Podcasts about vhl

Play Episode Listen Later Mar 4, 2024 12:33

Spartan talks about his history in the VHL's fantasy games and TPE opportunities, along with recent Moscow trades in the S93 offseason.

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E200 - Flyers Beat Another Top 10 Team

Gettin Gritty Wit It

Play Episode Listen Later Feb 8, 2024 108:05

Created By: Yariv Wolok & Vasili Gianarakos Music By: Jay Lubes Website: https://www.flyersnittygritty.com Like and subscribe if you want more of this content! Check Out Our Team Store: https://nitty-gritty-3.creator-spring.com/

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Mini Spartcast #39 - Down with New York and other VHL tidbits

Play Episode Listen Later Feb 7, 2024 11:21

Spartan talks about the recent tensions between NYA and MOS and other thoughts about the standings and VHL teams.

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Mini Spartcast #38 - Best Player on each VHL Team

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Play Episode Listen Later Jan 26, 2024 11:58

Spartan calls out who he thinks is the best player on each VHL team after about 30 games of the S92 regular season.

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Using Adversity as Motivation - Episode 1

Lauer Power Podcast

Play Episode Listen Later Dec 7, 2023 47:04

In this episode, Lauer Media Company President Chad Lauer and Chad Evans introduce you to the Lauer Power Podcast. Chad Lauer tells his personal story of dealing with a rare cancer disorder called Von Hippel Lindau, losing a friend and a father, and how he used that pain as fuel to do good in the world. Chad sets the stage for the podcast which will include interviews with inspirational guests, improving leadership together, and stories of entrepreneurship.

Spartcast #34 - I Bring on Guests!

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Play Episode Listen Later Nov 8, 2023 83:06

Spartan brings on Twists and Doomsday to discuss the origins of the VHL and sim leagues, our histories in the VHL, recruitment woes and outlook, and much more!

Spartcast #33 - A Rare Return to Podcasting

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Play Episode Listen Later Nov 2, 2023 27:43

Spartan chats about hybrid attribute ratios, the VHLE, the future of the Moscow Menace, and recruitment in the VHL

Eric Jonasch, MD - Optimizing Long-Term Care With Guideline-Recommended Systemic Treatment Options for von Hippel-Lindau Disease-Associated Renal Cell Carcinoma

CME in Minutes: Education in Primary Care

Play Episode Listen Later Jul 27, 2023 13:56

Please visit answersincme.com/XJR860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in oncology and urology discuss guideline-recommended systemic treatment options and strategies to optimize long-term care for patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC). Upon completion of this activity, participants should be better able to: Recognize unmet needs in the management of VHL disease-associated RCC; Describe the clinical impact of current guideline-recommended systemic treatment options for VHL disease-associated RCC; and Identify strategies to optimize long-term care for patients with VHL disease-associated RCC.

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2023 Research Round Up: Breast Cancer, Lymphoma, Multiple Myeloma, and Brain Tumors

Cancer.Net Podcasts

Play Episode Listen Later Jul 27, 2023 28:19

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. The theme of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting, and explain what it means for people with cancer. In today's episode, our guests will discuss new research in breast cancer, lymphoma, multiple myeloma, and brain tumors. First, Dr. Norah Lynn Henry discusses new research in early stage and metastatic breast cancer. Dr. Henry is Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the 2023 Cancer.Net Associate Editor for Breast Cancer. You can view Dr. Henry's disclosures at Cancer.Net. Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of the most exciting new research in breast cancer that was presented at the 2023 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both early-stage and metastatic breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen or anti-endocrine treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancer and are also often aggressive cancers. Most of the results I'm going to highlight today are treatments for estrogen receptor-positive and HER2-negative breast cancer. One of the main stories from the ASCO Annual Meeting was the result of the NATALEE trial. At the present time, for patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who were at high risk of having their breast cancer come back, the currently recommended treatment is anti-endocrine therapy. Based on the results of a prior trial called monarchE, we also consider adding a medicine called abemaciclib, which turns off some enzymes in the cell that are called CDK4 and CDK6, which are known to make estrogen receptor-positive breast cancer cells grow. Abemaciclib can further reduce the risk of cancer recurrence compared to endocrine therapy alone, but it does have some side effects, most commonly, diarrhea. In the NATALEE trial, which was presented for the first time at this ASCO meeting, researchers studied a similar type of medication called ribociclib. It acts similarly to abemaciclib, although it is more likely to cause low blood counts and less likely to cause diarrhea. Ribociclib is currently routinely used in combination with anti-endocrine therapy to treat patients with metastatic estrogen receptor-positive breast cancer but is not yet routinely used in the early-stage setting. In the NATALEE trial, patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who are at high risk of breast cancer recurrence were enrolled. Half the patients were treated with just standard anti-endocrine therapy and half also received ribociclib for 3 years. After the 3-year treatment period, those who received both ribociclib and anti-endocrine therapy were about 25% less likely to have their cancer come back compared to those who received only anti-endocrine therapy. Overall, the medication was quite well tolerated. It is important to note that this drug is not yet FDA-approved in the setting. The remaining trials I will highlight are for treatment of metastatic breast cancer. There were many trials examining how best to use drugs that we are actually already using in the clinic. For example, many presentations were about the CDK4/6 inhibitors that I just mentioned. Typically, patients who have just been diagnosed with estrogen receptor-positive, HER2-negative metastatic breast cancer get treated with anti-endocrine therapy plus a CDK4/6 inhibitor. One trial called SONIA examined whether this is the right approach, or whether patients should just get the anti-endocrine therapy up front and hold off on starting the CDK4/6 inhibitor medication until a later time. It appears that this delayed approach would reduce symptoms as well as cost of the medication, while not reducing benefit from the treatment. Therefore, it appears it is likely fine for some patients to get just anti-endocrine therapy alone initially. However, we don't know how to identify those patients. Researchers are still figuring out which patients should follow this new treatment plan and which should keep getting the double therapy at the beginning. Some more to come in the future. There was a different trial called PADA-1 that included patients taking anti-endocrine therapy and the CDK4/6 inhibitor, palbociclib, upfront. Those patients were monitored using a blood test, looking for a mutation or a change in the estrogen receptor in the cancer. Patients who had that mutation either remained on the same treatment that they'd been on or switched to the next line of therapy, even though their scans didn't show any progression of their cancer. Overall, this switching strategy looks like a very promising approach for managing patients since it may help patients' cancer respond to treatment for a longer period of time. Although this approach is not yet officially recommended according to our guidelines. In another example, many patients with all types of metastatic breast cancer are treated with a drug called capecitabine, also known as Xeloda. Although this drug is effective for many cancers, many patients experience hand-foot syndrome, nausea, diarrhea, and mouth sores. In the X7-7 clinical trial, the researchers compared the official standard FDA-approved dose based on a patient's height and weight and given for 14 days followed by 7 days off. That was compared to a fixed dose of treatment given 7 days on and 7 days off. The trial found that the fixed-dose regimen was easier to tolerate, but importantly, the benefit from the 2 doses and schedules of treatment appears to be similar. Therefore, we will likely be using this lower dose, 7 days on and 7 days off, for most of our patients who receive treatment with capecitabine for metastatic breast cancer, since it is likely to improve their quality of life while not negatively impacting the potential benefit they receive from the therapy. There were a lot of other research findings presented that are related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including a new antibody-drug conjugate against HER2, as well as other new anti-endocrine and targeted treatments. We eagerly await the results of large, randomized trials so the drugs that work can be used to treat patients with breast cancer. But for now, that's it for this quick summary of important research from the 2023 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. Next, Dr. Christopher Flowers discusses new research in lymphomas and multiple myeloma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Division Head ad interim of Cancer Medicine. He is also the 2023 Cancer.Net Associate Editor for Lymphoma. You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and interim division head for cancer medicine at the University of Texas MD Anderson. And it's my pleasure to talk to you today in this Cancer.Net podcast about latest updates in the hematological malignancies focused on lymphoid cancers from the American Society of Clinical Oncology Annual Meeting. The ASCO Annual Meeting every year is an exciting time for latest updates in the care of patients with cancer. And in particular this year, there were 3 abstracts that I'd like to highlight that were presentations at this meeting about lymphoid malignancies that have potential significant impact for patients over time. The first 2 come from a special session that was on late-breaking abstracts that were latest advances from clinical trials. The first is from the ZUMA-7 trial. This is a trial looking at axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, or CAR T-cell therapy. The CAR T-cell trial in question here was led by Jason Westin, who's a colleague of mine at MD Anderson. And MD Anderson is a partner with Kite pharmaceutical company that is a manufacturer of this and has a research alliance with that group. In the ZUMA-7 trial, this was a trial that involved the use of CAR T-cell therapy in comparison to standard-of-care therapy, which typically would be aggressive chemoimmunotherapy followed by autologous stem cell transplantation for patients with relapse of large B-cell lymphoma. As many of you may know, large B-cell lymphoma is a kind of lymphoma that is potentially curable with standard frontline therapy. And when patients relapse, the standard of care historically had been for patients to receive autologous stem cell transplantation, which is also potentially a curative therapy. This trial to do a ZUMA-7 trial compared patients who received the typical standard of care, the autologous stem cell transplant following the aggressive chemoimmunotherapy regimen for patients who had relapsed early after their initial therapy, so within 12 months, or were refractory, meaning that they did not respond to their initial therapy. And this was compared to the axicabtagene ciloleucel or axi-cel CAR T-cell therapy. The initial publication of the trial came out in the New England Journal of Medicine in 2022 and showed that the event-free survival for patients who receive CAR T-cell therapy was superior. This update of the ZUMA-7 trial at the ASCO Annual Meeting that was presented by my colleague, Jason Westin, discussed the overall survival of the study, and in this update, it showed that overall survival was also improved for patients who received axi-cel as opposed to standard-of-care therapy. And now with a median follow-up of a little bit more than 47 months, axi-cel demonstrated superiority that was statistically significant and clinically meaningful over the traditional standard of care. In that same session, there was another trial looking at CAR T-cell therapy for patients with multiple myeloma. This was a BCMA-targeted CAR T-cell therapy that was presented by Dr. Dhakal in that session providing results from the CARTITUDE-4 global randomized phase 3 clinical trial. That was a trial that involved 419 patients where patients were randomized to cilta-cel CAR T-cell therapy for myeloma or standard-of-care therapy, which in this case included combination therapy. And in this trial, this showed that single agent with a single cell-to-cell infusion significantly improved progression-free survival versus standard of care for patients with multiple myeloma who had 1 to 3 prior lines of therapy and were refractory to lenalidomide. This is also a meaningful advance for patients with this disease. And the final abstract that I'll mention is an abstract that was presented by Dr. Alex Herrera from City of Hope and was presented in the Plenary session. And it was really exciting to see a Plenary session presentation focusing on lymphomas. So this trial presented by Dr. Herrera was led by the Southwest Oncology Group. Dr. Sara Ahmed from MD Anderson, from my institution, was a participant and actively engaged in this clinical trial. This trial was a success in a number of ways. First, it involved both pediatric and adult patients and is one of the first trials of its kind to involve both large populations of patients with pediatric lymphomas as well as adults with lymphomas. It helps to consolidate the approaches that we use for Hodgkin lymphoma, both in the pediatric population and the adult population. It also represents a major advance in the ways that we conduct clinical trials in the United States in that this clinical trial finished ahead of schedule in terms of completion of the trial with collaboration from the adult and pediatric groups across the National Clinical Trials Network. As I mentioned, this was presented by Dr. Alex Herrera in the Plenary session and involved patients with stage 3, 4 Hodgkin lymphoma, where patients were randomized 1 to 1 either to receive an anti-PD-1 therapy, nivolumab, with chemotherapy, the AVD chemotherapy regimen, or the antibody-drug conjugate, brentuximab vendotin, combined with that same AVD chemotherapy. And what this showed in 994 patients who were enrolled from 2019 to 2022 was that there was a benefit for patients who received the combination of nivolumab AVD or NAVD versus the group that received brentuximab and AVD. It improved the progression-free survival in patients with advanced-stage Hodgkin lymphoma. In this trial, few immune-related adverse events were observed and a lesser number of patients went on to receive radiation therapy, which is also a benefit for patients with Hodgkin lymphoma. And this concludes my presentation of abstracts at the ASCO Annual Meeting and really exciting advances for patients with lymphoma that were presented this year. ASCO: Thank you, Dr. Flowers. Finally, Dr. Roy Strowd discusses new research in treating brain tumors, including those in people with von Hippel Lindau syndrome. Dr. Strowd is a neurologist and neuro-oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the 2023 Cancer.Net Associate Editor for Central Nervous System Tumors. You can view Dr. Strowd's disclosures at Cancer.Net. Dr. Strowd: Hello, everyone. This is Roy Strowd. I'm a physician neuro-oncologist at Wake Forest University School of Medicine in our comprehensive cancer center. And I'm really excited to be with you for this podcast on important CNS or brain tumor updates from the 2023 ASCO Annual Meeting. I don't have any relevant disclosures for the research that we'll discuss today. It was a really exciting meeting. It was actually a really fun meeting to be a brain tumor doctor at ASCO this year. So I'm really excited to talk with you about some important updates. And I think it's actually a really important time to be a patient and a caregiver and know some of the things going on in brain tumor care. So I'm going to dive into 3 studies. And one that we just have to talk about, and this was a really exciting study called the INDIGO study. At ASCO, if you present a study, you want to have a Plenary presentation, you want to be up on the big stage presenting your work. And brain tumor studies aren't always on the big stage. We just haven't had enough really good treatments out there for brain tumor patients over the years. And this year, we had a Plenary presentation, a really big study, making a big splash. And that was this INDIGO study. So I'm going to spend a few minutes talking about that study. I want brain tumor patients and caregivers to know about this and know about some of the important updates from the Annual Meeting. The study was called the INDIGO study, and it's a phase 3 study. So when you think about clinical trials, there's a phase 1, phase 2, phase 3. That phase 3 is that last step, that last hurdle that a drug needs to overcome to move towards approval. And a positive phase 3 study is really exciting for the field and means that we may have a new treatment that will change how we take care of brain tumor patients. And that's what this study was. It was also a really unique study. So it's looking at a different group of brain tumor patients, patients that have an IDH mutant glioma. Most common brain tumors that we see are the glioblastomas. And those are often and really, by rule, IDH wild-type. IDH is a gene. It's called the isocitrate dehydrogenase gene. And it's one of these really important genes for us to understand how brain tumors are going to work and how they act and it turns out, with this study, how they may respond to treatment. So this study looked at enrolling patients that had an IDH-mutant low-grade glioma, or a grade 2 glioma. Those are those often slower-growing, but they continuously grow tumors that occur early in life, typically in the 30s or 40s for young people. And we haven't really had a lot of good treatments for these patients. And so this study looked at giving a new drug that's called vorasidenib. It's hard to say vorasidenib. And it's an IDH mutant inhibitor. So it attacks that IDH mutant gene that makes these tumors what they are. And it's been undergoing development for many years. It's an exciting treatment because it's what we call a molecularly targeted treatment. It specifically targets that IDH gene that makes the low-grade tumors low-grade tumors. This study enrolled 331 patients, so a large group of patients. Half of those patients received the drug, the vorasidenib, and half received placebo. And that's pretty uncommon in cancer. We don't often do studies that are placebo-controlled studies. But for these patients, there's often not a good treatment early in the course, they get surgery. And for patients that don't need an additional treatment, we do surgery and then we wait and watch and see what happens. And that gives us an opportunity as a brain tumor community to figure out whether this type of treatment will help prevent the need for a next treatment, prevent the need for radiation and chemotherapy. And so that's what was looked at in this study. And there was some really exciting data. So I'm going to go through a few numbers, but we just got to talk about these numbers because they're really important. So at 14 months, 28% of the patients receiving the drug vorasidenib had progressions. That's about a quarter of patients compared to half that received placebo. So that's a big improvement in the number of patients whose tumor grew. So this drug prevented tumor growth in these patients. And that's exactly what we want. That's why we develop drugs, is to prevent tumor growth. When we look at the time that those patients had until they needed a next treatment or until their tumor grew, it was over 2 years of time patients receiving the drug when their tumor grew versus less than a year, 11 months for those receiving placebo. So it's adding a lot of time for brain tumor patients without tumor growth or without needing another treatment. And typically, these patients with low-grade gliomas would need something like radiation therapy or chemotherapy. And those are good treatments, and we need those treatments. But they can have toxicity. And so this is the type of drug that could prevent that toxicity, cognitive decline, other problems that can happen with chemotherapy that those patients didn't potentially suffer. So there are some important things that we learned from the INDIGO study that I would want you to take away, kind of what do these data mean? The first is that we can target this IDH gene. And that's really important for our field. And it means if you're a brain tumor patient, knowing whether your tumor is IDH mutant or IDH wild-type is important, and that's something I want brain tumor patients to ask me as a neuro-oncologist and ask their cancer doctor because that's important in deciding treatment for them. The second is this medicine vorasidenib, it gets into the brain. And that's one of the big challenges that we have in brain tumor care in developing drugs is we need things that get into the brain. And this study really shows that this is a good medicine. There's a number of IDH inhibitors, but this medicine vorasidenib is one that we want to specifically think about for our patients. And this is a practice-changing study. So for the first time, we now have a treatment that works for grade 2 gliomas and really prevents the need for radiation therapy and chemotherapy. So those are 3 important things to take away from this. There's a number of things that we don't yet know. This medicine is not available. So patients coming in and emailing me and calling me, we don't have it yet. And after a big phase 3 study like this, this is announced. There's still a number of steps that need to happen to make sure that this can be delivered to patients safely and we can get it out there. And that's in partnership with groups like the FDA, the Food and Drug Administration, and others. So this is an important conversation to have with patients, neuro-oncologists, and to know that this is something that's on the horizon. Two other things is we don't know if this is going to work for all brain tumors. In particular, for these IDH wild-type glioblastomas, the most common brain tumor, this probably is not a good therapy that we don't have any data to suggest that it would work. They don't have that IDH mutation. And so this is important for some brain tumor patients but not for everybody. And that needs to prompt a conversation with the cancer doctor. And it may not work at all times. So there's some data to suggest that this is really a drug that's best given early in the course of treatment and not later on. And so it is something that I want my patients to be aware of at the first time that I see them so we can be deciding what kind of the right time is. So I want to give folks 2 take-homes from this study and summarize a few of these things that we heard about because it's such an important study. So what are the 2 take-homes from the INDIGO Study? The first that I wrote down is targeting IDH mutation in glioma works. And that's a groundbreaking discovery from this. This is really important for our field. IDH mutations have been important to diagnose brain tumors but have never been really a therapeutic target. And this changes the landscape, and we can now target IDH mutations in gliomas. And that's really important. The second thing, the second real take-home message, is we can safely delay radiation therapy and chemotherapy in some patients with these lower-grade gliomas, potentially with IDH mutation and IDH inhibition. And that's really important. Chemotherapy and radiation therapy are important, but if we can delay those treatments and prevent side effects, that could be helpful for some of our patients. So really important update from ASCO and what I want to spend most of the time on our podcast focusing on this INDIGO study. But there were a bunch of other things going on in brain tumors at ASCO, as there always are. And I want to highlight 2 studies about some things that the groups of patients may be interested in knowing that happened at the meeting. The first is a study called the INB-200 study. And this is a phase 1 study, so it's earlier in development. But it's an immunotherapy study. And brain tumor patients and caregivers will know that we've really wanted to find an immunotherapy that works for brain tumors. And we haven't yet. And we're still not there, but this study is an important step in that direction. So this study from a group at the University of Alabama looked at something called gamma delta T cells. And T cells are really important. They're part of the anti-tumor response. They're what the body uses to attack the tumor. So we like those T cells. And particularly, these gamma delta T cells are important in targeting tumor cells in glioblastoma cells. They're also unique. They can avoid the toxicity of chemotherapy. Radiation therapy and chemotherapy suppresses the T cells. They make some go down, or decreased in number, which is not what we want. And these gamma delta T cells were genetically created so that they were resistant to chemotherapy. And that's really, really important. We want an immunotherapy that works and one that isn't suppressed by our other treatments. And that's been a real barrier for glioma patients. So in this phase 1 study, they found the right dose of these gamma delta T cells, and that's the goal of a phase 1 study. But there were some early signs that this may be changing the tumor. One of the patients underwent surgery before and after they got this infusion. And we were able to see this. Investigators were able to see the gamma delta T cells up in the tumor. So this doesn't change practice. Patients don't need to go out and seek out the gamma delta T cells yet. But it's one of those early findings that says that we need to keep looking at immunotherapy. And as a community, this is something we need to keep focusing on. And then the last abstract and study I wanted to focus on is for a rare disease. This would not be something that would be relevant for all of our listeners and the brain tumor patients but for a subgroup of patients that have a condition called VHL, or von Hippel-Lindau. And von Hippel-Lindau is a genetic condition. So, most brain tumors are not inherited. You don't get it from a mom or a dad or pass it on, except for these patients, you do. And it comes from a gene that's inherited in families called the VHL or the von Hippel-Lindau gene. And these patients are predisposed to get tumors all throughout the body and the kidneys and the brain and the eye. And this is a lifelong disease where these tumors can really grow slowly over time and cause significant problems. And in the past few years, there's been a new treatment called belzutifan. Belzutifan is the name of this drug that has been shown to be effective in the kidney tumors for patients with VHL. And at ASCO this year, there was a new study showing that it's also effective in treating the brain tumors for these patients. And that's really important. We just haven't had a treatment other than surgery or radiation therapy for these tumors. And oftentimes, they grow after surgery and radiation therapy and we need an additional treatment. So in this study, the investigators looked at, "Does this drug belzutifan work for treating the CNS tumors, hemangioblastoma?" And found that around 50% of patients had a response, so a shrinkage in the size of the tumor. 90% of patients had control of their brain tumor disease, which is really important. And it worked really quickly, so it worked in about 3 to 5 months, which is shorter than what we would see for the kidney tumors. So that's exciting news for VHL patients, patients with von Hippel-Lindau, and another important update from the 2023 ASCO. So thanks for listening to this update of CNS brain tumors at the 2023 ASCO Annual Meeting. Again, I'm Roy Strowd, a neuro-oncologist at Wake Forest University School of Medicine. Delighted to bring you this brief summary of new research in the field. ASCO: Thank you, Dr. Strowd. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Spartcast #31 - Catching Up and Chatting Drafts

catching up chatting spartan drafts vhl

Play Episode Listen Later Jun 8, 2023 17:39

Spartan catches up with life and discusses the upcoming VHL and VHLM drafts!

Spartcast #30 - Career Reflecting

Research To Practice | Oncology Videos

Play Episode Listen Later May 30, 2023 13:49

For the first time, I do a career task in podcast form. We chat about Nico's back story in the VHL, his upcoming depreciation and what might come in the future.

career reflecting vhl

Episode 232: Belzutifan in early and late renal cancer

The Uromigos

Play Episode Listen Later Apr 14, 2023 31:12

Toni Choueiri and Brian Shuch discuss Belzutifan alone and in combination for VHL syndrome and advanced sporadic RCC

cancer renal rcc vhl toni choueiri

Renal Cell Carcinoma | Cases from the Community: Investigators Discuss Available Research Guiding the Care of Patients with Renal Cell Carcinoma

Play Episode Listen Later Mar 16, 2023 88:44

Featuring perspectives from Prof Laurence Albiges, Dr Toni Choueiri and Prof Thomas Powles, moderated by Dr Brian Rini, including the following topics: • Available Data with and Ongoing Investigation of Immune Checkpoint Inhibitors for Nonmetastatic Renal Cell Carcinoma (RCC) — Prof Powles o Introduction (0:00) o Case: A woman in her early 60s after left nephrectomy (T3aN0M0 clear cell carcinoma) — Swati Vishwanathan, MD (1:39) o Cases: A man in his early 50s develops renal dysfunction after 2 cycles of adjuvant pembrolizumab for RCC and a man in his late 60s with Stage III clear cell RCC (ccRCC) discontinues adjuvant pembrolizumab due to severe musculoskeletal pain and joint swelling — Justin Peter Favaro, MD, PhD and Priya Rudolph, MD, PhD (6:05) o Faculty presentation: Prof Powles (11:03) • Evidence-Based Selection of First-Line Therapy for Metastatic RCC — Dr Choueiri o Case: A man in his early 70s with metastatic RCC enrolls on the PDIGREE trial and receives nivolumab/ipilimumab without response followed by cabozantinib — Helen H Moon, MD (21:32) o Cases: A man in his early 70s receives ipilimumab/nivolumab for widely metastatic RCC and develops autoimmune hepatitis and a man in his early 60s with metastatic ccRCC receives ipilimumab/nivolumab followed by nivolumab with response but develops hypothyroidism and hypoadrenalism — Victoria Giffi, MD and Philip L Brooks, MD (25:33) o Faculty presentation: Dr Choueiri (36:38) • Treatment Options for Relapsed/Refractory RCC — Dr Rini o Case: A woman in her early 60s with metastatic ccRCC receives lenvatinib/pembrolizumab but develops difficult-to-manage hypertension — Eric H Lee, MD, PhD (46:04) o Case: A woman in her mid 60s with metastatic ccRCC and somatic VHL gene mutation receives ipilimumab/nivolumab and develops a solitary brain metastasis — Sunil Gandhi, MD (52:36) o Faculty presentation: Dr Rini (57:54) • Management of RCC Among Special Patient Populations — Prof Albiges o Case: A man in his late 60s with Waldenström macroglobulinemia and metastatic papillary RCC receives first-line ipilimumab/nivolumab followed by nivolumab but develops disease progression, including brain metastases — Nikesh Jasani, MD (1:07:58) o Case: A woman in her early 70s with a history of psoriatic arthritis develops metastatic ccRCC, receives pembrolizumab/axitinib and develops elevated liver function tests — Georges Azzi, MD (1:12:38) o Faculty presentation: Prof Albiges (1:18:45) CME information and select publications

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179. Épisode # 179 avec Vikhaël et Jean-Raphaël Tô-Landry - 75min

Drette su'l tape

Play Episode Listen Later Mar 13, 2023 75:09

Vikhaël et Jean-Raphaël Tô-Landry sont deux frères qui ont su profiter de leur talent au hockey pour voyager et vivre des expériences de vie uniques! Le premier a gravi les échelons du hockey français jusqu'à devenir la vedette de l'équipe de Brest en Ligue Magnus, alors que le second est allé enseigner en Chine pour finalement jouer en VHL, la ligue-école de la KHL ! Les anecdotes se succèdent dans cette superbe conversation avec les deux frères complices !Viens voir le spectacle en rodage de ce cher hurluberlu de David, lui qui sera à Montréal le 17 mars, à Longueuil le 19 mai et nouvelle date à Québec le 13 septembre! Procure-toi tes billets au davidbeaucage.com !Vous voulez faire connaître votre marque / entreprise? Ayez votre propre pub sur Drette su'l tape pour rejoindre votre communauté! Écrivez à thomas@drettesultape.com pour plus de détails! Hosted on Acast. See acast.com/privacy for more information.

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The NHL trade deadline comes tomorrow. Where do Canada's teams stand?

Scott Thompson Show

Play Episode Listen Later Mar 2, 2023 78:19

The Hamilton Today Podcast with Scott Radley: The downbound lanes of the Claremont have been closed amid concerns of erosion. What brought this on. A meeting was held last night between HDSB, parents and stakeholders about the situation at Oakville Trafalgar high school and the status of the dress code policy. With this new health care deal, how will it impact doctors and the care you receive? The NHL trade deadline comes tomorrow. Where do Canada's teams stand? A survey done on behalf of the Canadian Organization for Rare Disorders has found that many Canadians living with rare diseases struggle for years to access care. It is all coming up on the Hamilton Today Podcast! Guests: Jackie Kennedy, Director, Engineering Services. Murray Costello, Director, Southeast Region Operations, Enbridge Gas. Sheba Siddiqui, Producer and On Air Co-ordinator for Toronto Today. Dr. Mekalai Kumanan, President of the Ontario College of Family physicians and family doctor in Cambridge. Duff Conacher, Co-Founder of Democracy Watch. Ryan Kennedy, Senior Writer, The Hockey News. Stephanie Gandulla, maritime archaeologist and the Resource Protection Coordinator for NOAA's Thunder Bay National Marine Sanctuary. Matt Francis. Ward 5 City Councillor, City of Hamilton. Steve Parrott, has two adult daughters with VHL disease and he serves as the Board Chair for the Canadian VHL Alliance. Grace Tong is the Vice President & Equity, Diversity and Inclusion Practice Lead, Ipsos Public Affairs, Canada. Host – Scott Radley Content Producer – Elizabeth Russell Technical/Podcast Producer – William Webber Podcast Co-Producer – Tom McKay News Anchor – Dave Woodard & Jennifer McQueen Want to keep up with what happened in Hamilton Today? Subscribe to the podcast! https://megaphone.link/CORU8835115919

Mice with renal-specific alterations of stem cell-associated signaling develop symptoms of chronic kidney disease but surprisingly no tumors

PaperPlayer biorxiv cell biology

Play Episode Listen Later Mar 1, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530413v1?rss=1 Authors: Myszczyszyn, A., Popp, O., Kunz, S., Sporbert, A., Jung, S., Penning, L. C., Fendler, A., Mertins, P., Birchmeier, W. Abstract: Previously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established organoids from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that the organoids resembled renewal of adult kidney tubular epithelia, since organoid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-{beta}-catenin-GOF together with Notch-GOF and Wnt-{beta}-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of {beta}-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the organoid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

deep dna llc develop symptoms copy jung mice mrna stem cells tumors notch renal signaling kunz popp chronic kidney disease ckd alterations penning gof wnt biorxiv vhl ccrcc

Ep. 81 Germline Testing in Kidney Cancer with Dr. Ari Hakimi and Dr. Nirmish Singla

BackTable Urology

Play Episode Listen Later Feb 15, 2023 46:52

In this episode of BackTable Urology, Dr. Aditya Bagrodia, Dr. Ari Hakimi (Memorial Sloan Kettering Cancer Center), and Dr. Nirmish Singla (Johns Hopkins University), discuss the value and indications for germline testing in renal cell carcinoma (RCC). --- SHOW NOTES First, the doctors explain basic information about germline mutations and kidney cancer. Although historical data has shown that 5% of kidney cancers are inherited, recent efforts to increase testing through commercial testing and large scale efforts at cancer centers have proven that 8-10% of kidney cancers are inherited. Von Hippel Lindau (VHL) syndrome is the most prototypical kidney cancer predisposition syndrome, but there are other less common ones as well. Extrarenal manifestations of VHL syndrome include pancreatic tumors, pancreatic cysts, pheochromocytomas, retinoblastomas, and CNS hemangioblastomas. These tumors have a variable penetrance, but African Americans and women are more likely to have hereditary RCC. The doctors recommend asking newly diagnosed RCC patients about a broad spectrum of their family history that includes cancer and non-malignant conditions, such as uterine leiomyomata. Dr. Hakimi notes that some patients will confuse germline testing with somatic tumor testing, so urologists will have to explain to patients that the VHL mutation was found in their tumor, not in their blood or saliva. Extended physical exams to look for syndromic conditions can also be performed. A thorough cutaneous exam to look for fibrofolliculomas, leiomyomas, facial angiofibromas, and cafe-au-lait spots can help indicate the presence of a familial syndrome. According to guidelines, all patients diagnosed with RCC under 46 years of age should be recommended to have germline testing. Dr. Bagrodia mentions that having experienced genetic counselors and setting up thorough dot phrases to send to patients explaining their results is helpful for him. Dr. Singla adds that medical geneticists have the ability to counsel the patients more extensively on the risks and benefits of giving consent to go forward with genetic testing. They can also provide psychosocial support and education for the patients. The doctors then move on to discuss how germline mutations may lead to different treatment modalities. Precision surgery, or utilizing pretest probability information about a tumor to guide surgical approach, may be possible with germline testing. Additionally, testing may help surgeons to decide whether to perform a retroperitoneal lymph node dissection (RPLND). Next, the doctors discuss belzutifan, which is an oral drug used to treat VHL familial syndrome tumors. Finally, they discuss the use of tumor sequencing for research purposes and share what they are most excited for in the field of RCC research.

african americans testing precision extended cns rcc kidney cancer singla germline vhl

Altitude training and hypoxic conditioning with Dr Grégoire Millet

Inside Exercise

Play Episode Listen Later Jan 15, 2023 85:46

Dr Glenn McConell chats with Professor Grégoire Millet from the University of Lausanne in Switzerland. He is an absolute world leader in research into altitude training and hypoxic conditioning. This area has progressed greatly from Live High-Train High (LHTH) to Live High-Train Low (LHTL), LLTH and LHTL (and High). The type of attitude training/hypoxic conditioning one would undertake depends on if training for endurance or team sports. We also discussed using low oxygen (hypoxia) and high oxygen (hyperoxia) for health benefits. 0:00. Introduction and Grégoire's background 4:58. History of altitude training 6:52. Many combinations of altitude training LHTH, Live High-Train Low (LHTL), LLTH, LHTL (and High) 9:45. Altitude and oxygen availability 12:45. Altitude vs breathing low oxygen: not the same 14:32. Immediate responses to hypoxia 20:12. Lower VO2 max at altitude 24:39. Absolute vs relative exercise intensity 25:46. Placebo effect? 28:45. Long-term responses to altitude 32:24. Need to exercise for optimal adaptations in muscle 33:34. LHTL 36:19. LLTH 41:34. Health effects of LLTH 43:04. Repeated sprints in hypoxia (RSH) 45:29. LLTH and improved blood vessel function 47:54. Health effects of low and high oxygen 54:50. Hypoventilation at low lung volume (VHL) to cause hypoxia 59:00. VO2 max training at altitude 1:00:55. Use more carbohydrate during exercise at altitude 1:02:30. Greater sympathetic activation (adrenaline etc) at altitude 1:04:52. Oxidative stress/ Reactive oxygen species 1:08:42. What doesn't kill you makes you stronger 1:10:12. Manipulating repeated sprints duration to alter aerobic/anaerobic contributions 1:13:20. Specificity of training to achieve required outcomes 1:13:51. LHTL (and High) in Rugby players 1:17:40. LHTL and LHTL (and High) for endurance 1:19:09. Ultramarathon star Killian Jornet and altitude training 1:21:15. Controversies in the area 1:24:47. Health benefits the most exciting for him 1:25:37. Outro (9 secs) Inside Exercise brings to you the who's who of exercise metabolism, exercise physiology and exercise's effects on health. With scientific rigor, these researchers discuss popular exercise topics while providing practical strategies for all. The interviewer, Emeritus Professor Glenn McConell, has an international research profile following 30 years of Exercise Metabolism research experience while at The University of Melbourne, Ball State University, Monash University, the University of Copenhagen and Victoria University. He has published over 120 peer reviewed journal articles and recently edited an Exercise Metabolism eBook written by world experts on 17 different topics (https://link.springer.com/book/10.1007/978-3-030-94305-9). Connect with Inside Exercise and Glenn McConell at: Twitter: @Inside_exercise and @GlennMcConell1 Instagram: insideexercise Facebook: Glenn McConell LinkedIn: Glenn McConell https://www.linkedin.com/in/glenn-mcconell-83475460 ResearchGate: Glenn McConell Email: glenn.mcconell@gmail.com Subscribe to Inside exercise: Apple Podcasts: https://podcastsconnect.apple.com/my-podcasts/show/inside-exercise/03a07373-888a-472b-bf7e-a0ff155209b2 YouTube https://www.youtube.com/channel/UChQpsAQVEsizOxnWWGPKeag Spotify Google Podcasts Anchor Podcast Addict Etc

Spartcast #28 - Depreciation Changes and Various League Happenings

league spartan happenings depreciation vhl

Play Episode Listen Later Dec 19, 2022 24:20

Spartan talks about recent changes to VHL depreciation, comments around moderation, the VHL playoff race and the state of the VHLM.

Von Hippel-Lindau Disease: Clinical Update and New Drug Therapy

Better Edge : A Northwestern Medicine podcast for physicians

Play Episode Listen Later Nov 16, 2022

Von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome caused by mutations in the VHL gene. These mutations predispose patients to the development of cysts and tumors in several systems and organs, including the central nervous system, retina, kidneys, pancreas, adrenal glands and reproductive organs. VHL is a complex disease that requires specialized advanced treatment from a multidisciplinary team of specialists.In this Better Edge podcast episode, the following experts from the Northwestern Medicine Von Hippel-Lindau Disease Program discuss VHL and the clinical management for this patient population: Rimas V. Lukas, MD, Associate Professor of Neuro-Oncology; Niraj K. Shenoy, MD, PhD, MS, Associate Professor of Hematology/Oncology and of Pathology; and Brittany M. Szymaniak, PhD, CGC, Instructor of Urology. They share a recent Northwestern Medicine study published in Neuro-Oncology that examined belzutifan, the first approved HIF-2α inhibitor, in VHL-associated tumors.

FBXL4 deficiency promotes mitophagy by elevating NIX.

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 11, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.11.511735v1?rss=1 Authors: Elcocks, H., Brazel, A. J., McCarron, K. R., Kaulich, M., Husnjak, K., Mortiboys, H. J., Clague, M. J., Urbe, S. Abstract: The selective autophagy of mitochondria is linked to mitochondrial quality control and is critical to a healthy organism. We have conducted a CRISPR/Cas9 screen of human E3 ubiquitin ligases for influence on mitophagy under both basal cell culture conditions and following acute mitochondrial depolarisation. We identify two Cullin RING ligases, VHL and FBXL4 as the most profound negative regulators of basal mitophagy. We show that these converge through control of the mitophagy adaptors BNIP3 and BNIP3L/NIX through different mechanisms. FBXL4 suppression of BNIP3 and NIX levels is mediated via direct interaction and protein destabilisation rather than suppression of HIF1-mediated transcription. Depletion of NIX but not BNIP3 is sufficient to restore mitophagy levels. Our study enables a full understanding of the aetiology of early onset mitochondrial encephalomyopathy that is supported by analysis of a disease associated mutation. We further show that the compound MLN4924, which globally interferes with Cullin RING ligase activity, is a strong inducer of mitophagy providing a research tool in this context and a candidate therapeutic agent for conditions linked to mitochondrial dysfunction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

llc e3 copy elevating promotes nix deficiency crispr cas9 depletion mccarron biorxiv urbe clague vhl

Renal Cell Carcinoma

Rio Bravo qWeek

Play Episode Listen Later Aug 5, 2022 24:06

Episode 105: Renal Cell Carcinoma. Manpreet and Jon-Ade explain how to diagnose renal cell carcinoma. Introduction about age and kidney transplant by Dr. Arreaza and Dr. Yomi. Introduction: Too old for a new kidney?By Hector Arreaza, MD. Discussed with Timiiye Yomi, MD.Today we will be talking about the kidneys, those precious bean-shaped organs that detoxify your blood 24/7. Amazingly, we can live normal lives with one kidney, but when the kidney function is not good enough to meet the body's demands, patients need to start kidney replacement therapy. Modern medicine has made a lot of advances with dialysis, but the perfection of a kidney has not been outperformed by any machine yet. That's why kidney transplant is the hope for many of our patients with end-stage kidney disease.The need for a kidney transplant is growing, likely due to increasing chronic diseases such as diabetes and hypertension, and also because of an increase in elderly population. About 22% of patients on the kidney transplant waiting list are over age 65. A cut-off age to receive kidney transplant has not been established across the globe. Different countries use different criteria for the maximum age for transplant. The American Society of Transplantation's guidelines states “There should be no absolute upper age limit for excluding patients whose overall health and life situation suggest that transplantation will be beneficial.” So, if your patient is older than 65 and needs a kidney, they may qualify for a transplant, and age should not be an absolute contraindication to receive it. Actually, older patients may have lower risk of rejection due to a theoretically weaker immune system. A live donor is likely to be a better option for elderly patients. A condition that would make your elderly patient a poor candidate for kidney transplant would be frailty. Common contraindications to kidney transplant include active infections or malignancy, uncontrolled mental illness, ongoing addiction to substances, reversible kidney failure, and documented active and ongoing treatment nonadherence.So, remember to take these factors into consideration when deciding if you need to refer your elderly patients for a kidney transplant, there is no such thing as being too old for a new kidney if your patient meets all the criteria for a transplant.This is Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care physician for additional medical advice. Renal Cell Carcinoma. By Manpreet Singh, MS3, Ross University School of Medicine, and Jon-Ade Holter, MS3 Ross University School of Medicine. Moderated by Hector Arreaza, MD. Definition:Renal cell carcinoma is a primary neoplasm arising form the renal cortex. 80-85 percent of renal tumors are renal cell carcinomas followed closely by transitional cell renal cancer and Wilms tumor. Epidemiology: In 2022, 79,000 new cases of kidney cancer were diagnosed with almost 14,000 mortalities. There is a 2:1 male to female ratio and the average age is 64 and normally 65-74. African Americans and American Indians have a higher prevalence rate compared to other racial groups. The lifetime risk for developing kidney cancer in men is about 1 in 46 (2.02%) and 1 in 80 (1.03%) in women. Risk Factors associated with RCC: Anything that causes assault to the kidneys and affects its function would cause increased demand, injury, and inflammation. This assault can lead to cell derangement and lead to cancer. The risk factors that have been associated with RCC are smoking, obesity, HTN, family history of kidney cancer, Trichloroethylene (a metal degreaser used in large manufacturing factories), acetaminophen, and patients with advanced kidney disease needing dialysis. Patients with syndromes that cause multiple types of tumors: VHL (von Hippel-Lindau) deficiency, a tumor suppressor, gives rise to clear cell renal cell carcinoma. Familial inheritance of VHL deficiency is mostly found in patients that have RCC at a very young age, before 40 y/o. Other tumors can be found in the eye, brain, spinal cord, pancreas, and pheochromocytomas.Hereditary leiomyoma-renal cell carcinoma due to FH gene mutations causing women who have leiomyomas to have a higher risk of developing papillary RCC.Birt-Hogg-Dube (BHD) syndrome mutation in FLCN gene who develop various skin and renal tumors.Cowden syndrome is a mutation in the PTEN gene giving rise to cancers associated with breast, thyroid , and kidney cancers.Tuberous sclerosis causes benign tumors of the skin, brain, lungs, eyes, kidneys, and heart. Although kidney tumors are most often benign, occasionally they can be clear cell RCC. Screening For RCC:Screening is unnecessary because of the low prevalence of this cancer in the general population, though certain groups require annual repeat imaging via US, CT, or MRI. Inherited conditions that are associated with RCC such as VHL syndrome or Tuberous SclerosisESRD patients who have been on dialysis for 3-5 yearsFamily history of RCCPrior kidney irradiation Clinical Picture: Most patients with RCC are asymptomatic until cancer grows large enough to cause disruption of local organs, such as the kidney, bladder, or renal vein, and dysregulates other organs via metastasis. Therefore, it's important to look at other signs and symptoms caused by RCC. The patient most likely will be an older male who presents with the classic triad of: Flank pain: caused by rapid expansion and stretching of the renal capsule.Hematuria: occurs from the invasion of the neoplasm into the collecting duct.Palpable abdominal mass: mass tends to be homogenous and mobile with respirations. Though this presents only in 9% of patients during the presentation, having physical symptoms is a sign of advanced disease and 25% of patients with these signs tend to have distant metastasis. Anemia: normally associated with anemia of chronic disease. It precedes the disease by at least 8 months to 1 year. Males can develop varicoceles because of decreased emptying due to neoplasm obstruction. Patients normally develop varicoceles on the left due to the spermatic vein emptying in the higher resistance left renal vein, which causes backup of the blood in the pemphigus plexus. Though a right-sided varicocele should raise a higher suspicion of obstruction due to the spermatic vein draining directly into the IVC which is lower in resistance. A right-sided varicocele is seen in approximately 11 percent of patients. The paraneoplastic syndrome can also arise from RCCEpo: Erythrocytosis with symptoms of weakness, fatigue, headache, and joint pain.PTHrP: PTH-related peptide acts like PTH which gives rise to hypercalcemia with the prevalent symptoms of arthritis, osteolytic lesions, confusions, tetany, ventricular tachycardia, shortened QTc, and nausea and vomiting.Renin: overproduction from the juxtaglomerular cells can cause disarrangement of the RAAS system causing hypertension.Others also like ACTH and beta-HCG. Other disorders present include hepatic dysfunction, cachexia, secondary amyloidosis, and thrombocytosis. Workup If a patient comes in with painless hematuria, then the first test should be abdominal CT or abdominal ultrasound. A CT is more sensitive than the US but it can quickly indicate if the abdominal mass felt can be a cyst or a solid tumor. US of kidneys should show if it's a simple cyst:-The cyst is round and sharply demarcated with smooth walls- It's anechoic – appears solid black-There is a strong posterior wall echo-Use the Bosniak classification to classify mass Bosniak I: benign simple cyst with thin wall less than equal to 2mm, no septa or calcifications. No future workup is needed. Bosniak II: benign cyst, 3 cm diameter, requires f/u with US/CT/MRI at 6 months, 12 months, and annually for the next 5 years. Chance of malignancy: 5%. Bosniak III: indeterminate cystic mass with thick, irregular or smooth walls. This requires nephrectomy or radiofrequency ablation. Chance of malignancy: 55% Bosniak IV: Clearly a malignancy its grade III with enhancing soft tissue components that its independent from the wall or septum. Requires total or partial nephrectomy. Chance of malignancy 100%. CT of the kidneys for a neoplasm should show:-Thickened irregular walls or septa -Enhancement after contrast injection are suggestive of malignancy-CT can also help detect invasion in local tissue areas such as renal vein and perinephric organs MRI is used if the patient cannot use contrast or kidney function is poor. MRI can also evaluate the growth of the cancer. Other imaging studies:Other imaging studies that may be useful for assessing for distant metastases include bone scan, CT of the chest, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Treatment and staging Nephrectomy, partial or total, will be used as the initial tissue collection for pathology. If the patient is not a surgical candidate, you can also obtain a percutaneous biopsy. The nephrectomy is preferred because first, it serves as a definitive treatment option, but also it allows for definitive staging of the cancer with tumor and nodal staging. Regardless of the size, any solid mass may indicate malignancy and point towards RCC, requiring resection. TNM staging Stage I: Tumor is 7cm across or smaller and only in the kidney with no lymph nodes or distant mets. T1N0M0 Stage IIa: Tumor size is larger than 7cm but still in the kidney but no invasion of lymph node or mets. T2N0M0 Stage IIb: Tumor is growing into the renal vein or IVC, but not into neighboring organs such as adrenals or Gerota's fascia and still lacks lymph node invasion and mets. T3N0M0. Stage III: Tumor can be any size but has not invaded outside structures such as adrenals, though nearby lymph node invasion is present but not distant. There is no distant mets. T3N1M0. Stage IV: The main tumor is beyond the Gerota's fascia and may grow into the adrenal gland . It may or may not spread to the lymph nodes or may not have distant mets. Stage IV also consists of any cancer that has any number of distant mets. T4 Adjuvant therapy can be done with immune therapy. Conclusion: Now we conclude our episode number 105 “Renal cell carcinoma.” This type of cancer may be asymptomatic until it is large enough to cause symptoms. Keep it on your list of differentials on patients with hematuria, flank pain, weight loss, and abnormal imaging. Keep in mind the features of simple kidney cysts vs complex cysts when assessing kidney ultrasounds. Your patient will be grateful for an early diagnosis of RCC and a prompt treatment. Even without trying, every night you go to bed being a little wiser.This week we thank Hector Arreaza, Timiiye Yomi, Manpreet Singh, Jon-Ade Holter. Thanks for listening to Rio Bravo qWeek Podcast. If you have any feedback, contact us by email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. Audio edition: Suraj Amrutia. See you next week! Bibliography: Is There a Cut Off Age for Kidney Transplant?, Mayo Clinic Connect, Jul 18, 2017, https://connect.mayoclinic.org/blog/transplant/newsfeed-post/is-there-a-cut-off-age-for-kidney-transplant/ Atkins, Michael. “Clinical Manifestations, Evaluation, and Staging of Renal Cell Carcinoma.” UpToDate, January 21. https://www.uptodate.com/contents/clinical-manifestations-evaluation-and-staging-of-renal-cell-carcinoma American Cancer Society. “Key Statistics About Kidney Cancer”. Cancer.Org, 2022, https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, Grünwald V, Gillessen S, Horwich A; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019 May 1;30(5):706-720. doi: 10.1093/annonc/mdz056. PMID: 30788497. https://pubmed.ncbi.nlm.nih.gov/30788497/. Gaillard, F., Bell, D. Bosniak classification system of renal cystic masses. Reference article, Radiopaedia.org. (accessed on 20 May 2022) https://doi.org/10.53347/rID-1006. Kopel J, Sharma P, Warriach I, Swarup S. Polycythemia with Renal Cell Carcinoma and Normal Erythropoietin Level. Case Rep Urol. 2019 Dec 11;2019:3792514. doi: 10.1155/2019/3792514. PMID: 31934488; PMCID: PMC6942735. https://pubmed.ncbi.nlm.nih.gov/31934488/. Leslie SW, Sajjad H, Siref LE. Varicocele. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448113/. Maguire, Claire. “Understanding Endoscopic Ultrasound and Fine Needle Aspiration.” Educational Dimension, Educational Dimensions, 1 Jan. 2007, educationaldimensions.com/eLearn/aspirationandbiopsy/eusterm.php. Maller, V., Hagir, M. Renal cell carcinoma (TNM staging). Reference article, Radiopaedia.org. (accessed on 20 May 2022) https://doi.org/10.53347/rID-4699. Palapattu GS, Kristo B, Rajfer J. Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma. Rev Urol. 2002 Fall;4(4):163-70. PMID: 16985675; PMCID: PMC1475999. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475999/.

Spartcast #20 - Birthdays and Boosters

covid-19 birthdays spartan boosters vhl

Play Episode Listen Later Jul 19, 2022 19:42

Spartan got his COVID booster and rambles about 15 years of the VHL incoherently.

2022-07-03 - VHL? What VHL?

PBE Podcast Network

Play Episode Listen Later Jul 6, 2022 133:15

Well, this just happened. I was going to record a solo podcast for the VHL (that's right PBE, I'm cheating on you) but I did it in a public channel and a bunch of PBE folks hopped in and PBE stuff happened so that is that. I apologize for nothing, but also I apologize for everything. Eso Diesel DRJ LSUFan101

pbe vhl

2022-07-03 - The one that was almost a VHL podcast but turned into a PBE podcast

Play Episode Listen Later Jul 3, 2022 132:42

I was whisky drunk and in good spirits and decided to record a 15 minute VHL spot... but I did it in a public voice channel where my PBE buds could jump in. So we discussed.... I don't know, the PBE Legends West conference? The draft? Shit I'm hammered and just want to go to bed.

pbe vhl

Key Posters on Advances in GU Cancers at ASCO22

ASCO Daily News

Play Episode Listen Later May 26, 2022 19:50

Guest host Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute and the ASCO Daily News editor-in-chief, discusses key therapeutic advances in mRCC and mUC, as well as new research that proposes periodic scans to monitor patients with mCSPC for disease progression, with Dr. Jeanny-Aragon-Ching of the Inova Schar Cancer Institute. Transcript: Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. My guest today is Dr. Jeanny Aragon-Ching, who is a medical oncologist and the Clinical Program Director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters in genitourinary (GU) oncology that will be featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcast. Jeanny, it is great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thanks, Neeraj. It's a pleasure for me to be here as well. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4510. This is a trial that represents a growing interest among researchers worldwide in the microbiome and how it is impacted by antibiotics and how it modulates immune checkpoint inhibitor response. Can you tell us about this study? Dr. Jeanny Aragon-Ching: Thanks, Neeraj, I would be happy to. So, the title of the abstract is, “Characterization of the Microbial Resistome in a Prospective Trial of CBM 588 in Metastatic Renal Cell Carcinoma Offers Mechanism for Interplay Between Antibiotic Use and Immune Checkpoint Inhibitor Activity.” So, this is an interesting abstract that originated likely from the observation that getting antibiotics while on checkpoint inhibitors typically results in worse outcomes, perhaps because antibiotics can clear the normal gut flora and thereby increase these pathogenic antibiotic-resistant bacteria. Now, on the other hand, there were some retrospective studies using a live microbial product called CBM 588, which seems to improve outcomes in patients on checkpoint inhibitors and getting antibiotics. So, the idea, therefore, is that shifting the genes encoding antimicrobial resistance could result in a better checkpoint inhibitor response. So, this Abstract 4510 is a small study conducted by Dr. Nazli Dizman and Dr. Sumanta (Monty) Kumar Pal, and colleagues, and enrolled 29 metastatic clear cell RCC patients with intermediate or poorest disease. And they were stratified into receiving either nivolumab or ipilimumab compared to nivo/IPI with CBM 588. Now stool samples were collected at baseline in week 12. And they did this whole metagenome sequencing to analyze a stool microbiome composition, and they also looked at the antibiotic resistance genes for the most common classes of antibiotics. The results showed an astounding improvement in objective responses. So, 58%, for instance, in nivo/IPI and the CBM 588 arm compared to only 20% in the nivo/IPI arm. And it seems like also the antibiotics resistance genes were also decreased in those getting the CBM 588 alongside nivo/IPI. Therefore, responses were improved by shifting the gut microbiome alone. So, these findings were published actually recently by these authors in Nature Medicine. So, in case anyone wants to take a deep dive, it would be a good interesting read for this dataset. Dr. Neeraj Agarwal: Very interesting, indeed. Jeanny, what is the main message here for our colleagues? Dr. Jeanny Aragon-Ching: I think, Neeraj, the key takeaway message is that this is a very provocative proof of concept trial that suggests shifting the gut microbiome has the potential to improve responses to checkpoint inhibitors and outcomes. So, this is a very up-and-coming trial and is seen also across the board in other cancers. Dr. Neeraj Agarwal: Thanks, Jeanny. Moving on to urothelial cancer, there is a poster that I think is a must-see for our colleagues. This is Abstract 4577 titled, “Defining Platinum Ineligible Patients with Metastatic Urothelial Carcinoma.” Dr. Jeanny Aragon-Ching: So, Neeraj, what can you tell us about this abstract? Dr. Neeraj Agarwal: So, over the past few years, there has been a tremendous evolution in the treatment landscape for patients with metastatic urothelial carcinoma. For over 40 years the standard of care for these patients has been cisplatin-based chemotherapy. However, approximately 50% of patients are cisplatin-ineligible, due to underlying comorbidities, and are offered carboplatin as an alternative. So, although the checkpoint inhibitors pembrolizumab and atezolizumab were approved as first-line therapy for these patients in 2017, the U.S. Food and Drug Administration (FDA) has now restricted the use of first-line pembrolizumab to platinum ineligible patients with metastatic urothelial carcinoma. The challenge we face as oncologists since the FDA restriction is the absence of a formal definition of platinum ineligibility and the inclusion of this definition in the guidelines. So, in Abstract 4577, Drs. Shilpa Gupta and Jonathan Rosenberg, along with the team present an updated consensus definition for platinum ineligibility based on an online survey of 60 genitourinary oncologists in the United States. Based on the results from this survey, any patient with metastatic urothelial carcinoma, meeting 1 of the following 5 clinical and or laboratory parameters should be considered platinum ineligible, and these are 1 of the following: an ECOG performance status of 3 or more, creatinine clearance of fewer than 30 mils per minute, or peripheral neuropathy of grade 2 or more, or heart failure class of 3 or more—so, this is NYHA heart failure class of 3 or more—and lastly, the combination of performance status of 2 or more, plus a creatinine clearance of less than 30 mils per minute. Dr. Jeanny Aragon-Ching: Well, this is a timely update, Neeraj. So, what do you think is a key takeaway from this abstract? Dr. Neeraj Agarwal: These criteria based on simple and easily available clinical and or laboratory parameters will now allow us to readily define platinum ineligibility in our patients with metastatic urothelial carcinoma, which is a need in busy clinics, both in academic and community settings. So, I think once published and obviously once endorsed by guidelines, we really would like to be able to use this criterion to quickly define platinum ineligibility in our clinics. Dr. Jeanny Aragon-Ching: Agree. Yeah. Dr. Neeraj Agarwal: So, Jeanny, let me switch the gears. PSMA testing is a hot topic this year. And there is an abstract that could potentially have an impact on future guidelines, and how we will practice further down the road. So, I'm referring to the Abstract 5088 titled, “Predictive Value of Extra Prostatic Disease Detection by Preoperative PSMAPET for Biochemical Recurrence-free Survival in Patients with Otherwise Localized Prostate Cancer and Who are Treated with Radical Prostatectomy.” So, this is a follow-up analysis of a multicenter prospective phase 3 imaging trial. So, could you please tell us more about this abstract where they are using PSMA PET scan in the preoperative localized prostate cancer setting? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, you may recall that the multicenter prospective phase 3 imaging trial that garnered gallium PSMA approval by the FDA was actually based on this study that looked at the intermediate and high-risk patients with prostate cancer undergoing radical prostatectomy and lymph node dissection, and they underwent prior gallium PSMA PET scanning for pelvic nodal metastases prior to surgery. So, this was actually previously reported by Dr. Calais and group. Now they are reporting on Abstract 5088 as a post hoc analysis of the same population and group of patients looking for extraprostatic disease. And the final pathology was also correlated to look at nodal disease in these patients in order to predict biochemical recurrence, so they follow these patients for biochemical recurrence occurrence. So, of the 36% of patients who did undergo radical prostatectomy after they underwent PSMA PET scan, about 41% of them recurred with biochemical recurrence, and 40% of them underwent some kind of salvage therapy or some treatment. What was very interesting was when they looked at the biochemical recurrence-free survival. It was better in those who were PSMA negative, and that recurrence-free survival was easily about 33 months, compared to only about 7.3 months in those who were PSMA-positive scans. Furthermore, the ones who had the longest and the highest biochemical recurrence-free survival, intuitively, were those who were node-negative and PSMA PET-negative, so probably not surprisingly. And that rate was about 46 months—close to 4 years. Whereas those who are node-positive on final pathology and their PSMA PET was also positive, they only had about 3 months of biochemical recurrence-free survival. Dr. Neeraj Agarwal: Very interesting. So, it looks like the PSMA PET scan is predicting biochemical recurrence-free survival in localized prostate cancer settings. So, Jeanny, what is the key takeaway from this trial? Dr. Jeanny Aragon-Ching: I think, Neeraj, the bottom line is that patients with extraprostatic disease that is detected by their preoperative PSMA PET scan does predict strongly a high risk of biochemical relapse, and this can really be an additional tool that clinicians can use to help inform and guide future therapy. Dr. Neeraj Agarwal: Thanks, Jeanny. The research on preoperative PSMA testing and its implications on future treatment strategies in the setting is going to be really interesting to watch in the very near future. Dr. Jeanny Aragon-Ching: Yes, absolutely. I really think we should also discuss Abstract 5072, along those lines, the importance really of radiographic monitoring for disease progression in patients with metastatic hormone-sensitive prostate cancer. Dr. Neeraj Agarwal: Yes, thanks for reminding and this is Abstract 5072. This is a post hoc analysis of the ARCHES trial, titled, “Radiographic Progression in the Absence of PSA Progression in Patients with Metastatic Hormone-sensitive Prostate Cancer.” During the last several years, we have seen many of these agents typically given for gastric resistant prostate cancer moving upfront to the castration-sensitive prostate cancer setting. This is especially true for androgen receptor access targeting agents such as abiraterone, enzalutamide, and apalutamide, all being now approved for patients with metastatic castration-sensitive prostate cancer. What is noteworthy from all these trials, and is reported in Abstract 5072, is the use of imaging studies to evaluate disease progression. So, in Abstract 5072, Dr. Andrew Armstrong and Dr. Arun Azad performed a post hoc analysis of the ARCHES trial to investigate the concordance between radiographic progression and the PSA Progression as defined by PCWG2 criteria, or between radiographic progression and any rise in the PSA above nadir, in patients who were being treated with this novel hormonal therapies, in this case, enzalutamide for metastatic castration sensitive prostate cancer. And as a quick reminder, ARCHES was a phase 3 trial that showed a significant reduction and radiographic progression-free survival and improved overall survival for patients with metastatic castration sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy (ADT) versus those treated with placebo plus androgen deprivation therapy. So, very interestingly, the findings from this study indicate that 67% of patients on the enzalutamide plus ADT arm did not have [Prostate Cancer Clinical Trials Working Group 2 criteria] PCWG2-defined prostate-specific antigen (PSA) progression at the time of radiographic progression. And discordance was present in the ADT-only arm as well, where they found 42% of patients on the ADT-only arm had radiographic progression but did not have PCWG2-defined PSA progression. Interestingly, this discordance of radiographic disease progression was also seen with any rise in the PSA above nadir. And I personally found this information to be very clinically relevant when we are seeing the majority of patients actually experiencing radiographic disease progression, not experiencing PSA progression at the same time. Dr. Jeanny Aragon-Ching: Yeah, absolutely. I agree with that, Neeraj. So, very interesting data. So, what do you think is the key takeaway message for the clinicians listening to us? Dr. Neeraj Agarwal: I'll make the message very simple. I think the message is that patients with metastatic castration-sensitive prostate cancer need to be monitored for disease progression with periodic scans, and PSA monitoring alone is not sufficient in the majority of these patients. Again, we cannot undervalue the role of periodic imaging studies in these patients so that we can timely diagnose them to have disease progression. Dr. Jeanny Aragon-Ching: I agree with that. Dr. Neeraj Agarwal: Jeanny, the last abstract I would like to mention before we wrap up the podcast is Abstract 4509, the results from the phase1 live SPARC 001 study. So, can you please tell us more about this study titled, “Phase-1 Live SPARC 001: The Study of Belzutifan in Advanced Solid Tumors,” which is an update of the renal cell carcinoma cohort with more than 3 years of total follow up? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. So, while the current therapeutic landscape for patients with metastatic clear cell renal cell carcinoma (RCC) has changed dramatically over the past several years, with significant improvement in patient outcomes. Most patients unfortunately still experience disease progression on current treatments. So, in-depth molecular profiling of clear cell RCC has revealed recurrent loss of function mutations in VHL in actually greater than 90% of patients. So, the VHL protein, as you will recall, is part of the oxygen-sensing pathway, regulating levels of HIF which is hypoxia-inducible factor protein, it's a transcriptional activator that mediates the response to hypoxic conditions. So, HIF-2α is a key oncogenic driver in RCC. So, previous data you may recall from the phase-1 Live SPARC 001 trial was designed to evaluate belzutifan so, this was a novel HIF-2α inhibitor which showed durable anti-tumor activity and acceptable safety profile in patients with metastatic clear cell RCC. So, in Abstract 4509, Drs. Jonasch and Toni Choueiri presented updated results from this trial after more than 3 years of follow-up. Of the 55 patients enrolled 16% of patients remained in treatment. And 62% of patients had discontinued treatment because of, unfortunately, disease progression. The median progression-free survival (PFS) for the total cohort was 14.5 months. And the overall disease control rate was 80%. Forty percent of patients experienced grade 3 treatment-related adverse events with the most frequent ones being anemia and hypoxia. There were no great 4 or 5 treatment-related adverse events. And these results, therefore, show that belzutifan monotherapy continues to show a high rate of disease control and a safety profile in a heavily treated population of patients with metastatic RCC. So, it is great to see that there were no new safety signals. Dr. Neeraj Agarwal: Very nice data indeed. So, Jeanny, what is the key takeaway message here for our listeners? Dr. Jeanny Aragon-Ching: Yeah, I think the message here is that the use of belzutifan monotherapy continues to show efficacy and safety in patients with metastatic clear cell RCC, which have progressed on multiple prior contemporary therapies, and there are phase 3 trials currently underway. Dr. Neeraj Agarwal: Jeanny, any final thoughts before we wrap up the podcast today? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. I think it's a really exciting time to be in genitourinary (GU) oncology, and I'm truly looking forward to seeing some great sessions at the 2022 ASCO Annual Meeting. Dr. Neeraj Agarwal: Thank you, Jeanny, for sharing your insight with us today. It was a great conversation. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on 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 podcast. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma 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 expressed 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.

united states university moving travel food speaker study cancer patients phase survival consulting fda pfizer psa forty drs absence gu advances astrazeneca bayer treated abstract oncology merck prostate cancer janssen calais novartis posters accommodations cancer care sanofi asco genentech disclosures amgen drug administration fda arches bristol myers squibb adt takeda characterization rcc pfs gilead sciences nature medicine ipi sparc nektar cbm hif eisai asco annual meeting jonathan rosenberg muc psma emd serono foundation medicine jeanny aveo andrew armstrong vhl ecog psma pet mrcc seattle genetics nyha dendreon arvinas pharmacyclics clinical program director janssen oncology mcspc neeraj agarwal toni choueiri mei pharma astrazeneca medimmune

2022-04-07 - The Return of the... Thing?

Play Episode Listen Later Apr 8, 2022 20:29

I have done a poor job of retiring forever from the VHL, and am back with a new player after just a few weeks. In this episode I discuss my reason for returning, my goals for my new player, and also give a bit of a retrospective on the career of my first player.

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Spartcast #15 - Hybrid Attributes and Offseason Tournaments

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Play Episode Listen Later Mar 15, 2022 21:52

Spartan discusses the creation and response to the new hybrid attribute system in the VHL, as well as the offseason tournaments that have just started up again!

Landmark Breakthrough for Tumor Treatment; How Doctors Can Handle "Causality" in Court; and more

Physician's Weekly Podcast

Play Episode Listen Later Feb 7, 2022 30:26

Welcome to this episode of Physician's Weekly Podcast. My name is Dr. Rachel Giles, from Medicom Medical Publishers, in collaboration with Physician's Weekly. There was a lot of interesting medical news this last week. Later in this episode, we interview Dr. Samer Al Hadidi, from Little Rock, Arkansas, who the lead author of a study about the lack of enrollment of African-American patients into trials in general, and here in particular, trials that were used to register the use of CAR-T cell therapies for the treatment of various hematological malignancies. He presents some interesting solutions that can be applicable to all trials. Also in this episode of Physician's Weekly Podcast, we speak to our regular contributor, who goes by the pseudonym, Dr. MedLaw all about what “Causality” means in the courtroom. When is a doctor the cause of a medical problem, and what can be done about it?But first, Physician's Weekly speaks with Dr. Eric Jonasch, from the University of Texas MD Anderson Hospital in Houston, about the results of the his recently published New England Journal of Medicine article reporting the registrational data for a small molecule belzutifan in patients with the rare tumor syndrome von Hippel-Lindau disease, abbreviated as VHL. I have had the distinct honor of knowing hundreds of VHL patients over the last 20 years, and this study has truly become a landmark breakthrough for patients dealing with tumors in their kidneys, pancreas, adrenal glands, brain or spinal cord, eyes, endolymph sacs, epididymis, or broad ligament. It was FDA approved in August 2021, and the patient and medical VHL community is so relieved to have a systemic treatment finally.Enjoy listening! More reading: Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425. PMID: 34818478. Al Hadidi S, Dongarwar D, Salihu HM, Kamble RT, Lulla P, Hill LC, Carrum G, Ramos CA, Heslop HE, Usmani SZ. Health disparities experienced by Black and Hispanic Americans with multiple myeloma in the United States: a population-based study. Leuk Lymphoma. 2021 Dec;62(13):3256-3263. doi: 10.1080/10428194.2021.1953013. Epub 2021 Jul 18. PMID: 34278937.Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

Spartcast #9 - Not One, but TWO New Jobs and Finals Losses!

Play Episode Listen Later Jan 18, 2022 26:47

Spartan discusses his two new VHL jobs and the recently concluded playoffs, as well as a sneak peek at the upcoming offseason.

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Spartcast #8 - Offseason Tournaments and GM Progression

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Play Episode Listen Later Jan 10, 2022 25:59

Spartan chats about all the different offseason events, whether the value of IIHF tournaments has dropped, and if it can be salvaged. In addition, he discusses what GM progression in the VHL could look like.

Spartcast #6 - Into the Multi-verse

Play Episode Listen Later Dec 28, 2021 25:37

Spartan chats about all the multis in the league, the biggest scandal of the holiday season, and how some rules and procedures could be improved in the VHL to prevent similar misconduct in the future. And of course, questionable driving moments.

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Spartcast #5 - Money, Meta, Many Bad Ideas

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Play Episode Listen Later Dec 14, 2021 37:45

Spartan chats about the sorry state of money and its uses in the VHL and ways to potentially improve it. Bundled in is how a money change could also open up build diversity and solve the meta issue, though it's probably all a shitty idea. I also learned that I hate Ford F150's.

Spartcast #4 - Recruitment, Retention, and Solving Problems

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Play Episode Listen Later Dec 7, 2021 39:17

Spartan discusses a few popular issues circulating the VHL community - league sizes and alignments, recruitment concerns, retention struggles, and other interesting topics, along with a few general solutions for these critical league issues.

One and a Half Aussies - Episode 16

The Talking Type 1 Podcast

Play Episode Listen Later Dec 2, 2021 81:05

After over 7 months, Berocka and Boot are reunited and shit talk about the VHL

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36. Andrew: 75% of my pancreas was removed - My life with type 3c diabetes and VHL

Play Episode Listen Later Nov 19, 2021 69:27

In this episode, I speak to Andrew who lives with type 3c diabetes. Andrew has also been living with Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare genetic disorder with multisystem involvement. [2] It is characterized by visceral cysts and benign tumours with the potential for subsequent malignant transformation (information taken from Wikipedia). Andrew openly shares his journey living with both conditions and all the challenges that it brings. We also discuss: The benefits of having an official type 1 diabetes diagnosis in gaining access to diabetes technologyLife with VHL and the impact this has on his type 3c diabetesQualities gained whilst living with chronic illnessUseful links:Andrew on InstagramDaniel on InstagramA bit about the show and hostThe Talking Type 1 podcast is a diabetes podcast by Daniel Newman. Daniel brings to you interviews from members of the diabetes community sharing their journeys of the ups and downs of living with type 1 diabetes. You'll hear from those who live with type 1 diabetes, provide care to those living with type 1, healthcare professionals and experts in their field. The interviews will be an open and honest insight into life with type 1 diabetes that you can relate to and also provide the opportunity to learn more about the condition. Daniel will share his insights into his life living with type 1 diabetes. Daniel has lived with the condition along with for over 25 years. He also lives with diabetic retinopathy and received a kidney transplant in 2018. Remember to hit the follow button.

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From Stressed to Dressed - Victoria Hamilton from Victoria Hamilton Lifestyle

Shine On You Crazy Daisy

Play Episode Listen Later Oct 19, 2021 16:48

Please listen to this podcast - I had a MASSIVE ah-ha moment in the middle of what and why work/life balance is backwards! Plus, Victoria talks about what style means for women and how she has found her destiny. Victoria Hamilton from VHL - https://www.victoriahamiltonlifestyle.co.uk/ MEMBERSHIP To join the Shine On You Crazy Daisy Membership and invest in the growth of your business, please click here to find out more. You will receive knowledge to grow your business and support to implement what you learn, putting time aside to work ON your business - and have FOCUSED-FUN whilst doing it! BOOKS To buy Shine On You Crazy Daisy – Volume 1, 2, 3, 4 & 5: Visit Amazon, iBooks or any good book retailer. YOUTUBE PODCAST EPISODES To watch our podcast episodes on Youtube - CLICK HERE.

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Navigating The Journey

Very Heroic Living

Play Episode Listen Later Oct 12, 2021 54:19

In this episode, Joseph and Aaron discuss the idea of Victim-Survivor-Navigator; a concept that has helped Joseph to acknowledge the changes and adaptations necessary to navigate life with von Hippel Lindau.Later in the show, we're joined by special guest, Chandra Clark, executive director of the VHL Alliance. Chandra helps us shed light on this shared path from circumstance and trauma to recovery and a return to living our hero's journey.For more information on the VHL Alliance visit VHL.org

navigating vhl

Very Heroic Living - Pilot Episode

Very Heroic Living

Play Episode Listen Later Sep 28, 2021 27:38

Welcome to Very Heroic Living. In this pilot episode, host Joseph Heisler introduces himself and his journey living with von Hippel-Lindau aka VHL. Diagnosed at a young age, Joseph has been through many stages of life having to navigate extraordinary circumstances for himself and his family. Joined by an old friend and show producer, Aaron Hodges, Joseph opens up about some of the dark days and experiences that have shaped his life and how he manages a lifestyle he never imagined.

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VSN S80 Mock Draft feat. MattyIce

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Play Episode Listen Later Sep 18, 2021 65:25

Spartan and Matty chat about recent moves around the VHL and mock draft the entire first round of the S80 VHL Draft!

Episode 67 - Comirnaty, COVID EUA, & Welireg

The Rx Daily Dose

Play Episode Listen Later Aug 31, 2021 14:46

Here are the links for everything discussed in Episode 67. Times are also below so feel free to skip around and get to the drugs that interest you. And I apologize for the echo - need to find a better place to record in the new home :) (1:18) COVID19 vaccine approved as brand name Comirnaty (8:10) Amended EUA for COVID vaccines (10:20) Welireg approved for VHL Connect with The Rx Daily Dose:Twitter Instagram YouTube Linkedin WebsiteEmail: therxdailydose@gmail.comConnect with Ian Parnigoni PharmD. on social media:Twitter Instagram Linkedin ★ Support this podcast on Patreon ★

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VHL Awards Carcast

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Play Episode Listen Later Aug 19, 2021 36:23

Spartan chats about VHL awards in the past and future, and then realizes he has no gas in his car while on the highway. What happens in this thriller that deserves an Emmy?!??!

2021-07-19 - Happy Birthday VHL!

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Play Episode Listen Later Jul 20, 2021 34:57

The one where I never actually mention the VHL birthday. I talk about sports, video games, LucasArts' 1994 masterpiece "TIE-Fighter" and eventually, the S78 VHL season and the Calgary Wranglers outlook.

Spartan Solo Bolo

Play Episode Listen Later May 31, 2021 59:24

Spartan answers questions sent to him by VHL members!

spartan vhl solo bolo

2021-05-30 - D&D and Beer League Sports

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Play Episode Listen Later May 30, 2021 16:51

Talk about what I've been up to in real life lately, the exciting finish to the PBE season (and the less exciting finish to Steve Eso's PBE career), beer league softball/hockey/curling, and how the Calgary Wranglers stack up in the crowded pack in the VHL's North American conference.

What is VHL? W/ Chandra Clark @ VHL Alliance

The business of vulnerability

Play Episode Listen Later May 12, 2021 18:01

Chandra Clark the Executive Director at the VHL Alliance swings by to help increase our awareness of the rare chronic disease: VHL or von Hippel-Lindau disease. Take a listen to learn how this disease effects individuals, how the alliance is helping and how you can help.

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2021-04-26 S77 Calgary Wranglers Season Wrap-up

calgary wrangler vhl calgary wranglers

Play Episode Listen Later Apr 26, 2021 20:57

Steve Eso of the Calgary Wranglers talks about the season that was in the VHL, looks ahead to the playoffs a little bit, but mostly focuses on the personnel moves that the Wrangers made.

Wheelie Pods, Ep 1: Thad & Guriin

PBE Podcast Network

Play Episode Listen Later Apr 2, 2021 64:34

by Guriinwoodo Come listen in as thadthrasher and myself discuss our origin stories, the PBE minor league, and the VHL! The inaugeral podcast of what hopefully will be many more to come!

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von Hippel-Lindau Chuvash Polycythemia

PodcastDX

Play Episode Listen Later Mar 30, 2021 43:05

Our guest this week is Shannon Wyatt. Shannon has an extremely rare condition called von Hippel-Lindau Chuvash Polycythemia (we will abbreviate to VHL). Her only symptom that led to finding VHL was that she was diagnosed with kidney cancer at 34 years old, that didn’t even have any noticeable symptoms, it was just an incidental finding on an MRI, but when they took it out, they found it was malignant. A few years later, it was pulmonary embolisms in both lungs after a routine gallbladder removal that pointed to Chuvash Polycythemia after many previous labs had raised suspicion of it. Common signs and symptoms for VHL include: Tumors and hemangiomas of the kidneys, pancreas, adrenal glands, liver, eyes, brain and spinal cord Chuvash Polycythemia is typical know for causing: Noticeable symptoms are fatigue, headaches, a reddish complexion, and itching. Dangerous underlying issues are blood clots and high pulmonary blood pressure with low systemic blood pressure. Chuvash polycythemia is a rare, inherited disorder that is endemic to the Chuvash Republic of Russia, though it does occur in other parts of the world. NIH studies rare diseases not only to help the people who have them, but also to gain insight into gene functions that may benefit people with more common conditions. Complications of Chuvash polycythemia include blood clots and cerebral hemorrhage. The condition results from a genetic mutation that makes people unable to break down hypoxia inducible factor 2α (HIF2α), a protein that helps stimulate red blood cell production. The inability to degrade HIF2α leads to higher red cell production, even under high-oxygen conditions.

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One and a Half Aussies - Episode 11 ft. gorlab

Play Episode Listen Later Jan 20, 2021 56:28

Berocka and Boot are joined by gorlab for the beginning of the episode and then do some around the VHL and a S68 redraft

boot aussies vhl

One and a Half Aussies - Episode 10

Better Edge : A Northwestern Medicine podcast for physicians

Play Episode Listen Later Jan 15, 2021 99:23

After an awful episode last week, Berocka and Boot look to give the listeners something good. With another edition of Beard or No Beard and an exciting off-season for around the VHL, we have our longest episode yet

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Life in China with Alannah Liem

Breaking the Ice

Play Episode Listen Later Dec 2, 2020 66:13

Alannah Liem, wife of Jordan Liem, who played the last three years in China in the VHL, joins me on the podcast!This was such a fun & interesting episode for me because I have never sat down and chatted with a fellow hockey wife about life in China! Given what is happening in the world with COVID, Alannah was in the middle of it in China and talks about what her experience was like getting home and hearing about it for the first time. She also tells me some hilarious stories about life in China including hotel living, shopping in back alleys, doing laundry in the tub and not having a kitchen!Life in china has meant years of tremendous personal growth for Alannah and she handles the set backs with humor. I loved this conversation and I hope you do too! :)

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Neurological Management of Von Hippel-Lindau Disease

Play Episode Listen Later Nov 23, 2020

Rimas Lukas, MD discusses the pathophysiology of Von Hippel-Lindau disease (VHL) and its nervous system manifestations. He walks us through the clinical diagnostic criteria, the therapeutic management of CNS hemangioblastomas and endolymphatic sac tumors and how recent advances have increased our understandings of pathologies of VHL. He tells us about the VHL clinic at Northwestern Medicine, what makes it unique and what he and his colleagues are doing to advance the understanding and treatment of VHL.

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One and a Half Aussies - Episode 6

Play Episode Listen Later Nov 23, 2020 69:27

Berocka and Boot talk about the VHL season starting, have a look at the S76 draft class, Berocka has a go at his first 2 minute quiz and then solves some more league problems

boot aussies vhl

The Spartan and Fishy Show #8 feat. Viper - The Return of a Young Stud

Play Episode Listen Later Nov 5, 2020 68:03

Spartan and Fishy chat with Viper on his return to activity in the VHL, what he's been up to, and what his goals are for his new player. Also, a very important question: Do AGM's deserve right?

young spartan viper stud fishy vhl

The Spartan and Fishy Show #7 feat. Cowboy - Introducing a New Face in the VHL!

London's Leadership Podcast

Play Episode Listen Later Oct 25, 2020 85:26

Spartan and Fishy sit down with Cowboy to introduce him to the VHL and chat about the various happenings around the league!

cowboy spartan fishy new face vhl

E aí, está tendo vôos direto para o Brasil?

Destino China PODCAST

Play Episode Listen Later Jul 2, 2020 5:41

Esta pandemia tem prejudicado e muito o setor de vendas, principalmente a compra de importados em diversas partes do mundo, mas a questão é que não parou por completo e sim diminuiu bastante. O volume da visita de importadores e as famosas feiras da China, tem diminuído bastante e os vôos da China para o Brasil, também acompanham esta mesma estatística, diminuíram drasticamente. O IMS, que seria o correio chinês, fazendo o envio de mercadorias no Brasil pelo correio, não estão funcionando. Outra opção para envio de mercadorias ao Brasil seria o envio pelo IUPS, FEDEX ou VHL. As mercadorias são enviadas, porém, estão em uma fila de espera, ou seja, o cliente deve esperar a mercadoria ser embarcada para entrega no destino final. O produto é colocado na alfândega e automaticamente entra nessa fila e os produtos são enviados aos poucos sem previsão exata de dias para serem enviados. A entrega não pode ser garantida já que não se sabe ao certo se o embarque do produto vai ser possível ou não. É preciso ter bastante cuidado nesta questão, principalmente quando os produtos são entregues via aérea. Sabe-se que a maioria das mercadorias, não estão sendo embarcadas, permanecendo nesta fila de espera. Esta situação tem sido mais crítica, na questão de entregas por via aérea que seria considerada a mais rápida e emergencial e os itens mais enviados tem sido máscaras, respiradores e produtos médicos devido a pandemia atual. As mercadorias são colocadas em vôos, que em situações normais, seriam somente de passageiros, isso por apresentarem custo mais barato, coisa que se fosse em avião fretado, na situação atual, com toda certeza sai bem mais caro. A previsão de chegada ao Brasil tem sido de aproximadamente 10,15 dias. Sendo assim, vôos da China diretamente para São Paulo não tem sido com frequência estando condicionados a fila de espera para embarque das mercadorias.

china brasil sabe fedex o brasil outra tendo direto vhl

EP 55 - How to find purpose in life with Tom Rath

Play Episode Listen Later Jun 15, 2020 24:50

Tom Rath is an author and researcher who has spent the past two decades studying how work can improve human health and well-being. His 10 books have sold more than 10 million copies and made hundreds of appearances on global bestseller lists.Tom’s first book, How Full Is Your Bucket?, was an instant #1 New York Times bestseller and led to a series of books that are used in classrooms around the world. His book StrengthsFinder 2.0 is Amazon’s top selling non-fiction book of all time. Tom’s other bestsellers include Strengths Based Leadership, Wellbeing, Eat Move Sleep, and Are You Fully Charged?. He has also co-authored two illustrated books for children, How Full Is Your Bucket? for Kids and The Rechargeables. Tom has two books slated for publication in 2020, Life’s Great Question: Discover How You Best Contribute to the World and It’s Not About You: A Brief Guide to a Meaningful Life, published in partnership with Amazon Original Stories.During his 13 years at Gallup, Tom led the organization’s strengths, employee engagement, wellbeing, and leadership consulting worldwide. Tom has served for the past five years as an external advisor and Gallup Senior Scientist. He also served as Vice-Chair of the VHL cancer research organization and has been a regular lecturer at the University of Pennsylvania.

university amazon world kids new york times pennsylvania wellbeing vice chair gallup meaningful life purpose in life strengthsfinder find purpose tom rath strengths based leadership vhl eat move sleep how full is your bucket are you fully charged

Episode 28: Targeting VHL Syndrome Renal Cancer with a HIF Inhibitor - A Game Changer

The Uromigos

Play Episode Listen Later May 29, 2020 13:31

Eric Jonasch discusses his ASCO presentation, which shows significant activity of HIF targeting in renal cancer patients with VHL syndrome.

cancer syndrome game changers targeting renal asco inhibitor hif vhl

ATP Hockey Talks Vol. 13 - Brandon Wong

Across The Pond HK Hockey Podcasts

Play Episode Listen Later May 7, 2020

My guest today grew up in beautiful Victoria, Canada. He’s played 8 seasons professionally across multiple continents. He was a BCHL MVP and leading scorer, a two-time Hobey Baker Award finalist, NCAA Rookie of the Year and an All-American. He’s currently playing In Beijing in the VHL. Please welcome to ATP Hockey Talks, Brandon Wong.

canada beijing all american hockey talk hobey baker award vhl brandon wong

VSN Australia - Learning the Ropes - Episode 8 (Featuring Victor)

learning australia ropes vhl

Play Episode Listen Later Mar 15, 2020 98:55

Today I talk to Victor and try and learn about the VHL and the history

073: Leadership Expert Tom Rath Explains How To Find Your Purpose Use Your Strengths To Succeed In Life

Quest for the Best with Stu Schaefer

Play Episode Listen Later Feb 24, 2020 27:53

Visit stuschaefer.com for complete show notes. Leave us a rating and review! Tom Rath is an author and researcher who has spent the past two decades studying how work can improve human health and well-being. In total, Tom's 10 books have sold more than 10 million copies and made hundreds of appearances on global bestseller lists. During his 13 years at Gallup, Tom led the organization's strengths, employee engagement, wellbeing, and leadership consulting worldwide. Tom has served for the past five years as an external advisor and Gallup Senior Scientist. He also served as Vice-Chair of the VHL cancer research organization and has been a regular lecturer at the University of Pennsylvania.

university pennsylvania succeed strengths vice chair gallup find your purpose leadership experts tom rath vhl

109: Life's Great Question, with Tom Rath

Finding Brave

Play Episode Listen Later Feb 6, 2020 37:59

Thank you for listening to our Finding Brave show, ranked in the Top 100 Apple Podcasts in Careers! “The main takeaway for me would be that we need to weave a discussion about contribution into more and more conversations, because it’s a way to repair the broken relationship between people and the work that they do today.” - Tom Rath When today’s Finding Brave guest was 16 years old, he learned he had a rare and catastrophic genetic mutation, one that would lead to cancers in multiple organs. After living for more than 25 years since his diagnosis—three years longer than doctors predicted—he has not only beaten the odds but has learned that time is more valuable when you can see your mortality on the horizon. His inspiring messages for listeners today focus on the impact of contribution, not only for others, but for yourself as well. Tom Rath is a renowned, bestselling author and researcher who has spent the past two decades studying how work can improve human health and well-being. His 10 books have sold more than 10 million copies and made hundreds of appearances on global bestseller lists. Tom’s first book, How Full Is Your Bucket? was an instant #1 New York Times bestseller and led to a series of books and activities for kids that are used in classrooms around the world. His book StrengthsFinder 2.0 is Amazon’s top selling non-fiction book of all time. His other bestsellers include Strengths Based Leadership, Wellbeing, Eat Move Sleep, and Are You Fully Charged? In Tom’s latest book, LIFE’S GREAT QUESTION: Discover How You Contribute to the World, Tom shares the details of his personal story, explores what makes life worthwhile, and offers actionable advice on how to create meaning by focusing on what you can contribute to others. During his 13 years at Gallup, Tom was the Program Leader for the development of Clifton StrengthsFinder, which has helped over 10 million people to uncover their talents, and went on to lead the organization’s employee engagement, well-being, and leadership practices worldwide. Tom has served for the past five years as a Gallup Senior Scientist. He also served as Vice-Chair of the VHL cancer research organization and has been a regular lecturer at the University of Pennsylvania. I find Tom’s writings so rich, and every single word he writes contains a universe of messages within them. I know you’ll get as much value from this episode as I did in speaking with him. To learn more about today's guest, visit: https://www.tomrath.org/

university amazon world new york times pennsylvania wellbeing careers vice chair gallup great questions strengthsfinder tom rath program leader clifton strengthsfinder strengths based leadership vhl eat move sleep how full is your bucket

The Kopecky (VHL Interviews) | WCBPodcast

The Windy City Benders Podcast

Play Episode Listen Later Nov 25, 2019 67:02

On this episode Poetz is back! He and Jarom talk about the ups and downs the Hawks have faced after winning 4 in a row and then dropping 3 straight. They continue to just talk about the Lehner/Crowford duo but ask if Colliton should consider tossing Crow in for all shootouts and Jarom asks how hard is it for goalies to be switching off each game and if there might be time to let one goalie run with the crease a little more. The Boys are then joined by Founder of the Veterans Hockey League and Goalie for the Level Zero Heroes Marine Veteran Alex Martinez who talks a little bit about what the VHL is, what they are trying to accomplish, and how you can get involved. For more info on the VHL: vetshockeyleague.com instagram.com/veteranshockey/ They are then joined by Marine Veteran William Lipke who plays for the Chicago Blackhawks Warriors and Level Zero Heroes. William talks about hockey being therapeutic and giving him a chance to escape and his personal experiences playing in the VHL For more info on the Chicago Blackhawks Warriors: chicagoblackhawkswarriors.com facebook.com/chicagoblackhawkswarriors/ Follow the Boys on all Social Media @WCBPodcast. There you can slide in to the DMs and leave some questions for future Riding Pine Segments. Use our WCBPodcast Hotline call and leave Voicemails with questions, would you rather, hypotheticals, and players for a game of Sign, Trade, Buy Out. Call or text us at 708-942-4829

founders boys trade dms crow hawks buyouts goalie voicemails jarom kopecky colliton vhl

Infusing Startup Culture into Tech Transfer

Dragons, Gazelles, & Unicorns

Play Episode Listen Later Nov 14, 2019 20:47

Dr. Thomas Stackhouse is the Associate Director for the Technology Transfer Center at the National Cancer Institute’s (NCI) campus at Frederick, Maryland. This campus includes the Frederick National Laboratory for Cancer Research (FNL), the only federally funded research and development center associated with the Department of Health and Human Services. In this position, Dr. Stackhouse oversees NCI-Frederick partnering activities through NCI Collaboration Agreements and CRADAs, and manages all of NCIs intellectual property portfolio. In addition to his role overseeing the technology activities of NCI-Frederick, Dr. Stackhouse manages the Marketing and Information Management Units for the NCI Technology Transfer Center. HE also has played the lead role in establishing the intellectual property parameters and guidelines for several key NCI initiatives that have been handled through the NCI campus at Frederick. Dr. Stackhouse works closely with local economic development groups such as TEDCO, and the Frederick and Montgomery county governments. He received his Ph.D. in Biochemistry from the University of California, Davis. Dr. Stackhouse worked for a major pharmaceutical company and was part of the research team of scientists who discovered the VHL tumor suppressor gene. He has twice received the National Institutes of Health Award of Merit for his outstanding management of the NCI-Frederick Technology Transfer Office. For his efforts on a team that developed the SBIR-Technology Transfer Program for the Institute, he received the 2012 Mid-Atlantic Region Technology Transfer Representative of the Year award.

Oncotarget editorial board members William G Kaelin Jr. and Gregg L Semenza win 2019 Nobel Prize

Oncotarget

Play Episode Listen Later Oct 14, 2019 2:21

PRESS RELEASE https://www.eurekalert.org/pub_releases/2019-10/ijl-oeb101019.php The 2019 Nobel Prize in Physiology or Medicine has been awarded jointly to Oncotarget Editorial Board Members William G. Kaelin Jr. and Gregg L. Semenza for their discoveries of "how cells sense and adapt to oxygen availability", said the Nobel Committee. The pair was named alongside the UK physician-scientist Sir Peter J. Ratcliffe. The Nobel Committee made the announcement Monday at the Karolinska Institute in Stockholm, Sweden and the discoveries have implications for how we understand and potentially treat a range of conditions like cancer, heart attack, stroke and anemia. The Nobel Laureates identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen. Gregg L. Semenza is a professor of Medicine at Johns Hopkins University and Director of the Vascular Research Program at Johns Hopkins Institute for Cell Engineering. Semenza received the Nobel Prize for the discovery of hypoxia-inducible factor 1 (HIF-1), protein, which controls genes in response to changes in oxygen availability. William G. Kaelin Jr., a Professor of medicine at Harvard Medical School and the Dana-Farber Cancer Institute, earned his share of the Nobel Prize for his work investigating a genetic syndrome called Von Hippel-Lindau's (VHL) disease. Kaelin discovered that the VHL protein prevents the onset of cancer and is involved in the oxygen sensing mechanism through its interaction with HIF-1. The awarded mechanism has a fundamental importance in physiology, and has far-reaching implications for the treatment of lw-oxygen health conditions such as coronary artery disease and tumor growth. ### Both William G. Kaelin and Gregg L. Semenza are founding members of Oncotarget, launched in 2010. Oncotarget is a weekly peer-reviewed open access bio-medical journal covering research on all aspects of oncology. The editors-in-chief are Mikhail (Misha) Blagosklonny and Andrei V. Gudkov. About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. Oncotarget is published by Impact Journals LLC. To learn more about Oncotarget, please visit http://www.ImpactJournals.com Media Contact: media@oncotarget.com 800.922.0957

HIF-independent synthetic lethality, Hilary Nicholson, Ph.D., Dana-Farber Cancer Institute

First Author Conversations

Play Episode Listen Later Oct 13, 2019 33:44

On Oct. 7th, 2019, the Nobel Assembly announced that William G. Kaelin, Jr., Dana-Farber Cancer Institute, shares the 2019 Nobel Prize in Physiology or Medicine with Sir Peter J. Ratcliffe of Oxford University and the Francis Crick Institute, and Gregg L. Semenza of Johns Hopkins University, for their discoveries of how cells sense and adapt to oxygen availability. In this episode Tracy interviews Hilary Nicholson, Ph.D., a postdoc research fellow in Kaelin Lab at Dana-Farber Cancer Institute. Hilary talked about her perspectives of Dr. Kaelin receiving the Nobel Prize, how Dr. Kaelin mentors and inspires her, and how her work is built upon this textbook discovery.Hilary is the first author of a recent publication on Science Signaling, "HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species". Kidney cancer is one of the top ten most common forms of cancer in developed countries, and the most common type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The von Hippel-Lindau tumor suppressor gene (VHL) inactivation is associated with ccRCC development, and hypoxia-inducible factor 2 alpha (HIF-2 alpha) is accumulated. Hilary talks about synthetic lethality between CDK4/6 inhibition and VHL loss in two species and across various human ccRCC cell lines in culture and xenografts; The study also shows that HIF-2 alpha was not required for the synthetic lethality. "These findings support testing CDK4/6 inhibitors as treatment for ccRCC, alone and in combination with HIF-2 alpha inhibitors".In addition, Hilary introduced the Science Cheer leaders, a non-profit organization comprised of 300+ current and former NFL, NBA and college cheerleaders pursuing STEM careers.

Cells & Oxygen Availability | Nobel Special | Episode 54 Bonus

The A&P Professor

Play Episode Listen Later Oct 7, 2019 25:25

Host Kevin Patton summarizes the 2019 Nobel Prize in Physiology or Medicine to three scientists "for their discoveries of how cells sense and adapt to oxygen availability." A special bonus episode. 00:41 | Introduction to Bonus Episode 02:00 | Sponsored by HAPS 02:24 | Summary of Discovery 04:13 | Oxygen at Center Stage 05:24 | HIF Enters the Scene08:08 | Sponsored by AAA 08:26 | VHL - An Unexpected Partner 11:37 | Oxygen sHIFts the Balance 13:20 | Oxygen Shapes Physiology & Pathology 15:15 | Sponsored by HAPI Online Graduate Program 15:48 | Our Course 23:46 | Staying Connected If you cannot see or activate the audio player click here. Questions & Feedback: 1-833-LION-DEN (1-833-546-6336) Follow The A&P Professor on Twitter, Facebook, Blogger, Nuzzel, Tumblr, or Instagram! Singing is like a celebration of oxygen. (Björk) 1 | Introduction to the Bonus Episode 1 minute Kevin introduces the bonus episode, explaining that he's sharing the press release for the 2019 Nobel Prize in Physiology or Medicine. It's chunked for clarity. Press release: The Nobel Prize in Physiology or Medicine 2019. NobelPrize.org. Nobel Media AB 2019. Mon. 7 Oct 2019. 2 | Sponsored by HAPS 2 minutes The Human Anatomy & Physiology Society (HAPS) is a sponsor of this podcast. You can help appreciate their support by clicking the link below and checking out the many resources and benefits found there. There are a bunch of 1-day regional workshops scattered all over the continent. There's probably one near you coming up this year (or next)! Anatomy & Physiology Society theAPprofessor.org/haps 3 | Summary of the Discovery 2 minutes 2019-10-07: The Nobel Assembly at Karolinska Institutet has today decided to award the 2019 Nobel Prize in Physiology or Medicine jointly to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza for their discoveries of how cells sense and adapt to oxygen availability. They identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen. 4 | Oxygen at Center Stage 1 minute During evolution, mechanisms developed to ensure a sufficient supply of oxygen to tissues and cells. 5 | HIF Enters the Scene 3 minutes Gregg Semenza studied the EPO (erythropoietin) gene and how it is regulated by varying oxygen levels. In cultured liver cells he discovered a protein complex that binds to the identified DNA segment in an oxygen-dependent manner. He called this complex the hypoxia-inducible factor (HIF). HIF was found to consist of two different DNA-binding proteins, so called transcription factors, now named HIF-1α and ARNT. 6 | Sponsored by AAA 0.5 minutes A searchable transcript for this episode, as well as the captioned audiogram of this episode, are sponsored by the American Association for Anatomy (AAA) at anatomy.org. Searchable transcript Captioned audiogram 7 | VHL - An Unexpected Partner 3 minutes When oxygen levels are high, cells contain very little HIF-1α. However, when oxygen levels are low, the amount of HIF-1α increases so that it can bind to and thus regulate the EPO gene as well as other genes with HIF-binding DNA segments. See figure (if you can't see it, go to https://my-ap.us/35fm0O6). At about the same time as Semenza and Ratcliffe were exploring the regulation of the EPO gene, cancer researcher William Kaelin, Jr. was researching an inherited syndrome, von Hippel-Lindau's disease (VHL disease). VHL is part of a complex that labels proteins with ubiquitin, marking them for degradation in the proteasome. Ratcliffe and his research group then made a key discovery: demonstrating that VHL can physically interact with HIF-1α and is required for its degradation at normal oxygen levels. This conclusively linked VHL to HIF-1α. When oxygen levels are low (hypoxia), HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4). https://my-ap.us/35fm0O6 8 | Oxygen sHIFts the Balance 1.5 minutes It was also shown that the gene activating function of HIF-1α was regulated by oxygen-dependent hydroxylation. The Nobel Laureates had now elucidated the oxygen sensing mechanism and had shown how it works. 9 | Oxygen Shapes Physiology & Pathology 2 minutes Thanks to the groundbreaking work of these Nobel Laureates, we know much more about how different oxygen levels regulate fundamental physiological processes. For example, muscles, blood vessel formation, immunity, RBC production, placenta development, etc. Oxygen sensing is central to a large number of diseases. For example, patients with chronic renal failure often suffer from severe anemia due to decreased EPO expression. See figure (if you cant's see it, go to https://my-ap.us/2LW2cIb) The awarded mechanism for oxygen sensing has fundamental importance in physiology, for example for our metabolism, immune response and ability to adapt to exercise. Many pathological processes are also affected. Intensive efforts are ongoing to develop new drugs that can either inhibit or activate the oxygen-regulated machinery for treatment of anemia, cancer and other diseases. https://my-ap.us/2LW2cIb 10 | Sponsored by HAPI Online Graduate Program 1 minute The Master of Science in Human Anatomy & Physiology Instruction—the MS-HAPI—is a graduate program for A&P teachers. A combination of science courses (enough to qualify you to teach at the college level) and courses in contemporary instructional practice, this program helps you power up your teaching. Kevin Patton is a faculty member in this program. Check it out! nycc.edu/hapi 11 | Our Course 8 minutes This set of discoveries touches on many of the core concepts of our course (the big ideas of our story of the human body). Nobel Prizes are a cultural touchstone that students can related to, and thus increase interest and motivation. Nobel Prizes can be a starting point for discussion the role of science in the context of society and culture. Additional resources: Main page for this prize: my-ap.us/31Wuc3Z Publications Semenza, G.L, Nejfelt, M.K., Chi, S.M. & Antonarakis, S.E. (1991). Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene. Proc Natl Acad Sci USA, 88, 5680-5684 my-ap.us/2ontmP8 Wang, G.L., Jiang, B.-H., Rue, E.A. & Semenza, G.L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA, 92, 5510-5514 my-ap.us/2IxLUD5 Maxwell, P.H., Wiesener, M.S., Chang, G.-W., Clifford, S.C., Vaux, E.C., Cockman, M.E., Wykoff, C.C., Pugh, C.W., Maher, E.R. & Ratcliffe, P.J. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 399, 271-275 my-ap.us/2op4XbP Mircea, I., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J.M., Lane, W.S. & Kaelin Jr., W.G. (2001) HIFa targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science, 292, 464-468 my-ap.us/2IxIf8t Jakkola, P., Mole, D.R., Tian, Y.-M., Wilson, M.I., Gielbert, J., Gaskell, S.J., von Kriegsheim, A., Heberstreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W. & Ratcliffe, P.J. (2001). Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292, 468-472 my-ap.us/35i4wR9 If the hyperlinks here are not active, go to TAPPradio.org to find the episode page. More details at the episode page. Transcript available at the script page. Listen to any episode on your Alexa device. Need help accessing resources locked behind a paywall? Check out this advice from Episode 32 to get what you need! https://youtu.be/JU_l76JGwVw?t=440 Sponsors Transcript and captions for this episode are supported by the American Association for Anatomy. anatomy.org The Human Anatomy & Physiology Society also provides marketing support for this podcast. theAPprofessor.org/haps Distribution of this episode is supported by NYCC's online graduate program in Human Anatomy & Physiology Instruction (HAPI) nycc.edu/hapi Clicking on sponsor links helps let them know you appreciate their support of this podcast! Referrals also help defray podcasting expenses. Amazon TextExpander Snagit & Camtasia The A&P Professor Logo Items Follow The A&P Professor on Twitter, Facebook, Blogger, Nuzzel, Tumblr, or Instagram! The A&P Professor® and Lion Den® are registered trademarks of Lion Den Inc. (Kevin Patton)

Phakomatoses for the FRCR 2A

Songs 4 FRCR: Radiology FRCR 2A Revision

Play Episode Listen Later May 19, 2019 36:25

NF1. NF2. VHL. STURGE-WEBER PHACE. TUBEROUS SCLEROSIS

nf1 vhl

Partner at McKinsey & Company, Kersten Heineke

Vehicle 2.0 Podcast with Scot Wingo

Play Episode Listen Later May 1, 2019 52:03

EP009 - Partner at McKinsey & Company, Kersten Heineke http://www.vehicle2.getspiffy.com Episode 9 is an interview with Kersten Heineke, Partner at McKinsey & Company; recorded on April 26th, 2019. Kersten and Scot discuss a variety of topics, including: Kersten’s career path at McKinsey and the creation of the McKinsey Center for Future Mobility. Differences in car sharing, ride hailing, and other ownership models between Europe and North America. The future of connectivity, including data sharing with cities/municipalities to improve infrastructure. Latest developments with electric vehicles and predicting the rate of customer adoption. Interesting and realistic use cases for autonomous vehicles, including robotaxis/shuttles and long haul trucking. Exploring the transition from AV geo-fencing and regulatory issues to complete autonomous mobility. Be sure to follow Kersten on LinkedIn and keep up with the latest from the McKinsey Center for Future Mobility! If you enjoyed this episode, please write us a review on iTunes! The four pillars of Vehicle 2.0 are electrification, connectivity, autonomy, and changing ownership models. In the Vehicle 2.0 Podcast, we will look at the future of the auto industry through guest expert interviews, deep dives into specific topics, news coverage, and hot takes with instant analysis on what the latest breaking news means for today and in time to come. This episode was produced and sound engineered by Jackson Balling, and hosted by Scot Wingo. Transcript: Scot: [00:51] Welcome to the vehicle 2.0 podcast. This is episode nine and it's being recorded Friday, April 26 2019. Welcome back vehicle 2.0 listeners this week on the show. We are really excited to have Kersten Heineke on the show. Kersten is a partner at McKinsey where he leads the McKinsey Center for Future Mobility in Europe. Uh, there he focuses on connected cars, autonomous driving, shared mobility, as well as the impact of all these developments on organizations across all industries. Welcome to the show. Kersten. Kersten: [01:29] Thank you so much for having me! Scot: [01:31] Cool. Let's, let's start off by kind of understanding how did you end up in the world of mobility? Kersten: [01:37] Well, I started at McKinsey doing a couple of engagements in, in banking initially and then I said, okay, banking is not really what I want to do. I need a physical product, something you it can be passionate about. And I went into automotive and did a couple of projects in an automotive, mostly traditional stuff and growth plans, expansion plans, material cost optimization, you know, the things that a consultancy is famous for and in some ways, and then we started getting more and more requests about automotive from automotive companies going into the new topics. So be that mobility, shared mobility. Also the question on what the impact of connectivity is and then eventually how you can make money with topics like eight us eventually autonomous driving. And we said as McKinsey, we need to approach this from a different angle because these disruptions, I was so significant that we need to build up our own perspective on this. Kersten: [02:32] And we created the McKinsey Center for Future Mobility as a, as a think tank. And I said, yeah, this is what I want to work on. This is much more exciting than trying to find 50 cents and some tiny piece on the car somewhere and trying to optimize the cost. I want to work on the future topics that can change the industry, but also can make our daily lives better. And I got the chance to dedicating 95 to 99%, so almost every, every single minute my day to these future mobility topics, um, started out a bit broader on all of the topics and then eventually when deeper and deeper and concentrated more on autonomous and connected and also shared. Um, and then I was fortunate to be allowed to take over even a leadership role in this McKinsey Center for Future Mobility. And that's sort of been the last couple of years of my career and it's, it's been a great ride so far. Scot: [03:23] Awesome. Uh, and then, um, I imagine, you know, when you, when you have a center that means something within the world of McKinsey, is there, is there kind of a whole team dedicated to this? And, and, uh, also, uh, I know you're in Europe, but do you, do you work with your colleagues and in the u s for example on a lot of this or does all the thought leadership come out of your, Kersten: [03:42] so as always when the Kinsey had set up a virtual organization, if you will, uh, and we do have colleagues working on future of mobility in, in Europe and the US also in Asia where we do have a team in China. We do have a team in Korea and one in Japan, one in India. And we do have a team for South America. And how we structured it is we usually have a couple of partners leading the charge in each of the continents. Also, we do have a couple of partners leading the charge in each of the topics we cover. So in an autonomous connected, electric and shared. And then there's a huge team of consultants around me to dedicate anything between 50% to a hundred percent of their time on these topics. And the entire group across all the continents, across all the topics within McKinsey has roughly 200 people. So it's grown tremendously over the last couple of years and months and we intend to grow it much further simply because the requests we're getting are now also not only from automotive companies, but increasingly so from outside of the automotive space. And we simply need to grow further to make sure we can keep up with the demand. Scot: [04:46] Yeah, that was actually going to be my next question. So, uh, I was going to guess, it's kind of obvious you're probably working directly with the manufacturers and people right in the heart of, of the bullseye there a of mobility. Um, what are some of the other types of customers that are interested in what's going on that or there abouts bid outside of that, that core? Kersten: [05:05] So we have, they have a couple of suppliers as well in there. We're interested, so automotive suppliers, um, there's other companies in the financial space. So can we ensure us that, I wondering how the change in car ownership is going to affect their portfolio. There was a lot of telco companies, um, that, I'm wondering what, what is our play there? How does five g maybe positively affect this? What can we do? The cities getting more and more interested in this and also public transport providers where any kind of mobility service provider interested, there's um, uh, tech companies. There is a even startups that got come to us for advice on sort of the market model and how they can, um, how they can optimize their portfolio and what their go to market strategy is going to be. So it's uh, an energy companies obviously interested in how electric vehicles are going to affect their business. Oil and gas companies similarly interested in this future of mobility, how their businesses impacted. So you could almost say it's, it's everybody, um, who, who somehow makes a product that is being transported somewhere or who was dealing with people that need to get to their respective establishment. So it's a broad, a very broad client group interested in this topic or on these topics. Scot: [06:24] Very cool. So, uh, here on the vehicle 2.0 podcast, the whole foundation is this framework where, uh, and uh, you know, since we came up with this framework, I've discovered everyone has one but, but in ours there's a, we, we look at kind of these four, I think of them as these ways of innovation and I come from the ecommerce industry and what you find is these waves just like waves in the real world, Dave, they kind of compound. Um, so there they're in in their own right, they're powerful, but when they compound, then it just really accelerates the rate of change. Um, so the four we look at our changing ownership models, connectivity, electrification and autonomy. Um, and I wanted to start with the new ownership models because that's how I found you. I was kind of, you know, really beefing up on all these new ownership models and read some of your, your reports that were excellent. So it's just wanted to start there. What's your point of view of where we're going on ownership? Kersten: [07:15] I think that's a, it's an exciting question and it's probably one of the key questions that keep the, some of the OEMs and also us awake at night. The Times I think he'd be honest, I say it depends. So it depends. Are you a, are we talking about people in their 20s or even though any 30th if in major cities while we talking about people in their fifties and sixties that live somewhere in the countryside. And in the end we believe that ownership netnet, um, on the whole is going to go down. At least when you take a look at the developed or the more developed countries, why simply because in cities and even in some use cases you have less and less reason to own a car and owning the car will also become less attractive going forward if you factor in what congestion, if you factor in, uh, probably charge us for production that you're creating. Kersten: [08:03] And at the same time also the increasing offer of subscription models of car sharing. And then as you said before, when you then throw an autonomy into the mix and you make car sharing or he hating autonomous and it becomes even, uh, even easier to use these services instead of owning your car. However, if you're now living in a rural area or if you're living in and the part of the work that this may be, you still still growing strongly and the car ownership, um, fingers will still roll for the next couple of years. So even for the next 10 years, we do see car ownership growing in a white chair and a white part of the world simply because it's either under penetrated or because it will take longer for the offers of car sharing. He hailing and then also autonomy to eventually get to these regions for a multitude of reasons. Scot: [08:52] Got It. Um, what are the, what are the models you're seeing in Europe? So in the U s we're really just starting to see, um, you know, so we had zipcar for a long time and had some adoption, but it's not a great customer experience cause you kind of have to go and find the car. And zipcar launched before phones, so, so it doesn't, you know, it wasn't 100% matched up to kind of a, a phone, a smart phone, kind of a use case. Um, but now we have, uh, get around and Turo, which are kind of like these micro releases. Uh, obviously we have the ride sharing companies. Um, you mentioned subscriptions. I've seen, it seems like the, the German manufacturers are really, really big on the subscriptions. I get, uh, something from Mercedes all the time from around what they're doing. Um, what are the models that you're seeing in Europe now and, and where do you think, you know, is that, are those going to be the models? Are there more models to come? And then do you have any thought of like, let's pick the city kind of a person? What kind of models they'll use? Kersten: [09:50] Europe, we still see a strong growth both in traditional cost sharing. So a couple of, couple of weeks ago it was announced that timeline sort of merging activities and also the other mobility activities. I think this might give another boost to, to Kasha adoption, especially in the major cities where this is already present. Uh, we do see continuous growth and he hailing, uh, there's an exciting discussion now in Germany with uh, Uber will at a certain point B I become, I don't want to say will it be legalized but we'll be more um, uh, allowed or allowed to to run their traditional business model. Also in European cities are in German cities. I think we'll see adoption off or an increasing adoption also in the hailing and ride hailing. Um, we've seen that a lot of adoption also micro mobility. So the e scooters eat kick scooters and bikes mopeds. Kersten: [10:44] And I think that's, that's a market that will grow for the next couple of years quite tremendously because for any trip that is below six kilometers, eight kilometers, that is simply a great option to get around quickly. And, and also with, with a lot of fun because you're enjoying the fresh air and it's just exciting to zip through traffic. Um, but eventually we do believe that most of these models, and probably all of the ones that I mentioned except for micro mobility will converge into autonomous shared mobility. And that can be Robo taxis or Robo shackles depending on the individual's price sensitivity, but also depending a bit on how cities who are regulators and, and that's really what in my mind, this is going to take off tremendously, um, simply because the price that you will pay per kilometer or per mile is going to go down so much that it's going to be super, super attractive to, to go from the type of mobility options. Scot: [11:36] Cool. Um, so when do you think will, from a macro sense, when do you think we'll get to a point when we see car sales kind of like decline? You know, it's been predicted for a while, but my understanding is that, that it hasn't happened quite yet. That, you know, it's definitely slowing, but we haven't seen kind of a decline of new car sales. It seems like that'll be a little harbinger that that were definitely kind of at the tipping point. Kersten: [12:02] It depends a bit on their perspective or if you say, hey, let's take a city like New York or London major city high density there. We do believe that this peak car might happen might already has happened or what happened very quickly because it's increasingly less attractive to own a car. Plus also in the cities there are so many mobility options to get from a to B at this will change. Then the next tier of cities which are a bit smaller, a bit less dense and where you have people commuting still to a certain extent by car. This would probably happen definitely the Twang before 2030 but depending a bit on the timeline for autonomous might happen. People foster and then in the countryside in the more rural areas or in cities that are in the neighborhood of say a hundred to 200,000 people there. It really depends on on how fast these models, these inhaling models and also the autonomous. He headed the models then trickled down to the cities, but eventually, and the can be anywhere between the late 2020s or the early 20, 30 years, it will also happen in these cities. And that's then when Lily, the total number of cars of old cars might be, um, might be impacted much more severely simply because the number of cars in these cities is much higher than if you'd take a look at as a city like New York or London. Scot: [13:20] Yeah. Interesting. Um, and just so I'm clear on your pointless like pick 20, 30, kind of the latest part of your prediction there. You think that's just when we're going to hit the tipping point? It's not that we're going to be kind of 100% change of ownership. It's going to be kind of a, you know, a gradual change over time. Kersten: [13:38] Exactly. Yeah, exactly. I think it will be a very gradual change also because, um, some people might already today be using shared mobility to a large share of the upper mobility they consume. It does still still, it doesn't mean that people ditch that car or sell that car off or don't replace the car. It might seem to be that people keep on adding this mobility consumption of shared mobility to the mobility they consume. Right. And then until people realize that actually the car that they have owned for quite a while, it's not needed anymore. They either sell it or they don't replace it, it might still take a bit longer. Right. Because there's a lot of people who are very much used to, uh, to owning a car. So I, for example, I own a car. I live in Hamburg. I don't really, to be honest, it doesn't really make economic sense for me to own a car, but I'm a, I'm a car guy, red, so I'm passionate about it. I think this will still keep the car sales up for quite a while. And I do think that's a good thing. Scot: [14:30] Very cool. Yeah. So when one thing that's near and dear to our heart here at Spiffy is, uh, there's, what we found is a lot of people are excited about all these models, but they forget some of the basics. Like, like who's going to service these vehicles as they move from, uh, an individual ownership to become more of a fleet or a BTB orientation. You're, you know, the, the utilization goes up, which is good, but that's more miles, more, more, you know, more service needed on these vehicles. Um, and here in the u s at least we have all these factions kind of, you know, starting to square off to, to fight for, you know, kind of the, the, the overall macro management of this. You've got the dealers and OEM's, you've got, um, you know, the new new folks like the Ubers and lifts, you've got car rental companies. Um, and you know, even, uh, other, other kinds of entrepreneurial companies trying to start like a Toro or whatnot. Do you think there's a winner take all in that or, or do you think there's going to be all kinds of different battles going on to figure out who, who operates these fleets of the future? Kersten: [15:31] I think it was going to be different ecosystems and the ecosystem. So going to solve this differently, right? So that will obviously be some people going almost exclusively onto let's say Uber or Lyft platform and using that model for a large share of their mobility requirements, others will still get them mobility contract and the can be a subscription from OEMs. And there will be many other ways that we don't know yet had many of the companies coming up and each of these companies within the ecosystem, we're find its own way to solve this problem. I'll be of the operations of the cleaning of the maintenance of repositioning the vehicle before we have autonomy off. Uh, once the vehicles are autonomous, sending the vehicles to the right locations where the demand is going to be. And in my mind that's a very exciting business opportunity because it combines a couple of very classic capabilities that you need. Kersten: [16:21] Like the rental car companies have today, uh, with, uh, the requirement to use algorithms and new technology to optimize the system. And, uh, in my mind for the customer, it will, it will become better, right? Because today, if you own a car, you need to think about where do I take my car for service? If you live in a coach, part of the world, you need to think about tire changes twice a year. You need to think about repairs. Uh, you need to think about things like parking and so on. But once you take all this away, somebody else will need to integrate this for the customer. And the customer only consumes mobility through the click of a button on the smartphone probably, or whatever we'll be using in 10 years. But, um, this, this sort of change in the entire value chain will be very exciting, um, for the companies and we'll have great opportunities, but at the same time also make the lives of the consumers much easier. Scot: [17:12] Yeah. Yeah. The, uh, you mentioned subscription in your answer there, and I forgot to kind of dig in on that a little bit. Uh, so far the subscription programs have been, they're really interesting and intriguing as a consumer, but they're really expensive, you know. So one of the Mercedes ones for example, um, kind of their premium tier is two or $300 a month, which is, you know, that's, that's, you know, more than two or three x. What, what folks are paying for kind of a lease of a single vehicle. Do you think the, do you think the economics there will eventually work out so that the subscription, uh, is, is cheaper than Elise? Uh, or is it going to take autonomy before we of get to something like that? Kersten: [17:50] I think it might, it might happen before autonomy, especially when when you're real at a certain point in time, be able to have different packages and also combine the subscription to a car with other mobility options. So imagine, um, so in my mind the perfect thing would be a package where pay x zero $6 a month depending on the sophistication of that and that can consume whatever mobility I want to. So I can take a taxi when I need one. I can get a car sharing vehicle over the weekend, I might even get a convertible somewhere or during the week when I, when I really needed, because I'm commuting every day. I have a car that I have guaranteed access to. Right. And I think once you combine these different offerings and also make sure that people don't necessarily or don't use a car that they subscribe to the same way as an old car is at least top because they keep it in their garage for, for um, seven days a week. Kersten: [18:42] And even on the days where they don't use it all the time when they don't use it, then you can cut down the cost of these models because they simply sharing the vehicle using the vehicle's much more efficiently. And then I think we'll go into something like, like what we had a couple of years ago with cell phones when they were minute packages and, and data packages and you had SMS packages and all that, all that stuff before flat rates it. But you will have different packages that you can buy and you will get access to different types of mobility depending on how sophisticated the package to you by is. And I think that's the way when a, it's going to again, become better for the consumer but also become more affordable. And when also the companies that offer this will have a better chance of making money. And again, it takes somebody to manage all of this right and somebody to service the vehicles and take the vehicles from point a to point B. And that's again where these fleet operators and also where the dealers are going to come in because somebody needs to do that. Scot: [19:37] Cool. Um, so let's transition from ownership to connectivity. Um, you know, I always kinda think of connectivity from a consumer perspective because it's a, I own a Tesla model three and it's, you know, it just really enhances the cabin experience to have a live connection to the Internet. The maps get better and you know, you can stream music and just the whole experience is kind of a nice, nice thing. And, um, and then so that's, that's I think when people hear connected car they think about those use cases. What are your thoughts on conductivity and, and you know, is that the right way to think about it or you know, it seems like you think a lot about infrastructure, you know, so municipalities and roads and cities and whatnot, is that really more where it's going to be interesting is the car is sharing their data with the cities. What's your view? Kersten: [20:24] as a ton of applications and a ton of use cases. So obviously it's a question, how can you use the data that is generated by the, by the car to make our lives better by making our last bit of this can be safety related, sharing data with other cars about incidents on the road, sharing data with other cars about, for example, a slippery surfaces or heavy rain or whatever it is to make sure that the driver, me other driver, a couple of a half a mile behind me on the highway or on the next round, the next corner already knows that there is a danger and, and can be crossing that dangerous section much more safely. And this is somewhat alluded to that. That's, that's one thing I think same type of data can also be used to inform cities and municipalities about bad spots on the road repairs that they need to make. Kersten: [21:11] It can help better guide traffic, not only on the way we doing it today with what we have in Google maps and other services, uh, but also, um, uh, making sure the traffic is actively steered in the morning to make the commuting time or reduced the commuting time for everybody. You could almost see then also do, um, uh, charging for, for city toiling based on that. So the faster route you want to do and want to get into the city, the more you have to pay for city toiling, manipulate, okay. With taking irrelevant, this may be going a bit around or is it a bit more congested in we have to pay more, you have to pay less for that. So these are all the options so that you can do this and there's a lot of stuff how to monetize, um, infotainment, upgrading the car. Kersten: [21:52] Anything you can do through over the air updates, what, what Tesla is already be doing quite quite successfully in my mind is a great opportunity to simply improve the user experience in the car because he can make sure that the vehicle that you buy today and you keep for two years or three years is always refresh to a certain extent that you get upgrades and updates to your smartphone. Um, there's a way how you can standardize all the cards that you have and you simply unlock the features by software. So you install the hardware, all of the hardware and the vehicle. You had significantly reduced production complexity and by going, if you will, into an APP store in the day, call you unlock certain functionalities. Is this then also a monetization opportunity for the, for the OEMs. So there's a ton of stuff that can be done in my mind was connectivity, connected cars and these teachers. The question is how do companies need to set up themselves to make sure that they can capitalize on this? And my mind just have a lot of work to be done from this on this end. Scot: [22:52] You think we need like an industry standard, you know how there's kind of like Hipaa for healthcare, which obviously is around privacy but it also is kind of like the format of data. Uh, it seems like if every OEM of has different data they're collecting and ways of delivering it, it's not going to be as useful. Um, are there, uh, I'm not aware of any but you, you probably are closer to it. Are there any in the efforts to standardize that kind of thing? There's a couple of efforts. M Kersten: [23:18] one one does an ISO norm that's being pushed forward in Europe by a consortium of players where they want to agree to share certain set of data accessible obviously in a, in a sanitized and anonymized fashion to um, a lot of companies and they can create use cases on it and then do safety relevant things with the data. That's a great starting point in my mind. Some of the companies also need to start thinking in a way, how can I create end to end use cases from, from the data that the car is collecting and how can I make money with it? But that's a question of also changing the incentivization structures of the companies because they've never, they haven't been trained to think in a way how I can make money off the data that are trained to send money, especially the other OEMs are trained to think, how can I make money with the car and how can I make money the car platform, but not so much with one specific piece of data that I'm collecting and how can I deliver great value to the customer. So yes, it's a, it's a way of standardizing a couple of the interfaces, but also do believe that the thinking and the organization and the way how they incentivize their people use to change in a couple of companies for this big to become even more a reality. Scot: [24:33] Uh, and this is a very tactical kind of connected car thing is I've read a lot of articles around package delivery. I think most of the German OEMs and then a lot of the uh, delivery companies like DHL and Amazon, um, you know, they have a connected car capability where they can deliver packages to your car is I've read this popular in Germany, but I haven't seen any data. Is that, you know, I'll ask since you're right there, have you, have you seen that being used a lot? Kersten: [24:59] I've heard it met a couple of, uh, a lot of companies are working on this and I think it's, it's an exciting new use case. Um, but it's, it's one use case, right? So, and it's a through it. It's a great one. But um, when you think about how much work needs to go into that use case and it's how much trust needs to go into you sort of unlocking or having somebody from VHL unlock your, not only the actual, it doesn't matter what company, right? Unlock your trunk so that they can put in a parcel. There's a lot of work that needs to go into that use case. But I think on that same level, there is not only one use case, there's probably a hundred use cases that will create tremendous value if the companies cooperate and make that happen. But yes, that's a, that's one example of a great boost case that can make everybody's daily life easier and save a lot of delivery costs and also save us a lot of hassle. They're not having to go to the post office to pick up a package. Scot: [25:48] Yeah. Um, let's, uh, let's move on to evs electric vehicles. Uh, you know, looking at the data, it looks like they're starting to get and make it a little bit of a dent in new car sales. Uh, here in the U S we're, we're kind of in the low percentages, like two, 3%. China. I saw some data that there's somewhere between five and 7%. Um, and then the Nordic countries, uh, you know, I think they're, they're really taken off there. Uh, what are you seeing today for evs and then what's your prediction? Uh, you know, when we had some kind of, uh, uh, material tipping point there. Kersten: [26:21] So in our mind, eating isn't, it's all a matter of execution, right? So every, every OEM, every car company is, has either already launched or is it a process of launch, a tremendous amount of electric vehicles over the next couple of months and years. So in our mind, this, this penetration rate of new car sales is going to go up steadily, um, still much more quickly in, in China and in parts of the US like California than in Europe at least in the, in the wider part of Europe. But simply because the OEMs have invested so much money in this vehicle platforms and we'll be launching the vehicles, they will also need to sell them. And I do believe that customer adoption is going up. The question marks that the consumer has around range, around all of the other vehicles around reliability, all these different things, they will, they will go down. Kersten: [27:13] These concerns will become less relevant with the number of vehicles and the number of models increasing. Um, it's a notion of customer education that is already happening today. And, um, quite honestly if you, but if everybody thinks about their daily use of, of a car, how many miles you actually drive. And this question of range isn't really a problem. So for me personally, when I think about my car usage behavior, again I live in the city. There are very few trips that would actually require me to have a range larger than the range of any electric vehicle. And the good thing is you can actually charge it at home. So it also saves you the trip to the gas station. So I do really think that this is going to keep increasing when it comes to penetration. Um, China obviously leading the way and the number of, um, of companies that have popped up there, but also due to the fact that the government is pushing strongly in this helping strongly there. So, uh, in our mind, the, the future of the vehicle is definitely, at least in some use cases and some areas increasingly electric. Scot: [28:14] Cool. It seems like one of the, one of the linchpins is the charging infrastructure and then China, uh, correct me if I'm wrong. It looks like the governments essentially said, hey, we're going to go kind of, you know, build all this out. Um, how about, uh, what's going on in Europe as far as charging structure and then at a 30,000 foot level, uh, you know, it's interesting in the US you have some commercial ones like a charge point then you Tesla's building out there and kind of proprietary network. Um, there's talks of independent companies building more generic kind of, you know, chargers. Uh, what do you see happening there at the macro and the micro level? Kersten: [28:49] Pretty much consistent with how you described it. So we do see a increasing the company is doing that on their own uh, alliances being formed across various OEMs that say, hey, we need to electrify not only in the past cost space, but also in the commercial vehicle space that are um, uh, pushing towards charging infrastructure. Cities are actively promoting it. A retail outlets are putting charging stations in front of the stores and so on. Now in some European cities, I'm always joking about it that I need to get an electric car just because I can then parked directly in front of the store because the charging spots and the parking spots for electric vehicles up closer to the entrance, then the parking spots dedicated to families and to two women with small children. So it's, it's also advantageous to have an electric car from that perspective. Um, but I think we will, we will see that charging infrastructure will remain a certain bottleneck and especially in cities where people don't have the individual parking spots that we remain a problem for the next couple of years, but the penetration of evs is still fairly low, so that that's not the one bottleneck. I think the consumer adoption, especially in some European countries is still the bigger bottleneck then the fact that charging infrastructure isn't available. Scot: [30:02] Okay. Interesting. All right, last topic. I know this is probably the one you're most passionate about is autonomy. Um, uh, we're, uh, you know, the timing's really good on this. I don't know if you had a chance to watch it Monday, but Tesla had their, their autonomy day. Um, there's been a ton of news this week just around autonomy and this is kind of obviously the hot topic. Um, I wanted to start it kind of like, it seems to be the, the most interesting question for me is, uh, you know what, it seems like Tesla has bet pretty big that cameras are going to be kind of how to solve this and, and know a family of cameras that can stitch together a three d scene. Uh, but then everyone else has kind of bet on Lidar. Uh, do you think that's going to be there has to be a winner there or are you think either method could possibly work? Kersten: [30:47] So I think even ever met that can possibly work if, if Tesla manages to get the cameras and the combination of the cameras to a quality that will get them an image that they, or a perspective on what is happening around the vehicle. It is good enough for them to trust the vehicles to go autonomous then, then that's, that's great. Um, I would always in the discussions with many of my clients be more excited about the lighter opinion, but there might be a certain bias to it because a lot of companies are pursuing it. And it, we are, we do know that this is going to work. Um, in the end, either solution that works, doesn't matter if it's lidar based camera based or if there's a third solution that might even require less sends us in the car because it relies a bit more heavily on infrastructure and we might see that or we'll see that in, in parts of China. Um, uh, either solution that is somewhat working, working well, we'll, we'll be, we'll be winning and we'll will see different, different stacks and different combinations in the next couple of years because it's, it's still a new technology and it will take some years for this all to become a fairly standardized and to become similar across different makes and models of legals. Scot: [32:02] Yeah. And then, uh, at, uh, so that was a super micro question. A big macro question is, uh, do you guys have a point of view of wind? We're going to see, you know, real real use of of Avs or, and um, do you think it's going to start in Metros or it's going to be kind of like long haul trucks. Uh, and then what, what's your timeframe? Is this a 2030 thing or is it pushed out past that? Kersten: [32:24] So in our mind, the two most interesting use cases, uh, I'm going to be Robo taxis, roadworks huddled. So basically, um, in cities or urban areas, what will it have? Robo Texas, similar to what other are doing today, drive around. And then the long haul trucking thing where at least the part of the, of the ride that is being done on the highway will be fully automated for the driver not being in the cab anymore. And the navy, the truck stops at a, at a rest stop in the last couple of miles to the depot, to the logistic center are being done with a driver. But you will still save a lot of costs because you take out the driver for the majority of the trip. And that's something we expect to see depending a bit on the exact geography, depending a bit on how much the extent the Geo fencing, but definitely in the early 2020 [inaudible]. Kersten: [33:12] So, uh, this year, next year and the next couple of years with a increasingly more pilots, the geo fencing becoming less rigid, um, more and more cities launching this type or more and more companies launching this type of service in different cities. And I think that by 2025 this will have been, would have become a sizable phenomenon that is recognizable to the naked eye by everybody who was, was driving around in, in, in major cities. And then by 2030 this at least one, when we take a look at our model, there's obviously still a lot of uncertainty at how hot sauce this is going to scale and then how big it is going to be. But we do believe it will be a massive phenomenon anywhere between 2028 and latest 2035. And that will all be possible in all my, we'll go look forward technology because in the end, even if you geo fence, I'm a city and then anything that the geo fence is technically level four, not level five, um, you can still get a majority the lion's share, 80%, 90% of the, of the use cases of the trips. And thus the market size is just tremendous human without being able to drive autonomously into, uh, into the woods somewhere close to a city or, or I'm taking every single trip that is theoretically conceivable in an autonomous fashion. Scot: [34:30] Um, and then, uh, but again, you know, you're thinking that they'll, there'll be, by that time, I'll pick the further south 20, 35 it'll, it'll be common to see it happening, but we're not going to be kind of like 100%. It's going to be more of one of these gradual kind of changes that, you know, certain certain use cases. Kersten: [34:49] Absolutely. I think when, let's, let's roll it forward and let's say 2030 arrived in 20, 30 years, sort of mass adoption of Ab. Even then if you have 20%, 30% of all passenger miles driven in a city in driven autonomously and be driven by Robo taxis, a robot shovels, they would always already be a huge penetration. And for some cities that would be up all the major cities. That would be a market of anywhere between 15 to 25, $30 billion a year in terms of a revenue generated by the, by the customers, by the mobility users. So a sizable market, even without every single kilometer being done autonomously. And I do thing that we will still see cars being driven by people for the next, um, uh, 50 and 20, even much longer years. Maybe if it's just for recreational purposes or in rural areas or because people still like to drive themselves. Um, but this wasn't ever, at least not in my lifetime. This will not go away. Scot: [35:48] Yeah. People still ride horses, not that many minutes. Definitely a hobby. Um, uh, who another intersting. Just kind of like the fleet question. We have a lot of people obviously trying to, this is such a big pie that that they're, they're trying to go after this thing. You have the, the OEMs, you have Google with Waymo, Uber lift, uh, and then a bunch of other kind of players do, do you think there's a certain winner there or uh, do you have a prediction on that? Kersten: [36:24] So we do believe it will be ecosystems in the end that will be, we'll be winning this right then the question is who is going to dominate which ecosystem and who's going to only play a minor role. And our mind Waymo has a lot of, a lot of reasons why. There's a lot of reasons why we, why we would believe that Waymo is going to be one of the key players. They are fairly early head off of many competitors, been doing a great job, spending a lot of money and they almost, they have an amazing team. Um, but there's also a couple of other companies, either the Oems, we talked about the rental car companies and companies who need to do the servicing of the feeds. There's the mobility platforms we have today. Companies like Uber and Lyft who have a lot of um, uh, a lot of users already and work generating a lot of traffic and creating a lot of revenue. Kersten: [37:13] So I think all of these companies will play a major role in these ecosystems. The question is a bit how much, how profitable are the different steps of the value chain going to be? And in our mind the closer you are to the, to the mobility user, um, how closer you are to this platform game of actually matching supply and demand and sort of owning the business, the more likely you are to create margins that are in excess of 10%, 15%. And that's why these areas are probably more more interesting. Um, CMS when you are one of the first companies to have a functioning ab kit that is going to be super profitable, so sizeable but also profitable. And, and I guess there is, there is going to be a play for all of the companies you mentioned. Some of them will just have a higher profitability and we do believe that this higher profitability is going to be, uh, um, closer to the customer or the closer you are to the customer that are more profitable. Scot: [38:08] You know, we, we had, uh, uh, this is a little bit out there, but we had a guest on the show and, and their logic path was if you kind of flash forward to autonomy, um, now, uh, now, you know, we don't, what differentiates a vehicle? You don't really care. It's kind of like, you know, when you summon an Uber, when you do your, you're calling an e hailing, you know, you don't really kind of say, well, I really would prefer a model, you know, a widget a versus widget B. They kind of commoditizes the vehicles. Um, and then since you're, you're not really having to pay attention driving his, his theory was, you know, you could almost see people choosing, um, what, what they take based on the interior experience. So, you know, maybe there's, maybe there's almost like a Netflix or Robo taxi or a, you know, if you're, if you're going to be on, let's say you're going to do a three hour ride and you're really just want to be entertained or another one would be, maybe you're going to work on the way and just having the cabin outfitted for those specific needs is what's going to drive things. Scot: [39:09] I thought that was just a, it kind of tilted everything on it said, and I thought that was an interesting perspective. What do you have any gut reaction to that? Kersten: [39:17] Agree. I think the, the factors that determine which product to choose would totally changed from today. So power train, uh, as we have today for many, for many cock customers, this is a super relevant thing and brand is a super relevant thing. Interior design, the way that US field and the [inaudible] make you feel and so on. That's important in my mind all going to go away with chef. And the fact that the factors you said are going to be super important, but it's also going to be important to how clean is the car. We're going to be all foster, they're going to come. And then also, especially in the initial years of autonomy and, and when I mean initial deals, I'm talking at least until 20, 30, the way how safe the car makes me feel and the way how confident the system is driving and how much the system feels like a human driver. Kersten: [40:00] That is also going to be a major driver on, on what systems will be successful in what systems won't be. And from a perspective of the operator, I want to, if I'm an operator of an ab fleet, I want to make sure that sort of my total cost of, of users or total cost of ownership is, is as good as possible. And that also factors in again how well the system is performing, how many hours a day I can actually drive autonomous. The uh, and then also how fast the vehicle gets from ADB. Because some abs might simply be a bit slower in the beginning. And thus the vehicle that has a higher performance or higher confidence to drive a bit faster to drive, like, like humans would be driving. We'll also get you a better, uh, a better profitability as an ag operator. So depending on, on where you, where you said this will, these factors will change dramatically, but there are still a couple of factors that are close at least to the traditional, if you will, OEM and automotive capabilities. Scot: [40:55] Hmm. Um, uh, you know, I'm sure you saw Tesla, they talked about having thousands or tens of thousands of potential robo taxis by next year. I think they're way ahead of the regulatory thing. And I want to talk to you about regulatory stuff, but then, you know, one of the interesting things that I saw was he talked about cost per mile and a current ride share, if you look at the TCO, is somewhere between two and $3. These are their numbers. You probably have your own view. But then he, you know, the thing that I think that was shocking is he said the Robo taxi, uh, because they are an EDI platform and, and, and whatnot, uh, we'll get to kind of 18 cents a mile. So, um, do you, do you think that's, do you agree with some of that math that, that, that we're going to really get the cost per mile or kilometer so low that, that that is one of the big catalysts for driving adoption of this? Kersten: [41:48] I'm not sure about 18 cents. Right. But we will get the cost down to something that is very close to what we see today in public transport, especially when you're thinking about pooling rather than taking an, a new autonomous, uh, vehicle. Um, so robo taxis would definitely be cost competitive, a price competitive to owning a car and Robo shuttles will be cost competitive to going on some kinds of public transit, which will a, and that's, that's by the way, one of the reasons that our model, why, um, why we do believe that this market is going to be so massive, right? Because I'm, we always think about what is the best next best alternative. That's a question of convenience, but in the end it's also a question of price. And if you offer to somebody a chance to be driven around from ADB at a cost competitive to taking your own vehicle, you don't have to worry about parking the vehicle, you don't have to worry about actually driving and you consider the back and work or watch a movie or do whatever, then the switching behavior is going to be, it's going to be a fairly intense and we will see a lot of people switching. Kersten: [42:53] And that's why we, we do believe that this market is going to be so huge. Scot: [42:58] It seems like you guys have put a lot of thought into these different ecosystems. Um, what do you know when you're sitting there in front of these, the, the OEMs? Uh, you know, one of the things here in the u s is they have these big dealer networks and you know, it's pretty easy to see a day where, where you don't really need that most, you know, if you ask a consumer, you know, uh, there, there's these funny TV ads where, you know, someone has to go buy a car and it's Kinda, you know, it's like the last thing they'd rather go get a root canal than it can kind of go buy a new car. Uh, so, so consumers don't love the existing, you know, experience of buying a car. Um, and then the service model for most Oems, you know, there's, there's luxury ones that that seemed to have cracked the code here. Uh, they don't live that either. What's that mean for kind of OEMs and dealers and this, this kind of future where we have robo taxis and different ownership models and all that stuff. Kersten: [43:50] So, I mean, we talked earlier about half the ownership structure is going to change, right? And then for sure we are still going to see Carl and this shape is a very relevant thing for the next 20 years, 20 plus years. Right. So the diva, we'll, we'll always stay. We'll always stay relevant. The question is just how does the role of, would you then need to change as in when we think about more online sales or more consumers that are getting all their information online and only having one point something visits per car per purchase rather than four or five in the past or the role of the dealer needs to change and also the retail experience to a certain extent needs to change. Do you think if we, if you figure all that in and if we think about how the ideal car purchasing journey look from a customer perspective and the dealer will still have a role in expanding the car, providing a test drive, delivering the car and obviously also in the whole servicing of the vehicle. Kersten: [44:44] Um, it's just a question of how you change this, um, this dealer network structure and also how you change the role of the dealer to accommodate a four. The fact that the whole car purchasing process is changing dramatically. And before the fact that at least in some geographies the number of cars owned will actually go down. But we talked extensively about all the fleet management things and also if we think about a different ownership models where people are using the subscription and so on. And there is definitely different roles for the dealers that need to be or different different activities that need to be done. And the dealers are in my mind, one of the most natural owners to to step in and do this. It would just be a change of the business model to a certain extent, but there will still be a requirement of a strong requirement for a diva like association with a new line of business. Scot: [45:31] Yeah. I guess one question is, you know, so, so I come from the ecommerce world and uh, one of the clear losers in this big kind of digitalization that we're seeing, uh, is, is traditional malls. Uh, and I don't, I guess cause you feel it in Europe as well, it's more of the high street retailers is what you guys would say. Um, but you know, that's, that's clearly we'll, we'll see like 30% of the malls in the u s go out of business because they just kind of don't offer a competitive offering. Do you think there'll be a big loser as we look at kind of these trends in the, in the ecosystem of mobility? Is there some are, I guess it's hard to be a consultant and say loser, but uh, let's say what industries most at risk by these changes we're talking about? Kersten: [46:14] So I think it's not an entire industry that's most at risk or an entire hypoplasia that's most at risk. I think for every single cause. This is, this is huge one and the whole ecosystem, the whole value chain is different. And at the same time it is still complex because cars are more complex and smartphones, just as an as an example, right? So think there won't be, entire industries are entire archetypes of players that we'll be using. They will simply be a couple of companies within each archetype. It will struggle either because they attack the change too late or because they didn't invest enough money or because they didn't have the right people or whatever. But that's, that's how I, how I would see it. And probably we will see a certain conservation and some parts of the market and we will see a change in the margin structure of the industry and also the revenue structure of the industry. But I don't think that entire industry is, we'll, um, we'll will cease to exist, um, simply because again, the potential is so huge. And Net net this will actually increase the number of miles driven and the mobility consumed because mobility will get easier to access, um, or to be accessed by the consumer and it will also be cheaper for the consumer. So therefore the total consumption is going to go up. And then the total pie if you will, it's going to get larger. It's just a different distribution of the pie. Scot: [47:30] Cool. Um, so I know you're super busy and we're getting right up against time. A couple of last questions. Any other thoughts or topics on your mind that we didn't cover about where you, where you see things going in the next five to 10 years? Kersten: [47:45] One, one thing that's, that's interesting to discuss. It's a bit what is going to happen to traffic into congestion in cities when you think about this. Because we take a look at the data today and we'll take a look at it, especially ride sharing and e hailing. It actually creates more traffic because it is more convenient for users to access and people are actually substituting trips that they would have otherwise driven by a bus or walked or not have taken by using, by using, for example, Uber or Lyft or something else. Right? And, um, the question is what can be done, especially by cities to make sure that this is, um, this doesn't increase congestion even further. And this doesn't completely stalled traffic. And in my mind, uh, cities have a very important role here and need to play a very active role and making sure that they shape this mobility transition for the respective city and think about what their target function is and how they want to optimize mobility and how would they want to make use of these technologies. Because in our mind, in the end, if you put, uh, autonomous shared electric mobility into the cities and this will make everybody's lives better if it is managed well. And that's for me something where one or the players need to cooperate but to also the cities need to play a very active role to make this happen. Scot: [49:00] Do you see a point if we kind of play that out? You know, a lot of folks are talking about, you know, cities just changing their design, getting rid of the parking and the roads become more, you know, maybe you have one lane for Avs and then a lot of more for, for like scooters and bikes. And, uh, do you, do you see a future there where we have these kind of cities that are drastically changed by these trends? Kersten: [49:24] Absolutely. I think if you, if you, if you are a city or the mayor or somebody in the transportation planning department and you take a look at the entire traffic pattern in the city and how people who want to get from a to B and how you want people to get from a to B, um, you could, you can redesign the city, you can take entire city, city blocks and areas where you don't a low cost at all, where you basically limit morbidity to either micro mobility or some type of public transport. Um, and yes, I think there's a tremendous opportunity, um, that by reshaping the way how the existing road infrastructure is used, we can accommodate more people and make mobility's cleaner and faster for everybody. Awesome. Two more economical at the same time. Scot: [50:10] Yeah. It's gonna be fun to see how all this plays out over the next 10 years. Um, so I, it's a little bit, yeah. One last question. I've really enjoyed reading a bunch of the content that, that you and your group put out there for listeners, where can they go to, uh, to learn more about your, your and McKinsey's thoughts around these topics. Kersten: [50:29] So we do have a presence of the McKinsey Center for Future Mobility at mckinsey.com. When you go to mckinsey.com and search for EMCFM, the McKinsey Center for Future Mobility, you will find our publications. You can also obviously stalk me on Linkedin if you want to. Um, I try to post all the new research that we have and if there are any other questions, obviously feel free to reach out to us. Um, we do have a ton of stuff available. Scot: [50:54] Awesome. So look forward to seeing, uh, there any, any uh, reports coming out that we should be aware of. Kersten: [51:00] We are working on a, on a major piece on autonomy and uh, the potential of Robo taxis from, uh, from, uh, from an adoption standpoint and also what the size of that value pool is going to be. That's something we should be launching in the next couple of weeks. I saw and I think that's going to be sparks. I'm exciting discussions about the market sizing. Scot: [51:19] Awesome. I look forward to seeing that. Uh, and we really appreciate you taking time to be on the Vehicle 2.0 Podcast. Kersten: [51:25] Again, thanks so much for having me. It's been an amazing experience and all the best for your next podcasts and guests.

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Aitor Sarasua: 'eman hegoari iparra, eta iparrari hegoak'

Hitza Jolas

Play Episode Listen Later Mar 17, 2019 9:54

'Hegotik Iparrerantz' bidaiatu zuen txoriaren alde bertsoak, kantuak eta antzerkia Aretxabaletan. Bildutako sosak VHL gaitzari aurre egiteko erabiliko dira....

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Episode 133: 2019 NHL Draft Preview

Leafs Geeks Podcast: Toronto Maple Leafs

Play Episode Listen Later Feb 3, 2019 73:58

Cam Robinson from Dobber Prospects joins me this week to break down some of our favourite players from the 2019 NHL Draft.Here's the link to my Patreon if you want to help support my work ($5 a month gets you a bonus episode every week!) www.patreon.com/iantulloch3:15 – Jack Hughes (5'10 168lb C, USNDP, USHL) 5:21 – Kaapo Kakko (6'2 190lb RW, TPS, Liiga)7:34 – Vasili Podkolzin (6'1 190lb RW, SKA, VHL)11:34 – Philip Broberg (6'3 203lb LHD, AIK, Allsvenskan)14:45 – Trevor Zegras (6'0 168lb C, USNDP, USHL)16:48 – Cole Caufield (5'7 157lb RW, USNDP, USHL)19:35 – Bobby Brink (5'10 165lb RW, Sioux City, USHL)22:50 – Jakob Pelletier (5'9 161lb LW, Moncton, QMJHL)25:00 – Arthur Kaliyev (6'2 190lb LW, Hamilton, OHL) 27:41 – Anttoni Honka (5'10 176lb RHD, JYP, Liiga)31:25 – Mikko Kokkonen (5'11 190lb LHD, Jukurit, Liiga)33:37 – Ville Heinola (5'11 176lb LHD, Lukko, Liiga)35:22 – Lassi Thomson (6'0 187lb RHD, Kelowna, WHL)37:35 – Victor Soderstrom (5'11 176lb RHD, Brynas, SHL)40:23 – Nils Hoglander (5'9 185lb LW, Rogle, SHL)43:04 – Albin Grewe (6'0 176lb RW, Djugardens J20, SuperElit)46:14 – Moritz Seider (6'4 198lb RHD, Adler, DEL)48:49 – Alex Newhook (5'11 190lb C, Victoria, BCHL)53:17 – Spencer Knight (6'3 198lb G, USNDP, USHL)57:26 – Brett Leason (6'5 198lb C, Prince Albert, WHL)1:00:40 – Samuel Fagemo (6'0 194lb RW, Frolunda, SHL)1:02:38 – Some of Cam's favourites: John Beecher, Jamieson Rees, Ryan Johnson, Billy Constantinou, Nicholas Robertson, Sasha Mutala1:04:51 – Philip Tomasino (6'0 181lb C, Niagara, OHL)1:05:53 – Pavel Dorofeyev (6'0 163lb LW, Magnitogorsk, MHL)1:06:41 – Yegor Afanaseyev (6'3 203lb F, Muskegon, USHL)1:07:07 – Nolan Foote (6'3 187lb LW, Kelowna, WHL)1:07:46 – Thomas Harley (6'3 183lb LHD, Mississauga, OHL)1:08:49 – Antti Saarela (5'11 176lb LW, Lukko, Liiga)1:10:03 – Kirill Slepets & Nando EggenbergerMusic by Punch DeckLearn more about your ad choices. Visit megaphone.fm/adchoices

hamilton ska adler nhl draft niagara kelowna tps mississauga ohl prince albert whl moncton aik ryan johnson rw sioux city allsvenskan jack hughes shl lw muskegon cole caufield qmjhl ushl kaapo kakko cam robinson bchl jyp liiga rhd philip broberg mhl jakob pelletier vhl vasili podkolzin 2019 nhl draft lhd magnitogorsk frolunda lassi thomson nolan foote rogle lukko victor soderstrom

LeagueArena.com Presents VHL Draft LIVE

Play Episode Listen Later Oct 9, 2009 120:49

JOIN MATTMICKO AND BROKENPOST LIVE FOR THE VHL DRAFT!!!! (IT WILL BE LIVE)

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LeagueArena.com Presents VHL Draft LIVE Part 2

Play Episode Listen Later Oct 9, 2009 86:12

Just in case

draft vhl

LeagueArena.com Presents VHL Draft LIVE

Play Episode Listen Later Oct 9, 2009 120:49

JOIN MATTMICKO AND BROKENPOST LIVE FOR THE VHL DRAFT!!!! (IT WILL BE LIVE)

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LeagueArena.com Presents VHL Draft LIVE Part 2

Play Episode Listen Later Oct 9, 2009 86:12

Just in case

draft vhl

LeagueArena.com Presents VHL Draft LIVE

Play Episode Listen Later Jul 19, 2009 98:29

Listen to the LeagueArena.com VHL Draft Live with your hosts MattMicko, and Gong X Show. HEAR THE PICKS HERE FIRST

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LeagueArena.com Presents VHL Draft LIVE