Podcasts about Temel

Týn nad Vltavou je díra světa, slyším od místních, když se jich ptám, jak se jim tu žije. Týn leží na soutoku Vltavy a Lužnice, v krajině modelované korytem řek. Dominantou širokého okolí jsou čtyři betonové věže Temelína, neustále chrlící různotvaré mraky páry. Většina obyvatel v Temelíně pracuje, nebo na tuto práci čeká. Žádné jiné velké pracovní příležitosti tady nejsou.

Týn nad Vltavou je díra světa, slyším od místních, když se jich ptám, jak se jim tu žije. Týn leží na soutoku Vltavy a Lužnice, v krajině modelované korytem řek. Dominantou širokého okolí jsou čtyři betonové věže Temelína, neustále chrlící různotvaré mraky páry. Většina obyvatel v Temelíně pracuje, nebo na tuto práci čeká. Žádné jiné velké pracovní příležitosti tady nejsou.Všechny díly podcastu Ranní úvaha můžete pohodlně poslouchat v mobilní aplikaci mujRozhlas pro Android a iOS nebo na webu mujRozhlas.cz.

Konuğumuz Düzce Üniversitesi Orman Fakültesi'nden Prof. Dr. Necmi Aksoy ile orman yangınlarının sebepleri ve nasıl önlenebileceği ve söndürme çalışmalarındaki temel eksikler hakkında konuşuyor; kendisinin tanık olduğu son Denizli Honaz Dağı ve geçen ay Geyve-Bilecik Havzası'nda yaşanan orman yangınlarından izlenimlerini dinliyoruz. 

Na jaře zastavil požár elektrické rozvodny provoz letiště Heathrow v Londýně, v dubnu ochromil obrovský blackout Španělsko, v červenci pak zažilo velký výpadek i Česko. Jak velkým bezpečnostním rizikem jsou kolapsy přenosových soustav?Hostem Ptám se já byl nastupující velvyslanec v Británii Václav Bartuška, který letos v létě po 19 letech skončil na pozici zvláštního zmocněnce ministerstva zahraničních věcí pro energetickou bezpečnost. Masivní výpadek elektrického proudu, který zažilo Česko 4. července, trval několik hodin a postihl asi milion odběratelů. Za blackout mohla mechanická závada - roztržení fázového vodiče, který přenáší elektřinu mezi elektrárnami a rozvodnami. Podrobnější příčiny výpadku se ještě vyšetřují.Podle bývalého zmocněnce pro energetickou bezpečnost Václava Bartušky není vyloučené, že se budou blackouty v budoucnu opakovat: „Máme vysokou míru na nestability v sítích v celé Evropě. Budeme ji mít v příštích letech. To je dáno tím, kam směřujeme: k většímu podílu neřiditelných zdrojů, z velké části obnovitelných. Klesá podíl toho, co se řídit dá, tedy uhlí, zemní plyn, jaderné elektrárny a voda. Takže ano, máme nové situace a budou nové situace. Nepochybně.“Výpadek ovšem může přijít opět až několik let, nebo nemusí po mnoho let dojít na žádný. „Blackout ve Španělsku (letos v dubnu) byl první velký v Evropě po 19 letech. Takže bych rozhodně nikoho nestrašil. Ale vědomí toho, že systém je křehký a že běží velkou část času na 100 procent výkonu i více, to je prostě pravda,“ prohlásil bývalý klíčový muž české energetiky.Václav Bartuška byl do roku 2001 generálním komisařem české účasti na Světové výstavě Expo 2000 v německém Hannoveru. Kromě zvláštního zmocněnce ministerstva poté také v letech 2010 až 2014 pracoval na pozici vládního zmocněnce pro rozšíření Jaderné elektrárny Temelín. V Londýně nyní nahradí velvyslankyni Marii Chatardovou.  S jakými pocity sleduje aktuální debaty o blackoutu v Česku? „Když mě před 19 lety jmenovali, tak jsem na první velké konferenci řekl, že by české energetice strašně prospěl takový pořádný dvoudenní blackout. Aby lidé pochopili, že elektřinu potřebují ke každodennímu životu. A za těch 19 let se to vědomí veřejnosti o elektřině výrazně změnilo,“ řekl Václav Bartuška a dodal: „Nás udržuje naživu spousta technologií, které nevnímáme. A křehkost této civilizace je něco, co si nechceme připustit. Elektřina je zásadní pro náš život, pro naše přežití. A jsem rád, že se dostala do popředí, je v centru pozornosti lidí.“Jaké poučení si z červencového výpadku vzít? Na jak velké investice do sítí se musíme připravit? Jaké nás čekají ceny energií? A na co se Česko musí v energetice v příštích letech zaměřit?--Podcast Ptám se já. Rozhovory s lidmi, kteří mají vliv, odpovědnost, informace.Sledujte na Seznam Zprávách, poslouchejte na Podcasty.cz a ve všech podcastových aplikacích.Archiv všech dílů najdete tady. Své postřehy, připomínky nebo tipy nám pište prostřednictvím sociálních sítí pod hashtagem #ptamseja nebo na e-mail: audio@sz.cz.

08.08.2025 | Dijital Hayat Bölüm546 - TRT Radyo1 | "Paradigmanın Değişimi: Dijital Yönetişim" Bilal Eren'in hazırlayıp, sunduğu Dijital Hayat programımızda bu hafta; İnnova Bilişim Genel Müdür Yardımcısı Emre Alıç ile; - Yönetişim Nasıl Tanımlanabilir? - Yönetim ile Yönetişim Arasındaki Fark Ne? - Dijital Yönetişim Nedir? - Yönetişimin Temel Özellik ve Unsurları Neler? - Başarılı Dijital Yönetişim için Sadece Bilgi ve İletişim Teknolojilerini İyi Kullanmak Yeterli mi? - Ülkemizden Başarılı Dijital Yönetişim Örnekleri Neler? - Bu Konuda Faaliyet Gösteren Kurumsal Yönetişim Derneği Amaç, Motivasyon ve Çalışmaları Neler? Başlıklarını konuştuk. Dijital Hayat, her cuma saat 15:30'da TRT Radyo1 mikrofonlarında canlı yayında... Tüm geçmiş ve gelecek yayınlarımız için; Web: https://www.dijitalhayat.tv

01.08.2025 | Dijital Hayat Bölüm545 - TRT Radyo1 | "Yapay Zeka İnsan Haklarını Nasıl Etkiliyor?" Bilal Eren'in hazırlayıp, sunduğu Dijital Hayat programımızda bu hafta; Yapay Zeka ve Dijital Politika Merkezi Başkanı Merve Hickok ile; - Yapay Zeka Temel İnsan Haklarını Nasıl Etkiliyor? - Günümüzde Yapay Zeka Sistemleri, Gizlilik ve Mahremiyet, Yaşam, Seyahat, İfade ve Bilgi Özgürlüğü gibi Temel İnsanlık Haklarını Tehdit mi Ediyor? - Donanım, Yazılım ve Dil Modelleri Bağlamında Büyük Yetenekler Kazanan Yapay Zeka Sistemlerinin Tehdit Ettiği En Karmaşık ve Acil Sorun Hangisi? - İnsan Haklarını Tehdit ve ihlal Eden Yapay Zeka Şirket ve Uygulamalarına Örnekler Neler? - Yaptığı Projeler ile Palantir Şirketi Örnek Olarak Verilebilir mi? - Bireysel ve Toplumsal Olarak Yapay Zeka Temelli Tehditlere Karşı Neler Yapılabilir? - Yapay Zeka ve Dijital Politika Merkezi'nin Amaç ve Çalışmaları Neler? Başlıklarını konuştuk. Dijital Hayat, her cuma saat 15:30​​​​​​​​​​​​​'da TRT Radyo1 mikrofonlarında canlı yayında... Tüm geçmiş ve gelecek yayınlarımız için; Web: https://www.dijitalhayat.tv

Dr. Joseph McCollom and Dr. Ramy Sedhom discuss precision palliative care, a new strategy that aims to align palliative care delivery with patient and caregiver needs instead of diagnosis alone. TRANSCRIPT ADN Podcast Episode 8-22 Transcript: What Is Precision Palliative Care? Rethinking a Care Delivery Problem Dr. Joseph McCollom: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Joseph McCollom. I'm a GI medical oncologist and palliative oncologist at the Parkview Packnett Family Cancer Institute here in Fort Wayne, Indiana. So, the early benefits of palliative care for patients with cancer have been well documented, but there are challenges in terms of bandwidth to how do we provide this care, given the workforce shortages in the oncology field. So today, we'll be exploring a new opportunity known as precision palliative care, a strategy that aims to align care delivery with patient and caregiver needs and not just diagnosis alone. Joining me for this discussion is Dr. Ramy Sedhom. He is the medical director of oncology and palliative care at Penn Medicine Princeton Health and a clinical assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine. Our full disclosures are available in the transcript of this episode.  Dr. Sedhom, it's great to have you on the podcast today. Thank you so much for being here. Dr. Ramy Sedhom: Thank you, Joe. It's a pleasure to be here and lucky me to be in conversation with a colleague and friend. Yes, many of us have heard about the benefits of early palliative care. Trials have shown better quality of life, reduced symptoms, and potentially even improved survival. But as we know, the reality is translating that evidence into practice, which is really, really challenging. So Joe, both you and I know that not every patient can see palliative care, or I'd even argue should see palliative care, but that also means there are still many people with real needs who still fall through the cracks. That's why I'm really excited about today's topic, which we'll be discussing, which is precision palliative care. It's a growing shift in mindset from what's this patient's diagnosis or what's this patient's prognosis, to what matters most for this person in front of me right now and what are their individual care needs. I think, Joe, it's very exciting because the field is moving from a blanket approach to one tailored to meet people where they actually are. Dr. Joseph McCollom: Absolutely, Ramy. And I think from the early days when palliative care was kind of being introduced and trying to distinguish itself, I think one of the first models that came to clinicians' eyes was Jennifer Temel's paper in The New England Journal of Medicine in 2010. And her colleagues had really looked at early palliative care integration for patients with advanced non–small cell lung cancer. And in that era – this is a pre-immunotherapy era, very early targeted therapy era – the overall prognosis for those patients are similar to the population I serve as a GI medical oncologist, pancreatic cancer today. Typically, median overall survival of a year or less. And so, a lot of her colleagues really wanted her to track overall survival alongside quality of life and depression scores as a result of that. And it really was a landmark publication because not only did it show an improvement of quality of life, but it actually showed an improvement of overall survival. And that was really, I think, revolutionary at the time. You know, a lot of folks had talked about if this was a drug, the FDA would approve it. We all in GI oncology laugh about erlotinib, which got an FDA approval for a 2-week overall survival advantage. And so, it really kind of set the stage for a lot of us in early career who had a passion in the integration of palliative care and oncology. And I think a lot of the subsequent ASCO, NCCN, COC, Commission on Cancer, guidelines followed through with that. But I think what we realized is now we're kind of sitting center stage, there's still a lot of resource issues that if we sent a referral to palliative care for every single patient diagnosed with even an advanced cancer, we would have a significant workforce shortage issue. And so, Ramy, I was wondering if you could talk a little bit about how do we help center in on who are the right patients that are going to have the greatest benefit from a palliative care specialist intervention? Dr. Ramy Sedhom: Thanks, Joe. Great question. So you mentioned Dr. Temel's landmark 2010 trial published in the New England Journal of Medicine. And it is still a game changer in our field. The results of her work showed not only improved quality of life and mood, but I think very surprisingly at the time, a survival benefit for patients with lung cancer who had received early palliative care. That work, of course, has helped shape national guidelines, as you've shared, and it also helped define early, as within 8 weeks of diagnosis. But unfortunately, there remains a disconnect. So in clinical practice, using diagnosis or stage as the only referral trigger doesn't really match the needs that we see show up. And I think unfortunately, the other part is that approach creates a supply demand mismatch. We end up either referring more patients than palliative care teams can handle, or at the opposite extreme, we end up referring no one at all. So, I actually just wanted to quickly give, for example, two real world contrasts. So one center that I actually have friends who work in, tried as a very good quality improvement incentive, auto-refer all patients with stage IV pancreas cancer to palliative care teams. And while very well intentioned, they saw very quickly that in a two-month period, they had 30 new referrals. And on the palliative care side, there were only 15 available new patient slots. On the other hand, something that I often see in practice, is a situation where, for example, consider the case of a 90-year-old with a low-grade B-cell lymphoma. On paper, low-risk disease, but unfortunately, when you look under the microscope, this gentleman is isolated, has symptoms from his bulky adenopathy, and feels very overwhelmed by many competing illnesses. This is someone who, of course, may benefit from palliative care, but probably doesn't check the box. And I think this is where the model of precision palliative care steps in. It's not really about when was someone diagnosed or what is the prognosis or time-based criteria of their cancer, but it's really fundamentally asking the question of who needs help, what kind of help do they need, and how urgently do we need to provide this help? And I think precision palliative care really mirrors the logic and the philosophy of precision oncology. So just like we've made strides trying to match therapies to tumor biology, we also need to have the same attention and the same precision to match support to symptoms, to context of a patient situation and their caregiver, and also to their personal goals. So I think instead of a blanket referral, we really need to tailor care, the right support at the right moment for the right person to the right care teams. And I think to be more precise, there's really four core elements to allow us to do this well. So first, we really need to implement systematic screening. Let's use what we already have. Many of our centers have patient reported outcomes. The Commission on Cancer motivates us to use distress screening tools. And the EHR is there, but we do very little to flag and to surface unmet care needs. We have seen amazing work from people like Dr. Ethan Bash, who is the pioneer on patient-reported outcomes, and Dr. Ravi Parikh, who used to be my colleague at Penn, now at Emory, who show that you could use structured data and machine learning to identify some of these patient needs in real time. The second piece is after a systematic screening, we really need to build very clear referral pathways. One very good example is what the supportive care team at MD Anderson has done, of course, led by Dr. Eduardo Brera and Dr. David Huey, where they have, for example, designed condition-specific triggers. Urgent referrals, for example, to palliative care for severe symptoms, where they talk about it like a rapid response team. They will see them within 72 hours of the flag. But at the same time, if the unmet need is a caregiver distress, perhaps the social work referral is the first part of the palliative care intervention that needs to be placed. And I think this helps create both clarity and consistency but also it pays attention to that provider and availability demand mismatch. Third, I really think we need to triage smartly. As mentioned in the prior example, not every patient needs every team member of the palliative care team. Some benefit most from the behavioral health intervention. Others might benefit from chaplaincy or the clinician for symptom management. And I think aligning intensity with complexity helps us use our teams wisely. Unfortunately, the greatest barrier in all of our health care systems is time and time availability. And I think this is one strategic approach that I have not yet seen used very wisely. And fourth, I really think we need to embrace interdisciplinary care and change our healthcare systems to focus more on value. So this isn't about more consults or RVUs. I think it's really about leveraging our team strengths. Palliative care teams or supportive care teams usually are multidisciplinary in their core. They often have psychologists, social workers, sometimes they have nurse navigators. And I think all of these are really part of that engine of whole person care. But unfortunately, we still are not set up in care delivery systems that unfortunately to this day still model fee for service where the clinician or the physician visit is the only quote unquote real value add. Hopefully as our healthcare systems focus more on delivery and on value, this might help really embrace the structure to bring through the precision palliative care approach. Dr. Joseph McCollom: No, I love those points. You know, we talk frequently in the interdisciplinary team about how a social worker can spend 5 minutes doing something that I could not as a physician spend an hour doing. But does every patient need every member every time? And how do we work as a unified body to deliver that dose of palliative care, specialized palliative care to those right patients and match them? And I think that perfect analogy is in oncology as a medical oncologist, frequently I'm running complex next-generation sequencing paneling on patients' tumors, trying to find out is there a genetic weakness? Is there a susceptibility to a targeted therapy or an immunotherapy so that I can match and do that precision oncology, right patient to the right drug? Similarly, we need to continue to analyze and find these innovative ways like you've talked about, PROs, EHR flags, machine learning tools, to find those right patients and match them to the right palliative care interdisciplinary team members for them. I know we both get to work in oncology spaces and palliative and supportive spaces in our clinical practice. Share a little bit, if you could, Ramy, about what that looks like for your practice. How do you find those right patients? And how do you then intervene with that right palliative oncology dose? Dr. Ramy Sedhom: So Joe, when I first started in this space as a junior faculty, one thing became immediately clear. I think if we rely solely on physicians to identify the patients for palliative care, we're unfortunately going to be very limited by what we individually, personally observe. And I think that's what reflects the reality that many patients have real needs that go unseen. So over the past few years, I've really worked with a lot of my colleagues to really work the health system to change that. The greatest partnership I've personally had has been working with our informatics team to build a real time EHR integrated dashboard that I think helps us give us a broader view of patient needs. What we really think of as the population health perspective. Our dashboard at Penn, for example, pulls in structured data like geriatric assessment results, PHQ-4 screens, patient reported outcomes, whether or not they've been hospitalized, whether or not these hospitalizations are frequent and recurrent. And I think it's allowed us to really move from a reactive approach to one that's more proactive. So let me give you a practical example. So we have embedded in our cancer care team, psycho-oncologists. They share the same clinic space, they're right down the hall. And we actually use this shared dashboard to review weekly trends in distress scores and patient reported outcomes. And oftentimes, if they see a spike in anxiety or worsening symptoms like depression, they'll reach out to me and say, “Hey, I noticed Mrs. Smith reported feeling very anxious today. Do you think it'd be helpful if I joined you for her visit?” And I think that's how we could really use data and teamwork to offer and maximize the right support at the right time. Like many of our other healthcare systems, we also have real-time alerts for hospitalizations. And I think like Dr. Temel's most recent trial, which we'll discuss at some point, I'm sure, it's another key trigger for vulnerability. I think whenever someone's admitted or discharged, we try to coordinate with our palliative care colleagues to assess do they need follow-up and in what timeline. And we know that these are common triggers, progression of disease, hospitalizations, drops in quality-of-life. And it's actually surprisingly simple to implement once you set up the right care structures. And I think these systems don't just help patients, which is what I quickly learned. They also help us as clinicians too. Before we expanded our team, I often felt this weight, especially as someone dual trained in oncology and palliative medicine, as trying to be everything to everyone. I remember one patient in particular, a young woman with metastatic breast cancer who was scheduled for a routine pre-chemo visit with me. Unfortunately, on that day, she had a very dramatic change in function. We whisked her down to x-ray and it revealed a pretty large pathologic fracture in her femur. And suddenly what was scheduled as a 30-minute visit became a very complex conversation around prognosis, urgent need for surgery and many, many life changes. And when I looked at my Epic list, I had a full waiting room. And thankfully, because we have embedded palliative care in our team, I was able to bring in Dr. Collins, the physician who I work with closely, immediately. She spent the full hour with the patient while I was able to continue seeing other patients that morning. And I think that's what team-based care makes possible. It's not just more hands on deck but really optimizing the support the patient needs on each individual day. And I think last, we're also learning a lot from behavioral science. So many institutions like Penn, Stanford, Massachusetts General, they've experimented with a lot of really interesting prompts in the EHR. One of them, for example, is the concept of nodes or the concept of prompt questions. Like, do you think this patient would benefit from a supportive care referral? And I think these low-level nudges, in a sense, can actually really dramatically increase the uptake of palliative care because it makes what's relevant immediately salient and visible to the practicing physician. So I think the key, if I had to maybe finish off with a simple message: It's not flashy tech, it's not massive change against staffing, but it's having a local champion and it's working smarter. It's asking the questions of how can we do this better and setting up the systems to make them more sustainable. Dr. Joseph McCollom: I appreciate you talking about this because I think a lot of folks want to put the wheels on in some way and they don't know where to get started. And so I think some of the models that you've been able to create, being able to track patients, screen your population, find the right individuals, and then work within that team to be able to extend, I think when you have an embedded palliative care specialist in your clinic, they expand your practice as a medical oncologist. And so you can make that warm handoff. And that patient and that caregiver, when they view the experience, they don't view you as a medical oncologist, someone else as a palliative care specialist, they view that team approach. And they said, "The team, my cancer team took care of me." And I think we can really harness a lot of the innovative technological advancements in our EHR to be able to prompt us in this work. I know that Dr. Temel had kind of set the stage for early palliative care intervention, and you did mention her stepped palliative care trial. Where do you see some of the future opportunities as we continue to push the needle forward as oncologists and palliative care specialists? What do you see as being the next step? Dr. Ramy Sedhom: So for those who are not familiar with the stepped palliative care trial, again, work by Dr. Temel, I think it's really important to explain not just the study itself, but I think more importantly, what it's representing for the future of our field. First, I really want to acknowledge Dr. Temel, who is a trailblazer in palliative oncology. Her work has not only shaped how we think about timing and delivery, but really about the value of supportive care. And more importantly, I think for all the young trainees listening, she had shown that rigorous randomized trials in palliative care are possible and meaningful. And I think for me, one quick learning point is that you could be an oncologist and lead this impactful research. And she's inspired many and many of us. Now let's quickly transition to her study. So in this trial, the stepped palliative care trial, patients with advanced lung cancer were randomized into two groups. One group followed the model from her landmark 2010 New England Journal of Medicine paper, which was structured monthly palliative care visits, again, within eight weeks of diagnosis. The second group, which is in this study, the intervention or the stepped palliative care group, received a single early palliative care visit. Think of this as a meet and greet. And then care was actually stepped up. If one of three clinical triggers happened. One, a decline in patient reported quality of life as measured by PROs. Two, disease progression, or three, hospitalization. And the findings which were presented at ASCO 2024 were striking. Clinical outcomes, very similar between the two groups. And this included quality-of-life, end-of-life communication, and resource use. But I think the take-home point is that the number of palliative care visits in the stepped group was significantly lower. So in other words, same impact and fewer visits. This was a very elegant example of how we can model precision palliative care, right sizing patient care based on patient need. So where do we go from here? I think if we want this model to take root nationally, we really need to pull on three key levers: healthcare systems, healthcare payment, and healthcare culture. So from a system alignment, unfortunately, as mentioned too often, the solution to gaps in palliative care is we need more clinicians. And while yes, that's partly true, it's actually not the full picture. I think what we first need to do and what's more likely to be achieved is to develop systems that focus on building the infrastructure that maximizes the reach of our existing care teams. So this means investing in nurse navigation, real-time dashboards with patient-reported outcomes and EHR flags, and again, matching triage protocols where intensity matches complexity. And the goal, as mentioned, isn't to maximize consults, but to really maximize deployment of expertise based on need. The second piece is, of course, we need payment reform. So the stepped palliative care model only works when it allows continuous patient engagement. But unfortunately, current pay models don't reward or incentivize that. In fact, electronic PROs require a very high upfront financial investment and ongoing clinician time with little to no reimbursement. Imagine if we offered bundled payments or value-based incentives for teams that integrated PROs. Or imagine if we reimbursed palliative care based on impact or infrastructure instead of just fee-for-service volume. There is a lot of clear evidence that tele-palliative care is effective. In fact, it was the Plenary at ASCO 2024. Yet we're still battling these conversations around inconsistent reimbursement, and we're always waiting on whether or not telehealth waivers are gonna continue. So I think most importantly is we really need to recognize the broader scope of what palliative care offers, which is caregiver support, improving navigation, coordinating very complex transitions. To me, and what I've always prioritized as a champion at Penn, is that palliative care is not a nice to have, and neither are all of these infrastructures, but they're really essential to whole person care, and they need to be financially supported. And last, we really need a culture shift. We need to change from how palliative care is perceived, and it can't be something other. It can't be something outside of oncology, but it really needs to be embraced as this is part of cancer care itself. I often see hesitancy from many oncologists about introducing palliative care early. But it doesn't need to be a dramatic shift. I think small changes in language, how we introduce the palliative care team, and co-management models can really go a very long way in normalizing this part of patient care. And I'm particularly encouraged, Joe, by one particular innovation in this space, which is really the growth of many startups. And one startup, for example, is Thyme Care, where I've seen them working with many, many private practices across the country, alongside partnerships with payers to really build tech-enabled navigation that tries to basically maximize triage support with electronic PROs. And to me, I really think these models can help scale access without overwhelming current care teams. So precision palliative care, Joe, in summary, I think should be flexible, scalable, and really needs to align based on what patients need. Dr. Joseph McCollom: No, I really appreciate, Ramy, you talking about that it really takes a village to get oncology care in both a competent and a compassionate way. And we need buy-in champions at all levels: the system level, the administrative level, the policy level, the tech level. And we need to change culture. I kind of want to just get your final impressions and also make sure that we make our listeners aware of our article. We should be able to have this in the show notes here as well to find additional tools and resources, all the studies that were discussed in today's episode. But, Ramy, what are some of your kind of final takeaways and conclusions? Dr. Ramy Sedhom: Before we wrap up, I just want to make sure we highlight a very exciting opportunity for residents considering a future in oncology and palliative medicine. Thanks to the leadership of Dr. Jamie Von Roen, who truly championed this cause, ASCO and the ABIM (American Board of Internal Medicine) have partnered to create the first truly integrated palliative care oncology fellowship. Trainees can now double board in just two years or triple board in three with palliative care, oncology, and hematology. And I think, Joe, as you and I both know, it's incredibly rewarding and meaningful to work at this intersection. To close our message, if there's one message I think listeners should carry with them, it's that palliative care is about helping people live as well as possible for as long as possible. And precision palliative care simply helps us do that better. We need to really develop systems that tailor support to individual need, value, and individual goals. Just like our colleagues in precision oncology mentioned, getting the right care to the right patient at the right time, and I would add in the right way. For those who want to learn more, I encourage you to read our full article in JCO, which is “Precision Palliative Care As a Pragmatic Solution for a Care Delivery Problem.” Joe, thank you so, so much for this thoughtful conversation and for your leadership in our field. And thank you to everyone for listening. Thank you all for being champions of this essential part of cancer care. If you haven't yet joined the ASCO Palliative Care Communities of Practice, membership is free, and we'd love to have you. Dr. Joseph McCollom: Thank you, Ramy, not only for sharing your insights today, but the pioneering work that you have done in our field. You are truly an inspiration to me in clinical practice, and it is an honor to call you both a colleague and friend.  And thank you for our listeners for joining us today. If you value the insights that you've heard on the ASCO Daily News Podcast, please subscribe, rate, and review wherever you get your podcasts. Thanks again. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Joseph McCollom @realbowtiedoc Dr. Ramy Sedhom @ramsedhom Follow ASCO on social media:   @ASCO on X (formerly Twitter) ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn   Disclaimer: Dr. Joseph McCollom: No relationships to disclose Dr. Ramy Sedhom: No relationships to disclose

Energetici by mohli do jaderné elektrárny Temelín dopravovat díly na opravu nebo případnou dostavbu po Vltavě. Pomocí vrtů teď kvůli tomu Povodí Vltavy prověřuje stav silnice u hráze Slapské přehrady. Chybí tam výtah pro lodě a těžký náklad by po ní z dolní části řeky musely na přehradu převážet tahače.

Dijital çağda savaşın ve egemenliğin derinliklerine iniyoruz. Carl Schmitt'in Partisan Teorisi'ni modern dijital alana uyarlayarak, Bitcoin ve kripto varlıkların neden açık birer askeri varlık ve asimetrik savunma teknolojisi olarak görülebileceğini inceliyoruz. Mahremiyetin devletler tarafından sistematik olarak yok edildiği, panoptikonun her yanı sardığı bir dünyada, "kripto-partisan" adında yeni bir tarihi figürün doğuşuna tanıklık ediyoruz.Bu devrimci figür, kimliğini ustaca gizleyerek ve kriptografi tekniklerini kullanarak devlete karşı şiddet içermeyen bir ekonomik savaş başlatıyor. Temel amaç, devletin fiat para ve seigniorage (para basma) yoluyla beslenen "Behemoth" yapısını ekonomik olarak aç bırakmaktır. Bitcoin'in ortaya koyduğu yeni ekonomik topografya, "cuius regio, eius economia" (Kimin hükümranlığıysa, onun ekonomisi) ilkesini "cuius economia, eius regio" (Kimin ekonomisiyse, onun hükümranlığı) şekline dönüştürüyor.Bu yeni savaşın temelinde, "Veritas, non auctoritas facit legem" (Gerçek, otoriteyi değil, meşruiyeti yaratır) prensibi yatıyor. Bu, Hobbes'un egemen güç tanımının doğrudan bir tersine çevrilmesidir ve yalanlarla yönetilen bir dünyada silahlı bir hakikat biçimi sunar. Kriptografi, bireyin kimliğini koruyarak devleti "dost" ya da "düşman" olarak sınıflandırma yeteneğinden mahrum bırakır ve total mahremiyet sağlar.Hükümetlerin, bireylerin mahremiyetini ve haklarını sürekli ihlal ederek "mutlak düşman" haline geldiği bu çağda, kripto-partisan, bu kâbus gibi gözetim rejimine karşı duran son devrimci figür olarak öne çıkıyor. Satoshi Nakamoto'nun başlattığı bu hareket, fiziksel sınırların ötesinde yeni bir sosyal düzenin kurulmasına zemin hazırlıyor. Bitcoin'in içerdiği radikal koruma ve ekonomik özgürlük araçlarıyla, her insanın bu güce sahip olma hakkı vurgulanmaktadır. Kripto çağının bu nihai safhasında, şifreli ağın her şeyi yutmaya başladığı bir dönemin eşiğindeyiz.Kaynak

Jay Woods, Chief Global Strategist, Freedom Capital Markets discusses how he is seeing signs of weakness with his favourite momentum indicator in the RSI is showing a slight bearish divergence. He believes much of the rally off the lows needs to be digested and accepted before climbing higher, especially in the S&P 500 stocks. Produced/Presented: Ryan Huang Image by Temel from PixabaySee omnystudio.com/listener for privacy information.

Önce bazı sert gerçekleri hatırlayalım. Dünyada uyuşturucu pazarı yıllık 450 milyar dolar ila 600 milyar dolar arasında bir ekonomiye oturuyor. Bu ekonomi, 290 milyonu aşkın ve çoğunluğu gençlerden oluşan bağımlılardan temin ediliyor. Dünyadaki tüm ölümlerin yüzde dört buçuğu da uyuşturucu ve alkol bağımlılığına bağlı olarak gelişiyor. Bağımsız kuruluşların ve STK'ların yaptığı güncel araştırmalar, Türkiye'de 2 milyon uyuşturucu bağımlısı olduğunu ortaya koyuyor.

Son bir yıldır Avrupa'nın ekonomik durumu hakkında pek çok yazı kaleme aldık. Temel fikrimiz iki konu üzerindeydi birincisi Avrupa'lı şirketlerin yaşlanan sahiplik, kadro ve gerileyen motivasyonları gibi sebeplerden dolayı kapanma veya el değiştirme sürecinde olduğu diğeri ise Avrupa Birliği'nin siyasi ve ekonomik olarak kendini en az elli yıl genç gösteren aynada görme çabasının getirdiği stratejik körlüktü.

Bezemoční šprtka, kterou maminka v dětství nebrala na hrady a zámky, ale na výlety do dolů. Tak s nadsázkou popisuje sama sebe Adéla Chalupová, první ženská operátorka jaderné elektrárny Temelín a členka letošního Forbes výběru 30 pod 30. A jak už to u nadsázky bývá, podstatná část vychází ze skutečných událostí. S Adélou Chalupovou si povídal šéfredaktor Forbesu Zdravko Krstanov v rámci živé série rozhovorů Forbes Misfits Talks. Tu letos Forbes Česko pořádá společně s J&T Bankou na nejlepším místě karlovarského filmového festivalu. Akce staví na lidech, kteří nešli vyšlapanými cestami, ale vykročili mimo systém. Adéla je nepochybně jednou z nich.

Emek, sermaye, doğal kaynak, teknoloji ve girişimcilik geleneksel olarak kabul edilen temel üretim faktörleridir. Temel üretim faktörleri olarak emek ve nitelikli işgücü ve özellikle günümüzde bilgiye dayalı ekonomilerinde teknolojik ilerlemeler ekonomik büyümenin vazgeçilmez faktörlerindendir.

Akika kurbanı nedir?Akika kurbanı, bir çocuğun doğumu vesilesiyle Allah'a şükür ve çocuğu koruma niyetiyle kesilen bir kurbandır. Temel olarak bir Arap geleneğidir ve içinde günah barındırmadığı, aksine sadaka manası içerdiği için Hz. Peygamber (sallallahu aleyhi vesellem) bu geleneğe müdahale etmemiş, kendisi de uygulamıştır.

Yetkili Biri'nin bu bölümünde konuğumuz, dermatoloji uzmanı Doç. Dr. Ezgi Özkur!

„Vlastně je to podobně jako u toho Homera Simpsona: Sedím spolu s dalšími třemi kolegy v místnosti plné tlačítek, displejů v blokové dozorně, tedy na velíně jaderné elektrárny,“ popisuje Adéla Chalupová, operátorka JE Temelín a mimo jiné i atomová influencerka.

„Vlastně je to podobně jako u toho Homera Simpsona: Sedím spolu s dalšími třemi kolegy v místnosti plné tlačítek, displejů v blokové dozorně, tedy na velíně jaderné elektrárny,“ popisuje Adéla Chalupová, operátorka JE Temelín a mimo jiné i atomová influencerka.Všechny díly podcastu Hovory můžete pohodlně poslouchat v mobilní aplikaci mujRozhlas pro Android a iOS nebo na webu mujRozhlas.cz.

Kitap 1 (ing)Kitap 2 (tr)Kitap 3 (tr)Sokratik Sorular PDFChatGPT soruları:Bu durumun tam tersi ne olurdu? – Bir durumu ya da argümanı tersine çevirmek, farklı perspektifler kazanmanızı sağlar.Bu görüş, ne tür bir çıkar sağlıyor? – Hangi değerler veya çıkarlar bu düşünceyi savunmayı tetikliyor olabilir?Buna tamamen katılmasam da, savunulan görüşün güçlü yönleri nedir? – Karşıt görüşleri anlamak ve takdir etmek, daha yapıcı bir tartışma ortamı yaratır.Bu konuya dair göz ardı ettiğimiz temel bir faktör var mı? – Tartışmanın gölgede kalan, belki de önemsenmeyen unsurlarına dikkat çekmek faydalıdır.Bu durumu daha geniş bir bağlama yerleştirsek, ne gibi çıkarımlar yapabiliriz? – Küresel, tarihsel veya daha geniş bir toplumsal bağlamda bir durumu ele almak, derinlemesine analiz yapılmasına olanak tanır.Bu durumda, en büyük risk nedir? – Kararların ve düşüncelerin olası olumsuz sonuçları üzerine düşünmek, daha dikkatli ve sorumlu bir yaklaşım gerektirir.Eğer bu düşünceyi sadece mantıklı bir şekilde savunmamız gerekseydi, nasıl savunurduk? – Duygusal veya ideolojik etmenlerden bağımsız bir mantıklı savunma yapmayı düşündürür.Bu görüş, insan doğasıyla ne kadar uyumlu? – İnsan psikolojisini ve doğasını göz önünde bulundurmak, felsefi derinlik kazandırabilir.Birinin bu görüşe katılmasının ardında ne tür bir yaşam deneyimi olabilir? – İnsanların düşünce biçimlerinin kişisel geçmişlerinden nasıl etkilendiğini anlamak, empati kurmayı sağlar.Gerçekten de bu çözüm, uzun vadede gerçekten etkili olabilir mi? – Kısa vadeli çözümlerin yanıltıcı olabileceğini göz önünde bulundurmak, daha derin bir perspektif sunar.Bu önerilen çözüm, en çok kimlere yarar sağlar? Kimler zarar görebilir? – Farklı sosyal grupların çıkarlarını incelemek, daha adil ve dengeli çözümler üretmeye yardımcı olabilir.Bu görüş, hangi varsayımlar üzerine inşa ediliyor? – Temel inançlar veya kabuller üzerine düşünmek, daha sağlam ve tutarlı argümanlar üretmeye yönlendirir.Bu fikir sadece teorik mi, yoksa pratikte de uygulanabilir mi? – Gerçek dünya uygulamaları, soyut düşüncelerle yüzleşmeye olanak tanır.Bu durumu kabul edersek, bundan sonra ne yapmalıyız? – Somut adımlar ve pratik sonuçlar üzerine düşünmek, tartışmayı daha verimli hale getirebilir.Eğer bu görüşün geçerliliği sınanırsa, hangi kriterlerle ölçmeliyiz? – Ölçülebilir kriterler ve somut veriler, tartışmaların daha objektif hale gelmesini sağlar.Bunun karşısındaki düşüncenin savunucusu olsaydım, nasıl bir argüman kurardım? – Empati kurarak karşı görüşü anlamak, daha adil bir tartışma ortamı oluşturur.Bu argüman ne kadar genellenebilir? Her durumda geçerli mi? – Her durum için geçerli olup olmadığına dair bir sorgulama, sağlıklı bir tartışmanın temelini atar.Bunu savunmak, belli bir ideolojiye ya da dünya görüşüne hizmet ediyor olabilir mi? – İdeolojik etkilerin farkında olmak, daha bilinçli bir şekilde tartışmayı yönlendirebilir.Bu düşünceyi ne kadar 'kesin' kabul etmemiz gerekir? – Mutlak doğrular yerine, olasılıkları ve belirsizlikleri tartışmak daha esnek bir yaklaşım yaratır.Bu durum, bizim için hangi ahlaki sorumlulukları doğuruyor? – Ahlaki sorumlulukları tartışmak, kişisel değerlerin tartışmaya dahil edilmesini sağlar.

S jedním procentem větrné elektřiny nepatří Česko v tomto ohledu mezi velké tahouny. Zvlášť třeba oproti Dánsku, které vítr pohání víc než z poloviny, nebo dalším devíti evropským zemím, kde je podíl větru na spotřebě víc než pětinový.Zpoždění Česka by měl urychlit nový zákon, který se na poslední chvíli a expresním způsobem schvaluje v parlamentu. Zavádí garantované poplatky pro obce a hlavně nový povolovací režim v těch místech, kde turbíny nebudou v žádném konfliktu s jinými soukromými či veřejnými zájmy.Nový zákon je podle předsedy Komory obnovitelných zdrojů Štěpána Chalupy poslední součástkou legislativních úprav z poslední doby, díky kterým by se mohla větrná energetika po letech strádání v Česku odblokovat. Výhledově by mohla vyrábět víc než Dukovany či Temelín, uvedl Chalupa v Agendě SZ Byznys.Agenda. Rozhovory s top lídry českého byznysu, zakladateli firem, odborníky. Čtvrthodinka o byznysu z první ruky.Každý všední den na SZ Byznys a ve všech podcastových aplikacích.Odebírejte na Podcasty.cz, Apple Podcasts nebo Spotify.

SESLİ DERGİ

Bölüm içeriği ve zaman damgaları:00:00 Giriş | Takip Et, Bildirimleri Aç00:15 PNAS ve araştırma hakkında00:58 İki Teori, İki Zıt Sonuç01:43 Kim için Ne Kadar Para, Ne Kadar Mutluluk?03:28 Bu Ne Anlama Geliyor?04:07 Peki Bunu Hayatımıza Nasıl Uyarlarız?04:45 Kapanış | Bölümü PaylaşBölümle ilgili bağlantılar:PNAS: Income and emotional well-being: A conflict resolved (Matthew A. Killingsworth, Daniel Kahneman, Barbara Mellers) https://www.pnas.org/doi/epdf/10.1073/pnas.2208661120Bir "Zorlu Ekonomilerde Servet Edinme ve Varlık Yönetimi" yayını olan Finans Podcasti, tüm sosyal ağlarda @‌finanspodcasti kullanıcı adıyla, tüm podcast platformlarında ise adıyla bulunabilir. Soru, öneri ve diğer iletişim ihtiyaçları için finanspodcasti@gmail.com e-posta adresinden bana ulaşabilirsiniz. Tüm önemli sayfaların bağlantıları https://linktr.ee/finanspodcasti adresinde.Bölümü bulmanızı kolaylaştıracak diğer ilgili konu başlıkları: Paranın Psikolojik Etkisi, Gelir ve Yaşam Tatmini, Finansal Güvence ve Huzur, Temel İhtiyaçları Karşılamak, Parayla Gelen Özgürlük, Mutluluğun Maddi Boyutu, Ekonomik Refah ve Ruh Hali, Para ve Tatmin Düzeyi, Harcama Alışkanlıkları, Deneyim Harcamaları, Statü Yarışı ve Mutluluk, Tüketimle Gelen Geçici Tatmin, Parayla Zaman Satın Almak, Özgürlük İçin Para, Para ve Sosyal İlişkiler, Finansal Güç ve Kontrol Hissi, Yeterince Paraya Sahip Olmak, Mutluluğun Eşiği, Gelir Seviyesi ve Memnuniyet, Zenginlik ve Yalnızlık, Parayla Gelen Sorumluluklar, Maddi Varlık ve Manevi Denge, Para Bir Araçtır Amaç Değil, Tatmin Edici Harcama Davranışları, Gelir Artışı ve Yaşam Kalitesi, Finansal Hedeflere Ulaşmanın Etkisi, Kıyaslamalı Refah Algısı, Finansal Stres ve Ruh Sağlığı, Paranın Getirmediği Şeyler

Bölüm içeriği ve zaman damgaları:00:00 Giriş | Takip Et, Bildirimleri Aç00:29 Neden küçük firmalar?00:59 Potansiyelli firmaları nasıl bulacağız?01:39 Yönetimin önemi02:06 Haber akışı ve raporlar02:32 Riskler ve ihtimaller02:53 Keşfedilmemişi keşfetmek ve temel analiz03:30 Forumlar ve diğer görüşler04:51 Kapanış | Bölümü PaylaşBir "Zorlu Ekonomilerde Servet Edinme ve Varlık Yönetimi" yayını olan Finans Podcasti, tüm sosyal ağlarda @‌finanspodcasti kullanıcı adıyla, tüm podcast platformlarında ise adıyla bulunabilir. Soru, öneri ve diğer iletişim ihtiyaçları için finanspodcasti@gmail.com e-posta adresinden bana ulaşabilirsiniz. Tüm önemli sayfaların bağlantıları https://linktr.ee/finanspodcasti adresinde.Bölümü bulmanızı kolaylaştıracak diğer ilgili konu başlıkları: Gelecek Vaat Eden Şirketleri Keşfetmek, Erken Aşama Yatırımlar, Yüksek Getiri Potansiyeli, Girişim Sermayesi Mantığı, Küçük Şirket Analizi, Büyüme Odaklı Yatırım, Potansiyel Taşıyan Hisseler, Şirket Temellerini İncelemek, İş Modeli Analizi, Karlılık ve Büyüme Oranları, Finansal Tabloları Okumak, Rekabet Üstünlüğü Tespiti, Yönetim Kadrosu Değerlendirmesi, Sektör Trendlerini Takip Etmek, Risk ve Getiri Dengesi Kurmak, Küçük Sermaye Büyük Getiri, İnovasyon Odaklı Şirketler, Piyasa Değeri Düşük Ama Güçlü Temel, İyi Fikir Kovalayan Girişimler, Hisse Senedi Seçimi, Stratejik Yatırım Kararları, Uzun Vadeli Potansiyel, Değer Yatırımcılığı Yaklaşımı, Borsa Dışı Potansiyel İşletmeler, Derinlemesine Şirket Araştırması, Geleceğin Devleri Olacak Firmalar, Hızlı Büyüyen Sektörlerde Firma Seçimi, Yenilikçi İş Fikirlerine Yatırım Yapmak, Riskli Ama Kazançlı Yatırımlar

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Česko má dvě jaderné elektrárny – v Dukovanech a v Temelíně. Přestože jsou v té první čtyři reaktory a ve druhé pouze dva, jejich výkon je v součtu prakticky totožný. V roce 2024 však patřilo prvenství Temelínu, který dodal do sítě 15 terawatthodin elektřiny.

Adéla Chalupová se chtěla původně zabývat leteckou dopravou. Díky chybě v přihlášce se však nakonec stala operátorkou sekundárního okruhu jaderné elektrárny Temelín. „Ta práce spočívá hlavně v tom provozovat zodpovědně elektrárnu, takže kontrolujeme její chod a zároveň plníme činnosti dle denního plánu,” vysvětluje ve speciálním vysílání Dobrý den Radiožurnálu Chalupová.Všechny díly podcastu Host Lucie Výborné můžete pohodlně poslouchat v mobilní aplikaci mujRozhlas pro Android a iOS nebo na webu mujRozhlas.cz.

Kobraların gündeminde bu hafta; cezası ev hapsine çevrilen Mahir Polat, demokrasinin sonunu getiren The Guardian, işkence ve çıplak arama yok diyerek yargı bağımsızlığını vurgulayan Adalet Bakanı, yavaş yavaş serbest bırakılan gençler, tutuklu 139 genç için istenen 3 yıl hapis cezası, sadece baltalılar içerde diyen Milli Eğitim Bakanı, iddianamesi hazırlanan Ümit Özdağ, babaevine baskın yapılan ve hiçbir şey bulunamayan Ekrem İmamoğlu, mazlumların imdadına koşan dev yürek Mahmut Tanal ve Adalet Bakanlığı önündeki gece nöbeti, gözaltına alınan ardından serbest kalan gazeteciler TimurSoykan ve Murat Ağırel, CHP'nin olağanüstü kurultayına olağanüstü aday adayı Berhan Şimşek damgası ve son sürat giden Özgür Özel, "cuntacı" meselesi ve yaşananlar, yeniden aramıza dönen Bahçeli, imara açılan Kanal İstanbul arazileri, Amerika'da başlayan Trump karşıtı protestolar, gümrük vergileriyle çocuk gibi oynayan Trump, Netenyahu görüşmesine damga vuran Erdoğan açıklaması, Trump'ın yeni ekonomi modeli; içgüdü var. Cumhurbaşkanı köşesinde ise; CHP tarihi anlatılan bir garip grup toplantısı, koltuk sevdalısı liderler ve fırtına öncesi sessizlik var. Haftanın bütün gündemini konuştuğumuz yepyeni bölüm yayında! Kobralara destek olmak için: http://kreosus.com/kobrakobrapodcastTwitter: http://twitter.com/kobrapodInstagram: http://instagram.com/kobrakobrapodcast

What if your birth chart could help you find the parts of you longing to be witnessed? What if the stars weren't about prediction—but about reflection? In this rich and expansive conversation, I'm joined by Sarah Temel, licensed trauma therapist, IFS practitioner, and founder of No Bad Charts, to explore the deeply supportive intersection of Internal Family Systems (IFS) and evolutionary astrology. ____________________________ We dive into:

Anadolu'nun Şifacı Kadınları'nı sunduğum programın bu haftaki konuğu Berfu Ergenekon. 1975 yılında Almanya'da doğan Berfu, Kocatepe Üniversitesi Kamu Yönetimi bölümünden mezun oldu. Bir süre bir holdingde yöneticilik yapan Berfu, hamile kaldıktan sonra bir süre çalışmadı. 30'lu yaşlarında senaryo yazmaya başlayan Berfu, ruhsal olarak arayışta olduğu bir dönemde rehberliyle tanıştı. Nero koçluk, human design, Temel kuantum alanı ve tarot eğitimleri alan Berfu, rüyalarında tarot açılımlarını görmesiyle, insanların tekamül yolculuklarına rehberlik sunan Kolektifte hal ve ahval adında bir kanal açtı. Halen senaryo yazarlığına devam eden Berfu'nun çalışmalarını ve paylaşımlarını https://www.instagram.com/kolektifte_hal_ve_ahval/?igsh=ZmEzbWwyOWtkMnJz# Instagram adresinden veya https://www.youtube.com/@Kolektiftehalveahval Youtube kanalından takip edebilirsiniz. Keyifli dinlemeler :)*****Mart Ayı AŞK Buluşması'nda buluşalım :)11 Mart Salı saat 21:00'de zoomdan gerçekleşecek buluşmada Sevgili Funda Yüksekdağ Arap ile somatik pratikler, ardından Sevgili feride Gürsoy ile Atalar Meditasyonu yapacağız. Bu buluşmalar kadın/erkek herkese açık. Buluşma kaydı, buluşma sonrası kayıt yaptıran herkesle paylaşılacak. Canlı katılamazsan bile kayıttan yapabileceksin. Buluşmanın detaylarına ve kayıt formuna aşağıdaki linkten ulaşabilirsin.https://forms.gle/eTZjdi8TjAQNARK1A*****Anadolu'nun Şifacı Kadınları'nı Desteklemek İster Misin? :)Hiçbir maddi destek almadan 5 yıldır gönüllü sürdürdüğüm bu programın içeriğini beğeniyor ve hayatına bir katkı sunduğuna inanıyorsan, beni ve programı maddi olarak da desteklemek istersen, https://kreosus.com/ask üzerinden ister aylık, ister tek seferlik katkı sunabilirsin :)*****Artık Anadolu'nun Şifacı Kadınları'nın Whatsapp Grubu var :)https://chat.whatsapp.com/D29r8vCHBN6ARYI6UTJtYpDuyuruları, geri bildirimleri paylaştığımız bu alanda olmak istersen, yukarıdaki linkten gruba dahil olabilirsin.*****Yazılarımı ve yolculuklarımı takip etmek istersen; https://www.instagram.com/didemmollaoglu/*****Anadolu'nun Şifacı Kadınları'nı aynı zamanda Spotify ve Apple Music'den podcast olarak dinleyebilirsin. https://open.spotify.com/show/312t5k7BqvGSv7c9l88Y6Z https://podcasts.apple.com/tr/podcast/anadolunun-şifacı-kadınları/id1519077215*****Ben Kimim? 2016'da tüm eşyalarını satarak çıktığı yolculukta henüz kendine doğru bir yolculukta olduğunu bilmiyordu. Ta ki yuvasından binlerce kilometre uzaklıkta Anadolu onu çağırana kadar. Yuvasına dönüşüyle birlikte kendi şifa yolculuğu başladı. Çünkü bir ağacın yeşermesi için önce köklerinin iyileşmesi gerektiğini biliyordu ve kökleri bu kadim topraklardaydı. Çıktığı bu yolculukta Maya Şamanizmden yogaya, yogadan tasavvufa uzanan farklı ilimlerin peşinden gitti, birçok eğitim aldı. Anadolu'nun Şifacı Kadınları'nı konuk ettiği bir podcast yapan Didem kendi deyimiyle Aşk'ı arayan bir aciz kul, yolcu. ***** Light Of Daytime by Vlad Gluschenko | https://soundcloud.com/vgl9 Music promoted by https://www.free-stock-music.com Creative Commons / Attribution 3.0 Unported License (CC BY 3.0) https://creativecommons.org/licenses/by/3.0/deed.en_US

⁠⁠Heltia ⁠⁠ile online terapiye başlayın. 500'den fazla uzmanın yer aldığı ⁠⁠Heltia⁠⁠, sizi ihtiyaçlarınıza en uygun klinik psikolog ile buluşturur. * TERAPİ20⁠⁠ kodu ile indirimden faydalanın. İyi ki Heltia!⁠ ⁠https://www.podcastbpt.com/heltia?utm_campaign=spot_reklam&utm_campaign_id=Kasim&utm_medium=cpm&utm_source=Podcast * "⁠⁠⁠⁠⁠⁠⁠⁠⁠Heltia⁠⁠" hakkında reklamı içerir. Evrende 4 temel kuvvet vardır. Modern fizikteki kuvvet algısı fizikçiler için temel parçacıkların etkileşimi sayesinde olur. Buna örnek olarak protonun ve nötronun pion (bir çeşit mezon) alışverişi sayesinde birbirine bağlanması verilebilir. Bu sebeple, etkileşim kelimesi kuvvet yerine daha doğru bulunmaktadır.… Seslendiren: Yunus Sahin

ÇAKICI'YI VURMAK İÇİN TİM KURDU-CEVHERİ GÜVENAlaattin Çakıcı'yı vurmak için tim hazırlayan yeni nesil mafya lideri. Kim bu Sinan Memi-Dalton Şabo-Serhat Azad şeklinde üç ismi olan yeni nesil mafya lideri? Çakıcı'nın himayesindeki Kemal Çağlar Temel'i vurduktan sonra Çakıcı için neden tim hazırladı? Yeraltı dünyasında bir devrin kapandığı olayda neler yaşandı? Savcılık tutanakları, ilk kez duyacağınız bilgilerle...

Kısa Dalga Parantez'in bu haftaki konuğu DEVA Partisi Balıkesir Milletvekili Burak Dalgın oldu. Berna Can'ın sorularını yanıtlayan Dalgın, Türkiye'nin ekonomik kalkınmada karşılaştığı beş temel tuzağa dikkat çekerek, bu tuzakların aşılması için kapsamlı bir reform ve seferberlik çağrısında bulundu. Dalgın, demografi, orta gelir, bölgesel kalkınma, küresel gelişmeler ve sıkışmışlık tuzaklarını çözmenin gerekliliğine vurgu yaptı. Learn more about your ad choices. Visit megaphone.fm/adchoices

If palliative care was a drug, one question we would want to know before prescribing it is what dose we should give.  Give too little - it may not work.  Give too much, it may cause harm (even if the higher dose had no significant side effects, it would require patients to take a lot of unnecessary additional pills as well as increase the cost.) So, what is the effective dose of palliative care? On today's podcast, we talk about finding an evidence-based answer to this dosing question with three leaders in palliative care: Jennifer Temel, Chris Jones, and Pallavi Kumar.  All three of our guests were co-authors of a randomized control trial on “Stepped Palliative Care” published in JAMA this year. We talk about what stepped palliative care is, how it is different from usual care or intensive palliative care, why these palliative care dosing questions are important, and dive deep into the results of their trial.  We also discuss some of the other important trials in palliative care, including Jennifer Temel's landmark NEJM study on outpatient palliative care and another study that gave an intervention we dubbed “fast-food palliative care” in an older GeriPal blog post.  

KURT KOCADI: ÇAKICI'NIN ADAMINA İNFAZ Alaattin Çakıcı'nın yeğeni olarak bilinen Çağlar Temel vurularak hayatını kaybetti. Çakıcı'nın Bahçeli ile başbaşa görüşmesinde yanında götürdüğü tek kişi olan Çağlar Temel'i vurmaya kim cesaret edebildi? Çakıcı'yı ve Bahçeli'yi takmadan Çağlar Temel'i indirmeyi göze alan güç bize ne anlatıyor? Çakıcı bir diğer has adamı Abdurrahman Keskin'in vurulmasına da ses çıkartamamıştı. Çakıcı cephesinde neler oluyor? Ayhan Bora Kaplan davasında akılalmaz işler oluyor. Mahkemeye etkin pişmanlık için başvuran Fethi Koyuncu'nun başına neler geldi? Hakim nasıl bir skandala imza attı? Mahkemede "Süleyman'ı alacaksanız alın" diye Soylu'yu kasteden avukat kimdi? Lağım videolarımdan sonra İhsan Hızarcı nasıl tutuklandı. Hızarcı, oğlu ve çetesi Ankara Büyükşehir Belediye Başkanvekili Faruk Köylüoğlu'nun oğlunu neden vurdular?

Trápí ho ekonomická politika současné vlády a chtěl by z její strany vidět větší podporu tvůrčí činnosti a obrany. „Vidím velké riziko, že na několik desetiletí bude v České republice cena energií vyšší. Je hezké říct, že kvůli bezpečnosti potřebujeme vlastní zdroj energie, tudíž druhý Temelín a Dukovany. Ale málo se mluví o modulárních jaderných zdrojích a jiných řešeních,“ říká odborník na finance a investiční bankovnictví žijící ve Spojených státech Ondřej Jonáš.

Vláda rozhodla o největší zakázce v novodobé historii Česka. Dva nové jaderné bloky v Dukovanech a později možná i dva další v Temelíně postaví pro polostátní energetickou firmu ČEZ jihokorejská státní společnost KHNP. Její nabídka byla podle premiéra Fialy lepší ve všech hodnotících kritériích. Obří tendr vyvolává řadu otázek, Filip Titlbach je položil předsedkyni Státního úřadu pro jadernou bezpečnost Daně Drábové.  Nové epizody Studia N najdete každý všední den odpoledne na našem webu, na YouTube a v podcastových aplikacích Spotify, Apple Podcasts, Google Podcasts a dalších. Sledovat nás můžete také na Instagramu.

Když jihokorejská jaderná firma KHNP stavěla reaktory ve Spojených arabských emirátech, získal americký Westinghouse kus této zakázky. Rádi bychom to viděli i tady, říká předsedkyně Státního úřadu pro jadernou bezpečnost Dana Drábová v pořadu Českého rozhlasu Plus Peníze a vliv. Podle ní šlo totiž o systém kontroly řízení Eagle, který Westinghouse dodal i do jaderné elektrárny Temelín.

Česko postaví svoji energetiku především na jádru. Strategické dokumenty se ale liší v počtu plánovaných reaktorů. Kabinet Petra Fialy oznámil, že s jihokorejskou KHNP uzavře smlouvu na dva bloky v Dukovanech s možností opce na další dva v Temelíně. Jsou plány Česka reálné a realizovatelné? Moderuje Šárka Fenyková.

Kabinet Petra Fialy (ODS) oznámil, že s jihokorejskou KHNP uzavře smlouvu na dva bloky v Dukovanech s možností opce na další dva bloky v Temelíně. Celková energetická strategie Česka navíc počítá se zaměřením hlavně na jádro. „Prioritu tady má rozvoj jádra, pro to se upravují zákony. Ale pro obnovitelné zdroje to má všechno velké zpoždění,“ komentuje v Interview Plus Edvard Sequens, energetický konzultant neziskového hnutí Calla a člen Zelených.

Dva nové jaderné bloky v Dukovanech postaví společnost KHNP. Vláda upřednostnila jihokorejskou firmu před francouzskou EDF. Kabinet bude zároveň se společností jednat o opci na výstavbu dalších dvou bloků v Temelíně. První reaktor by se měl v Dukovanech začít stavět v roce 2029. Cena za jeden reaktor je při současných cenách 200 miliard korun, původně se mluvilo o 160 miliardách. Navýšení předpokládané ceny podle kabinetu odpovídá inflaci v posledních letech. Pořadem provázela Nikola Reindlová https://www.ceskatelevize.cz/porady/11412378947-90-ct24/224411058130717/

Drs. Vamsi Velcheti and Nathan Pennell discuss novel approaches and key studies in lung cancer that were showcased at the 2024 ASCO Annual Meeting, including the Plenary abstracts LAURA and ADRIATIC.   TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. Today, I'm joined by Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and the vice chair of clinical research at the Taussig Cancer Center in Cleveland Clinic. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Today, we will be discussing practice-changing abstracts and the exciting advances in lung cancer that were featured at the ASCO 2024 Annual Meeting. You'll find our full disclosures in the transcript of the episode. Nate, we're delighted to have you back on the podcast today. Thanks for being here. It was an exciting Annual Meeting with a lot of important updates in lung cancer. Dr. Nate Pennell: Thanks, Vamsi. I'm glad to be back. And yes, it was a huge year for lung. So I'm glad that we got a chance to discuss all of these late-breaking abstracts that we didn't get to talk about during the prelim podcast. Dr. Vamsi Velcheti: Let's dive in. Nate, it was wonderful to see all the exciting data, and one of the abstracts in the Plenary Session caught my attention, LBA3. In this study, the investigators did a comparative large-scale effectiveness trial of early palliative care delivered via telehealth versus in-person among patients with advanced non-small cell lung cancer. And the study is very promising. Could you tell us a little bit more about the study and your take-home messages? Dr. Nate Pennell: Yes, I think this was a very important study. So just to put things in perspective, it's now been more than a decade since Dr. Jennifer Temel and her group at Massachusetts General Hospital did a randomized study that showed that early interventions with palliative medicine consultation in patients with advanced non-small cell lung cancer significantly improves quality of life and in her initial study, perhaps even overall survival. And since then, there have been numerous studies that have basically reproduced this effect, showing that getting palliative medicine involved in people with advanced cancer, multiple different cancer types, really, has benefits.  The difficulty in applying this has been that palliative care-trained specialists are few and far between, and many people simply don't have easy access to palliative medicine-trained physicians and providers. So with that in mind, Dr. Temel and her group designed a randomized study called the REACH PC trial, where 1,250 patients were randomized with advanced non-small cell lung cancer to either in-person palliative medicine visits which is sort of the standard, or one in-person assessment followed by monthly telemedicine video visits with palliative medicine. Primary endpoint was essentially to show that it was equivalent in terms of quality of life and patient satisfaction. And what was exciting about this was that it absolutely was. I mean, pretty much across the board in all the metrics that were measured, the quality-of-life, the patient satisfaction, the anxiety and depression scores, all were equivalent between doing telemedicine visits and in-person visits. And this hopefully will now extend the ability to get this kind of benefit to a much larger group of people who don't have to geographically be located near a palliative medicine program. Dr. Vamsi Velcheti: Yeah, I think it's a great abstract, Nate and I actually was very impressed by the ASCO committee for selecting this for the Plenary. We typically don't see supportive care studies highlighted in such a way at ASCO. This really highlights the need for true interdisciplinary care for our patients. And as you said, this study will clearly address that unmet need in terms of providing access to palliative care for a lot of patients who otherwise wouldn't have access. I'm really glad to see those results. Dr. Nate Pennell: It was. And that really went along with Dr. Schuchter's theme this year of bringing care to patients incorporating supportive care. So I agree with you.  Now, moving to some of the other exciting abstracts in the Plenary Session. So we were talking about how this was a big year for lung cancer. There were actually 3 lung cancer studies in the Plenary Session at the Annual Meeting. And let's move on to the second one, LBA4, the LAURA study. This was the first phase 3 study to assess osimertinib, an EGFR tyrosine kinase inhibitor, in patients with EGFR mutant, unresectable stage III non-small cell lung cancer. What are your takeaways from this study?  Dr. Vamsi Velcheti: This is certainly an exciting study, and all of us in the lung community have been kind of eagerly awaiting the results of the study. As you know, for stage III non-small cell lung cancer patients who are unresectable, the standard of care has been really established by the PACIFIC study with the consolidation durvalumab after definitive concurrent chemoradiation. The problem with that study is it doesn't really answer the question of the role of immunotherapy in patients who are never-smokers, and especially in patients who are EGFR positive tumors, where the role of immunotherapy in a metastatic setting has always been questioned. And in fact, there have been several studies as you know, in patients with EGFR mutation positive metastatic lung cancer where immunotherapy has not been that effective. In fact, in the subgroup analysis in the PACIFIC study, patients with EGFR mutation did not really benefit from adding immunotherapy.  So this is an interesting study where they looked at patients with locally advanced, unresectable stage III patients and they randomized the patients 2:1 to osimertinib versus placebo following concurrent or sequential tumor radiation. The primary endpoint for the study was progression free survival, and a total of 216 patients were enrolled and 143 patients received a study treatment, which is osimertinib, and 73 received placebo. And 80% of the patients on the placebo arm crossed over to getting treatment at the time of progression.  So most of us in the lung cancer community were kind of suspecting this would be a positive trial for PFS. But however, I think the magnitude of the difference was truly remarkable. The median PFS in the osimertinib arm was 39.1 months and placebo was 5.6 months and the hazard ratio of 0.16. So it was a pretty striking difference in terms of DFS benefit with the osimertinib consolidation following chemoradiation. So it was truly a positive study for the primary endpoint and the benefit was seen across all the subgroups and the safety was no unexpected safety signals other than a slight increase in the radiation pneumonitis rates in patients receiving osimertinib and other GI and skin tox were kind of as expected. In my opinion, it's truly practice changing and I think patients with EGFR mutation should not be getting immunotherapy consolidation post chemoradiation. Dr. Nate Pennell: I completely agree with you. I think that this really just continues the understanding of the use of osimertinib in EGFR-mutant lung cancer in earlier stages of disease. We know from the ADAURA trial, presented twice in the Plenary at the ASCO Annual Meeting, that for IB, stage II and resectable IIIA, that you prolong progression free or disease free survival. So this is a very similar, comparable situation, but at an even higher risk population or the unresectable stage III patients. I think that the most discussion about this was the fact that the osimertinib is indefinite and that it is distinct from the adjuvant setting where it's being given for three years and then stopped. But I think all of us had some pause when we saw that after three years, especially in the stage III patients from ADAURA, that there were clearly an increase in recurrences after stopping the drug, suggesting that there are patients who are not cured with a time limited treatment, or at least with 3 years of treatment.  The other thing that is sobering from the study, and was pointed out by the discussant, Dr. Lecia Sequist, is if you look at the two-year disease-free survival in the placebo arm, it was only 13%, meaning almost no one was really cured with chemo radiation alone. And that really suggests that this is not that different from a very early stage IV population where indefinite treatment really is the standard of care. I wonder whether you think that's a reasonable approach. Dr. Vamsi Velcheti: I completely agree with you, Nate, and I don't think we cure a majority of our patients with stage III, and less so in patients who have EGFR-mutant, stage III locally advanced. As you just pointed out, I think very few patients actually make it that far along. And I think there's a very high rate of CNS micrometastatic disease or just systemic micrometastatic disease in this population that an effective systemic therapy of osimertinib can potentially have long term outcomes. But again, we perhaps don't cure a vast majority of them. I think that the next wave of studies should incorporate ctDNA and MRD-based assays to potentially identify those patients who could potentially go off osimertinib at some point. But, again, outside of a trial, I would not be doing that. But I think it's definitely an important question to ask to identify de-escalation strategies with osimertinib. And even immunotherapy for that matter, I think we all know that not all patients really require years and years of immunotherapy. They're still trying to figure out how to use immunotherapy in these post-surgical settings, using the MRD to de-escalate adjuvant therapies. So I think we have to have some sort of strategy here. But outside of a clinical trial, I will not be using those assays here to cite treatments, but certainly an important question to ask.  Moving on to the other exciting late-breaking abstracts, LBA5, the ADRIATIC study. This is another study which was also in the plenary session. This study was designed to address this question of consolidation immunotherapy, post chemo radiation for limited-stage small cell cancer, the treatment arms being durvalumab tremelimumab, and durvalumab observation. So what do you think about the study? This study also received a lot of applause and a lot of attention at the ASCO meeting. Dr. Nate Pennell: It was. It was remarkable to be there and actually watch this study as well as the LAURA study live, because when the disease free survival curves and in the ADRIATIC study, the overall survival curves were shown, the speakers were both interrupted by standing ovation of applause just because there was a recognition that the treatment was changing kind of before our eyes. I thought that was really neat. So in this case, I think this is truly a historic study, not necessarily because it's going to necessarily be an earth shakingly positive study. I mean, it was clearly a positive study, but more simply because of the disease in which it was done, and that is limited-stage small cell lung cancer. We really have not had a change in the way we've treated limited-stage small cell lung cancer, probably 25 years. Maybe the last significant advances in that were the advent of concurrent chemotherapy and radiation and then the use of PCI with a very modest improvement in survival. Both of those, I would say, are still relatively modest advances.  In this case, the addition of immunotherapy, which we know helps patients with small cell lung cancer - it's of course the standard of care in combination chemotherapy for extensive stage small cell lung cancer - in this case, patients who completed concurrent chemo radiation were then randomized to either placebo or durvalumab, as well as the third arm of durvalumab tremelimumab, which is not yet been recorded, and co primary endpoints were overall survival and progression free survival. And extraordinarily, there was an improvement in overall survival seen at the first analysis, with a median overall survival of 55.9 months compared to 33.4 months, hazard ratio of 0.73. So highly clinically and statistically significant, that translates at three years to a difference in overall survival of 56.5%, compared to 47.6%, or almost 10% improvement in survival at three years.  There was also a nearly identical improvement in progression-free survival, also with a hazard ratio of 0.76, suggesting that there's a modest number of patients who benefit. But it seems to be a clear improvement with the curves plateauing out. In my opinion, this is very comparable to what we saw with the PACIFIC study in stage III, unresectable non-small cell lung cancer, which immediately changed practice back when that first was reported. And I expect that this will change practice pretty much immediately for small cell as well. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think it's an exciting advance in patients with limited-stage small cell lung cancer. For sure, it's practice-changing, and I think the results were exciting.  So one thing that really intrigued me was in the extensive-stage setting, the benefit was very mediocre with one-to-two month overall survival benefit in both the PACIFIC and in IMpower trial. Here we are seeing almost two-year of median OS benefit. I was kind of puzzled by that, and I thought it may have to do with patients receiving radiation. And we've seen that with the PACIFIC, and makes you wonder if both the CASPIAN and the IMpower studies actually did not allow consolidation thoracic radiation. Hypothetically, if they had allowed consolidation thoracic radiation, perhaps we would have seen better outcomes. Any thoughts on that? Dr. Nate Pennell: We've been trying to prove that radiation and immunotherapy somehow go together better for a long time. Going back to the first description of the abscopal effect, and I'm not sure if I necessarily believe that to be the case, but in this setting where we truly are trying to cure people rather than merely prolong their survival, maybe this is the situation where it truly is more beneficial. I think what we're seeing is something very similar to what we're seen in PACIFIC, where in the stage IV setting, some people have long term survival with immunotherapy, but it's relatively modest. But perhaps in the curative setting, you're seeing more of an impact. Certainly, looking at these curves, we'll have to see with another couple of years to follow up. But a three-year survival of 56% is pretty extraordinary, and I look forward to seeing if this really maintains over the next couple of years follow up.  Moving beyond the Plenary, there were actually lots of really exciting presentations, even outside the Plenary section. One that I think probably got at least as much attention as the ones that we've already discussed today was actually an update of an old trial that's been presented for several prior years. And I'm curious to get your take on why you thought this was such a remarkable study. And we're talking about the LBA8503, which was the 5-year update from the CROWN study, which looked at previously untreated ALK-positive advanced non-small cell in cancer patients randomly assigned to lorlatinib, the third generation ALK inhibitor, versus crizotinib, the first generation ALK inhibitor. What was so exciting about this study, and why were people talking about it?  Dr. Vamsi Velcheti: Yeah, I agree, Nate. We've seen the data in the past, right? Like on the CROWN data, just first like a quick recap. This is the CROWN study, like the phase 3 study of third generation ALK inhibitor lorlatinib. So global randomized phase 3 study in patients with metastatic disease randomized to lorlatinib versus crizotinib, which is a controller. So the primary endpoint was PFS, and we've seen the results in the past of the CROWN readout quoted, with a positive study and the lorlatinib received FDA approval in the frontline setting. But the current study that was presented at the ASCO annual meeting is a kind of a postdoc analysis of five years. The endpoint for the study with central review stopped at three years, and this is actually a follow up beyond that last readout. Interestingly, in this study, when they looked at the median PFS at five years, the lorlatinib arm did not reach a median PFS even at five years and the hazard ratio is 0.19, which is kind of phenomenal in some ways. At 5 years, the majority of the patients were still on the drug. So that's quite incredible. And the benefit was more profound in patients with brain mets with a hazard ratio of 0.08. And again, speaking to the importance of brain penetrant, small molecule inhibitors, and target therapy, the safety profile, there were no additional safety signals noted in the study. We kind of know about the side effects of lorlatinib already from previous studies readouts. No unusual long-term toxicities.  I should note though, about 40% of patients did have CNS, AEs grade 1, 2 CNS toxicities on the  lorlatinib arm. And the other interesting thing that was also reported in the trial was dose reduction of lorlatinib did not have an impact on the PFS, which is interesting in my opinion. They also did some subgroup analysis, biomarker testing, biomarker populations. Patients who had P53 cooperation did much better with lorlatinib versus crizotinib. So overall, the other thing that they also had shown on the trial was the resistance mechanisms that were seen with lorlatinib were very different than what we are used to seeing with the earlier generation ALK inhibitors. The majority of the patients who develop resistance have bypass mechanisms and alterations in MAP kinase pathway PI3K/MTOR/PTEN pathway, suggesting that lorlatinib is a very potent ALK inhibitor and on target ALK mutations don't happen as frequently as we see with the earlier generation ALK inhibitors.  So I think this really begs the question, should we offer lorlatinib to all our patients with metastatic ALK-positive tumors? I think looking at the long-term data, it's quite tempting to say ‘yes', but I think at the same time we have to take into consideration patient safety tolerability. And again, the competitor arm here is crizotinib. So lorlatinib suddenly seems to be, again, cross trial comparisons, but I think the long-term outcomes here are really phenomenal. But at the same time, I think we've got to kind of think about patient because these patients are on these drugs for years, they have to live with all the toxicities. And I think the patient preferences and safety profile matters in terms of what drug we recommend to patients. Dr. Nate Pennell: I completely agree with you. I think the right answer, is that this has to be an individual discussion with patients. The results are incredibly exciting. I mean, the two-year progression free survival was 70%, and the five-year, three years later is still 60%. Only 10% of people are failing over the subsequent three years. And the line is pretty flat. And as you said, even with brain metastases, the median survival is in reach. It's really extraordinary. Moreover, while we do talk about the significant toxicities of lorlatinib, I thought it was really interesting that only 5% of people were supposedly discontinued the drug because of treatment related AEs, which meant that with dose reduction and management, it seems as though most patients were able to continue on the drug, even though they, as you mentioned, were taking it for several years.  That being said, all of us who've had experience with the second-generation drugs like alectinib and brigatinib, compared to the third-generation drug lorlatinib, can speak to the challenges of some of the unique toxicities that go along with it. I don't think this is going to be a drug for everyone, but I do think it is now worth bringing it up and discussing it with the patients most of the time now. And I do think that there will be many people for whom this is going to be a good choice, which is exciting. Dr. Vamsi Velcheti: Absolutely, completely agree. And I think there are newer ALK inhibitors in clinical development which have cleaner and better safety profiles. So we'll have to kind of wait and see how those pan out.  Moving on to the other exciting abstract, LBA8509, the KRYSTAL-12 study. LBA8509 is a phase 3 study looking at adagrasib versus docetaxel in patients with previously treated advanced metastatic non-small cell cancer with KRASG12C mutation. Nate, there's been a lot of hype around this trial. You've seen the data. Do you think it's practice-changing? How does it differentiate with the other drug that's already FDA approved, sotorasib?  Dr. Nate Pennell: Yeah, this is an interesting one. I think we've all been very excited in recent years about the identification of KRASG12C mutations as targetable mutations. We know that this represents about half of KRAS mutations in patients with non-small cell lung cancer, adenocarcinoma, and there are two FDA-approved drugs. Sotorasib was the first and adagrasib shortly thereafter. We already had seen the CodeBreaK 200 study, which was a phase 3 study of sotorasib versus docetaxel that did modestly prolong progression free survival compared to docetaxel, although did not seem to necessarily translate to an improvement in overall survival. And so now, coming on the heels of that study, the KRYSTAL-12 study compared adagrasib, also the KRASG12C  inhibitor versus docetaxel and those with previously treated non-small cell with KRASG12C. And it did significantly improve progression free survival with a hazard ratio of 0.58. Although when you look at the median numbers, the median PFS was only 5.5 months with the adagrasib arm compared to 3.8 months with docetaxel. So while it is a significant and potentially clinically significant difference, it is still, I would say a modest improvement.   And there were some pretty broad improvements across all the different subgroups, including those with brain metastases. It did improve response rate significantly. So 32% response rate without adagrasib, compared to only 9% with docetaxel. It's about what you would expect with chemotherapy. And very importantly, in this patient population, there was activity in the brain with an intracranial overall response rate among those who had measurable brain metastases of 40%. So certainly important and probably that would distinguish it from drugs like docetaxel, which we don't expect to have a lot of intracranial toxicity. There is certainly a pattern of side effects that go along with that adagrasib, so it does cause especially GI toxicity, like diarrhea, nausea, vomiting, transaminitis. All of these were actually, at least numerically, somewhat higher in the adagrasib arm than in docetaxel, a lot more hematologic toxicity with the docetaxel. But overall, the number of serious adverse events were actually pretty well matched between the two groups. So it wasn't really a home run in terms of favorable toxicity with that adagrasib.  So the question is: “In the absence of any data yet on overall survival, should this change practice?” And I'm not sure it's going to change practice, because I do think that based on the accelerated approval, most physicians are already offering the G12C inhibitors like sotorasib and adagrasib, probably more often than chemotherapy, I think based on perceived improvement in side effects and higher response rates, modestly longer progression-free survival, so I think most people think that represents a modest improvement over chemotherapy. And so I think that will continue. It will be very interesting, however, when the overall survival report is out, if it is not significantly better, what the FDA is going to do when they look at these drugs.  Dr. Vamsi Velcheti: Thanks so much. Very well summarized. And I do agree they look more similar than dissimilar. I think CodeBreaK-200 and the KRYSTAL-12, they kind of are very identical. I should say, though I was a little surprised with the toxicity profile of adagrasib. It seemed, I mean, not significantly, but definitely seemed worse than the earlier readouts that we've seen. The GI tox especially seems much worse on this trial. I'm kind of curious why, but if I recall correctly, I think 5% of the patients had grade 3 diarrhea. A significant proportion of patients had grade 3 nausea and vomiting. And the other complicating thing here is you can't use a lot of the antiemetics because of the QT issues. So that's another problem. But I think it's more comparable to sotorasib, in my opinion.  Dr. Nate Pennell: While this is exciting, I like to think of this as the early days of EGFR, when we were using gefitinib and erlotinib. They were certainly advances, but we now have drugs that are much more effective and long lasting in these patients. And I think that the first-generation inhibitors like sotorasib and adagrasib, while they certainly benefit patients, now is just the beginning. There's a lot of research going on, and we're not going to talk about some of the other abstracts presented, but some of the next generation G12C inhibitors, for example, olomorasib, which did have also in the same session, a presentation in combination with pembrolizumab that had a very impressive response rate with potentially fewer side effects, may end up replacing the first generation drugs when they get a little bit farther along. And then moving on to another one, which I think potentially could change practice. I am curious to hear your take on it, was the LBA8505, which was the PALOMA-3 study. This was interesting in that it compared two different versions of the same drug. So amivantamab, the bispecific, EGFR and MET, which is already approved for EGFR exon 20 non-small cell lung cancer, in this case, in more typical EGFR-mutated non-small cell lung cancer in combination with osimertinib with the intravenous amivantamab, compared to the subcutaneous formulation of amivantamab. Why would this be an important study? Dr. Vamsi Velcheti: I found this study really interesting as well, Nate. And as you know, amivantamab has been FDA approved for patients with exon 20 mutation. And also, we've had, like two positive readouts in patients with classical EGFR mutations. One, the MARIPOSA study in the frontline setting and the MARIPOSA-2, in the second-line post osimertinib setting. For those studies, the intravenous amivantamab was used as a treatment arm, and the intravenous amivantamab had a lot of baggage to go along with it, like the infusion reactions and VTEs and other classic EGFR related toxicity, skin toxicities. So the idea behind developing the subcutaneous formulation of amivantamab was mainly to reduce the burden of infusion, infusion time and most importantly, the infusion related reactions associated with IV formulation.  In a smaller phase 2 study, the PALOMA study, they had looked at various dosing schemas like, subcutaneous formulation, and they found that the infusion related reactions were very, very low with the subcutaneous formulation. So that led to the design of this current study that was presented, the PALOMA-3 study. This was for patients who had classical EGFR mutations like exon 19, L858R. The patients were randomized 1:1 to subcutaneous amivantamab with lazertinib versus IV amivantamab plus lazertinib. The endpoints for the study, it's a non-inferiority study with co primary endpoints of C trough and C2 AUC, Cycle 2 AUC. They were looking at those pharmacological endpoints to kind of demonstrate comparability to the IV formulation. So in this study, they looked at these pharmacokinetic endpoints and they were essentially identical. Both subcutaneous and IV formulations were compatible. And in terms of clinical efficacy as well, the response rate was identical, no significant differences. Duration of response was also identical. The PFS also was comparable to the IV formulation. In fact, numerically, the subcutaneous arm was a little better, though not significant. But it appears like, you know, the overall clinical and pharmacological profile of the subcutaneous amivantamab was comparable. And most interestingly, the AE profile, the skin toxicity was not much different. However, the infusion reactions were substantially lower, 13% with the subcutaneous amivantamab and 66% with IV amivantamab. And also, interestingly, the VTE rates were lower with the subcutaneous version of amivantamab. There was still a substantial proportion of patients, especially those who didn't have prophylactic anticoagulation. 17% of the patients with the subcutaneous amivantamab had VTE versus 26% with IV amivantamab. With prophylaxis, which is lower in both IV and subcutaneous, but still subcutaneous formulation at a lower 7% versus 12% with the IV amivantamab.  So overall, I think this is an interesting study, and also the authors had actually presented some interesting data on administration time. I've never seen this before. Patients reported convenience using a modified score of patient convenience, essentially like patients having to spend a lot of time in the infusion site and convenience of the patient getting the treatment. And it turns out, and no surprise, that subcutaneous amivantamab was found to be more convenient for patients.  So, Nate, I want to ask you your take on this. In a lot of our busy infusion centers, the time it takes for those patients to get the infusion does matter, right? And I think in our clinic where we are kind of fully booked for the infusion, I think having the patients come in and leave in 15, 20 minutes, I think it adds a lot of value to the cancer center operation.  Dr. Nate Pennell: Oh, I completely agree. I think the efficacy results were reassuring. I think the infusion related reaction difference, I think is a huge difference. I mean, I have given a fair amount of amivantamab, and I would say the published IRR rate of 66%, 67% I would say, is maybe even underestimates how many patients get some kind of reaction from that, although it really is a first dose phenomenon. And I think that taking that down to 13% is a tremendous advance. I think fusion share time is not trivial as we get busier and busier. I know our cancer center is also very full and it becomes challenging to schedule people, and being able to do a five-minute treatment versus a five-hour treatment makes a big difference for patients.  It's interesting, there was one slide that was presented from an efficacy standpoint. I'm curious about your take on this. They showed that the overall survival was actually better in the subcu amivantamab arm, hazard ratio of 0.62. Now, this was only an exploratory endpoint. They sort of talk about perhaps some rationale for why this might be the case. But at the very least, I think we can be reassured that it's not less effective to give it and does seem to be more tolerable and so I would expect that this hopefully will be fairly widely adopted. Dr. Vamsi Velcheti: Yeah, I agree. I think this is a welcome change. Like, I think the infusion reactions and the resources it takes to get patients through treatments. I think it's definitely a win-win for patients and also the providers.  And with that, we come to the conclusion of the podcast. Nate, thank you so much for the fantastic insights today. Our listeners will find all the abstracts discussed today in the transcripts of the episode. Thank you so much for joining us today, Dr. Pennell.  Dr. Nate Pennell: Oh, thanks for inviting me. It's always fun to talk about all these exciting advances for our patients. Dr. Vamsi Velcheti: Thanks to our listeners for your time today. You will find links to all the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:    Dr. Vamsi Velcheti  @VamsiVelcheti    Dr. Nathan Pennell  @n8pennell    Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:  Dr. Vamsi Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus  Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Dr. Nathan Pennell:    Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron   Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi