from Selling My Company to Shopify 09:55 Where Does Shopify Suck at Product: Lessons from that? 17:37 What makes Truly Great product Design: The Five Pillars 31:02 The Future of Design in an AI-Driven World 36:00 Do We Skip the Design Phase in AI: Figma's Evolving Role in Design 40:09 Remote Work vs. In-Person Collaboration: Where Remote Loses? 42:43 What Happens to the Vibe Coding Market 47:06 Product Management and Team Dynamics 59:48 Does AI Favour Incumbents or Startups  

Send us a text if you want to be on the Podcast & explain why!Most new trainers don't fail because they're lazy—they fail because they were set up to memorize, not to coach. We sit down with Cori, a dedicated runner navigating NASM overwhelm, and turn tangled chapters into clear, usable coaching. You'll hear how to translate planes of motion into exercises you can demo immediately, how to spot agonists and antagonists without guessing, and how to use synergists and stabilizers to make your cues land.We walk through the OPT model the way hiring managers want to hear it: Phase 1 builds control and competency, Phase 2 pairs stable with less stable for smarter supersets, Phase 3 drives muscle, Phase 4 loads heavy for strength, and Phase 5 blends power and strength with purpose. You'll get a no-fluff take on energy systems and fiber types—anchored to duration and intensity—so exam questions become quick wins. Then we make assessments useful: identify what “arms fall” and “knees cave” really mean, apply the red-versus-green muscle lists, and choose fixes that actually change movement. Foam roll and stretch what's tight, strengthen what's sleepy, and cue breathing and bracing so reps look and feel better.Safety and screening matter, so we hit the essentials: PAR-Q, hypertension basics, the SA node, and knowing when to refer out. More importantly, we show how hands-on learning, live feedback, and mentorship build confidence faster than any textbook—because clients won't ask about amortization, they'll ask for results. If you've been grinding through chapters and still feel stuck, this conversation gives you a study map, coaching language, and a training method you can use tomorrow.If this helped you see the path more clearly, follow the show, share it with a trainer friend, and leave a quick review—it helps more future coaches find their footing.Want to ask us a question? Email email info@showupfitness.com with the subject line PODCAST QUESTION to get your question answered live on the show! Our Instagram: Show Up Fitness CPT TikTok: Show Up Fitness CPT Website: https://www.showupfitness.com/Become a Personal Trainer Book (Amazon): https://www.amazon.com/How-Become-Personal-Trainer-Successful/dp/B08WS992F8NASM / ACE / ISSA study guide: https://www.showupfitness.com/collections/nasm

"All you folks that want $5,000 gold and $10,000 gold — be careful what you wish for. That's not the kind of world you want to live in." — Frank GiustraIn today's interview with Daniela Cambone at the Precious Metals Summit in Zurich, Giustra delivers a masterclass on the seismic shifts reshaping global finance, the explosive run in gold, and the looming battle for monetary supremacy.He argues that the weaponization of the U.S. dollar has fueled an unstoppable de-dollarization trend, paving the way for a China-led “digital superhighway” that could challenge the dollar's global standing. Giustra breaks down why efforts to “dollarize” other economies are a non-starter — and why the real threat to U.S. dominance may be the gold-backed system already taking shape across the Global South.✅ FREE RESOURCESDownload The Private Wealth Playbook — a data-backed guide to strategically acquiring gold and silver for maximum protection, privacy, and performance. Plus, get Daniela Cambone's Top 10 Lessons to safeguard your wealth (FREE)

The Friday Five for November 14, 2025: iPhone Pocket Brings Back… Pockets. CMS Rural Health Transformation Program Government Shutdown Update Most-Favored Nation Drug Pricing CMS GENEROUS Model   Get Connected:

Welcome to the NeurologyLive® Mind Moments® podcast. Tune in to hear leaders in neurology sound off on topics that impact your clinical practice. In this episode, "NEALS 2025: Takeaways That Matter for ALS Care," ALS experts Jinsy Andrews, MD, MSc, and James Berry, MD, MPH, reflect on key themes from the 2025 NEALS Annual Meeting, now reintroduced as the Network of Excellence for ALS. They discuss format changes that elevated lightning science, the expanding gene therapy pipeline, and a growing slate of NEALS-affiliated trials. The conversation highlights updates from the HEALEY Platform Trial, the MY-MATCH biomarker-guided precision trial, SOD1 program data, and new antisense and viral vector therapies aimed at sporadic ALS. They also explore the impact of Act for ALS on trial access, the ALL ALS biospecimen repository, and NIH-supported expanded access cohorts. The discussion closes with insights on combination therapy strategies, genetic subtypes, presymptomatic enrollment, and how new collaborations, digital endpoints, and infrastructure advances are shaping momentum heading into 2026. Looking for more Neuromuscular discussion? Check out the NeurologyLive® Neuromuscular clinical focus page. Episode Breakdown: 1:05 – Reflections on meeting highlights and NEALS rebranding into a global network 5:00 – Notable NEALS-affiliated trials and promising new mechanisms in ALS care 12:45 – Combination therapy strategies and future approaches in ALS research 15:20 – Neurology News Minute 18:00 – Expanding clinical trial access for rare and genetic ALS subtypes 22:10 – Building momentum and expectations for the 2026 NEALS Annual Meeting The stories featured in this week's Neurology News Minute, which will give you quick updates on the following developments in neurology, are further detailed here: FDA Approves Doxecitine and Doxribtimine Combination Therapy as First Treatment for Thymidine Kinase 2 Deficiency Supplemental New Drug Application Submitted for AXS-05 as Treatment for Alzheimer Disease Agitation BTK Inhibitor Fenebrutinib Meets Primary End Points in Phase 3 Trials for Both Relapsing and Primary Progressive MS  Thanks for listening to the NeurologyLive® Mind Moments® podcast. To support the show, be sure to rate, review, and subscribe wherever you listen to podcasts. For more neurology news and expert-driven content, visit neurologylive.com.

We had a few technical issues with last week's broadcast so we've cut to the chase and brought you a mini episode featuring the launch of Phase 3 of our Safeguarding work. You can donate to the podcast via our Paypal link @21stCenturySaints or via https://donorbox.org/21st-century-saints-fundraiserDon't forget to subscribe to our channel here on YouTube. You can also like our Facebook page https://www.facebook.com/21stcenturysaints

14 Nov 2025. Dubai Chambers is heading to the US, opening its first American office in New York, an announcement made at the Dubai Business Forum. Executive reporter Georgia Tolley speaks to H.E. Eng. Sultan Bin Saeed Al Mansoori about what this means for global trade ties. Plus, with the Dubai Airshow just days away, we check in with DXB Airport CEO Paul Griffiths on what to expect. And Parsons has secured a 56-million-dollar contract for Phase 2 of the Diriyah development, we hear what’s next for one of Saudi Arabia’s biggest giga-projects.See omnystudio.com/listener for privacy information.

For the second time in 4 weeks, Jim "Smitty" Smith joins Joe for an "off the cuff" podcast conversation! Specific topics discussed include: Behind-the-scenes insight into Phase 2 of Built Different; A nuanced approach to training variability (and programming in 4-week blocks); 3 things that the "happiest people in the world" always have; Valuable gym lessons from high achievers; How to get your weaker limb stronger in record time; Remembering Mike Mentzer; The difference between "science-based coaches" & "science-based KIDS"; How to blow up your biceps in ONE iNsAnE set...And so much more! *For a full list of Show Notes + Timestamps visit www.IndustrialStrengthShow.com. IMPORTANT LINKS Team Forever Strong [FREE Trial] Iron Business Blueprint [Apply Now] Smitty's Instagram Joe D's Instagram Manukora Honey

Hello Beloved. In a world where our attention spans are shrinking, true hope for our livelihoods—and our lives—emerges when we step beyond binary thinking. Embracing shades of gray opens the door to richer, more nuanced perspectives on every situation.By accepting that multiple truths can coexist, we lift the crushing weight of forcing every decision into a rigid right-or-wrong box.Nurturing trust in our intuition and inner wisdom erodes the compulsion for constant external approval or lengthy defenses.This quiet inner confidence fortifies the seamless harmony of body, mind, heart, and soul, while awakening our natural capacity to weather doubt and exhaustion.What Holds Us Back from Revelations of Self-CompassionThe Moment Everything Changes — exists at a threshold in a moment when the familiar path and the unknown future collide. Here, we stand at the Choice Point.It's not a single decision. It's a recurring crossroads where we face the most primal question: Asking: Do I stay with what I know, or do I step toward what calls me?The First SOVEREIGN SOUNDS SERIES Podcast showcases the etymological breakdown (more fun than you think - super empowering) through the story of Florence Nightingale back in 1854, choosing to leave her comfortable English life to revolutionize medicine in a war-torn hospital that told through the ETYMOLOGY of “COMPASSION".”If you want to hear and transform your relation to this word, you can upgrade at any point to unlock The Light Between Oracle App + Private Episodes where I channel these downloads. Dismantling the Four Walls of Self-DoubtYou face it every time you consider leaving a job, ending a relationship, speaking a truth, or claiming your authentic self.The Choice Point is where transformation begins. But it's also where most of us freeze.Understanding the forces that keep us paralyzed at the threshold—and more importantly, how to move through them—is the work of reclaiming our power.The Four Walls of the PrisonFear of the Unknown: The Primary ObstacleFear is the gatekeeper of the Choice Point.Not the fear of failure or consequences—though those exist. The deepest, most paralyzing fear is the fear of not knowing what comes next. Our nervous systems are wired for certainty. Uncertainty triggers our threat-detection systems.When we contemplate the unknown, our amygdala fires. Our breath shortens. We retreat to what we know, even if it's painful, because painful and known feels safer than uncertain and new.This is why people stay in unfulfilling jobs, relationships that drain them, and lives that don't fit. The devil you know is more manageable than the devil you don't.The truth: The unknown is not dangerous—it's just unfamiliar. And familiarity is not safety; it's often just habit wearing the mask of security.Attachment to Past Patterns and “Known Suffering”There's a paradox at the heart of human psychology: We become attached to our pain.Our wounds become our identity. Our limiting beliefs become our armor. The story we've told ourselves for years—“I'm not worthy,” “I'm too broken,” “People like me don't get to have that”—becomes so familiar that it feels like truth.When offered the possibility of transformation, we unconsciously cling to the pattern. Because at least we know how to survive it. At least there's a narrative. At least there's a reason.This is what psychologists call the “comfort in suffering”—the twisted familiarity that makes even pain feel like home.The Choice Point asks us to grieve what we're leaving behind, even if it was killing us. And that grief is real. That loss is real. Even when the old pattern was destructive, letting it go means losing an identity we've spent years constructing.The truth: Healing requires grieving. But the cost of staying is always higher than the cost of going.Narrow Paths vs. Opening to Infinite PossibilitiesHere's something CRITICAL and why active concious thinking is foundational. Our minds are pattern-recognition machines designed for efficiency, not expansion.The mind works by creating neural pathways. The more we travel a particular thought or behavior, the deeper the groove becomes. Over time, these grooves feel like the only paths available. The mind literally cannot perceive possibilities outside these worn tracks.This is called “cognitive narrowing,” and it's hardwired into our neurology.When faced with a Choice Point, the mind does what it's trained to do: it generates only the solutions it's already mapped. It says, Here are your three options” when actually there are 300. It insists, “This is realistic” while dismissing what's possible as fantasy.We are collectively re-aligning the “all is mind.”The Choice Point isn't just about willpower or courage. It's about expanding the mental field itself—opening to possibilities the conditioned mind cannot yet perceive.This requires what we might call a “frequency shift”—a change in consciousness that literally opens new neural pathways and allows previously invisible solutions to appear.Trust: The Key That Unlocks the TransitionAll three obstacles—fear, attachment, and mental narrowing—lock together into one immovable wall: lack of trust.Trust in ourselves. Trust in the process. Trust that the ground will hold us when we take a step into the unknown.Without trust, we're trying to move through the Choice Point while our nervous system screams “danger.” We're negotiating with fear rather than transcending it.But trust isn't blind faith. It's not ignoring real risks or pretending danger doesn't exist.True trust is remembering that you've already survived every difficult moment in your life. You've moved through uncertainty before. Your body knows how to adapt. Your spirit has weathered storms you thought would destroy you.Trust is recognizing that there's an intelligence working through you—not just your rational mind, but your intuition, your embodied wisdom, your spiritual knowing. Align with that larger intelligence and each Choice Point becomes navigable.This is where language transforms the nervous system itself. When we reclaim the word Trust from its distorted meanings—blind obedience, naïveté, passivity—and return it to its root (a Germanic word meaning “to comfort” or “to strengthen”), we literally change our nervous system's response to the unknown.The truth: You have everything you need to move through the Choice Point. You just need to remember it.The Evolution of Language: How We Lost Our WayFrom Collective Intuition to Fragmented Mind - our ancestors didn't face the Choice Point as we do.Early human societies operated from a place of collective intuition—a kind of group consciousness where decisions emerged from shared sensing rather than individual analysis. Bodies, hearts, and minds moved as one intelligence.There was no paralyzing individual choice. There was knowing. A seamless trust in the collective direction.Then came language.Language was revolutionary and traumatic simultaneously.Words gave us the ability to communicate across time and space. They allowed civilization to build. But they also fragmented us. Words separated the knower from the known. They created subject and object, self and other, safety and danger.As language developed, it slowly replaced embodied knowing with mental analysis. We stopped trusting our gut. We started overthinking. We moved from intuition to ideology.By the time we reached the Enlightenment, trust in the mind had become supreme—and trust in the body, intuition, and collective wisdom had atrophied almost completely.This is why the Choice Point feels so isolating and terrifying now. We're making the decision alone, with only the overthinking mind as our guide. We've lost access to the embodied wisdom and collective knowing that would make the transition feel natural.The Body, the Heart, and Language All Different Channels of KnowingHere's a crucial distinction: The body and mind speak different languages.The body knows through sensation and intuition. It receives information instantaneously—what some call “gut feeling” or “heart knowing.” This wisdom doesn't require analysis. It just is.The mind knows through logic, language, and analysis. It requires evidence, reasoning, and time to process.Neither is superior. They're complementary intelligence systems.But as language became the dominant channel of communication, the body's wisdom became marginalized. We learned to doubt our gut. We were told to “think logically” and ignore our feelings. We were trained to second-guess intuition and defer to external expertise.This created a crisis at the Choice Point: We're using only half our intelligence to make full-life decisions.The path through the Choice Point requires both channels:The mind to discern the practical details and logistics The body to feel the rightness or wrongness of the direction The heart to connect with why this choice matters The spirit to sense the alignment with our larger soul purposeWhen all four are integrated, the Choice Point becomes a place of clarity rather than paralysis.Language as a Living Entity: How Words Shape Our ChoicesHere's where things get deeply revolutionary: Language is not fixed. It breathes.Words are living frequencies that carry the imprint of human consciousness across time. When a culture shifts, words shift with it. And when we understand how a word has been distorted, we can reclaim its original power.Consider how certain words—like Trust, Faith, Surrender, Intuition—have been shaped and twisted by different historical periods.Medieval Europe: Trust was tied to God and divine order. There was a collective framework holding the trust.Industrial Revolution: Trust narrowed. It became about institutions and external authority. Trust in the system. Trust in the expert. Trust in the hierarchy.Modern Era: Trust fragmented further. We distrust institutions. We distrust expertise. We distrust each other. And most dangerously, we distrust ourselves.The result: We're trying to move through the Choice Point with no trust at all.And, my beloved…. here's the liberation: By understanding how the word has been distorted, we can restore its original frequency.When we trace Trust back to its roots—to mean “to comfort,” “to strengthen,” “to hold steady”—we access a different nervous system response. We're not just intellectually deciding to trust. We're activating a frequency in our body that remembers trust as a felt experience, not a concept. Words are spells and shape consciousness.The Architecture of the Choice Point: Three PhasesTransformation at the Choice Point unfolds in distinct phases:Phase 1: Awareness (The Recognition)You begin to see that the current path no longer fits. Something is calling. The discomfort that once seemed normal now feels intolerable.This is where most people get stuck—they see the problem but convince themselves to adjust to it rather than change it. They re-narrate the suffering as meaningful. They spiritualize their dysfunction.True awareness requires honest grief: admitting that something in your life is not working.Phase 2: The Threshold (The Fear)You stand at the actual Choice Point. The old path is visible behind you. The new path is invisible ahead of you.This is where all four obstacles crystallize: Fear screams Attachment pulls backward The mind insists the new path doesn't exist Trust evaporatesThis phase is not meant to be comfortable. Discomfort at the Choice Point is a sign of integrity, not a sign to turn back.Phase 3: The Leap and Landing (The Integration)You move through. The ground holds. You begin to integrate the new frequency. The new path becomes visible as you walk it—not before.Most people want to see the entire new path before they step forward. But that's not how transformation works. We get vision as we move, not before.Four Practices for Moving Through the Choice Point* Embody Your BodyPractice feeling sensation without narrative. Place your hand on your heart. Notice: What does your body know that your mind hasn't admitted yet?Your body doesn't lie. It carries wisdom your mind has trained itself to ignore.Reclaim Trust as a FrequencyRepeat: “I remember the word. I reclaim the root. I restore the power.”Place your hand on your heart and feel what trust actually feels like—not as a concept, but as a sensation of being held, strengthened, comforted.* Expand Your Mental FieldAsk: “What possibilities exist beyond what I can currently imagine?”This simple question opens neural pathways. It signals your brain that there are more options than the three the conditioned mind has offered.Connect to Collective KnowingYou don't have to figure this out alone. There's an intelligence working through human history, through your bloodline, through the zeitgeist of this moment.Ask: “What wants to emerge through me? What is my soul's larger purpose in this transition?”Express Your Choice Point ExerciseIn Closing: While the new paradigm hasn't fully materialized yet. We're all standing in the threshold together.The opportunity is that we're not paralyzed alone anymore. We're standing at the threshold with millions of others who are also choosing to evolve. The Mantra for the Choice PointAs you contemplate your own threshold, return to this again and again:I remember: My body knows. My intuition knows. My spirit knows. I've survived every difficult moment. I have access to more wisdom than my overthinking mind.Surrender as power, not weakness.Intuition as light intelligence, not fantasy.I restore: The power to choose. The power to transform. The power to walk into the unknown and have it become known as I move. CHOOSE to Deepen Your ExplorationThis deep exploration is a small reflection of The Sovereign Sounds Series Podcast that creates one word as a conceptual map of a Choice Point. The vertical energetic origin and the horizontal effects through time as it became a frequency of power over and power under. The Choice Point is calling. Trust is the key. And you have everything you need to move through.Incantations and Reflections for IntegrationAs you sit with this exploration, journal on:* Where am I standing at a Choice Point right now—even if I haven't fully admitted it?* What pattern am I most attached to, even though it no longer serves me?PS: Be on the lookout for the first privast podcast drop and over $258+ intuitive enriching resources to help you on your evolutionary journey. Join and upgrade HERE!Kassandra Get full access to The Light Between at thelightbetween.substack.com/subscribe

We had a few technical issues with last week's broadcast so we've cut to the chase and brought you a mini episode featuring the launch of Phase 3 of our Safeguarding work. You can donate to the podcast via our Paypal link @21stCenturySaints or via https://donorbox.org/21st-century-saints-fundraiserDon't forget to subscribe to our channel here on YouTube. You can also like our Facebook page https://www.facebook.com/21stcenturysaints

Buy/Stream: https://overview.fanlink.tv/OVR118-Phase Widely acclaimed Belgian producer Phase steps forward for his Overview Music debut, the incredible ‘Blinded EP'. No stranger to heavy club orientated Drum & Bass, Phase embarks further into this territory, experimenting with new mid range led synth work, resulting in some of his most aggressive yet distinct music yet. Out 14.11 Phase Instagram → https://www.instagram.com/phasednb Facebook → https://www.facebook.com/phasednb Soundcloud → https://soundcloud.com/phasednb Overview Music Patreon → https://patreon.com/overview Facebook → https://facebook.com/overviewuk Instagram → https://instagram.com/overviewuk Soundcloud → https://soundcloud.com/overviewuk YouTube → https://youtube.com/@OverviewMusic

Mike Maloney: Gold, Silver Bull Run in Final Phase, I Expect "Spectacular" Prices Mike Maloney of ‪@Goldsilver explains why this time really is different for gold and silver, pointing to factors including growing mainstream adoption, and noting that much more of the world's population is able to buy precious metals than in previous cycles. "This is just like a whole new world — this to me signals the beginning of the third and final phase of the bull market — and that is where you have the greatest amount of gains in the shortest period of time. So we should be seeing some fireworks coming," he said.   Watch this video at- https://youtu.be/Yl7B9tFCicY?si=JktrazBIo4z-WbCT Investing News 59.9K subscribers 14,720 views Nov 11, 2025 #Investing #Gold #Silver ❓ Is the gold-silver ratio part of your buying strategy? Tell us in the comments! Read free chapters of Mike's book: https://ggsr21.com/ This interview was filmed on November 3, 2025. #Investing #Gold #Silver 0:00 - Intro 1:20 - This time is really different 4:47 - Final phase of bull market 7:49 - "Giant crisis" in the works 11:21 - Trigger for market crash 13:15 - Farmland offers protection 15:25 - Gold-silver ratio strategy 19:47 - Gold, silver price potential 23:11 - Outro ________________________________________________________________ Investing News Network (INN) Find out more about investing by INN @ https://investingnews.com/ Browse our 2025 outlook reports: http://bit.ly/3JHyR1M Follow us on Facebook:   / investing.news.your.trusted.source   Follow us on Twitter: https://x.com/inn_resource

In this episode, ARK's Cathie Wood and Brett Winton sit down with Sean McClain, Founder and CEO of AbSci, to explore how generative AI is reshaping drug discovery, development timelines, and clinical costs. Sean walks through real-world examples of AI-designed antibodies—such as AbSci's breakthrough HIV antibody and a regenerative treatment for hair loss—and explains how these platforms are helping unlock previously “undruggable” biology.They discuss AbSci's Phase 2-ready hair growth antibody (BS201), the company's partnerships with Caltech and AMD, and why the FDA's evolving embrace of AI could accelerate the end of animal testing. The conversation closes with a forward-looking discussion on the role of regenerative medicine in longevity—and why AI drug discovery might just pull biotech out of its multi-year bear market.Key Points From This Episode:(00:00:00) How AbSci uses generative AI to design antibodies from scratch(00:02:42) HIV, ion channels, and the promise of targeting "undruggable" biology(00:06:28) AbSci's BS201 drug for hair regrowth: mechanism, speed, and cost advantages(00:13:20) Clinical timeline: From concept to Phase 2 readout in 3.5 years(00:15:34) Bringing costs down: $100–150M vs. the industry average of $2.4B(00:17:36) Why AI enables “keys designed for specific locks” in drug targeting(00:22:58) What AbSci's models are trained on—and how prompts work in drug inference(00:25:32) The future of clinical testing: AI replacing animal models(00:36:43) Sarcopenia, strength loss, and regenerative approaches to aging(00:48:10) BS201 as a long-acting pulse therapy—and how it compares to transplants

Welcome back for another dose of the Refill! Bringing you the latest insights and news in the world of mental health and pharmacy. If you want more tips and conversations about mindfulness, and mental health, checkout the Mindful PharmD Podcast on major platforms. Connect with me --> https://drmatmonharrell.bio.link/Written by Dr. Matmon Harrell ReferencesNBC News. After a suicide attempt, doctors told the Benz-Bushlings their son needed residential treatment; insurance denied his mental-health treatment anyway. (2025). NBC News. Insurance denied his mental-health treatment anyway. Retrieved from https://www.nbcnews.com/health/mental-health/insurance-denied-psychiatric-inpatient-mental-health-treatment-rcna230207MSN. FDA advisors explore a possible future with chatbot mental-health care. (2025). MSN. FDA advisors explore a possible future with chatbot mental-health care. Retrieved from https://www.msn.com/en-us/health/other/fda-advisors-explore-a-possible-future-with-chatbot-mental-health-care/ar-AA1QbcE3?ocid=BingNewsVerpSickle Cell Anemia News. Sickle Cell Anemia News. (2025). Hydroxyurea doesn't ease sleep issues in children with SCD: Study Retrieved from https://sicklecellanemianews.us5.list-manage.com/track/click?u=52c64784d386bd00ea57ee792&id=500eedf533&e=dcba61ae7aSickle Cell Anemia News. (2025). Newsletter item: First SCD patient enrolled in Phase 1b trial of oral therapy iadademstat. Retrieved from https://sicklecellanemianews.us5.list-manage.com/track/click?u=52c64784d386bd00ea57ee792&id=50c6873aa4&e=dcba61ae7aSubscribe. Share. Rate.A thousand thanks!drmatmonharrell.bio.link Hosted on Acast. See acast.com/privacy for more information.

13 Nov 2025. Dubai Exhibition Centre’s AED 10 billion expansion is powering ahead, with Phase 1 on track for completion in Q1 2026. We speak to the man leading the push, Amer Al Farsi, Vice President of Real Estate Development at DWTC, about what’s coming and why it matters for Dubai’s events economy. Plus, Dubai’s residential construction cycle is reportedly compressing, but what does that actually mean for developers, buyers and delivery timelines? Zacky Sajjad of Cavendish Maxwell breaks it down.See omnystudio.com/listener for privacy information.

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of compelling updates that underscore the dynamic nature of our industry, marked by scientific breakthroughs, strategic shifts, regulatory advancements, and more.Starting with Pfizer's ambitious endeavors in oncology, the company has initiated Phase 3 trials for its bispecific antibody PF-08634404, targeting non-small cell lung cancer. This innovative approach aims to supersede Keytruda by simultaneously targeting the PD-1 and VEGF pathways, crucial in tumor growth and immune evasion. Pfizer is making substantial strides with its PD-1xVEGF bispecific antibodies by announcing seven near-term trials, including a pivotal phase 3 trial comparing this agent to Keytruda in non-small cell lung cancer. This underscores Pfizer's commitment to developing next-generation immunotherapies that could redefine cancer treatment paradigms by offering more targeted options. The implications are significant; by enhancing therapeutic efficacy through this dual-targeted strategy, Pfizer could set new standards in lung cancer treatment, potentially improving patient outcomes and redefining first-line therapies.Meanwhile, a strategic merger between Mallinckrodt and Endo has culminated in a $6.7 billion transaction, resulting in the rebranding of the combined entity as Keenova. This merger is particularly notable for its decision to spin off the Par Health generics business. Such a move indicates a focused shift towards specialty pharmaceuticals aimed at rare diseases—a trend increasingly seen across the industry as companies pivot towards niche markets with high unmet needs.In financing news, Vor Bio's successful $100 million public offering highlights growing investor confidence in companies addressing autoimmune diseases. This capital will likely accelerate Vor Bio's clinical-stage programs, potentially transforming patient care in this challenging therapeutic area through new and effective treatments.On the regulatory front, Glenmark's Ryaltris has secured approval from China's National Medical Products Administration for treating moderate to severe allergic rhinitis. This approval is pivotal as Glenmark expands its footprint in respiratory therapeutics with innovative small molecule therapies designed to alleviate allergy symptoms—a sign of their strategic growth within this domain.Recent clinical trial results also offer promising news. CeleCor Therapeutics' zalunfiban has shown Phase 3 success for segment elevation myocardial infarction, while UbiVac's DPV-001 has demonstrated improved survival rates in head and neck squamous cell carcinoma. Engene's Detalimogene voraplasmid exhibited a 63% response rate in bladder cancer patients unresponsive to BCG therapy. These findings reflect ongoing advances in targeted therapies and personalized medicine approaches that continue to reshape the oncology landscape.In policy changes, the UK government has unveiled a five-year roadmap aimed at replacing animal testing with AI and 3D tissue models. This initiative marks a pivotal shift towards more ethical and technologically advanced methods in drug development, potentially accelerating discovery processes while reducing reliance on animal models—a significant move that aligns with global trends towards more humane scientific practices.Meanwhile, Richard Pazdur's appointment as director of the FDA's Center for Drug Evaluation and Research signals strategic leadership changes amidst ongoing organizational investigations. His extensive experience in oncology is expected to guide regulatory oversight during this transformative period for the agency. Dr. Richard Pazdur's appointment as director of CDER representsSupport the show

In the second part of this two-part series, Dr. Bradley Ong explains the four clinical phases of a typical migraine attack.  Show citation:  Lipton RB, Stokes J, Evans CJ, et al. Characterizing the patient experience during the prodrome phase of migraine: A qualitative study of symptoms and their timing. Headache. 2025;65(8):1355-1368. doi:10.1111/head.15024 

Explore expert tips for post-operative ACL rehab, including avoiding pitfalls like lacking extension & recommended biofeedback units. Q: What is your favorite phase of post-operative care for ACL repair? A: Phase 2 is a favorite because the athlete is getting off the table, which is exciting both mentally and physically. During this phase, significant gains are made, and progress continues toward returning to running. Q: What is your biggest tip to avoid pitfalls, such as lacking extension, in post-operative care? A: Consistently checking and actively feeling for extension daily is crucial. Make it a habit and an integrated part of the treatment flow to catch any issues early. Even a little bit of load when athletes start doing more of their daily activities can affect extension, so early detection is key. Q: Is lacking extension from one treatment to the next a red flag? A: It is not necessarily a red flag, but it should definitely be noted. This observation prompts consideration of what might have changed between sessions that could have caused the lack of extension. For example, it might indicate that too much activity was introduced. Q: Should fibular head mobilizations be immediately used for lacking extension? A: No, one should not immediately jump to using fibular head mobilizations. However, they can be a successful intervention in certain cases. Q: Can this ACL rehabilitation program be used for other surgeries? A: The framework of this ACL rehabilitation program can definitely serve as a guide for other knee surgeries. However, modifications are necessary based on the specific structures that have been surgically altered. For example, a meniscus repair would require avoiding weight-bearing, unlike an isolated ACL reconstruction. Q: What biofeedback units do you recommend? A: I recommend Mtrigger. It's an app-based unit with an easy setup, and it can be used more functionally beyond just table exercises. Additionally, it is versatile and can be applied in various other post-operative cases.

In this segment, Mark is joined by David Stokes, the Director of Municipal Property at the Show Me Institute. He shares his thoughts on Governor Kehoe's plan to phase out Missouri's income tax and more.

In part one of this two-part series, Dr. Bradley Ong discusses the prodrome phase of migraine and how it represents the earliest stage of the attack.  Show citation:  Lipton RB, Stokes J, Evans CJ, et al. Characterizing the patient experience during the prodrome phase of migraine: A qualitative study of symptoms and their timing. Headache. 2025;65(8):1355-1368. doi:10.1111/head.15024 

Puny Podians Assemble! Ryan and David are back in the Super Secret Spoiler Show vault, this time diving into Iron Man 3—the movie that kicked off Phase 2 and split fans faster than Tony's suits falling apart mid-flight. They're breaking down Shane Black's snarky, Christmas-set spin on the Iron Avenger: the Mandarin twist, PTSD Tony, an army of exploding Extremis soldiers, and a whole lot of suits. From Iron Man 3's divisive legacy to its surprising emotional depth, this episode covers what worked, what whiffed, and why it still sparks debate across MCU fandom. Plus, the usual SSSS chaos—Skrull of the Movie, product placement awards (looking at you, Audi), facial hair rankings, and the eternal question: which role would Nicolas Cage absolutely overact to perfection? Whether you think Iron Man 3 is underrated brilliance or Tony's weakest link, this spoiler-filled deep dive is loaded with armor, attitude, and absurdity. Hit play and let's power up! Learn more about your ad choices. Visit megaphone.fm/adchoices

Bei Gesprächen über die Gaza-Friedenspläne in Jerusalem haben US-Sonderberater Jared Kushner und Israels Regierungschef Benjamin Netanjahu sowohl über die derzeitige erste Phase, als auch über die nächste Phase beraten.

Kingfisher Metals reported additional drill and soil results from its 2025 program at the HWY 37 Project in British Columbia's Golden Triangle. Nevada King Gold Corp. reported final results from ten remaining holes of its Phase III drill program at the Silver Park East (SPE) target. Collective Mining announced that drilling is now fully underway at the high-grade, tungsten-rich zones of its **Apollo system**. Great Pacific Gold announced Phase 1 diamond drill results from the Sinivit target at its flagship Wild Dog Project in Papua New Guinea. First Mining Gold announced additional 2025 exploration results from the Miroir target at its Duparquet Gold Project in Quebec's Abitibi region. Foran Mining announced H2 2025 exploration results from the Tesla Zone at its McIlvenna Bay Project in Saskatchewan.This episode of Mining Stock Daily is brought to you by… Integra ResourcesIntegra is a growing precious metals producer in the Great Basin of the Western United States. Integra is focused on demonstrating profitability and operational excellence at its principal operating asset, the Florida Canyon Mine, located in Nevada. In addition, Integra is committed to advancing its flagship development-stage heap leach projects: the past producing DeLamar Project located in southwestern Idaho, and the Nevada North Project located in western Nevada. Learn more about the business and their high industry standards over at integraresources.comThe Mining Stock Daily morning briefing is produced by Clear Commodity Network. It is distributed throughout the world through your podcast network of choice, and by our friends at the Junior Mining Network. The information presented should not be considered investment advice. Mining stock daily and its affiliates are not responsible for any loss arising from any investment decision in connection with the material presented herein. Please do your own research or speak with a licensed financial representative before making any investment decisions.

Listener feedback on non-culprit PCI in STEMI, a major cardiac result in patients on hemodialysis, news on GLP-1 agonists, a dubious stroke trial, and an AHA preview are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I Listener Feedback Meta-analysis of MI as a surrogate https://pubmed.ncbi.nlm.nih.gov/34694318/ Compare Acute Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1701067 DANAMI-3–PRIMULTI 10.1016/S0140-6736(15)60648-1 External Link CULPRIT-SHOCK https://www.nejm.org/doi/full/10.1056/NEJMoa1710261   II  Huge Cardiac News for Patients with ESRD PISCES article EMBARGOED Till 1130 AM EST PISCES Trial www.nejm.org/doi/full/10.1056/NEJMoa2513032 REDUCE-IT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1812792 STRENGTH Trial https://jamanetwork.com/journals/jama/fullarticle/2773120 FISH trial https://jamanetwork.com/journals/jama/fullarticle/1150094 III Obesity Agents White House announces deal with Lilly and Novo on GLP-1 drugs https://www.reuters.com/business/healthcare-pharmaceuticals/novo-lilly-shares-rise-trump-obesity-drug-deal-nears-2025-11-06/ Amylin Agonists Amylin Analog Eloralintide Reduces Weight in Phase 2 Trial https://www.medscape.com/viewarticle/amylin-analog-eloralintide-reduces-weight-phase-2-trial-2025a1000uqf Eloralintide Phase 2 Study https://doi.org/10.1016/S0140-6736(25)02155-5 GLP-1 Comparisons SURMOUNT-5 Trial https://www.nejm.org/doi/10.1056/NEJMoa2416394 Tirzepatide vs Semaglutide in 10-year CVD Risk Reduction https://doi.org/10.1093/ehjopen/oeaf117 IV A Problematic Trial in Stroke Care LAMP trial https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2840370 V AHA Preview AHA 2025: Mandrola's Four Trials to Look For https://www.medscape.com/viewarticle/aha-2025-mandrolas-four-trials-look-2025a1000u80 You may also like: The Bob Harrington Show with the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net