POPULARITY
5 episodes with marelli
5 episodes with marelli
2 episodes with marelli
2 episodes with marelli
6 episodes with marelli
2 episodes with marelli
2 episodes with marelli
5 episodes with marelli
4 episodes with marelli
- Major Suppliers Consider Buyout Plan - Nissan Could Sell Its Headquarters - ICEs Drag Down EU Market in April - Volvo Plans 3,000 Job Cuts - Toyota Starts Making GR Corolla in the UK - BMW Brings Back Clown Shoe Design - Alpine Reveals Its 1st SUV - Autoline Poll Results
- Major Suppliers Consider Buyout Plan - Nissan Could Sell Its Headquarters - ICEs Drag Down EU Market in April - Volvo Plans 3,000 Job Cuts - Toyota Starts Making GR Corolla in the UK - BMW Brings Back Clown Shoe Design - Alpine Reveals Its 1st SUV - Autoline Poll Results
Ascolta l'episodio post-partita: https://pod.fo/e/2d04deDalla moviola al clean sheet, Zalewski e l'analisi di Inter-Verona 1-0 con 5 curiosità.
Intervista esclusiva a Luca Marelli su Passione Inter. Giudizio su Arbitri e Var, gli episodi più discussi in casa Inter: Lautaro-Ismajli, Thuram-Skorupski e il fallo di Morata su Asllani in finale di Supercoppa Italiana. Tutte le domande ESCLUSIVE dei membri della nostra Community.
Ottavo appuntamento con OCW Talk! Il podcast condotto da Pancio e Manfredi che scava tra vita e carriera dei suoi ospiti.Oggi si sgabella con noi : LUCA MARELLI!
CT Automotive CEO, Simon Phillips and CFO, Anna Brown present the group's results for the half year ended 30 June 2024, followed by Q&A. Simon Phillips, CEO 00:16 - Introduction 00:34 - About CT Automotive Anna Brown, CFO 03:16 - HY24 Financial highlights Simon Phillips, CEO 05:18 - HY24 Operational highlights Anna Brown, CFO 07:06 - Income statement 09:13 - Revenue bridge 10:41 - Gross profit margin bridge 12:26 - Adjusted EBITDA bridge 13:47 - Balance sheet 14:42 - Net debt bridge 16:17 - ESG Simon Phillips, CEO 17:09 - Operational review 19:23 - Automation 20:31 - Outlook 22:00 - Q&A CT Automotive is engaged in the design, development and manufacture of bespoke automotive interior finishes (for example, dashboard panels and fascia finishes) and kinematic assemblies (for example, air registers, arm rests, deployable cup holders and storage systems), as well as their associated tooling, for the world's leading automotive original equipment suppliers ("OEMs") and global Tier One manufacturers. The Group is headquartered in the UK with a low cost manufacturing footprint. Key production facilities are located in Shenzhen and Ganzhou, China complemented by additional manufacturing facilities in Mexico, Türkiye and Czechia. CT Automotive's operating model enables it to pursue a price leadership strategy, supplying high quality parts to customers at a lower overall landed cost than competitors. This has helped the Group build a high-quality portfolio of OEM customers, both directly and via Tier One suppliers including Forvia and Marelli. End customers include volume manufacturers, such as Nissan, Ford, GM and Volkswagen Audi Group, and premium luxury car brands such as Bentley and Lamborghini. In addition, the Group supplies all our customer base with a range of products for PHEV and BEV platforms and supplies electric car manufacturers, including Rivian and a US based major EV OEM. The Group currently supplies component part types to over 57 different models for 22 OEMs. Since its formation, the Group has been one of the very few new entrants to the market, which is characterised by high barriers to entry.
MARELLI IMPUL ZがひさびさにスーパーGTの表彰台に戻ってきた。直近に行われた鈴鹿と富士の2ラウンドで、ともにニッサンZニスモGT500の最上位となる4位と5位を記録するなど、調子の上向きを感じさせるなかで第6戦SUGOに臨んだ2022年王者は、雨に翻弄された週末の決勝で3位を獲得し1年3カ月ぶりに表彰台に上がった。レース後、12号車MARELLIの平峰一貴に聞いた。 「調子としては悪くありませんでした」と平峰が言うように、12号車MARELLI IMPUL Zは9月21日（土）午前の走り始めから上位につけた。悪天候が予想されたため、事前に午後の予選に代わって決勝レースのグリッドを決めるセッションになる可能性があるとされた公式練習で、平峰が1分26秒115の5番手タイムを記録。その後、実際に予選がキャンセルされたため12号車MARELLIは3列目5番グリッドから決勝レースをスタートすることとなった。 投稿 MARELLI IMPUL Zがひさびさの表彰台。2位バトルに平峰一貴「楽しかったが、スープラには敵わなかった」 は autosport web に最初に表示されました。
Benedetto Marelli is a biomedical engineer by training and a materials scientist. He is an associate professor in MIT's Department of Civil and Environmental Engineering. His work is focused on the fabrication of new biopolymers that can interact with biomolecules, living matter, and the environment. Here, Benedetto speaks with MIT President Sally Kornbluth about the advantages of using silk-based coatings in agriculture as well as for water filtration, and why being bold and creative can lead to powerful discoveries.Links:Laboratory for Advanced BiopolymersCivil and Environmental EngineeringMIT Climate ProjectTimestamps:(01:23) - The benefits of silk use for agriculture(06:00) - MIT's Climate Grand Challenges(07:12) - Using silk to filter out forever chemicals(09:31) - MIT's Climate ProjectShow notes and transcript:https://news.mit.edu/podcast/podcast-curiosity-unbounded-episode-8-hard-facts-soft-skillsJoin the mailing list or send us feedback:https://eepurl.com/ixPQPA
Fascia is the Wi-Fi of your insides, with over 250 million sensory receptors weaving through its matrix - it's how emotions are made and where we feel our sensations, instincts and intuition. But if you tend to overthink, ruminate, catastrophize or stress out, you're compromising your fascia which impacts your body's ability to function optimally + think clearly. Discover why fascia is the missing puzzle piece for perfectionists and how to detect if there's dead zones in your own fascial network- where your sensations, instincts and intuition intersect. On paper, you've got it together— isn't it time you felt like it? Perfectionism Optimized, private 1-1 coaching gives you the life-long skills to *finally feel* as amazing on the inside as your life looks on the outside. Get your stress-free start today at https://courtneylovegavin.com/optimized EP 228 TIMESTAMPS:01:38-The Role of Fascia in Mental Clarity and Confidence02:10-Where fascia is found and its impact on your body03:03-Fascia's Role in Breaking Generational Belief Patterns04:06-How fascia sends and receives information at the speed of light05:01-Wi-Fi of your Insights + Intuition06:10-What Skin is to Touch, Fascia is to Your Feelings07:25-How To 10x Your Emotional Intelligence09:18-The flexibility of fascia for quick improvements10:15-Benefits of upgrading your fascia's communication system. Truth + Accuracy Brought To You By:Bordoni, B., & Marelli, F. (2017). Emotions in Motion: Myofascial Interoception. Complementary Medicine Research, 24(2), 110–113. https://doi.org/10.1159/000464149Bordoni, B., & Simonelli, M. (2018). The Awareness of the Fascial System. Curēus. https://doi.org/10.7759/cureus.3397Fede, C., Petrelli, L., Guidolin, D., Porzionato, A., Pirri, C., Fan, C., … Stecco, C. (2021). Evidence of a new hidden neural network into deep fasciae. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-92194-zPalomero-Gallagher, N., & Katrin Amunts. (2021). A short review on emotion processing: a lateralized network of neuronal networks. Brain Structure & Function, 227(2), 673–684. https://doi.org/10.1007/s00429-021-02331-7
Cos'è la Data Governance e perché è importante? Quali sono le sfide per implementare un reale controllo sui dati? Quali sono le migliori strategie per vincere queste sfide? In che modo il Cloud di AWS è un facilitatore? In questo episodio ospitiamo Francesco Marelli, Principal Solutions Architect di AWS, per parlare dell'importanza della Data Governance e di come Amazon Data Zone può aiutare nell'implementarla. Link utili: - Cos'è la governance dei dati? https://aws.amazon.com/it/what-is/data-governance/ - Amazon DataZone: https://aws.amazon.com/datazone/
Japan's Top Business Interviews Podcast By Dale Carnegie Training Tokyo, Japan
Previously Tim was an Associate General Counsel at Marelli, Director Indirect Sales at Colt Technology Services, Senior Lawyer Minter Ellison Lawyers. He has a Law Degree, Bachelor of Asian Studies and is a graduate from the from the Kellogg-HKUST Executive MBA
In this episode of the 'Life in Transition' podcast, Art Blanchford speaks with Sherry Vasa, Executive Vice President and Chief People & Organization Officer at Marelli, who shares her transformative journey of learning to find peace in the midst of chaos.Sherry shares her journey from corporate burnout through a health crisis to discovering profound inner peace. She elaborates on the transformative power of meditation, her shift from identifying with her job and her illness to finding her true self, and managing a demanding role with intention and resilience. Sherry's story offers valuable insights on resilience, self-awareness, and the power of taking time for inner reflection.On this episode, we'll talk about:Exploring the core components of emotional intelligenceUnderstanding the role of self-awareness in emotional regulationTechniques for navigating challenging emotions and stressorsBuilding empathy and fostering stronger interpersonal connectionsLeveraging emotional intelligence for effective leadership and communicationCultivating resilience and adapting to change in dynamic environmentsLet's connect! Follow us on social media for a daily dose of inspiration, updates, and behind-the-scenes moments.FacebookInstagramXLinkedInExplore our website for more in-depth information, resources, and to download the 8-step guide to mastering mid-life transitions.My new book PURPOSEFUL LIVING is out now. Order it now: https://a.co/d/cJKOpo6The views and opinions expressed on the Life In Transition podcast are solely those of the author and guests and should not be attributed to any other individual or entity. This podcast is an independent production of Life In Transition, and the podcast production is an original work of the author. All rights of ownership and reproduction are retained—copyright 2024.
Chiara Delporto, VP Advanced Sales for SDV from Marelli joins Sonatus Chief Marketing Officer John Heinlein, Ph.D., to discuss leading automotive Tier-1 supplier Marelli and their perspective on latest trends in the automotive industry ranging from software, vehicle personalization, the importance of the cloud, machine learning, sustainability and much more. Recorded live at CES 2024.
Have a question you want Katie to answer on an upcoming episode? Submit your Colorful Question now!When it comes to color and textile trends, Europe typically is ahead of the U.S. market—but what if you could finally walk alongside European designers? What if you had access to the same trend forecaster and color consultant they do? Well, join me in welcoming Nello Marelli to the show! Nello is a color consultant and trend forecaster. In today's episode, we're talking about the importance of color in design, how to create harmonious environments using color, and the significance of trends. And as an added bonus, we've partnered with Nello on an exclusive design resource to help you stand out from the competition. Press play and make sure you stay til the end to see if today's Colorful Question is yours!In this episode, you will:Discover the deeper importance of color and textile trends in design.Learn how you can successfully use trends in your design work.Learn about an exclusive resource we've partnered with Nello to bring to U.S. designers.Full Show Notes Here!
Testo e foto di openIA Testo trasformato in audio progetto cultura per ipovedenti di @tepare
Tune into episode 357 of the Mobile Tech Podcast with guests Bill Stewart (Infineon) and Adam Doud (SlashGear) -- brought to you by Infineon. Today's episode comes in two parts. First, we explore how semiconductors in EVs accelerate Infineon's mission towards digitalization and decarbonization. Second (18:12), we recap CES 2024 by sharing our favorite tech from the show -- including the Clicks keyboard case for iPhone, Rabbit R1 pocket companion, Realme 12 Pro+, and more. Enjoy :)Episode Links- Support the podcast on Patreon: https://www.patreon.com/tnkgrl- Donate: https://tnkgrl.com/tnkgrl/- Infineon: https://www.infineon.com/cms/en/product/promopages/oktobertech/americas/ (sponsor)- Bill Stewart: https://www.linkedin.com/in/stewart-bill/- Adam Doud: https://twitter.com/DeadTechnology- Clicks keyboard case: https://www.theverge.com/2024/1/11/24034555/clicks-keyboard-case-iphone-hands-on- Rabbit R1: https://www.tomsguide.com/reviews/rabbit-r1- Lenovo booth tour: https://hothardware.com/news/lenovo-booth-tour-ces2024- BMW Xreal AR demo: https://www.techradar.com/vehicle-tech/bmw-just-put-ar-in-a-car-and-it-finally-makes-perfect-sense- Realme 12 Pro+: https://www.engadget.com/the-realme-12-pro-is-the-first-mid-range-device-with-a-3x-periscope-zoom-camera-233636358.html- Brane X speaker: https://www.slashgear.com/1492118/ces-2024-innovation-spotlight-brane-x-portable-smart-speaker/- Marelli, Mudra, and more: https://www.slashgear.com/1490726/best-moments-ces-2024-day-3-recap/- New Asus ZenBook Duo: https://www.slashgear.com/1488923/asus-zenbook-duo-dual-screen-laptop-displays-ces-2024/
- EV Inventory Much Higher Than ICE Inventory - Cummins Gets Hit with Record Fine - SEC Wants Money from Bankrupt Lordstown - UAW Turns Its Attention to Mercedes - BMW Converting Main Plant to EV Only - U.S. Public Charger Rollout on Track - Marelli Can Recover Energy from New Suspension System - All Porsche Macan EVs Will Have Over 500KM Range - Kia Working on Uber-Specific PBV
- EV Inventory Much Higher Than ICE Inventory - Cummins Gets Hit with Record Fine - SEC Wants Money from Bankrupt Lordstown - UAW Turns Its Attention to Mercedes - BMW Converting Main Plant to EV Only - U.S. Public Charger Rollout on Track - Marelli Can Recover Energy from New Suspension System - All Porsche Macan EVs Will Have Over 500KM Range - Kia Working on Uber-Specific PBV
Tredicesima puntata della sesta stagione di J-TACTICS, la rubrica di radiomegliodiniente.com, dedicata alla vecchia signora bianconera.Focus sulla, sempre ostica sfida, di Marassi contro il Genoa di Gilardino.Genoa e Juventus pareggiano 1-1 quindi.Al rigore di Chiesa per i bianconeri risponde nella ripresa Gudmundsson per il grifone.La squadra di Allegri manca il sorpasso e si fa distanziare fall'Inter, che domenica sera infligge un perentorio 2-0 alla Lazio in casa.Ora i nerazzurri milanesi hanno un vantaggio di 4 punti sui bianconeri secondi in classifica. Andando ad analizzare il match, prestazione non eccelsa della squadra di Allegri, mentre il Genoa fa il suo e strappa un buon punto.Gilardino schiera la sua squadra senza una punta di ruolo vera e propria, data l'assenza dell'argentino naturalizzato italiano Retegui, Messias e Malinovskyi dietro Gudmundsson.Nella Juve manca Rabiot che viene sostituito con Miretti.La partita è sin dall'inizio combattuta ma sicuramente non bella a livello estetico.Un primo tempo scandito da pochi tiri in porta per entrambe le squadre.La Juve passa finalmente in vantaggio al 28′ quando Chiesa trasforma un rigore che lui stesso si era procurato.I rossoblù padroni di casa sbagliano la ripartenza dal basso, ne approfitta Vlahovic che recupera un buon pallone al limite dell'area e serve il n.7 bianconero che è lestissimo e viene abbattuto dal portiere Martinez.Dal dischetto a sorpresa non si presenta Vlahovic, che aveva sbagliato tre degli ultimi quattro rigori, il serbo cede l'onere a Federico che calcia il penalty da manuale spazzando il portiere.1-0 e palla al centro. Nel finale della prima frazione di gioco il Genoa ha tuttavia l'occasione migliore, Vasquez con un affondo perentorio si fa largo tra gli avversari e mette un bel pallone in mezzo, Gudmundsson corre veloce e prova a calciare, ma cicca clamorosamente la palla. Al duplice fischio dell'arbitro la Juve rientra negli spogliatoi in vantaggio di una rete.Gilardino mischia le carte, entra Ekuban.Una punta vera per i Grifoni che tre minuti dopo trovano un pareggio non proprio inaspettato.La difesa della Juve si dimostra lenta e poco attenta come poche volte lo era stata nelle ultime settimane.Frendrup raccoglie al limite dell'area di rigore, passa a Ekuban che di testa serve l'islandese Gudmundsson che praticamente davanti alla porta non può sbagliare e insacca con un tap in al volo, è 1-1.Dubbi, molti dubbi su un presunto controllo di braccio di Ekuban che sembra aggiustarsi la palla prima di servirla al suo compagno.Per Massa, addetti VAR e compagnia cantante tutto regolare.La Juve prova a farsi sotto per riportarsi in vantaggio.Chiesa appare essere il più attivo ma poco assistito dal resto della squadra.Dopo l'episodio che vede protagonista Ekuban nel gol del pareggio genoano altri dubbi e polemiche per un tocco di mano di Bani, che non viene giudicato da rigore né dall'arbitro né dal VAR.Sugli sviluppi di un'azione dalla destra, nata da un calcio di punizione conquistato da Gatti, percussione di Cambiaso che mette un pallone velenoso quasi dal fondo.Tentativo di cross da parte dell'ex genoano che finisce sul braccio di Bani palesemente troppo largo, e subito dopo sul guantone di Martinez che sventa il pericolo.L'ex arbitro Marelli interpellato in merito fuga ogni dubbio: "Il braccio di Bani è molto largo tra l'altro non si chiude ma si apre verso il pallone".Marelli stesso auspica in definitiva almeno un intervento del Var che invece, anche in questo caso, è rimasto silente, nonostante le proteste della formazione di Allegri.Altro errore/orrore di una terna arbitrale e VAR ai limiti dell'indecenza.Un'altra situazione che ha fatto molto discutere è stata un'entrata con i tacchetti spianati di Malinovskyi direttamente sulla caviglia del giovane Yildiz, che stramazza al suolo contorcendosi dal dolore, con il giocatore rossoblù in versione padrone della baracca che urla ogni tipo di improperio al malcapitato ragazzo.Per Massa tutto regolare evidentemente.L'ex atalantino viene sanzionato semplicemente con il cartellino giallo.Altri dubbi, altre polemiche.Con il passare del tempo il Genoa spinge sempre più, Danilo, McKennie e Milik vengono ammoniti nel forcing bianconero.Nel finale la Juve pare averne di più anche grazie all'esuberanza dei giovani Yildiz e Iling Jr.Martinez all'88' si guadagna gli applausi per una paratona su un colpo di testa ravvicinatissimo di Bremer.L'intervento durissimo ed impunito di Malinovskyi rende teso il finale di gara, il risultato tuttavia non cambia.Finisce 1-1 Genoa-Juventus, tra polemiche, recriminazioni e amarezze juventine per aver perso il treno del momentaneo sorpasso all'Inter in classifica.Non mancherà poi uno sguardo più che interessato alla freschissima ed attesissima sentenza della Corte di giustizia dell'unione europea che pare aver messo un punto sulla diatriba legale-sportiva che andava avanti da quasi due anni: “Esiste un abuso di potere dominante da parte di Uefa e Fifa che esercitano un monopolio”, si legge nella decisione dei giudici.Cosa accadrà ora?Il verdetto è rivoluzionario ed avrà ripercussioni enormi nel mondo del calcio così come fu a suo tempo la celeberrima "sentenza Bosman".Di questo e altro parleremo in questa puntata! Diteci la vostra, interagiremo con voi in chat live!Ecco i link dei nostri social:CANALE TELEGRAM:https://t.me/+TYOn7FZAQwet7MAtINSTAGRAM:https://instagram.com/jtactics_?igshid=YmMyMTA2M2Y=TWITTER:https://twitter.com/RadioMDN?t=woKQltSFRUTw9qibbRZaJA&s=09
Ad #AriaPulita Simone Selmi, Segr. Fiom Cgil Bologna.
Il Morning Show Martedi 03 Ottobre 2023
Torna a Bologna, per la sua 40° edizione, il Cersaie, il Salone Internazionale della Ceramica per l'Architettura e dell'Arredobagno, il più importante appuntamento mondiale per la ceramica, l'arredobagno, l'architettura ed il design. Partito ieri martedì 25 settembre, durerà fino a venerdì 29 settembre. L'industria delle piastrelle di ceramica vale 7,2 miliardidi fatturato, 19mila addetti con il 97% a contratto a tempo indeterminato e oltre 440 milioni di investimenti fatti nel solo 2022 (pari al 6,2% dei ricavi). L'85% della produzione italiana (fatturato export da 6 miliardi) viene esportata concorrendo con Cina, India, Turchia che non solo benificiano di costi di lavoro, energia e materie prime irrisori rispetto ai nostri ma non devono sostenere balzelli sulle emissioni inquinanti. Ne parliamo con Giovanni Savorani, Presidente di Confindustria Ceramica.Le difficoltà della Marelli sono l'anticipo di una difficile transizione verso l'elettrico?La settimana scorsa è arrivata la notizia che la Marelli, maggiore produttore italiano di componenti auto, l'ex Magneti Marelli, ha deciso di chiudere la fabbrica di Crevalcore, nel Bolognese. La produzione verrà trasferita nello stabilimento di Bari. Rischiano il posto i 230 dipendenti dell'impianto. La decisione nasce in un contesto industriale difficile, stressato dalla transizione verso la mobilità elettrica e reso complesso dalla necessità di Marelli di superare lo schema fragile della monofornitura. Queste difficoltà si ineriscono in un orizzonte in cui a Bruxelles hanno deciso che dal 2035 non si potranno più vendere auto a combustione alimentate a diesel e benzina. L'Italia si farà trovare pronta? Ospiti: Bruno Dalla Chiara, professore ordinario in Trasporti al Politecnico di Torino, Dipartimento di Ingegneria dell'ambiente, del territorio e delle infrastrutture (Diati) e mobility manager di Ateneo e Gianni Silvestrini, Direttore scientifico di Kyoto Club e QualEnergia e Presidente Exalto Energy&Innovation.
Ad #AriaPulita il Sindaco di Crevalcore (BO) Marco Martelli ci racconta la crisi della Magneti Marelli.
- UAW Cripples Mercedes-Benz Production in the U.S. - More Plants Could Strike by Noon Tomorrow - A Flaw in the UAW's Strike Strategy? - EV Batteries Can Last the Life of a Car - NIO 1st Car Maker with Its Own Smartphone - EV Sales Up 102% in Europe - Marelli Closes ICE Plant Due to EV Growth - Geely Helps Launch China's 1st Auto-Grade 7NM Chip - Continental and Ethernovia Developing 7NM Chip - Mercedes Turns to Tech to Improve Manufacturing
- UAW Cripples Mercedes-Benz Production in the U.S. - More Plants Could Strike by Noon Tomorrow - A Flaw in the UAW's Strike Strategy? - EV Batteries Can Last the Life of a Car - NIO 1st Car Maker with Its Own Smartphone - EV Sales Up 102% in Europe - Marelli Closes ICE Plant Due to EV Growth - Geely Helps Launch China's 1st Auto-Grade 7NM Chip - Continental and Ethernovia Developing 7NM Chip - Mercedes Turns to Tech to Improve ManufacturingThis show is part of the Spreaker Prime Network, if you are interested in advertising on this podcast, contact us at https://www.spreaker.com/show/3270299/advertisement
Gestern wurde in der Wiener Staatsoper „La Sonnambula“ von Vincenzo Bellini wieder ins Repertoire aufgenommen. Es war die 54. Aufführung in der Inszenierung von Marco Arturo Marelli. Unser Opernexperte Richard Schmitz berichtet. Es war ein großer Opernabend. „La Sonnambula“ entfaltete den Zauber des belcanto. Die Oper ist nicht zufällig die meistgespielte Oper Bellinis. Brenda Rae ist als Amina wirklich eine Diva, was sie ja am Ende bei Marelli auch sein soll. Der Aufstieg von der Küchenhilfe zur gefeierten Sängerin wirkt durchaus glaubhaft. Die anfangs unsichere junge Frau mit ihrer somnambulen Veranlagung singt sie zurückhaltend und steigert sich gekonnt in die Selbstsicherheit hinein. Ihr Koloratursopran brilliert mit außergewöhnlichen Verzierungen und sicheren Spitzentönen. Die beiden Schlafwandelszenen sind berührend. Javier Camarena singt das einfältige Muttersöhnchen Elvino mit einigen Spitzentönen verlässlich und entspricht damit der Intention des Regisseurs. Imponierend in Stimme und Auftreten Roberto Tagliavini als Graf Rodolfo. Maria Nazarova zeigt als Lisa ihre Wandlungsfähigkeit und besteht neben den großen Stimmen achtbar; Szilvia Vöros muss die Mutter Teresa statisch anlegen. Jack Lee als Alessio bleibt der Rolle entsprechend unauffällig. Giacomo Sagripanti dirigiert einen inspirierenden Abend. Manchmal wünscht man sich etwas mehr Tempo und Drive. Das durchdachte Bühnenkonzept von Marelli packt noch immer und gibt den Sängern genügend Freiraum ihre Rollen zu gestalten. Die Verlegung der Handlung in ein Schweizer Nobelsanatorium wirkt logisch. Das Publikum reagierte mit Sachverstand und spendete reichlich Szenenapplaus. Allgemeiner Jubel. 8,5
Podcast 05.07.2023 Luca Marelli Learn more about your ad choices. Visit megaphone.fm/adchoices
Christian Marelli pasó por el aire de Radio Atomika en Semanario Tras el Fin del Mundo, él es el vocalista de Aguafuertes, un sexteto fusión de tango y rock. Un programa semanal en busca del después. Lunes de 10 a 14 horas, por radio atomika. Semanario tras el fin del mundo, vanguardia old school. Conduce Fede Dipa y Julian Apellido. Operación Tomi Gauna.Mostrar menos --- Send in a voice message: https://podcasters.spotify.com/pod/show/radio-atomika/message
Phil MarelliSee omnystudio.com/listener for privacy information.
Jan Becker is President, CEO and Co-Founder of Apex.AI, Inc. He is also the Managing Director of the Apex.AI GmbH. Key topics in this conversation include: Understanding software defined vehicles Apex.Grace, Apex.Ida, and Apex.OS Building the operating system for autonomous vehicles that is designed to never fail Apex.AI's role enabling autonomy outside of automotive Functional safety considerations for modular software How Apex.AI is making their mark on the industry Links: Show notes: http://brandonbartneck.com/futureofmobility/janbecker https://www.apex.ai/ https://www.linkedin.com/in/janbecker23/ Jan's bio Jan Becker is President, CEO and Co-Founder of Apex.AI, Inc. He is also the Managing Director of the Apex.AI GmbH, our subsidiary in Germany. Prior to founding Apex.AI, he was Senior Director at Faraday Future responsible for Autonomous Driving and Director at Robert Bosch LLC responsible for Automated Driving in North America. He also served as a Senior Manager and Principal Engineer at the Bosch Research and Technology Center in Palo Alto, CA, USA, and as a senior research engineer for Corporate Research at Robert Bosch GmbH, Germany. Since 2010, Jan is Lecturer at Stanford University for autonomous vehicles and driver assistance. Previously, he was a visiting scholar at the University's Artificial Intelligence Lab and a member of the Stanford Racing Team for the 2007 DARPA Urban Challenge. In 2019, Jan was appointed to serve on the external Advisory Board of MARELLI to provide strategic advice to the MARELLI Board. In 2018, he co-founded the Autoware Foundation and was on the foundation's board of directors until 2020. Jan earned a Ph.D. in control engineering from the Technical University of Braunschweig, Germany, a master's degree in mechanical and aerospace engineering from the State University of New York at Buffalo, USA, and a master's degree in electrical engineering from the Technical University of Darmstadt, Germany. About Apex.AI Apex.AI is a Palo Alto, Munich, Berlin, Stuttgart and Gothenburg-based company that is developing breakthrough safe, certified, developer-friendly, and scalable software for mobility systems. Our software products are based on proven open-source software, such as ROS or Eclipse iceoryx, so that we don't spend time redeveloping what already works. Instead, we fork software that has been developed and proven in use by large developer communities. We then add what is missing: Functional safety, flawless performance, and support for application in commercial and safety-critical products. In order to do so, we have developed a proprietary process to rework open-source software in record time such that it conforms to the highest requirements of the applicable functional safety standard. We launched our award-winning first product Apex.Grace, formerly known as Apex.OS, after three years in 2020 and have taken it through certification in record time for launch in 2021. Future of Mobility: The Future of Mobility podcast is focused on the development and implementation of safe, sustainable, effective, and accessible mobility solutions, with a spotlight on the people and technology advancing these fields. Edison Manufacturing: Edison manufacturing is your low volume contract manufacturing partner for build and assembly of complex mobility and energy products that don't neatly fit within traditional high-volume production methods.
Puntata speciale col nostro Luca Marelli, la voce arbitrale di Dazn. Tante chicche sul nuovo regolamento, storie che non conoscevate sui grandi arbitri italiani del passato e del presente. Spoiler: contiene una dedica speciale di Stefano Borghi e Pierluigi Pardo.
Come ogni anno arriva la puntata in cui vengono azzardate più previsioni del solito e puntualmente smentite a distanza di pochi mesi: quella sui premi. E come ogni anno non ci sentiamo di prenderci questa responsabilità da soli e con noi non può che esserci Federico Marelli.
CT Automotive Executive Chairman, Simon Phillips, CEO, Scott McKenzie, COO, Stuart Lorraine and CFO, David Wilkinson present the half year results for the period ended 30 June 2022, which shows revenues ahead in H1 and production recovery gaining momentum. Simon Phillips, Exexutive Chairman 00:17 - Introduction 00:54 - H1 22 highlights 02:15 - Growth Progress Scott McKenzie, CEO 05:00 - Increasing visibility 06:00 - UK plant closure 06:53 - China update Stuart Lorraine, COO 08:44 - Improvement initiatives David Wilkinson, CFO 13:06 - Income Statement 14:49 - Balance Sheet Scott McKenzie, CEO 15:54 - Outlook Simon Phillips, Exexutive Chairman 17:25 - Summary About CT Automotive CT Automotive is engaged in the design, development and manufacture of bespoke automotive interior finishes (for example dashboard panels and fascia finishes) and kinematic assemblies (for example air registers, arm rests, deployable cup holders and storage systems), as well as their associated tooling, for the world's leading automotive original equipment suppliers ("OEMs") and global Tier One manufacturers. The Group is headquartered in the UK with a low-cost manufacturing footprint. Key production facilities are located in Shenzhen and Ganzhou, China complemented by additional manufacturing facilities in Turkey and the Czech Republic. CT Automotive's operating model enables it to pursue a price leadership strategy, supplying high quality parts to customers at a lower overall landed cost than competitors. This has helped the Group build a high-quality roster of OEM end customers, both directly and via Tier One suppliers including Faurecia and Marelli. End customers include volume manufacturers, such as Nissan, and luxury car brands such as Bentley and Lamborghini. In addition, the Group supplies electric car manufacturers, including Lucid. The Group currently supplies component part types to over 47 different models for 19 OEMs. Since its formation, the Group has been the only significant new entrant into the market, which is characterised by high barriers to entry.
San Marino Design Workshop 2022 — CONTAMIN_AZIONI A cura di Unirsm Design - Università degli Studi della Repubblica di San Marino
Dopo gli anni della pandemia riprende a pieno ritmo la collaborazione tra NTT Data e il mondo delle startup. Da questa edizione con una nuova formula, per ora unica nel panorama mondiale di questo evento: una collaborazione operativa tra aziende tradizionali, che hanno lanciato la sfida, e startup da tutto il mondo, che l'hanno raccolta proponendo soluzioni innovative. Delle oltre 100 candidature accompagnate da altrettante idee raccolte, la giornata finale ha visto le undici aziende introdurre la propria sfida e presentare la startup scelta per affrontarla. Poco importa chi abbia vinto, non è quello l'obiettivo, anche se il vincitore vedrà evolvere la propria proposta in un PoC proprio grazie a NTT Data.E' dall'esperienza raccontata da Nicolò Mazzocchi , CEO e fondatore di Algo AI, startup attiva in ambito HR che ne comprendiamo il valore: confrontarsi con i bisogni del mercato, espressi dalle aziende strutturate con cui collaborano.La stessa Marelli, per voce di Luca Bertoglio , Global Chief Information Security office sottolinea l'importanza di questa contaminazione, purché la controparte comprenda l'importanza non solo dell'impatto industriale dell'innovazione proposta ma anche economico. Ecco dunque che il business case diventa elemento centrale e discriminante all'interno di una collaborazione.Contaminazione e integrazione che diventano chiave d'accesso al mercato, come ha dichiarato David Kat , imprenditore e cofondatore della startup israeliana in ambito medicale Olive Diagnostics: la partnership con Generali Spagna è stata determinante per riuscire a penetrare un mercato così complesso e regolamentato come quello della sanità pubblica.E per concludere, come in un percorso circolare che riparte dall'inizio per sostanziarne valore e importanza, la voce di Walter Ruffinoni , CEO di NTT Data Italia e autore di Italia 5.0 Un nuovo umanesimo per rilanciare il Paese: l'open innovation è uno dei capisaldi della crescita delle aziende e potenzialmente del Paese. E' necessario che ogni portatore di interesse faccia la sua parte affinché possa contribuire a migliorare la produttività e la competitività del Sistema Italia. Buon ascolto! Avete una storia di "trasformazione digitale" da raccontare o segnalare? Scriveteci a radionext@radio24.it
Struggling Japanese auto parts supplier Marelli Holdings Co. said Friday it has filed with Tokyo District Court for a simplified bankruptcy protection procedure under Japan's civil rehabilitation law.
Thema heute: PEUGEOT 9X8: Debüt am 10. Juli in Monza bei der FIA WEC Foto: Peugeot/Stellantis Weniger als ein Jahr nach der Präsentation des Konzepts und fünf Monate nach dem ersten Test des Fahrzeugs auf der Rennstrecke hat das Team PEUGEOT TotalEnergies in Portimão im Süden Portugals seinen neuen Langstrecken-Rennwagen vorgestellt: den PEUGEOT 9X8. Das neue Hypercar mit Allradantrieb und Hybrid-Elektroantrieb wird im Juli bei der vierten Runde der FIA World Endurance Championship (FIA WEC) 2022 in Monza, Italien, sein Renndebüt geben. Für PEUGEOT läuft der Countdown auf Hochtouren. Foto: Peugeot/Stellantis Dieses leistungsstarke Hypercar, das durch den fehlenden Heckflügel sofort ins Auge fällt, entspricht dem Reglement der ACO- und FIA-Kategorie Le Mans Hypercar (LMH), die zugänglicher ist als die LMP1, aber genauso wettbewerbsfähig. Das Modell präsentiert das unverwechselbare Design von PEUGEOT, das sich durch eine katzenartige Linienführung, eine klare Silhouette, die starke Markenidentität und dieselbe vertraute Licht-Signatur mit drei Krallen wie bei den Straßenmodellen des Herstellers auszeichnet. Als Beispiel für die technologische Kompetenz von PEUGEOT in den Bereichen Hybridisierung und Elektrifizierung, beides Schlüsselelemente der Energiewende-Strategie der Marke, unterstreicht das Hypercar das Bekenntnis des Unternehmens zu Exzellenz. Sowohl im Hinblick auf seine Wettbewerbsanstrengungen als auch auf seine Kunden. Auffälliges Design, Leidenschaft für den Motorsport und technologische Höchstleistung sind die drei Werte, die PEUGEOT bei diesem ehrgeizigen Projekt angeleitet haben. Es soll die Rückkehr der Löwenmarke in den Langstreckensport markieren, mit besonderem Augenmerk auf das 24-Stunden-Rennen von Le Mans – ein außergewöhnliches Ereignis, das nur wenige Konkurrenten hat, wenn es um die Bewertung und Validierung innovativer Ideen und Technologien geht. Vorbereitung: eine sportliche und technologische Herausforderung Der PEUGEOT 9X8 ist ein Prototyp für den Rennsport mit Allradantrieb, dessen Antriebsstrang unter der Leitung der Spezialistinnen und Spezialisten von PEUGEOT Sport entwickelt wurde. Seine Hinterräder werden von einem 2,6-Liter-V6-Bi-Turbo-Verbrennungsmotor mit 520 kW Leistung angetrieben, während ein Hochleistungs-Elektromotor mit 200 kW die Vorderräder bewegt. Wie der Motor wurde auch der auf Siliziumkarbid basierende Wechselrichter in Zusammenarbeit mit Marelli entwickelt. Diesen Beitrag können Sie nachhören oder downloaden unter:
SUZUKI AND STELLANTIS DIESELS INVESTIGATEDProsecutors in Germany, Italy and Hungary are investigating Suzuki, Stellantis and supplier Marelli, over use of defeat devices in Suzuki vehicles. Stellantis are engine suppliers for Suzuki and Marelli are a supplier of engine parts. For more, click the Nikkei Asia article link here. FEAR OF FINES FOR BOX JUNCTION MISTAKESWith local authorities outside of London, allowed to prosecute those who misuse yellow box junctions from June 2022, the fear that drivers could be mistakenly fined was announced. The RAC said that many are incorrectly painted, laid out, located and even hidden from clear view for those approaching. They have called on the Government to clarify the guidance on yellow box junctions, clarifying their use, design and maintenance once in place. To find out more, click the link here for the Motoring Research article. MOT TEST COULD BE EVERY TWO YEARSWith a suggestion that has been roundly condemned by nearly everyone who has heard it, the idea to move MOT tests to every other year has not gone down well. To be clear, this is only a suggestion, apparently it will help with the cost of living crisis the UK is currently suffering. For more information, click the Autocar link here. BMW AND AUDI STOP FREIGHT TRAIN TO CHINABMW and Audi have ceased sending cars to China via the rail link from Europe, due to the war in Ukraine. To learn more about that story, click the link to the Reuters article here.To learn more about the rail link to China, click the link here to Rail Magazine's article. VOLTA TRUCKS REVELAS SMALLER LORRIESNew 7.5 tonne and 12 tonne lorries have been unveiled but the electric truck company Votla Trucks. They will follow the 16 tonne lorry, being added to the line up in 2025.The previously announced model is undergoing final preparations before they start customer testing and production later in the year. More on this story can be found by clicking this Move Electric link. VW AND BP ROLL OUT NEW CHARGING INFRASTRUCTUREBP will be partnering with Volkswagen to install their new rapid chargers that have integrated batteries that mean they can be deployed at low voltage sites, avoiding the need for extra infrastructure to ensure a suitable electrical supply is maintained. They will be starting in Germany and moving across Europe. Click here for the Business Motoring article, to learn more. GOVERNMENT TO LEGALISE PRIVATE E-SCOOTER USEGrant Shaps, the Transport Minister, has stated the Government plans to legalise the use of private scooters on public roads. Exactly how they will mandate for their safe use is yet to be established. To learn more, click the Move Electric article link here. PARIS'S ELECTRIC BUSES TAKEN OFF THE ROADFollowing two incidents where Bolloré electric buses caught fire, all have been removed from the roads as a precaution whilst investigations into the causes are run. No one was hurt in either incident. To learn more, click this France24 link here. MCLAREN NAME NEW BOSSEx-Ferrari technology chief, Michael Leiters, has been announced as the new CEO of McLaren. Leiters has worked at Porsche and recently Ferrari. His resume includes developing the Cayenne, prancing horse mid-engined V8s and their first ever hybrid super cars. To learn more, click the EVO article link here. MORGAN NAME NEW BOSSEx-Lamborghini Chief Project Management Officer, Massimo Fumarola, has been named as Morgan's new CEO. He will lead the company during their most innovative and progressive period since inception. For more on who Massimo is and the challenges he faces, click the PistonHeads article here. ——————————————————————————-If you like what we do, on this show, and think it is worth a £1.00, please consider supporting us via Patreon. Here is the link to that CLICK HERE TO SUPPORT THE PODCAST——————————————————————————-SMMT DRIVE DAY 2022 ROUND UP:Below is a list of the cars Alan managed to find time to drive, whilst at the annual SMMT Drive Day, held at Milbrook. Thank you to SMMT, the manufacturers and other motoring journalists for organising, being there and actually talking to Alan so he didn't feel lonely. Hyundai Kona NMustang Mach-E (Extended Range)BMW 220i Luxury Active TourerPeugeot 508 SW PSESsangYong Musso RhinoPorsche Macan SToyota RAV-4 AdventureToyota Supra 3.0 Jeramy Racetrack EditionA look at the Genesis GV60Skoda Enyaq iV 80 SportlineAlpine A110 GTVolvo C40 Dual MotorAND FINALLY: WHAT IS RUSSIAN FOR “OH DEERE”Following the invasion of the Ukraine, Russian forces have stolen John Deere manufactured farming equipment and taken it back to their country. However, John Deere has spotted this and ‘bricked' the tractors and harvesters, rendering them inoperable. Whilst this is a good thing, that John Deere has done, it raises once again the awful concept of remote deactivation capability. Always relieves on you meeting arbitrary standards someone else has decided on, which you have no ability to appeal against. For more, click here to read The Register's article.
Partendo da una riflessione sulla canzone di Franco Battiato oggi parliamo di 'cura' nelle sue diverse forme e declinazioni, insieme all'amica, collaboratrice e sempiterna Marchesa, Maria Vittoria Marelli. Prendersi cura, avere cura e soprattutto la cura di sé stessi come principale portale di accesso alla possibilità di prendersi cura degli altri. Questo e altri aspetti sono alcune delle tappe nel viaggio di oggi attraverso noi stessi e la cura che ci prendiamo. Iscriviti al #podcast, commenta e condividi con i tuoi amici le #puntate di #thebigfatvoice, seguiti sui #social, rimani in contatto e buon ascolto! Visita il sito http://www.mbgvoice.com (www.mbgvoice.com) Segui la pagina Facebook https://www.facebook.com/thebigfatvoice (https://www.facebook.com/thebigfatvoice) Segui il profilo Instagram https://www.instagram.com/thebigfatvoice (https://www.instagram.com/thebigfatvoice) Puoi metterti in contatto con Massimiliano scrivendo a info@mbgvoice.com Fai girare la voce… o meglio… fai girare #thebigfatvoice Musica originale by #audiio @helloaudiio www.audiio.com
Con oggi inizia la serie delle nostre chiacchierate con Maria Vittoria Marelli, counselor somato-relazionale a indirizzo bioenergetico, anche identificata dai compagni di avventure come 'la Marchesa', celebrazione semiseria e giocosa sulla maschere che tutti noi indossiamo in maniera più o meno cosciente e con cui affrontiamo il mondo e noi stessi. Partendo da questo spunto, la riflessione di oggi si concentra esattamente contatto con noi stessi, sulla propriocezione, sull'ascolto e sullo sguardo verso noi stessi, partendo e prendendo spunto dalle testimonianze dei nostri adolescenti e dall'esperienza diretta nell'ascolto dei giovani uomini e donne e dei loro sogni, aspirazioni, bisogni, problemi, dolori, necessità. Iscriviti al #podcast, commenta e condividi con i tuoi amici le #puntate di #thebigfatvoice, seguiti sui #social, rimani in contatto e buon ascolto! Visita il sito http://www.thebigfatvoice.com (www.thebigfatvoice.com) Segui la pagina Facebook https://www.facebook.com/thebigfatvoice (https://www.facebook.com/thebigfatvoice) Segui il profilo Instagram https://www.instagram.com/thebigfatvoice (https://www.instagram.com/thebigfatvoice) Per avere maggiori informazioni puoi visitare i siti: http://www.mbgvoice.com (www.mbgvoice.com) http://www.counselingtorino.com (www.counselingtorino).it Puoi metterti in contatto con Massimiliano scrivendo a thebigfatvoice@gmail.com Fai girare la voce… o meglio… fai girare #thebigfatvoice Musica originale by #audiio www.audiio.com
Detroit offers new payment plan to limit water shutoffs during coronavirus crisis, Duggan aims for to preserve affordable housing, Marelli to create North American headquarters in Southfield, stock market sees a meltdown after oil prices plunge, and Michigan State's Cassius Winston named to Big Ten first-team again.
Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Centre and Duke National University of Singapore. Our featured paper this week is an in-depth paper on the cardiovascular and metabolic heterogeneity of obesity, and we will have a discussion with the authors on the clinical challenges, implications for management, and much more coming right up after these summaries. How does MRI quantification compare with standard Doppler echo approach to identify organic mitral regurgitation and predict adverse outcomes? Well, our first paper this week addresses this question, led by first and corresponding author, Dr. Penicka from the Cardiovascular Center OLV Clinic in Belgium. These authors studied 258 asymptomatic patients with preserved left ventricular ejection fraction and chronic moderate and severe organic mitral regurgitation by echo. All patients underwent MRI to quantify regurgitant volume of this organic mitral regurgitation by subtracting aortic flow volume from the total left ventricular stroke volume. Severe organic mitral regurgitation was defined as a regurgitant volume of greater or equal to 60 milliliters. The authors found that mean echo-derived regurgitant volume was an average 17 milliliters larger than the MRI-derived regurgitant volume. Concordant grading of organic mitral regurgitation severity with both techniques was observed in 76% of individuals. In the remaining 24% of individuals with discordant findings between the two techniques, this was mainly observed in patients with late systolic, eccentric, or multiple jets. The MRI-derived regurgitant volume showed the highest discriminative power among all the imaging parameters to predict all cause mortality or its combination with development of indication for mitral valve surgery. Thus, this study demonstrates that MRI-derived assessments of organic mitral regurgitation are clinically accurate to identify asymptomatic patients with severe organic mitral regurgitation and at first outcomes. This may be particularly so when the mitral regurgitation is late systolic, eccentric, or multiple in jets where misclassification may occur with echo-derived approach. The next study is the first large population-based study to analyze the association between low-dose ionizing radiation from cardiac procedures and incident cancer in adults with congenital heart disease. First author Dr. Cohen, corresponding author Dr. Marelli from McGill University, studied the population from the Quebec Congenital Heart Disease Database and performed a nested case control study comparing cancer cases with controls matched on sex, congenital heart disease severity, birth year, and age. They found that the cumulative incidence of cancer in adults with congenital heart disease between the ages of 18 and 64 years was 15%. The cumulative low-dose ionizing radiation exposure from cardiac procedures was independently associated with incident cancer after adjusting for age, sex, year of birth, congenital heart disease severity and comorbidities. Results were similar using either the number of procedures or estimates of the effective doses with a possible dose-related response relationship between the low-dose ionizing radiation exposure level and cancer risk. Thus, increasing exposure to low-dose ionizing radiation from cardiac imaging in adults with congenital heart disease raises concerns about life-long risk of malignancy. Confirmation of these findings by prospective studies is needed to reinforce policy recommendations for radiation surveillance in patients with congenital heart disease. The next study characterizes the long-term dynamics of potassium in heart failure and its associated risk of mortality. First and corresponding author, Dr. Nunez from Hospital Clinic University of Valencia in Spain, evaluated the prognostic implications of long-term longitudinal monitoring and dynamics of serum potassium in a prospective and consecutive cohort of patients following a hospitalization for acute heart failure. In these patients, serum potassium was measured at every physician-patient encounter, including hospital admissions and ambulatory settings. The authors found that on a continuous scale, the followup trajectory of serum potassium levels independently predicted mortality through a U-shaped association with higher risk at both ends of the distribution, and the same was true using potassium categories. Furthermore, dynamic changes in potassium were independently associated with substantial differences in mortality risk. Persistence of normal potassium levels was linked to a higher risk of death compared to patients who maintained or returned to normal values. Conversely, potassium normalization was independently associated with a lower mortality risk. These findings support the need for close monitoring of serum potassium after an episode of acute decompensated heart failure and suggest that maintaining serum potassium levels within normal range may be considered a therapeutic target. The next study gives us an example of how functional metabolomics can translate into metabolomics derived biomarkers of disease mechanisms. Co-first authors, Dr. Zhang, Wei, and Li; co-corresponding authors, Dr. Zhu, Li, and Qi from Nanjing, China, studied a cohort of 2324 patients who underwent coronary angiography from four independent centers. They used a combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode for untargeted analysis of metabolites in the plasma. The authors identified a total of 36 differential metabolites related to coronary artery disease progression. In particular, N-Acetyl-neuraminic acid, a metabolic marker highly elevated during coronary artery disease progression, acted as a signaling molecule to trigger RhoA and Cdc42 dependent myocardial injury via activation of the Rho-RACK signaling pathway. Silencing neuraminidase-1, which is the enzyme that regulates N-Acetyl-neuraminic acid generation, ameliorated myocardial injury in vitro and in vivo. Pharmacologic inhibition of neuraminidase by anti-influenza drugs protected cardiomyocytes and the heart from myocardial injury. Thus, in summary, functional metabolomics identified a key role for N-Acetyl-neuraminic acid in acute myocardial injury, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for coronary artery disease. The final study addresses the controversy of whether high density lipoprotein, or HDL cholesterol, plays a causal role in cardioprotection. First and corresponding author, Dr. Jensen from Harvard T.H. Chan School of Public Health and colleagues, hypothesized that subspecies of HDL defined by apolipoprotein C3, a key regulator of lipoprotein metabolism, may contribute new information to prediction of cardiovascular risk. They used immunoaffinity chromatography to measure the apo A1 concentrations of HDL that contained or lacked apolipoprotein C3, or apo C3, in two prospective studies of adults free of coronary heart disease, the Multiethnic Study of Atherosclerosis and the Danish Diet, Cancer and Health Study. They then conducted a meta-analysis that combined these results with the previously published findings from two cohort studies that used similar laboratory methodology to measure lipoproteins. The authors identified a subspecies of HDL that contained apo C3. HDL that contained apo C3 comprised 5 to 6% of apo A1 or 10 to 15% of HDL cholesterol. In the four prospective studies, HDL containing apo C3 was associated with a greater risk of coronary heart disease, whereas HDL that lacked apo C3 was inversely associated with risk more strongly than the total HDL. These findings support the hypothesis that apo C3 may mark a subfraction of HDL cholesterol that is associated with higher risk of coronary heart disease. These findings therefore provide novel insights for cardiovascular risk that extend beyond traditional plasma HDL cholesterol concentrations. And that brings us to a close for the summaries. Now for our feature discussion. For today's featured discussion, we are talking about obesity, a universal issue, or is it? And when we talk about obesity, are we talking about one thing or many things? Today's in-depth review is just such a great paper. I highly recommend it to everyone. So pleased to be discussing it with Dr. Ian Neeland today from UT Southwestern Medical Center. Ian, first of all, congratulations. A beautiful paper. I learned so much reading it, and I've got so many questions. You started off pointing out that we talk about obesity. We've always defined it by body mass index, but that may not be the ideal biomarker. I love the way you said that. So, tell us a bit more about the reason for this review. Dr Ian Neeland: Obesity, like you said, we define it by body mass index, but body mass index is such a crude marker. It's great to use for the clinic. It's easy to implement, but it doesn't really tell us a lot of information about the person. And so you can just look at a third of the population in the US right now is thought to be obese. And if you take a third of the population, clearly not everyone has diabetes and heart disease. So, obesity in and of itself, defined by the body mass index really is very heterogeneous, and it's not possible to use that alone to tell an individual if they're really at risk for disease. And so this review is really about getting deeper under the skin, no pun intended, to really get a sense of what it means to be obese, how the body fat plays a role in disease, and really getting to the different aspects of obesity and how we can understand it a little bit better. Dr Carolyn Lam: Yeah. You know, Ian, you had me at hello if I could say when I read your paper because I'm from Asia, and here, the World Health Organization actually even suggests that we use lower body mass index cutoffs to define obesity, simply because there's a different relationship as well with cardiometabolic disease. So, so true, but before we get there, to maybe ethnic differences, I want to ask you something. I heard the term, obesity paradox, thrown around a lot, and sometimes I think we don't really know what we're talking about when we say obesity paradox. I love the way, in your paper, you broke it down into four types. There are four paradoxes. Do you want to just clarify this for the audience? I think it's important. Dr Ian Neeland: So, the obesity paradox, what we mean by that is we think that obesity causes disease and gives someone an increased risk for disease and mortality and death, but the obesity paradox means that some people who are obese we see actually have better outcomes than those who are not obese. And how to describe that paradox and why that exists is really the subject of lots and lots of research and discussion. And so when we talk about the obesity paradox, really it's important to understand that most of the time we're talking about people who already have established disease. Let's say, for example, heart disease. So people with heart disease who are obese tend to have better outcomes than those who are not, and there are a few ways to understand that. So people who have obesity with established disease who may have better outcomes; that's the classic obesity paradox. Then there's a paradox really about fitness and being fat and fit, and that concept that you can be fat, but if you're fit, if you're able to do exercise and you have good cardiorespiratory fitness, that you actually may be protected from disease as well. And then there's also the obesity paradox of basically the pre-obesity paradox, so that overweight, right, where you haven't yet met the threshold for obesity can also be protective in people who don't have disease. And so being a little bit plump may be protective for different diseases down the road. And then the final one is that the metabolically health obesity. When we say that, it means that the person who is obese by body mass index but doesn't really have any hypertension or diabetes or lipid abnormalities. So, that's the metabolically healthy obese person. Those are the four types of individuals we see who may be obese but actually have better outcomes long term, and the question is why that exists. So there's a lot of thinking about it. Maybe it has to do with the fact that being normal weight nowadays, often we have older folks that are normal weight. Well, they tend to be more deconditioned. They may be frail. They may have undiagnosed disease like cancer. And that might be why those people are the worst. And there are the naysayers out there who think that it's all just about what we call confounding, so things we can't account for when we look at that. People who smoke tend to be lower weight, and obviously they have worse outcomes, and then also people who are older. So it's kind of a conundrum, this obesity paradox, but there's lots and lots of data out there coming out all the time that we keep seeing it again and again and again. One of the areas in the paper that I wanted to address was this concept of obesity heterogeneity in the obesity paradox, meaning to say is it potentially where the body fat is that may be playing a role in which obese person gets disease, and which obese person may be protected from disease. So it could be that it's not how much fat you have but where that fat is that is really telling about what someone's risk is, and that might help to describe the obesity paradox and get us a little bit more understanding. Dr Carolyn Lam: Yeah, now, I thought that bit was just so key and important. Not how much fat, not weight per se, but where that fat is. Do you want to elaborate on that a bit? Dr Ian Neeland: Sure. For, I don't know, 50, 60 years we've had this concept of the apple and the pear. Right? Fat in the belly being the apple shape and fat in the pear being fat in the hips and buttocks and that being two different body types of body fat. So we have a lot of technology nowadays, and we can actually directly image body fat and where it is in the body. So we can do MRI, we can do CT, and we can actually see where the body fat is distributed and how much body fat in one area may be related to disease compared with another area. So we've gone away from the apple and pear and really getting down to what we call body fat depots or adipose tissue depots where we deposit fat. And the area that we deposit fat that has the most risk for cardiometabolic diseases is this visceral adipose tissue or VAT. VAT is fat that's around the intra-abdominal organs, also near the kidneys, and you can't actually tell how much visceral fat someone has just by BMI or waist circumference or just looking at them. You really have to do this dedicated imaging to find out. And the reason for that is that in the belly there's two types of fat. There's the visceral fat, and there's the subcutaneous, which is the fat under the skin. Both those fat areas make up the belly fat, but they're very different. And part of the review is really going into depth about why these are different and how they're different. They have completely different metabolic profiles, so if you would take blood, lipids, inflammatory markers, they would look completely different even in a single individual. And then if you look at the genetics of where the fat is, they're different. If you look at what these fat areas secrete, they're completely different. So it's really important to know where the fat is, and that's why I think this concept of sick fat versus healthy fat comes into play. So, sick fat is fat that's usually in this visceral fat depot, and that is really the three central tenets we talk about are visceral fat or ectopic fat. Ectopic means fat where it doesn't belong. Then inflammation and cytokines, so secretion of abnormal factors in the blood from this fat, and then insulin resistance. So those are the three kind of tenets of this sick fat. So that's why we think that the sick fat plays a role in disease, and then there's a concept of less sick fat or healthy fat, which is maybe a sink. It actually buffers some of these cytokines and inflammation from causing disease in the body. Dr Carolyn Lam: Yeah. I found that concept so fascinating, and just to bring it back to the obesity paradox. So, some larger people may enjoy better outcomes because they actually have a predisposition to put the fat subcutaneously perhaps, rather than viscerally. Would that be correct? You worded it so eloquently in your paper. There are some ethnicities or some genetic predispositions that could make one lose that inability to put it peripherally, and therefore it all goes viscerally, is what I got from it. And that's the stuff that puts people at risk. Dr Ian Neeland: Yeah. We find that fat in the lower body, the hips and the buttocks, is actually in epidemiology, protective against heart disease, protective against cancer. And the problem is we don't know why some people put fat in the belly and some people put it in the hips and buttocks. There's very interesting twin-twin studies that show if someone has a predisposition for obesity, so twins may be both obese, but there is some difference in where they actually put the fat. So I think genetics certainly plays a role, but environment also plays a role. And environments, things like appropriate nutrition and physical activity can really alter genetics and help someone to put fat where it should be and prevent disease. So this obesity paradox, this concept of putting fat where it should be, is really the next frontier for this type of research. How can we modulate it? How can we fix it? Dr Carolyn Lam: Exactly, and I love the way you ended your review when you said, "Therefore, maybe in all our complaints and so on, saying that we want weight loss, we should actually be focusing on waist loss. You could redistribute the fat to healthy areas, not change your weight, and still become healthier." That was the concept, right? Dr Ian Neeland: That's right. Yeah. It really is amazing, and it's been shown again and again that people can stay the same weight, but their body fat really is very plastic. It can change, and it's modifiable. And that really makes a difference with health outcomes. So whether we can do that with lifestyle changes, so there's some data to support that. There's also some data to support pharmacology, so medications may be able to move fat from one area to another. And then certainly surgery, which is now getting a lot of popularity for people who are really high risk for cardiometabolic disease. Bariatric surgery has been shown to decrease visceral fat significantly, and that may be one of the reasons why it works so well. Dr Carolyn Lam: Exactly, Ian. Fascinating, fascinating. I tell you what. Could I just ask you to give us some take-home messages? Dr Ian Neeland: Sure. So one take-home message I think is that we can move beyond the BMI, beyond the body mass index. Obesity is no longer just a number. It's really about the entire individual, biologic systems, what's going on, and there's just remarkable heterogeneity in the structure of obesity, where body fat is, the activity of body fat, the physiology of it, and also how it relates to diseases, either causing disease and potentially being protective for harmful outcomes. I think it's also a key message to understand that there's sick fat and there is healthy fat and they're very different. And we can get to the bottom of those using specialized tools like imaging and special testing, but they're really very different, and not all body fat is created equal. And then lastly, I think it's important to consider, like you mentioned earlier, that really public health and lifestyle going forward is going to be so important, and focusing on those areas that will have the biggest impact for people such as trying to promote waist loss, like you said, as opposed to weight loss. Really focusing and using our knowledge of body fat and obesity and how it's so different across individuals and populations, that it's really important to use that knowledge for our future goals and to have that mind when we recommend weight-modifying therapies for our patients. It's really going to be a new frontier in weight. We're really moving beyond this concept of just check your weight and your height, and we can tell you what your risk is. No, it's really much more complex and complicated and much more interesting than that. Dr Carolyn Lam: Oh, Ian, that's just so wonderful. I cannot help this last question. Who knows whether we'll put it in, but I just have to ask you. So how do you monitor your own status or your patients' status? Do you really get them DEXAs, all of them? Or PETs, FDGs? Or do you take your own weight? Dr Ian Neeland: Yeah. I do. One thing I have noticed, I actually started an exercise and diet program for myself to improve my health about a year and a half ago. I took the research, and I said, "Okay, I'm really going to use this and apply this to my life." So, what's interesting is what I found and actually what other colleagues of mine in research are finding is that you can actually melt away visceral fat just with exercise alone, even if you don't actually go on a diet. And they've done studies like this where they do DEXA scans, and they give people high-intensity interval training. They don't give them a special diet. They just say maintain your current diet, and the visceral fat goes away. It's really remarkable how lifestyle can be so important and make such a change. And you can see people who have diabetes who can cure their diabetes with a lifestyle program by really decreasing the visceral fat. Even if their weight doesn't change or only changes by a small amount, but their weight may change by, I don't know, five, 10 pounds, but their visceral fat may go away by 50%. And that really makes the difference. It's obviously hard to monitor. We don't really have these tools clinically every day. Not everyone can do a DEXA and has the software to measure the visceral fat. Certainly could be coming in the future, but right now we should use the tools we do have and use the biomarkers we have and the clinical use, the waist circumference, triglycerides. These things are all surrogates for visceral fat but can be very useful to monitor for change. And it's not just about the scale. It's really about more than that with a person's metabolic status. Dr Carolyn Lam: That is so helpful. Thank you so much, and I'm so glad you said that it was exercise, and you don't jump into a ice pool or something to try and convert the fat to brown fat or something. That's really, really encouraging to me. Thank you, Ian. This was so enjoyable. I'm sure all our listeners are thanking you as well. Listeners, you've been listening to Circulation on the Run. Please tune in again next week.
Dr. Lam: Welcome to Circulation on the Run. Your weekly podcast summary and backstage pass to the Journal and it's editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center, and Duke National University of Singapore. Dr. Sanjay Kaul and Darren McGuire will be joining me in just a moment to share their perspectives on the EMPA-REG OUTCOME trials. Are the results with empagliflozin in diabetic patients at high risk, are they too good to be true. First, here are the highlights from five original papers in this week's issue. The first paper is from Dr. Gilboa, from the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention in Atlanta, Georgia, and Dr. Marelli from the McGill Adult Unit for congenital heart diseases in Montreal, Quebec, and colleagues. These authors recognize that because of advancements in care there has been a decline in mortality from congenital heart defects over the last several decades. However, there are still no current empirical data documenting the number of people living with congenital heart defects in the United States. These authors address this gap in knowledge by using prevalence data from Quebec, Canada, in the year 2010, as a foundation for a mathematical model, and estimated that in the United States in the year 2010, approximately 2.4 million people, including 1.4 million adults, and 1 million children were living with congenital heart defects. This estimate is significant, because it corresponds to a 63% increase in the estimated size of the adult population with congenital heart defects in the United States since the year 2000. This has significant implications for resource allocation for health services delivery that will need to account for this growing population of adults with congenital heart defects. The second paper is from first author Dr. Tabot, and corresponding author Dr. Liao, from the University of Chicago, and colleagues who aim to understand better the common complication of angiodysplasia leading to nonsurgical bleeding in patients with left ventricular assist devices. The authors studied 101 patients with heart failure, left ventricular assist devices, or orthotopic heart transplants. They found that compared to patients with heart failure, or transplant patients, patients with left ventricular assist devices had elevated serum levels, and endothelial expression of angiopoietin-2, which is a potent angiogenic mediator. Elevated levels of angiopoietin-2 in these patients increase angiogenesis in vitro, and were associated with bleeding events. Furthermore, they found that increased thrombin levels in left ventricular assist device patients were associated with elevated angiopoietin-2 levels. In aggregate, therefore, the results indicate that high levels of thrombin induced endothelial angiopoietin-2 expression, which may then contribute to angiodysplasia and non-surgical bleeding in patients with left ventricular assist devices. The clinical implications are that clinical studies angiopoietin-2, and factor 12 inhibitors may therefore be indicated to prevent nonsurgical bleeding in patients with left ventricular assist devices. The third paper is Dr. Gordon from Hasbro Children's Hospital in Rhode Island, and Dr. Kieran from the Dana Farber Cancer Institute in Boston, Massachusetts, and colleagues who addressed the Hutchinson Gilford Progeria Syndrome. An extremely rare, fatal segmental premature aging syndrome, where without specific treatment, death usually occurs at an average age of 14 1/2 years from an accelerated atherosclerosis. A PRIA single arm clinical trial has demonstrated that the protein farnesyltransferase inhibitor, Lonafarnib, ameliorates some aspects of cardiovascular and bone disease in this syndrome. The current trial sought to further disease outcomes by additionally inhibiting progerin prenylation using pravastatin and zoledronic acid on top of Lonafarnib in 37 participants with the Progeria syndrome. Results showed that the composite primary study outcome of increased rate weight gain and decreased carotid artery echodensity was achieved. Overall, participants experienced increased bone density, size, and structural properties. However, unlike the PRIA single arm Lonafarnib monotherapy trial, mean carotid-femoral pulse wave velocity and mean carotid artery adventitial echodensity were not improved. In addition, rates of carotid and femoral artery plaques and extraskeletal calcifications all increased. In summary, compared PRIA Lonafarnib monotherapy treatment, additional bone mineral density benefit, but likely no additional additional cardiovascular benefit was obtained with the addition of pravastatin and zoledronic acid. The authors concluded that since increased bone fracture is not a disease feature, the addition of a combination of statin and biphosphonate to Lonafarnib therapy is not recommended for clinical treatment of Progeria syndrome. However, it is reasonable to consider statins if concurrent lipid abnormalities need to be treated. This paper is accompanied by an excellent editorial by Dr. Francis Collins, who describes our journey in seeking a cure for this rare disease of Progeria. The fourth paper is by first author, Dr. Grisenti and corresponding author Dr. Tilley from Lewis Katz School of Medicine, Temple University in Philadelphia, and colleagues who aimed to better understand the role of leukocyte expressed beta-2 adrenergic receptors in regulating immune cell responses to acute cardiac injury. The authors achieved this aim by studying wild type mice who were irradiated, and then transplanted either with isoform specific beta adrenergic receptor knock out bone marrow, or wild type bone marrow. These chimeric mice, after full reconstitution then underwent myocardial infarction surgery. Results showed that immune cell specific beta-2 adrenergic receptor expression was essential to the repair process following myocardial infarction. In the absence of beta-2 adrenergic receptors, vascular cell adhesion molecule-1 expression was increased in leukocytes, inducing their splenic retention following injury, and leading to impaired scar formation, followed by rupture and death. Splenectomy partially restored the beta-2 adrenergic receptor deficient leukocyte infiltration into the heart, but gene therapy to rescue the leukocyte beta-2 adrenergic receptor expression completely restored all injury responses back to normality. This study is clinically important because it highlights a bit of a tension that we're facing. On the one had, beta adrenergic receptors are known to regulate cardiac function and remodeling following myocardial injury, by their effects through cardiomyocytes. That's why we use beta blockers to prevent, at first, cardiac remodeling. However, the current studies now indicate that inhibition or deletion of the immune cell expressed beta-2 adrenergic receptor causes leukocyte dysfunction, and impaired immunomodulatory responses to myocardial injury. These results may, therefore, have implications on the use of beta blockers around the time of acute myocardial injury, such as myocardial infarction, or perioperatively. This is really an area that needs further research and understanding. The fifth paper is by Dr. Herman, from the hospital of the University of Pennsylvania, and colleagues who report on the one year clinical outcomes of SAPIEN 3 transcatheter aortic valve replacement in high risk and inoperable patients with severe aortic stenosis. Now, as a refresher, in the initial partner trial of transcatheter aortic valve replacement for high risk and inoperable patients with severe symptomatic aortic stenosis, there was a demonstration of marked survival advantage compared to medical management ... But a high one year mortality of 24% in the high risk, and 31% in inoperable patients. More recently, the lower profile SAPIEN 3 prosthesis system has become available. Which has a balloon expandable cobalt chromium frame, with bovine pericardial leaflets, and an external fabric seal. The early 30 day outcomes of this system have been reported, and show a very low rate of adverse events. The current study now reports the one year survival, and showed that all cause survival was more than 85% for all patients, above 87% in the high risk, and above 82% in the inoperable subgroups. Furthermore, there was a high rate of transfemoral access at 84%, and a high all cause and cardiovascular one year survival in the high risk transfemoral subgroup of 89% and 93%, respectively. Between 30 and 365 days, the incidence of moderate perivalvular aortic regurgitation did not increase. There was no association between mild perivalvular leak and one year mortality. Although, a small increase in disabling stroke occurred. These results, which likely reflect device iteration and procedural evolution, support the use of Taver as a therapy to consider in high risk and inoperable patients with aortic stenosis. Those were the highlights from this week's issues, and now for our feature paper. We will be discussing the perspective paper entitled "Is the Mortality Benefit With Empagliflozin in Type 2 Diabetes Too Good to be True?". To discuss this, we have two very special guests. First, Dr. Sanjay Kaul, writer of this paper, and from Cedars-Sinai Medical Center. Second, Dr. Darren McGuire, deputy editor of circulation from UT Southwestern. Welcome, Sanjay and Darren. Dr. McGuire: Thanks, Carolyn. Dr. Kaul: Thank you, Carolyn. Dr. Lam: To start us off, I'd really love if Darren could please introduce this new content category of circulation. Frame of reference section, of which this is one of the papers, a perspective article. Dr. McGuire: Sure, so we envisioned, as we're evolving circulation to our new editorship, an opportunity for authors, luminaries in the field, to give us in a very encapsulated form, a laser focus perspective on a specific topic. These come in two flavors, the perspectives piece, which this is, is a little more evidence and scientific quantitatively based. Then we'll also have a section called on my mind, which is more of a free-flowing opinion editorial targeting possibly a contentious or controversial issue. These are going to be very short, and hopefully very entertaining, and kind of teasers for the readership of the Journal. Dr. Lam: Sanjay, you made it very personal, and I like that, too. Share with us how this idea came about. Dr. Kaul: Well, I was very impressed at the reception that the results of the EMPA-REG outcome trial received at the EAST meeting at Starcom last year. While I was witnessing the applause, I had polar reactions. On one hand, I thought that after nearly five decades of trials with checkered history, with regards to cardiovascular outcomes, here we have for the first time a trial demonstrating not only cardiovascular benefit, but a mortality benefit. I thought maybe it's time to take the trumpets out and sort of herald this holy grail, which we had failed to achieve. On the other hand, realizing that we had been fooled before many times by trials, yielding implausibly large treatments actually, that were never replicated at subsequent trials. I had a skeptical response to it, and sort of asked this question rather tongue-in-cheek, or maybe used as a rhetorical tool to address whether this mortality benefit was too good to be true. Dr. Lam: You know, you didn't just question it. You examined the data, and provided even more evidence. That's what I was impressed with in your paper. That table where you provided base factor, as well as a Bayesian analysis. Could you break that down for us, and explain what you found? Dr. Kaul: Yes, I was trying to sort of examine the strength of the evidence, in terms of the quantitative aspect. Yes, the effect size for the cardiovascular benefit was quite impressive. For the primary endpoint, which was a compositive cardiovascular, death, non-fatal MI, and non-fatal stroke, the p-value was not very robust. It was .04. The p-value tends to overestimate the strength of evidence. I utilized base factor, which basically is a metric that allows the two competing hypotheses to predict the data. Using the base factor, I was able to demonstrate that the alternative hypothesis was stronger than the null hypothesis by eight-fold. The p-value of .04 translated into a base factor of .13. Which is not strong evidence against the null hypothesis. It requires independent confirmation and subsequent trials. A p-value of .04, while meeting the superiority criteria, would not be sufficient enough to meet the FDA's requirement of substantial effectiveness. Substantial effectiveness just basically means that the FDA requires two trials, each with a p-value less than .05. In 1998, they modified their regulatory requirement, and accepted that one single trial would be sufficient, provided that there would be a persuasive p-value. Persuasive basically is defined as a p-value less than .001. The base factor allows us to sort of interpret the strength of the evidence, with respect to the primary composite endpoint was not strong enough to meet this requirement. With respect to cardiovascular mortality, as well as all cause mortality, which trumps all other endpoints, it was persuasive enough. Dr. Lam: What's your conclusion on that? Dr. Kaul: What is controversial about that was that in the three specified statistical plan, the so-called hierarchical testing strategy, the non-inferiority for three point MACE, followed by non-inferiority for four point MACE, and followed by superiority of three point MACE, and lastly, superiority of four point MACE. Because the p-value of four point MACE superiority was .08, one can argue purely from a statistical perspective that you stop your testing strategy, and any analysis beyond that would be deemed exploratory. Even though cardiovascular mortality and all cause mortality was prespecified, the purist would argue that since you failed superiority for four point MACE, you really can't proceed further. You can analyze, but it will be considered an exploratory analysis. I sort of wept and said that because Christopher Columbus had prespecified that he will be discovering the route to India, the fact that he stumbled upon America does not mean it doesn't exist because he had not prespecified it. I think all cause mortality is the most meaningful endpoint, and the least subjective measurement error. It meets the key attributes of regulatory decision making. Which it's prespecified, it's highly persuasive, therefore, it meets the replication criteria, and the p-value is so robust that even if you adjust for nearly 100 multiple comparisons, the p-value would still hold. It meets all the regulatory criteria for approval. Dr. McGuire: Sanjay, let me just chime in here. I think it's also important, not only were these prespecified, but it's important, I think, for readers of these diabetes programs to realize that hospitalization for heart failure ... Although it's not part of the primary outcome ... In virtually every one of these trials, it is prospectively collected, chartered to find, and essentially adjudicated by blind endpoint adjudicators. You know, death is death. Cardiovascular death in these programs are all adjudicated, as well. I think the prospective collection and central adjudication also adds legitimacy to the hospitalization for heart failure are above and beyond the analytic issues. Dr. Lam: Darren and Sanjay, I hear both of you kind of saying it does look like, even looking at it from different angles, the data do look strong. At the end of the day, Sanjay, you concluded that it does need another trial. Results do need to be replicated. That was your conclusion. I'd love to hear Darren's take on this. Dr. McGuire: I think what Sanjay is saying there, and I think what we all believe, was we would really love to see this observation with another member or members of the class. We're learning a lot in hindsight based on these observations, and people are exploring potential mechanistic underpinnings. We're learning a lot about the mechanisms of these medications, above and beyond their glucose uric effects. There's a lot of implication about renal physiology and hemodynamics, and altered myocardial metabolism. I think as Sanjay points out in the paper, some of this looks like a possible arrhythmic effect. We have a lot to learn about this mechanism of action, and whether or not this will be unique to impact gliflozin. It has been publicly announced, Boehringer Ingelheim is planning, they're in the planning phases for heart failure trials with empagliflozin to further explore this signal. I think they will address Sanjay's desire to have some replication in a different patient population. Still, we would love to see these extended into other patient populations. To both extend the use of the medications if they're found, but also provide further confirmation of the observations from EMPA-REG outcome. Dr. Kaul: Carolyn, let me also add, I used the title as a rhetorical tool, as I stated earlier. I do conclude that the mortality data is not likely to be spurious. In the back of my mind, I still have that 1% skepticism that I would like to eliminate, because the findings were totally unexpected, and unprecedented, as we discussed earlier. If all the pathways, including the mechanistic pathways are aligned, I would have substantial reassurance, beyond any reasonable doubt that the findings are true. That's why I'm asking for replication. Not necessarily by empagliflozin in other trials, but by another molecule within the same class. I think that would be sufficient. Dr. McGuire: Yeah, and I think it's really interesting to note there, is that I was involved in the early days of some of these drugs as they're being developed. When the other two members of this class went to the FDA, dapagliflozin and canagliflozin, they provided FDA's requirement and meta analysis from all of the phase 2B and 3 trials that had been completed to date. The meta analysis of the cardiovascular outcomes. Both dapagliflozin and canagliflozin had point estimates of cardiovascular death reduction of 30%, and 35%, respectively. When we saw those data, they were based on 25 to 40 total events. We chuckled, thinking this is spurious, from small events being analyzed. That there's no way they would prevent cardiovascular death. Sure enough, you know, you could almost superimpose those point estimate plots from the phase 2B-3 meta analysis, with the ultimate outcomes from EMPA-REG. There's some promising, although again, very statistically imprecise estimates that this may well be a class effect. As many of the listeners will know, there are ongoing cardiovascular outcomes trials for all of these medications. That will come some time in the next year or two. Dr. Lam: That's fantastic. Thank you both for sharing those perspectives. I mean, I learned so much. I really think, Sanjay, your paper achieved exactly what you had meant for it to achieve, and exactly what circulation was hoping to create the discussion, as well. Dr. McGuire: Thank you, Carolyn. Dr. Kaul: Thank you very much. Dr. Lam: You've been listening to Circulation on the Run. Thank you for listening. Don't forget to join us next week for more highlights and discussions.
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