Podcasts about Tar

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotHoróscopo mensal ELLE Brasil: https://elle.com.br/lifestyle/horoscopo-de-setembro-previsoes-signos-madama-bronaConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Att ta emot livet som det är, i tillit till att Gud är där. Om det reflekterar Susanne Dahl, universitetspräst i Umeå. Lyssna på alla avsnitt i Sveriges Radio Play. I andakten pratar Susanne Dahl om skuld, skam och självanklagelse.- Nåd är inte att släta över eller att förminska. Det är inte en omskrivning av verkligheten. Nåden bor i det blottlagda livet - de stunder jag är naken inför dig. Det är när allt det som är mitt liv vilar i ljuset från ditt ansikte. Jag tänker intuitivt att jag borde skämmas men skammen är bruten, den har ingen makt över mig när jag är hos dig, säger Susanne Dahl i andakten.Text1 Johannesbrevet 3:20b-21MusikAmbre – Nils FrahmProducent Helena Andersson HolmqvistMoskit medialiv@sverigesradio.se

Att ta emot livet som det är, i tillit till att Gud är där. Om det reflekterar Susanne Dahl, universitetspräst i Umeå. Lyssna på alla avsnitt i Sveriges Radio Play. I andakten pratar Susanne om världen som en inte bara vacker plats, utan också ful och grym.- Gud är här. Också i det fulaste. Också i det brustna och trasiga. I smutsen. Så ber jag om en blick som vågar se. Kanske är det så att världen är vacker för att den är älskad, också i sin fulhet, säger Susanne Dahl i andakten.TextJesaja 53:2-3MusikAmbre – Nils FrahmProducent Helena Andersson HolmqvistMoskit medialiv@sverigesradio.se

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Att ta emot livet som det är, i tillit till att Gud är där. Om det reflekterar Susanne Dahl, universitetspräst i Umeå. Lyssna på alla avsnitt i Sveriges Radio Play. I andakten pratar Susanne om oron som vissa dagar drabbar själen.- De senaste dagarna har jag bett om din hjälp. Att du ska ge mig sinnesro. Ge styrka åt svaga ben. Blåsa på den falnande lågan i bröstet. Jag vet inte när hjälpen kommer, men jag fortsätter att be. Detta kan jag göra. Detta ska jag göra. Fortsätta att be om hjälp och vägledning. Tids nog svarar du, säger Susanne Dahl i andakten.TextPsaltaren 139:1-5MusikAmbre – Nils FrahmProducent Helena Andersson HolmqvistMoskit medialiv@sverigesradio.se

Dr. Sumanta (Monty) Pal and Dr. Petros Grivas discuss innovative new intravesical therapies and other recent advances in the treatment of non-muscle invasive bladder cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello and welcome. I'm Dr. Monty Pal here at the ASCO Daily News Podcast. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. And I'm really delighted to be your new host here. Today's episode is going to really sort of focus on an area near and dear to my heart, something I actually see in the clinics, and that's bladder cancer. We're specifically going to be discussing non-muscle invasive bladder cancer, which actually comprises about 75% of new cases. Now, in recent years, there's been a huge shift towards personalized bladder-preserving strategies, including innovative therapies and new agents that really are reducing reliance on more primitive techniques like radical cystectomy and radiation therapy. And I'm really excited about this new trend. And really at the forefront of this is one of my dear friends and colleagues, Dr. Petros Grivas. He's a professor in the Department of Medicine and Division of Hematology Oncology at the University of Washington. It's going to take a while to get through all these titles. He's taken on a bunch of new roles. He is medical director of the International Program, medical director of the Local and Regional Outreach Program, and also professor in the Clinical Research Division at the Fred Hutch Cancer Center. Petros, welcome to the program. Dr. Petros Grivas: Thank you so much, Monty. It's exciting for me to be here. Dr. Sumanta (Monty) Pal: Just FYI for our audience, our disclosures are available in the transcript of this episode.  We're going to get right into it, Petros. Non-muscle invasive bladder cancer, this is a really, really challenging space. We see a lot of recurrence and progression of the disease over time, about 50% to 70% of patients do have some recurrence after initial treatment, and about 30% are ultimately going to progress on to muscle-invasive or metastatic disease. Now, I will say that when you and I were in training, non-muscle invasive bladder cancer was something that was almost relegated to the domain of the urologist, right? They would use treatments such as BCG (Bacillus Calmette-Guérin) in a serial fashion. It was rare, I think, for you and I to really enter into this clinical space, but that's all changing, isn't it? I mean, can you maybe tell us about some of the new therapies, two or three that you're really excited about in this space? Dr. Petros Grivas: Monty, you're correct. Traditionally and conventionally, our dear friends and colleagues in urology have been managing patients with non-muscle invasive bladder cancer. The previous term was superficial bladder cancer. Now, it has changed, to your point, to non-muscle invasive bladder cancer. And this has to do with the staging of this entity. These tumors in superficial layers of bladder cancer, not invading the muscularis propria, the muscle layer, which makes the bladder contract for urine to be expelled. As you said, these patients have been treated traditionally with intravesical BCG, one of the oldest forms of immunotherapy that was developed back in the 1970s, and this is a big milestone of immunotherapy development. However, over the years, in the last 50 years, there were not many options for patients in whom the cancers had progression or recurrence, came back after this intravesical BCG. Many of those patients were undergoing, and many of them still may be undergoing, what we call radical cystectomy, meaning removal of the bladder and the lymph nodes around the bladder. The development of newer agents over the last several years has given the patients the option of having other intravesical therapies, intravesical meaning the delivery of drugs, medications inside the bladder, aiming to preserve the bladder, keep the bladder in place. And there are many examples of those agents. Just to give you some examples, intravesical chemotherapy, chemotherapy drugs that you and me may be giving intravenously, some of them can be given inside the bladder, intravesical installation. One example of that is a combination of gemcitabine and docetaxel. These drugs are given in sequence one after the other inside the bladder, and they have seen significant efficacy, good results, again, helping patients keeping the bladder when they can for patients with what we call BCG unresponsive non-muscle invasive bladder cancer. And again, there's criteria that the International Bladder Cancer Group and the FDA developed, how to define when BCG fails, when we have BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: And we're actually going to get into some of the FDA requirements and development pathways and so forth. What I'm really interested in hearing, and I'm sure our audience is too, are maybe some of the new intravesical treatments that are coming around. I do think it's exciting that the gemcitabine and docetaxel go into the bladder indeed, but what are some of the top new therapies? Pick two or three that you're excited about that people should be looking out for in this intravesical space. Dr. Petros Grivas: For sure, for sure. In terms of the new up-and-coming therapies, there are a couple that come to mind. One of them is called TAR-200, T-A-R 200. This agent is actually a very interesting system. It's an intravesical delivery of a chemotherapy called gemcitabine, the one that I just mentioned a few minutes ago, that is actually being delivered through what we call a pretzel, which is like a rounded [pretzel-shaped] structure working like an osmotic pump, and that is being delivered inside the bladder intravesically by urologists. And this drug is releasing, through the osmotic release mechanism, this chemotherapeutic drug, gemcitabine, inside the bladder. And this can be replaced once every 3 weeks in the beginning. And the data so far from early-phase trials are really, really promising, showing that this agent may be potentially regulatory approved down the road. So TAR-200 is something to keep in mind. And similarly, in the same context, there is a different drug that also uses the same mechanism, and this osmotic release, this pretzel, it's just encoded with a different agent. The different agent is an FGFR inhibitor, a target therapy called erdafitinib, a drug that you and me may give in patients with metastatic urothelial carcinoma if they have an FGFR3 mutation or fusion. And that drug is called TAR-210. Dr. Sumanta (Monty) Pal: And can I ask you, in that setting, do you have to have an FGFR3 mutation to receive it? Or what is the context there? Dr. Petros Grivas: So for TAR-210, TAR-2-1-0, usually there is a checking to see if there is an FGFR3 mutation or fusion. And the big question, Monty, is do we have adequate tissue, right? From a limited tissue on what we call the TURBT, right, that urologists do. And now there is a lot of development in technology, for example, urine circulating tumor DNA to try to detect these mutations in the urine to see whether the patient may be eligible for this TAR-210. Both of those agents are not FDA approved, but there are significant promising clinical trials. Dr. Sumanta (Monty) Pal: So now let's go to a rapid-fire round. Give us two more agents that you're excited about in this intravesical space. What do you think? Dr. Petros Grivas: There is another one called cretostimogene. It's a long name. Dr. Sumanta (Monty) Pal: They really make these names very easy for us, don't they? Dr. Petros Grivas: They are not Greek names, Monty, I can tell you, you know. Even my Greek language is having trouble pronouncing them. The cretostimogene, it's actually almost what we call a growth factor, a GM-CSF. The actual name of this agent is CG0070. This is a replicating mechanism where GM-CSF is replicating in cells. And this agent has shown significant results again, like the TAR-200, in BCG unresponsive non-muscle invasive bladder cancer. I would say very quickly, two agents that actually were recently approved and they're already available in clinical practice, is nadofaragene firadenovec, another long name. That's a non-replicating vector that has the gene of interferon alfa-2b that stimulates the immune system in the bladder. It's given once every 3 months. And the last one that was, as I mentioned, already FDA approved, it's an interleukin-15 superagonist. It's another long name, which is hard to pronounce, but I will give it a try. It's a drug that was recently actually approved also in the UK. The previous name was N-803. It's given together with BCG as a combination for BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: This is a huge dilemma, I think, right? Because if you're a practicing, I'm going to say urologist for the moment, I guess the challenge is how do you decide between an IL-15 superagonist? How do you decide between a pretzel-eluting agent? How do you decide between that and maybe something that's ostensibly, I'm going to guess, cheaper, like gemcitabine and docetaxel? What's sort of the current thinking amongst urologists? Dr. Petros Grivas: Multiple factors play into our account when the decision is being made. I discuss with urologists all the time. It's not an easy decision because we do not have head-to-head comparisons between those agents. As you mentioned, intravesical chemotherapy with gemcitabine and docetaxel has been used over the years and this is the lowest cost, I would say, the cheapest option with good efficacy results. Obviously, the nadofaragene firadenovec every 3 months and the interleukin-15 superagonist, N-803, plus BCG have also been approved. The question is availability of those agents, are they available? Are they reimbursed? Cost of those agents can come into play. Frequency of administration, you know, once every 3 months versus more frequent. And of course, the individual efficacy and toxicity data, preference of the patients; sometimes the provider, the urologist, may have something that they may be more familiar with. But we lack this head-to-head comparison. Of course, I want to make sure I mention that radical cystectomy may still be the option for appropriate patients. So that complicates also the decision making and has to be individualized, customized, and personalized, taking into account all those factors. And there is not one size fitting all. Dr. Sumanta (Monty) Pal: So I think we discussed five intravesical therapies. As you point out, and you know, I'm going to get some calls about this: I think I referred to radical cystectomy as being a more primitive procedure. Not true at all. I think it's something that still is, you know, a mainstay of management in this disease space. But I guess it gets even more complicated, am I right, Petros? Because now we have systemic therapies that we can actually apply in this non-muscle invasive setting for at this point, refractory disease. Can you maybe just give us a quick two-minute primer on that? Dr. Petros Grivas: Absolutely, and systemic therapies now come into play, as you said. And a classical example of that, Monty, came from the KEYNOTE-057 trial that we published about 6 years ago. This is intravenous pembrolizumab, given intravascularly, intravenously, as opposed to the previously discussed intravesical administration of agents. Pembrolizumab was tested in that KEYNOTE-057 trial and showed efficacy about, I would say, one out of five patients, about 20%, had a complete response of the tumor in the bladder in a year after starting the treatment. Again, it's hard to compare across different agents, but obviously when we give something intravenously, there is a risk of toxicity, side effects systemically, what we call immune-related adverse events. And this can also play in the decision making, right? When you have intravesical agents versus intravascular agents, there is different toxicity profiles in terms of systemic toxicity. But intravenous pembrolizumab has been an option, FDA approved, since, if I remember, it was early 2020 when this became FDA approved. There are other agents being tested in this disease, but like atezolizumab through the SWOG study that Dr. Black and Dr. Singh led, but atezolizumab is not FDA approved for this indication. Again, this is for BCG unresponsive, high-risk, non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: So maybe teach us how it works, for instance, at an expert center like the Fred Hutch. When you see a patient with non-muscle invasive bladder cancer, there's obviously the option of surgery, there's the intravesical therapies, which I imagine the urology team is still really at the helm of. But then, I guess there has to be consideration of all options. So you've got to bring up systemic therapy with agents like pembrolizumab. In that context, are you involved that early on in the conversation? Dr. Petros Grivas: That's a great discussion, Monty. Paradigm is shifting as we mentioned together. The urologists have been treating these patients and still they are the mainstay of the treaters, the managers in this disease. But medical oncologists come to play more and more, especially with the FDA approval of intravenous pembrolizumab about 5 years ago [GC1]  [KM2] . We have the concept of multidisciplinary bladder cancer clinic here at Fred Hutch and University of Washington. This happens every Tuesday morning, and we're very excited because it's a one-stop shop for the patients. We have the urologist, a medical oncologist, radiation oncologist, and experts from radiology and pathology, and we all review cases specifically with muscle-invasive bladder cancer. But every now and then, we see patients with BCG unresponsive non-muscle invasive bladder cancer. And this is where we discuss and we talk to the patient about pros and cons of all those options. And that's a classic example where medical oncologists may start to see those patients and offer their input and expertise. In addition to that, sometimes we have clinical trials, we may see these patients because there are systemic agents that may be administered in this setting. We have the SunRISe trial program that includes also a systemically administered checkpoint inhibitor. So that's another example where we see patients either in the context of multi-clinic or in individual solo clinics to counsel the patients about the pros and cons of the systemically administered agents in the context of clinical trials. Usually checkpoint inhibitors are the class of agents that are being tested in this particular scenario. Dr. Sumanta (Monty) Pal: I can see a scenario where it's really going to require this sort of deep dive, much in the way that we do for prostate cancer, for instance, where the medical oncologist is involved very early on and planning out any sort of systemic therapy component of treatment or at the very least, at least spelling out those options. I think it's going to be really interesting to see what this space looks like 5 or 10 years down the road. In closing, I wanted to go through something that I think is so different in this space, at least for the time being, and that is the paradigm for FDA approval. When you and I have our fellows in the clinics, we always say, “Look, you know, the paradigm in this disease and that disease and the other disease needs to be phase 3 randomized trials, right? Big thousand patient experiences where you're testing clinical endpoints.” That's tough in non-muscle invasive bladder cancer, right? Because thankfully, outcomes can actually be quite good, you know, in this setting, right? It's tough to actually estimate overall survival in some of these early-stage populations. Tell me what the current regulatory bar is, and this is a tough thing to do in 2 minutes or less but tell me where you see it headed. Dr. Petros Grivas: You alluded to that before, Monty, when I was giving the background and we talked about the regulatory approval. And I have to very quickly go back in time about 10 years ago because it's important for context that can help us in other disease types too. We had workshops with the FDA and the NCI with the help of the International Bladder Cancer Group and other colleagues. And we try to define a framework, what endpoints are meaningful for those patients in this disease. It was a multidisciplinary, multiple stakeholders meeting, where we tried to define what is important for patients. What are the available agents? What are the trial designs we can accept? And what are the meaningful endpoints that the regulatory agencies can accept for regulatory approval? And that was critical in that mission because it allowed us to design clinical trials, for example, single-arm trials in a disease where there was no standard of care. There was intravesical valrubicin and chemotherapy anthracycline that was approved for many years, but was not practically used in clinical practice, despite being approved, the valrubicin. And because of that, the FDA allowed these single-arm trials to happen. And obviously the endpoint was also discussed in that meeting. For example, for carcinoma in situ, complete response, clinical complete response, because the bladder remains intact in many patients, clinical complete response was a meaningful primary endpoint, also duration of response is also very important. So what is the durable clinical complete response in 1 year or 18 months is relevant. And when you have papillary tumors like Ta or T1 with CIS, for papillary tumors, event-free survival becomes one of the key endpoints and you look at it over time, for example, at 12 or 18 months, what is the event-free survival? So clinical complete response, duration of response, event-free survival, depending on the CIS presence or papillary tumors, I think these are endpoints that have allowed us to design those trials, get those agents approved.  Now, the question going forward, Monty, and we can close with that is, since now we have the embarrassment of riches, many more options available compared to where we were 6 and 7 years ago, is now the time to do randomized trials? And if we do randomized trials, which can be the control group? Which of those agents should be allowed to be part of the control group? These are ongoing discussions right now with the NCI, with other agencies, cooperative groups, trying to design those trials and move forward from here.[GC3]  Dr. Sumanta (Monty) Pal: Well, it's awesome to have you here on the program so we can get some early looks into some of these conversations. I mean, clearly, you're at the table at a lot of these discussions, Petros. So I want to thank you for sharing your insights with us today. This was just tremendous. Dr. Petros Grivas: Thank you, Monty. You know, patients in the center, I just came back from the Bladder Cancer Advocacy Network meeting in Washington, D.C., and we discussed all those questions, the topics you very eloquently mentioned and asked me today, and patients gave us great feedback and patients guide us in that effort. Thank you so, so much for having me and congratulations for the amazing podcast you're doing. Dr. Sumanta (Monty) Pal: Oh, cheers, Petros, thanks so much.  And thank you to the listeners who joined us today. If you really like the insights that you heard on this ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:      Dr. Sumanta (Monty) Pal  @montypal  Dr. Petros Grivas @PGrivasMDPhD   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Petros Grivas: Consulting or Advisory Role: Merck, Bristol-Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Strata Oncology, Abbvie, Bicycle Therapeutics Replimune, Daiichi Sankyo, Foundation Medicine, Bicycle Therapeutics, Eli Lilly, Urogen Pharma, Tyra Biosciences Research Funding (Inst.): Bristol-Myers Squibb, Merck, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, ALX Oncology, Genentech Travel, Accommodations, Expenses: Gilead Sciences

Gıda israfı Türkiye'de yıllık 23 milyon tona ulaştı. Türkiye İsrafı Önleme Vakfı'nın (TİSVA) son raporu bunu kanıtlıyor. Gıda israfını önlemek amacıyla Cumhurbaşkanlığı Tarım ve Gıda Politikaları Kurulu kapsamlı bir çalışma başlattı. Özellikle açık büfe ve serpme kahvaltı uygulamaları mercek altında. Peki bu durum sağlıklı beslenme açısından ne anlama geliyor? Bielefeld'de beslenme uzmanlığı yapan Hülya Kartal ile konuştuk. Mikrofonda Gökçe Göksu ve Eren Mahir Gencer var. Von Gökçe Göksu und Eren Mahir Gençer.

The Remarkable Retail Podcast kicks off Season 11 with a powerful episode featuring a first-ever guest co-host: Ethan Chernofsky, Chief Marketing Officer of Placer.ai. The episode opens with a lively discussion of tariffs and trade turbulence, a recurring theme reshaping global retail strategies. Ethan shares data-driven insights from Placer.ai on how consumer behavior is shifting under economic uncertainty, while Steve highlights how pricing power and category positioning determine which retailers can weather cost pressures. Together, they unpack what's next as outsized tariffs hit key markets like India, Brazil, and Switzerland.The conversation then pivots to retailer performance, starting with Target's leadership shake-up. Steve critiques the choice of an insider CEO while Ethan provides Placer.ai traffic data showing continuing traffic declines. The group debates Target's future—whether its famed “Tar-zhay” positioning can be revived by refocusing on differentiation. From there, they contrast Target's struggles with Walmart's momentum, exploring how digital sales, retail media, and membership growth continue to power the world's largest retailer's outsized performance..Speaking of Amazon, the trio examines the company's great expanded same-day grocery delivery, setting up a fresh battleground with Walmart. They also analyze the broader bifurcation of retail, where premium players and discounters gain share while middle-market brands face mounting challenges.Moving on the episode digs into the most talked about stories making headlines. Topics include the Cracker Barrel rebrand backlash, American Eagle's bold Sydney Sweeney campaign, and the AI battle for talent, which borders on the ridiculous..Finally, the team peers around the corner, curious about whether iconic brands in transition such as Gap, Kohl's, Macy's, Nordstrom, and Bloomingdale's can regain any traction in the fae of growing headwinds. They also discuss shifting enclosed mall dynamics of malls. Ethan underscores that while A-class malls thrive with innovative tenants, some moribund B-class centers are finding new life by reinventing themselves. About UsSteve Dennis is a strategic advisor and keynote speaker focused on growth and innovation, who has also been named one of the world's top retail influencers. He is the bestselling authro of two books: Leaders Leap: Transforming Your Company at the Speed of Disruption and Remarkable Retail: How To Win & Keep Customers in the Age of Disruption. Steve regularly shares his insights in his role as a Forbes senior retail contributor and on social media.Michael LeBlanc is the president and founder of M.E. LeBlanc & Company Inc, a senior retail advisor, keynote speaker and now, media entrepreneur. He has been on the front lines of retail industry change for his entire career. Michael has delivered keynotes, hosted fire-side discussions and participated worldwide in thought leadership panels, most recently on the main stage in Toronto at Retail Council of Canada's Retail Marketing conference with leaders from Walmart & Google. He brings 25+ years of brand/retail/marketing & eCommerce leadership experience with Levi's, Black & Decker, Hudson's Bay, CanWest Media, Pandora Jewellery, The Shopping Channel and Retail Council of Canada to his advisory, speaking and media practice.Michael produces and hosts a network of leading retail trade podcasts, including the award-winning No.1 independent retail industry podcast in America, Remarkable Retail with his partner, Dallas-based best-selling author Steve Dennis; Canada's top retail industry podcast The Voice of Retail and Canada's top food industry and one of the top Canadian-produced management independent podcasts in the country, The Food Professor with Dr. Sylvain Charlebois from Dalhousie University in Halifax.Rethink Retail has recognized Michael as one of the top global retail experts for the fourth year in a row, Thinkers 360 has named him on of the Top 50 global thought leaders in retail, RTIH has named him a top 100 global though leader in retail technology and Coresight Research has named Michael a Retail AI Influencer. If you are a BBQ fan, you can tune into Michael's cooking show, Last Request BBQ, on YouTube, Instagram, X and yes, TikTok.Michael is available for keynote presentations helping retailers, brands and retail industry insiders explaining the current state and future of the retail industry in North America and around the world.

This week on the pod, we welcome Bobby Coppola, Chief Strategy Officer and Bryant Gauthier, Vice President of Legal Technology at PLUSnxt. Bobby shares how his path from big law to legal tech shaped his focus on client service and strategy, while Bryant returns to the show to talk about what drew him to PLUSnxt after his time at Celerity.We break down what sets PLUSnxt apart in the crowded eDiscovery space, from helping clients separate hype from reality to focusing on innovation that actually makes life easier for corporations and law firms. The conversation turns to artificial intelligence in document review, obviously, where Bobby and Bryant highlight where adoption is real, where skepticism remains, and how GenAI is shifting client expectations. They also weigh in on whether the future lies in best-of-breed solutions or all-in-one platforms, sharing why no one really wants to manage a “franken-stack.” To wrap up, Bobby and Bryant share their takeaways from ILTACON and what trends they see shaping the next phase of legal tech.Along the way, the group reminisces about the dot-com era, old chat rooms (ASL anyone?), answering machines, fax machines, the Movie Phone guy, and even the “Callin' Oates” hotline. Definitely check this one out!At the intersection of law, business, and technology, Bobby Coppola  is focused on delivering industry leading legal technology and services to achieve the best outcome for his clients. He leverages his unique skill set based on his big law background and decades long-experience in the eDiscovery space to solve business and legal problems for companies and law firms globally. As Chief Strategy Officer at PLUSnxt, he is focused on the development of the company's short- and long-term strategy from both an operational and growth perspective. The underpinning of his approach to client relationships is a fanatical focus on client service and a vision of always putting himself in his client's position when developing a strategic plan for success.Bryant Gauthier is Vice President of Legal Technology at PLUSnxt, where he advises law firms and corporate counsel on building efficient eDiscovery programs. With more than 20 years of experience, he helps clients leverage technology, processes, and analytics to reduce costs and manage risk across the EDRM. He has led the launch of eDiscovery departments using advanced tools such as CAL, TAR, AI, text-to-audio search, and image recognition to streamline document review and investigations. His background includes leadership roles at Huron Consulting, Skadden Arps, Buckley Sandler, Finnegan Henderson, and Xerox.  Bryant supports legal teams in litigation, investigations, and regulatory matters, including SEC, DOJ, and CFPB inquiries, across industries such as banking, energy, healthcare, intellectual property, and technology. His expertise covers data identification, analysis, governance, privacy, and cross-border matters. PLUSnxt is a legal technology and services provider that helps law firms and corporations manage complex eDiscovery challenges with a focus on practical innovation and client service. They emphasizes building solutions that cut through the noise of legal tech hype, offering tools and expertise that actually improve how legal teams review, analyze, and manage data. PLUSnxt brings a mix of deep technical knowledge and real-world legal experience to its clients. Their approach combines advanced technologies such as AI and analytics with a clear understanding of business and legal priorities, making them a trusted partner for organizations navigating litigation, investigations, and regulatory matters.

A young man comes of age, and meets his soulmate, thanks to his garage renovation therapy project.In 3 parts, by Member389. Listen to the Podcast at Steamy Stories. “She could be just the thing.”Derek was glad that he'd thought of this apartment remodel. It was a project he and his son Luke could work on together. He hoped that it would get Luke to come out of his shell. Ever since his mother passed away a few years ago he'd been closed off and anti-social. Luke gets his handiness from his dad. He loved to work with his hands, and it was not boasting to say that he was pretty good at it too. Fortunately the push, from Derek's dad, to be more took him to state college to study engineering and into a lucrative career afterward. Derek met his wife of 20 years at that college, Theresa was the world to him, and he would have done anything to lay the world at her feet. Fate had a different idea though. Her loss had left a deep scar on their family. It was hard at first, friends and relatives did their best to keep them upbeat and one or two even mentioned that Derek wasn't too old to start again. Those ideas were brushed aside. He would never love anybody like he loved Terri.Luke took it hard, he was only 14 when Terri found out she had cancer. The doctors did everything they could. Throughout her treatment he would give up being a normal teenager to be home for her when his father couldn't be. She'd get upset with him and tell him to try out for sports at school or join a club, and especially ask a girl that he like out on a date. He'd just brush it off and come home as soon as he could to take care of her. She wasted away before their eyes and in less than a year she was gone. It was a crushing blow to both of them, and as hard as Derek had it, he could tell Luke felt like he was set adrift, and had no guidance. Derek worked, he worked a lot, to keep his mind busy, to keep from thinking about her. Luke just hung around, and kept to himself mostly. He had a few friends but they, for the most part, had moved on after graduation. Luke was accepted to the college where his folks went to and was looking at a similar career to his fathers, no matter how much Derek urged him to do something he wanted. He insisted that he wanted to do what his father does, and build things. He was going to start as a freshman this fall.Derek, in the interest of keeping Luke from hiding in his room until fall, figured he'd give him a project. They lived in a big house with an large 2 car garage. Above the garage was a space that was large enough to turn into an in-law apartment. He presented Luke with the project to clean it out, and design an apartment. As soon as he had a plan they would build it and rent it out. Thanks to the college there's never any shortage of students looking for off campus apartments. They weren't really close, a few miles, but these days all the kids had cars anyway.Like anything he put his mind to, Luke had a plan in place pretty quickly. We worked out details for the major demolition and installing plumbing, and electrical etc. He really did his homework, even shopping for materials for finishing like the flooring and appliances. He got it in his head to fully decorate it with the help of some ideas from magazines. What they ended up with was a very nice small 1 bedroom apartment with a nice view over the backyard. Luke had already started school and they didn't think it likely that they'd get a lot of offers right away but they listed the apartment in the paper anyway.They interviewed a couple students and even a visiting professor who was teaching here for a year, but nobody fit what they had in mind and too many wanted them to come down on the price. There was no way Derek was going to let anybody devalue the work that he and Luke had put into it, the only one who was going to budge on price was going to be Luke. It was his baby.It was a warm Saturday afternoon when Derek heard a woman's voice call out. He was in the back yard puttering around with a rake. He leaned it against the house and walked around to the front where he saw a lovely blonde haired girl walking towards the other corner of the house heading to the yard. He called out to her and she jumped slightly startled. In only a few moments Derek took in the sight of her. She was very pretty, her blond hair fell around her shoulders. She smiled and held out her hand to shake."Hi, I'm Ellie. I was wondering if you've rented the apartment yet?" He let her know that they hadn't yet, and that his son Luke was in charge of that. He went in and got the keys and let her see it, and she marveled. "Who decorated it? They did an awesome job." Dad let her know that the whole place was done by his son, Luke, from design to decoration. He smiled at her shock, when he told her Luke was starting school at the local university this year. "This was done by a teenager?""He should be home any minute if you want to hang around. A few of the ground rules that we've placed are that guests please park on the street so as to not block the garage downstairs. Use of the yard and pool are a given so long as you keep it down to a dull roar." He said chuckling. "There's a washer and dryer downstairs in the garage that you can use rather than go to a laundromat. As you probably saw in the ad, utilities are provided including cable and Internet. We can get you telephone if you need it but it's not wired for it up here. We figured most students use cellphones anyway.""It's perfect. Now I see why you're asking so much for it. Any chance we can haggle on the price?" She cocked her head smiling, her eyes sparkling. Derek chuckled."That's up to Luke. This is his baby, start to finish." Derek paused as he heard the garage door opener beneath them start up. "You can ask him yourself in a minute. I'll let him know you're here." He stepped out onto the landing and looked at the door as he closed it. He thought for a moment that they may have found the right person for the apartment. He smiled as he trotted down the stairs and ducked into the garage where Luke was getting out of the car. His hair was mussed from driving with the window down, his shirt was tight over his well-formed chest and arms. The work had leaned him out and toned him up."Hey Luke,” Derek greeted his son. “You have someone upstairs looking at the apartment.""I'll guess by the grin on your face it's a girl." Luke said in a slightly annoyed tone."Is there anything wrong with a girl renting your place?""No; I just want somebody normal and quiet."Luke passed dad on his way to the stairs and his father put his hand on his shoulder. "I have a good feeling about this one. Trust your instincts." He nodded and made for the stairs taking them two at a time. Luke opened the door and close it behind him, and Derek went back to the yard whistling a little tune; hopeful she could be just the thing.A short while later, Luke popped around the corner of the garage and slowly wandered through the yard."Well?" Derek asked."She tried to get me to come down on the price.""Really?" He smiled trying not to laugh. "How did that go?""I asked her how much she could reasonably afford, and I halved the difference. She took it." He smirked."How much lower did you go?" Derek was eager to learn."A hundred bucks. Non-smoker, no boyfriend and she says she not a partier. She's a senior in culinary arts and nutrition. She offered to cook for us occasionally if we don't mind being her test subjects. Her name is Ellie Love." Luke grinned, but didn't say that he'd thought about dropping two for the pretty coed."No shit?" Derek laughed.Luke just shrugged. "She's calling her folks to let them know she's found a place."Ellie started moving in the next day. Luke was out in the driveway washing his car, the sound of music filtered down from Ellie's open window as she unpacked. Derek watched Luke from the window for a moment and caught him looking up at the window off and on. He would bet anything she was intentionally wandering back and forth to get a look at him too."Hey Luke?" Ellie called down."Yea?" He replied."Any chance you could take me shopping for some kitchen stuff? There isn't much up here in the way of plates, glasses, silverware, you know.""Sure, let me know when you're ready.""Give me 10 minutes and I'll be down."Ellie went and changed. She knew she was older than him by a couple years. His father mentioned he'd turned 19 last month. Luke was hot with his dark hair and dark brown eyes, but he seemed so quiet and shy. After the wild roommates and crazy party atmosphere of the apartment she shared last year, this was going to be a nice change.She worked in a small café, after high school and found she loved it and thought it might be a cool idea to start her own. So she'd decided that getting it right was going to require some learning and went back to school. Now at 23 she was close to finishing her degree and moving on to realizing the dream. She threw on a striped tee and pushed her sweats off and found a pair of jeans in one of her bags and went to the bathroom to check herself in the mirror. She knew she wasn't a knockout but she was pretty cute. She knew that from the double-takes she got from guys at school. She was short, in her opinion, at five foot three, her sandy blonde hair hung past her shoulders, and her dark brown eyes were always sparkling. Her dad said they were full of mischief. If he only knew.She pulled the door shut behind her checking that it had locked and bounced down the stairs like she was on springs. She watched Luke for a moment as he wiped down the car, and got a tingling sensation as he leaned forward, his jeans tightened around his cute ass. 'Get a hold of yourself girl' she thought. She reached her hands behind her causing her shirt to tighten across her small breasts, and cleared her throat.Luke looked over his shoulder at Ellie. Damn she was cute, but she didn't act like she knew it. He gave her a small smirk."Sorry about the kitchen. I didn't stop to think that someone moving in wouldn't have dishes of their own.""Oh, no problem." Ellie countered quickly. "It's just that my last place, everything belonged to my room mates, and as long as I kept them fed they didn't care what I used." She smiled. "I could use a couple towels too. I'm on a budget so let's hit up that little French boutique, Tar-jay." Luke laughed at her joke and reached for the passenger side door opening it for her. He bowed with a flourish."After you milady."Luke was already winning points as she climbed into the car. He hopped in and started the car backing out of the driveway. On the way to the to the store Ellie drew him out asking what he was going to school for, and what he planned for after. He didn't do sports or really anything with friends. She could tell he was one of those quiet loner types, and he had a lot going on in there that nobody ever saw. She decided then and there that she'd make it her goal to draw him out of his shell."Maybe you can build my swanky café for me when you graduate." She winked at him.Luke looked over at her for a moment and smiled. "Yea I'll get right on that.""Seriously, that apartment is awesome. I bet it wouldn't be much of a stretch. Your dad said you planned it nearly free hand. You don't do something like that without real talent."Luke just shrugged and said thanks.They pulled into a parking space and Ellie grabbed a cart and hopped up on the rail, riding it a few feet towards the store like a kid. This gave Luke a great view of her backside and she knew he was looking by the expression she saw when she looked over her shoulder. He looked slightly shocked then looked down and away. She bit her lower lip and grinned. This was going to be fun, she thought.They made their way into the store and Ellie took the long way around to housewares and chose a cheap set of dinnerware, then some glasses and flatware. She went over the cooking stuff with a fine tooth comb looking at labels and chose a few items. The cart filled up fast with the large items. She decided that she'd done enough damage there and wandered around a corner and started up the aisle. Luke just pushed the cart along behind her watching her walk. He was pretty sure she hadn't wiggled her ass like that on the way in. She reached out to a blouse hanging next to the aisle and felt the fabric and held it out and let it go and she walked past a rack of lingerie.Ellie let out a little ooh when she saw a little yellow bra and panty set hanging up and took it off the rack. "What do you think?" She asked holding the cups up to her chest, grinning devilishly at Luke. His face turned red and he looked around."It's definitely your color." He said and mumbled something after."What?" She asked, making him repeat it.He breathed deep and replied. "Did you want to pick up some food while we're here? The basics at least?"Ellie gave him a sly smile. "Chicken.""I don't know if they have chicken, but they've got groceries. You know, canned, boxed and frozen food, stuff like that."She walked right up close to him and reached over and set the lingerie right in the top of the basket where he was sure to keep it at the forefront of his mind. "Sure, let's go stock the cupboards." She chose some basic dry goods, a couple cans here and there. "If I'm going to be a chef, I can't be relying on packaged goods too much, but sometimes a girl needs a night off." She grabbed a couple cans of soup and found some microwave popcorn piling it all on top of the cart. They made their way to the check out and the lady behind the counter was scanning away and looked up at the two of them noting what they were buying."You kids setting up home for the first time?" The lady smiled.Ellie wrapped an arm around Luke pulling them together and laid her head on his shoulder. "Yes, we're going to be so happy." She peeked out of the corner of her eye and noticed Luke had gone red again. She pursed her lips and slid her hand across his lower back taking her time letting it drop and grazing his ass. The feeling sent a shock through Luke and he wasn't sure how to react so he did his best to forget it happened. They brought their cart out to the car and packed it away. On the trip home they didn't speak, and just listened to the radio. Luke turned off the car and reached for the door when he felt Ellie put her hand on his and give it a squeeze."Sorry, I was just;” She said softly, biting her lower lip.Luke looked at her and nodded, and got out and began unloading the car. The little table was piled with boxes and bags were strewn around the floor.Luke was about to turn and leave when Ellie stopped him."I was just having a little fun. I didn't mean to embarrass you." She winked."I know, it's okay.""Are you busy this afternoon? I could use a hand unpacking all this stuff and washing the dishes.""Sure, I can help." He took the first box and opened it up and brought it into the kitchen and started loading the dishwasher with the plates and bowls. "We forgot cleaning supplies. I'll run downstairs I'm sure we've got plenty. He headed for the door and trotted down the stairs, and his own kitchen.Ellie decided to get more comfortable and wandered into the bedroom and lost the shirt and jeans. She had just pulled on her sweat pants when the door opened and Luke walked in. She hadn't bothered to close the bedroom door and he got a full on look at her standing there in her sweat pants and a lacy pink bra. His eyes locked on hers and he froze. Ellie just smiled and reached for her hoodie putting it on and zipping it up to mid chest just barely concealing the bra. She walked out of the bedroom."Relax it's the Internet age, I'm sure you've seen a girl in lingerie before.""Uh yea, sorry I should have knocked. It's just that I've been up here so much while decorating that I forgot someone lives here now."Ellie shrugged , "Mi casa es su casa. You're welcome up any time. I don't make it a habit to walk around like a lingerie model, don't worry. I don't have the body for it."Luke mumbled something, and Ellie was sure it was a denial of that claim but she just bit her lip to keep from smiling. Luke started running water to clean the larger items in the sink and Ellie started putting things into cupboards. The tight space meant they were brushing against each other often. Luke noticed Ellie used him as a balance whenever he was in reach, a hand on his shoulder when she leaned into a cabinet. She placed a hand on the small of his back again to see what he was cleaning."No abrasives, just soapy water on that one. That's a pro quality non-stick sauté pan right there." She winked. "It said so on the label."As she leaned back Luke got a light scent of her perfume. He hadn't noticed it before but it was sweet and flowery. Had she put it on after he'd gone downstairs he wondered. It was having an intoxicating effect, along with her touch. He was glad he was facing the sink to hide the bulge that was forming in his jeans."I'm going to go throw these towels in the wash real quick.""Okay I'll just stay here and slave away in your kitchen like a drudge." Luke's response was surprising causing Ellie to bust out laughing."Yes! I have my own kitchen drudge!" She did a little fist pump in triumph.Luke peeked over his shoulder as she made for the door watching her cute little ass with the store name plastered across the seat of her sweats. He'd better get out of here fast or he wasn't going to make a safe exit with the tent in the front of his jeans. He wiped down the last dish and headed down the stairs and poked his head into the garage telling her that he was done, and if she needed anything else to just let him know. She thanked him and he rushed into the house.Ellie went back up to find the dishes all cleaned and laid out waiting for her to decide where they'd be put. She worked efficiently putting things in their logical places and had just enough room to fit everything she'd bought. She saw the yellow lingerie she'd bought and smiled. She hadn't intended to buy it, but wanted to tease Luke. They were cute though so she put them in with her wash.The weekly grind began, everybody leaving the house and heading off in their respective directions. Ellie got home late from her job at the little café, and hit the books for an hour or so before taking a shower. She wandered into the bedroom and looked out the window hearing something moving around. She spied Luke hauling a trash can and recycling to the curb.Luke turned and looked up at the light in the window and saw her outlined in soft yellow light. She stood there in a long sleeve shirt, unbuttoned part way down the front. She lifted a hand and gave him a little wave and he waved back.Ellie noticed that after he waved he didn't go back inside right away and she pointed to the door and beckoned him. She smiled when he knocked on the door this time."Come on in. You already know I'm dressed this time.""Well I couldn't tell if you were wearing pants. What's up?""Nothing, I was bored and wondered if you wanted to hang out and watch TV or something.""Sure, I guess.""I'm in a junk food mood. Would you like some cookies and ice cream?""Yes, please." He replied with a little more gusto."I baked the cookies myself. The ice cream is store bought." She chuckled. "Go ahead and turn on the TV, find us something to watch.""What do you feel like?""Anything really, nothing to cerebral I get enough of that from school books." She scooped up a couple bowls of the ice cream, adding a couple cookies to each, and added spoons.She walked into the living room handing him a bowl and sat next to him curling her legs under her. The fact that her nipples were rock hard from standing in front of the open freezer wasn't lost on Luke, but he didn't stare. They sat watching the last few minutes of a sitcom, only the sounds of spoons tapping bowls and an occasional chuckle interrupted the silence. When the show ended Luke took the bowls into the kitchen and rinsed them out. When he came back Ellie noticed he had a little ice cream on his lower lip and did her best not to laugh."What?"She shook her head and patted the cushion next to her. When he sat she lifted his arm wrapping around her shoulders. "It's just that you missed a spot." She leaned in and licked the drying ice cream from his lower lip and smiled. It was make or break time, what would he do she wondered. The answer was only a moment away when the shock left his eyes it was replaced by hunger. Luke leaned into her and kissed her, she responded quickly returning it in kind. He was slow and a little clumsy, but he made up for it in ardor."Hmm , you taste like cookies and cream.""You do to." Luke said breathing in deeply. "I uh;”"Stop thinking so much." She leaned in and kissed him again, this time her tongue slipped past his lips looking to play. Luke parted his lips and was quickly assaulted, Ellie grabbed the front of his shirt for leverage as her tongue delved deeper luring him out. She felt bold and went with it, and threw a leg over his lap and settled down wrapping her arms around the back of his head and took the upper hand. A few minutes of oral assault and she stopped and smiled, their foreheads touched."You know you can touch me." She whispered. "I don't bite." He looked back at her wide-eyed, his chest heaving as he gasped for breath. She reached down and took his hands and placed them on her hips as she began again. She nudged his hands imploring him to explore and he began by lowering them around her flannel covered rear, massaging it with his strong hands. She responded with a soft moan, hoping to encourage him. It worked as he gripped her harder pulling her hips down against his. She could feel how hard he was through his jeans and was making her wet to know only a few layers of clothing kept this from getting out of hand."I uh;” Luke started."What?" Ellie asked softly kissing the tip of his nose."I uh, I've never really done this before." He said his cheeks coloring even more."You've never made out with a girl before?" She sat back on his knees, genuinely surprised. Luke was hot and he didn't even realize it."No." He said looking downward embarrassment apparent on his face.She lifted his chin and kissed him softly. "Well you're doing just fine for a first-timer, just relax." His hands slid upward lifting the hem of her shirt and his hands wrapped around her waist, his touch was hot on her skin kindling the fire burning inside. She wasn't sure if it was luck or instinct that made him break their kiss and graze her neck with his lips kissing softly down then back up to her ear but his lips were eager and she gasped as he nibbled her neck. His hands began exploring upward, her shirt rising with them when he suddenly stopped right at the base of her breasts. Her body was screaming to have him continue as her lips latched back on to his, their tongues dueling."Please?" She whispered softly. His thumbs were so painfully close but not completing the journey up her torso. He took a moment to realize what she was asking, and he lifted his thumbs brushing the bottom of her breasts. She gasped, she was nearly ready to rip her shirt off and bury his face into her chest but the buildup he was creating was so intense she didn't want it to end. His hands found her nipples, applying pressure and rolling them around. Ellie leaned her head back and whimpered as Luke just stared at his hands working underneath her shirt.In a swift movement Ellie had crossed her arms over her chest and whipped the shirt over her head, her hair falling wildly over her face. Luke's mouth dropped open as he saw what he was doing. Ellie noted that he'd stopped to stare, and reached up with her hands taking his and massaging her breasts with his large rough hands. She let out a delighted hum from deep in her throat as he began taking the initiative. He began to lean forward, then looked up into her eyes and sat back. Ellie wasn't going to let him off the hook and shook her head slowly, before reaching for the back of his head and pulling it to her breast."Don't shy away, follow your instincts." Ellie said softly."They're beautiful." He said before planting a kiss in the center of her chest. He kissed his way over and nibbled on the nipple with his lips before gently stroking it with his tongue. Ellie's breathing was getting more ragged and shallow. She grabbed him by the cheeks and tilted his head back and dove into his mouth tongue first."We should stop, before things get out of hand." She gasped between kisses. His hands were roaming up and down her back pulling her hard against him."Do we have to?" He gasped."Yes." She said rolling off of his lap, her bare chest shone with a flush of pink, her nipples were bright pink as well. She tugged her shirt out from behind her and held it to her chest as she got her breath back. "I don't want to be known as the kind of girl who puts out before the first date." She giggled.Luke just stared at her confused, longing to have her back in his arms. "Yea, I guess." After a few more minutes he spoke up again. "What are you doing Friday night?"Ellie's eyebrows went up and a smile spread across her face. "Working, but I'm off Saturday night.""Would you like to go out, with me I mean?" Luke said sheepishly."On one condition.""What's that?""That this isn't why you're asking." She said lifting the shirt and flashing her breasts at him.He stared at her chest for a moment and she covered back up. When their eyes met his expression softened and he shook his head. "You're beautiful, but that's not the only reason I'd like to go out with you.""Why then?" Her curiosity peaked.He shrugged. "You're fun, smart, you make me laugh, and you're beautiful, even fully dressed."She beamed up at him. "So what are we doing on Saturday?"Luke shrugged. "I'll think of something, trust me.""I'd better get some sleep; class in the morning."Ellie suppressed a giggle when he stood, the front of his jeans was prison for the raging monster that she'd whipped into a frenzy."Sorry." She said softly, and bit her lip."Don't worry, I'll take matters into my own hands." He sighed and she chuckled. She walked him to the door. As he turned to say goodnight she wrapped her arms around his neck dragging him down to her kiss while crushing her breasts against his chest. His hands instinctively went to her waist pulling her to him while their mouths locked. She brought her hand down between them and stroked him through his jeans."Don't beat him too bad, he's been a good boy tonight." Luke chuckled and left, taking the steps slowly.Ellie leaned back against the cool door, her eyes closed thinking about how the little things in life change when you least expect them. She hadn't had a steady boyfriend since last school year, and even then that wasn't very involved, they were more like friends with benefits. Luke on the other hand gave her a tingle that she hadn't felt since she was a teenager. She fret for a minute at the fact that she was older than him, but brushed that aside. Besides, Luke was a lot more mature than any 19 year old she'd met before. She stopped and grabbed a towel from the bathroom before heading to bed. She was going to need it after the evening she'd just had. She tossed her shirt onto the bed and spread out the towel and pushed off her flannel bottoms, her panties were soaked. She lay back on the towel rubbing herself slowly through the damp lace as she recalled the feel of his rough hands on her skin and the fire from his lips. She circled her clit through the fabric, with a sharp intake of breath she dragged her fingers over it. She reached over into her nightstand drawer, reaching for a small pink vibrator. She couldn't get out of the panties fast enough, pushing them down and kicking them onto the floor. She flipped the switch and it came to life and found the mark quickly. She didn't hesitate, she went right for the quick release while she imagined Luke between her legs performing the act she now performed upon herself. Her orgasm hit her like a rogue wave, ripping through her as she arched her back and moaned loudly. After a long moment of tension she relaxed back to the mattress, the vibrator slipping free onto the towel as she panted. She felt electrified a slight tremble overtook her. Eventually she wiped up the considerable mess she'd made, and sheepishly wondered how well sound proofed the walls were. There was a good ten or twelve foot breezeway between the main house and the garage so she didn't worry that she was overheard.Luke leaned back against the wall, his hard cock finally beginning to soften. He had quietly stepped into the garage when he got downstairs and leaned against the hood of his car to think about what had happened. He was also hoping that his erection would relax a bit before he went into the house, just in case he bumped into his father. He heard Ellie moving around upstairs and mentally followed her footsteps as she walked. He heard the creek of her getting into bed just above his left shoulder. He stood there for a moment longer and started hearing her making noises like she had only a little while before, but louder. It took him a moment to realize what she must be doing and the thought took him by surprise. She was upstairs getting herself off. He had a major ego boost from that, and her sounds were doing just the opposite for his jeans than he'd hoped. He decided to release the tension. He reached over for a couple of the heavy paper towels that were on a shelf there in the garage. He opened his fly releasing his engorged cock and began stroking it, while listening to her muffled moans. The feel of her strong, lithe body in his hands, the feel of her spread across his lap from only a few minutes earlier, the smell of her, so sweet and flowery. It wasn't long before he was hitting the point of no return. He heard her moan, and call out his name, the shock nearly made him stop mid stroke as his eyes opened instantly. A few sharp moans came from over his left shoulder and then silence. The realization hit just as his orgasm did, he hurried to catch his load with the paper towels. He leaned his head back catching his breath, then quickly cleaned up, ditching the evidence into one of the trash cans. He silently made his way into the house.Friday morning came and Ellie hopped into her car and after several attempts, it didn't start. She pounded on the steering wheel a few times, and thankfully the windows were up or the entire neighborhood would have heard a lovely young lady swearing like a sailor. She got out and peeked into the garage door window. Great, Luke's car was still there. She knocked on the door and he opened the door wearing only jeans. She was caught by surprise staring into his chest, a few dark wispy hairs curled against the lightly tanned skin. She looked up slowly seeing he was standing there with a toothbrush hanging out of his mouth."Hi, my car shit the bed, are you headed into school soon?" She asked smiling. Damn he looked this good rolling out of bed in the morning?"I don't have class for another hour, but I can give you a ride. C'mon in while I grab a shirt.""Not on my account, I hope, you look just fine without one." Ellie thought. Luke grabbed his books and laptop and they headed to school."Listen, I can get a ride to work after classes. What I was wondering was; would you be a sweetheart and pick me up after my shift? Nobody at work lives on this end of town."“Mmm; sure, no problem." He smiled. She gave him the address and time, and told him to come early if he wanted and she'd buy him dinner too.To be continued in part 2, by Member389 for Literotica.

Vicente Matías y Tarín Cortés han explicado en Más de uno como está siendo la entrega de las 400 toneladas de forraje que los profesionales cordobeses de AGACOR han donado a los ganaderos del norte de Cáceres. La desolación de Dominga tras perder su casa en los incendios: "Mires por donde mires es negro"Edilberto Rodríguez, pastor de la Cabrera: "Aquí hemos vivido siempre con el fuego"

BE WARNED: It's LuAnna, and this podcast contains honest, upfront opinions, rants, bants and general explicit content. But you know you love it! It's time to get TOTALLY EXTRA. Extra chat, extra rants, extra bants, extra stories, nonsense and more.On this week's Totally Extra: Kids smuggling a tortoise internationally, remote control revenge, your travel icks, misheard lyrics, the tale of Tar and Tar 2 and a moustache challenge.Remember, if you want to get in touch you can:Email us at luanna@everythingluanna.com OR drop us a WhatsApp on 07745 266947Please review Global's Privacy Policy: https://global.com/legal/privacy-policy/

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Laboratório de Tarô com Madama e Edy de Lucca: https://www.madama.site/laboratoriodetarotConsultas particulares: https://madama.gendo.app/Newsletter Madamail: https://substack.com/@madamailSiga @br000na e @horoscopinho no instagramcontato@madamabrona.com.br

Rob, Nico and Nick discuss cigarette companies, pumping gas, lotto tickets, the Menendez brothers, Regis & Kelly on 9/11, interstellar comets, DMT elves, the Biggest… The post Two Cents Radio: Episode #414 – Child Inventor of the Week appeared first on Too Many Thoughts.

Brooke and Brice are wrapping up their Amazing Race Season 15 rewatch in style with a special finale episode featuring the champs themselves. Meghan Whitney & Cheyne Whitney, winners of TAR 15, join the pod to break down that unforgettable Vegas finish, share behind-the-scenes tea, and reflect on their journey around the world. From wild taxi rides to Detours that tested their limits, we're reliving all the moments that made this season one for the books. Meghan & Cheyne also open up about what it truly felt like stepping on that final mat and hearing those magic words from Phil himself.