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「ラジコン出身レーシングドライバー・奥本隼士（25）レース経験ゼロからプロへ 夢に懸けた情熱と行動力【スーパー耐久・スーパーGT2024】」 9月29日（日）、鈴鹿サーキットで行われたスーパー耐久第5戦。そこに、大きな夢に挑む異色のドライバーがいた。「なんとかスーパーGT500とスーパーフォーミュラで走りたい。目標はその1点なんで、突っ走っています」ST2クラスで今シーズン2勝を挙げている強豪チーム、KTMSでステアリングを握る奥本隼士（おくもとしゅんじ）25歳。レース歴はわずか3年。超異色な「レース人生」を歩むドライバーなのだ。驚くべきは奥本のレースのルーツ。それはラジコン。「5歳でラジコンを始めて小学校5年でタミヤのワールドチャンピオンシップで優勝しました」幼い頃からレースに憧れを抱いていた奥本が最初に手にしたのはラジコンカー。2011年には世界一の称号を手にした。――（ラジコンは）今のレースのトレーニングになっている？なっていますね。やっぱり反射神経とか、動体視力とか、集中力とか。車の動きも外から見て「こうやったら早く走れるんや」とか。そんな奥本がリアルレースの世界に足を踏み入れたのは、大学卒業を控えた2021年。幼い頃の夢を諦められず、インターネットで検索した地元のレーシングチームの門を叩いた。株式会社HERO'Sの青合（あおあい）正博社長は語る。「大学生で就職活動しているということだったんで、今からレースするって、お金もかかるし時間もかかるし、『プロドライバーを目指したい』って言っているから、何を言っているんだろうと思った（笑）。何を言っているんだとうと思ったんですけど、彼の『やりたい』という情熱は伝わってきました」現状、プロのドライバーのほとんどは、幼少期からカートを始め、ステップアップしてきた者ばかり。大学卒業を控えたレース経験ゼロの奥本がプロを目指すのは、無謀な挑戦と捉えられても不思議ではなかった。それでも奥本の情熱に共感した青合社長は全面バックアップを決意。その決断の理由の一つ、それは奥本の特別な才能にあった。青合社長は当時を振り返る。
Episode 101 is on the scene and we are discussing the love for F45's in response to the tire situation that has been a subject of conversation all season long on the CARS Tour. We discuss the impact of the switch back to the Hoosier F45's from the controversial ST2's plus give our analysis of Friday's Drive For Puryear 125 from Wake County Speedway. Landen Lewis added his name to a growing list of winners on the tour this season and we discuss that, the incident between him and teammate Brent Crews, the points shake up and how some of the local ringers did. Donovan Strauss is a name rising through the short track ranks that you need to keep an eye out on. The Philadelphia native is in the midst of his first full year running late models at Florence Speedway in Florence South Carolina and joins the podcast this week. We discuss his recent breakthrough win at Florence in weekly competition, his upcoming CARS Tour debut, his start in racing, competing in ESports, his successful Legends career and love for the Philadelphia Eagles. Kaleb Hall has been around the sport his entire life. Growing up near Franklin County Speedway in Virginia, he was always destined to try his hand in racing at the track. Over the weekend, he scored his first ever win in the Rookie Division and notched two three place finishes in Stock 4. He joins the show to discuss this, his Visual Works Company and any secrets he may have about his Co-Host Uncle Julian. We discuss Harrison Burton's upset win at Daytona and the impact the 100th win for the Wood Brothers has on the industry, how this win disrupts the playoffs, keeping cars on the ground after two more blowovers and who has the edge at Darlington in the regular season finale among more topics. Layne Riggs may have separated his shoulder celebrating his first win in the NASCAR Craftsman Truck Series but it didn't put a damper on breaking through the win column on what has been a tough year for the former CARS Tour star and South Boston Speedway weekly competitorSpeaking of South Boston, we set the stage for Halifax County Farm Bureau Championship Night this weekend at South Boston Speedway. Who will come out of this as season long champion in the Sentara Late Models, Budweiser Limited Sportsman, Southside Disposal Pure Stock and VSP HEAT Hornet Divisions? You will need to listen to find out.We also preview the upcoming SMART Modified Tour doubleheader from New River All-American Speedway and Carteret County Speedway this weekend, STAR Super Stock Tour race from Florence, review championship night at Bowman Gray Stadium and so much more on a jam packed episode of DLN!
Dengan peningkatan sebanyak 208.1 ribu jawatan dalam sektor ekonomi, bilangan jawatan telah mencapai 8.83 juta, melebihi bilangan pada tahun sebelumnya iaitu 8.62 juta dalam tempoh yang sama (ST2 2022).
Like many of our guests Chris grew up in a motorsports family.Chris raced jet skis and has a funny Late To Grid story that he shares. He made it to the Jet Ski World Finals in 1998! When he was done racing on water he found the SCCA and started racing RX-7s.In 2004 he started LMS-EFI and has been focused on engine management systems, data loggers, dashes, and complete vehicle wiring. While his focus is on Mazda and rotary, Chris works on many other makes and models.He now races an ex-NASCAR car in GTA and ST2 in NASA. How fun! He set a track record at Gingerman in GTA and won a sprint race at Mid-Ohio in the RX-7 that I now own. He's fast! What keeps interested in motorsports? Customers become friends. He likes the people and the smell of race fuel.He's very thankful that his wife and sons are supportive of his racing and the business.How to connect with the Chris & LMS-EFI:LMS-EFI WebsiteLMS-EFI FacebookLMS-EFI InstagramEmail: chris@lms-efi.comCheck out our sponsors:Show Sponsor LMS-EFI Website, Facebook, InstagramShow Sponsor Track-First Website, Facebook, InstagramFollow us!Late to Grid - InstagramLate To Grid - Facebook
Today's featured guest is Tarn Shant, Senior Vice President, Transformation and Governance at iQor. Tarn leads a team of digital customer experience experts, engineers, and security analysts focused on building out the technology infrastructure by which iQor delivers outsourced customer services for our clients. Tarn has been in the BPO industry for more than twenty years. He began his career as an agent handling customer phone calls. This background inspires Tarn to keep the agent at the center of the conversation when planning technologies that enable them to deliver great customer service. As Tarn's career has progressed, he's held different roles achieving a Certified Black Belt Six Sigma along the way. Many of his roles were business-centric responsibilities while leading large scale operations[ST1] . About seven years ago he got the opportunity to move into technology, which he embraced. Earlier in 2021, Tarn was heading up infrastructure and operations technology. Around the middle of 2021 he got the opportunity to lead transformation and governance. His team is devoted to helping customers optimize the CX experience for their end customers. iQor's Approach to Digital Experience Transformation Tarn's team is focused on deploying technology that results in a great customer experience along with a happy and productive contact center agent. Their approach to building CX technology is built on these three pillars. Call Deflection This entails creating an end customer experience that is as effective as possible through self-service to reduce the chance of a customer calling to speak with an agent to resolve simple questions such as “where is my shipment?” This can be achieved through intelligent automation such as IVR technology, chatbots, in app messaging, etc. The result is a great experience for the end customer that also benefits the agent by resolving simple questions before they get to an agent through a voice call. This allows agents to get more fulfillment from their customer interaction by helping them solve more complex issues. Digitization of the infrastructure that enables the CX experience. Tarn is extremely proud of the iQor private CX cloud. It provides stability and scalability that delivers great value for our clients and for our business. He explains further that we are moving toward a hybrid cloud that enables us to choose workloads that can be executed better in a public cloud, and keep certain workloads on our private cloud, within our data centers. We are accelerating the hybrid cloud model because it's paying dividends for our clients. The Agent Experience Every decision we make considers the impact on the contact center agent. We ask how will this technology impact the agent? It starts with the hiring process. Once an agent is hired, the onboarding process is all about training the agent. There are technologies that help agents train faster, reducing their learning curve. Once training is completed, the focus is ensuring that we enable them to perform well. Agents want to be productive, meeting the KPIs established by and for our clients. Agents benefit from tools such as chatbots, knowledge management tools, speech analytics and AI powered coaching as well as feedback from their supervisors. The combination of these tools and the human supervisor element enables our agents to perform at a high level of performance and job satisfaction. The iQor Differentiator is Speed and Security Tarn points out that successful execution comes down to speed and security. When it comes to speed, he shares an example of a client who had a need to stand up 500 agents in 7[ST2] days. Due to our established technology infrastructure coupled with our robust and proven recruiting processes, we got it done, much to the thrill of the client. Naturally, clients want to know that our customer care service delivery is secure. In today's hybrid CX delivery model where some frontline staff are located in an iQor facility and others are work-at-home agents, security is paramount. Tarn explains our approach to data security is partnering with best-of-breed partners such as Palo Alto Networks, CrowdStrike, NICE and Thinscale to deliver end point security that scales. He ensures that his staff gets proper training, so they are up to speed on the technology ensuring effective deployment of secure CX service delivery regardless of an agent's location. Collaboration with our partner's security team ensures the right controls are in place for us to deliver highly secure customer service to our client's end customers. Balancing People with The Technology Infrastructure Another element that exists as a layer above the four pillars is change management. As technology is planned, Tarn works closely with his team to ensure that cultural change is inclusive so that everyone is part of the common story. For Tarn, it's always been about people, making sure everyone understands what they are trying to achieve. People ask is each technology initiative aligned to the company goals? Investing in people's skills development, giving them the proper tools and an environment where they can share their ideas and flourish is an important part of the culture. He regularly reaches out to frontline staff to have skip level meetings to give them an opportunity to be heard. Another important consideration is technology training. Whenever we sign up for a new technology, we ensure the partner offers training directly or through an authorized partner to train our team. What Tarn Does for Fun Tarn started playing tennis for exercise and fun during COVID. Since he lives in the northeastern U.S. where outdoor tennis is not available six months of the year, he also enjoys going for long walks and listening to podcasts to stay up-to-date on topics of interest. Learn more about iQor digital customer experience capabilities. Read the blog post here. Watch the video here.
Whitetail deer herd health and trophy buck management are 2 crucial components to effectively managing your land for a successful hunting season. Zack Vucurevich invited us down to show us how he manages his land. He explained things like how you should look at deer population management, how to think about the habitat and browse before food plots come into the equation, his strategy on using trail cameras, how he suggests using feeders, and yes, he'll address food plots.Gearbox Talk is brought to you by GoWildDownload GoWild today. Join a community of shooters, hunters, anglers and outdoor enthusiasts.http://bit.ly/DownloadGoWildNowGear Mentioned:Cuddylink trail cam https://timetogowild.com/gearbox/products/sportsmansguide-G-5055-cuddeback-cuddeback-cuddelink-dual-flash-camera-and-cap-kitRattling antlers https://timetogowild.com/gearbox/products/cabelas-2209354-flextone-flextone-battle-bones-rattling-call-systemBanks 300 pound gravity feeder https://timetogowild.com/gearbox/products/sportsmansguide-FB300-banks-outdoors-banks-outdoors-feed-bank-gravity-feeder-300-lb-capacityBanks Outdoors The Stump 2 Hunting Blind https://timetogowild.com/gearbox/products/sportsmansguide-ST2-banks-outdoors-banks-outdoors-the-stump-2-hunting-blindTrophy Rock 12 lb Rock Supplement https://timetogowild.com/gearbox/products/academyoutdoors-502500-trophy-rock-trophy-rock-12-lb-rock-supplementEagle seed soy beans wildlife managers blend https://www.eagleseed.com/forage.htmlAntler king 7 card stud https://www.evolved.com/7-card-studEagle seed smorgasbord https://www.eagleseed.com/fallblends.htmlShow Notes:Website: http://www.whetstonehabitat.com/ Facebook: https://www.facebook.com/WhetstoneHabitat Instagram: https://www.instagram.com/whetstonehabitat/
Mesta yndi og kjarnakona kom til okkar í stúdíóið og það er ekkert eðlilega skemmtilegt að spjalla við Evu Laufey. Njótið vel kæru hlustendur - við mælum með að glósa smá því þessi þáttur er fullur af snilld!
In this episode, Dr. Ahmed discusses how trainees can improve your communication skills. Learn more: visit www.mrcgpdoctors.com today.
Langar þig að skrásetja minningar sem sækja á þig? Siturðu uppi með fróðleik um ættingja, vini eða tímabil sem þú veist ekki hvað skal gera með? Langar þig jafnvel að skrifa bók? Að rita ævisögur og endurminningar er námskeið sem haldið er á vegum Endurmenntunar Háskóla Íslands. Á námskeiðinu verður fjallað um ævisögur og endurminningar frá ýmsum sjónarhornum og við fengum Pál Valsson bókmenntafræðing og rithöfund og stjórnanda námskeiðsins í þáttinn til þess að segja okkur frá því hvernig á að bera sig að í þessu. Já, það var námskeiðadagur hjá okkur í Mannlega þættinum í dag og við héldum áfram að spyrja: Er eitthvað sem þig langar til að gera en þú gerir það samt ekki? Langar þig til að breyta til? Skipta um starf eða jafnvel að fara í eigin rekstur? Skrifa bók? Fara í pólitík? Spyrja eða koma með tillögu á vinnufundi? Bjóða á stefnumót? Setja mörk? Við sögðum frá ókeypis námskeiði fyrir konur sem vilja standa með sjálfri sér og hafa meiri trú á eigin getu til að láta drauma sína rætast. Ragnhildur Vigfúsdóttir, markþjálfi, kom í þáttinn. Halldór Logi Friðgeirsson hefur stundað sjóinn og ýmiskonar veiðiskap frá unga aldri. Hann er núna skipstjóri á Grímsey ST2 og Kristín Einarsdóttir, okkar kona á Ströndum, fór um borð og ræddi við hann um sjómennsku og annan veiðiskap. UMSJÓN GUNNAR HANSSON OG GUÐRÚN GUNNARSDÓTTIR
Langar þig að skrásetja minningar sem sækja á þig? Siturðu uppi með fróðleik um ættingja, vini eða tímabil sem þú veist ekki hvað skal gera með? Langar þig jafnvel að skrifa bók? Að rita ævisögur og endurminningar er námskeið sem haldið er á vegum Endurmenntunar Háskóla Íslands. Á námskeiðinu verður fjallað um ævisögur og endurminningar frá ýmsum sjónarhornum og við fengum Pál Valsson bókmenntafræðing og rithöfund og stjórnanda námskeiðsins í þáttinn til þess að segja okkur frá því hvernig á að bera sig að í þessu. Já, það var námskeiðadagur hjá okkur í Mannlega þættinum í dag og við héldum áfram að spyrja: Er eitthvað sem þig langar til að gera en þú gerir það samt ekki? Langar þig til að breyta til? Skipta um starf eða jafnvel að fara í eigin rekstur? Skrifa bók? Fara í pólitík? Spyrja eða koma með tillögu á vinnufundi? Bjóða á stefnumót? Setja mörk? Við sögðum frá ókeypis námskeiði fyrir konur sem vilja standa með sjálfri sér og hafa meiri trú á eigin getu til að láta drauma sína rætast. Ragnhildur Vigfúsdóttir, markþjálfi, kom í þáttinn. Halldór Logi Friðgeirsson hefur stundað sjóinn og ýmiskonar veiðiskap frá unga aldri. Hann er núna skipstjóri á Grímsey ST2 og Kristín Einarsdóttir, okkar kona á Ströndum, fór um borð og ræddi við hann um sjómennsku og annan veiðiskap. UMSJÓN GUNNAR HANSSON OG GUÐRÚN GUNNARSDÓTTIR
In this episode, Dr. Ahmed discusses the various resources that are available to help IMGs to become good UK GPs. Learn more: visit www.mrcgpdoctors.com today.
Since my latest ST2 eps have been all about LucasArts, I decided to broadcast a LIVE special all about them too! For my first show of 2021, I present tracks from some of their earliest releases, right up to the very last game they developed that wasn't based on Star Wars. As a result, this playlist is stacked with some of the very best VGM ever composed, and it was a lot of fun to be back with the show.In addition, don't miss this episode's new SFX Showdown, where you can win your own physical copy of "Lost Astronaut" by Empty Tables; a great album from a fresh new talent, which you can hear a couple of tracks from in this playlist!This week's playlist:Ballblazer (feat. Beastie Boys) – Romeo Knight (originally composed by Peter Langston & Russell Lieblich)Fear is the Mind Killer – Adam Freeland [Rez]Not in Control – Empty Tables [Lost Astronaut]Hostile Space – Empty Tables [Lost Astronaut]Dave's Theme – David Warhol, George Sanger, David Hayes and/or Dave Govett [Maniac Mansion]BGM #02 – Mark Cooksey [Indiana Jones and the Last Crusade: The Action Game]Hetchel and the Elders – George Sanger (originally composed by Tchaikovsky) [Loom]Opening Themes & Intro – Michael Land and/or Patrick Mundy [The Secret of Monkey Island]Beach – Michael Land, Peter McConnell and/or Clint Bajakian [Monkey Island 2: LeChuck's Revenge, Special Edition]Jawa Sandcrawler – Paul Webb (originally composed by John Williams) [Super Star Wars]Mission Debriefing – Michael Land, Peter McConnell and/or Clint Bajakian [Star Wars: X-Wing]Tentacle Disco – Michael Land, Peter McConnell and/or Clint Bajakian [Day of the Tentacle]Zombie Panic – Eric Swanson (originally composed by Joe McDermott) [Zombies Ate My Neighbors]Highway Surfing – Michael Land, Peter McConnell and/or Clint Bajakian [Sam & Max Hit the Road]Born Bad – Gone Jackals [Full Throttle]Mission to the Asteroid – Michael Land [The Dig]The Ballad of Dr. Death – Clint Bajakian [Outlaws]Wing Commander Surf – Team Fat (originally composed by Dave Govett)A Cartographer Reformed – Michael Land [The Curse of Monkey Island]The Enlightened Florist – Peter McConnell [Grim Fandango]Imperial Rage (Leviathan Remix) – Peter McConnell and/or David Levison (originally composed by John Williams) [Star Wars: Force Commander]Nazi Infiltration 1 ALT – Clint Bajakian [Indiana Jones and the Emperor's Tomb]Star Wars Disco – David Whittaker (originally composed by John Williams) [LEGO Star Wars: The Video Game]??? – Yohann Boudreault, Steve Szczepkowski and/or Jean-Sebastien LeBlanc[Thrillville: Off the Rails, DS]Main Title – Chris Tilton and/or Chad Seiter [Fracture]Off On a Comet – Jesse Harlin [Lucidity]Coolpunk Paradise – Lee Tyrrell [One-Night VGM] MAIN THEME:Mahito Yokota, Toru Minegishi, Koji Kondo & Yasuake Iwata - World 8 [Super Mario 3D World]Discord:https://discord.gg/xeMfzWyRequests and contact:https://twitter.com/GreenT128"The Sound Test" on Facebook:https://www.facebook.com/thesoundtest/Original episodes of The Sound Test LIVE, with Dale Fowler, are available through Patreon:https://www.patreon.com/_secretcaveAlso available through:YouTubeSpotifyiTunesStitcher
A pair of biomarkers are being used to guide treatment and predict mortality in patients with graft-versus-host disease (GVHD), according to James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York. In this episode, Dr. Ferrara explains how measuring these biomarkers – REG3-alpha and ST2 – can prevent over- and undertreatment of acute GVHD. The biomarkers have also been shown to predict nonrelapse mortality more accurately than a change in clinical symptoms. Before reviewing these findings, Dr. Ferrara tells host David H. Henry, MD, what GVHD is, how to recognize it, and how it’s typically treated. GVL and GVHD GVHD is “very tightly associated” with the graft-versus-leukemia (GVL) effect, Dr. Ferrara explained. The GVL effect refers to the ability of donor immune cells to eliminate host malignant cells after allogeneic hematopoietic stem cell transplant (allo-HSCT). The donor T cells respond to minor histocompatibility antigens on malignant cells but also on normal cells. When the donor T cells attack the normal cells, the patient develops GVHD. To prevent GVHD, patients may receive cyclosporin, tacrolimus, methotrexate, sirolimus, or other drugs in various combinations. Despite prophylaxis, slightly under half of allo-HSCT recipients will still develop some form of GVHD, Dr. Ferrara said. Acute GVHD Acute GVHD typically occurs in the first month or two after transplant, and about 50% of cases happen in the first month, Dr. Ferrara said. There are three primary targets – the skin, liver, and GI tract. The rash observed with skin GVHD is vesiculopapular, and the extent of the rash determines the stage of GVHD in the skin. Increase in total bilirubin is used to measure the stages of liver disease. GVHD in the GI tract is characterized by persistent nausea and vomiting or diarrhea (up to liters a day). Evaluating the skin, liver, and GI tract together can provide the overall GVHD grade, between 1 and 4. Grade 4 GVHD is the most severe, and grade 1 is a skin rash that usually affects less than 50% of the body surface area. Over- and undertreatment When GVHD is mild and limited to the skin, topical steroid creams are adequate treatment. When GVHD progresses into the GI tract and liver, patients require systemic immunosuppression. However, it’s difficult to tell whether GVHD is going to be mild, moderate, or severe. So when patients with acute GVHD receive systemic steroids at a starting dose of 1 mg/kg, many of these patients are overtreated “and a fair number of them are undertreated because we don't actually know which patients are going to progress and which patients are going to respond to treatment,” Dr. Ferrara said. He noted that the JAK1/2 inhibitor ruxolitinib was approved to treat steroid-refractory acute GVHD last year. Prior to that, the only approved treatment for GVHD was systemic steroids. Biomarkers signal disease severity Through their research, Dr. Ferrara and colleagues identified two biomarkers of GVHD severity – REG3-alpha and ST2. “When the GI tract is damaged early, these proteins flood into the systemic circulation, and they can actually tell us who's got a damaged GI tract very early, even before one has symptoms like diarrhea,” Dr. Ferrara explained. The biomarkers can be used to assess, at the onset of GVHD, whether or not a patient has crypt damage and needs more intensive treatment. Biomarkers guide treatment, predict outcomes Dr. Ferrara and colleagues used serum samples collected by the Mount Sinai Acute GVHD International Consortium (MAGIC) to develop MAGIC Algorithm Probability (MAP). MAP is calculated from patients’ levels of REG3-alpha and ST2 and can be used to predict the risk of severe GVHD. “You put these two biomarkers into an equation, you get a single number, and that number tells you whether [the patient is] high risk, low risk, or intermediate risk,” Dr. Ferrara explained. He and his colleagues found they could use MAP to predict patients’ response to treatment and mortality. In fact, MAP was able to predict nonrelapse mortality more accurately than a change in clinical symptoms (Blood Adv. 2019. 3[23]:4034-42. https://bit.ly/39QNUVn). Standard practice, ongoing trials MAP is increasingly becoming a part of standard practice, Dr. Ferrara said. A company called Viracor Eurofins Clinical Diagnostics licensed MAP and provides tests for consumer use (https://bit.ly/33RhRBa). Centers can send blood samples to Viracor to test. More than 50 centers in the United States sent at least 1,000 samples to Viracor for testing in 2019, Dr. Ferrara said. He and his colleagues are also utilizing MAP in ongoing clinical trials: A phase 2 study of natalizumab plus standard steroid treatment for high-risk acute GVHD (NCT02133924; https://bit.ly/3grvsUK). A pilot trial of alpha1-antitrypsin for preemption of steroid-refractory acute GVHD (NCT03459040; https://bit.ly/3qy48c9). A phase 2 trial of itacitinib for low-risk GVHD (NCT03846479; https://bit.ly/37GkaYK). Disclosures: Dr. Ferrara has a patent for serum biomarkers of acute GVHD and receives royalties from Viracor. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd
This week's episode features author Torbjørn Omland and Senior Guest Editor Vera Bittner as they discuss the artile "Growth Differentiation Factor-15 Provides Prognostic Information Superior to Established Cardiovascular and Inflammatory Biomarkers in Unselected Patients Hospitalized with COVID-19." TRANSCRIPT BELOW: Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary, and backstage pass to the journal and its editors. We are your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn our feature this week gets into inflammatory biomarkers in patients that have been hospitalized with COVID-19, but before we get to that, how about we grab a cup of coffee and work through some of the papers in the issue. Would you like to go first? Dr. Carolyn Lam: Absolutely. With both the coffee and the papers. So great, for this first paper, have you thought about concentric versus eccentric cardiac hypertrophy? We traditionally associate them with pressure versus volume overload respectively in cardiovascular disease, both though conferring an increased risk of heart failure. These contrasting forms of hypertrophy are characterized by asymmetric growth of the cardiac myocytes in mainly width or length respectively. However, the molecular mechanisms determining myocyte preferential growth in width versus length remain poorly understood. Dr. Carolyn Lam: That is until today's paper, and it is from Dr. Kapiloff from Stanford University, and Dr. Rosenfeld from UCSD, School of Medicine and their colleagues, and what they did was used primary adult rat ventricular myocytes, as well as Adeno associated virus mediated gene delivery in mice, to define a regulatory pathway controlling pathological myocyte hypertrophy, and they found that asymmetric cardiac myocyte hypertrophy is modulated by serum response factor phosphorylation, constituting an epigenomic switch balancing the growth in width versus length of adult ventricular myocytes In vitro, and In vivo. Dr. Carolyn Lam: Serum response factor phosphorylation was bi-directionally regulated at signalosomes organized by the scaffold protein muscle, A kinase anchoring protein beta. This newly identified molecular switch controlled a transcriptional program responsible for modulating changes in cardiomyocyte morphology that occurs secondary to pathological stressors. Dr. Greg Hundley: Very nice, Carolyn. So switches controlling this transcriptional program. Tell us a little bit, and bring us back to the clinical relevance of this and starting with that concentric versus eccentric hypertrophy? Dr. Carolyn Lam: I thought you may ask. The identification of a molecular mechanism regulating that asymmetric cardiomyocyte growth, really provides a new target for the inhibition of pathological cardiac hypertrophy. Studies in mice using these Adeno associated virus based gene therapies to modulate that signalosome, really provided proof of concept for translational potential in the treatment of pathological cardiac remodeling and prevention of heart failure. Dr. Greg Hundley: Oh, wow. Very nice, Carolyn. Well, my first paper comes to us from Professor Dirk Westermann from Hamburg, and focuses on cardiogenic shock patients, and veno-arterial ECMO, the results from the international multicenter cohort study. So Carolyn this study evaluated data from 686 consecutive patients with cardiogenic shock treated with VA ECMO with or without left ventricular unloading using an Impella, and they conducted this at 16 tertiary care centers across four countries. They examined the association between left ventricular unloading and 30 day mortality. Dr. Carolyn Lam: Huh, so what did they find? Dr. Greg Hundley: Okay. Carolyn. Well, left ventricular unloading was used in 337 of the 686 patients enrolled, and after propensity matching 255 patients with left ventricular unloading were compared with the 255 patients without left ventricular unloading. In the match cohort, left ventricular unloading was associated with lower 30 day mortality without differences in the various subgroups. However, complications occurred more frequently in patients with left ventricular unloading, like severe bleeding, which happened in 38.4% versus only 17.9% in those without unloading. There was also access-related ischemia and renal replacement therapy. Dr. Greg Hundley: So Carolyn, the take-home message from this International multi-center cohort study, is that left ventricular unloading is associated with lower mortality, and cardiogenic shock patients treated with VA ECMO, despite higher complication rates. In the absence of randomized trial data these findings support the use of left ventricular unloading and cardiogenic shock patients treated with VA ECMO, and call for further validation, ideally in a randomized controlled trial. Dr. Carolyn Lam: Very nice. Well for my next paper, Greg, it's all about desmin. Now we know that mutations in the human desmin gene caused myopathies and cardiomyopathies. Well, today's authors, Dr. Hermann and Schroeder from University Hospital Erlangen in Germany and Dr. Lilienbaum from University of Paris and France and their colleagues, report an adolescent patient who underwent cardiac transplantation, due to restrictive cardiomyopathy caused by a heterozygous R406W desmin mutation. Sections of the explanted heart were analyzed with antibodies specific to 406W-desmin, and to intercalated disc proteins. Effects of this mutation on the molecular properties of desmin were then addressed by cell transfection and In vitro assembly experiments. They further generated these desmin mutation knock-in mice haboring the orthologous form of the human, R406W-desmin. Dr. Greg Hundley: So Carolyn, what did they find? Dr. Carolyn Lam: Well, they demonstrated a novel pathomechanism in which cardiotoxic R406W-desmin, could adapt dual functional status with the abilities to integrate into the indogenous intermediate filament network, and to cause formation a protein aggregates. This R406W-desmin modified the extra sarcomeric cytoskeleton, such that desmin filaments were not anchored to desmosomes anymore. Thereby destroying the structural, and functional integrity of intercalated discs. Dr. Greg Hundley: What are the clinical implications? Dr. Carolyn Lam: Well, since these cardiotoxic desmin mutations could affect the integrity of intercalated discs, thereby inducing conduction defects and malignant arrhythmias, they suggest early implantation of pacemaker, or cardioverter defibrillator devices, may be considered to prevent certain cardiac death in patients with these mutations. Furthermore, state-of-the-art basic molecular risk stratification of desmin mutations may encompass a multidisciplinary experimental approach as exemplified by the approach taken here, which comprises assessment of the tissue pathology in conjunction with genome analysis and desmin assembly studies as well as patient mimicking cell and animal models for the In vivo validation of these mutations. Dr. Greg Hundley: Well, fantastic, Carolyn. Well, my next paper comes to us from Dr. Ravi Shah from the Massachusetts General Hospital. This study evaluated 2,330 white and black young adults, average age of 32 years, in the Coronary Artery Risk Development in Young Adults, or the cardiac study, to identify metabolite profiles associated with an adverse cardiovascular disease phenom that included, myocardial structure and function, fitness, vascular calcification, and then also mechanisms, and other cardiovascular outcomes that would occur over the next two decades. Statistical learning methods, including elastic nets and principal component analysis, and Cox regression generated parsimonious metabolite based risk scores, validated in over 1800 individuals in the Framingham Heart Study. Dr. Carolyn Lam: Wow. What did they show, Greg? Wow, that's a lot of work. Dr. Greg Hundley: Yeah. So Carolyn, the authors found two multiparametric metabolite-based scores linked independently to vascular, and myocardial health. With metabolites included in each score specifying microbial metabolism, hepatic steatosis, oxidative stress, nitric oxide modulation, and finally collagen metabolism. Over nearly 25 year median follow-up, and cardia, this metabolite based vascular score, and the myocardial score, and the third and fourth decade of life were associated with clinical cardiovascular disease. Importantly, the authors replicated these findings in 1,898 individuals in the Framingham Heart Study followed over two decades, such that young adults with poor metabolite based health scores had higher hazard ratios of future cardiovascular disease related events. Dr. Carolyn Lam: Oh wow. Greg, what an elegant study with both development and validation cohort evaluating the metabolome. Dr. Greg Hundley: Yes. Carolyn. So metabolic signatures of myocardial, and vascular health in young adulthood specify known novel pathways of metabolic dysfunction, relevant to cardiovascular disease associated with outcomes in two independent cohorts. So these data suggests that efforts to include precision measures of metabolic health in risk stratification to interrupt cardiovascular disease at an early at stage, are warranted. Dr. Carolyn Lam: Wow. So interesting. Other very interesting articles in today's issue, there's an In Depth article by Dr. Angiolillo entitled, “The Antithrombotic Therapy for Atherosclerotic Cardiovascular Disease Risk Mitigation in Patients with Coronary Artery Disease and Diabetes.” There's also Research Letters, one by Dr. Sultan on, “The Longterm Outcomes of Primary Cardiac Lymphoma” and one by Dr. Wang on, “Loss of Phosphatase and Tensin Homolog Promotes Cardiomyocyte Proliferation and Cardiac Repair Following Myocardial Infarction.” Dr. Greg Hundley: Great, Carolyn. Well, I've got a couple other articles in this issue as well. One is by Professor Ganesan Karthikeyan who has an On My Mind piece entitled an “Alternative Hypothesis to explain Disease Progression in Rheumatic Heart Disease.” Dr. Stuart Chen has an ECG challenge entitled, “Alternating QRS Duration and a Normal T-waves. What is the mechanism?” Then finally, Carolyn, a series of Letters to the Editor, one by Dr. Peterzan and the other by Dr. Mehmood regarding the prior published article, entitled “Cardiac Energetics in Patients with Aortic Stenosis and Preserved Ejection Fraction.” Well, Carolyn, how about we get onto that feature article and learn more about inflammatory biomarkers in hospitalized patients with COVID-19? Dr. Carolyn Lam: Yes. Let's go. Greg. Biomarkers are really playing an increasingly important role in cardiovascular disease, and even in the current COVID 19 pandemic, there's been a lot of news about how biomarkers such as traponin may be prognostic, and in fact, we're all wondering about maybe even newer biomarkers. In fact, today's feature discussion does bring to light one of the newest, and in fact, this is the first publication on the role of Growth Differentiation Factor 15 or GDF-15 in COVID-19. We're so pleased to be discussing this with the corresponding author, Dr. Torbjørn Omland from University of Oslo, in Norway, as well as our senior guest editor, Dr. Vera Bittner from University of Alabama at Birmingham. So welcome both. Tobjorn, could you tell us a little bit about GDF-15 and what made you look at it, and what did you find? Dr. Torbjørn Omland: Yeah, so GDF-15, that's a very interesting biomarker. It's considered a biomarker of biological aging cellular stress, and perhaps also the inflammation, and tests being studied within the cardiovascular field for some years now, and it has been shown to be a strong prognostic indicator across the cardiovascular spectrum, actually. So it is a new biomarker in one sense, but there are some data already in the cardiovascular field. Dr. Carolyn Lam: Not in COVID. So this is the first study to really look at its prognostic value in COVID 19. So congratulations Torbjorn, and if I may also to the first author, Dr. Peter Meer, a good friend as well, but please, could you tell us about your study and what you found? Dr. Torbjørn Omland: Yes. So when the COVID pandemic hit Norway in the spring, we thought that we should plan a prospective biomarker study. So we had to really fast track approval by the IRB and so forth, and we're able to actually cover most of the patients that were hospitalized in our hospital, Akershus University hospital, which is right outside of Oslo, and it's a pretty large hospital by Norwegian standards. It covers about 11% of the Norwegian population. Dr. Torbjørn Omland: So in that period, when we were including, we had 136 patients hospitalized with confirmed COVID 19, and we have biobank bank samples from 123 of these, and then there have been reports from retrospective studies, first from China, that seemed to suggest that markers like cardiac troponin, Anti-Troponin T, and Ferritin were associated with outcome, but those studies were prone to selection bias in that the measurements were performed in the most sick patients. So in this study we included all patients and then we thought we should examine a broad panel of biomarkers, and that included Interleukin 6, CRP, Procalcitonin, Ferritin, and the D-dimer Cardiac troponin, and N-terminal pro B, and GDF-15. Dr. Carolyn Lam: Wow. Thank you, Torbjorn. Even before you carry on with the results, can I just say having visited your hospital in pre-COVID days, I can only imagine what a work of love this was to do it prospectively. Any particular experiences to talk about, to get a fast-track even in the midst of to perform a well done prospective study, that must have taken a lot. Dr. Torbjørn Omland: Yes. But it's also interesting in that the whole sort of ablation on Norway was very much into this from the highest political level. Also, the decision that the older research on COVID should be prepared to retire, then the IRB had an eight hour and deadline for them to approve or not approve the study. So that's went surprisingly smoothly, I must say. Dr. Carolyn Lam: Wow, that's great. So what did you find? Dr. Torbjørn Omland: Yeah, so we found that among these biomarkers, several seem to predict outcome, and the primary end point of this study was to combined end-point of the hospitalization in the ICU, or death. We found that also markers like cardio traponin, BNP, ferritin, and the D-dimer and so forth, in univariable analysis, were very associated with outcome, but when we perform a more comprehensive, mostly variable modeling, then the prognostic value of some of these markers disappeared. In contrast, for GDF-15, it seemed to perform very strongly, both on the baseline sample, and interestingly also it increased in those reaching the primary end-point during the hospitalization. So it provided a very strong and independent information also when we adjusted for clinical risk scores, like the NEWS score. So that was a very pleasant surprise to see that there was one marker that's actually performed so well. The other marker that's also performed well was Ferritin. Dr. Carolyn Lam: Very interesting, and so the new score being the National Early Warning Score. Thank you. Verra, I really love to bring in your thoughts. I mean, could you take us behind the scenes with the editors? What did you think when you saw this paper? Dr. Vera Bittner: As you know, I mean, a lot of journals have been inundated by COVID papers, and so this one stuck out to us, because it's the first time that we had seen that anybody linked GDF-15 to a COVID population, even though it has been out in the literature for ACS, and in my prognostication, and in a healthy populations, and in chronic coronary disease populations, heart failure, and so on. So this is the first time that we've seen it applied there. Dr. Vera Bittner: Then I would echo some of the things that Torbjorn said, that we were also impressed, that it was prospective, because when you look at some of the other biomarker studies, what was prognostic in one with then not shake out the other one, because either different variables were included in the models, because the population's differed. So to have something that was representative of the population that was actually admitted to this, Norwegian Academic Hospital, stood out to us. So we're excited to get this paper basically for circulation, and hope that it also will be impetus for future research. Dr. Carolyn Lam: Thank you so much for sharing that end for helping us publish such a beautiful paper. Did you have some questions for two of your own? Dr. Vera Bittner: Yeah. So what stuck out to me is that you had this a whole crew of biomarkers, and then when you looked ultimately at the final model, there were two that were standing out, that was ferritin, and it was the GDF-15, and then when I looked at your graph, it looks like not only did these biomarkers measure different contrasts, but their time-course also seemed to be different, and so I was just wondering whether you had thought about, maybe using these to joint the model outcome, and whether we might even be able to get more information that way. Dr. Torbjørn Omland: I think that's an excellent suggestion, and as you correctly pointed out, they do have different sort of profiles and ferritin being an acute phase reactant, having various sort of dramatic early rise whereas we see that GDF-15 increased progressively during the course of hospitalization in the most severe patients. I think when combining them, is actually a great IMT that we should look further into. Dr. Carolyn Lam: Very nice. Torbjorn, if I could, I've got a couple of questions too. So 123 patients, 35 of whom had the primary outcome, right? So that may be sort of seen as, is this too small? and they're all hospitalized patients. So could I ask, what do you predict maybe seen in a larger population or outside of Norway or in a non-hospitalized population? Dr. Torbjørn Omland: So as you say, we were early with this report, but since it was submitted, there has been a couple of smaller studies that seemed to confirm our results. So that is reassuring, but of course we would like to have studied this in logical patients. We are in touch with the other biobank samples that could possibly confirm the data. So that's one obvious step. Then it's very interesting, as you say, could we sort of expand this to also apply to non-hospitalized patients? I think that it would be a very interesting hypothesis to test, and I think there's still a pretty good rationale for this. Dr. Torbjørn Omland: It's interesting that the insoluble group actually showed a correlation that when the soluble ST2 concentrations and GDF-15. So there might be that those with more susceptibility to COVID infections, actually, I thought that, that is actually reflected by GDF-15 concentrations, but the challenge is how to sort of get a representative non-hospitalized population, but interestingly, I was approached by some of the hospital staff that actually are in contact with general practitioners, and wanted sort of implement this test also for this group. Dr. Carolyn Lam: So Verra, we're really grateful that Allan Jaffe was working with you in managing this beautiful paper, and if you don't mind me cheekily paraphrasing that you said you might channel him, if you could, what would the channeled Allan Jaffe perhaps say about what's needed in this whole biomarkers fear in COVID-19? Dr. Vera Bittner: Hopefully, many. A channeling element is obviously difficult, because he is such an incredible expert on biomarkers that I can't even pretend to be able to see, that you might be thinking, but it seems to me that one thing that we could all agree on is that it would be really exciting if something like the: get with the guidelines COVID registry, could decide to measure this marker perspectively in the participating hospitals, for example. Dr. Vera Bittner: Then be able to look at this in a much, much larger population. I mean, especially with different ethnic backgrounds as well. I mean, I noticed actually to my surprise that, this Norwegian study how to fairly high proportion of Asians in the sample, but that may not be the ethnic distribution that we might see in different regions of the US, or different regions of the world. So it would be really nice to incorporate the measurement of this biomarker in much larger datasets. So things can be explored a bit further. Dr. Carolyn Lam: That's excellent, and Torbjorn, if you could channel Allan. What would you say? Dr. Torbjørn Omland: That's a difficult path, but absolutely just to me what Verra said. Then I think the importance of prospective studies in the COVID biomarker field, I think is our at most importance. Dr. Carolyn Lam: I think on behalf of both Torbjorn and I, and in fact everyone in circulation. Thank you, Verra for the amazing work that you and your team do for circulation as well. Thank you so much for making the time to share your thoughts today and thank you for that beautiful, beautiful paper both of you. Thank you. (singing). Listeners you've been listening to Circulation on the Run. Thank you for joining us from Greg and I. Don't forget to tune in again next week. Dr. Greg Hundley: This program is copyright, the American Heart Association 2020.
This week’s episode features author Jaime Layland and Associate Editor Dharam Kumbhani as they discuss the ariticle "Colchicine in Patients with Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial." TRANSCRIPT BELOW: 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 Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center, VCU Health, in Richmond, Virginia. Dr. Carolyn Lam: Greg, for our feature discussion we're talking about a very hot topic these days, the role of colchicine, this time in patients with acute coronary syndrome, with Australian data. I cannot wait to get to that, but I'm going to make you wait because I want to tell you about a whole lot of other really cool papers in today's issue. Dr. Carolyn Lam: First, have you ever wondered what is the association between risk factor control and cardiovascular disease risk in type 2 diabetes? Well, today's paper answers that. It's from Dr. Wright from University of Manchester and her colleagues who looked at a retrospective cohort using data from the English practices from Clinical Practice Research Datalink, or CPRD, and the Scottish Care Information diabetes dataset. They also linked to hospital and mortality data and identified more than 101,000 patients with type 2 diabetes in CPRD matched with almost 379,000 controls without diabetes and almost 331,000 patients with type 2 diabetes in the Scottish Care Information diabetes database between 2006 and 2015. The main exposure was a number of optimized risk factors, and these are: (1) Nonsmoker; (2) total cholesterol less than 4 mmol/L; (3) triglycerides less than or equal to 1.7 mmol/L; (4) HB A1c less than 7%; and (4) systolic blood pressure less than 140 or less than 130 mmHg of high risk. Dr. Greg Hundley: Carolyn, I am very curious. Lots of data here. What did they find? Dr. Carolyn Lam: So the key findings were: Dr. Carolyn Lam: First, even with optimally managed risk factors, people with type 2 diabetes still had a 21% higher risk for all cardiovascular disease events and non-fatal coronary heart disease, and a 31% higher risk of heart failure hospitalization compared to patients without diabetes. Dr. Carolyn Lam: 2. Only 6% of people with type 2 diabetes had optimal risk factor controls, so a very low percent. Dr. Carolyn Lam: 3. The association between the number of elevated risk factors and cardiovascular disease events and mortality was much stronger in patients with type 2 diabetes but without cardiorenal disease compared to those with established cardiorenal disease. People without cardiorenal disease were also younger and more likely to have suboptimal risk factor control and fewer prescriptions for risk-factor-modifying medication. Dr. Carolyn Lam: So take-home message: Greater use of guideline-driven care, clinical decision support, drug intervention, and self-management support should be encouraged for risk factor control, and people with type 2 diabetes and without cardiorenal disease may especially benefit greatly from cardiovascular disease risk factor intervention. Dr. Greg Hundley: Very nice, Carolyn. Dr. Greg Hundley: Well, my first study comes from Dr. Gregory Lewis from Mass General Hospital in Boston, Massachusetts. Carolyn, another quiz: Have you wondered about differences in metabolism in those who exercise versus those that do not? Dr. Carolyn Lam: Greg, I wonder about that all the time when I'm running out there. Dr. Greg Hundley: In this study, cardiopulmonary exercise testing, or CPET, and metabolite profiling was performed on Framingham heart study participants aged about 54 years with 63% of them being women with blood drawn at rest in 471 subjects and then again at peak exercise in 411. Dr. Carolyn Lam: Nice, and kudos for the majority women. So what were the results? Dr. Greg Hundley: The authors observed changes including reductions in metabolites implicated in insulin resistance and increases in metabolites associated with lipolysis, nitric oxide bioavailability, and adipose browning. Exercise-induced metabolite changes were variably related to the amount of exercise performed, peak workload, sex, and body mass index. There was attenuation of favorable exercise excursions in some metabolites in individuals with higher BMI and greater excursions in select cardioprotective metabolites in women despite less exercise being performed. Four metabolite signatures of exercise response patterns were analyzed in a separate cohort. The Framingham offspring study of 2,045 were about age 55 years and 51% were women, two of which were associated with overall mortality over a median follow-up at 23 years. Dr. Greg Hundley: So Carolyn, in conclusion, the authors found acute exercise elicits widespread changes in the circulating metabolome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise that could be useful in future studies. Dr. Carolyn Lam: Beautiful. I'm going to keep exercising and I bet you will, too, Greg. Dr. Carolyn Lam: So this next paper is a mechanistic study that revealed a special population of tissue regulatory T-cells in the heart with a unique phenotype and pro-repair function. So this comes from corresponding author Dr. Cheng from Tongji Medical College of Huazhong University of Science and Wuhan Hubei, China. He and his colleagues studied the dynamic accumulation of regulatory T-cells in the injured myocardium in mouse models of myocardial infarction, myocardial ischemia re-perfusion injury, or cardiac cryo injury, and using state-of-the-art methods such as bulk RNA sequencing, photo conversion, parabiosis, single-cell TCR sequencing, adoptive transfer, and functional assays. Dr. Greg Hundley: Carolyn, interesting. What did they find? Dr. Carolyn Lam: They showed that regulatory T-cells that accumulate in the injured myocardium after myocardial infarction or myocardial ischemia re-perfusion injuries had a distinct transcriptome which differs from lymphoid organ regulatory T-cells and other non-lymphoid tissue, and this represents a novel population of tissue regulatory T-cells in the heart. These heart regulatory T-cells were mainly thymus driven and recruited from the circulation showed active local proliferation with the IL-33/ST2 axis promoting their expansion. With the phenotype of promoting tissue repair, heart regulatory T-cells over-expressing spark contributed to elevated collagen content and enhanced maturation in infarct scars to prevent cardiac rupture and improve survival after myocardial infarction. Dr. Carolyn Lam: So in summary, this paper identified and characterized a phenotypically and functionally unique population of heart regulatory T-cells, which may lay the foundation to harness these cells for cardiac protection in myocardial infarction or other cardiac diseases. Dr. Greg Hundley: Wow, Carolyn. Very interesting. Dr. Greg Hundley: Well, my next paper comes from Dr. Michael Rubart from Indiana University School of Medicine, and as some background it's going to discuss calmodulin. So calmodulin mutations are associated with arrhythmia syndromes in humans. Exome sequencing previously identified a de novo mutation in CALM1 resulting in a P.N98S substitution in a patient with sinus bradycardia and stress-induced bidirectional ventricular ectopy. The objectives of the present study were to determine if mice carrying this N98S mutation knocked into CALM1 replicate the human arrhythmia phenotype and then to examine some of the arrhythmia mechanisms. Dr. Carolyn Lam: Okay. So what did they find? Dr. Greg Hundley: Carolyn, several techniques were used in this study. Mouse lines heterozygous for the CALM1 N98S allele generated using CRISPR and caspase 9 technology. Also, adult mutant mice and their wild-type litter mates underwent electrocardiographic monitoring. Ventricular D and re-polarization was assessed in isolated hearts using optical voltage mapping, and action potentials in wholesale currents as well as calcium influx were measured in single ventricular myocytes using patch-clamp techniques and fluorescence microscopy, respectively. Microelectrode techniques were employed for in situ membrane voltage monitoring of ventricular conduction fibers. Carolyn, it was really a comprehensive study. Dr. Greg Hundley: So what did the authors find? Heterozygosity for the CALM1 N9S mutation was causative of an arrhythmia syndrome characterized by sinus bradycardia, QRS widening, adrenergically mediated QTC interval prolongation, and bidirectional ventricular tachycardia. Second, beta adrenergically induced calcium influx L dysregulation contributed to the long QT phenotype. And finally third, they found that pause dependent early after depolarizations and tachycardia induced delayed after depolarizations originating in the His-Purkinje network and ventricular myocytes, respectively, constituted potential sources of arrhythmia in the CALM1 N98S positive hearts. Dr. Carolyn Lam: Wow. Sounds like a really comprehensive study. Thanks, Greg. Dr. Carolyn Lam: Let's talk about some other papers in this issue, shall we? There is a Perspective piece by Dr. Klassen on the COVID-19 pandemic, a massive threat for those living with cardiovascular disease among the poorest billion. There's an ECG challenge by Dr. Littman on a malignant electrocardiogram. Here's a hint: It's a pseudo-infarct pattern with important learnings. They're in an exchange of letters between Drs. Packard and Schwartz regarding the role of lipoprotein A and modification by alirocumab, a pre-specified analysis of ODYSSEY Outcomes randomized clinical trial. Dr. Greg Hundley: Oh thanks, Carolyn. I've got a couple other papers. Dr. Venkateswaran Subramanian has a Research Letter entitled Lysyl Oxidase Inhibition Ablates Sexual Dimorphism of Abdominal Aortic Aneurysm Formation in Mice. Professor Jan Cornell has another research letter entitled Colchicine Attenuates Inflammation Beyond the Inflammasome in Chronic Coronary Artery Disease. The LoDoCo2 proteomic substudy. And then finally, Dr. Sanjay Kaul from Cedars-Sinai Medical Center has a white paper reviewing the benefit/risk trade-offs in assessment of new drugs and devices. Dr. Greg Hundley: Well, Carolyn, how about we get on to that feature discussion and learn more about colchicine and acute coronary syndromes. Dr. Carolyn Lam: Yeah. Let's go, Greg. Today's feature discussion is all about colchicine, that commonly used treatment for gout that has recently emerged as a novel therapeutic option in cardiovascular medicine. I am so pleased to have with us the corresponding author of today's paper, Dr. Jamie Layland from Monash University, as well as our associate editor, Dharam Kumbhani, from UT Southwestern to discuss this very important trial data from Australia. Jamie, could you start us off by telling us all about this Australian COPS trial? Dr. Jamie Layland: We performed the Australian COPS trial back in 2015, and it finished recruiting in 2018. Essentially the trial was a trial to look at the safety and efficacy of colchicine being used in acute coronary syndromes, and this was prior to the release of important trial COLCOT. So essentially we randomized patients who presented to the hospital with an acute coronary syndrome to receive colchicine twice daily for one month followed by colchicine once a day for 11 months, and we followed these patients up for a minimum of 12 months. This was performed across 17 sites across Australia, and we looked at a composite endpoint of total death, acute coronary syndromes, unplanned urgent revascularization, and stroke. Dr. Carolyn Lam: Nice. So Jamie, could I first clarify that this was an investigator-led trial, I'll bet, and man, first of all, applause for doing this. I can only imagine how much work this took and maybe then tell us about the results. Dr. Jamie Layland: Yeah. So this was an investigator-initiated trial through a network of academic investigators across Australia on limited research funding, so through philanthropic and institutional support. So it was a huge effort over a number of years, and I'm very thankful to the support of Circulation and Dharam in supporting the paper, which I think was a great success. Dr. Jamie Layland: So the results of this trial were a surprise to us all, but essentially this was a negative trial in the sense that colchicine did not improve the primary outcome, so there was no improvement in the rate of the COLCOT outcome. And interestingly, there was an increase in total mortality, in particular non-cardiovascular deaths were higher at five compared to the placebo at one. That was over a 12-month follow-up period. Dr. Carolyn Lam: Interesting. So Jamie, I'm going to ask the question that's on everyone's mind then: What's the difference between your trial and COLCOT? Dr. Jamie Layland: That's a great question. Obviously, COLCOT was a much larger trial. COLCOT was an international trial of over 4,000 patients. Similar patient demographics, similar patient subgroup of acute coronary syndromes. However, importantly, COPS was a trial of inpatient initiation of colchicine. So patients when they had their STEMI, or non-STEMI most commonly, they were given colchicine usually within 72 hours of their index hospitalization and sometimes sooner, and this was given prior to discharge. With COLCOT, the median time of administration of colchicine was around 14 days, so slightly different groupings there. However, in COLCOT you were allowed to administer colchicine as an inpatient. You can see obviously from the European side of cardiology the impressive data when colchicine was given earlier in COLCOT how this translated to improved outcomes. So clearly, there is a potential benefit there for early administration of colchicine when you look at these two trials. Dr. Jamie Layland: But we administered colchicine acutely when patients presented in their index hospitalization. We also importantly used a different dosing schedule to COLCOT. So COLCOT was 0.5 mg daily and we used 0.5 twice daily. This was for the first 30 days, and this was based on early data from the group from western Australia who showed that when colchicine was given to patients at a BD dosing in those patients who were already on aspirin and high-potency statins, there was a significant reduction in hsCRP, obviously a commonly used marker of inflammation at four weeks, and also based on data showing that there was a heightened inflammatory response in the early days following an acute coronary syndrome. So we felt that using this twice-daily dose would be advantageous and potentially helpful for our patients. So they're the two main differences between the studies. Dr. Carolyn Lam: Thanks for explaining that so clearly. Dharam, could I have your thoughts? This was, of course, discussed heavily, right, by the editors. Could you give us a sneak peek of what else was discussed? Dr. Dharam Kumbhani: The trial is very important, although it is smaller perhaps in sample size and kind of done with less resources than COLCOT. I do think this adds to the body of literature on colchicine for secondary prevention of CAD. And one of the interesting things is that we see we also have the LoDoCo2 trial, which was a slightly different population, Jamie, which was the chronic coronary artery disease patients, but also still looking at secondary prevention. What is really striking to me is that a very similar signal in non-CV death was noted in that trial as well. Again, it was not seen in COLCOT and LoDoCo1, but it was very interesting that a similar finding was there. So I do think this is something that the field will need to investigate more and really try to understand is this just noise and by chance alone, or is this something that that's a real signal for. Dr. Carolyn Lam: Jamie, what are your thoughts about that and in LoDoCo differences with your trial? Dr. Jamie Layland: Good question, and a very important topic that obviously is currently under discussion amongst the colchicine community. As I said, it was a surprising result. We weren't anticipating this non-CV death signal, but as Dharam said when LoDoCo2 came out, a fantastic trial again, but this signal of non-CV death. I don't know whether it's merely just a noise as you say or whether it's a significant finding, but clearly we need to do more research in this field to understand the mechanism and whether this is a real signal or not. It seems a little bit discordant with previously published work. So if you look at the literature in patients with gout from across the world, there's no real signal of increased non-CV death in those patients. However, with patients with acute coronary syndrome as we are administering the colchicine on a daily basis and then commonly this isn't used for gout, so that is a slight difference. But certainly, there was no signal in the non-CV literature to support the findings that we had and the signal in LoDoCo2. Dr. Jamie Layland: The other thing to note is in a cohort of five non-CV deaths, three out of those five patients were actually not taking colchicine at the time of their death. They stopped the drug prematurely. So I think we just need to take a step back and really await the results. Obviously, we've got two-year and five-year data coming out from the COPS trial which will be interesting to look at, but also the Clear Synergy trial from the McMaster team, that would be a very important trial providing more data on this potential signal. But reassuringly, and I feel more reassured knowing the COLCOT data, which is a slightly similar cohort to ours, showing that there was no trend towards increased non-CV deaths. So I think it's something that we have to be aware of and there will be lots of metro-analysis I'm sure being published in the coming months looking at this specifically. But yeah, I think we shouldn't cast any aspersions on colchicine yet. I think that's too early, but I do think we need more data. Dr. Carolyn Lam: Thanks, Jamie. Speaking of looking deeper in your data and looking at those who died and were they taking the medication and so on, you did some other post-hoc analysis, right? And maybe you could just describe briefly, for example, the 400-day followup. Dr. Jamie Layland: Yes. So the interesting thing with our data, and I had mentioned this before, is that we had limited resources, so we really wanted to do this trial, and obviously competitive funding is tricky at the best of times, but we were really committed to doing this trial and we had a group of investigators who were all committed to doing this trial. But for this to work, we had a single research nurse and a fellow performing the follow-up. So at times, there was a little lag between the timing of the follow-up. So we ended up getting follow-up which was slightly prolonged over the 12-month window. On average, it was around 400 days. When we looked at the 400-day data, we saw that there was an increasing separation of the biomarkers after 365 days. Dr. Jamie Layland: The results, this was obviously not the primary outcome, this was a sensitivity analysis, but there was a suggestion or a significance out to 400 days with an improvement with colchicine. However, this is the primary composite outcome, so revascularization, acute coronary syndrome, stroke, and total death notwithstanding this positive outcome, there was still this trend to high rate of mortality, so that has to be taken into consideration. But there was a suggestion that the longer the duration of colchicine was given for, it culminated into these lights affect. And we see from CT data that colchicine actually has some plaque-modulating effects and reduces high-risk or low-attenuation plaque. So you could hypothesize that as the majority of the benefits seen in colchicine in LoDoCo2, in COLCOT, and in COPS was the reductions in urgent revascularization, stroke, and acute coronary syndromes. Dr. Jamie Layland: So perhaps there is this effect that colchicine is having on plaque stabilization so we're seeing less longer-term events, but this is just hypothesis generated and we need more data to support that. But it is a very interesting finding nonetheless. Dr. Carolyn Lam: Thank you. Dharam, could I hand you the last word on where you think this field is going or where you think it should go? Dr. Dharam Kumbhani: I think Jamie put it really nicely. I think he outlined the study nicely with its strengths and its limitations, and I think this is obviously a debate between perhaps the colchicine believers and the ones that are still perhaps trying to understand a little bit more about its true role, because as was mentioned I think there's really a benefit in ischemia-driven revasc. I think we've seen that in almost all the colchicine trials. There is no reduction in mortality, and as we saw in the COPS data maybe it goes the other way. So I think from a pathophysiological standpoint it makes sense. I think there's good translational data to suggest that it would be beneficial in this patient population, but I think that's the beauty of having clinical trials and the ones that are done by different investigators and perhaps in different settings, because they help us answer the truth. And whether colchicine becomes a stable part of our armamentarium for secondary prevention of CAD going forward, I think the jury is still out and as was mentioned I think Clear Synergy would probably be very helpful in hopefully tying all this together. Dr. Dharam Kumbhani: So again, I want to congratulate Jamie and his team for really providing us with a very interesting trial done in a very pragmatic setting, and I think the field is very thankful to them for providing us with this information. Dr. Carolyn Lam: Thank you, audience, for joining us today. You've been listening to Circulation on the Run. Don't forget to join me and Greg again next week. Dr. Greg Hundley: This program is copyright the American Heart Association 2020.
For this episode, I'm joined about halfway for a brand new chat with TDK. He's a regular name on my show, and one of the contributors to ST2, so it's fantastic to welcome him back to The Sound Test. This time, we catch up about his latest album - "Retrospect" - currently available through https://marktdkknight.bandcamp.com !Besides my talk with TDK, I also take a look at various intriguing peripherals and bits of hardware that have popped up through the history of gaming. Whether it's Rez's Trance Vibrator or Donkey Konga's bongos, you'll hear about some of the most (and least) successful gadgets throughout the years.Of course, we continue the VGM SongFight battle, move into a challenging round of the SFX Showdown and the News Cop seems particularly irate this week...This week's playlist:Build Finish – ??? [Nintendo Labo]Bustin' Season – DJ Shadow [DJ Hero]Fear – Adam Freeland [Rez: Infinite]Rumble – U-God [Wu-Tang: Shaolin Style]Route 66 – Derek Duke [OverWatch]Bike 1 3 – Eishin Kawakami [Chibi-Robo!: Park Patrol]Planet Screen Credits 2 – Hirokazu Tanaka [Game Boy Camera]Level Theme 1 – Kazumi Totaka [Virtual Boy Wario Land]Street Phase – Hirokazu Tanaka [Gumshoe]GAME A – Hirokazu Tanaka [Gyromite/Robo Gyro]Raid Battle – Junichi Masuda [Pokemon Go]Howl – Gareth Coker [Ori and the Will of the Wisps]Stonetown – Lorne Balfe [Skylanders: Spyro's Adventure]You Wouldn't Know – Jonathan Coulton & Ellen McLain [Lego Dimensions]Put in a Bullet – Kazuhiro Nakamura and/or Junichi Nakatsuru [Time Crisis II]??? – ??? [Point Blank 2]finishline – ??? [Buzz!: The Sports Quiz]Hoovering with a Hangover – TDK [Retrospect]Sunrise – TDK [Retrospect]CAREFUL WITH THE WALLS! – Shinya Sakamoto, Shigehiro Takenouchi and/or Atsushi Fujio [Falsion]Café Cubano – Scott Martin [Tropico 5]Select – Junk Ozawa and/or Jesahm [Donkey Konga]Shake What Your Mamma Gave Ya – Skeewiff [BeatMania]Eve - ??? [Gran Turismo 5]Final Boss - Tokuhiko Uwabo and/or Shigenori Kamiya [Castle of Illusion Starring Mickey Mouse]MAIN THEME:Mahito Yokota, Toru Minegishi, Koji Kondo & Yasuake Iwata - World 8 [Super Mario 3D World]Discord:https://discord.gg/xeMfzWyRequests and contact:https://twitter.com/GreenT128"The Sound Test" on Facebook:https://www.facebook.com/thesoundtest/Original episodes of The Sound Test LIVE, with Dale Fowler, are available through Patreon:https://www.patreon.com/_secretcaveAlso available through:YouTubeSpotifyiTunesStitcher
Following on from my ST2 Racing Special, I take a look at some of my personal favourite racing games over the years. Unlike how I usually structure playlists, I've made this one follow a bit of a timeline. Across the course of the show, it dips in and out of different consoles, showing off their capabilities and general style.Also, this show is shorter than most, coming in at about half length. I was very tired after hard work on ST2 this week but, oddly, it results in a surprisingly professional demeanour! Maybe I should always be a bit knackered before a broadcast...This week's playlist:Board Shop – Isao Kasai and/or Tomohiko Sato [Snowboard Kids]Passing Breeze – S.S.T. Band (originally composed by Hiroshi Kawaguchi) [Outrun]Red Canyon – Yumiko Kanki and/or Naoto Ishida [F-Zero]Mario Circuit – Soyo Oka [Super Mario Kart]Palm Desert – Michael Bartlow [Road Rash]07 – Messy Studios [Micro Maniacs]Crash Cove – Mutato Muzika, Mark Mothersbaugh and/or Josh Mancell [CTR: Crash Team Racing]Plasticity – CoLD SToRAGE [WipeOut 2097]Ancient Lake – David Wise and/or Graeme Norgate [Diddy Kong Racing]Dolphin Park – Kazumi Totaka [Wave Race 64]Daft Punk Is Playing at My House (Soulwax Shubiya Mix) – LCD Soundsystem [Burnout Revenge]Hot Beats – Wes Smith [Table Top Racing: World Tour]SNES Donut Plains 3 – Originally composed by Soyo Oka [Mario Kart 8] MAIN THEME:Mahito Yokota, Toru Minegishi, Koji Kondo & Yasuake Iwata - World 8 [Super Mario 3D World]Requests and contact:https://twitter.com/GreenT128"The Sound Test" on Facebook:https://www.facebook.com/thesoundtest/Original episodes of The Sound Test LIVE, with Dale Fowler, are available through Patreon:https://www.patreon.com/_secretcaveAlso available through:YouTubeSpotifyiTunesStitcher
A GP VTS guide for 2020 with Dr Jamie Green of HEEM. Including all the updates to GP training, leadership MSF, CATS, RCA, and more.
Return of baseball, do we get past ST2, guest Lou from Hoboken
For this season finale, Lee takes a look at some of his all-time favourite side scrolling beat 'em ups! Of course, the show is bolstered by an array of requests and other unrelated choices, which all come together to form a particularly bass-heavy playlist. The show will return with a fourth season on July 17th, 2020; allowing Lee to catch his breath and focus a little on ST2. Hopefully, this closing mix of VGM joy will satisfy until ST LIVE comes back!#DefundNewscopThis week's playlist:Title – David Wise [Battletoads]Dervish D (Multisid) – LMan (originally composed by Vangelis) [Commodore 64 Remix Classics - 80s Synth Hits, Vol. 1]Comets That Are Crazy – Hubbard & Donne [Hubbard ‘80]Thing on a Spring – Rob Hubbard [Commodore 64 Sid Anthology, Vol. 3]Echoes in My Mind – Mandrill [The Warriors]Saints of Rage - Stage 3 – Malcolm Kirby Jr [Saints Row IV]If You Dare – Megan McDuffee [River City Girls]ROUND 4 INDUSTRIAL AREA 2 ROUND 6 – Manami Matsumae, Yoshihiro Sakaguchi, Yasuaki Fujita, Hiromitsu Takaoaka, Yoko Shimomura, Junko Tamiya and/or Harumi Fujita [Final Fight]Moe's Tavern – Norio Hanzawa [The Simpsons]Kick ‘n' Punch – David Wise [Battletoads/Double Dragon]Cluffy Flouds 1 – TDK [CyberSpeed Unleashed]Northern Kremisphere (Restored) – Eveline Novakovic [Donkey Kong Country 3: Dixie Kong's Double Trouble!]Thirty Seven After Six – Mike Morasky [Half-Life: Alyx]Deep Jungle – Yoko Shimomura [Kingdom Hearts]The Instinct – Robin Beanland [Killer Instinct]Mach Rider – Hideki Kanazashi and/or Hiroaki Suga [Super Smash Bros. Melee]Power Drift – Chris Abbott (originally composed by Hiroshi Kawaguchi or Alberto Jose Gonzales)Rydeen (Daley Thompson's Decathlon C64) – Chris Abbott (originally composed by Yellow Magic Orchestra) [Commodore 64 Remix Classics - Imagine/Ocean Vol. 2]Labyrinth Zone Remix – Plasma 3 Music (originally composed by Masato Nakamura) [Sonic the Hedgehog]In the Poachers' Forest – Isao Abe and/or Syun Nishigaki [Cadillacs and Dinosaurs]Dilapidated Town – Yuzo Koshiro [Streets of Rage]Blast Power – Yuzo Koshiro [Bosconian]Chase – Grant Kirkhope [Project Dream]Bully – Grant Kirkhope [Project Dream]Daybreak (Staff Roll) – Takayuki Iwai, Yuki Iwai, Isao Abe, Hideki Okugawa and/or Tetsuya Shibata [Street Fighter Alpha 3]MAIN THEME:Mahito Yokota, Toru Minegishi, Koji Kondo & Yasuake Iwata - World 8 [Super Mario 3D World]Requests and contact:https://twitter.com/GreenT128"The Sound Test" on Facebook:https://www.facebook.com/thesoundtest/Original episodes of The Sound Test LIVE, with Dale Fowler, are available through Patreon:https://www.patreon.com/_secretcaveAlso available through:YouTubeSpotifyiTunesStitcher
Sea of Thieves is a multiplayer pirate adventure complete with sailing, cutlasses, sea monsters and even interactive shanties. Though given a cartoonish and playful feel, as is often the case with Rare, its creation and continued evolution are taken very seriously. That's exemplified in Sea of Thieves' music, which uses an arsenal of intriguing instruments in its authentic sound. In fact, its composer, Robin Beanland, received an Ivor Novello award in 2019 for his inventive OST. But its strength, and clever use of generative elements, are to be expected from Robin – a Rare mainstay who cut his teeth on Killer Instinct before writing immensely popular scores like Conker's Bad Fur Day.After leaving a huge Robin Beanland-shaped hole in my first series of VGM podcasts, I was particularly eager to speak to him for ST2. As a result, this is only the first of two appearances, with the second covering his output on the Nintendo 64.Lee Tyrrell on Twitter:https://twitter.com/GreenT128Robin Beanland on Twitter:https://twitter.com/TheRealBeanoAlso available through:YouTubeiTunesSpotifyStitcherand many more...Early access, unedited interviews, LIVE shows and more:http://patreon.com/_secretcave
I always wanted the second episode of ST2 to cover a classic, and I think I got that in spades when I spoke to Russell Shaw about the Fable series. Its first release is a real RPG benchmark, and though the games slowly slipped into a less enthusiastic reception, Russell Shaw's music was always highly regarded as some of the best in the industry.After an interesting collaboration with Danny Elfman, Russell really made Fable his own. Despite being new to orchestration, he stepped up to the lofty task more than admirably, making huge improvements in his approach with every successive game. Even considering his growth as an orchestral composer, the first Fable's music undoubtably holds up to this day, providing VGM with some of its most accomplished and satisfying themes.Russell and I talk about every release in the series, from Fable itself to the unreleased Fable: Legends, which had a whole soundtrack composed before its cancellation. This releases alongside a much shorter Black & White episode, and the two together serve as an extended special on Lionhead Studios. That Black & White edition premieres straight after this one, available here:https://audioboom.com/posts/7415440-st2-bonus-black-white-w-russell-shawLee Tyrrell on Twitter:https://twitter.com/GreenT128Russell Shaw on Twitter:https://twitter.com/_GoesLikeThis_Available through the following platforms:YouTubeSpotifyiTunesStitcherand many more...Support, early access, unedited interviews, backdated LIVE shows and more:http://patreon.com/_secretcave
This BONUS episode of ST2 is actually the second part of a Lionhead Studios double bill, with the first focusing on Fable (available here).After Peter Molyneux left Bullfrog Productions in 1997, he soon started his new venture - Lionhead Studios. Though they were unfortunately ill-fated with money across their run, they were nonetheless responsible for a number of interesting and imaginative games. Their first, Black & White, was a innovative take on the God genre, featuring music from Bullfrog's own Russell Shaw.The soundtrack itself is as forward-thinking as it is mercilessly ambient. Though mostly resting on a variety of sparse backing tracks, it also makes clever use of many smaller elements, and aspects that change depending on your playstyle. Throughout this BONUS episode, Russell outlines some of the thought processes behind Black & White, which occupies an interesting space in both his career and VGM in general.Lee Tyrrell on Twitter:https://twitter.com/GreenT128Russell Shaw on Twitter:https://twitter.com/_GoesLikeThis_Available through the following platforms:YouTubeSpotifyiTunesStitcherand many more...Support, early access, unedited interviews, backdated LIVE shows and more:http://patreon.com/_secretcave
To kick off this first pre-Christmas mini-run of ST2, Minecraft seemed perfect. As I type this, it's the best-selling video game of all time, and it's a safe bet that practically every gamer has dipped into its blocky world at some point. Many of us, myself included, have done far more than simply dip in, using its subjective gameplay and nearly infinite possibilities to construct an addictive other life.Along with its influential mechanics, Minecraft is known for its unique approach to music and sound. Its original soundtrack, by C418, is an intensely minimal slow burn through gorgeous piano melodies and soft strings. Once Microsoft acquired the brand, publishing a string of commercial ports and updates, Gareth Coker (known for Ori and the Blind Forest) came on board to score a variety of mash-up packs and minigames. His five albums for Minecraft are just as impressive and interesting as C418's initial work, and I'm honoured to welcome both talents onto this debut episode of ST2. As if that weren't enough, the incredible Laura Shigihara makes a short cameo appearance, discussing her previous collaboration with C418. Laura will later appear in two further episodes of ST2, covering Plants vs. Zombies and Rakuen, and it was great to include her in this huge celebration of Minecraft's audio.We discuss Minecraft's music in painstaking depth, and I hope you enjoy hearing their insights!Lee Tyrrell on Twitter:https://twitter.com/GreenT128C418 on Twitter:https://twitter.com/C418Gareth Coker on Twitter:https://twitter.com/garethcokerLaura Shigihara on Twitter:https://twitter.com/supershigiAvailable through the following platforms:YouTubeSpotifyiTunesStitcherand many more...Support, next week's Fable episode with Russell Shaw, unedited interviews, backdated LIVE shows and more:http://patreon.com/_secretcave
Hanna Scott on our state's firearms database, and its 3-year backlog // Matthew Dennis, U-Oregon history prof, on Thanksgiving traditions // PW Singer, author of LikeWar, on treating misinformation as a sickness // Sports Insider Danny O'Neil on the Chiefs-Rams game/ James Paxton headed for the Yankees // David Fahrenthold live on presidential misspellings/ Donald Trump Jr. // Chris Sullivan's Chokepoint -- Thanksgiving airport travel/ Apple cup travel // Chris Sullivan on the new federal funding for ST2
Kevin & Steve return from Comic Con to share some stories. Seeing Neil Degrasse Tyson, Kevin Smith, The Legends of Tomorrow, Arrow, beer stains, NOT getting recognized, wrapping up ST2, Tacoma FD and MORE POLLS! ENJOY THE CHEW!
Kevin & Steve run down their live show schedule, ST2 updates and some things THEY HATE. They cover how to pack a cold cooler, "this A.I. is a Dick," Viking fork holders, how Lemme would ruin Fight Club, their Storage Unit horror movie, "I can't," clingy T-shirts, lemon seed attacks & MORE. ENJOY THE CHEW!
Kevin & Steve's pilot, Tacoma FD has been ordered to series! They share their excitement re: that as well as... Steve's private moments, ST2 keeps chugging along, going for Best Poster Award, Lemme finally shaves his mustache, wing sauce, 6pm comedy shows, eating McGriddles, Cobra Kai, the Yankees AND MORE! ENJOY THE CHEW!
Kevin & Steve are back on the ROAD. It's a CAR CAST as they drive through Wisconsin & Iowa going from show to show. They cover the menu in Wisconsin, the Packers, the awesome response to ST2, Happiness in your Household, fans having sex to their movies, Fanta soda, pretzels pro and con, Lemme's mustache, the Ozark Mountain Daredevils, taking a ride down Oyster Mountain AND MORE. ENJOY THE CHEW!
Titles: Super Troopers [Wikipedia] [IMDb], Super Troopers 2 [Wikipedia] [IMDb] Director: Jay Chandrasekhar Producer: Richard Perello Writer: Broken Lizard Stars: Jay Chandrasekhar, Kevin Heffernan, Steve Lemme, Paul Soter, Erik Stolhanske, Brian Cox, Marisa Coughlan, Rob Lowe (Super Troopers 2) Release date: February 15, 2002 (Super Troopers); April 20, 2018 (Super Troopers 2) SHOWNOTES: What up, stoners? Collateral Cinema is back with Part 2 of our 4/20 Holiday Special, where hosts Beau and Robert head out to our local cinema on #420day to witness the first run release of Broken Lizard's brand new sequel to the 2001 police/stoner comedy Super Troopers. We had a blast getting blazed out and watching Super Troopers 2 for this episode, and we also have a lot of fun discussing both films, as well as the rest of Broken Lizard's filmography. In the discussion part of the episode, we give a short breakdown of the first film, talk about our overall experience seeing ST2 at the movies, and we give a spoiler-free review of the new movie! So come with us, as we go down the rabbit hole that is Super Troopers 2! Collateral Cinema is on Apple Podcasts, Chill Lover Radio, Podcoin, and wherever else you get your podcasts. Also, support us on Patreon, where you can find exclusive full-length commentaries on our favorite movies! (Collateral Cinema is an LCompany Production. Intro song is a license-free beat by @DarkSunn. All music and movie clips are owned by their respective creators and are used for educational purposes only. Please don’t sue us; we’re poor!)
Dinner with Schmucks - Episode 35 “Permanent Sidekik” This Week’s Cast: Yajaira, Lisa Bo-Besa, Kris w/a Special K, (regular) Chris, & Junior (aka June Bug) This Week’s Dinner: Asian Cabbage & Beef Stir-fry w/Wasabi Aioli - Take 2 Happy belated 4/20 to everyone! We are back with a special Friday night podcast, after seeing Super Troopers 2 a few hours earlier. We are joined by special guest Junior (aka June Bug) as he joins us for our 1st non-game night episode. We spend the episode dropping a ton of references to ST2, so if you haven’t seen it, and want to, maybe hold off on listening! Yajaira cooks her Asian Cabbage & Beef Stir Fry again, this time with the correct cabbage! Our SOTW’s come from far & near, and we come up a few minutes short of our second consecutive podcast recording after midnight. This week clocks in at 1:17, and features a few different tunes to bring you in and out of the episode. If you saw ST2, you’ll recognize the ending tune. Enjoy the episode! Wanna rock some Dinner with Schmucks SWAG??? You know you do! dinnerwithschmucks.threadless.com is the official Dinner with Schmucks shop! We hope you enjoy listening to our Podcast, if you do, please make sure to subscribe, rate, and review on iTunes and Soundcloud! You can find us on YouTube as well! Also you can drop us a line to let us know! We’d love to hear from you! We may even read it back on the Podcast! We enjoy having guests, if you know of someone local to #erotic #riverview flori-DUH, let us know! Patches are in!!! Peel & Stick backs, just $5! 2 color options available! Email us or drop us a line on Facebook for more information! dinnerwithschmucks@gmail.com Check out High Stick Creative on Facebook & Instagram facebook.com/highstickcreative instagram.com/high_stick_creative Check out Hair by Lisa Michelle on Facebook & Instagram facebook.com/hairbylisamichelle instagram.com/hair_by_lisamichelle Check out Cuesta on Facebook Soundcloud facebook.com/musicbycuesta soundcloud.com/music_by_cuesta Check out our Facebook page & Twitter feed for the videos we watch! www.facebook.com/dinnerwithschmucks www.twitter.com/dwspodcast #dinnerwithschmucks #eroticRiverview
Kevin & Steve are still on the road promoting ST2! They are back in Chicago updating the Chew Crew on the happenings of the last 2 wks. They cover the VT screening, Kevin's suit on Jimmy Fallon, setting up Jay at the NYC screening, an emergency at the CT screening, the cover of High Times, Rob Lowe & the LA Premiere, dodging the autograph stalkers, a snow out at the Cubs Game AND MORE! ENJOY THE CHEW! AND GO SEE ST2 IN THEATERS THIS WKND!!!
Tyler Labine (Super Troopers 2, Deadbeat, Tucker & Dale, Voltron) joins Kevin & Steve. They talk shooting ST2, the accent, fucking a moose, hittin' the gym, weight flux, Dirk Gently, Voltron, The Hunk Club, his new movie The Maze, acting roles: you win some you lose some, pitching TV AND MORE! ENJOY THE CHEW!
Hayes MacArthur (Super Troopers 2, Angie Tribeca) joins Kevin & Steve. They have plenty of laughs as they cover shooting ST2, mustaches, Big Dick Nick & his line of subs, Canadian accents, returning to stand up, The Rock, sports, Haye's inner film geek & MORE. ENJOY THE CHEW!
The amazing & talented Emmanuelle Chriqui joins Kevin & Steve to talk Super Troopers 2! They also cover her French accent, working with dudes, Waltham, Freaky Chriqui, The Iron Chriq, how we were lucky enough to get her for ST2, vegans, pitching, auditioning, her new movie: Hospitality, Rob Lowe, the Coffee & Butter Diet AND MORE! ENJOY THE CHEW!
Kevin & Steve are joined by Jay Chandrasekhar & Paul Soter (sans Stolhanske!) on the day that the Super Troopers 2 Trailer "dropped." They cover Super Bowl talk, hot pockets, SF Sketchfest, an Animal House reunion, the Pork Belly Movement, the jokes in the trailer, the other guys' thoughts on Leaker Lemme, Stolhanske's man boobs, the Piscopo-ization of Broken Lizard, the ST2 promo tour, Super Troopers 3, Potfest AND MORE! ENJOY THE CHEW!
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 Center and Duke National University of Singapore. This week's feature paper takes a deep dive into nitric oxide signaling, that extremely important pathway in cardiovascular health and disease. This time, taking a novel look at genetic predisposition, phenotypic consequences, and therapeutic implications. All that coming right up after these summaries. The first original paper describes the derivation and validation of a novel model to stratify the risk of death due to circulatory etiology in patients resuscitated from cardiac arrest without an ST elevation MI. First author, Dr. Bascom, corresponding author Dr. Setter from Maine Medical Center in Portland and their colleagues use the International Cardiac Arrest Registry to derive a novel model termed the CREST Model, which describes an incrementally high risk of circulatory etiology death with an increasing score. Now, CREST is a simple score with components of C for prior coronary artery disease. R for non-shockable rhythm. E for ejection fraction less than 30% on admission. S for shock at the time of admission. T for ischemic time more than 25 minutes. The authors showed that this CREST tool may allow for estimation of circulatory risk and improve triage of cardiac arrest survivors without STEMI at the point of care. The next study reports associations between usual sodium, potassium and blood pressure using gold standard 24-hour urinary data collected for the first time among a nationally representative sample of adults in the United States. First and corresponding author Dr. Jackson from Centers for Disease Control and Prevention used cross-sectional data from 766 participants aged 20 to 69 years with complete blood pressure and 24-hour urine collections in the 2014 national health and nutrition examination survey. They found that there was a strong direct relationship between higher sodium excretion and higher blood pressure and hypertension. In addition, there was an inverse relationship between potassium excretion and blood pressure and hypertension. When added to the evidence based from longitudinal and interventional studies, these results support clinicians dietary advise to lower sodium intake and increase consumption of potassium containing foods. The next two studies in this week's journal examine the utility of circulating biomarkers to aid in the diagnosis of acute aortic dissection. As a reminder, the AHA/ACC guidelines published in 2010, proposed using the aortic dissection detection risk score or ADD risk score as a primary screening tool based on scoring the presence of three categorical risks. Number one, high risk conditions such as Marfan Syndrome, a family history of aortic disease, known aortic valve disease, known thoracic aortic aneurysm or previous aortic manipulation. Number two, The pain features such as chest, back or abdominal pain described as being of abrupt onset severe intensity or ripping, tearing. Number three, the examination features such as evidence of profusion deficit, systolic blood pressure difference, spoken neurological deficit or aortic diastolic murmur and hypertension or shock. The presence of one or more markers within each of these categorical features is given an ADD score of one with a maximum cumulative score of three if all three categorical features are present. In the first of these two papers in this week's journal, first author Dr. Nazareen, corresponding author Dr. Morello and colleagues from Molinette Hospital in Italy performed the advised International Multi Centers Study, which prospectively assessed the diagnostic performance of standardized strategies integrating pre-test probability assessment and D-dimer in 1,850 patients from the emergency department. They found that in patients with an ADD risk score above one and D-dimer less than 500 nanograms per milliliter, the rate of acute aortic syndromes was significant at one in 22 cases. Rule out strategies for acute aortic syndromes integrating an ADD risk score of zero or one with D-dimer less than 500 were found to miss only around 1 in 300 cases of acute aortic syndrome. Integrating the ADD risk score with D-dimer could help to standardize diagnostic decisions on advanced imaging for suspected acute aortic syndrome balancing the risks of misdiagnosis and over testing. The authors concluded that patients at high probability of acute aortic syndrome such as with an ADD risk score above one should proceed to computer tomography and geography or other conclusive imaging irrespective of D-dimer levels. However, in those with an ADD risk score of zero or one, with a D-dimer of less than 500 were possible rule out diagnostic strategies for acute aortic syndrome. The second manuscript in the present issue suggests that soluble ST2 might be an even better biomarker than D-dimer to rule out aortic dissection. In this paper by first author, Dr. Wang, co-corresponding authors, Dr. Du and Guo from Beijing Anzhen Hospital and Peking University respectively, the authors measured plasma concentrations of soluble ST2 using the R&D Systems assay in 1,360 patients including 1,027 participants in the retrospective discovery set and 330 patients with an initial suspicion of acute aortic dissection and ruled in a prospective validation cohort. The proportion of acute aortic dissection, this acute chest pain cohort was high at more than 40%. The authors found that soluble ST2 measured using this research grade assay showed higher levels in acute aortic dissection than in acute myocardial infarction or in acute pulmonary embolism. The result suggested that soluble ST2 levels could be useful as a rule out marker possibly even to an extent moderately superior to D-dimer. A cut-off level of around 35 nanograms per milliliters using the research grade soluble ST2 assay appeared to reliably rule out acute aortic dissection if used within 24 hours after symptom onset with a negative likelihood ratio of 0.01 and a negative predictive value of more than 99%. These intriguing findings are discussed in an accompanying editorial by Dr. Toru Suzuki from University of Leicester and Dr. Kim Eagle from University of Michigan. Well, that wraps it up for our summaries. Now, for our future discussion. Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. In fact, the pharmacologic stimulation of nitric oxide pathway is emerging as a therapeutic strategy in cardiovascular medicine in many areas including in heart failure preserved dejection fraction. Today's paper is therefore all the more intriguing because it seeks to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on the risk for cardiovascular disease as a way of informing of the potential utility of pharmacologic stimulation of the nitric oxide pathway. Intrigued? Well, I certainly and I'm so glad to have with us the corresponding author, Dr. Sekar Kathiresan from Massachusetts General Hospital as well as a familiar voice, Dr. Peipei Ping, associate editor from UCLA here to discuss this paper. Sekar, could I ask you as an introduction to tell us a little bit more of the general approach of looking at genetic predisposition as a way of perhaps forecasting potential utility of pharmacologic stimulation? Could you tell us a little bit more about that? Dr. Sekar Kathiresan: Yes. I'm delighted to speak a little bit more about this idea of using naturally occurring genetic variation to understand if a medicine developed against a target is going to work in terms of efficacy and also potentially lead to on target side effect. As you know, there are lots of variants for mutations in genes that eventually become targets for medicines. Over the last 10, 15 years, there's been an explosion in our understanding of human genetic variation, specifically in genes targeted by medicines. The idea here is that if there's a naturally occurring mutation in that target gene, you can simply ask what are the phenotypic consequences of carrying that mutation. Also use that information to predict, as I said, the efficacy of pharmacologic manipulation and potentially on-target side effects. This approach has become a very powerful approach. A famous recent example of gene, PCSK9, where mutation in this gene occur naturally. A lower function of PCSK9 and individuals who carry this mutations have lower LDL levels and lower risk of heart attack. This information has led to the development of medicine that mimic those mutations and those medicines have been proven now to lower LDL as well as lower risk of heart attack, a phenomenon anticipated by the genetics. Dr. Carolyn Lam: If I understand it right then, with regards to today's paper, the idea is that if a genetic predisposition to enhanced nitric oxide signaling associates with reduced risk of cardiovascular disease, then that would support the hypothesis that pharmacologic stimulation of the nitric oxide pathway would prevent or treat the cardiovascular disease, right? Could you further expand? Because you also did a meditation analysis. How would we understand that? Dr. Sekar Kathiresan: Let me walk you through the basics of this paper. Our hypothesis initially was a genetic predisposition to enhance nitric oxide signaling would actually affect a range of cardiovascular diseases. Nitric oxide is a well-known molecule, a regulator of a number of important processes; vascular tone, blood pressure, platelet aggregation. A couple of important genes in the nitric oxide pathway are, one, nitric oxide synthase, the key enzyme that generates NO. Second is a soluble guanylyl cyclase that is a regulatory molecule involved in NO biology. One of the genes that is part of that pathway is called GUCY183, which is basically a subunit of the soluble guanylyl cyclase. What we did was we looked at those two genes and asked, "Are there naturally occurring variations in those two genes that actually give us a sense that they gain function that they actually activate nitric oxide signaling. It turned out there are two polymorphisms. One in nitric oxide synthase and the other is in the soluble guanylyl cyclase subunit that are essentially gain of function. They're common polymorphisms. We know their gain of function because the carriers of these DNA variants have lower blood pressure. An indicator that there's enhanced NO signaling. We use these two polymorphisms as an instrument to understand the phenotypic consequences of having lifelong enhanced nitric oxide signaling. What we looked at was the relationship of individuals who carried both of the gene variants or gained a function and asked whether these individuals what the relationship of carrying the variant was to a range of cardiovascular diseases as well as a range of quantitative traits like blood pressure or kidney function. We looked at this in extremely large human population samples where genotype and phenotype had been collated. Most important of these samples is a recent study of a population-based cohort study called the UK Biobank, which has involved about a half million people where genotype and have phenotype have been assembled. What we found was that genetic predisposition to enhance nitric oxide signaling was associated with reduced risk of several important cardiovascular diseases. First, coronary heart disease. Second, peripheral arterial disease, and third, ischemic stroke. That provide a very compelling evidence that atherosclerotic cardiovascular disease would be lower based on enhanced nitric oxide signaling. What was surprising to us is we also found a couple of other diseases where it seemed to benefit from enhanced nitric oxide signaling namely kidney function and pulmonary function. These were a little surprising to us, but I think it really suggest that NO plays an important role in a range of diseases. In terms of your question about what aspect of NO biology is leading to be relationship to these diseases, is it simply the blood pressure effect for example or could you actually infer a mechanisms beyond the blood pressure? We looked at that specifically in the context of cardiovascular disease and we're able to show that the protection afforded by the enhanced nitric oxide signaling gene variants, that protection exceeded the amount predicted by the blood pressure change. In fact, by quite a bit suggesting that there are probably non-blood pressure mechanisms that are at play in terms of the protection afforded by enhanced nitric oxide signaling gene variants. Dr. Carolyn Lam: Peipei, I have to invite your thoughts now. This is such an amazing paper. We had great discussions as an editor team. Tell us your thoughts. Dr. Peipei Ping: The editorial team as well as the reviewers have been very impressed with the quality of the datasets and the value and detail, the metadata analysis together with the appropriate analytical approach. The study is done in our view in a very careful manner and the analysis was performed through the highest standards. What we also recognized is the potential impact that this particular study may have on multiple areas of studies, in particularly with their findings, the spectrum of individuals, how they carry nitric oxide signaling trends. You could appreciate that the individual score or genetic score paired with the analysis of the genetic variance that they have done, they see from the mental idea that examine both genetic as well as phenotype of each individual is critically important for medicine to be prescribed in the next step of therapies. Dr. Carolyn Lam: Building on that thought, Sekar, could I ask you? You found some rare inactivating variance. Are these the patients then you think should be targeted for NO enhancing therapies? What's the clinical implications of your findings? Dr. Sekar Kathiresan: I think there are two ways to think about the implications of these findings. One is there's just a simple biologic insight, the pharmacologic activation of NO signaling maybe protective beyond pulmonary hypertension. As you know, there are actually compounds in the clinic right now that are pharmacologic activators of soluble guanylate cyclase. Those medicines work in the rare condition of pulmonary hypertension. our work suggest that those medicines are likely to work in a broader range of indications including atherosclerotic cardiovascular disease, kidney disease and pulmonary function. At a simple level, those experiments, I think, should be looked at. Those indications should be looked at. Whether we've identified a subset of a population that particularly will respond versus it will be a general phenomenon across a range of different individuals that have impaired nitric oxide signaling, I think time will tell. Certainly, one group to think about would be those who are indigenously deficient in nitric oxide signaling and we did find that there are small subset of patients who have inactivating mutations in these two genes and they have higher blood pressure and increased risk for cardiovascular disease. It was a pretty rare phenomenon, so very small number of individuals would be relevant there. I'm not sure actually that you necessarily want to limit the potential benefit of NO signaling, enhanced NO signaling to just that subgroup. In fact, my prediction would be that the medicine would be relevant for a very large percentage of the population. That you do not need to limit the potential application of this therapy to just those who carry the inactivating mutations. Dr. Peipei Ping: I agree largely of what Sekar has discussed. I would add that in situations where genetic information are available with the patients, what the study has offered is fairly clear in the patients where rare variance that inactivate the NOS3 or the guanylyl cyclase off the genes. Maybe a failure it is with a higher systolic blood pressure risk. I'm entirely supportive with the general conclusion that we have come to a time point where NOS outside signaling activation is a critical new element of therapy in cardiovascular health and disease. Dr. Sekar Kathiresan: Thank you Peipei. Thank you Sekar for taking the time to share your thoughts with us. We are so proud to be publishing paper in circulation. So proud and happy to be chatting about this on this podcast. You've been listening to Circulation on the Run. Thank you for joining us and please tune in again next week.
Things get a little heated as we discuss the 2nd season of Stranger Things. Listen as we discuss/argue the 80's nostalgia, great cast, week mythos, and flat ending of ST2. Subscribe & Review on iTunes Also stream at www.notaboringsoup.com @nabspodcast - Twitter, Facebook, Instagram
In this bonus episode, Nick Jarin and Dyer Oxley review Thor: Ragnarok and Stranger Things 2. Spoiler Alert! They talk about the endings to both, especially what happens to ST2's Bob.Support the show (https://www.patreon.com/nwnerd)
This week the first teaser trailer dropped for ST2. Kevin & Steve discuss the teaser and tell stories about past Broken Lizard trailers. They also cover a "Lemme the Leaker" update, fried chicken, "creature of deliciousness," Chandrasekhar's silver fangs, Jim Gaffigan, Lemme brings his talents to South Beach, the Cincy Brew Ha Ha, breakfast buffets, synth jazz pop, key fobs and MORE! ENJOY THE CHEW!
Love is in the air! Kevin & Steve share their Birds & Bees lessons with their kids and in turn recount their B & B convos with THEIR parents. They also cover 15 lb lobsters, the Fat Guy Award, ST2, "Don't worry about it!," Day of the Animals, old Playboys, Steve's first dance, cartoon fleshlights, Carlos Cafe, Sesame Street after sex, stealing rubbers from Dad, "My Mom taught me this move," Is that egg on your pants?, NYC voyeurs, G.O.T. nudity AND MORE. ENJOY THE CHEW!
The Greek Tragedy of ADCs Parker With the success of the Raspberry Pi Compute Module LVDS test board. I started putting together the PinHeck REV8 board More Python and OpenCV work (fun!) Have the webcam taking pictures Auto Crops and records all the images of parts Looking into a higher resolution camera, more info on that later Stephen Parts for the filter finally shipped! Started putting together the boards Like the multi colored jumpers Veroboard - Strip Board Mouser Part Number 854-ST2 80 x 100 mm with mounting holes Use a 7/32" drill bit and a jeweler's drill to cut traces and brillow pad to clean up Going to add a tube preamp to the synth output Already have the preamp built. Just need to connect it. Schematic Tritrix speakers and the nutube amp. Kicking up the nutube amp again The speakers are almost built just need to paint and finish 3d printed a plate for soldering the crossover to Pick Of the Week (POW) Nuvoton NAU7802 - found on the Nice Chips Subreddit Precision low-power 24-bit ADC , with an onboard low-noise PGA, onboard oscillator, and a precision 24-bit sigma-delta ADC . Capable of up to 23-bit ENOB (Effective Number Of Bits) performance. SOP-16 or DIP-16 I2C $2.22 in singles Gotcha @10SPS, PGA=1 Rapid Fire Opinion (RFO) At Last, (Almost) A Cellphone With No Batteries! - HackADay University of Washington The first-ever battery free cell phone, able to make calls by scavenging ambient power. Not really a cellphone. Its really a remote handset for a base station. 3.5 microwatts and transmits 31 ft away. Evaluation boards for USB type-C power delivery - Electronics Weekly Rohm has announced USB Power Delivery (USBPD) transmitter/receiver evaluation boards. 15 to 100WTags: 854-ST2, AND!XOR, BM92A21MWV-EVK-001, Click Bait, MacroFab, macrofab engineering podcast, MEP, NAU7802, Nuvoton, OpenCV, pinheck pinball system, Podcast, Python, RPI3 CM, Tritrix Speakers, Tube Preamp, USB Type-C, Veroboard
The hates are back! Kevin & Steve catch up after their 4th of July celebrations and run through more things they hate. They cover an ST2 update, meatloaf, warm underwear, iPhone typing, dildo drawers, feather cocks, handicap parking morality, spray starch, skipping ads in 5 seconds, Robotron fist fights, stinky sponges AND MORE! ENJOY THE CHEW!
Happy 4th Chew Crew! To honor cook outs everywhere, Kevin & Steve run down their Top Ten Summer Foods. Along the way they cover ST2, Baby Driver, "My Monday Morning Beer," burnt hot dogs, Eddie the Pig, Ruffles vs. Pringles, shellfish shellfish shellfish, "pa-tayda salad," busting' out the Boursin, what can you lick but not bite?, Sam Elliott: Ice Cream, it ain't just for Summer any more, hamburguesa con queso, everything is better sawlty, The Purple Freak, snorting Old Bay and MORE. ENJOY THE CHEW!
Actor, Writer Paul Walter Hauser (Super Troopers 2, I, Tonya) returns to talk nut salt, Wrestlemania, lower body tattoos, Kingdom, Margot Robbie, Tonya Harding, ST2, hot dogs, high school dance teams, taking the bus, Twitter hacks, Big Bird's tits and MORE! ENJOY THE CHEW!
As companion piece to last week, Kevin & Steve get positive and run down Things They Love. They cover their ST2 test screening build up, Steve's puns, fat wet veiny sharpies, why teriyaki is bullshit, beef in a box, food that smells like B.O., abreevs like unforch & appreesh, Kong, sweaty cheese, pissin' on ice AND MORE! ENJOY THE CHEW!
Jay Chandrasekhar is back because he WROTE A BOOK! "Mustache Shenanigans" is Jay's autobiography coming out MARCH 28TH. He joins Kevin & Steve to share stories from the book about Super Troopers and the early Broken Lizard days. They also cover an ST2 update, why Jay wouldn't let Lemme pre-read, why terrorism is not his "jam," Buttfuck Egypt, what his Dad thought of the book, Ben Gay, how being Indian made him a director, the Indian Jackie Robinson of comedy, Burt Reynolds blowback, Dev Patel, independent film, how to write a book, the hidden dick on the book cover AND MORE! Enjoy the Chew!
An UPDATE from the edit room of Super Troopers 2! Steve & Kevin visit with the ST2 Editor Spencer Houck. They cover editing the sequel, Dutch fish, Houckamania, Lemme's paunch, Kevin's new glasses, Spencer's edit glove, the challenges of ST2, tech specs, cock socks, best edit room fights, Downton Abbey edit room farts, La La Land edit room farts, Canadian Classic Rock, melatonin junkies AND MORE! ENJOY THE CHEW!
With Thanksgiving behind them and the Christmas shopping season ahead, Kevin & Steve run down what THEY want for Christmas. Among other things they cover Thanksgiving, road rage, why Farva is crazy, the ST2 edit UPDATE, Black Friday, Dumb Saturday, fat moles, fluffy towels, the problem with Genies, hanging with Santa, the belly jiggle band, Christmas Spirit and MORE! ENJOY THE CHEW!
Paul Walter Hauser (Kingdom, ST2!) joins Kevin & Steve. They talk 3 name actors, P-Dumps, crackers in your soup, Milanos, shooting Kingdom, Nick Jonas, abs, Super Troopers 2, Ed Harris, auditions, WWE, crying w/ Shia Labeouf & so much more! ENOY THE CHEW!
Hayes MacArthur (Angie Tribeca, ST2!) joins Kevin & Steve. They talk about heart attacks, mustaches, shooting Super Troopers 2, drinking during Super Troopers 2, accents, Narcos!, football, Bowdoin, first concerts, Angie Tribeca, auditions, the Cubs, Gary Busey, BIG MAC & MORE! ENJOY THE CHEW!
The lovely & talented Emmanuelle Chriqui (Entourage) joins Kevin & Steve from the shoot of ST2 (with additional guest Jay Chandrasekhar!) They talk about her ST2 role, her French accent, Lemme's nude scene, Freaky Shreeky the Rockin' Moroccan, egg drop shots, Kevin's trip to IHOP, Lemme gets his milkshake, Entourage the TV Show vs. Entourage the Movie, Lemme vs. E, Cheetara, Australian Waze voice and much more. ENJOY THE CHEW!
History is made on the Chew! This is first episode that includes ALL the members of Broken Lizard. On the eve of shooting ST2, Kevin & Steve are joined by Erik, Jay, Paul & a surprise guest the one and only Officer Ursula Hanson, MARISA COUGHLAN! They talk about the upcoming shoot, rehearsal, fantasy football draft grades, weight loss, how many hairs in a mustache, ST1 jokes, does Farva have sex?, the Billy Goat Curse, respecting Jay, hostile call backs, ST3! AND MUCH MORE ENJOY THE CHEW!
Kevin & Steve continue to prep for shooting ST2 in Boston and discuss the stupid shit actors do to get camera ready. They cover the Boston accent, Fenway, teeth whitening, spray tans, hair extensions, wig shit, gettin' nude, dimpled asses, Superman exercises, Sting's tantric stink AND MORE! ENJOY THE CHEW!
One week of ST2 is in the can! Kevin & Steve recount the week, the future shooting plan, the reunion with Brian Cox, real cops on the set, New England weather, Farva 2.0, going High & Tight and of course they throw in some Halloween & Fantasy Football talk as a bonus. Enjoy the Chew!
Yesterday was the launch of the SUPER TROOPERS 2 crowdfunding campaign on Indiegogo! Kevin & Steve are joined by Jay Chandrasekhar & Erik Stolhanske in the Broken Lizard War Room on the day of the launch. As they watch the contribution tally, they talk about making ST2, the philosophy of crowdfunding, angry anti-crowdfunders, pissing sitting down, putting on the old uniforms, impersonating cops, growing mustaches & much more! ENJOY THE CHEW!!
Релиз Rails 3.2.18, 4.0.5, 4.1.1 Победители премии Ruby Hero DHH: TDD is dead Ruby Perfomance 2014 Musterman, парсер строк из внутренностей Sinatra Про array/hstore типы в Postgres Git conventions Mina не умерла! Capistrano team notifications от Evrone Minicron Gourmet service objects Про Policy Objects Hound, автоматический ревью кодстайлов Documentation driven development Lurker, проект Володи Бокова про генератор документации Открытие исходников Atom Фишки ST2 для рельсовиков Конференция RubyC в Киеве 31 мая — 1 июня А также выражаем благодарность Стасу Спиридонову за помощь с мастерингом этого выпуска.
ST2 - session 4 - Church government
The cell type-, organ-, and species-specific expression of the pattern-recognition receptors (PRRs) are well described but little is known about the respective expression profiles of their negative regulators. We therefore determined the mRNA expression levels of A20, CYLD, DUBA, ST2, CD180, SIGIRR, TANK, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, SHP1, SHP2, TOLLIP, IRF4, SIKE, NLRX1, ERBIN, CENTB1, and Clec4a2 in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. Additionally, we characterized their expression profiles in mononuclear blood cells upon bacterial endotoxin, which showed a consistent induction of A20, SOCS3, IRAK-M, and Clec4a2 in human and murine cells. Furthermore, we studied the expression pattern in transient kidney ischemia-reperfusion injury versus post-ischemic atrophy and fibrosis in mice. A20, CD180, ST2, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, IRF4, CENTB1, and Clec4a2 were all induced, albeit at different times of injury and repair. Progressive fibrosis was associated with a persistent induction of these factors. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to PRR-mediated innate immunity, which seems to be involved in tissue injury, tissue regeneration and in progressive tissue scarring.
Last week BMJ Careers published “The new lost tribe,” describing the cohort of surgical trainees moving from ST2 to ST3. In this podcast Edward Davies, BMJ Careers editor, and Tom Dolphin, a member of the BMA junior doctors' committee, describe how competition for training places is affecting career progression.
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