Podcasts about Lag

Dos historias reales. Dos rostros del crimen. Dos destinos marcados por el horror, la violencia y la ambición. En este video te contamos la caída de dos figuras clave del crimen organizado en México. Por un lado, "El Hummer", exmilitar y uno de los fundadores de una de las células más temidas del país. Su nombre aparece ligado a delitos de alto impacto e incluso al asesinato del cantante Valentín Elizalde. Su destino: la extradición y una condena que lo sepultó en prisión. Por otro lado, "La Güera Loca", una mujer que rompió todos los estereotipos. Encabezó un grupo de mujeres armadas que operaban con impunidad y brutalidad. Su leyenda terminó de forma salvaje, víctima de la misma violencia que ayudó a sembrar.   Entra a happymammoth.com usando PEPEMISTERIO y recibe 15 % de descuento en tu primer pedido._________________Distribuido por Genuina Media

Mit Hans Ulrich Otto, Präsident der Rechtsanwaltskammer Hamm, & Dr. Holger Schrade, Präsident des Landesarbeitsgerichts Hamm und Präsident des Deutschen Arbeitsgerichtsverbandes e.V. diskutiere ich die bevorstehende Reform. Bislang existiert nur ein Eckpunktepapier des Ministeriums, das in einem ersten Schritt - ergebnisoffene - Diskussionen mit Stakeholdern in Aussicht stellt. Wir orakeln: Liegt vielleicht doch schon etwas in der ministeriellen Schublade? Erwartet uns Schleswig-Holstein 2.0? Ist "Konsilidierung" gleichbedeutend mit Schließung? Wird die Anwaltschaft wirklich in den Reformprozess einbezogen? Die Rechtsanwaltskammer Hamm will es jedenfalls genau wissen und lädt daher zu einer Diskussionsveranstaltung am 30.07. ab 15 Uhr ein, damit sich betroffene Arbeitsrechtlerinnen udn Arbeitsrechtler aus dem Kammerbezirk Hamm einbringen können. Natürlich ist auch Holger Schrade am Start. Was jetzt schon klar ist: Der Zugang zur Arbeitsgerichtsbarkeit muss auch in der Fläche gewährleistet bleiben!

durée : 00:04:38 - Le Son d'Avignon - par : Marie Sorbier - Autour des spectacles, de nombreux temps d'échange sont organisés à la fois pour les festivaliers, pour les artistes et pour tous les professionnels de la culture qui se retrouvent chaque été à Avignon pour interroger leurs pratiques. - invités : Stéphane Gornikowski Metteur en scène, directeur du collectif artistique La Générale d'Imaginaire, co-fondateur de la compagnie Vaguement compétitifs

Nadat Trump vannacht bekendmaakte dat Amerika TOCH weer wapens gaat leveren aan Oekraïne, stuurt nu ook Zweden nieuwe wapens. Het gaat om tien zogenoemde Archer-kanonnen. De Europese Commissie en Amerika nemen meer tijd om tot een handelsakkoord te komen. Dat heeft Eurocommissaris Dombrovskis vanmiddag gezegd. De deadline LAG op morgen, maar die is nu verschoven naar 1 augustus. Netanyahu nomineert Trump voor de Nobelprijs voor de Vrede. Iets waar Trump al langere tijd op aast, maar kan het werkelijkheid worden? De gevolgen van het Post Office-schandaal - waarbij honderden postkantoor-beheerders ten onrechte zijn beschuldigd van diefstal - zijn rampzalig! Dat is de harde conclusie van een rapport over dit schandaal dat vanmiddag is gepresenteerd. See omnystudio.com/listener for privacy information.

Please visit answersincme.com/XWB860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in melanoma discusses combination anti–programmed cell death protein 1 (PD-1) plus anti–lymphocyte-activation gene 3 (LAG-3) therapy. Upon completion of this activity, participants should be better able to: Review the latest clinical evidence supporting use of combination anti–PD-1 plus anti-LAG-3 therapy in the first-line setting for patients with unresectable, advanced melanoma; Identify eligible patients with unresectable, advanced melanoma who can benefit from the use of combination anti–PD-1 plus anti–LAG-3 therapy in the first-line setting; and Outline strategies for managing adverse events associated with combination anti–PD-1 plus anti–LAG-3 therapy.

Please visit answersincme.com/XWB860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in melanoma discusses combination anti–programmed cell death protein 1 (PD-1) plus anti–lymphocyte-activation gene 3 (LAG-3) therapy. Upon completion of this activity, participants should be better able to: Review the latest clinical evidence supporting use of combination anti–PD-1 plus anti-LAG-3 therapy in the first-line setting for patients with unresectable, advanced melanoma; Identify eligible patients with unresectable, advanced melanoma who can benefit from the use of combination anti–PD-1 plus anti–LAG-3 therapy in the first-line setting; and Outline strategies for managing adverse events associated with combination anti–PD-1 plus anti–LAG-3 therapy.

Please visit answersincme.com/XWB860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in melanoma discusses combination anti–programmed cell death protein 1 (PD-1) plus anti–lymphocyte-activation gene 3 (LAG-3) therapy. Upon completion of this activity, participants should be better able to: Review the latest clinical evidence supporting use of combination anti–PD-1 plus anti-LAG-3 therapy in the first-line setting for patients with unresectable, advanced melanoma; Identify eligible patients with unresectable, advanced melanoma who can benefit from the use of combination anti–PD-1 plus anti–LAG-3 therapy in the first-line setting; and Outline strategies for managing adverse events associated with combination anti–PD-1 plus anti–LAG-3 therapy.

I denne episoden snakker jeg om å skape det vi ønsker.Kan brukes når det er nytt år, nytt halvår som nå, ny måne, nymåne :) , ny uke, ny dag eller nytt øyeblikk :)Her er ressursene jeg nevnte di episodenLag deg et 1 års prosjekt - minikurs Lag deg et 1 års prosjekt med meditasjonLag deg et 1 års prosjekt med manifesteringLag deg et 1 års prosjekt med lydfilerLag deg et 1 års prosjekt med din businessLag deg et 1 års prosjekt med nettkurs Hosted on Acast. See acast.com/privacy for more information.

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And 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. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Greeting's from Saint Thomas Island! Jason's on the Real Estate Guys' Investor Summit at Sea cruise and reminds his listeners to sign up for the FREE MASTERCLASS every second Wednesday of the month! https://jasonhartman.com/wednesday Jason and Edward Dowd discussed the book "Cause Unknown: The Epidemic of Sudden Deaths" and its focus on the increase in all-cause mortality during the pandemic, as well as the group life insurance policies provided to employees at fortune 500 companies and mid-sized companies. They also discussed the significant increase in excess mortality rates among the insured population, particularly in the age group of 5 to 44, and the potential link between vaccine mandates and the forced vaccination of employed individuals. The conversation also touched on the economic impact of the influx of immigrants, the potential for a recession in the US, and the deflationary effects of tariffs. Follow Edward on X.com https://x.com/DowdEdward https://phinancetechnologies.com/ #EdwardDowd #CauseUnknown #EpidemicOfSuddenDeaths #AllCauseMortality #ExcessMortality #VaccineInjuries #MRNAShot #VaccineAdverseEvents #DisabilityData #GroupLifeInsurance #MillennialMortality #SuddenDeaths #EconomicOutlook #RecessionForecast #IllegalImmigrationImpact #GovernmentSpending #DeficitSpending #Tariffs #DeflationaryTariffs #FederalReserve #InterestRates #Deregulation #TrumpEconomy #BidenEconomy #RFKJr #VaccineImmunity #PublicHealth #MacroEconomics Key Takeaways: 1:30 Carl Sagan predicts the future 2:46 https://jasonhartman.com/wednesday Edward Dowd interview 4:27 Meet Edward and the "Epidemic of of Sudden Deaths" 13:29: Sponsor: https://www.monetary-metals.com/Hartman 15:27 Lag time 17:34 Infertility and Miscarriages 19:49 Illegal immigration and the Economics from a demographic POV 25:14 Trump and big bumps on the road 28:54 Tariffs- inflationary or deflationary 31:32 The FED and rate cuts 33:30 Vaccine deaths and immunities     Follow Jason on TWITTER, INSTAGRAM & LINKEDIN Twitter.com/JasonHartmanROI Instagram.com/jasonhartman1/ Linkedin.com/in/jasonhartmaninvestor/ Call our Investment Counselors at: 1-800-HARTMAN (US) or visit: https://www.jasonhartman.com/ Free Class:  Easily get up to $250,000 in funding for real estate, business or anything else: http://JasonHartman.com/Fund CYA Protect Your Assets, Save Taxes & Estate Planning: http://JasonHartman.com/Protect Get wholesale real estate deals for investment or build a great business – Free Course: https://www.jasonhartman.com/deals Special Offer from Ron LeGrand: https://JasonHartman.com/Ron Free Mini-Book on Pandemic Investing: https://www.PandemicInvesting.com  

Así navega el mundo entre la normalización de cosas que parecen extraídas de un mal viaje Bienvenidos a las noticias del mundo y a esta ruta comandada por una cuerda de locos, desquiciados, alterados. Sábado a la noche. La esfera de espejos y las luces rebotando. Es ahora. Estados Unidos anuncia que fue un día apasionante. Tenemos en imagen a Donald Trump y su sequito informando al mundo que el águila calva acaba de bombardear Irán ECDQEMSD podcast episodio 6071 Locos, desquiciados, alterados - Operación Martillo de Medianoche Conducen: El Pirata y El Sr. Lagartija https://canaltrans.com Noticias del Mundo: La Operación Martillo - El avión que parece OVNI - USA bombardeó Irán - Noticias impactantes - La solución Trump para todo conflicto - Cómprelo Ya! - Real Madrid vence al Pachuca - Análisis de Un Príncipe en NY Historias Desintegradas: Los noventa - Grunge y Salinas de Gortari - Nunca me faltara agua - Los ex vecinos - Perro blanco esponjoso - Caída libre - Lag accidental - Payaso con zancos - Las botargas felices - Muñecos y princesas - Las elecciones judiciales - Conviviendo con los vecinos - Señoras fuertes - Organización perfecta - Renta de video juegos y consolas - Día de la mujer en la ingeniería - La hoguera de San Juan y más... En Caso De Que El Mundo Se Desintegre - Podcast no tiene publicidad, sponsors ni organizaciones que aporten para mantenerlo al aire. Solo el sistema cooperativo de los que aportan a través de las suscripciones hacen posible que todo esto siga siendo una realidad. Gracias Dragones Dorados!! NO AI: ECDQEMSD Podcast no utiliza ninguna inteligencia artificial de manera directa para su realización. Diseño, guionado, música, edición y voces son de  nuestra completa intervención humana.

Baixe o Lagofast e Jogue com menos Lag: https://www.lagofast.com/pt-br/?cid=594Use o Código FASTY e Ganhe 30% de Desconto!Nesse episódio do FOFOCALL, trazemos as últimas polêmicas que agitaram a comunidade de COD Warzone no Brasil, dessa vez envolvendo o polêmico Blade, Airinho Joga e desabafos do NGVieira

Om hur Sverige blev bäst i klassen på stram migrationspolitik. Vi följer dom som lever med konsekvenserna. Lyssna på alla avsnitt i Sveriges Radio Play. Migrationsminister Johan Forsell har målet klart för sig och försöker tillsammans med andra EU-länder förändra migrationspolitiken. Lagändringarna drabbar inte bara enskilda, utan också små kommuner som Harads i Norrbotten. Där har äldreboendet plötsligt svårt att få tillräckligt med personal när reglerna för migranter ändrats i rask takt.Och på förvaret i Märsta möts kvinnor från hela världen som plötsligt tvingas lämna sina barn.Medverkande: Simret Ghidey Tewelde från Upplands-Väsby, Johan Forsell, migrationsminister för moderaterna, Louise Dane, jurist vid Asylrättscentrum, Dure Dadacha, arbetar vid äldreboendet i Harads i Bodens kommun, Marie Mattsson, personalplanerare vid äldreboendet i Harads, Tobias Sundberg, moderat gruppledare i Bodens kommun, Bernd Parusel, forskare i statsvetenskaps vid SIEPS, Svenska institutet för europapolitiska studier. Programledare: Fernando Arias fernando.arias@sr.se Producent: Ulrika Bergqvist ulrika.bergqvist@sr.se Reporter: Johanna Sjöqvist Harland johanna.sjoqvist@sr.se Tekniker: Maria Stillberg

Lag es wirklich nur an Ausfällen und Pech, dass Nagelsmanns Team zweimal verloren hat? Martin Rafelt und Karo Kipper über zweifelhafte Mannorientierung, Probleme im Offensivspiel und einen Spieler, der sich in die Startelf gespielt haben könnte.

Efter nya krav på åldersverifiering i Frankrike får fransoserna inte längre surfa in på världens största porrsajt. I Morgonpasset pratar vi mer om varför Pornhub stängs ner, och vad som kan hända härnäst. Lyssna på alla avsnitt i Sveriges Radio Play.

In honor of Lag b'Omer, study actual excerpts of the text of Zohar as illuminated by the teachings of the Rebbe. A livestream event from the SoulWords House.

Apple (AAPL) catches a rare downgrade as the analyst at Needham lowers its rating to Hold from Buy. Rachel Dashiell eyes the chart and says the stock has traded more like a "Lag 7 stock, than a Mag 7 stock," She compares AAPL to the broader information technology sector over the past year, but on a longer-term chart dating back to 2022 she finds the overall uptrend still intact. ======== Schwab Network ========Empowering every investor and trader, every market day.Subscribe to the Market Minute newsletter - https://schwabnetwork.com/subscribeDownload the iOS app - https://apps.apple.com/us/app/schwab-network/id1460719185Download the Amazon Fire Tv App - https://www.amazon.com/TD-Ameritrade-Network/dp/B07KRD76C7Watch on Sling - https://watch.sling.com/1/asset/191928615bd8d47686f94682aefaa007/watchWatch on Vizio - https://www.vizio.com/en/watchfreeplus-exploreWatch on DistroTV - https://www.distro.tv/live/schwab-network/Follow us on X – https://twitter.com/schwabnetworkFollow us on Facebook – https://www.facebook.com/schwabnetworkFollow us on LinkedIn - https://www.linkedin.com/company/schwab-network/About Schwab Network - https://schwabnetwork.com/about

In honor of Lag b'Omer, study actual excerpts of the text of Zohar as illuminated by the teachings of the Rebbe. A livestream event from the SoulWords House.

Dr. John Sweetenham shares highlights from Day 5 of the 2025 ASCO Annual Meeting, including data from large trials in advanced malignant melanoma and mCSPC plus a new approach to first-line treatment for patients with multiple myeloma who are not transplant eligible. Transcript Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 5 of the 2025 ASCO Annual Meeting. My disclosures are available in the transcript of this episode. The selected abstracts from this final day of ASCO25 include important new data from large, randomized trials in patients with advanced malignant melanoma and patients with metastatic castration-sensitive prostate cancer, as well as a new approach to the first-line treatment of patients with multiple myeloma who are not transplant eligible.  Starting with LBA9500, this study was conducted in patients with completely resected stage III or IV malignant melanoma and compared the combination of relatlimab plus nivolumab versus nivolumab alone in this population. The study, named the RELATIVITY-098 trial, was presented by Dr. Georgina Long from the University of Sydney, Australia. In her introduction to the study, Dr. Long explained that the current standard of care for adjuvant therapy of resected stage III/IV melanoma is with PD-1 monotherapy with nivolumab, but that about 50% of patients will suffer from a subsequent relapse. In the first-line setting in patients with advanced or unresectable melanoma, the combination of nivolumab with the LAG-3 inhibitor, relatlimab, has been previously shown to improve progression-free survival in the RELATIVITY-047 trial. The current study evaluated this same combination in the adjuvant setting. More than 1,000 patients from 24 countries were randomized to receive either nivolumab alone (546 patients) or the combination of nivolumab with relatlimab (547 patients). Both treatments were given for a maximum of 1 year or until progression of disease, unacceptable toxicity, withdrawal, or death. Various biomarker studies were also undertaken including LAG-3 and PD-1 expression on CD8-positive T cells. The primary endpoint of the study was relapse-free survival, and Dr. Long reported that this was the same in both arms of the study. For example, at 24 months, the relapse-free survival was 64% in the monotherapy arm compared with 62% in the combination arm. The hazard ratio was 1.01 and the P value was 0.928. Metastasis-free survival was also identical in both arms. No benefit was observed for the combination in any of the prespecified subgroups. No new toxicity signals emerged compared with the RELATIVITY-047 trial. Interestingly, the baseline surface expression of LAG-3 and co-expression of LAG-3 and PD-1 on CD8 T cells in the 098 adjuvant trial were lower than in the 047 advanced disease trial, perhaps explaining why the combination did not confer benefit over nivo alone in the adjuvant setting. This is an important result, demonstrating that results from one clinical setting cannot always be extrapolated to another. Although the combination has gained some use in the adjuvant setting, this study clearly demonstrates that more drug in this situation is no better and that monotherapy remains the current standard of care. Results from the AMPLITUDE trial for patients with metastatic castration-sensitive prostate cancer with alterations in homologous recombination repair (HRR) genes, in LBA5006, were presented today by Dr. Gerhardt Attard from University College London, UK. This international, multicenter study evaluated the combination of the selective PARP inhibitor, niraparib, in combination with abiraterone acetate and prednisone. The same combination has been previously shown to improve outcomes in castration-resistant metastatic prostate cancer harboring BRCA mutations in the MAGNITUDE study. The current trial included patients with castration-sensitive disease with HRR mutations including BRCA1/2. Six hundred and ninety-six patients were randomized between niraparib, abiraterone, and prednisone plus androgen deprivation therapy, or the same combination with placebo instead of niraparib. Permitted prior therapies included no more than 6 months of prior androgen deprivation therapy and the use of docetaxel, or prior palliative radiation therapy. The primary endpoint of the study was radiographic relapse-free survival. Dr. Attard reported that the risk for radiographic progression-free survival in the whole population was significantly reduced by 37% with niraparib and abiraterone acetate plus prednisone compared with the placebo arm. The radiographic progression-free survival risk reduction with niraparib in the prespecified BRCA1/2 subgroup was 48% and reached statistical significance compared with the placebo arm. The secondary endpoint of time to symptomatic progression was also improved with niraparib in the HRR population and the BRCA1/2 subgroup. There was a trend for overall survival favoring the niraparib combination. However, the overall survival data were immature at this first interim analysis and did not yet reach statistical significance. No new safety concerns emerged with the toxicity data consistent with the MAGNITUDE study. Less than 5% more of the patients on the experimental arm discontinued treatment in comparison to the control arm. The authors conclude that the AMPLITUDE study results support the use of niraparib, abiraterone, and prednisone as a new treatment option for patients with metastatic castration- sensitive prostate cancer and BRCA and homologous recombination repair gene alterations. The results certainly support this conclusion and are potentially practice-changing. Turning to hematologic malignancies, my final selection from today's presentations is Abstract 7504, presented by Dr. Hang Quach from St Vincent's Hospital, Melbourne, Australia, and describes a novel combination of elranatamab, daratumumab, and lenalidomide in patients with newly diagnosed multiple myeloma who are not transplant-eligible – the so-called MagnetisMM-6 trial part 1. Elranatamab is a novel bispecific T-cell engaging antibody directed against BCMA and CD3, which has previously been approved for certain patients with relapsed and refractory multiple myeloma. In the present study, this was combined with lenalidomide and daratumumab in newly diagnosed patients. The report today describes the dose-finding phase of this study, which was part 1, specifically addressing so-called dose level ‘G', comprising elranatamab 76mg subcutaneously every 4 weeks plus daratumumab 1800mg subcutaneously and lenalidomide 25mg given orally. Thirty-seven patients were entered at this dose level, of whom 32 were on treatment at the time of analysis. Early response data show an overall response rate of 97.3%. With median follow up of 7.9 months, the current CR rate is 27% with a VGPR rate of almost 68%. The most frequent toxicities were hematologic, with neutropenia observed in 75%. Some cytokine release syndrome was observed in about 60% of patients, but none was greater than grade 2. The authors conclude that this combination is active in untreated multiple myeloma, with manageable toxicity and evidence of responses which appear to deepen over time. The dose-finding component of this trial is continuing and will subsequently progress into a phase 3 trial based on the data from the current study. This will compare daratumumab plus lenalidomide with the same combination plus elranatamab in previously untreated patients. That concludes our special coverage from the 2025 ASCO Annual Meeting. Thanks for listening and we hope you have enjoyed listening to our top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember 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.  Find out more about today's speaker:    Dr. John Sweetenham    Follow ASCO on social media:     @ASCO on Twitter    @ASCO on Bluesky    ASCO on Facebook    ASCO on LinkedIn     Disclosures:   Dr. John Sweetenham:    No relationships to disclose

Resumen semanal de noticias correspondiente a la semana del al de , 2021. Pueden ver el vídeo de este programa a través del siguiente enlace. Únanse a nuestro Discord para compartir noticias, vacilar y jugar (https://discord.gg/K9NPjHP). No olviden seguirnos en nuestras redes sociales: Canal de YouTube. LAG en Spotify. Facebook. Twitter - @LivingGamingCR. iTunes Podcast. Suscripción por RSS. Agradecimientos: The Couch. Central Gaming. Música de Semana con LAG: It's-a-Me (Super Mario World) del álbum Super Cartography Bros: https://cartography.ocremix.org/. Special Guests: Francisco Montero, Herberth Castro, Michael Quesada, Moisés Mora, and Óscar Roa.

Pueden ver el vídeo de este programa a través del siguiente enlace. Únanse a nuestro Discord para compartir noticias, vacilar y jugar (https://discord.gg/K9NPjHP). No olviden seguirnos en nuestras redes sociales: Canal de YouTube. LAG en Spotify. Facebook. Twitter - @LivingGamingCR. iTunes Podcast. Suscripción por RSS. Agradecimientos: The Couch. Central Gaming. Música de Semana con LAG: It's-a-Me (Super Mario World) del álbum Super Cartography Bros: https://cartography.ocremix.org/. Special Guests: Francisco Montero, Herberth Castro, Michael Quesada, Moisés Mora, and Óscar Roa.

En este programa hemos tenido la suerte de contar con dos de los participantes del concurso de creación de videojuegos C:DOSCONTEST, se trata de Jedive, autor de «La Gándara», juego ambientado en Santander que podéis encontrar en este repositorio de itch.io y de Warrior, autor de «Out of Cash», aventura gráfica que podéis consultar en este repositorio de itch.io. Nos hablarán de sus motivaciones, método de trabajo y penurias vividas para sacar adelante un juego de MS-DOS en pleno 2025. ¡Adelante programa! Si te gusta nuestro contenido puedes apoyarnos en Paypal, Patreon y recomendando el podcast. ¡Gracias de antemano!

Merparten av regeringen står bakom nya könstillhörighetslagen. Men inte alla, Ebba Busch vill riva upp den. Och hur allmänbildade måste statsråden vara? Lyssna på alla avsnitt i Sveriges Radio Play. Den första juli blir den nya könstillhörighetslagen verklighet. Förra året ledde lagen till omfattande interna bråk för Tidögänget, nu fortsätter bråken. Varför vill vice statsminister Ebba Busch riva upp lagen som redan är klubbad av riksdagen och är konflikten ett tecken på att Sverige har importerat ett amerikanskt kulturkrig?På senare år har det varit en trend där medier ställer kunskapsfrågor till våra folkvalda. Bland annat har kulturminister Parisa Liljestrand haft svårt att svara på frågor om filmskapare. Är det verkligen viktigt att statsråd får alla rätt på tipsrundan och vad tycker väljarna, egentligen?Hör också när Helena Gissén och Fredrik Furtenbach gör ett test för att se vem av dem som kan bli schweizisk medborgare.Medverkande: Fredrik Furtenbach och Helena Gissén, Ekots inrikespolitiska kommentatorer.Programledare: Parisa HöglundProducent: Mattias Dellert

Nyheter och fördjupning från Sverige och världen. Lyssna på alla avsnitt i Sveriges Radio Play.

Lag ba Omer time for the darkness to be revealed into light

Have any questions, insights, or feedback? Send me a text!Length of article: 1.5 pagesLength of audio: 5 minutes 55 secondsSynopsis: This is the audio version of the 1.5-page article I wrote and published on rabbischneeweiss.substack.com/ on 5/15/25, titled: Lag ba'Omer PSA: The Falsehood of Rabbi Shimon bar Yochai's Yahrzeit. Mark Twain said, “Be careful about reading health books. You may die of a misprint.” Rumors of Rashbi's death on Lag ba'Omer have been greatly exaggerated. They trace back to a misprint from 1802.Note: This is a corrected and expanded version of this morning's WITATM post. I decided to issue it as a free article today because tomorrow, on Lag ba'Omer, I'm planning to post a paid subscriber article about the Zohar that'll probably get me crucified, and I wanted to get this PSA out before I die.-----SPECIAL OFFER: I'm planning to write more on my Substack this summer than I have in the past few years, including a ton of paid subscriber posts I've been eager to publish. From now until Shavuos, for every week of content you sponsor, I'll add a full month of paid subscription access. If you're interested in sponsoring, let me know!-----If you've gained from what you've learned here, please consider contributing to my Patreon at www.patreon.com/rabbischneeweiss. Alternatively, if you would like to make a direct contribution to the "Rabbi Schneeweiss Torah Content Fund," my Venmo is @Matt-Schneeweiss, and my Zelle and PayPal are mattschneeweiss at gmail. Even a small contribution goes a long way to covering the costs of my podcasts, and will provide me with the financial freedom to produce even more Torah content for you.If you would like to sponsor a day's or a week's worth of content, or if you are interested in enlisting my services as a teacher or tutor, you can reach me at rabbischneeweiss at gmail. Thank you to my listeners for listening, thank you to my readers for reading, and thank you to my supporters for supporting my efforts to make Torah ideas available and accessible to everyone.-----Substack: rabbischneeweiss.substack.com/Patreon: patreon.com/rabbischneeweissYouTube Channel: youtube.com/rabbischneeweissInstagram: instagram.com/rabbischneeweiss/"The Stoic Jew" Podcast: thestoicjew.buzzsprout.com"Machshavah Lab" Podcast: machshavahlab.buzzsprout.com"The Mishlei Podcast": mishlei.buzzsprout.com"Rambam Bekius" Podcast: rambambekius.buzzsprout.com"The Tefilah Podcast": tefilah.buzzsprout.comOld Blog: kolhaseridim.blogspot.com/WhatsApp Content Hub (where I post all my content and announce my public classes): https://chat.whatsapp.com/GEB1EPIAarsELfHWuI2k0HAmazon Wishlist: amazon.com/hz/wishlist/ls/Y72CSP86S24W?ref_=wl_sharel

A busy Thursday Thoughts on SDH AMWe look back at the ATLUTD draw in AustinTodd Lewis, from the Free Kick Pod, breaks down Philly against LAG and ATLUTDGOLTV's Nino Torres talks Libertadores, Sudamericana, Portugal, and PeruPulso Sports and Sounder at Heart's Niko Moreno looks at MLS from the Pacific Perspective

Todd Lewis, fresh off his morning show at the Free Kick Pod, drops by SDH AM to talk about the big comeback win for the Union against LAG and what to expect against ATLUTD

Theemen haut: Ried zur Lag vun der Natioun vum Luc Frieden a Reaktioune vun der Oppositioun, Ofstig vun der Fola an éischt Impressioune vum ESC zu Basel.

Sounder at Heart and Pulso Sports Niko Moreno drops by SDH AM for his Thursday spin around MLS and an Open Cup discussion in TacomaWe talk LAG, Seattle, Austin, Philly, Columbus, and the weekend that will be

MLSSoccer.com's Dylan Butler drops in to SDH AMWith the season one-third done, we look at the surprises (VAN and LAG), and the tops of the conferences (PHI, CLB, MIA) and the chaos of places like SJ, ATX, FCD, and RBNY

On this episode of Dynabro, Sinski recaps the draw with LAG.Be sure to follow us on Instagram and Twitter @Dynamo_Faithful and let us know what you think!We appreciate any feedback on how to improve the pod, just reach out.Appearing on this episode are Manny Farciert & Kyle McGuire.Edited by Ian Gregory-GraffMedia by Zacj BellotMusic from Pixabay, Song: Crag - Hard Rock by Alex Grohl

Vous aimez notre peau de caste ? Soutenez-nous ! https://www.lenouvelespritpublic.fr/abonnementUne émission de Philippe Meyer, enregistrée au studio l'Arrière-boutique le 7 février 2025.Avec cette semaine :Thorniké Gordadzé, chercheur, universitaire, spécialiste du Caucase.Béatrice Giblin, directrice de la revue Hérodote et fondatrice de l'Institut Français de Géopolitique.Nicole Gnesotto, vice-présidente de l'Institut Jacques Delors.Lionel Zinsou, ancien Premier ministre du Bénin et président de la fondation Terra Nova.THÉMATIQUE : LE CAUCASE, AVEC THORNIKÉ GORDADZÉThorniké Gordadzé est chercheur et universitaire. Franco-géorgien, il a dirigé le centre de recherche et d'études de l'Institut des hautes études de défense nationale ; il a également joué un rôle politique, comme ministre d'État pour l'intégration européenne et euro-atlantique de la République de Géorgie. Il enseigne actuellement à l'Institut d'études politiques de Paris et est chargé de programme pour le voisinage oriental et la mer Noire à l'Institut Jacques Delors.Le Caucase a toujours fait partie des zones d'influence russes puis soviétiques. L'intégration dans l'URSS des Républiques soviétiques de Géorgie, d'Arménie et d'Azerbaïdjan a ensuite permis à la Russie de contrôler entièrement cette région, gagnant ainsi un précieux accès à la mer Noire. Depuis la chute de l'Union soviétique, l'influence russe est partout remise en cause, en particulier sous la pression de révolutions populaires : révolution des roses en Géorgie, révolution orange puis de Maïdan en Ukraine. Le pays maintient néanmoins des liens forts avec ses anciens protecteurs, notamment par le biais de l'Organisation du traité de sécurité collective.Face à une population supportant de plus en plus mal le joug de Moscou, de nombreux pays ont fait le choix d'un tournant autoritaire pro-russe. Dans un entretien accordé en octobre 2024 au journal Libération, l'ex-présidente de la Géorgie, Salomé Zourabichvili, déclarait que le pays « [faisait] face au vol manifeste des élections », après la victoire contestée du parti pro-russe au pouvoir Rêve géorgien lors des élections législatives d'octobre 2024. Depuis, Mme Zourabichvili mène la contestation face au pouvoir en place. Depuis près de deux mois, de nombreux Géorgiens manifestent tous les soirs à Tbilissi, la capitale, pour protester contre un scrutin entaché d'irrégularités. Alors que la Russie occupe toujours militairement environ 20% de l'ancienne République soviétique, le Rêve géorgien, dirigé par le milliardaire Bidzina Ivanichvili, continue de promulguer des lois de plus en plus restrictives, éloignant un peu plus la perspective d'une adhésion à l'Union européenne.La Géorgie n'est pas le seul pays caucasien où l'influence de la Russie décline. La conquête du plateau du Haut-Karabakh par l'Azerbaïdjan en 2020, au cours d'une guerre brève mais sanglante, a révélé la faiblesse de Moscou qui n'a pas su protéger son traditionnel allié arménien. Le grand vainqueur de cette guerre a été l'Azerbaïdjan, qui a profité de son partenariat avec la Turquie pour prendre le dessus sur son voisin. Les relations entre Moscou et Bakou se sont encore dégradées avec la destruction en vol, par un tir russe, d'un avion de la compagnie Azerbaijan Airlines. Cet incident a été l'occasion pour Bakou de réaffirmer son rôle de puissance régionale, le pays étant riche de ses ressources pétrolières et gazières qu'elle exporte notamment vers l'Union européenne.Chaque semaine, Philippe Meyer anime une conversation d'analyse politique, argumentée et courtoise, sur des thèmes nationaux et internationaux liés à l'actualité. Pour en savoir plus : www.lenouvelespritpublic.frDistribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

On this episode of Dynamo Faithful, the lads review the draw vs LAG, hit dynamo club & transfer news, preview the match vs Colorado, then wrap up by picking the dynamo player they'd want to travel with.Be sure to follow us on Instagram and Twitter @Dynamo_Faithful and let us know what you think! We appreciate any feedback on how to improve the pod going forward, and please consider rating and reviewing us on your favorite podcast platform!Appearing on this episode are Chris Sinski, Kyle McGuire, and Krystopher Scroggins.Produced & Edited by Ian Gregory-GraffSocial Media & Design by Zacj BellotMusic from Pixabay: Intro/Outro Song: Indie Folk (King Around Here) by Alex Grohl

Welkom bij Gamekings Daily, de podcast annex video over de laatste ontwikkelingen binnen de wereld die videogames heet. Elke doordeweeks dag staat er een nieuwe episode voor je klaar. In 20 minuten tijd bespreken twee Gamekings-presentatoren het laatste nieuws. Vandaag voegt Koos zich vanuit zijn studio bij JJ. De twee hebben het in deze episode over de plotselinge verhoging van de prijs van de PS5 Digital Edition, de boosheid van EA over het vele lekken vanuit de community die Battlefield 6 al mag spelen en de presentatie van de nieuwe game van EA, Marathon. Deze onderwerpen zie en hoor je voorbijkomen in de GK Daily van maandag 14 april 2025.Sony maakt de PS5 Digital Edition 50 euro duurderGK Daily is er maandag, dinsdag, woensdag en donderdag. Op de vrijdag hebben we EvdWL, onze lange podcast over al het nieuws van de week. In GK Daily praten we je in 20 minuten bij over wat er zich allemaal afspeelt in de wereld van videogames. Koos en JJ behandelen in deze aflevering onder andere de eerste beelden en details van Marathon, de nieuwe game van developer Bungie (onder andere bekend van de Halo- en Destiny-franchise). Tijdens een stream van ruim twee uur tijd werd het spel voor het eerste aan de wereld getoond. Wat vond Koos er van. Hij is echt een Bungie-kenner en speelde al hun games. Beviel hem wat ie zag?Bungie maakt gewaagde keuzes bij MarathonDe twee bespreken ook de plotselinge prijsverhoging van de PS5 Digital Edition. Er komt 50 euro boven op de prijs. Dat terwijl er vorig jaar ook al een identieke prijsverhoging was geweest. Lag dit alleen aan de recessie en inflatie of is er meer aan de hand? Het antwoord krijg je op een presenteerblad in deze video.

On this episode of Dynabro, Sinski recaps the draw with LAG.Be sure to follow us on Instagram and Twitter @Dynamo_Faithful and let us know what you think!We appreciate any feedback on how to improve the pod, just reach out.Appearing on this episode is Chris Sinski.Edited by Ian Gregory-GraffMedia by Zacj BellotMusic from Pixabay, Song: Crag - Hard Rock by Alex Grohl

In this episode of Soar Financially, Kai Hoffmann sits down with Chris Vermeulen, Chief Market Strategist at The Technical Traders, to break down the current market turbulence and what lies ahead. With gold hitting new highs and the S&P flashing warning signs, is a multi-year bear market on the horizon?#gold #recession #technicalanalysis---------------------Thank you to our sponsor: Yukon MetalsMake sure to pay them a visit: https://yukonmetals.com/

On the 164th episode of the Ego Chall Podcast, Justin Binkowski and Preston Byers discuss former OpTic Texas player Pred joining the Vegas Falcons, the Los Angeles Guerrillas M8 (aka Gentlemates) making a change, and the guys predict how the first week of CDL Major 3 qualifiers will go.0:00 Intro1:24 Pred joining Vegas Falcons17:29 LAG signs FeLo and oJohnny27:34 Will Kenny sign with the Minnesota ROKKR?40:34 Who else will make a change?49:18 CDL Major 3 Week 1 qualifiers1:03:39 Thank you

Tom Bodrovics welcomes Florian Grummes back to the show to discuss his outlook for silver, gold, and the broader economic landscape. Grummes, a veteran technical trader and analyst, set a target of $50 per ounce for silver by late spring 2025, noting that silver often lags behind gold but tends to surge at the end of a bull market. He highlighted silver's industrial demand, particularly in the solar and electric vehicle sectors, as key drivers for its price appreciation. Grummes also pointed to physical silver shipments from London to New York as a sign of an impending spike. Grummes emphasized the role of macroeconomic factors, including central bank policies and geopolitical tensions, in shaping precious metals markets. He warns that while gold has reached record highs, significant volatility could emerge if stock market corrections deepen. Grummes also touches on the importance of seasonality, suggesting that summer months might see reduced trading activity. Discussing mining stocks, Grummes acknowledges their underperformance relative to metal prices but expressed optimism about future gains, particularly as larger producers with strong margins begin acquiring smaller companies. He stresses the importance of scaling in and out of positions to manage risk effectively. Grummes concludes by emphasizing the psychological aspects of trading, urging listeners to take responsibility for their decisions and learn from past mistakes. Time Stamp References:0:00 - Introduction0:49 - Silvers Behavior & Upside5:04 - Phys. Demand Bottleneck9:47 - Risks & Volatility16:05 - Seasonality & Metals20:02 - Caution & Taking Profits23:10 - Physical Vs. Trading26:30 - Signposts of the End33:08 - Gold Bugs & Objectivity36:00 - Dollar Impact on Metals39:37 - Geopolitical Risks & Ukraine45:23 - Lag with Mining Equities52:13 - Taking Profits56:02 - Wrap Up Guest Links:Website: https://www.midastouch-consulting.comLinkedIn: https://www.linkedin.com/in/floriangrummes/Twitter: https://twitter.com/FlorianGrummesSubstack: https://substack.com/@midastouchconsultingSeeking Alpha: https://seekingalpha.com/author/florian-grummesTelegram: https://t.me/MidasTouchConsultingFacebook: https://www.facebook.com/MidastouchconsultingFree Newsletter: http://eepurl.com/d5Euf Florian Grummes is an independent financial analyst, advisor, consultant, mentor, trader & investor as well as an international speaker with more than 30 years of experience in financial markets.  Florian is the founder and managing director of his company Midas Touch Consulting, which is specialized in trading & investments as well as consulting, analysis & research with a focus on precious metals, commodities and digital assets. Via Midas Touch Consulting he is publishing daily and weekly gold, silver, bitcoin & cryptocurrency analysis for his numerous international readers. Florian is well known for combining technical, fundamental/macro and sentiment analysis into one often accurate conclusion about the markets.

Inflation - Transitory again.. April 2 dealing approaching! Doctor Copper! Mag 7 = Lag 7 A New Closest to The Pin! PLUS we are now on Spotify and Amazon Music/Podcasts! Click HERE for Show Notes and Links DHUnplugged is now streaming live - with listener chat. Click on link on the right sidebar. Love the Show? Then how about a Donation? Follow John C. Dvorak on Twitter Follow Andrew Horowitz on Twitter  Warm-Up - Inflation - Transitory again - End of month - March not so good for US Markets - investors may try to squeeze toward the end - Tariff waves - now there is talk of softening - April 2 is the day - next Wednesday. - A restaurant Chain at ALL-TIME highs.... - Turkey - Market Mayhem - An fun Limerick from a Listener Markets - Doctor Copper! - Mag 7 = Lag 7 - Tesla Woes- Stock bouncing but challenges still remain - March Sadness for Markets... Attention Collectors!  - The New DHUnplugged shirts are finally here! We are going to sell only 6 - the donations received by the end of the month above $250 will get a shirt - Nice white swim/light long sleeve. (The rest are reserved for winners and special occasions) - We will also have the #1 as the first shirt ever out to the public for $1,000. -  Put your address and size in the comments Tariff Day - April 2nd is the date that the retaliatory tariffs go on - Why April 2nd? Why not April 1st?????? --- Worried that is April Fool's day and no one would take them seriously? Copper Prices - 45 year high - What is this? Usually a predictor of the economic conditions - - Seems like a little inflation (China also pumping) - FYI - An average single-family home contains roughly 439 pounds (or 200 kilograms) of copper, primarily in wiring, plumbing, appliances, and hardware Doctor Copper What about Coffee? - Chart - Cents per pound - These increases are driven by climate-related impacts on major coffee-producing countries like Brazil and Vietnam, as well as financial speculation in the market - DOUBLE THE PRICE of last year Coffee Prices Housing Prices - Reports that tariff induced panic is prices of raw materials is pushing prices up - Developers are not going to get behind and this may push prices up - on average $10,000 per new home (at least) Powell on Inflation - Back to Transitory - In his latest speech/commentary last week, he hinted that he believes that the current - During his post-decision press conference last Wednesday, Powell said tariff-induced inflation could be “transitory,” or temporary. - Here we go again! Stagflation Anyone? - Fed sees higher inflation and an economy growing by less than 2% this year - The rate-setting Federal Open Market Committee downgraded its collective outlook for economic growth to 1.7%, down from the last projection of 2.1% in December. In the meantime, officials hiked their inflation outlook, seeing core prices growing at a 2.8% annual pace, up from the previous estimate of 2.5%. - In a statement, the FOMC noted the "uncertainty around the economic outlook has increased," adding that the central bank is "attentive to the risks to both sides of its dual mandate." Meanwhile... - The 3-month Treasury rate inverted against the 10-year for a bit earlier this month. - Currently they are locked at the same rate... - This is the Fed's "preferred" measure of the potential for a recession in the future. Boeing - Boeing wins $20-billion contract for Next Generation Air Dominance program - Win comes after Boeing annual loss, strike, other setbacks - On the news, Boeing's shares rise, Lockheed's fall - Lockheed has been plagued by delays in F-35 upgrade - New name of the aircraft? The F-47 ! New-Clear Energy - A nuclear power plant on the shores of Lake Michigan is aiming to make history this fall by becoming the first reactor in the U.S. to restart operations after shutting down to be eventually dismantled.

The guys open the pod talking about illness, Disneyworld & life. Then it's on to the nights beers, and a discussion about the Loons draw against LAG. They discuss the changes to the lineup with 5 players being on international duty, the terrible officiating to start the match, a Yeboah goal, a defensive mistake, Dotson getting injured, playing some great ball for 5-10 in the second half, a hand ball leading to a Yeboah PK, and a late equalizer by LAG that was both lucky & unlucky. They then make their predictions on the Loons matchup against RSC, which is followed by some MN soccer history. They end the podcast with a story about a man who tried to get through airport security with a turtle in his pants.

Money psychology by way of Buddhist teachings. Consumer confidence- waning. Markets - March Sadness with Lag 7. This week's guest: Wesley Gray - Founder, Alpha Architect.     NEW! DOWNLOAD THIS EPISODE'S AI GENERATED SHOW NOTES (Guest Segment) Wes Gray - After serving as a Captain in the United States Marine Corps, Dr. Gray earned an MBA and a PhD in finance from the University of Chicago where he studied under Nobel Prize Winner Eugene Fama. Next, Wes took an academic job in his wife's hometown of Philadelphia and worked as a finance professor at Drexel University. Dr. Gray's interest in bridging the research gap between academia and industry led him to found Alpha Architect, an asset management firm dedicated to an impact mission of empowering investors through education. He is a contributor to multiple industry publications and regularly speaks to professional investor groups across the country. Wes has published multiple academic papers and four books, including Embedded (Naval Institute Press, 2009), Quantitative Value (Wiley, 2012), DIY Financial Advisor (Wiley, 2015), and Quantitative Momentum (Wiley, 2016). Dr. Gray currently resides in Palmas Del Mar. Puerto Rico with his wife and three children. Follow @alphaarchitect Check this out and find out more at: http://www.interactivebrokers.com/ Follow @andrewhorowitz Looking for style diversification? More information on the TDI Managed Growth Strategy - HERE Stocks mentioned in this episode:

Welcome to “Onward! A Rose City Podcast”; a place for all your Portland Thorns, Portland Timbers, 107IST, Timbers Army, & Rose City Riveters news, along with stories of our club and culture's history plus a look into the future of soccer support in Portland, Oregon.   ON THIS EPISODE! PTFC Chat: Thorns tie Angel City FC and Timber tie LAG and crush the Rapids Riveters Bonfire Booked! Club and more! LINKS! Green is the Color live episode - RSVP Hygiene4All Riveters Bonefire RSVP Featured Partner: Beulahland Coffee & Alehouse Partnerships volunteering Donation Drives Ticket Exchange Facebook - Discord Have a ticket to donate? Send it to ticketdonation@107ist.org 107ist.org

Laurent Kretz reçoit une seconde fois Audrey Lecoq, après un premier épisode en novembre 2023, La Gérante associée de Pharmazon, revient sur la progression de la première plateforme d'achat groupé dédiée aux pharmacies indépendantes.Pharmazon, c'est un modèle inédit en France : permettre aux pharmacies de mutualiser leurs achats pour gagner en compétitivité tout en respectant un cadre réglementaire exigeant.

David and Tom are ready to dig into the 2025 season. This is the first of their team by team previews that are going to come out before MLS Is Back. Soccerwise is teaming up with the best local hosts for every club to bring you all your preview coverage. Each team will have its own separate segment (you can find via timestamps below). In the first episode we are lucky enough to be joined by good friend of the show Sam Jones of Five Stripe Final in Atlanta, Mark Fishkin of the legendary Seeing Red Podcast, Mark Goodman of the elite Holding The Highline & of course the champions are represented by Josh Guesman of Corner Of The Galaxy Podcast. 2:20: ATL w/Sam Five Stripe Final30:17 RBNY w/Mark Seeing Red1:03:58 COL w/Mark Holding The Highline1:39:53 LAG  w/Josh Corner Of The Galaxy Soccerwise Live 2pm ET Every Tuesday/Wednesday/Thursday on Youtube/Twitch/Twitter

In today's episode, we address listener Kieren's question about the differences between LAG, MLAG, MC-LAG, and stacking. We tackle the nuances of Link Aggregation (LAG) and the Link Aggregation Control Protocol (LACP), and explain their roles in redundancy and bandwidth efficiency. We also discuss the complexities and differences among vendors and overall benefits of Multi-Chassis... Read more »

In today's episode, we address listener Kieren's question about the differences between LAG, MLAG, MC-LAG, and stacking. We tackle the nuances of Link Aggregation (LAG) and the Link Aggregation Control Protocol (LACP), and explain their roles in redundancy and bandwidth efficiency. We also discuss the complexities and differences among vendors and overall benefits of Multi-Chassis... Read more »