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Come find Elvis and Barb in 2025! Vision 21 at Caesar's Palace in Las Vegas - January 16-18 (https://www.nadl.org/vision-21) Cal Lab Meeting at the Swissôtel in Chicago February 20-21 (https://cal-lab.org/) LMT Lab Day Chicago in the IVOCLAR BALLROOM - February 20-22 (https://cal-lab.org/) IDS 2025 in the EXOCAD booth in Cologne, Germany - March 25-29 (https://www.english.ids-cologne.de/?_gl=1*10atn6b*_ga*NzI2NTMzNjguMTcyOTQ0NDMzMA..*_ga_F5WGQ8B9S7*MTcyOTk4ODM5Ny4zLjEuMTcyOTk4ODg5Mi42MC4wLjA.) When choosing implant components, there are a lot of options out there. You COULD go OEM, but there is a lot to be said about cost and workflow when going with a third party option. How do you choose which option to go with? This episode we discuss why two people have chosen DESS Dental Solutions (https://www.dess-usa.com/?srsltid=AfmBOop0MkxSp_PWNT-yIBXnCm-22lVq4PeYO5AXuhvZdLfC2Zi0nMDR) for their implant workflow. Jimmy Stegall has been educating in our industry for years. Now he has opened his own company to help educate more called Here To Serve Dental (https://heretoservedental.com/). Saro Hatzakortzian is the CEO of Alien Milling Technologies (https://www.alienmilling.com/?srsltid=AfmBOopkvXYwLdILQLUhO3gnz08osI8m7pwVPTgt0LeyT0m2Q1nCqftx) that mill many different situations on probably every platform available. After a brief update on what they have been up to since their last episode, Jimmy and Saro get into why they use DESS for their cases. We talk about MUAs, ti bases, screws, drivers, millable blanks, overdenture abutments, and so much more. Hear it from people that use them and not sell them. Molar City: https://youtu.be/uDGVFDcgKbM?si=70rnaLl46IHt4zkq Listen to John Wilson from Sunrise Dental Lab (https://www.sunrisedentallaboratory.com/index.php) and take your own lab to the next level by getting in on some of Ivoclar's End of the Year deals (https://www.ivoclar.com/en_us/campaigns/ivoclar-equipment-promotions-2024?utm_source=website&utm_medium=content_tile&utm_campaign=equipment_promo) on equipment. If you are looking for your first or looking to expand your capabilities, Ivoclar (https://www.ivoclar.com/en_us) has just what you need at a time where it's best to invest. Head over to Ivolcar.com or contact your local rep for all the deals today. Don't let the new year come thinking you should have bettered your lab. Special Guests: Jimmy Stegall and Saro Hatzakortzian.
Episode 140I spoke with Professor Jacob Andreas about:* Language and the world* World models* How he's developed as a scientistEnjoy!Jacob is an associate professor at MIT in the Department of Electrical Engineering and Computer Science as well as the Computer Science and Artificial Intelligence Laboratory. His research aims to understand the computational foundations of language learning, and to build intelligent systems that can learn from human guidance. Jacob earned his Ph.D. from UC Berkeley, his M.Phil. from Cambridge (where he studied as a Churchill scholar) and his B.S. from Columbia. He has received a Sloan fellowship, an NSF CAREER award, MIT's Junior Bose and Kolokotrones teaching awards, and paper awards at ACL, ICML and NAACL.Find me on Twitter for updates on new episodes, and reach me at editor@thegradient.pub for feedback, ideas, guest suggestions. Subscribe to The Gradient Podcast: Apple Podcasts | Spotify | Pocket Casts | RSSFollow The Gradient on TwitterOutline:* (00:00) Intro* (00:40) Jacob's relationship with grounding fundamentalism* (05:21) Jacob's reaction to LLMs* (11:24) Grounding language — is there a philosophical problem?* (15:54) Grounding and language modeling* (24:00) Analogies between humans and LMs* (30:46) Grounding language with points and paths in continuous spaces* (32:00) Neo-Davidsonian formal semantics* (36:27) Evolving assumptions about structure prediction* (40:14) Segmentation and event structure* (42:33) How much do word embeddings encode about syntax?* (43:10) Jacob's process for studying scientific questions* (45:38) Experiments and hypotheses* (53:01) Calibrating assumptions as a researcher* (54:08) Flexibility in research* (56:09) Measuring Compositionality in Representation Learning* (56:50) Developing an independent research agenda and developing a lab culture* (1:03:25) Language Models as Agent Models* (1:04:30) Background* (1:08:33) Toy experiments and interpretability research* (1:13:30) Developing effective toy experiments* (1:15:25) Language Models, World Models, and Human Model-Building* (1:15:56) OthelloGPT's bag of heuristics and multiple “world models”* (1:21:32) What is a world model?* (1:23:45) The Big Question — from meaning to world models* (1:28:21) From “meaning” to precise questions about LMs* (1:32:01) Mechanistic interpretability and reading tea leaves* (1:35:38) Language and the world* (1:38:07) Towards better language models* (1:43:45) Model editing* (1:45:50) On academia's role in NLP research* (1:49:13) On good science* (1:52:36) OutroLinks:* Jacob's homepage and Twitter* Language Models, World Models, and Human Model-Building* Papers* Semantic Parsing as Machine Translation (2013)* Grounding language with points and paths in continuous spaces (2014)* How much do word embeddings encode about syntax? (2014)* Translating neuralese (2017)* Analogs of linguistic structure in deep representations (2017)* Learning with latent language (2018)* Learning from Language (2018)* Measuring Compositionality in Representation Learning (2019)* Experience grounds language (2020)* Language Models as Agent Models (2022) Get full access to The Gradient at thegradientpub.substack.com/subscribe
After such a great response to our recent episode on the topic, our hosts, Dom and John, revisit the topic of GLP-1 Analogue development and the role bioanalysis plays in this relatively new and popular topic. In the words of John, “Everyone else is talking about this; why shouldn't we?” And wow, do they have a lot to say about it on this second pass at the advances being made in this ever-growing and ever-changing field. The guys talk about the latest developments in the GLP-1 Analogue space, KCAS Bio's experience with GLP-1 Analogs, options when choosing the right technology for these studies, some of the challenges associated with the LC-MS Approach, the options available around Ligand Binding Assays for GLP-1 Analogues in tissues, and whether there may even be value in conversation about a Hybrid LC-MS approach!“The Weekly Bioanalysis” is a podcast dedicated to discussing bioanalytical news, tools and services related to the pharmaceutical, biopharmaceutical and biomarker industries. Every month, KCAS Bio will bring you another 60 minutes (or so) of friendly banter between our two finest Senior Scientific Advisors as they chat over coffee and discuss what they've learned about the bioanalytical world the past couple of weeks. “The Weekly Bioanalysis” is brought to you by KCAS Bio.KCAS Bio is a progressive growing contract research organization of well over 250 talented and dedicated individuals with growing operations in Kansas City, Doylestown, PA, and Lyon, France, where we are committed to serving our clients and improving health worldwide. Our experienced scientists provide stand-alone bioanalytical services to the pharmaceutical, biopharmaceutical, animal health and medical device industries.
Sep 4, 2024 – Gold is now up over 20% year to date and silver is just slightly behind at over 18%. Amazingly, both precious metals are outperforming all the major US indices. Today, we discuss some of the drivers of the current bull market in gold and silver...
In this episode, my guest is Dr. Gabrielle Lyon, D.O., a board-certified physician who did her clinical and research training at Washington University in geriatrics and nutrition. She is also an expert in how diet and exercise impact muscle and whole-body health and longevity. Dr. Lyon is a bestselling author and public educator. We discuss how healthy skeletal muscle promotes longevity, brain health, disease prevention, ideal body composition, and the health of other organs and bodily systems. She makes specific nutritional recommendations for optimal health: what to eat, how much to eat, the timing of meals, the essential need for adequate quality protein (including animal and plant-based options), supplementation, and how our dietary requirements change with age. She explains why specific types of resistance training are essential to build and maintain muscle and overall metabolic health. She also describes how to include resistance training as part of your exercise regimen — regardless of age or sex. She also provides specific mindset tools to encourage sustained adherence to healthy eating and exercise practices. Women and men of all ages will benefit from Dr. Lyon's practical, evidence-based protocols to improve muscle and whole-body appearance, function, and health. Access the full show notes, including referenced articles, books, people mentioned, and additional resources at hubermanlab.com. Andrew's New Book Protocols: An Operating Manual for the Human Body: https://protocolsbook.com Thank you to our sponsors AG1: https://drinkag1.com/huberman Maui Nui Venison: https://mauinuivenison.com/huberman Levels: https://levels.link/huberman Helix Sleep: https://helixsleep.com/huberman InsideTracker: https://insidetracker.com/huberman Timestamps 00:00:00 Protocols Book; Dr. Gabrielle Lyon 00:03:23 Sponsors: Maui Nui, Levels & Helix Sleep 00:07:40 Skeletal Muscle & Longevity 00:11:25 “Under-muscled”, Leucine & Muscle Health 00:15:55 Muscle Health 00:19:45 Tool: Carbohydrate Consumption & Activity, Glycogen 00:25:14 Tools: Nutrition for Healthy Skeletal Muscle, First Meal 00:31:57 Sponsor: AG1 00:33:46 Quality Protein, Animal & Plant-Based Proteins 00:37:36 Dietary Protein Recommendations, Meal Threshold 00:41:19 Muscle Health & Aging 00:46:02 Supplements & Creatine; Dietary Protein 00:50:07 Tool: Dietary Protein Recommendation; Gout & Cancer Risk 00:52:43 Effects of Dietary Protein & Exercise on Body Composition 01:03:06 Thermic Effects, Protein 01:05:02 Sponsor: InsideTracker 01:06:14 Protein & Satiety, Insulin & Glucose 01:12:04 Tool: Older Adults, Resistance Training & Dietary Protein 01:17:48 Dietary Protein, mTOR & Cancer Risk 01:21:36 Muscle Span & Aging, Sedentary Behaviors 01:24:00 Mixed Meals, Protein Quality, Fiber 01:29:21 Inactivity & Insulin Resistance, Inflammation 01:38:43 Exercise & Myokines, Brain Health & BDNF 01:44:11 Tool: Resistance Training Protocols, Hypertrophy, “High Ground” 01:52:51 High Ground Exercises; Tendon Strength; Training Duration, Blue Zones 01:58:19 Movement, Exercise & Older Adults 02:04:25 Tool: Protein Timing & Resistance Training; VO2 Max, Aging, Blood Work 02:11:13 Supplements: Creatine, Urolithin A, Whey Protein, Fish Oil, Collagen 02:20:18 Fasting, Older Adults; Tool: Meal Timing 02:25:18 Animal Proteins & Dairy; Organ Meats, Vegan; Magnesium, Zinc 02:30:59 Medications & Muscle Health 02:32:49 Obesity & GLP-1 Analogs, Ozempic, Mounjaro, Skeletal Muscle 02:40:48 Benefits of Skeletal Muscle & Aging 02:42:16 Tools: Nutrition & Resistance Training for Muscle Health 02:45:44 Mindset Tools: Standards vs. Goals; Vulnerability Points 02:52:00 Mindset Tools: Neutrality; Health & Worth 03:01:14 Zero-Cost Support, Spotify & Apple Follow & Reviews, YouTube Feedback, Social Media, Neural Network Newsletter, Protocols Book Disclaimer
In this episode, my guest is Dr. Casey Means, M.D., a physician trained at Stanford University School of Medicine, an expert on metabolic health and the author of the book, "Good Energy." We discuss how to leverage nutrition, exercise and environmental factors to enhance your metabolic health by improving mitochondrial function, hormone and blood sugar regulation. We also explore how fasting, deliberate cold exposure and spending time in nature can impact metabolic health, how to control food cravings and how to assess your metabolic health using blood testing, continuous glucose monitors and other tools. Metabolic dysfunction is a leading cause of chronic disease, obesity and reduced lifespan around the world. Conversely, improving your mitochondrial and metabolic health can positively affect your health span and longevity. Listeners of this episode will learn low- and zero-cost tools to improve their metabolic health, physical and mental well-being, body composition and target the root cause of various common diseases. For show notes, including referenced articles and additional resources, please visit hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Maui Nui Venison: https://mauinuivenison.com/huberman Eight Sleep: https://eightsleep.com/huberman AeroPress: https://aeropress.com/huberman InsideTracker: https://insidetracker.com/huberman Momentous: https://livemomentous.com/huberman Timestamps 00:00:00 Dr. Casey Means 00:02:18 Sponsors: Maui Nui, Eight Sleep & AeroPress 00:06:32 Metabolism, Metabolic Dysfunction, Medicinal Blindspot 00:14:17 Trifecta of Bad Energy 00:24:02 Western Living, United States, Specialization & Medicine 00:27:57 Insulin Resistance, Tool: Mitochondrial Capacity & Exercise 00:33:33 Sponsor: AG1 00:35:03 Tools: Walking & Glucose; Frequent Movement 00:44:25 Tools: Exercises to Improve Mitochondrial Capacity; Desk Treadmill 00:51:18 Soleus Push-Ups & Fidgeting, Non-Exercise Activity Thermogenesis (NEAT) 00:57:14 Sponsor: InsideTracker 00:58:21 Tool: Blood Test Biomarkers, Vital Signs & Mitochondrial Function 01:11:16 Navigate Medical System & Blood Tests, Consumer Lab Testing 01:16:46 Tool: Environmental Factors; Food, Life as a Process 01:21:58 Tool: Ultra-Processed vs. Real Food, Obesity, Soil & Micronutrients 01:32:03 Ultra-Processed Foods: Brain & Cellular Confusion 01:39:10 Tools: Control Cravings, GLP-1 Production, Microbiome Support 01:51:42 Ozempic, GLP-1 Analogs; Root Cause & Medicine 02:00:54 Tool: Deliberate Cold & Heat Exposure, Brown Fat 02:07:27 Tool: Intermittent Fasting & Metabolic Flexibility; Insulin Sensitivity 02:17:03 Tool: Continuous Glucose Monitors (CGMs) & Awareness, Glucose Spikes 02:24:34 Tool: CGMs, Glycemic Variability, Dawn Effect, Individuality 02:33:10 Sleep; Continuous Monitoring & Biomarkers 02:37:39 Mindset & Safety, Stress & Cell Danger Response 02:44:04 Tool: Being in Nature, Sunlight, Fear 02:54:44 Zero-Cost Support, Spotify & Apple Reviews, Sponsors, YouTube Feedback, Social Media, Neural Network Newsletter Disclaimer
How can you increase NAD+ levels? And do higher NAD+ levels really lead to better metabolic health? What does the research say on their benefits for longevity? These topics and more are discussed in the latest episode of Longevity by Design with Dr. Joe Baur. Dr. Baur, Professor at the Perelman School of Medicine of the University of Pennsylvania, has made key contributions to the understanding of how metabolism and dietary factors influence longevity, for example, resveratrol's effect on insulin sensitivity. His lab looks at small molecules like NAD+ to understand how they can mimic the health-promoting effects of caloric restriction in rodents. Listen to all episodes of Longevity by Design at https://info.insidetracker.com/longevitybydesign Episode highlights8:08-10:13: What are the Potential Benefits of Resveratrol Supplements? 17:36-19:53: How Does NAD Affect Metabolism?22:49-25:13: Do NAD+ levels decline with age? 25:14- 31:27: How to Combat Declining NAD Levels as You Age 43:54- 49:12: How do NAD Analogs Affect Target Tissues? 50:11-51:06: What are the potential health benefits of taking NMN? 54:17- 1:04:21: Safety, Dosage, and Benefits of NMN + NR Supplements 1:04:22-1:04:31: Should you take NMN supplements?
Luisteraar Christijn vraagt zich af of er inmiddels nog wat nieuws te vertellen valt over die mysterieuze ster van Tabby. Verpakt in sneeuw en gelardeerd met zoetsappige kerstmis geluiden is dit dan de kerst-aflevering van "Zimmerman en Space".2757 - Understanding the origin of Boyajian's Star occultations:https://www.stsci.edu/jwst/phase2-public/2757.pdfA Search for Analogs of KIC 8462852 (Boyajian's Star): A Second List of Candidates:https://arxiv.org/pdf/2111.01208.pdfJames Webb Telescope Discoveries Tracker:https://www.jameswebbdiscovery.com/KIC 8462852 in Simbad database:https://simbad.u-strasbg.fr/simbad/sim-basic?Ident=KIC+8462852Tabby's Star:https://en.wikipedia.org/wiki/Tabby%27s_StarKepler space telescope:https://en.wikipedia.org/wiki/Kepler_space_telescopeWhere's the Flux?https://www.wherestheflux.com/De Zimmerman en Space podcast is gelicenseerd onder een Creative Commons CC0 1.0 licentie.http://creativecommons.org/publicdomain/zero/1.0
Endocrine Review Course Episode 16 Learning Objectives: - Describe the differences between regular insulin and regular insulin analogs- Describe the difference in pharmaco-kinetics between concentrated U-500 regular insulin and U-100 regular insulin - List the clinical benefits of using concentrated insulin in specific populations
Leif Routman joins us today to discuss all things food. Leif is a musician, forager, and local food advocate. By day he dips his toes into part-time farming and a little cooking, and by night he makes his living on stage as a bandleader, performer, and composer. Corinne and Leif discuss the richness of a deep food culture, both in the production and the consumption. Also, Leif's childhood in the upper-midwest, to his journey to the intermountain west, and the changing landscape in-between. He shares stories around his own journey to local food, foraging, and food advocacy— searching for flavor and quality, and ultimately finding so much more. This conversation was warm, engaging, and of-the-moment. We know you'll enjoy it. Covered today:Leif's food background and upbringing The sacredness of family dinner Analogs between music and foodRitualizing food traditions to connect with family and loved onesThe gradual process of connecting to a local food system through friends and community Leif's college experiences cooking and pursuing quality & flavor The freedom and broadening in a “narrowing” How Leif developed his land ethic The interplay between resilient health and interaction with wild landscapes Building up cultural traditions and rituals in the modern age to be better stewards of the landscape Celebrating seasons, change, impermanence The powerful, yet fragile, nature of the Teton Wilderness Leif's shift-of-consciousness from his experiences foraging and engaging with the wild For the love of huckleberries, currants, and mushrooms “The Unprejudiced Palate” by Pellegrini“The Third Plate” by BarberIf you want to connect with Leif, you can find him and his musical exploits on IG @leifroutman. Be sure to check out his exploits in local sourdough baking and cooking with local foods. And as always, we'd love to hear from you. Did you love this episode? Did it make you think? Let us know. Reach out via email hello@latebloomerranch.com or on Instagram @latebloomerranch Please subscribe, rate and review the show. See you next time.
An FBI investigation in New York leads to the discovery of 764, an online offshoot of the occult Order of 9 Angles, dedicated to pushing vulnerable children into self harm and sexual abuse. A hydrologist writes in to answer some of Ben, Matt and Noel's earlier questions about saltwater intrusion. A fellow Conspiracy Realist explores the dangers of drug analogs. All this and more in this week's listener mail segment.They don't want you to read our book.: https://static.macmillan.com/static/fib/stuff-you-should-read/See omnystudio.com/listener for privacy information.
Erik Torenberg sits down with film executive, producer, tech investor, and CEO/founder of Stampede Ventures, Greg Silverman. Riverside.fm is a presenting sponsor of Media Empires. Go to https://creators.riverside.fm/MediaEmpires + use code MEDIAEMPIRES for 20% off individual plans.Media Empires is part of the Turpentine podcast network. To learn more: www.turpentine.coIn this interview they compare and contrast the film and tech industries in all aspects, what makes a successful project, and investment practices.We're hiring across the board at Turpentine and for Erik's personal team on other projects he's incubating. He's hiring a Chief of Staff, EA, Head of Special Projects, Investment Associate, and more. For a list of JDs, check out: eriktorenberg.com.RECOMMENDED PODCAST:Founding a business is just the tip of the iceberg; the real complexity comes with scaling it. On 1 to 1000, hosts Jack Altman and Erik Torenberg dig deep into the inevitable twists and turns operators encounter along the journey of turning an idea into a business. Hear all about the tactical challenges of scaling from the people that built up the world's leading companies like Stripe, Ramp, and Lattice. Our first episode with Eric Glyman of Ramp is out now: https://link.chtbl.com/1to1000TIMESTAMPS(00:00) Episode Preview(02:33) Why Greg got into the film industry(08:22) Analogs of the film world vs tech(10:45) Learnings from film versus tech(12:20) Product launching in film vs tech(13:39) Leverage in the tech vs entertainment world(17:15) Where investments comes from in Hollywood(18:15) Where did Stampede come from?(23:11) Raising venture money(26:50) Where does the money from hits come from?(28:10) Moats in Hollywood(29:27) Can the Hollywood approach work in tech?(31:04) The cultural impact of the theater(32:40) How similar is it with the music industry?(33:44) The hints of a successful project (or resistance and persistence make for successful projects)(37:05) How technology has changed the entertainment industry(39:00) Will AI change the game of entertainment?(41:48) NFTs and Web-3(44:30) Greg's Investing Practices(47:21) What is the value in short form content?LINKS:Stampede Ventures: https://stampedeventures.com/SOCIALS:Greg's Twitter: https://twitter.com/gregsilvermanStampede Venture's Twitter: https://twitter.com/stampede_ventStampede Venture's LinkedIn: https://www.linkedin.com/company/stam...Erik's Twitter: https://twitter.com/eriktorenberg This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit mediaempires.substack.com
Come see Elvis and Barb on stage together for the first time as we record an episode in front of a live audience! Register for the Ladies of the Mill Summit in Chattanooga, TN on July 21-22 (https://www.ladiesofthemill.com/) Let's say you get a nice implant case in the lab. Obviously, there is a need for custom abutments. You can do everything in the lab quickly, except the abutments. You already must scan and design them, but when you send them out, how long do you have to wait to get them back? 4 days? A week? Two Weeks? How would you like it in 20 minutes? The Vice President of Preat (https://www.preat.com/), Ruben Arebalo, comes on the podcast to talk about his history getting to Preat and taking them from attachments to a complete digital implant restorative solution. The CEO of Digital Dental (https://www.digitaldental.com/), Jon Barnes, comes on to talk about getting into dental and running a company that has been making mills since the 70s. They have partnered up to provide a FDA compliant workflow for your lab to mill abutments in your own lab! From validating the mill and milling strategies, to documentation protocol, these two have provided a path for your lab to successfully and safely mill custom abutments. The new PrograScan PS3 and PS5 (https://www.ivoclar.com/en_us/products/digital-equipment/prograscan-ps5-and-ps3-laborscanner) provide true-to-detail, high-resolution and accurate scans for coordinated digital workflows that are precise, fast, and always accurate. The PS3 and PS5 are powered by the popular and intuitive DentalCAD software from Exocad (https://exocad.com/). Whether you are looking for your first scanner, to upgrade or add to your existing scanners, the PrograScan may be the one for you. Reach out to your friendly Ivoclar (https://www.ivoclar.com/en_us) sales representative to select a scanner that matches the needs of your lab Today and tell them you heard about it on the podcast! Special Guests: Jon Barnes and Ruben Arebalo.
Today we're taking a stroll down memory lane with a look back episode. From time to time I like to go back through episodes to refresh my memory of things I should be thinking of as the season approaches. In this session I pulled sections of episodes past from our friend's Justin Hollandsworth, Jacob Emory, KC Smith, Dr. Strickland and our favorite...Greg Litzinger. Hope you guy dig it - thanks for listening! To listen to the podcast click the purple play button at the top of the page. You can also download the podcast via iTunes, Stitcher Radio and Google Play—don't forget to share with your friends! If you like the podcast, please leave us a 5 star iTunes rating…we'd really appreciate it. Click here to listen/subscribe on iTunes (best for iOS devices) Click here to listen/subscribe on Stitcher (best for Android devices) WHAT TO EXPECT FROM PODCAST 339 Drifting tracks and entry/exit strategy First P&Y Early season and trail cam strategy Evolving your hunting style by traveling The truth about the October lull and buck bedding Mid October dates And Much More SHOW NOTES AND LINKS: —Truth From The Stand Merch — Exodus anniversary sale for 25% off (code TFTS) - ENDS JUNE 12 —Support our partners: Exodus Outdoor Gear, Genesee Beer & Tethrd — Visit my local archery shop Bob and AJ's Archery World —Waypoint TV Learn more about your ad choices. Visit megaphone.fm/adchoices
Comparing next year's Purdue team to teams of the past
In this episode, Joe interviews Nick Kadysh: Founder and CEO of PharmAla Biotech and member of the board of directors for The Canadian Psychedelic Businesses Association. PharmAla Biotech is a Toronto-based Life Sciences company with two focuses: contracting with manufacturers to provide researchers with GMP MDMA (created under Good Manufacturing Practice regulations), and creating and researching novel analogs of MDMA. And just today, they announced that Health Canada has authorized them (and their distribution partner, Shaman Pharma) to supply their LaNeo™ MDMA for the treatment of a patient under Canada's Special Access Program – the first time this has happened in Canada. He discusses the creation of PharmAla and why their model changed from primarily researching analogs to manufacturing; why they're operating out of Canada and using manufacturers instead of running the lab themselves; the excitement around Australia's recent about-face on MDMA and psilocybin-assisted therapy; the bureaucracy of U.S. drug policy and how much a broken supply chain affects the whole industry; bad IP and companies filing rapid fire patents; why creating new analogs of MDMA is so important; and why the psychedelic space needs to bring culture along with us. He also talks about Spravato, cannabis and risks of cancer, THC nasal sprays, and research he's most excited about: that MDMA seems to alleviate dyskinesia caused from Parkinson's disease, and that MDMA could improve social anxiety in people with autism. He's aiming to run a clinical trial and believes they have developed a safe MDMA analog that the autistic community will respond to very well. www.psychedelicstoday.com
Audionautic | Covering the Latest in Music Production, Marketing and Technology
This is our weekly music production, technology and marketing podcast. Today we're joined by our label mate Frequency Control Centre to listen to his new pastoral IDM album "Analogs of Traces". We'll also talk some free impulse responses from GPU Audio, a recently announced Behringer eurorack LFO and a nice new feature in Spotify's editorial pitch for new tracks. ------------------------------------ Time Stamps: 2:00 hello/what we're up to 8:00 FCC Listening party 55:00 Behringer Eurorack 1:05:00 Free impulse responses from GPU audio 1:12:00 Marketing Minute ------------------------------------ Check out our new Eco T-Shirts: https://audionauticrecords.bandcamp.com/merch/audionautic-space-eco-tee Special thanks: McKinleyA - Audionaut Engineer Lars Haur - Audionaut Producer Help Support the Channel: Patreon: https://www.patreon.com/audionautic PayPal: https://www.paypal.com/paypalme/AudionauticRecords Join the conversation:
This is the Weight and Healthcare newsletter! If you like what you are reading, please consider subscribing and/or sharing!In part 1 we talked about a request that has been submitted for the World Health Organization (WHO) to add diet drugs (specifically GLP1 agonists like Novo Nordisk's Saxenda and Wegovy) to their list of “essential medicines.” We discussed who was making this request and the justification that they were using. In part 2 we took a deeper dive into the research that they used to try to support this request, and in this final installment, we will look at the research around efficacy, harm, and cost-effectiveness.First I'll offer a summary for each issue and then I'll give a breakdowns of the research that they cite. Just a quick reminder that this request is asking the World Health Organization (WHO) to add these drugs to their list of “essential medications” globally.Before we get into the sections, I want to mention two overarching issues that are found throughout the entirety of this request and the studies that are used to support it.First, in general, a belief has been fomented (predominantly by those in the weight loss industry) that being higher-weight is so terrible then it's worth “throwing anything at the problem.” This leads to acceptance of poor, short-term, and/or incomplete data as “good enough” to foist recommendations onto higher-weight people, which means that part of weight stigma in healthcare is that higher-weight people are afforded less right to ethical, evidence-based medicine than thinner people.Second, is clinging to correlation (without any mechanism of causation) when it comes to weight, health, and health outcomes, including the abject failure to consider confounding variables. So throughout these studies “being higher-weight is associated with [health issue(s)]” stated uncritically in support of weight loss interventions. There is an utter failure to explore the idea that the reason for the outcome differences is not weight itself but, instead, exposure to weight stigma, weight cycling (which these medications actually perpetuate by their own admission,) and healthcare inequalities. Issues with research supporting effectiveness, harms, and benefitsStudy Duration:This is the main issue. While there was one study that went up to 106 weeks, the vast majority of the studies are between 14 and 56 weeks. We know that these drugs can have significant, even life-threatening side effects (earning them the FDA's strongest warning.) 14-56 weeks is not not nearly enough time to capture the danger of long-term effects, or to capture long-term trends around weight loss/weight regain.Study PopulationMany of the studies included have small samples. Many have study populations are overwhelmingly white, which is a huge issue when making a global recommendations.Small effect and overlapMany of the studies show only a bit of weight loss (often 15lbs or less) and often there was overlap in weight lost between the treatment group and the placebo group. Even using the “ob*sity” construct that this request is based on, for many people, this amount of weight loss wouldn't even change their “class” of “ob*sity.”Failure to capture adverse eventsMuch of the research they use to support their claims of safety didn't actually capture individual adverse events or serious adverse events. Often they only captured subjects who reported leaving treatment due to side effects.Issues with research supporting cost effectivenessThe cost-effectiveness analyses they cite are based on Quality Adjusted Life Years (QALYs). This is a measurement of the effectiveness of a medical intervention to lengthen and/or improve patients' lives.The calculation for this is [Years of Life * Utility Value = #QALY]So if a treatment gives someone 3 extra years of life with a Health-Related Quality of Life (HRQL) score of 0.7, then the treatment is said to generate 2.1 [3 x 0.7] QALYs.This is a complicated and problematic concept that deserves its own post sometime in the future, but looking just at this request I think it's important to note that they are working on two main unproven assumptions:1. That being higher weight causes lower health-related quality of life and/or shorter life span (rather than any lower HRQL being related to experiences that higher-weight people have including weight stigma, weight cycling, healthcare inequalities et al.) 2. That this treatment induces weight loss and/or health benefits that increase the life span and/or health-related quality of life of those who take it.I don't believe either of these assumptions are proven by the material cited in the request to the WHO. Specifically, it's very possible that it's not living in a higher-weight body, but rather the experiences that higher-weight people are more likely to have (weight stigma, weight cycling, healthcare inequalities) that impact their HRQL.Further, the short-term efficacy data available (and Novo Nordisk's own admission about high rates of regain) fall far short of proving any assumptions about these drugs ability to actually improve or extend life. Further, the failure of the literature to adequately capture negative side effects of the drugs, both short and long-term, means that this calculation cannot be properly made.Incremental Cost-Effectiveness Ratio (ICER)ICER is how QALYs are turned into a monetary value. It is calculated by dividing the difference in total costs by the difference in the chosen measure of health outcome or effect.[(Cost of intervention A -Cost of Intervention B) / (Effectiveness of Intervention A – Effectiveness of Intervention B)]The result is a ratio of extra cost per extra unit of health effect of a more vs less expensive treatment which can then be measured in QALYs.Again, this is worthy of its own post because there are all kinds of ethical issues around things like how we value life, how we define “healthy” and the ethics of determining whether or not prolonging someone's life is “cost effective.” I'm not going to do a deep dive into that today, but I do want to note that it is a serious issue in these kinds of calculations.In this specific case, even if one was to get past the ethical issues, an accurate calculation is impossible to make on both of the measures of the equation.Cost of these drugs varies wildly between countries and sometimes within countries because, for example, Novo Nordisk is a for-profit corporation whose goal is to create as much profit as possible. Per the WHO request letter, the monthly cost of liraglutide is $126 in Norway and $709 in the US. Semaglutide is $95 per 30 days in Turkey, but $804 per 30 days in US.When it comes to effectiveness of the treatment, again, there is virtually no long-term data. We do know that in Novo Nordisk's own studies, weight is regained rapidly and cardiometabolic benefits are lost when the drugs are discontinued and even when people stay on the drugs, weight loss levels off after about a year, at 68 weeks weight cycling begins, and at 104 weeks (when follow-up ended) weight was trending up. It's possible that these drugs are utterly ineffective over the long-term and/or that the prevalence of long-term side effects renders any treatment effects moot. We simply do not know.I do not think that this is a remotely appropriate basis from which to request that these drugs be declared globally essential by the WHO.Here are the citation breakdowns. These are not deep dives since there are enough issues with the research on a simple surface analysis.Breakdowns of evidence of comparative effectivenessEffects of liraglutide in the treatment of ob*sity: a randomised, double-blind, placebo-controlled study, Astrup et al.)This is a 20-week study funded by Novo Nordisk. It included 564 people on various doses of liraglutide and a placebo group who didn't get the drug and a group on orlistat. There were no more than 90-98 people in each group.The study explains “Participants on liraglutide lost significantly more weight than did those on placebo” by which they meant that those on the highest dose of liraglutide lose about 9.7lbs more than those on the placebo over the 20 weeks.III LEAD studiesThese are four studies that look at liraglutide in combination with other drugs for the treatment of Type 2 Diabetes that also included some information on weight changes. One was 52 weeks, the others were 26, the maximum amount of weight lost was only about 5lbs. The first [Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU), Marre et al] was a study that looked at the efficacy of adding liraglutide or rosiglitazone 4 to glimiperide in subjects with Type 2 Diabetes to test effects on blood sugar and body size.The study followed 1041 adults for 26 weeks. The study found that those on .6mg of liraglutide gained 0.7kg, those on 1.2mg gained 0.3kg, and those on 1.8mg of liraglutide lost 0.2kg, while those on placebo lost 0.1kg.The second [Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care, 2009. 32(1): p. 84-90. Nauck, M., et al.,]looked at the efficacy of adding liraglutide to metformin therapy for those with Type 2 Diabetes. They found that over the 26-week study those on liraglutide lost 1.8 ± 0.2, 2.6 ± 0.2, and 2.8 ± 0.2 kg for 0.6, 1.2, and 1.8 mg doses. Those on placebo lost 1.5 ± 0.3kg.The third [Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet, 2009. 373(9662): p. 473-81. Garber, A., et al.,] This was a study of the comparative effectiveness of Liraglutide versus glimepiride for type 2 diabetes, with small weight loss as an ancillary finding. Those in the liraglutide group lost an average of 2kg.The final study [Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD), Zinman et al.] was a 26-week study with 533 total subjects. The goal was to study the efficacy of liraglutide when added to metformin and rosiglitazone for people with type 2 diabetes. They found that those on liraglutide lost between 0.7 and 2.3kg (1.5lbs to 5.1lbs) in 26 weeks.Meta-Analyses and Systematic Review FindingsEfficacy of Liraglutide in Non-Diabetic Ob*se Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Barboza, J.J., et al., None of the included studies were more than 56 weeks and one was only 14 weeks. One had as many as 3731 subjects, but one had only 40. Some had body weight loss as a primary outcome, but some did not. Maximum doses ranged from 1.8 to 3.0mg. The mean body weight reduction was 3.35 kg (7.4lbs) but in one study there was no difference in weight loss. The maximum difference was 6.3kg (13.9lbs)They also refer to Iqbal et al which we discussed in part 2.Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. Vilsbøll, T., et al.The included studies are between 20 and 53 weeks long, and include some of the studies they already cited individually above. Of the 25 included studies only 3 had “ob*sity” as the main inclusion criteria, the rest were Type 2 Diabetes.The mean weight loss for those on the highest dose of the drug was between 0.2kg and 7.2kg. For those in the control group it was 2.9 kg, so there was actually overlap between the treatment and placebo groups.Summary of evidence of safety and harmsThey begin with the claim “The safety profile of GLP-1 receptor agonists is also well studied”To support this they cite: Efficacy and Safety of Liraglutide 3.0 mg in Patients with Overweight and Ob*se with or without Diabetes: A Systematic Review and Meta-Analysis, Konwar, M., et al.,This included 14 total studies, many of which the authors of the WHO request had cited individually and were included in other systematic reviews and meta-analyses above. The smallest study included 19 people, the largest included 2,487. The total number of subjects was 4,142.Their conclusion was “Liraglutide in 3.0 mg subcutaneous dose demonstrated significant weight reduction with a reasonable safety profile for patients with overweight or ob*sity regardless of diabetic status compared to placebo.”Their methodology says that they omitted studies from analysis due to “short duration.” They included studies that had a minimum of 12 weeks and a maximum of 56 weeks of follow-up.While they included 14 studies, only 11 of them actually included information about adverse events.In terms of adverse effects (AEs,) they found that the pooled estimate of nine studies in nondiabetic patients and two studies in diabetic patients revealed a significant proportion of patients experiencing the adverse events in liraglutide 3.0 mg group when compared with placebo., and the pooled estimate of the eleven studies showed that liraglutide 3.0 mg had higher risk of AEs compared to placebo.When it came to “serious adverse events” they found that there was a similar risk level between the drug and placebo groups, but remember that's for only 12 to 56 weeks, and Novo Nordisk is recommending that people take these drugs for the rest of their lives. A few months to a little over a year is not enough time to capture long-term serious adverse events.The efficacy and safety of liraglutide in the ob*se, non-diabetic individuals: a systematic review and meta-analysis. Zhang, P., et al.,This included five RCTs (which were included in various of the above systemic reviews and meta-analyses) ranging in follow-up from 14 to 56 weeks.The only adverse event information captured was the number of people who withdrew from treatment due to adverse events (which they found was similar between drug and placebo) and nausea (which was experienced more by people on the drug.)So, in addition to being short in duration, this was far from a comprehensive list of side effects. They made no attempt to capture serious adverse side effects and their short-term nature would have made this difficult anyway.Association of Pharmacological Treatments for Ob*sity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. Khera, R., et al.This looked at weight loss and adverse events with a number of different weight loss drugs. Interestingly liraglutide did not show the highest amount of weight loss but was associated with the highest odds of adverse event–related treatment discontinuation. It should also be noted that high drop-out rates of 30-45% plagued all of the trials which the study authors admit means that “studies were considered to be at high risk of bias.“Given that those who drafted the WHO request are asking that these drugs be considered essential globally, it is disappointing that they included this study and didn't bother to mention this issue in their written request.This included 28 RCTs (most of which were included in other citations above) and only 3 that included liraglutide. They didn't capture individual adverse events, but only “Discontinuation of Therapy Due to Adverse Events.” They only evaluated a year of data so, again, while it is likely that these studies would have captured common adverse events had they bothered to try, there isn't long enough follow-up to have any information about serious (possibly life-threatening) long-term adverse events.Association of Glucagon-like Peptide 1 Analogs and Agonists Administered for Ob*sity with Weight Loss and Adverse Events: A Systematic Review and Network Meta-analysis. Vosoughi, K., et al.,This study included 64 RCTs with durations from 12 to 160 weeks, with a median of 26 weeks. As is common in these studies, the majority of the sample (74.9%) was white.Like those above, they only looked at treatment discontinuation from adverse events, they did not capture specific adverse events (common or serious.) Of the seven GLP-1 drugs they tested, liraglutide was tied with taspoglutide for the highest discontinuation of treatment due to adverse events.The study authors also note that “Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%).”Breakdowns for Comparative Cost-effectiveness StudiesFirst, the WHO request authors themselves admit that when it comes to cost-effectiveness, “the analyses have generally been performed only for high-income countries.” This is significant since they are asking the WHO to consider these drugs essential for the entire world.It's also important to understand that none of the data looks at a comparison of cost effectiveness for weight-neutral health interventions to these drugs. Without that information there is no way to calculate actual “cost effectiveness” since it's possible that weight-neutral health interventions would have greater benefits with less risk and dramatically lower cost. NICE's guidance: Liraglutide for managing overweight and ob*sity Technology appraisal guidance [TA664]Published: 09 December 2020.Do recall that NICE is involved in the current scandal with Novo Nordisk for influence peddling.These guidelines are created based on a submission of evidence by Novo Nordisk. The committee's understanding of “clinical need” was based on the testimony of a single “patient expert” who “explained that living with ob*sity is challenging and restrictive. There is stigma associated with being ob*se.”Once again we see a rush to blame body size for any “challenges” and “restrictions” of living in a higher-weight body, accompanied by the immediate decision that those bodies should be subjected to healthcare interventions that risk their lives and quality of life in order to be made (temporarily, by Novo and NICE's own admission) thinner. There did not seem to be a patient expert to discuss the weight-neutral options.It was not immediately apparent if the patient expert was provided/paid by Novo Nordisk, but they certainly forwarded their narrative that simply living in a higher-weight body is a disease requiring treatment.It should be noted that while the trial Novo Nordisk submitted covered a wider range of people, they specifically submitted for this recommendation only the subgroup of that population who were diagnosed with “ob*sity,” pre-diabetes, and a “high risk of cardiovascular disease based on risk factors such as hypertension and dyslipidaemia.”So, even if we accept this guidance as true, the WHO Essential Medicines request applies to a population much wider than this and so this fails to justify the cost-effectiveness for that population.This guidance is also based on the costs associated with obtaining the drugs through a “specialist weight management service” since an agreement is in place for Novo Nordisk to give a discount to these services.In calculating the ICER per QALY gained, the recommendations note that “Because of the uncertainties in the modelling assumptions, particularly what happens after stopping liraglutide and the calculation of long-term benefits, the committee agreed that an acceptable ICER would not be higher than £20,000 per QALY gained”Again, this recommendation is based on a trial submitted by Novo Nordisk that included 3,721 people and lasted for three years, but only 800 met the criteria for this cost-effectiveness recommendation. The trial failed to show a significant reduction in cardiovascular events. Novo's calculation of risk reduction was based on surrogate outcomes, which NICE points out “introduces uncertainty because causal inference requires direct evidence that liraglutide reduces cardiovascular events. This was not provided in the company submission because of lack of long-term evidence.”The NICE committee admits “relying on surrogates is uncertain but accepted that surrogate outcomes were the only available evidence to estimate cardiovascular benefits.”I just want to point out that another option would be to refuse to experiment on higher-weight people without appropriate evidence.These cost-effectiveness calculations are based on someone using the drug for two years, with no actual data on reduction in cardiovascular events, and with the admitted assumption that “any weight loss returned to the base weight 3 years after treatment discontinuation.” Said another way, this committee decided that it was cost effective to spend up to £20,000 per QALY for people to take a weight loss drug with significant side effects for two years, with no direct evidence of reduced cardiovascular events, and with the acknowledgment that people will be gaining all of their weight back when they stop taking it.Those who wrote the request for WHO to consider these drugs “essential” chose to characterize this as “At the chosen threshold of £20,000 per quality-adjusted life year (QALY) gained, the report concluded that liraglutide is cost-effective for the management of ob*sity.” I do not think that is an accurate characterization of the findings.The request cites “A report by the Canadian Agency for Drugs and Technologies in Health (CADTH) found that compared to standard care, the ICER for liraglutide was $196,876 per QALY gained”For the US, they cite a study that found that to achieve ICERs between $100,000 and $150,000 perQALY or evLY gained, the health-benefit price benchmark range for semaglutide was estimated as $7500 - $9800 per year, which would require a discount of 28-45% from the current US net price.They also cite “Cost-effectiveness analysis of semaglutide 2.4 mg for the treatment of adult patients with overweight and ob*sity in the United States, Kim et al.Let's take a look at their conflict of interest disclosure (emphasis mine)“Financial support for this research was provided by Novo Nordisk Inc. The study sponsor [that means Novo Nordisk] was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication.Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.”Given that, you probably won't be shocked to learn that this concluded that Novo Nordisk's drug, semaglutide, was cost-effective. The reason I bolded the text above is that this study is based on modeling – they are taking what is, by their own admission, a “new drug” and making predictions for 30 years. Everything was simulated based on trial data (you know, those trials that we've been discussing that often have horrendous methodology…) and “other relevant literature.” The construction of the modeling and the interpretation of the results was directed by the company who stands to benefit financially from the findings, and carried out by that company's employees and consultants. Also, and I'll just quote again here since I don't think I can improve on their text “Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained” I do not think that this WTP is based on a global assessment.In their (and by their I mean Novo Nordisk's) modeling they find that semaglutide was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators.And, again, this is without any kind of actual long-term data. I think that the best way to characterize this information is “back of the envelope calculations” at best.To sum up, I do not think that the research they cite comes anywhere close to proving that these drugs have levels of efficacy, safety, or cost-effectiveness that warrant their addition to the WHO list of essential medicines. I believe that if the WHO grants this request I think it will be an affront to medical science, it will cheapen the concept of “essential medicines,” and it will harm untold numbers of higher-weight people all over the world.Did you find this post helpful? You can subscribe for free to get future posts delivered direct to your inbox, or choose a paid subscription to support the newsletter and get special benefits! Click the Subscribe button below for details:Liked this piece? Share this piece:More research and resources:https://haeshealthsheets.com/resources/*Note on language: I use “fat” as a neutral descriptor as used by the fat activist community, I use “ob*se” and “overw*ight” to acknowledge that these are terms that were created to medicalize and pathologize fat bodies, with roots in racism and specifically anti-Blackness. Please read Sabrina Strings' Fearing the Black Body – the Racial Origins of Fat Phobia and Da'Shaun Harrison's Belly of the Beast: The Politics of Anti-Fatness as Anti-Blackness for more on this. Get full access to Weight and Healthcare at weightandhealthcare.substack.com/subscribe
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.29.534814v1?rss=1 Authors: Chang, W.-J., Harpel, Z., Circelli, J., Chen, R., Chang, I., Rivera, J., Wu, S., Wei, Z. Abstract: Tetrahymena are ciliated protists that have been used to study the effects of toxic chemicals, including anticancer drugs. In this study, we tested the inhibitory effects of six pyrimidine analogs (5-fluorouracil, floxuridine, 5-deoxy-5-fluorouridine, 5-fluorouridine, gemcitabine, cytarabine) on wild-type CU428 and conditional mutant NP1 Tetrahymena thermophila at room temperature and the restrictive temperature (37{degrees}C) where NP1 does not form the oral apparatus. We found that cytarabine was the only tested analog that did not inhibit growth, and phagocytosis was not required for pyrimidine analog entry. IC50 values did not significantly differ between strains for the same analog at either temperature. To investigate the mechanism of inhibition, we used two pyrimidine bases (uracil and thymine) and three nucleosides (uridine, thymidine, 5-methyluridine) to help determine whether the inhibitory effects from analogs were reversible. We found that the inhibitory effects from 5-fluorouracil could be reversed by uracil and thymine, from floxuridine could be reversed by thymidine, and from 5-deoxy-5-fluorouridine could be reversed by uracil. None of the tested nucleobases or nucleosides could reverse the inhibitory effects of gemcitabine or 5-fluorouridine. Our results suggest that the five pyrimidine analogs act on different sites to inhibit T. thermophila growth and that nucleobases and nucleosides are metabolized differently. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Rose Smith, Stream Ecologist and Lead on the Sageland Collaborative's Riverscape Restoration Program discusses her work with Beaver Dam Analogs (BDAs). BDAs are a surprisingly simple solution to landscape change and bringing watersheds back into balance. By slowing the flow in the watershed BDAs can assist with sedimentation issues in reservoirs, fire mitigation, and water quality gains. A fun conversation with a colleague doing interesting and impactful work.
In this episode, we review the high-yield topic of Platinum Analogs from the Oncology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://anchor.fm/medbulletsstep1/message
The Big Themes: This is about adaptation, not ageism: Native digitals are not better or worse than native analogs, but they are actually a new category of human being. That may sound like an exaggeration, but it's not.Businesses at risk of obsolescence: Leaders who do not account for the differences of native digitals are going to face (1) the failure to hire and retain anybody under 35 and (2) the inability to market and sell to anybody under 35.The Mentor Myth: Chris says that the secret to native analogs thriving in our native digital world is understanding that the older generations have as much to learn from the younger ones as vice versa. Read more in "The Mentor Myth" ebook. The Big Quote: "We are the last native analogues to walk Planet Earth. period. Human beings have embedded technology into the core experience of life. And that will be true forever going forward." Want more from Christopher Lochhead and Category Pirates? Explore his podcasts, blog, and books
On this Monday morning I wake and bake with the Indica Grand Daddy Purple! I start by speaking a little on the death of Aaron Carter and my speculation on the cause. RIP. From there I give a review and some lineage details of the Grand Daddy purp I was puffing on. I then go into my weekend and two orders I made, one for a new bong and a THC-P vape from 420everything, as well as a THC-V and THC-P vape from Delta Extrax. Both on the way that I will review. I then speak a bit on the new Delta and THC analogs that are coming out. The safety of it? The effects? Long and short term
Hello and Welcome!!! This is a podcast where I will be sharing some of my favorite short stories from Fiction ,Fantasy, and Science Fiction that I have enjoyed over the years. These tales and anecdotes have expounded upon me some of the great humors and lessons of life. I hope this podcast can aid you in taking mindful moments amidst the storm of a hectic day; or during the even hours as you decompress and unwind for the night. It has taken me some time to get to this point and I hope you will join me through this journey. So…Take a moment, a walk, a seat and listen These are THE ANALOGS. I hope you enjoy Aoleon Niobe Aelegun “The Narrator”
Infrared variability of young solar analogs in the Lagoon Nebula by C. Ordenes-Huanca et al. on Tuesday 18 October T Tauri stars are low-mass pre-main sequence stars that are intrinsically variable. Due to the intense magnetic fields they possess, they develop dark spots on their surface that, because of rotation, introduce a periodic variation of brightness.In addition, the presence of surrounding disks could generate flux variations by variable extinction or accretion. Both can lead to a brightness decrease or increase, respectively. Here, we have compiled a catalog of light curves for 379 T Tauri stars in the Lagoon Nebula (M8) region, using VVVX survey data in the Ks-band. All these stars were already classified as pre-MS stars based on other indicators. The data presented here are spread over a period of about eight years, which gives us a unique follow-up time for these sources at this wavelength. The light curves were classified according to their degree of periodicity and asymmetry, to constrain the physical processes responsible for their variation. Periods were compared with the ones found in literature, on a much shorter baseline. This allowed us to prove that for 126 stars, the magnetically active regions remain stable for several years. Besides, our near-IR data were compared with the optical Kepler/K2 light curves, when available, giving us a better understanding of the mechanisms responsible for the brightness variations observed and how they manifest at different bands. We found that the periodicity in both bands is in fairly good agreement, but the asymmetry will depend on the amplitude of the bursts or dips events and the observation cadence. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2210.09242v1
Infrared variability of young solar analogs in the Lagoon Nebula by C. Ordenes-Huanca et al. on Tuesday 18 October T Tauri stars are low-mass pre-main sequence stars that are intrinsically variable. Due to the intense magnetic fields they possess, they develop dark spots on their surface that, because of rotation, introduce a periodic variation of brightness.In addition, the presence of surrounding disks could generate flux variations by variable extinction or accretion. Both can lead to a brightness decrease or increase, respectively. Here, we have compiled a catalog of light curves for 379 T Tauri stars in the Lagoon Nebula (M8) region, using VVVX survey data in the Ks-band. All these stars were already classified as pre-MS stars based on other indicators. The data presented here are spread over a period of about eight years, which gives us a unique follow-up time for these sources at this wavelength. The light curves were classified according to their degree of periodicity and asymmetry, to constrain the physical processes responsible for their variation. Periods were compared with the ones found in literature, on a much shorter baseline. This allowed us to prove that for 126 stars, the magnetically active regions remain stable for several years. Besides, our near-IR data were compared with the optical Kepler/K2 light curves, when available, giving us a better understanding of the mechanisms responsible for the brightness variations observed and how they manifest at different bands. We found that the periodicity in both bands is in fairly good agreement, but the asymmetry will depend on the amplitude of the bursts or dips events and the observation cadence. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2210.09242v1
The Quenched Satellite Population Around Milky Way Analogs by Ananthan Karunakaran et al. on Monday 10 October We study the relative fractions of quenched and star-forming satellite galaxies in the Satellites Around Galactic Analogs (SAGA) survey and Exploration of Local VolumE Satellites (ELVES) program, two nearby and complementary samples of Milky Way-like galaxies that take different approaches to identify faint satellite galaxy populations. We cross-check and validate sample cuts and selection criteria, as well as explore the effects of different star-formation definitions when determining the quenched satellite fraction of Milky Way analogs. We find the mean ELVES quenched fraction ($langle QFrangle$), derived using a specific star formation rate (sSFR) threshold, decreases from $sim$50% to $sim$27% after applying a cut in absolute magnitude to match that of the SAGA survey ($langle QFrangle_{SAGA}sim$9%). We show these results are consistent for alternative star-formation definitions. Furthermore, these quenched fractions remain virtually unchanged after applying an additional cut in surface brightness. Using a consistently-derived sSFR and absolute magnitude limit for both samples, we show that the quenched fraction and the cumulative number of satellites in the ELVES and SAGA samples broadly agree. We briefly explore radial trends in the ELVES and SAGA samples, finding general agreement in the number of star-forming satellites per host as a function of radius. Despite the broad agreement between the ELVES and SAGA samples, some tension remains with these quenched fractions in comparison to the Local Group and simulations of Milky Way analogs. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2210.03748v1
CLASSY IV: Exploring UV diagnostics of the interstellar medium in local high- z analogs at the dawn of the JWST era by Matilde Mingozzi et al. on Wednesday 21 September The COS Legacy Archive Spectroscopic SurveY (CLASSY) HST/COS treasury program provides the first high-resolution spectral catalogue of 45 local high-z analogues in the UV (1200-2000AA) to investigate their stellar and gas properties. We present a toolkit of UV interstellar medium (ISM) diagnostics, analyzing the main emission lines of CLASSY spectra (i.e., NIV]$lambdalambda$1483,87, CIV$lambdalambda$1548,51, HeII$lambda$1640, OIII]$lambdalambda$1661,6, SiIII]$lambdalambda$1883,92, CIII]$lambdalambda$1907,9). Specifically, we focus our investigation on providing accurate diagnostics for reddening, electron density and temperature, gas-phase metallicity and ionization parameter, taking into account the different ionization zones of the ISM. We calibrate our UV toolkit using well-known optical diagnostics, analyzing archival optical spectra for all the CLASSY targets. We find that UV density diagnostics estimate ne values that are ~1-2 dex higher (e.g., ne(CIII]$lambdalambda$}1907,9)~10$^4$cm$^{-3}$) than those inferred from their optical counterparts (e.g., ne([SII]$lambdalambda$6717,31)~10$^2$cm$^{-3}$). Te derived from the hybrid ratio OIII]$lambda$1666/[OIII]$lambda$}5007 proves to be a reliable Te diagnostic, with differences in 12+log(O/H) within ~$pm$0.3dex. We also investigate the relation between the stellar and gas E(B-V), finding consistent values at high specific star formation rates, while at low sSFR we confirm an excess of dust attenuation in the gas. Finally, we investigate UV line ratios and equivalent widths to provide correlations with 12+log(O/H) and log(U), but note there are degeneracies between the two. With this suite of UV-based diagnostics, we illustrate the pivotal role CLASSY plays in understanding the chemical and physical properties of high-z systems that JWST can observe in the rest-frame UV. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2209.09047v2
CLASSY IV: Exploring UV diagnostics of the interstellar medium in local high- z analogs at the dawn of the JWST era by Matilde Mingozzi et al. on Tuesday 20 September The COS Legacy Archive Spectroscopic SurveY (CLASSY) HST/COS treasury program provides the first high-resolution spectral catalogue of 45 local high-z analogues in the UV (1200-2000{AA}) to investigate their stellar and gas properties. We present a toolkit of UV interstellar medium (ISM) diagnostics, analyzing the main emission lines of CLASSY spectra (i.e., NIV]{lambda}{lambda}1483,87, CIV{lambda}{lambda}1548,51, HeII{lambda}1640, OIII]{lambda}{lambda}1661,6, SiIII]{lambda}{lambda}1883,92, CIII]{lambda}{lambda}1907,9). Specifically, we focus our investigation on providing accurate diagnostics for reddening, electron density and temperature, gas-phase metallicity and ionization parameter, taking into account the different ionization zones of the ISM. We calibrate our UV toolkit using well-known optical diagnostics, analyzing archival optical spectra for all the CLASSY targets. We find that UV density diagnostics estimate ne values that are ~1-2 dex higher (e.g., ne(CIII]{lambda}{lambda}1907,9)~10^4cm^{-3}) than those inferred from their optical counterparts (e.g., ne([SII]{lambda}{lambda}6717,31)~10^2cm^{-3}). Te derived from the hybrid ratio OIII]{lambda}1666/[OIII]{lambda}5007 proves to be a reliable Te diagnostic, with differences in 12+log(O/H) within ~+/-0.3dex. We also investigate the relation between the stellar and gas E(B-V), finding consistent values at high specific star formation rates, while at low sSFR we confirm an excess of dust attenuation in the gas. Finally, we investigate UV line ratios and equivalent widths to provide correlations with 12+log(O/H) and log(U), but note there are degeneracies between the two. With this suite of UV-based diagnostics, we illustrate the pivotal role CLASSY plays in understanding the chemical and physical properties of high-z systems that JWST can observe in the rest-frame UV. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2209.09047v1
CLASSY IV: Exploring UV diagnostics of the interstellar medium in local high- z analogs at the dawn of the JWST era by Matilde Mingozzi et al. on Tuesday 20 September The COS Legacy Archive Spectroscopic SurveY (CLASSY) HST/COS treasury program provides the first high-resolution spectral catalogue of 45 local high-z analogues in the UV (1200-2000{AA}) to investigate their stellar and gas properties. We present a toolkit of UV interstellar medium (ISM) diagnostics, analyzing the main emission lines of CLASSY spectra (i.e., NIV]{lambda}{lambda}1483,87, CIV{lambda}{lambda}1548,51, HeII{lambda}1640, OIII]{lambda}{lambda}1661,6, SiIII]{lambda}{lambda}1883,92, CIII]{lambda}{lambda}1907,9). Specifically, we focus our investigation on providing accurate diagnostics for reddening, electron density and temperature, gas-phase metallicity and ionization parameter, taking into account the different ionization zones of the ISM. We calibrate our UV toolkit using well-known optical diagnostics, analyzing archival optical spectra for all the CLASSY targets. We find that UV density diagnostics estimate ne values that are ~1-2 dex higher (e.g., ne(CIII]{lambda}{lambda}1907,9)~10^4cm^{-3}) than those inferred from their optical counterparts (e.g., ne([SII]{lambda}{lambda}6717,31)~10^2cm^{-3}). Te derived from the hybrid ratio OIII]{lambda}1666/[OIII]{lambda}5007 proves to be a reliable Te diagnostic, with differences in 12+log(O/H) within ~+/-0.3dex. We also investigate the relation between the stellar and gas E(B-V), finding consistent values at high specific star formation rates, while at low sSFR we confirm an excess of dust attenuation in the gas. Finally, we investigate UV line ratios and equivalent widths to provide correlations with 12+log(O/H) and log(U), but note there are degeneracies between the two. With this suite of UV-based diagnostics, we illustrate the pivotal role CLASSY plays in understanding the chemical and physical properties of high-z systems that JWST can observe in the rest-frame UV. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2209.09047v1
The key parameters controlling the photodesorption yield in interstellar CO ice analogs: Influence of ice deposition temperature and thickness by N. -E. Sie et al. on Monday 19 September The overabundance of gas molecules in the coldest regions of space point to a non-thermal desorption process. Laboratory simulations show an efficient desorption of CO ice exposed to ultraviolet radiation, known as photodesorption, which decreases for increasing ice deposition temperature. However, the understanding of this abnormal phenomenon has remained elusive. In this work we show the same phenomenon, and in particular, a dramatic drop in the photodesorption yield is observed when the deposition temperature is 19 K and higher. Also the minimum ice thickness that accounts for a constant photodesorption yield of CO ice is deposition temperature dependent, an observation reported here for the first time. We propose that the key parameters that dominate the absorbed photon energy transfer in CO ice, and contribute to the measured photodesorption yields are the energy transfer length, single ice layer contributed desorption yield, and relative effective surface area. This set of parameters should be incorporated in astrophysical models that simulate photodesorption of the top CO-rich ice layer on icy dust populations with the size distribution which is ice thickness related. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2209.08489v1
Lobe Sciences Ltd (CSE:LOBE, OTCQB:LOBED) CEO Phillip Young tells Proactive's Stephen Gunnion that a $1.3 million private placement, together with a recently-announced $1.5 million convertible note through Cantheon Capital, will be dedicated to its clinical and medical development programs, starting in Australia. The company also plans to file an investigational new drug (IND) application in the US to enable it to conduct studies in the US, next year and beyond. Proceeds from the offering are expected to be used for manufacturing and regulatory activities necessary to support initial human clinical trials with novel psilocin analogs L-130 and L-131, Young said. #ProactiveInvestors #LobeSciences #CantheonCapital #Psilocin #CSE #OTCQB
What?!?! Another Implant company? You bet. But this one is different. Patrick Dewey, the General Manager from S.I.N. Dental USA (https://sindentalusa.com/) and Blake Roney, the Digital Solutions Specialist come on the podcast to talk about the companies dedication and process to a completely modeless digital full arch workflow. Patrick and Blake talk about the process and while using Photogrammetry with the Imetric4D (https://sindentalusa.com/products/equipment/imetric-icam4d-photogrammetry-camera/), an Intraoral scanner, ExoCAD (https://exocad.com/), and some slick tips and tricks, anyone can make accurate modeless full arch restorations. Did I mention a new implant? You'll want to hear about all that too. Follow along with the S.I.N. Dental USA Digital Modeless Workflow HERE (https://bit.ly/3Pj788a) Did you know Asiga (https://www.asiga.com/) has over 500 validated materials on their open material system. And it's growing everyday? By harnessing Asiga's proprietary layer monitoring technology with its smart positioning system and integrated internal radiometer, as a laboratory, you will be able to produce any indication you desire. Whether models, splints, temporaries, or even permanent crowns. Your investment will be future proofed by Asiga's rugged engineering. Providing you with a fast, accurate, and repeatable machine, with a reputation that is time tested in the laboratory industry. If you would like to learn about Asiga's machine or material offerings, please visit the website at asiga.com or contact your favorite dental reseller. ExoCAD is excited to present their next Insights event October 3-4, 2022, on the sun-drenched island of Mallorca, Spain. Learn how DentalCAD (https://exocad.com/our-products/exocad-dentalcad?utm_campaign=Insights%202022&utm_source=Introtext%20Insights%20sub%20page%20EN&utm_medium=DentalCAD%20product%20web%20page%20EN&utm_term=link), ChairsideCAD (https://exocad.com/our-products/exocad-chairsidecad?utm_campaign=Insights%202022&utm_source=Introtext%20Insights%20sub%20page%20EN%20ChairsideCAD&utm_medium=ChairsideCAD%20product%20web%20page%20EN&utm_term=Link) and exoplan (https://exocad.com/our-products/exoplan?utm_campaign=Insights%202022&utm_source=Introtext%20Insights%20sub%20page%20EN%20exoplan&utm_medium=exoplan%20product%20web%20page%20EN&utm_term=link) can streamline and improve workflows. Connect with friends and colleagues in the industry while collecting CE points* during a full program of software education, partner shows and international guest speakers. Enjoy the exclusive welcome party, featuring fantastic music and food. Join us in making Insights 2022 an event to remember! Register at exocad.com/insights2022 The fastest growing product at Gro3X (https://www.gro3x.com/) are the Gro3X Aligners. Gro3X Aligners are only available from Gro3X Aligner certified labs: Why? Because they believe in the synergies that are being created between you, the dental office, and your lab. And they want to further leverage these synergies. Their aligners are used as a pre-treatment to a larger restorative esthetic case, to widen gaps prior to placing implants, to close a diastema, ease crowding, and simply enhance your patient's smiles. Even for your Essix retainer needs your Gro3X aligner certified lab can help. Look for a Gro3X Aligner certified lab near you, such as Castle Dental Lab (http://www.castlelab.com/) in San Antonio, TX (ask for Blaine), AMK Dental Lab (https://www.amkdentallaboratory.com/) in O'Neill, NE (ask for Anne), Staggs Dental Lab (https://www.facebook.com/staggsdental) in McCoole Maryland (ask for Derrick), AA Dental Design (https://www.aadentaldesign.com/) in Murrieta, CA (ask for Frankie), and many, many more… For a complete listing of Gro3X Aligner Certified Labs go to www.gro3x.com Whip Mix (https://www.whipmix.com/) introduces the CUREbox Plus (https://www.whipmix.com/products/curebox-plus/), a new curing unit that ensures the proper and full polymerization of 3D printed resins. It really is the ideal curing unit for dental labs and dentists because the CUREbox Plus uses light and heat energy, with controlled time and temperature, to provide an ideal environment suitable for post-curing SLA and DLP type 3D printed models. The American-made, competitively priced curing unit is very easy to use and has a large capacity curing chamber for high production, is super easy to clean and maintain, and offers a one-year warranty which covers everything but the inexpensive, long-lasting UV LED lamps. Though the CUREbox Plus can cure virtually any printed resin, it has been qualified with the following Whip Mix resins: Veriguide OS (https://www.whipmix.com/products/veriguide-os-clear/), VeriSplint OS (https://www.whipmix.com/products/verisplint-os-3d-print-resin/), Dentca denture base (https://www.whipmix.com/products/dentca/), denture teeth, try-in, and Temporary Crown and Bridge (https://www.whipmix.com/products/dentca-temporary-crown-bridge-resin/). If you'd like to learn more about this in-demand product, visit www.whipmix.com. Special Guests: Blake Roney and Patrick Dewey.
Ctrl+Alt+Delete with Lisa Duerre: For Leaders In Tech Escaping Burnout and Rebooting Leadership
What brings a human system alive? When we think about tech and leadership in tech, how many times have we talked about the code that is written and what it takes to get the product out the door but the truth is there's a bunch of humans running around inside that system. Who better to answer that question than Jon Berghoff. Jon's team has changed the game when it comes to how you lead and convene groups whether it's in person or online. Jon is really good at explaining how to get the best out of your team and how to unlock the collective wisdom which is your team. We go really deep on practical methods, questions you can ask, choreographies and how you want to look at bringing people together. We talk about what really matters most and how to get the best out of your groups. We also delve into what's really happening in the workplace today between the different generations and the in-office or remote discussion. Jon Berghoff is the founder of the XCHANGE Approach and is considered the Godfather of conversational choreography, a new way for coaches, consultants and faciliators to unlock collective intelligence in any group. CTRL+ALT+DELETE with Lisa Duerre is brought to you by RLD Group on a mission to reboot leadership drive, eradicate burnout in tech, and help transform technical experts lacking people leadership skills from being a company's biggest liability into their greatest asset. Show Notes: Unlocking Collective Intelligence [4:18] Collective Wisdom in a Hybrid World [8:08] A New World Needs New Solutions [15:09] Generational Clash of Analogs and Digitals [20:31] The First Step for Leaders for Better Meetings [26:08] Finding Your Source in Burnout [33:40] The Question You Need to Ask [40:19] Resources: Jon Berghoff's LinkedIn: https://www.linkedin.com/in/jonberghoff/ Jon Berghoff's Twitter: https://mobile.twitter.com/jon_berghoff Jon Berghoff's Facebook: https://www.facebook.com/jon.berghoff The XCHANGE Approach Website: https://xchangeapproach.com/about/ The XCHANGE Approach Facebook: https://www.facebook.com/Xchange-Approach-106338757740048 The XCHANGE Approach LinkedIn: https://www.linkedin.com/company/xchange-approach/?trk=public_profile_experience-item_profile-section-card_image-click&originalSubdomain=pa RLD Group's website: https://rldgroupllc.com RLD Group's LinkedIn: https://www.linkedin.com/company/rldgroupllc RLD Group on Twitter: https://twitter.com/rldgroupllc Lisa Duerre on Instagram: https://www.instagram.com/lisaduerrecoaching/ Lisa Duerre on Facebook: https://www.facebook.com/lisaduerrecoaching Lisa Duerre on Twitter: https://twitter.com/lisaduerre CTRL+ALT+DELETE with Lisa Duerre on YouTube: https://youtube.com/playlist?list=PLnVM-c8OdQ2Xfg70hyysiMU2Pnu-qCDGK
Robbie and Abby Martin continue their psychedelic series with an episode about the DEA raid on the LSD missile silo manufacturing plant, Robbie's quest for psychedelics online, his experience taking 2-C-T-7 and dangerous attempts to synthesize DMT at his home. They discuss the fear campaign around several overdoses of 2-C-T-7 and introduce the groundbreaking life and work of the brilliant chemist behind 200+ psychedelic analogs, including MDMA, Alexander “Sasha” Shulgin and his wife Anne. This is Episode 5 of an ongoing series on Psychedelic History, Episodes 1-5 are availible now. Patreon subscribers at the $5 tier get access to Episode 4 of the series: www.patreon.com/mediarootsradio Previous: Episode 1: A Brief History of Hallucinogens, MK-Ultra, the CIA, LSD, Leary & the Psychedelic 60s / 70s Episode 2: How Raves Brought Back the Psychedelic Subculture, DanceSafe, Pill Tests & the DEA vs MDMA Episode 3: Terrence McKenna, Johnathan Ott, DMT, Pharmahuasca, Heroic Dosing, Utopianism & the Psychedelic New Age Episode 4: When Microsoft Employee #9 Boosted an Online Psychedelic Revolution, Erowid.org, DXM & Salvia FOLLOW // twitter.com/AbbyMartin // twitter.com/FluorescentGrey //
Jordan Roy-Byrne reviews gold bull market correction analogs, 2-year treasury yields, and high oil prices in relation to gold mining stocks.
CastSusan ThanabalasingamDana LarsenMythri ShankarSandy SureshReferencesNeal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. New England Journal of Medicine. 2017 Aug 17;377(7):644–57.Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019 Jun 13;380(24):2295–306.Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in Patients with Chronic Kidney Disease. New England Journal of Medicine. 2020 Oct 8;383(15):1436–46.Joshi SS, Singh T, Newby DE, Singh J. Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure. Heart. 2021 Jul 1;107(13):1032–8.Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine. 2015 Nov 26;373(22):2117–28.ScriptContributors: Susan Thalabalasingam, Mythri Shankar, Dana Larsen, Sandhya SureshHost (Susan):Hey everyone! Welcome to our episode of 2 truths and a lie, an NSMC podcast.Let's go over the ground rules.One at a time each member of our elite education panel will state two truths and one lie about Nephrology.This episode will focus specifically on SGLT2 inhibitors. The other panelist will then discuss which statement they think is The Lie.Our presenter will then educate us all on which statement is incorrect and why.So let's warm up our lie detectors.Let's meet our four players for today.I'm your host Susan Thanabalasingam and I'm a first year internal medicine resident at Queen's University in Kingston, Ontario, Canada. I'm really excited to be your host today and to have an amazing discussion with these wonderful women today! Our second panelist is Dr. Mythri Shankar from India. Hi Dr. Mythri, can you please introduce yourself?Mythri: Hello everyone. I am Dr. Mythri Shankar, Assistant Professor in Nephrology from Institute of Nephro-urology, Bengaluru, India.I am also the Associate Program Director of the NSMC. Glad to be here and I have no conflicts of interest to declare.Our third Panelist Dr. Dana Larsen from the United States of America! Hi Dr. Larsen, can you please introduce yourself? Dana: Hi all! I am Dana Larsen, a second year nephrology fellow at University of California, San Francisco and so grateful to get to be on this podcast with this great group today. I have no conflicts of interest in today's topics. Our fourth Panelist is Dr. Sandhya Suresh from India. Hi Dr. Suresh, can you please introduce yourself?Sandhya: Hi to all my fellow members of the 4th Pod, the Distal convoluted Pod and also… Hi to everyone listening to this podcast. I am Dr. Sandhya Suresh and I'm an early career nephrologist working in a medical college in Southern India. My only declaration here is that I am a flozinator who is continually amazed by everything that the SGLT inhibitors can do. Susan: Great, so let me start, I'll give you 3 statements. My statements all focus on the use of SGLT2i in the non-diabetic CKD setting, which is a cohort that merits special attention when discussing the benefits of SGLT2i use (Susan)SGLT-2 inhibitors are nephroprotective in diabetic and non-diabetic CKD (TRUE)SGLT2 inhibitors decrease proteinuria in non-diabetic CKD (TRUE)SGLT2 inhibitors are indicated for all etiologies of non-diabetic CKD (FALSE) Explanation for 1 → Statement 1 is TRUE. SGLT-2 inhibitors are in fact nephroprotective in BOTH diabetic and non-diabetic CKD. The CREDENCE trial was the first to specifically examine kidney outcomes in patients with diabetic, proteinuric CKD, and it demonstrated significant decrease in risk for kidney failure and cardiovascular events in patients treated with canagliflozin (Perkovic et al, 2019). As the effects were independent of glucose lowering effects, further studies have been conducted in the non-diabetic CKD setting. DAPA-CKD included patients with both diabetic and non-diabetic CKD and found that the use of dapagliflozin was associated with decreased risk of >= 50% decline in eGFR, ESKD or death from renal or cardiovascular causes (Heerspink et al, 2020). Explanation for 2 → Statement 2 is ALSO TRUE. We do in fact have compelling data that proteinuria is reduced with the use of SGLT2i in non-diabetic kidney disease. Pre-specified analyses from the DAPA-CKD trial demonstrated that dapagliflozin significantly reduced proteinuria in both diabetic and non-diabetic CKD, although the effect was larger in the diabetic subset. Because clinical outcomes were similar with dapagliflozin initiation between diabetic and non-diabetic patients, despite this difference in effect size on proteinuria, it has been postulated that the observed nephroprotection may not actually be related to reduction in proteinuria. Explanation for 3 → Statement 3 was the FALSE statement. In DAPA-CKD, included etiologies of non diabetic CKD were FSGS, minimal change disease, chronic pyelonephritis, chronic interstitial nephritis and hypertensive, IgA, membranous, and obstructive nephropathies. However, patients with lupus nephritis, polycystic kidney disease and vasculitis were excluded. The results of EMPA-Kidney are highly anticipated, in part as it includes a larger number of participants without diabetes, in particular those with glomerular disease, which will hopefully give us more answers about whether these patients will also benefit from SGLT2i initiation. EMPA-Kidney does however also exclude patients with PKD (The EMPA-KIDNEY Collaborative Group, 2022). That was fun, I can't wait to hear more from the rest of our panelists. Moving on to Dr. Mythri now, can you please give us your 2 truths and a lie?Mythri:SGLT2i are the initial therapy for T2DM (FALSE)SGLT2i are beneficial in heart failure with reduced ejection fraction as it reduces both preload and afterload (TRUE)SGLT2i are analogs of Phlorizin (TRUE)Explanation for 1. SGLT2i are not the initial therapy. Initial therapy consists of lifestyle modifications, diet and exercise (American diabetes association guidelines 2021).Explanation for 2. SGLT2 inhibitors promote osmotic diuresis and natriuresis in patients with and without diabetes, and thus may reduce preload. SGLT2 inhibitors may also have vascular effects (including improving endothelial function) that promote vasodilation and thus may also reduce afterload. It has also been postulated that SGLT2 inhibitors may improve myocardial metabolism and thus improve cardiac efficiency. SGLT2 inhibitors promote osmotic diuresis and natriuresis in patients with and without diabetes, and thus may reduce preload (Joshi et al, 2021).Explanation for 3:A natural compound, phlorizin, was isolated from apple trees in the early 1800s and for decades played an important role in diabetes and renal physiology research. The compound is poorly absorbed from the gastrointestinal tract and inhibits both SGLT1 (primarily found in the gastrointestinal tract) and SGLT2. Analogs of phlorizin have been developed that circumvent these two problems. These are the current SGLT2i (Atanasov et al, 2016).Susan: That was great Dr. Mythri, thank you, I feel like I learned so much! Moving on to Dr. Dana, can you give us your 2 truths and a lie?Dana:Awesome, thank you Susan! Alright, please identify the lie from among these statements all concerning potential SGLT2 side effects:SGLT2 inhibitors definitively increase the risk of vulvovaginal candidiasis and may increase the risk of urinary tract infections. (TRUE)SGLT2 inhibitors do not definitively increase risk of bladder cancers. (TRUE)SGLT2 inhibitors definitively increase risk for limb amputations. (FALSE)Do you think you have the answer!?! Let's take a closer look…My first statement, SGLT2 inhibitors definitely increase the risk of urinary tract infections and vulvovaginal candidiasis is TRUE. Multiple studies on SGLT2 inhibitors including a 2018 canagliflozin RCT and a 2013 dapagliflozin RCT have shown 2-4 fold increase in vulvovaginal candidiasis in 10-15% of patients on SGLT2 inhibitors compared with placebo (Neal et al, 2017). A 2019 meta-analysis of over 100 RCTs with SGLT2s compared with other anti-diabetic agents or placebo did NOT show an increase in risk of UTIs for SGLT2s as a group, though there was a signal for increased risk of UTIs specifically for dapagliflozin, mechanistically it is unclear why this would be the case (Donnan et al, 2019). At this time, where there is definitive increased risk of vulvovaginal candidiasis, increased risk of UTI is likely not something you need to counsel your patients on.Alright, moving on, our second statement, SGLT2 inhibitors do not definitely increase risk of bladder cancers is also TRUE. While few cases of bladder cancers have been diagnosed in patients taking dapagliflozin, half of these occurred within the first 6 months, which is thought to be too soon for tumorigenesis promotion by dapagliflozin itself. EMPA-REG trial did not find increased incidence of bladder cancer once event rates that occured within the first 6mo of drug therapy were removed (Kohler et al, 2017). Currently, the FDA recommends ongoing postmarketing surveillance And finally, moving on to our final statement which must be FALSE given the name of the game, the statement says SGLT2 inhibitors definitively increase risk for limb amputations. While the CANVAS program found that in the over 10,000 combined patients from their two major trials there was an increased risk of amputations 6.3 vs 3.4 per 1000 participants with hazard ratio 1.97, these amputations were primarily at the level of the toe or metatarsal, not the limb (Neal et al, 2017). Furthermore, there is ongoing discussion over true risk of amputation attributed to SGLT2 inhibitors as post hoc analysis of empa-reg and CREDENCE, the renal outcomes trial for canagliflozin, no association for increased risk of lower extremity amputation was found (Perkovic et al, 2019). While further investigation into the topic is warranted, we can rest assured that this is our FALSE statement on side effects of SGLT2-inhibitors. Susan: Wow Dana, thanks so much for those very important lessons on SGLT2i side effects, I certainly have a lot of take home points from your discussion! Perfect, now we'll move on to Dr. Sandhya. Please join me in welcoming her to give us our final set of 2 truths and a lie today.Sandhya:Thank you Susan. So here, I will be focussing my 2 truths and a lie on the cardioprotective effects of SGLT2 inhibitors. Without further ado, here are my 3 statements:Statement 1: Increased ketone body production is postulated as one of the mechanisms for the cardioprotective effects of SGLT2 inhibitors (TRUE)Statement 2: Glucose lowering effect and cardiovascular benefits both decline at lower GFRs (FALSE)Statement 3: Sotagliflozin in a combined SGLT2 and SGLT1 inhibitor which has demonstrated cardioprotective benefits (TRUE)Explanations for the above statements: Let me go through the explanation for each statement one by one.Statement 1 is true. The cardioprotective effects of SGLT2 inhibitors may be multifactorial. While they target the traditional cardiovascular risk factors through their glycosuric and natriuretic effects, it is also postulated that SGLT2 inhibitors improve the cardiac metabolism and bioenergetics. 90-95% of cardiac energy is derived from mitochondrial oxidative metabolism for which the predominant fuel is free fatty acids. In a diabetic heart, the metabolic flexibility in terms of substrate utilization is impaired and the myocardium becomes more dependent on free fatty acids as fuel leading to build up of free fatty acid intermediates which lead to lipotoxicity and myocardial dysfunction. SGLT2 inhibitors produce a starvation simulation with reduced insulin and higher glucagon levels which promotes lipolysis and ketogenesis. They also reduce the excretion of ketone bodies by reducing the GFR. These ketone bodies like beta hydroxybutyrate serve as an alternate super fuel for myocardial cells producing ATP more efficiently and help to preserve the mitochondrial integrity and these factors lead to improved cardiac efficiency (Joshi et al, 2021).Now coming to statement 2. The glucose lowering effect of SGLT2 inhibitors does decrease with declining GFRs because the magnitude of glucose excretion and consequently the HbA1c reduction is dependent on the filtered glucose load. This filtered glucose load is high in diabetic patients with normal GFR and reduced in patients with renal impairment thereby leading to reduction in the glucose lowering effect of SGLT2 inhibitors (Kelly et al, 2018). Conversely, the cardioprotective effects of this class of drugs seems to be remarkably preserved at lower GFRs as has been demonstrated in several trials. For example, in the EMPAREG OUTCOME trial, analysis of a subgroup of patients with prevalent kidney disease was done which included type 2 diabetic patients with established cardiovascular disease and an estimated GFR between 30-60 . There was significant reduction in the cardiovascular and all-cause mortality as well as hospitalization for heart failure in this subgroup and this effect was consistent across different categories of GFR (Wanner et al, 2017). So statement 2 is false.So by that logic statement 3 has to be a truth. We often talk about the 4 traditional flozins so I just wanted to throw in a statement about this new subclass within this class of agents. Sotagliflozin is an SGLT2 inhibitor which also inhibits the intestinal SGLT1 transporters. It was originally targeted for use in patients with type 1 diabetes mellitus with the hope that SGLT1 inhibition in the intestine could reduce postprandial hyperglycemia and improve overall glycemic control in these patients. Studies have also shown excellent efficacy for this purpose. However they also showed a higher incidence of Diabetic ketoacidosis episodes. 2 cardiovascular trials were conducted, both of which unfortunately, ended early as they lost funding sometime during the COVID pandemic. The SCORED trial included CKD patients and the SOLOIST-WHF trial included patients who had recently recovered from an episode of decompensated heart failure. I won't go into the strengths and limitations of these trials but they did show benefit in terms of cardiovascular endpoints in the sotagliflozin group compared to placebo (Bhatt et al, 2021; Bhat et al, 2021). The drug isn't commercially available as of now and is not FDA approved yet but it remains as a novel agent within the SGLT2i landscape.Susan (Conclusion by host):Amazing, thank you so much Dr. Sandhya! That was an enlightening discussion on cardioprotection with SGLT2i use. And this has been so much fun! I hope you've all found our conversation really helpful and informative - I certainly know that I have learned a lot from my colleagues today. I can't thank them enough for sharing their time and expertise with us. Be sure to tune in next time for more FOAMed nephrology education.
W 15 odcinku rozmów moim gościem jest Wiktor Lekston, który jako Cult Nug (a wcześniej jako Sztuka Naiwna) tworzy analogowe teledyski dla zespołów z różnych zakątków świata. W polsce zadebiutował video "Butelka pełna łez" The Analogs. Pogadaliśmy o tym, jak i po co się to robi :) Zapraszam!
W 11 odcinku rozmów moim gościem jest Kamil Rosiak, wokalista i gitarzysta The Analogs. Z Kamilem porozmawialiśmy o jego muzycznej drodze, Ruin Cats, Analogsach i nowych projektach, z którymi ostatnio kombinuje na boku ;) Zapraszam.Nagrywaliśmy w trakcie wichury, co niestety odbiło się na jakości audio.
Sean McMillan (aka the guy who does all our promo and YouTube graphics) joins the Bandits for the last Bandit Bits episode of the year! We're still in the Season of Superman, so we're reviewing all the different versions of the Man of Steel. First, we run through Superman's evolution chronologically. Then, it's on to alternate versions of the Big Blue Boy Scout. And finally, we look at Supermen from other companies: analogs like Apollo, Sentry, and Supreme. Get to listening, Banditos!____________________________________Check out and subscribe to YEET Presents on Patreon: patreon.com/yeetmagazine.Email us at dollarbinbandits@gmail.com. Follow us @dollarbinbandits on Facebook and Instagram, and @DBBandits on Twitter.
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How do our bodies know what to become? There are no instructions in our genes that code for the exact 3D structure of our bodies. There's no tiny human contained in our DNA. So, what powers the transformation of the first cell in the embryo to a full-blown organism? Dr Michael Levin is attacking this problem and, in the process of answering it, his lab is uncovering an entirely new way of looking at biology. == What we talk about == 0:04 - Introduction 1:20 - You were a software engineer. How did you get interested in biology? 6:50 - Can bacteria exhibit intelligent behavior? 7:46 - How do organisms take their final shape? 22:51 - How do cells in our body know when to stop multiplying? 27:49 - Analogs of software and hardware in developmental biology 34:20 - Where are the body plans stored in complex organisms like ours? 43:33 - What post-DNA paradigms are important in biology? 48:20 - What is regenerative medicine? 50:20 - How far have we progressed in regenerative medicine? 52:52 - Xenobots: world's first synthetic organisms 1:00:12 - How to program Xenobots 1:05:13 - How do you handle the ethical dilemma while you are working with conscious organisms? 1:10:22 - How do you enable the scientific creativity in your lab and amongst your students? And is it a teachable skill? == About the guest == Michael Levin is a Distinguished Professor in the Biology department at Tufts and serves as director of the Allen Discovery Center. He holds a PhD in biology from the Harvard University. At Tufts, his research group is interested in figuring out how our bodies know what to become. He believes that what guides our body plans is bio-electric communication between different units. Our bodies take shape the way they have because each of our subunits - cells, tissues, organs - collectively decides it to be that way.
In this episode, I have talked about Autonomous Adaptation in Climate Change.Topics Covered:IntroductionConceptual WorkTypes of adaptionsAdaptation strategies/ methodsAdaptive capacityAdaptation characteristicks Systems, scales and actorsFuture AdaptationsModels, Analogs, Empirical analysisReasons to adopt it nowTwitter: https://twitter.com/realyashnegiSuggestions are always welcome: yashnegi@climatology.inWebsite: climatology.inSupport the show (https://paypal.me/yashnegi27?locale.x=en_GB)
Inside Ozadia Ep. 8 - Mark and Christian discuss various "model/analog" plants for Cannabis cultivation and commercial production. Tomato morphology, hop familial similarity, and grape cultivation intensity are compared to cannabis. www.ozadia.com
Travis is back for a lengthy Sunday/Monday show. Kevin Dern joins the program to discuss Miami's defensive scheme and the fits for the players in the new scheme. Can Christian Wilkins do more than 1-gap? Can Jerome Baker function as a pass rusher? Where does Eric Rowe slot it? Tons of great content and analysis, plus a discussion on Miami's uniforms, logo, and grown men wearing football jerseys.@WingfieldNFL@LockedOnPhins@KevinMD4LockedOnDolphins.comLockedOnPodcasts.com Learn more about your ad choices. Visit podcastchoices.com/adchoices
Travis is back for a lengthy Sunday/Monday show. Kevin Dern joins the program to discuss Miami's defensive scheme and the fits for the players in the new scheme. Can Christian Wilkins do more than 1-gap? Can Jerome Baker function as a pass rusher? Where does Eric Rowe slot it? Tons of great content and analysis, plus a discussion on Miami's uniforms, logo, and grown men wearing football jerseys.@WingfieldNFL@LockedOnPhins@KevinMD4LockedOnDolphins.comLockedOnPodcasts.com Learn more about your ad choices. Visit podcastchoices.com/adchoices
Travis is back for a lengthy Sunday/Monday show. Kevin Dern joins the program to discuss Miami's defensive scheme and the fits for the players in the new scheme. Can Christian Wilkins do more than 1-gap? Can Jerome Baker function as a pass rusher? Where does Eric Rowe slot it? Tons of great content and analysis, plus a discussion on Miami's uniforms, logo, and grown men wearing football jerseys. @WingfieldNFL @LockedOnPhins @KevinMD4 LockedOnDolphins.com LockedOnPodcasts.com Learn more about your ad choices. Visit podcastchoices.com/adchoices
Before we send any planet-trotting robot to explore the landscape of Mars or Venus, we need to test it here on Earth. Two such robotic platforms being developed for future missions are undergoing testing at European Space Agency facilities: one that rolls, and one that hops. The rolling one is actually on the books to head to the Red Planet as part of the ESA's Mars 2020 program.
In the May 2015 Southwest Climate Podcast, Zack Guido and Mike Crimmins reconvene to talk about the Winter patterns that fed into our current situation, and how it has actually been pretty moist and cool (for this time of year) after a very warm winter. They then turn back to El Niño - which despite being hard to predict, forecast, or describe - has given us a lot to think about. They exercise some warranted caution in putting too much stock in forecasts given the "excitement" surrounding a strong El Niño event, but the patterns in place are suggesting this enthusiasm might not be misplaced. They move on to talk about how El Niño may affect tropical storm activity and monsoon patterns looking into Summer and Fall 2015, as well as the impacts of last year's monsoon (and mild weather this Spring) on fire season. Drought and water availability present a less optimistic scenario - below average winter precipitation and above average winter temperatures for most of the Western U.S. mean snowpack is well below average heading into summer, with implications for water storage and availability. 0:00 -- Intro - Our Most (Least) Favorite Month of the Year, Winter Recap & El Niño 2:20 -- Recapping Winter Patterns - Precipitation, Temperature, Record Setting Averages & "Warm West / Cold East" Jetstream Patterns 5:00 -- Jetstream as ENSO Precursor Pattern - Transition into an El Niño Event Now That the Atmosphere is Finally Cooperating 8:30 -- Different from Last Spring - Despite Similarities with Spring 2014 (in the Models) - "Excitement" in the Models 11:00 -- Caution in Forecasting El Niño - Spring Predictability Barrier - Difficulty in Modeling in the Spring, Analogs, and Small Sample Size 15:00 -- Shifts in Global Circulation - How this Affects Tropical Storm Activity & Monsoon Precipitation (for the Southwest, mainly) - Flooding Hazards with El Niño 19:30 -- Monsoon & Fire Season - Heading into Fire Season - Mixed Precipitation but Late/Wet/Cool Spring Tamping Down Early Fire Season - California and NW may be in trouble regarding Fire, while Monsoon Patterns will bring Summer Relief (for AZ and NM) 23:30 -- Recap of Winter/Spring Patterns & Streamflow - Split Flow Jetstream and Character of Spring Storms - Very "El Niño-ish" - Recap of Streamflow Projections - Below Average Winter Precipitation Across the West (Plus High Temperatures) 27:00 -- Looking Forward to the Monsoon - Hoping for a Good Monsoon That Starts on Time If you have a question you'd like answered, you can email Ben McMahan (bmcmahan@email.arizona.edu) with "CLIMAS Podcast Question" in the subject line. You can also tweet us @CLIMAS_UA or post a question on facebook Suggested Source/Citation: CLIMAS: Climate Assessment for the Southwest, (2015) May 2015 SW Climate Podcast - Winter Recap Following a Mild Spring, El Niño Slotting into Place, and Looking Towards Summer - with Wildfire, Tropical Storms, and the Monsoon on Tap [podcast] CLIMAS Southwest Climate Podcast. Available at: climas.arizona.edu/podcast/may-2015-sw-climate-podcast-winter-recap-following-mild-spring-el-ni%C3%B1o-slotting-place-and [Date Accessed] CLIMAS Member(s): Michael Crimmins Zack Guido
In the May 2015 Southwest Climate Podcast, Zack Guido and Mike Crimmins reconvene to talk about the Winter patterns that fed into our current situation, and how it has actually been pretty moist and cool (for this time of year) after a very warm winter. They then turn back to El Niño - which despite being hard to predict, forecast, or describe - has given us a lot to think about. They exercise some warranted caution in putting too much stock in forecasts given the "excitement" surrounding a strong El Niño event, but the patterns in place are suggesting this enthusiasm might not be misplaced. They move on to talk about how El Niño may affect tropical storm activity and monsoon patterns looking into Summer and Fall 2015, as well as the impacts of last year's monsoon (and mild weather this Spring) on fire season. Drought and water availability present a less optimistic scenario - below average winter precipitation and above average winter temperatures for most of the Western U.S. mean snowpack is well below average heading into summer, with implications for water storage and availability. 0:00 -- Intro - Our Most (Least) Favorite Month of the Year, Winter Recap & El Niño 2:20 -- Recapping Winter Patterns - Precipitation, Temperature, Record Setting Averages & "Warm West / Cold East" Jetstream Patterns 5:00 -- Jetstream as ENSO Precursor Pattern - Transition into an El Niño Event Now That the Atmosphere is Finally Cooperating 8:30 -- Different from Last Spring - Despite Similarities with Spring 2014 (in the Models) - "Excitement" in the Models 11:00 -- Caution in Forecasting El Niño - Spring Predictability Barrier - Difficulty in Modeling in the Spring, Analogs, and Small Sample Size 15:00 -- Shifts in Global Circulation - How this Affects Tropical Storm Activity & Monsoon Precipitation (for the Southwest, mainly) - Flooding Hazards with El Niño 19:30 -- Monsoon & Fire Season - Heading into Fire Season - Mixed Precipitation but Late/Wet/Cool Spring Tamping Down Early Fire Season - California and NW may be in trouble regarding Fire, while Monsoon Patterns will bring Summer Relief (for AZ and NM) 23:30 -- Recap of Winter/Spring Patterns & Streamflow - Split Flow Jetstream and Character of Spring Storms - Very "El Niño-ish" - Recap of Streamflow Projections - Below Average Winter Precipitation Across the West (Plus High Temperatures) 27:00 -- Looking Forward to the Monsoon - Hoping for a Good Monsoon That Starts on Time If you have a question you'd like answered, you can email Ben McMahan (bmcmahan@email.arizona.edu) with "CLIMAS Podcast Question" in the subject line. You can also tweet us @CLIMAS_UA or post a question on facebook Suggested Source/Citation: CLIMAS: Climate Assessment for the Southwest, (2015) May 2015 SW Climate Podcast - Winter Recap Following a Mild Spring, El Niño Slotting into Place, and Looking Towards Summer - with Wildfire, Tropical Storms, and the Monsoon on Tap [podcast] CLIMAS Southwest Climate Podcast. Available at: climas.arizona.edu/podcast/may-2015-sw-climate-podcast-winter-recap-following-mild-spring-el-ni%C3%B1o-slotting-place-and [Date Accessed] CLIMAS Member(s): Michael Crimmins Zack Guido
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