Person at the head of a monarchy
News (1:31)1. Super Giant Robot Bros2. Camp Cretaceous Season 5 - When are we covering it?3. MonsterVerse update - Kong film and Monarch show updatesJurassic Park The Game discussion (13:54)So many gruesome deaths! Hope our characters have plenty of save points ready.
This week's EYE ON NPI will pique your curiosity... it's Microchip's AVR-IoT Cellular Mini Development Board featuring the Sequans Monarch 2 GM02S cellular module (https://www.digikey.com/en/product-highlight/m/microchip-technology/avr-iot-cellular-mini-development-board) This dev board really knows how to get us interested with an AVR128DB48 128KB-flash AVR chip (https://www.digikey.com/short/4pq3d2q3), Sequans GM02S compact LTE cell module (https://www.digikey.com/short/4qbfcn17), Feather format (https://learn.adafruit.com/adafruit-feather), Stemma QT / Qwiic connector (https://learn.adafruit.com/introducing-adafruit-stemma-qt/what-is-stemma-qt) and Arduino library support (https://github.com/microchip-pic-avr-solutions/avr-iot-cellular-arduino-library) This is an excellent dev board to use if you want to take advantage of the huge ecosystem afforded by Arduino, Feather, Qwiic/QT - you should be able to use the many thousands of libraries and hardware accessories for quick prototyping. As mentioned, this dev board is Feather shaped, with a USB Type C connector, Li-poly battery charger, and built in programmer/debugger/serial interface for the AVR chip. The individual microcontroller is a AVR128DB48 AVR (https://www.digikey.com/short/4pq3d2q3) which comes with 128KB flash and 16KB RAM. Think of it as a super-beefy ATmega328P! A SAMD21E 'curiosity' chip is used as the programming interface and also serial interface. When plugged in, the board shows up as a disk drive, with a getting started guide bookmark and some other specification files. While following the getting started guide we found that you can also drag hex files over to program it, very handy for quick-start! To program it, MCP suggests using the DxCore from SpenceKonde (https://github.com/SpenceKonde/DxCore) in Arduino so you'll want to get that installed while you follow the rest of the guide. Next up, time to activate the included SIM card from Truphone (https://activate.truphone.com/) that comes with the dev kit. This SIM is free to activate and is good for up to 150 MB of data transfer and 90 days, which is plenty of time to explore the board before needing to renew. Activating the SIM only took us 5 minutes - don't forget to power cycle after activation to make sure the module and SIM re-authorize. One of the surprises we had while trying this eval board is the really good documentation and learning system that is over at https://iot.microchip.com/avr-iot-cellular-mini - we're kinda used to verbose text-based documentation or using specialized software that only runs on Windows. This is the first time we've seen a really nice documentation system with simple step-by-steps, lots of photos, links and a clear navigation system. There are also two interesting in-browser compilation and serial monitor widgets that we spotted, which is a good sign that folks are starting to move towards browser-and-filesystem replacements for tool-chains. The Arduino library code is available over at https://github.com/microchip-pic-avr-solutions/avr-iot-cellular-arduino-library which looks like it's got platform.io support and you can download a release for installation into the Arduino IDE. (We do recommend someone at MCP try to add a proper release to the Arduino library manager to save one extra step if possible!) Once installed, there are a few helpful examples to get you going. The first one is just connecting to an HTTP endpoint and parsing out the result and it worked...really well! We were able to connect to the AT&T cellular network and fetch the data within a minute. We'd request an HTTPS example since most folks will want a TLS method of connection! Since the board is Arduino and Stemma QT compatible, we were able to connect an OLED and extend the example to display the HTTP-gotten data to the OLED - it only took us 10 minutes to install everything for Arduino library support and extend the code which is amazingly fast! You know what else is really fast? Digi-Key shipping for the AVR-IoT Cellular Mini Development Board, cause it's in stock right now! (https://www.digikey.com/short/bn7mp80w) Order today and you'll be connecting to the LTE cellular network by tomorrow afternoon.
House Warming Podcast, Episode 011: Hell No To Hilco - Our Bodies Are Not Dollar Signs with Edith Tovar from the Little Village Environmental Justice Organization In this episode, Sarah talks with Edith Tovar about the impact of Hilco's implosion of the coal plant smokestacks and the Hell No To Hilco campaign, which fights the installation of polluting industry and works for regenerative community-based land use in the community.Edith Tovar is the Community Organizer at the Little Village Environmental Justice Organization (LVEJO) focusing on Just Transition* visions and efforts in the Little Village community. They focus on the "Hell No Hilco" campaign, informing residents about the new Target warehouse facility at the former Crawford Coal Plant -- Exchange 55 -- and connecting ongoing EJ efforts across the community and city. #FueraHilco #HellNoHilco #Exchange55 #LaVillitaRespiraEdith is a life-long resident of La Villita community. As a first generation college student and youngest of four, she was the second in her family to graduate with a university degree. She obtained her Bachelor of Arts in Spanish-Economics with a minor in Political Science from the University of Illinois at Chicago (UIC). Edith also obtained her Master's in Urban Planning and Policy from the College of Urban Planning and Public Affairs at UIC with a concentration in Environmental Planning and Policy. Edith is a sister, tía, prima, a bestie to many, she has three fur babies; Xico & Mango (cats) and Kapi (dog), and enjoys creating habitats for pollinators like the Monarch butterfly.*Just Transition is a principle, a process and a practice. The principle of just transition is that a healthy economy and a clean environment can and should co-exist. The process for achieving this vision should be a fair one that should not cost workers or community residents their health, environment, jobs, or economic assets. Any losses should be fairly compensated. And the practice of just transition means that the people who are most affected by pollution – the frontline workers and the fenceline communities – should be in the leadership of crafting policy solutions. - Just Transition Alliance, http://jtalliance.org/ Here is the link to their second website focusing on Just Transition in the Little Village community: https://lavillitarespira.com/Follow LVEJO on Facebook (Little Village Environmental Justice Organization (LVEJO)), Twitter (@lvejo) and Instagram (@lvejo20).Subscribe to the podcast on Apple Podcasts, Spotify, Stitcher, or wherever you listen to podcasts. Support the show
Steve Harper Interviews Tom Marino Owner of Monarch Life Coaching LLC --www.monarchlifecoaching.comhttps://onlineradiobox.com/search?cs=us.pbnnetwork1&q=podcast%20business%20news%20network&c=ushttps://mytuner-radio.com/search/?q=business+news+networkhttps://streema.com/radios/search/?q=podcast+business+news+network
Andrew Morton is perhaps the most famous royal biographer of all time, with his book Diana: In Her Own Words changing the way the world looked at The Firm forever. This week he sits down with Zoe Forsey to talk about his latest book, The Queen, which celebrates the Monarch's 70 years on the throne. He also shares his thoughts on the latest royal dramas, including what he believes Diana would have thought of Princes William and Harry's fallout and the mistake the Duchess of Cambridge made when the Queen expressed her wish for Camilla to become Queen Consort.
Monarch butterflies are threatened by a fatal parasite and a reason for infection may be that conservationists rear these butterflies and plant Milkweeds for them under crowded conditions.
Just like every sitcom has the "learning the dangers of credit cards" episode, every cartoon must have the "rich person realizes they're broke" episode. Maybe that's just this and the Simpsons. Regardless, the Monarch learns that he's broke after completely renovating his parents' condemned mansion, and now he has to work the steps to get back on his feet. This involves finding his way back into Dean's life, even though the boy just escaped his father's clutches to live in the dorms at Stuyvesant University. Special thanks to Joshua Jarett (http://jjarrett.work) for our cover art, Gwen May (https://soundcloud.com/deepwhale) for our theme song, and Brayton Cameron (https://twitter.com/braytonjc) for being our announcer.
On today's This Green Earth, hosts Claire Wiley and Chris Cherniak speak with Jordan Clayton (1:42), Supervisor with the Utah Snow Survey and Natural Resources Conservation Service about snowfall, rainfall, soil moisture and water storage levels throughout Utah.Then (24:49), we speak with Andy Davis, research scientist at the University of Georgia, about this data and the life of a Monarch. For years, scientists have warned that monarch butterflies are dying off in droves. New research coming from the University of Georgia suggests that the population of monarchs has remained relatively stable over the past 25 years.Published in Global Change Biology, the study states that population growth during the summer compensates for butterfly losses duet to migration, winter weather and changing environmental factors.
Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, and Dr. Hope Rugo, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discuss the practice-changing DESTINY-Breast04 trial as well as novel therapies in metastatic HR+/HER2- breast cancer from the TROPiCS-02 and MAINTAIN studies, all of which were featured at the 2022 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your host for the ASCO Daily News Podcast today. I'm a vice-chair and breast medical oncologist at the Sidney Kimmel Cancer Center, Jefferson Health in Philadelphia. My guest today is Dr. Hope Rugo, a professor of medicine and the director of Breast Oncology and Clinical Trials Education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. We'll be discussing key advances in breast cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes, and disclosures of all guests on the podcasts can be found on our transcripts at asco.org/podcasts. Hope, it's great to talk to you today. Dr. Hope Rugo: Nice to talk to you, too. Dr. Allison Zibelli: Let's begin with perhaps the most exciting abstract at ASCO this year, which was the DESTINY-Breast04 study, that's LBA3, a randomized phase 3 study of trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-low, unresectable and/or metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: Well, of course, this is a hugely practice-changing study as was noted in the second-to-last slide by the discussant [Dr.] Pat LoRusso. So, antibody-drug conjugates are really the next step in delivering chemotherapy to cancer cells. The antibody-drug conjugates allow targeted delivery of a toxin to the cancer cell. I think we didn't understand how important this was going to be. These second, sort of, verging on third-generation antibody-drug conjugates use an antibody approach and to then have a new generation of linkers, which allow the drug to be released locally, but to then have drugs which pack a big bang for the buck. So, the way antibody-drug conjugates are constructed, you need to have a drug that actually can't be given as a naked drug because it's too toxic because you're giving just very small amounts of this drug that are delivered directly to the cancer cell. And the other really critical part of this is that the drug-to-antibody ratio of at least the successful and new antibody-drug conjugates (ADC) is quite high in the 7.5 to 8 toxins per antibody. Now, what that's resulted in is really interesting, is that there's a bystander effect. So, the toxin itself can leak out of the cancer cell that it's targeted and kill neighboring cells, but also because of the construct of these antibody-drug conjugates, what's likely happening is even if the cancer cell's a very low expression of the target, really low, you're able to actually get that ADC into the cancer cell to kill the cancer cell. So that may be a big part of the so-called bystander effect. So trastuzumab deruxtecan is biosimilar trastuzumab linked to a topoisomerase inhibitor deruxtecan, and what happened here was that of course, we saw remarkable data in HER2+ disease, unbelievable p-values in DESTINY-Breast03 compared to T-DM1, a first-generation ADC. But in DESTINY-Breast04, we targeted a population of patients largely with hormone receptor-positive disease who had a little expression of HER2, 1 plus or 2 plus by immunohistochemistry and no gene amplification. And this trial, which randomly assigned patients 2:1 and included just 58 patients with triple-negative disease. So in this trial, 480 had hormone receptor-positive breast cancer, a median of 1 line of prior chemotherapy. They were only allowed up to 2. They were refractory to endocrine therapy, a median of 3 lines of endocrine therapy. In the overall patients and in the hormone receptor-positive patients, there was actually a doubling in progression-free survival (PFS). It started very early, and it continued throughout, and at every landmark analysis, T-DXd was better than the treatment of physician choice that patients were randomly assigned to. It's also important when you're thinking about trials like this to think about what the treatment of physician choice was, and it was all chemotherapy regimens we would use. Paclitaxel, nab-paclitaxel, capecitabine, eribulin, or gemcitabine. And, so, I think that that doesn't bring up any questions. When they looked at the hormone receptor-positive group, they saw, if anything, even a bigger benefit overall. Now, the other endpoint of this trial was overall survival, and at this first analysis, they saw an improvement in overall survival that was quite dramatic. The absolute difference was 6.4 months, which is pretty amazing for an overall survival difference. And then they looked at this exploratory endpoint at the 58 patients who were valuable at triple-negative breast cancer, and then that group of patients, also saw an improvement in PFS of 5.6 months, an improvement in overall survival of 9.9 months, very small group, but amazing data. The forest plots are exactly what you want to see, all the dots line up to the left of 1, and overall responses improved. One of the concerns with this drug has been toxicity. The toxicity showed no new toxicity signals, which is really important. Nausea is the biggest issue that we deal with. It's mostly grade 1 and 2, but still something that's important to manage. A little bit of hair loss, not much in the way of bone marrow suppression, which is interesting. Interstitial lung disease (ILD) or pneumonitis continues to be an important issue to follow. 12% of patients had ILD of any grade. Most of it was grade 1 and 2, but 3 patients died, representing 0.8%. So, this really highlights the importance of monitoring and managing pneumonitis. Regardless of that, few patients had a reduced ejection fraction, but again, very, in general, low grade. This is really a new standard of care, and the standing ovation was really due to the fact that all we do is dedicate ourselves to trying to help patients live longer and better with their cancers, and in this trial, we have a huge win that has no qualifications. We can help patients not only control their disease longer but live longer with T-Dxd compared to standard chemotherapy. Dr. Allison Zibelli: So, Hope, I know as a practicing medical oncologist, I find that our metastatic triple-negative patients are often the biggest therapeutic challenges for us. Will they be doing larger studies with these patients that are HER2-low? Dr. Hope Rugo: It's a really good point. About 65% of patients with hormone receptor-positive disease or so-called HER2-low, centrally confirmed in the study. So, a fair number of people, about a quarter, did not have HER2-low disease when they were tested centrally. In the triple-negative population, who really are ER, PR, HER2- by standard definitions, about a third of the patients might have HER2-low disease. So, there's a lot of interest in further exploring that and looking at the patients who have ultra-HER2-low disease, so between and 1 plus a little bit of expression. That's been studied in the hormone receptor-positive population in DESTINY-Breast06. But there's a lot of interesting further defining that triple-negative population, so to speak, they're going to be triple-negative plus now and understanding what the benefit is in that population. So definitely will be looked at more now moving forward. Dr. Allison Zibelli: Thank you. So, let's move on to Abstract 1002. And the results from the phase 1, 2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate, and patients with HER3 expressing metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: That's a really interesting, another one of these second- to third-generation antibody-drug conjugates. It's just the antibody, instead of being the usual, sort of, HER2 or TROP2 that we're used to thinking about is directed to HER3, 1 of the HER family of proteins. This is interesting. There's actually been a lot of work trying to target HER3 with naked antibodies with disappointing results, although I have to say most of the studies really didn't push it too far. So, with this antibody drug construct, deruxtecan, which is the same as in T-DXd and another TROP2 ADC Dato-DXd is used. So, I will say they do need to change the toxin in the next generation of ADCs. But they looked at, at first did a dose-finding study which has previously been presented, and then a dose expansion in both hormone receptor-positive HER2-negative disease and triple-negative disease. All the triple-negative patients had HER3 high disease by immunohistochemistry, and the hormone-receptor-positive patients were enrolled in 2 cohorts, HER3 high and HER3 low. And the median number of prior treatment regimens that patients had received in the hormone-receptor-positive group was 6 and 2 for the triple-negative group, but there was a huge range, up to 13 lines of treatment. They only had 14 patients with HER2+ disease. So, it's a little bit hard to know what to do with that patient group, but they were heavily pretreated 5.5 prior lines of therapy. The confirmed overall response rate in the 113 patients with combined HER3 high and low was 30%, very impressive, heavily pretreated patients. For triple-negative disease all HER3 high, it was 23%. Again, very nice. And there were 14 patients with HER2+ disease that also were HER3 high. It was about 43%. So those are nice responses, but we always want to know how durable is that. The duration of response ranged from 6 to over 8 months in those 3 different groups. So, these were quite durable. It wasn't any 2- to 3-month duration of response. So very impressive. And then when they looked to see, did it matter whether you had HER3 expression that was high or low in the hormone-receptor positive group, they actually did see responses in the HER3-low group, some very good responses. Overall, there were less patients in that group, but it does suggest that maybe you would still see responses in the HER3-low group, very impressive. And then 1 really interesting correlative study they did was they looked to see what happened to the HER3 expression on the tumor cell over time, and it went down. So, you treated the HER3 expression in most of the patients just dropped off completely, which is really interesting. It didn't have any association with clinical activity, but it's sort of an interesting correlative endpoint. This is a drug that overall was pretty well tolerated. They saw a similar toxicity to T-DXd with a lot of nauseous, a little bit of alopecia, a little bit more bone marrow suppression than we're used to seeing with T-DXd. So, neutropenia was seen in about 10% of patients at the lower dose and about a quarter of the patients at the higher dose. Overall, pretty well tolerated. Now, interstitial lung disease is a toxicity with this construct, and they saw ILD of 7% but most cases were grade 1 and 2. The other interesting toxicity that's unique to this agent is thrombocytopenia. So, they saw a grade 3 or greater rate of thrombocytopenia of 27% in the lower dose group, and in the larger group that received the higher dose, 39% of grade 3 or greater thrombocytopenia, so platelets less than 100,000. Turns out that when you stop the drug, the platelets do come back, so that's a good thing. Sometimes we saw long-term thrombocytopenia with T-DM1. They didn't see bad toxicity like bleeding, but it is something that needs to be managed with this drug because we're not great at managing thrombocytopenia. In any case, it has fast-track designation for another solid tumor, not breast cancer, and we'll have to see where this fits into our dizzying array of very effective ADCs now. Dr. Allison Zibelli: The practicing medical oncologist is not used to testing for HER3 in our patients with breast cancer. How common is it? Dr. Hope Rugo: HER3 expression is quite common in hormone receptor-positive disease, a little less common in triple-negative breast cancer. So, I think that we would see expression if we were going to be treating patients with this particular approach. Dr. Allison Zibelli: All right. Let's move on to Abstract 507, which reported long-term outcomes of adjuvant denosumab in breast cancer, specifically fracture reduction and survival results from 3,425 patients in a randomized double-blind, placebo-controlled ABCSG-18 trial. What are your thoughts about this study? Dr. Hope Rugo: Well, this trial, this is an update of a study that previously has been presented and published, most recent publication was in Lancet Oncology in 2019, and these patients were randomly assigned to receive denosumab at 60 milligrams, important to note the dose, subcutaneously every 6 months versus placebo every 6 months, and they did get placebo subcutaneous injections. And this treatment continued through their endocrine therapy. They showed a dramatic reduction in fracture rate, and that has been maintained over time. We were really surprised enough to suggest that maybe Austrian people didn't go into the sun, so they got more Vitamin D deficiency, hard to know, but the hazard ratio is 0.5. It's unbelievable the number of fractures, 92 for denosumab but 176 for placebo, a P value of less than .0001. So, this is a real endpoint, treating patients who are receiving endocrine therapy that, in this case, non-steroidal aromatase inhibitor therapy that can increase bone loss, have a reduced fracture rate when they received denosumab. So that is the big take-home message, and a medium follow-up of 8 years. But the secondary endpoints included disease-free survival. They had about 20% disease-free survival events and 8% deaths, and what they saw was really interesting. So, the caveat is that 16% of patients were unblinded at the first analysis and half of them got denosumab, so it messed up their results a little bit, but the disease-free survival was significantly better in patients who received denosumab, and the hazard ratio of 0.83 and the hazard ratio does not cross 1. So that's very interesting, and even overall survival, they looked at 2 other endpoints, bone metastasis-free survival, and overall survival. They also trend towards an improvement with a hazard ratio of 0.8 for both of them. And they didn't actually see toxicity. So, patients' brittle bone fractures and osteonecrosis of the jaw (ONJ) are all concerning, but they really just did not see any risks in this patient population. I think there was 1 patient that had what they thought was a brittle bone fracture. Obviously, they watched the mouth very carefully as well. Really dramatic, and I think it's kind of disappointing that we never had any registration approach in this, and also not well-understood why the D-CARE study did not show a benefit, but I think D-CARE was designed differently. This is a better design to focus on our patients and the specific issues, and I think it's intriguing and should be considered as part of our treatment regimen for patients who are at risk for bone loss and have early-stage breast cancer on an aromatase inhibitor. Dr. Allison Zibelli: I've been using DEXA scans and offering denosumab to my patients on AIs that have osteopenia or osteoporosis. Should we be considering it in women with normal bone mass? Dr. Hope Rugo: I think not yet. Unfortunately, this trial was not immediately powered for cancer outcome, although the data are very encouraging. We don't know what the relationship is to bone loss, and providing an environment that's friendlier for cancer cells. So, do you have to have bone loss in order to have the risk that you're reducing with these agents? Certainly, that's what we've seen with zoledronate. So, I think that we don't have sufficient data to use this simply to treat cancer, but I do think that we should be considering this as an agent to give patients who have bone loss, either when you're starting an aromatase inhibitor or during the course of therapy. I think it's well tolerated, and a subcutaneous injection is not difficult. One of the questions that's come up for people is do you get bone loss that increases your risk of fracture after you stop therapy. But clearly from these updated data, these patients were off therapy. They did not have an increase of fractures and the patients treated with denosumab fared much better, I mean the hazard ratio of 0.5. Dr. Allison Zibelli: Let's move on to TROPiCS-02. That's LBA1001. This is a randomized phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive, HER2-negative advanced breast cancer. How do you think this study will impact practice? Dr. Hope Rugo: That's a great question. I presented this data, and I think I presented it on a Saturday, and on Sunday we saw the plenary talk of DESTINY-Breast04. These patients enrolled in TROPiCs-02 had a median number of lines of prior chemo 3 with a range of up to 8 actually, compared to a median number of lines as 1 in the DESTINY-Breast04 population. We included all hormone receptor-positive HER2 negative-advanced breast cancer, not centrally confirmed. They included just the HER2 low subset that was centrally confirmed. Everybody in our study had received prior CDK4/6 inhibitors compared to about 70% in DB04. And then 95% of patients in this trial had visceral mets. So, we did really treat a patient population who had very advanced high risk hormone receptor-positive breast cancer. As you know, we saw an improvement and progression-free survival with a hazard ratio of 0.66 meeting the endpoint. We needed a hazard ratio of 0.7, highly statistically significant P value .0003, but the median difference in PFS was only 1.5 months, and overall survival data is not yet mature. So that's brought up the question about how this drug should be used because there was a big fall off in the first 2 months where patients had rapid disease progression with heavily pretreated chemotherapy-resistant disease. We did landmark analyses and there were big separations in PFS at 6, 9, and 12 months, and 12 months, it was 21% patients free of progression and death at 1 year versus 7% for the TPC arm. So, it was a tripling of patients who were free of progression at one year. I think that's clinically relevant. This drug is associated with more neutropenia. That's the primary issue to manage, and probably half of the patients need growth factors at some point. When we looked at other endpoints response to ratio response, etc., we're better with Sacituzumab. So where does this all fit into our treatment paradigm. I think there's the HER2-low patients who will now receive T-DXd up in the, I hope, second line and not in lieu of endocrine therapy, when they're ready for chemo. But there are patients who don't have HER2-low disease and then there are patients who are going to be in the later line setting. So, I do think it still has a place in the treatment department, receptor-positive metastatic breast cancer. The results show that it was better than chemotherapy, physician choice based on our national and international guidelines, and that's better for our patients to have that option. Overall survival data obviously is looked for with great interest and that will help us put this into the right paradigm. And then I also hope that real world data will help us understand how sequential treatment with these different ADCs will benefit our patients. Dr. Allison Zibelli: This is really exciting. Do you think that we're maybe coming toward the end of conventional chemotherapy, especially for women with HER2-positive disease? Dr. Hope Rugo: I wonder if we are. I think we were interested in T-DM1 for HER2-positive disease early on. We've seen some really nice pathologic complete response data as well as adjuvant data in the attempt trial in patients who had stage I disease. Now that we have these second-, third-generation ADCs, T-DXd, I think this could potentially completely replace our chemotherapy. We still have to deal with alopecia. And I will point out ADCs are still chemotherapy. They're just a much more efficient and effective way of delivering treatment, and we need to be very careful to manage the toxicity. Dr. Allison Zibelli: Next, we're going to talk about the main pain trial that's LBA1004, which is a randomized phase 2 trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or hormone receptor-positive HER2-negative metastatic breast cancer, in other words CDK4/6 after CDK4/6. What are your takeaways here? Dr. Hope Rugo: First, just amazing that an investigator-initiated trial could do this well and be placebo-controlled. So, kudos to the principal investigator (PI) [Dr.] Kevin Kalinsky. This trial is a small phase 2 trial. A reasonable number, 119 patients were randomly assigned and evaluable patients could have received up to 1 line of prior chemotherapy for metastatic disease. If you had received prior exemestane, you received fulvestrant, if you received prior fulvestrant, you received exemestane, and actually if you looked at the number of patients who had received fulvestrant, it was 99 versus only 20 with exemestane. So important to keep in mind. If you looked at the overall population where the primary endpoint was progression-free survival, the hazard ratio is 0.57, just median PFS of 2.8 months in patients receiving endocrine therapy and placebo and 5.3 months for patients receiving endocrine therapy and ribociclib. So was this ribociclib after ribociclib or ribociclib after something else. 86% of patients had received palbociclib as their prior CDK4/6 inhibitor, and only about 10% to 14% had received prior ribociclib. So, there's a predominance of palbociclib followed by ribociclib. The other thing that's important to keep in mind is how sick this patient population was. Very few had received prior chemotherapy in the less than 10% range, visceral metastases in about 60%. So that's helpful. Only 19% or so had received 2 or more endocrine therapies from metastases. So, most people did this as their second line treatment. The PFS, when you looked at fulvestrant or exemestane, looked like the benefit was relatively similar, but you know you got 20 patients in the exemestane arm. The hazard ratios, looking at the subgroup analyses, all looked pretty similar, and the overall response and clinical benefit rate were better with continuing the cyclin dependent kinases (CDK) inhibitor. There was interesting sub-analysis looking at mutations and how that affected things. And they looked at patients who had ESR1 mutations or had wild-type ESR1. 42% had ESR1 mutations at study entry, very similar to what we've seen. In that group of patients, remember it's only 33 where they had this analysis, they saw a lot of other mutations. So p53, PIK3CA, FGFR, CCND1—those patients did not benefit. Only 33 patients. No benefit at all, very short PFS, about 3 months. The patients who had ESR1 wild type seemed to benefit a lot, 45 patients going from about 3 months to a little over 8 months. So, this is all hypothesis-generating data. I wouldn't run out and use this as your standard of care now because it is small data. But when the patient doesn't have other good options, I certainly would consider switching the CDK and going on, add that to the next line endocrine therapy. It's important to switch the endocrine therapy. I think we really need to look at the ongoing phase 3 trials to give us better evidence basis and understand the impact of mutations and prior therapy on who might benefit from continued CDK inhibitors after progression on a CDK inhibitor. Dr. Allison Zibelli: I think this is a really exciting trial. We all have a lot of patients on palbociclib and letrozole who've been on for 4, 5 years, and would like to continue with this kind of treatment because the side effects are really manageable. So, I look forward to seeing what's coming in the future with the phase 3 trials. So, let's talk about Abstract 1015, which I thought is a great idea. It looks at the quality of life with ribociclib plus aromatase inhibitor versus abemaciclib plus AI as first-line treatment of hormone receptor-positive, HER2-negative advanced breast cancer, assessed via matching adjusted indirect comparison. Could you tell us what matching adjusted indirect comparison is and why you chose this for the study? Dr. Hope Rugo: It's an interesting question. How do you compare across trials? So, matching this kind of make analysis, we'll call it a make analysis for the purposes of this discussion, allows you to match patients and weight based on their characteristics that might affect patient reported outcomes. And that actually is a way of trying to do a fair cross-trial comparison. So basically, take the study population, you match the inclusion and exclusion criteria, and then you weigh the different criteria so that you can try and make a better association. It's the best way we know of comparing across trials. You know, a lot of people ask why we didn't have PALOMA-2 in here, and that's because they used a different patient reported outcome tool. So, you have to use the same patient reported outcome tool in order to compare. So that's why we did this analysis, and it sort of came on the heels of a survey that Fatima Cardoso presented at San Antonio in 2021, where patients identified diarrhea as a symptom they really didn't like more than everything else. And you can imagine, I think we all have that experience in practice, the unexpected nature of diarrhea and the fact that it does limit your activities and, therefore, quality of life are important. In this analysis, interestingly but not surprisingly, ribociclib favored abemaciclib in diarrhea, and there can be associated appetite loss, so ribociclib also favored abemaciclib for appetite loss. And I thought the last one was interesting—fatigue—because I wouldn't have assumed that fatigue would be different. And maybe it's associated with diarrhea. They have these funny arm symptoms that were better. We don't really know why that was, and it's hard to assess again. We're really not clear based on the differences between the drugs. So, there are limitations to the analysis, but I think that it helps us really in individual patients try and match patients' underlying symptoms with the best treatment to offer them the best quality of life as they're being treated in the metastatic setting. Dr. Allison Zibelli: I thought this study was great because it really centered the experience of the patient and the wishes of the patient. You don't see that designed into many clinical trials, the way this was. So, I thought that was a great feature of this study. Dr. Hope Rugo: I will say that all of the 3 studies that looked at CDK inhibitors, all those 3 studies included patient-reported outcomes. That's an important new approach that is really being focused on. Dr. Allison Zibelli: Do you consider the CDK4/6 inhibitors equivalent in efficacy, and could you substitute them to try to get the side effect profile that you want? Dr. Hope Rugo: Well, I think that we saw in the early stage setting that there are differences. Now, across the different trials, there are big differences in patient populations and inclusions as we saw in the PALOMA-2 results that were presented at ASCO [Annual Meeting], whether the patients had prior chemotherapy like in PALOMA-3, whether they had a short disease-free interval, the higher risk patients in PALOMA-2. The PALOMA trials were more broadly inclusive than the other 2 studies, the MONALEESA and MONARCH series of trials. So, we do have to be a little bit careful about comparing apples to oranges, but we have the early-stage results of MONARCH E showing a clinically important difference in outcome whereas the PALLAS and Penelope-B trials didn't. So that sort of puts us into a little bit of a question period. Are these all patient populations or are there differences between the agents? The PFS and the metastatic setting, all the hazard ratios line up. So, in truth, although I know the activity against cyclin-independent kinases are different between agents, we don't still really understand the clinical differences in efficacy, but I think we all are practicing using evidence-based medicine. I wouldn't, for example, substitute a different CDK4/6 inhibitor for abemaciclib in the treatment of early-stage breast cancer. We have to just learn how to manage the diarrhea and use prophylaxis and dose reduce early to manage this and make it tolerable for our patients. And in the metastatic setting, I think we need to follow evidence-based guidelines and use the best data available to decide on the right treatment approach and sequencing for our patients. Dr. Allison Zibelli: Thank you, Hope, for coming on the podcast today. This was a really interesting review of one of the most exciting ASCO [Annual Meetings] I've been to. And thanks for sharing your valuable insights with us and helping us make sense of all this really new exciting data. We really appreciate it. Dr. Hope Rugo: Thank you. And thank you so much for inviting me. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. That really helps other listeners find us. Thank you. Disclosures: Dr. Allison Zibelli: None disclosed. Dr. Hope Rugo: Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Blueprint Medicines Consulting or Advisory Role: Napo Pharmaceuticals Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals, Astellas Pharma, Seattle Genetics, Macrogenics, Boehringer Ingelheim, Polyphor 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.
During her Platinum Jubilee celebration this year, Queen Elizabeth greeted the crowds from the balcony at Buckingham Palace, dressed in bright blue with a cane in hand, at 96 years old… there's no denying change is coming. On her left: William, Kate, and the kids. On her right: Charles and Camilla. The message was clear — this is the future of the monarchy, with Charles at the helm. In our final episode, we're taking a look at what's next for the royal family. From Charles to William to little George, what does a modern monarchy look like? Where do Harry and Meghan fit in? And after 70 years of Queen Elizabeth's reign, is the world ready for King Charles?
JD & The Brass Saddle Band on Van Sessions. Recorded during Ogden's First Friday Art Stroll. Supported by a generous grant from Ogden City Arts along with love from Roosters Brewing. Thanks to everyone who came out to the live show! Join us every First Friday for recordings at The Monarch Building in Ogden, Utah. MUSICIAN/BAND JD & The Brass Saddle Band: https://www.reverbnation.com/jdandthebrasssaddleband SUPPORTERS The Monarch Building: https://themonarchogden.com/ Ogden City Arts: https://www.ogdencity.com/707/Arts Roosters Brewing: https://www.roostersbrewingco.com/ CREDITS Producer / Host / Editor: R. Brandon Long, The Banyan Collective Logistics / Bookings / Front of House: Todd Oberndorfer, The Banyan Collective Photographer: Ruth Silver Photo Editor: Jeff Madsen FOLLOW Van Sessions Instagram: https://www.instagram.com/vansessions/ Van Sessions Facebook: https://www.facebook.com/thevansessions Like what you hear, buy us beer: https://www.buymeacoffee.com/banyanmedia Bookings: email@example.com
JD & The Brass Saddle Band on Van Sessions. Recorded during Ogden's First Friday Art Stroll. Supported by a generous grant from Ogden City Arts along with love from Roosters Brewing. Thanks to everyone who came out to the live show! Join us every First Friday for recordings at The Monarch Building in Ogden, Utah. MUSICIAN/BAND JD & The Brass Saddle Band: https://www.reverbnation.com/jdandthebrasssaddleband SUPPORTERS The Monarch Building: https://themonarchogden.com/ Ogden City Arts: https://www.ogdencity.com/707/Arts Roosters Brewing: https://www.roostersbrewingco.com/ CREDITS Producer / Host / Editor: R. Brandon Long, The Banyan Collective Logistics / Bookings / Front of House: Todd Oberndorfer, The Banyan Collective Photographer: Ruth Silver FOLLOW Van Sessions Instagram: https://www.instagram.com/vansessions/ Van Sessions Facebook: https://www.facebook.com/thevansessions Like what you hear, buy us beer: https://www.buymeacoffee.com/banyanmedia Bookings: firstname.lastname@example.org
Steve Harper Interviews Tom Marino Owner of Monarch Life Coaching LLC --www.monarchlifecoaching.comhttps://onlineradiobox.com/search?cs=us.pbnnetwork1&q=podcast%20business%20news%20network&c=ushttps://mytuner-radio.com/search/?q=business+news+network
Welcome to another episode of The Action and Ambition Podcast! Joining us today is Praveen Penmetsa, Founder and CEO of Monarch Tractor, a company that is leading the transformation of farming. Monarch helps farmers by addressing labor availability, meeting consumer demands for sustainability, and providing actionable data-driven farming insights. It enables economically competitive organic and beyond farming through intelligent electro-mechanical solutions that replace harmful chemicals. Praveen is also the Founder and CEO of Motivo Engineering, a product-engineering firm with clients in the Mobility, Energy, AgTech, and Aerospace sectors. Tune in to learn more!
Thanks for listening! If you would like to see the YouTube video click here: Please check out our live event tonight! Sam and I hosted a Monarch open house! Look how much my baby has grown!!!!!! And to hear him talk about our Monarch company, books, author world, and his own writing just makes this momma's heart so proud. Love y'all! Thanks for always supporting us. Continue to pray for us and the business! We appreciate you all! https://youtu.be/aS9h6GysVkk --- Send in a voice message: https://anchor.fm/jen-lowry-writes/message Support this podcast: https://anchor.fm/jen-lowry-writes/support
Gloriana had illuminated an era, for which she gave it her name. A grand ceremony was about to begin. Her Majesty was dressed for the occasion and coiffed in style. Good Queen Bess always dominated special occasions and today would be no exception. Her subjects would pay her homage, as they should. Although Regina's Monarch and Sovereign official portraits had not changed in decades—propagating intemporal youth and vigor throughout her realm—today her mask would be removed, finally exposing her true visage. Anyone who was ‘anyone' in the Kingdom was present. The Monarch's favorite seamstress remained close by, at her post, assuring her anointed Sovereign's costume was impeccable. The Virgin Queen was ready. She lay still, dignified, royal, arms to either side, reposed in regal attire, attended by her ladies in waiting, ready for one last opulent public appearance... her funeral. Check out the YouTube version of this episode at https://youtu.be/N7y4fYbjNuw which has accompanying visuals including maps, charts, timelines, photos, illustrations, and diagrams. Support our channel by watching and clicking on the ads in this video. It costs you nothing and by doing so gives us extra credit and encourages, supports & helps us to create more quality content. Thanks! A Patreon member sent in this question: Mark, I saw your posts on a few online History Groups. How many such groups are you a member of? Mark's answer: I've put together a complete list of the over 100 free online History Groups I've joined which I posted for you and all my other Patreon members to exclusively peruse and enjoy at https://patreon.com/markvinet Denary Novels by Mark Vinet are available at https://amzn.to/33evMUj Mark Vinet's TIMELINE video channel at https://youtube.com/c/TIMELINE_MarkVinet Website: https://markvinet.com/podcast Instagram: https://www.instagram.com/denarynovels Twitter: https://twitter.com/TIMELINEchannel Facebook: https://www.facebook.com/mark.vinet.9 YouTube Podcast Playlist: https://www.bit.ly/34tBizu Podcast: https://anchor.fm/mark-vinet Linktree: https://linktr.ee/WadeOrganization
King Thurber on Van Sessions. Recorded during Ogden's First Friday Art Stroll. Supported by a generous grant from Ogden City Arts along with love from Roosters Brewing. Thanks to everyone who came out to the live show! Join us every First Friday for recordings at The Monarch Building in Ogden, Utah. MUSICIAN/BAND King Thurber: https://kingthurber.com/ SUPPORTERS The Monarch Building: https://themonarchogden.com/ Ogden City Arts: https://www.ogdencity.com/707/Arts Roosters Brewing: https://www.roostersbrewingco.com/ CREDITS Producer / Host / Editor: R. Brandon Long, The Banyan Collective Logistics / Bookings / Front of House: Todd Oberndorfer, The Banyan Collective FOLLOW Van Sessions Instagram: https://www.instagram.com/vansessions/ Van Sessions Facebook: https://www.facebook.com/thevansessions Like what you hear, buy us beer: https://www.buymeacoffee.com/banyanmedia Bookings: email@example.com
King Thurber on Van Sessions. Recorded during Ogden's First Friday Art Stroll. Supported by a generous grant from Ogden City Arts along with love from Roosters Brewing. Thanks to everyone who came out to the live show! Join us every First Friday for recordings at The Monarch Building in Ogden, Utah. MUSICIAN/BAND King Thurber: https://kingthurber.com/ SUPPORTERS The Monarch Building: https://themonarchogden.com/ Ogden City Arts: https://www.ogdencity.com/707/Arts Roosters Brewing: https://www.roostersbrewingco.com/ CREDITS Producer / Host / Editor: R. Brandon Long, The Banyan Collective Photographer: Ruth Silver Logistics / Bookings / Front of House: Todd Oberndorfer, The Banyan Collective FOLLOW Van Sessions Instagram: https://www.instagram.com/vansessions/ Van Sessions Facebook: https://www.facebook.com/thevansessions Like what you hear, buy us beer: https://www.buymeacoffee.com/banyanmedia Bookings: firstname.lastname@example.org
Jefferson Farms was founded in 1995. This farm is a unique farm with a fantastic location and spacious barns and pastures. We found our calling raising alpacas for baby alpaca yarn and other products, she said. Alpaca fiber is used for making knitted and woven items. These items include blankets, sweaters, hats, gloves, scarves and many more products.My guest is also a Super Host that Offers you a Mountain view, privacy, peace and quiet yet only a mile from town! Salida is the best-kept secret of Colorado! Monarch ski area, natural hot springs and hot springs pool, river rafting, premier biking and fly fishing.... too many things to mention as well as the best kept little mountain with great restaurants. 8815 CR-150 Salida, CO 81201. www.jeffersonfarmsnaturalfibers.com http://www.yourlotandparcel.org
The royal family is no stranger to controversy — and Prince Charles has often been at the center of the scandal-du-jour. What happens when he takes on the job of maintaining the monarchy's public image… the one he's been accused of tarnishing over the years? We'll take a look at the more recent scandals Charles has had to manage alongside the Queen – from questions about how some of his charities raise money to his brother Prince Andrew's settlement in a sexual abuse lawsuit, to his son Prince Harry's departure from the Firm. What other challenges might lie ahead for the future king, and how will he manage them?
In 1954, a young Queen Elizabeth embarked on her first tour of Australia, including townships in regional Australia that would never again experience the hype of a visit by a ruling Monarch. One of those towns was Shepparton in Victoria's Goulburn Valley. At the time, the people of the Yorta Yorta nation had made their home on a stretch of a flood plain between Shepparton and Mooroopna. This place was known as the Flats.
I've had so much going on in the author world and now I finally get to sit down for a little bit and share the news! --- Send in a voice message: https://anchor.fm/jen-lowry-writes/message Support this podcast: https://anchor.fm/jen-lowry-writes/support
Steve Harper Interviews Tom Marino Owner of Monarch Life Coaching LLC --www.monarchlifecoaching.comhttps://onlineradiobox.com/search?cs=us.pbnnetwork1&q=podcast%20business%20news%20network&c=ushttps://mytuner-radio.com/search/?q=business+news+network
Welcome back to another episode Everything Under The Sun! This week we have the brilliant historian and author Dominic Sandbrook, answering Penny's question ‘Who was the first monarch of England?' We also work out the answer to River's question how are books made? And discuss a pressing question from Jemima which is what are the world's smallest and biggest islands? Lots of fun questions to delve into this week and we look forward to exploring them with you. Have a lovely weekend! Do check out the BOOK www.mollyoldfield.com/everything-under-the-sunDo check out Dominic Sandbrook's books, including his ‘Adventures in Time' series, which we think you'll love! https://dominicsandbrook.com/booksInstagram: @mollyoldfieldwrites and @everythingunderthesunpodTwitter: @mollyoldfield THANK YOU! Do send me a question for the new EUTS book and share with your friends!Molly x See acast.com/privacy for privacy and opt-out information.
-carbon dioxide in the atmosphere hits all time high -Southern California imposes mandatory water cutbacks -California judge halts of spraying pesticides on public lands -Climate change could push 200 million to migrate. -U.S will reduce rents and fees to put solar on public lands -Colorado bans single-use plastic bags and foam takeout containers -Monarch butterfly population sees 35% increase in the number
King Philippe seeks to make amends for his country's brutal colonial legacy. His aunt tells us it's long overdue. Also: the World Bank warns that much of the world is heading for recession. And millions of Chinese students grapple with a gruelling three-day university entrance exam.
While the Ventures are trying to solve the curse of the haunted PROBLEM, the Monarch gets in way over his head with Wide Wale. Attempting to cinch the arching rights for Rusty gets the Monarch kidnapped, and it's up to 21 and Dr. Mrs. the Monarch to try and extract him from a delicate situation. Meanwhile, Enrico Matassa is back on the scene... Special thanks to Joshua Jarett (http://jjarrett.work) for our cover art, Gwen May (https://soundcloud.com/deepwhale) for our theme song, and Brayton Cameron (https://twitter.com/braytonjc) for being our announcer.
Vier Tage lang war ganz England anlässlich des 70. Thronjubiläums von Queen Elizabeth II. im Ausnahmezustand. Die Briten lieben ihre Königin, die mit ihren 96 Jahren so lange wie keine andere britische Monarchin oder ein Monarch vor ihr auf dem Thron sitzt. Während die Queen vom berühmten Balkon des Buckingham Palace winkt und das Volk jubelt, werden die Monarchie-Gegner in Großbritannien aber immer lauter. In dieser Folge des ntv-Podcasts "Ditt & Datt & Dittrich" sprechen Verena und Ronny über die Feierlichkeiten rund um das Platinjubiläum.Außerdem Thema: Misstrauensvotum gegen Premierminister Boris Johnson, kalte Flure in royalen Anwesen sowie die Frage, welche Rolle der mittlerweile 73-jährige Prinz Charles für die Zukunft der Monarchie einnimmt.Mehr dazu? Queen grüßt zum großen Finale vom PalastbalkonIhr habt Fragen oder ein spannendes Thema für "Ditt & Datt & Dittrich"? Hier geht's zu Verena.]]
In 1981, the world watched as Prince Charles married the perfect royal bride: Lady Diana Spencer. Young, beautiful, and stylish, Diana breathed new life into the monarchy. But the fairytale didn't last long. In the years that followed, Diana and Charles's troubled marriage and bitter divorce was a constant in the tabloids, and Diana's death in a car accident in 1997 shook the world. And through it all, Charles gained a reputation as an unfaithful husband to the “people's princess” as he carried on an affair with friend Camilla Parker Bowles. But today, Camilla — once known as the notorious “other woman” — is poised to become Queen Consort when Charles takes the throne. It's a reflection of the changes the monarchy has undergone in the aftermath of the Charles and Diana saga… and the fulfillment of Prince Charles's decades-long quest to have the love of his life accepted by the royal establishment and the British public.
- Pod Trivia (2x!) - Ethan's Having a Baby! - Monarch's Minute - New Signing - Damir Kreilach Injury Update - Vancouver Review - San Jose Preview --- Support this podcast: https://anchor.fm/thehivesports/support
Let's examine the clever and effective use of political art during the reign of Queen Elizabeth while visiting Jesus College founded in 1571 under the reign of the Monarch, making it the only Elizabethan College within the University of Oxford. Paintings of her likeness demonstrated the Tudor concept of power. The portraiture of Queen Elizabeth the First of England illustrates the evolution of English royal portraits from the representations of simple likenesses to the later multifaceted imagery used to convey the power, authority, supremacy and aspirations of the state, as well as of the monarch at its head. Elizabeth paid more attention to propaganda than art, disseminating her portraits widely throughout her realm, including North America. Check out the YouTube version of this episode at https://youtu.be/izUNMacYZic which has accompanying visuals including maps, charts, timelines, photos, illustrations, and diagrams. Support our channel by watching and clicking on the ads in this video. It costs you nothing and by doing so gives us extra credit and encourages, supports & helps us to create more quality content. Thanks! Visit our sponsor https://athleticgreens.com/EMERGING to take ownership over your health and get a FREE 1 year supply of immune-supporting Vitamin D and 5 FREE travel packs with your first purchase! Get exclusive access to Bonus episodes, Ad-Free content, and Extra materials when joining our growing community on Patreon at https://patreon.com/markvinet or Donate on PayPal at https://bit.ly/3cx9OOL and receive an eBook welcome GIFT by Mark Vinet. Denary Novels by Mark Vinet are available at https://amzn.to/33evMUj Mark Vinet's TIMELINE video channel at https://youtube.com/c/TIMELINE_MarkVinet Website: https://markvinet.com/podcast Instagram: https://www.instagram.com/denarynovels Twitter: https://twitter.com/TIMELINEchannel Facebook: https://www.facebook.com/mark.vinet.9 YouTube Podcast Playlist: https://www.bit.ly/34tBizu Podcast: https://anchor.fm/mark-vinet Linktree: https://linktr.ee/WadeOrganization
Seit 70 Jahren sitzt Elizabeth Alexandra Mary aus dem Hause Windsor - kurz: Elizabeth II. - auf dem britischen Königsthron. Damit herrscht sie länger als jede andere Monarchin und jeder andere Monarch des Vereinigten Königreichs vor ihr. In London wird das Jubiläum seit Donnerstag vier Tage lang gefeiert. In der heutigen Folge des KURIER Daily spricht Moderator Johannes Arends mit der Journalistin Anna-Maria Bauer, die für den KURIER die Feierlichkeiten in London begleitet. Anschließend analysiert unser ständiger London-Korrespondent Georg Szalai, warum die Queen für die Briten so wichtig ist - und ob die positive Stimmung im Land dem krisengebeutelten Premier Boris Johnson eine Atempause verschafft. Dieser Podcast entsteht mit freundlicher Unterstützung der Bundesregierung: Alle Infos zur aktuellen Impfkampagne der Bundesregierung findet ihr auf gemeinsamgeimpft.at Abonniert unseren Podcast auch auf Apple Podcasts, Spotify oder Google Podcasts und hinterlasst uns eine Bewertung, wenn euch der Podcast gefällt. Mehr Podcasts gibt es unter www.kurier.at/podcasts
This week, the U.K. is celebrating Queen Elizabeth II's Platinum Jubilee, marking 70 years on the throne. She rose to the throne in 1952 at the age of 25 upon the death of her father King George VI. Per TIME's Feb.
The people of the UK are currently enjoying a four day long weekend as up and down the country, millions of people are celebrating the Queen's 70 years on the throne. So what exactly are the plans for the Platinum Jubilee, and which members of the Royal Family will be front and centre given so many of them are embroiled in public scandals and family bust-ups? The Quicky speaks to two Royal experts to find out about all the celebrations that will be happening, who will be front and centre and who will be hidden from all the public pomp and ceremony. Subscribe to Mamamia GET IN TOUCH Feedback? We're listening! Call the pod phone on 02 8999 9386 or email us at email@example.com CONTACT US Got a topic you'd like us to cover? Send us an email at firstname.lastname@example.org CREDITS Host: Claire Murphy With thanks to: Maddalena Mastrostefano - Europe Correspondent for Royal Central, who has written extensively about all of the world's Royal families Holly Wainwright - Head of Content at Mamamia, and co-host of Mamamia Out Loud and Lowbrow Producer: Claire Murphy Executive Producer: Siobhán Moran-McFarlane Audio Producer: Jacob Round Subscribe to The Quicky at...https://mamamia.com.au/the-quicky/ Mamamia acknowledges the Traditional Owners of the Land we have recorded this podcast on, the Gadigal people of the Eora Nation. We pay our respects to their Elders past and present, and extend that respect to all Aboriginal and Torres Strait Islander cultures. Just by reading our articles or listening to our podcasts, you're helping to fund girls in schools in some of the most disadvantaged countries in the world - through our partnership with Room to Read. We're currently funding 300 girls in school every day and our aim is to get to 1,000. Find out more about Mamamia at mamamia.com.au Support the show: https://www.mamamia.com.au/mplus/ See omnystudio.com/listener for privacy information.
Queen Elizabeth feiert ihr 70. Thronjubiläum und Grossbritannien macht vier Tage Party mit allem Drum und Dran. Warum hängen die Britinnen und Briten so an ihrer Queen? Und was ist mit den anderen Monarchien in Europa, brauchts die noch im Jahr 2022? Wir vergleichen drei der zwölf Monarchien in Europa, schauen, welche Monarchin oder welcher Monarch am meisten Macht hat und wie die Bevölkerung über die Monarchie in ihrem Land denkt. Habt ihr Inputs, Feedback oder Kritik zum Podcast? Dann schickt uns eine Sprach- oder Textnachricht an 076 320 10 37 oder eine Mail an email@example.com
‘With his beautiful use of language, Proctor has Bernard Darwin's gift of bringing a moment to life. Delightful and insightful, capturing the very spirit of the age. The Long Golden Afternoon is an instant classic' - Roger McStravick - Author & Historian Stephen Proctor joins us today to chat about his second book, a followup to Monarch of the Green and the golfing feats of Young Tommy Morris. The Long Golden Afternoon tells the story of the transformative generation of golf that followed the rise of Young Tom Morris - an era of sweeping change that saw Scotland's national pastime become one of the rare games played around the world. It begins with the first epochal performance after Tommy - John Ball's victory at Prestwick in 1890 as the first Englishman and the first amateur to win the Open Championship - and continues through to the outbreak of the Great War. If Tommy ignited the flame of golf in England, Ball's breakthrough turned that smoldering fire into a conflagration. The generation that followed would witness the game's coming of age. It would see an explosion in golf's popularity, the invention of revolutionary new balls and clubs, the emergence of professional tours, the organization of the game and its rules, a renaissance in writing and thinking about golf, and the decision that the Royal and Ancient Golf Club of St Andrews must always remain the sport's guiding light. Stephen's books can be purchased from the book publishers' website links below: https://birlinn.co.uk/product/the-long-golden-afternoon/ https://birlinn.co.uk/product/monarch-of-the-green-3/ The Classics of Golf library website can be viewed here (https://classicsofgolf.com/) Tony Jacklin & Dave Marr recreate the 1860 Open Championships at Prestwick (https://www.youtube.com/watch?v=nDN6KWp2WNY) Askernish - the 'Lost' Old Tom Morris Golf Course | Scotland From The Sky | BBC Scotland (https://www.youtube.com/watch?v=2BFhbec7b0s) Special Guest: Stephen Proctor.
Prince Charles has long been seen as an eccentric - his passion for gardening and watercolor painting combined with his love of the luxurious royal life has given him the reputation of being out-of-touch with the average person. But Charles might also be considered ahead of his time - a long-time environmentalist who's been spearheading initiatives for sustainable living for more than 50 years. Many of the prince's ideas, at first quickly dismissed, have turned out to be prescient. We're taking a deeper look at this complex man. Did he become Prince Charles because of his upbringing or despite it? And how will the Prince Charles that we have come to know evolve into King Charles when he must meet his destiny.
Papa Bear Hikes welcomes back trail family member Stan Sutter, and new friend Tonya Lonsbury. Tune in for a fun episode with conversation about hostels and keeping it real on the trail. Stan Sutter:Stan Sutter (@stanthemanhikes) • Instagram photos and videosStan the Man Hikes - YouTubeStan's Solo Episode (12/10/21):https://www.buzzsprout.com/1467697/9694523Tonya Lonsbury 2022 AT Thru-Hiker "Monarch"
This year, Queen Elizabeth II celebrates her Platinum Jubilee, marking 70 years on the throne. At age 96, the Queen is the longest-reigning monarch in British history, and her eldest son, Prince Charles, has waited longer than any heir presumptive in British history to ascend the throne. Practically no one alive today in the UK can remember a time before the Queen. But as his moment approaches, so does widespread apprehension: Can Prince Charles fill his mother's shoes? Will the people accept him as king? Is there even a place for monarchy in our modern world?
Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, highlights key advances from the EMBER study and promising data on QOL for HR+/HER2- patients taking checkpoint inhibitors featured at the 2022 ASCO Annual Meeting. Transcript: ASCO Daily News: Hello and welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Allison Zibelli, a breast medical oncologist and assistant professor of medicine at the Sidney Kimmel Cancer Center Jefferson Health. Dr. Zibelli will highlight key posters on breast cancer that will be featured at the 2022 ASCO Annual Meeting. Dr. Zibelli's full disclosures are available in our show notes, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Zibelli, it's great to have you on the podcast today. Dr. Allison Zibelli: Thank you. It's nice to be here. ASCO Daily News: Let's begin with Abstract 1021 and the “Phase 1 EMBER Study.” Can you tell us why this study should be on our radar? Dr. Allison Zibelli: This study was very interesting because it's testing a novel therapy, which is imlunestrant, an orally bioavailable SERD, or a selective estrogen receptor degrader. This drug is for patients with ER-positive, HER2-negative advanced breast cancer. And they're presenting updated data from the dose-escalation phase and the dose-expansion phase of the EMBER trial. This trial enrolled 138 patients at a median age of 62 years. The median number of prior therapies for these women was 2. The adverse events were low. They could have prior platinum therapy but no prior fulvestrant or aromatase inhibitor. The premenopausal women in the study received concomitant GnRH antagonist. They had substantial clinical benefit with this therapy with no dose-limiting toxicities. It had a favorable side effect profile with no cardiac or ophthalmic safety signals, and it had excellent efficacy in patients with heavily pretreated ER-positive advanced breast cancer. This is the first study showing efficacy and safety with an oral SERD. And we're all looking for new oral, well-tolerated therapies for our patients with metastatic estrogen receptor-positive breast cancer. These patients were heavily pretreated, and they had a median of 2 prior therapies. Most of the patients with advanced breast cancer had prior endocrine therapy, 92% had a prior CDK 4/6 inhibitor, 50% had fulvestrant, and 26% had chemotherapy. Despite this, they had an overall response rate of 5% with a clinical benefit rate of 47%. So, it'll be very interesting for us to see what happens with this new class of SERDs in the future. ASCO Daily News: Excellent! So, moving on to Abstract 514. This study addressed patients with high-risk early breast cancer who received pembrolizumab within the new adjuvant biomarker rich I-SPY 2 trial. Can you tell us more about this study? Dr. Allison Zibelli: This is a very interesting study, which is a platform study comparing various investigational treatments to a standard therapy which was ACT, with or without herceptin, depending on the HER2 status of the patient versus an experimental agent. One arm of the I-SPY study was neoadjuvant pembrolizumab. This paper is very interesting to me because it's hard to know in advance who will respond to immune checkpoint inhibitors. And that's what this study was designed to answer. So, they took 69 patients who were on the I-SPY study, they all had high-risk MammaPrint scores, and all of them were HER2 negative, and with these patients, they had 31 complete responses to neoadjuvant pembrolizumab and 38 patients with a residual disease after neoadjuvant pembrolizumab. Notably, of the 31 complete responses, 12 were ER-positive, and 19 were triple-negative. In the residual disease patients, 28 were ER-positive and 10 were triple-negative. If you compare this with historical data, the response rate for pembrolizumab is about 20% for patients who are triple-negative and about 12% for patients who are ER-positive. So, the response rates that they had were higher in general. So, what the study did was they found a signature of 53 genes which they named imprint, which was identified with a greater than 90% sensitivity and greater than 80% specificity for predicting complete response to pembrolizumab in all patients. This worked equally well for the patients who are estrogen receptor-negative and estrogen receptor-positive. In KEYNOTE-086 cohort B, which was presented at the American Association for Cancer Research Annual Meeting (AACR), PD-L1 of greater than 1% only predicted a 23% response rate to pembrolizumab. So, if we could use the imprint study to predict patients who would respond to pembrolizumab, it would save a lot of needless toxicity and a lot of needless expense, in treating the patients who would have benefit. So, this is going to be a very useful method to identify patients that we want to treat with pembrolizumab, and perhaps other immune checkpoint inhibitors as well. I think this might be the next “Oncotype” as it were, in that it will be able to predict who will benefit from a specific therapy. ASCO Daily News: Thank you! Let's move on to Abstract 519. This is a randomized pre-surgical trial of alternative dosing of exemestane in postmenopausal women with early ER-positive breast cancer. What are your key takeaways here? Dr. Allison Zibelli: I thought this was a great design of a study. It was a window of opportunity for the test. So, what they did was, they tested 3 different dosing schedules of exemestane in patients waiting for surgery for ER-receptor-positive breast cancer. The patients were randomly assigned to either receive exemestane 20 milligrams a day, the standard schedule, 25 milligrams 3 times a week, or 25 milligrams once a week for 4 to 6 weeks prior to surgery. Their endpoint was percent decrease in circulating estradiol and what they found was the 3 times a week schedule was comparable to the daily schedule. The once-a-week schedule didn't seem to be adequate to decrease estradiol, but 3 times a week was equivalent to daily. This was really interesting because we know that our patients have difficulty tolerating aromatase inhibitors. We know from formal studies that about 25% of patients discontinue aromatase inhibitors prematurely because of side effects. Small studies in actual practice settings show it's probably even higher than that—between 30 and 50% of patients discontinue aromatase inhibitors. So, for the patient that can't tolerate daily therapy, 3 times a week therapy is an attractive option, that may be just as good as daily. I think it is very important for patients who have to take these drugs for years that they have a way to take them that is tolerable. ASCO Daily News: Absolutely. Well, the last study I'd like to ask you about is Abstract 1015. This looks at the quality of life for patients with HR-positive, HER2 negative advanced breast cancer. So, what does this study tell us about quality of life with different CDK 4/6 inhibitors? Dr. Allison Zibelli: So, we have a lot of studies of CDK 4/6 inhibitors. And we know that they dramatically improve the overall survival of women with ER-positive metastatic breast cancer. What we also know is that they have a lot of side effects. And for women that have to take these drugs for years, that's important. So, this study was a matching adjusted indirect comparison study. This is a method that uses individual patient data to create balanced trial populations across separate studies, and they use patients from the MONALEESA-2 trial, which was ribociclib plus AI, compared to MONARCH 3, which used abemaciclib plus AI, the endpoint was something they called “time to sustain deterioration,” which was a decrease in 10 points in the quality of life score, they use the QLQ-C30 questionnaire. The upshot of their data was that ribociclib was more tolerable, mostly with less appetite loss, less diarrhea, and less fatigue than abemaciclib. So, this is 1 of the first studies we've seen that directly compares, well sort of directly compares the quality of life between these 2 drugs, and this may be a data point that favors ribociclib. ASCO Daily News: Well, thank you, Dr. Zibelli, for highlighting some really important advances in breast cancer that will be featured at the 2022 ASCO Annual Meeting. We really appreciate it. Dr. Allison Zibelli: Thank you very much for having me. ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the ASCO Daily News podcast. Please take a moment to rate review and subscribe wherever you get your podcasts. Disclosures: Dr. Allison Zibelli: None disclosed. 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.
Beloved by Monarch butterflies, Mead's milkweed has become threatened as prairie habitats disappear. Now researchers at the Missouri Botanical Garden have made a surprising discovery that is giving the species a fighting chance at survival. MoBot scientist Christy Edwards discusses how her research changed conservation practices.
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This year marks Queen Elizabeth II's Platinum Jubilee, her 70th year as Queen of the United Kingdom. As the world prepares to celebrate an icon, the British royal establishment is working quietly behind the scenes to prepare the stage for Prince Charles to replace his mother and become King. It's the moment he was destined for – and at 73, he's been waiting a long time. But as his moment approaches, so does widespread apprehension: Can Prince Charles fill his mother's shoes? Will the people accept him as king? Is there even a place for monarchy in our modern world? In Born to Rule, NBC's Keir Simmons talks to journalists and royal insiders who've followed Prince Charles for decades to help us understand the man who will be king.
Ahead of the Queen's Platinum Jubilee, royal writer and photographer Ian Lloyd has written a fascinating book on the Monarch's 70 years on the throne. He joins host Zoe Forsey to talk about his career so far, telling us what it's like to photograph the Queen and the changes he noticed in Prince Harry in recent years. He also shares funny stories about some awkward encounters between members of the royal family and celebs and the Queen's unusual approach to Christmas shopping.
This week Prince Charles stepped in for the Queen at the State Opening of Parliament, reading out his mother's speech. Zoe Forsey and Russell Myers discuss the historic day and what it means for the future of the Monarch. Russell also reflects on his visit to Manchester with the Duke and Duchess of Cambridge for an emotional engagement. We also discuss the Sussexes' Jubilee announcement and Prince Harry's acting gig.
Dine and Design Series Part VIII “This isn't just me on the menu…There's a bunch of beautiful minds that go into it.” -Sieger Bayer Episode Description: Most people want to eat the healthiest foods available, but it can be difficult to do when we don't know where our food comes from. Buying directly from local farmers gives us the ability to shop at places that care about our health as much as we do. In addition, when we buy locally sourced food, we know that we're getting quality foods year-round rather than eating something grown elsewhere, which might have been sitting in storage for weeks, in conditions that aren't ideal for taste or nutrition. Buying local produce allows us to savor crisp, fresh flavor and foods' nutrients at their peak. However, freshness isn't everything when it comes to food. A lot of products have been sprayed with chemicals that can be harmful to our health, so it makes sense to buy locally wherever possible. This gives us the opportunity to advocate for our well-being and support farmers who practice sustainable farming. Not only that, buying directly from local farmers means getting access to more varieties of produce than what might be available in stores. We can also find vendors who are happy to explain how they grow their food and answer any questions we might have about their products. It's also a great place to get inspiration for cooking as many vendors are thrilled to share recipes and cooking tips. Etta Culver City is a celebrated neighborhood restaurant that serves delicious, wood-fired food in a fun, relaxed dining environment. Led by two-time Michelin Chef/Partner Danny Grant and the What If Syndicate restaurant group, Etta and its sister companies Monarch, Maple&Ash, Celestina, and Kessaku aim to serve nutritious, savory, and high-quality food. To do this, they make sure they only buy fresh ingredients directly from local farmers. In this episode of EI's Dine & Design, Justine and Bridget interview Etta's Executive Chef, Sieger Bayer. Listen to their fun exchange as Chef Sieger talks about the beginning of his journey with food, building relationships with local farmers, capturing the eyes and palates of diners through the art of plating, and how he helps chefs in-training to be better at their craft. Chef Sieger also reveals his passion project for the first time and tells the audience how they can get involved! Meet Sieger: Sieger Bayer is the Executive Chef of Etta Culver City, a neighborhood restaurant that serves delicious, wood-fired food in a fun, relaxed dining environment. True to its namesake, “Keeper of the Hearth”, Etta is known for its perfectly baked wood-fired pizza and other familiar dishes that are perfect for the whole family. Sieger understands the impact of buying directly from local farmers on the quality of food served, the well-being of their customers, and its benefit to the farmers themselves and the environment. Sieger has also partnered up with Erika Chan and other artists on an art-driven cookbook, re.c.o.o.k.e.d You can connect with Sieger and the fellow cookbook authors and artists via instagram using the links below. Instagram Connect with Etta: Website Instagram Twitter Connect with re.c.o.o.k.e.d Instagram Connect with Erika Chan: Instagram Connect with Alec Battistoni: Instagram Connect with Ryan Roxy Kinsley: Instagram Connect with Bridget Cooper (Co-Host, Dine & Design): A native of NZ, Bridget Cooper moved to NY when she was 18 to pursue a career in Interior Design. This journey started a life of the international jet set for Cooper, as travel became the source of inspiration and resource for herself and so many of her clients. Her innate ability to seek out the extraordinary is the foundation for curating layered interiors and unforgettable experiences. This has built her a reputation in the design world as the “one in the know” and “to know”. Bridget's interior work ranges from chic high-rise apartments in Chicago and NY to modern farmhouses in Northern California. In recent years, Bridget Cooper has expanded her creative talents by working on many commercial projects and events creating unforgettable experiences on both big and small scales. Bridget delights in over-thinking every detail and loves pushing the boundaries to keep things fresh and unexpected. Currently, Bridget and her husband Rob have moved from SF to Ojai, Ca (a small town north of Los Angeles) where they are building the Iverson House. Website Instagram LinkedIn Pinterest Connect with NextGenChef: Website Facebook Twitter Instagram YouTube Episode Highlights: 02:09 You Need to Join! 05:02 Plating and Design 07:53 When Food Critics Arrive 09:42 More Than a Cookbook 11:14 Expand Your Network