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National election is over. There were winners and there were losers. So the bhoys must discuss all of it. - The general feelings after it all (like how 1 in 4 nonwhites voted for President Trump. HUH?) - What does this all mean with a Democratic President-Elect in reality (Train Daddy and SALT-bae all over the Jersey tax meat) - What does this all mean with a Democratic President-Elect when you throw poop at the wall (Walsh vs. Wu vs. Campbell is still on, look deeper) - Are your State GOPs walking corpses? There is a very weak pulse. Someone have the defibrillator on standby. We made it. Enjoy a cold glass of milk.
Oh hey guys I just woke up. Huh? What's COVID? The summer? It's January! I'm still excited about the possibilities 2020 could bring for us! We're joined by Shoggoth to discuss how Episode 3 of Van-Pires: "A Few Good Cars" is secretly a brilliant metaphor for the military industrial complex. Maybe. Shoggoth's podcast: Homo Vulgaris Dirk's new podcast: Shonen Flop Mission Ignition's Twitter Shonen Flop's Twitter
Hey you're finally awake! That was some fall you had. Huh? What pandemic? Anyway, let's go before we're late. The beach silly! It's almost over so let's enjoy it while we can! www.kmusiceveryday.com www.instagram.com/kmusiceveryday www.twitter.com/kmusiceveryday BSKP 128 Tracklist: 1. SSAK3 - Beach Again 2. DJ DOCC - Summer Story 3. Weeekly - To My Boyfriend 4. PARKMOONCHI - MBTI (with. PARKMOONCHI UNIVERSE) 5. Ravi, Yeri, Kim Woo Seok - Woman On the Beach (COOL Remake) 6. COOL - 이 여름 Summer 7. Circle - Sweetest Love 8. Papaya - Listen to Me 9. CSVC - Summer Love… 10. Seo Yeon - In Summer 11. SSAK3 - Play the Summer 12. Shinhwa - Eusha! Eusha! (으쌰! 으쌰!) 13. PARKMOONCHI - We're Cool (with. PARKMOONCHI UNIVERSE) 14. Kirin x Hoody - ORE ORE 15. H.O.T. - Candy 16. Jinusean - How Deep Is Your Love 17. DIA - Somehow 18. S.E.S. - Just A Feeling 19. Apink - My My 20. PARKMOONCHI - 널 좋아하고 있어 (with. 기린, Dala, 준구)
So You Made 100K on a Land Deal Now What (LA 1302) Transcript: Steve: Steve and Jill here. Jill: Hey. Steve: Welcome to the Land Academy Show, entertaining land investment talk. I'm Steven Jack Butala Jill: And I'm Jill Dewitt broadcasting from sunny Southern California Steve: Today Jill and I talk about, so you made a hundred grand on that last land deal, now what? Jill: I know what. Steve: Well. Jill: Do it again. Steve: Celebrate. Yes, first you need to take 10 minutes and celebrate. Maybe do shot of tequila or something. Jill: Yeah, tens good. Ten minutes is good. Steve: Whatever works for you. Eat a piece of chocolate cake, I don't know whatever works for you. Jill: What is yours? Steve: And that's the whole show. Jill: Quick. You want to celebrate? What? Can I have a budget? I made a hundred thousand dollars. How much money can I spend from my separation? Steve: You know, Jill and I made a huge amount of money one time on a real estate deal. You know what we did? Bought new computers. Jill: Yeah. It went to the business and it made us more effective and it, and I was just so happy. Yep. All right. Quick, you give yourself $500. What are you going to do? Steve: God, I haven't thought about something like this in a long time. Because usually I just go do whatever I want. Jill: I know but- Steve: For 500 bucks, what would I do? You know what I would do? Call up my buddies, probably bring you and your friends, girlfriends, and just pay for everybody's night out. Jill: That's very sweet. Well, now I feel like a little bit like a heel because mine's different. Mine is I call no one. Steve: Oh my God. Is this a spa day at that MZ diamond acquisitions? Jill: No because I have $500, it's just a spa day. That's it. I call no one, I turn off my phone, I leave it in the car and I'm gone for several hours. That's how I celebrate. Steve: Jill, I speak frankly, here. You should be doing that once a week anyway. Jill: I know. I should but spa's are kind of closed right now. Steve: Why don't you schedule that? Jill: Because the spa's are closed right now. That's, trust me, don't you, don't think I'm not, that's not on my list. Steve: Can't you have like a masseuse come to the house? Jill: I haven't really tried that hard but I could probably work on that. So, but thank you, that's not what this show's about. Thank you. Steve: Yes it is. This is about a hundred grand. It's totally about this. Jill: Okay, I guess so. Okay, yes because I just learned, I didn't know of any that would come to the house. And I just heard from somebody recently that they know someone. So that's in the works. But do you know what? I still don't want to do it in my own house. I have to go somewhere because I don't want to have to hide. And you know, I want to just, I'd like to go and be treated. Steve: You want to go somewhere and do that? Huh? What if I leave the house? And then- Jill: It's still not that great. I want to go be treated. Steve: This is interesting. Jill: You know what I want to do? Steve: You learn new stuff about your mate every day. Jill: I want to go to Terranea, or something equivalent, and just really have a nice, nice time. Thank you. Steve: Before we get into it, let's take a question posted by one of our members on the landinvestors.com online community. It's free. Jill: Okay. Mohad wrote, I've been practicing using Real Quest Pro to pull data in an area I'm looking to send my first mailer. Once I enter all the criteria and submit, it seems like a lot of the data I pull has some sort of housing on it. I'm entering in zero to 0% improvement and I'm still getting many buildings slash houses. I don't want to waste money on records with houses. I've gone through each land use to figure out which is pulling the records with the houses, but it looks like they are just blended in with several uses. Any suggestions on how to get rid of the houses, to be sure I'm doing something wrong? Steve:
想关注或与我们联系么？Wanna stay up to date or get in touch?Like us on FacebookFollow us on Instagram: breadtoastchinese微信公众号搜索 Search for our public WeChat account ：BreadToast Chinese 面包吐思给我们发个邮件 Send us an email: breadtoastpodcast@outlook.com----四川，我们来啦! LET'S GO TO SICHUAN!Get a taste for Sichuan and its culture and dialects as we kick off a series of episodes on this southwestern behemoth of a province which is geographically isolated, historically significant, and utterly fascinating. Part one is an engaging interview with three natives--all hailing from different regions but also all currently living in Chengdu. The interview is conducted by 7岁 amateur reporter 果果, with some sweet 四川话 BGM provided by 衣湿乐队，罗先举，and J-Chill. Stay tuned in the coming weeks for more awesome Sichuan-related content!巴蜀文化历史悠久，除了深厚的文化底蕴外，四川话的迷人也是实力上榜。他们正常说话的时候，你以为在吵架；等到他们真的吵架，你又以为在唱rap。四川人说话有多可爱，大概就和大熊猫一样可爱吧。四川话系列第一集，我们邀请了三位来自四川不同地区、现居于成都的朋友。7岁的成都宝贝果果将担任本期特邀嘉宾，在13个提问中探寻当地人对家乡文化与方言的独特记忆。伴随着来自衣湿乐队、罗先举和and J-Chill的四川话BGM，四川，我们来啦～----时间轴 TIME MARKERS0:00 - 开场白 Opening Remarks (面包 + Vicky) 0:18 - BGM: 胖娃儿上成都 - 衣湿乐队 1:57 - 绕口令 4:08 - BGM: 见（四川话）- 罗先举7:40 - 快问快答 Interview (果果) 嘉宾自我介绍，四川省冷知识，四川方言分析，四川文化，等30:47 - 结语 Closing Remarks (面包) 31:11 - BGM: 四川话freestyle - J-Chill----等等，啥子安？WAIT, WHAT DID THEY SAY?绕口令 TONGUE TWISTER #1鸟岛是岛，鸟岛有鸟。鸟岛的鸟多得数不清了。要想到鸟岛，一定要爱鸟。你不爱小鸟, 就别到鸟岛。 绕口令 TONGUE TWISTER #2知道就说知道，不知道就说不知道，不要知道说不知道，也不要不知道说知道，你知道不知道？ 方言科普 DIALECT BREAKDOWNgua: 这个饭（gua）好吃。有一点、挺。这个形容词是四川巴中人日常口语中必不可少的部分。How you can say "a bit" in Bazhong.抵拢导拐: 走到尽头转弯（指路）。有人向四川人问路时，当地人总会用这句话来给别人指路。Used when giving directions.啥（sa）子: 什么。当人听别人说话，没听懂时，就会说“啥子安？”意思就是你说的什么呀，可以再说一遍吗？Huh? What?客猫儿: 青蛙。Frog.雀善儿: 蚯蚓。当地人钓鱼需要诱饵时，就喜欢说“挖雀善儿”，意思就是用锄头在地里挖出蚯蚓来作为钓鱼的诱饵。Earthworm.麻麻得儿: 蜻蜓。当地人常说“麻麻得儿飞得矮，要落雨”，意思就是看到天上有成群的蜻蜓飞的很低时，就表示要下雨了，提醒人们赶紧回家，收衣服，收晾晒的农作物等。Dragonfly.苍蚊儿: 苍蝇。Housefly.割（ga）儿: 猪肉。当地长辈喜欢对自己家的小孩说“你一天到黑就想都吃割儿”，意思就是你每天就想着吃肉，离开了肉，这日子就没法过了。This one is definitely the most impossible to guess: Pork!堂客: 老婆 Term of endearment for your serious girlfriend or wife.你这回子涮得烦哦: 你这次遇到麻烦了，环境很糟糕，摊上事了。Dang, that's rough.打闷（巴中话）: 程度加强，相当于一个副词。例：你打闷搞快点（你赶紧/抓紧快点）Intensifier.巴适得拌（ban）: 巴适，舒服；拌（动词），一种兴奋得打滚的动作。通俗来讲就是十分舒服；舒服得很 For when you're feelin' it.--Thanks 尔卓 and 强哥 for your 四川话 expertise！--And of course big thanks to our reporter 果果，our guests 天天妈，袁威 and 铁环， and our BGM artists 衣湿乐队，罗先举 and J-Chill. ----Is this stuff helpful? What else would you like to see here? Got any questions, comments or complaints? Send us an email: breadtoastpodcast@outlook.com----制作人 Producers：面包 + Vicky + 尔卓 + Clara主播 Hosts: 面包 + Vicky + 果果音乐人 Featured Musicians: 衣湿乐队 + 罗先举 + J-Chill
Happy Mother's Day Randos! Listen in as we discuss our top 10 consensus fictional Mom's from all realms of Fandom! We've got the most loving, nurturing, badass, and homicidal Mom's to ever grace Fandom rounding out our top 10! You don't want to miss this one! Huh? What's that? Did someone say...MARTHAAAA!?!? -F@R- --- Support this podcast: https://anchor.fm/fandom-at-random/support
Welcome to the heart of our course! We are going to learn how to discount a future stream of dividend income. Huh? What that means is that we are going to learn how to assign a value to the stock on the basis of the cash flows that result from the dividends that the stock is paying. To do this, we will use the Dividend Discount Models. This is it, Dear Students! This is the heart of our course!
With 2020 just around the corner, now is (hopefully) the time when you’re laying the groundwork for what you’re doing in the New Year. From mapping out your big business goals to figuring out where you want to travel in 2020, it’s an exciting time where you get to think about all the possibilities. Of course, we believe that the best way to plan for the future is by assessing the whole picture — even the not-so-fun stuff. That is why we’re sharing a few things you should be aware of in 2020 in this episode. Our hope is that, by sharing what the New Year might bring, you can build some buffer into your plans and create a really strong strategy that helps you weather anything that comes your way. WHAT YOU’LL LEARN [01:30] How the global economy may affect your business in 2020 [02:03] Things you should be planning and preparing for next year [03:22] How small business was affected in the Great Recession of 2008 [05:41] Why every recession is different and why it’s unlikely to see another crisis [06:23] How lower interests rates and political upheaval can affect our economy [07:43] The difference between a hot and cold war [09:05] Why the Feds keep lowering the interest rates [10:06] The self-fulfilling prophecy of recessions [12:57] The yin and yang of a recession [14:08] Why we can see all of this upheaval as a sort of “rebirth” [15:51] The first step in preparing for 2020 [16:26] How to assess your income/expenses and contracts to see what’s not serving you [18:57] Why debt is a tool and how you can use it to your advantage in 2020 [20:11] The importance of maintaining your savings and investing despite a market slowdown [22:15] Why you shouldn’t wait for a recession to start (or stop) investing [24:10] The value of a financial advisor when the going gets tough LET’S TAKE A LITTLE TRIP DOWN MEMORY LANE When we talk about planning for 2020, we should consider all of the possibilities. On average, an economic cycle lasts about 4.7 years. This means we have about 3.2 years of growth and about 1.5 years of recession. By those numbers, we’re pretty overdue for a recession (we haven’t had one since 2008!). That’s why, on this week’s episode we want to get you prepared for 2020 in the event that a recession does hit. We can never predict what will happen, but based on historical data, a recession will occur eventually. So why not plan accordingly, right? INDICATORS OF RECESSION During this episode, Dustin talks about a few of the things you might be seeing on the news lately — from lowered federal interest rates to struggles in global economies. While a lot of this can feel complex and overwhelming, there are a few ways that these “events” affect you here on U.S. soil (and might affect your business): Federal interest rates: A lower federal interest rate is a tool the Federal Reserve uses to spark the economy, but it also means they believe we’re on the verge of a recession, so they’re trying to stimulate the economy. Hot wars are up: Hot wars, meaning on-the-ground fighting, guns, military, etc. are up all over the world. This leads to volatility and uncertainty, which can affect the markets as well as global economies. Global growth is slowing: Nations all around the world are experiencing slower growth, which could be in part to political upheaval, those hot wars, etc. This, of course, comes home to roost here in the U.S. Low economic growth in America: All of our economies are intertwined and when global economies slow, so does ours. But remember: a recession merely means that the economy is not growing. So… how do you navigate all these potential signs of recession and their potential effects on your business? You plan for 2020… and listen to this week’s episode! HOW TO PLAN (AND PREPARE) FOR 2020 In this episode, we walk you through the 4 steps you should be building into your 2020 planning so you can handle whatever comes your way. These steps include: Making sure your emergency fund is funded. That means 3-6 months of living expenses and 3-6 months business operating expenses, cash on hand. If you don’t have that cash saved up already, it’s time to start. Applying for financing before you need it. You know we hate all that “debt is dumb” talk — and that’s never more true than in a recession. When a recession hits, banks are less likely to give out loans because, guess what! The risk is on them! They might not get paid if things go south. So, we recommend that, if you’re planning on asking for a business loan, car loan, or even mortgage in 2020, look at applying now. This way, you can have the cash you need when you need it, and you don’t have to worry about banks making it hard to apply for loans down the road. P.S. to hear more about what we think about debt, check out this about this in Episode 84. Taking advantage of the stock market. As we always say, the last innings before a recession are some with the best growth. You should be saving and investing at a steady rate and you should not stop if things slow down (or fall). This allows you to “buy shares on sale.” Huh?? What does that even mean? A share today might cost $100, but during a recession you might get 4 shares for that same $100. It may seem like you’re investing in a losing game, but when the market rebounds, you’ll have 4 shares that are now worth $100 each. That’s $400 for the investment of $100. This is oversimplified, of course but you get the gist! Hiring an advisor. When a recession hits, a good advisor is going to help you invest properly, manage your fears, and set yourself up for success. He or she is also going to help you prepare for a recession before it hits, from a business and personal financial perspective. DON’T GET SCARED. GET PROACTIVE. We know that this can feel like a lot of information, and it might be a bit overwhelming or scary if you’ve never thought about a recession before. But you’re a business owner and you need to know that, sometimes, you can’t control everything. What you can control is how you prepare. This episode was designed to give you some helpful tips to build into your 2020 planning and we hope you actually use them. They could really save your
On Today's Show: - Huh? What happened - offense missteps - Soft Defense gives up too much
On Monday college basketball analyst Jeff Goodman picked the Huskies to make the Final Four. That's heady stuff, considering the last Washington team to make the Final Four (the only time) was back in 1953. Those were the days of Tippy Dye and Bob Houbregs. UW Head Coach Mike Hopkins said he didn't know about the news, which is unsurprising. It's usually his wife Tricia who keeps him abreast of current events, especially while Hop and the rest of the Huskies are focused on preparing for their season-opener against Baylor Friday in Anchorage as part of the Armed Forces Classic. And honestly, even if he did know, Hopkins has been around enough tournament teams during his days at Syracuse to pooh-pooh such preseason talk. It's great for the fans and it can energize a team, but it's just that...talk. Hopkins' response to all of it? DMGB. Huh? What's that? Sounds like something a player would take to help them recover after a grueling game. Doesn't Matter. Get Better. That's the mantra. Those are the four words the team is living by. They showed a ton of promise in their exhibition win over Western Washington on Halloween, but the team got even better on paper the next day when it was announced Quade Green's waiver for immediate eligibility came through. It feels like things are coming together nicely for Hop's Huskies. Doesn't matter. Get Better. Learn more about your ad choices. Visit megaphone.fm/adchoices
Huh? What?! We're finally here to bring you the second half of our two-parter on The Residents' Bunny Boy project from 2008. In this episode of Home Age Conversations, we continue hopping down the bunny trail (HA!) as we sum up the later parts of the series and our thoughts on the project as a whole. So! Join us for Part 2 as we go through the project guided by the webseries and do our best to get to the bottom of our dear friend's tale. After all, he's going to save the world... or maybe he already has?
I don't know about you, but I was raised around competition. Not so much from my parents, but from culture. In school, you compete in all sorts of tasks... trying to prove how smart, how good, how talented, how athletic, how whatever you are... compared to the others. It doesn't stop there, but keeps on going. Win or lose. That's all that matters. Well, winning. That's what matters. Remember Ricky Bobby from the movie, Talladega Nights? "If you ain't first, you're last!" In other words, you win... or you have lost. (Do remember, though, that at another point in the movie, Ricky Bobby is talking with his Dad... and gets challenged: Ricky Bobby: "Wait, Dad. Don’t you remember the time you told me 'If you ain’t first, you’re last'?" Reese Bobby: "Huh? What are you talking about, Son?" Ricky Bobby: "That day at school." Reese Bobby: "Oh hell, Son, I was high that day. That doesn’t make any sense at all, you can be second, third, fourth… hell you can even be fifth." Ricky Bobby: "What? I’ve lived my whole life by that!" There you go... a first... a quote in a Will Ferrell movie to make a point about thriving!) We grow up on that whole "win or learn" thing... which ties us tightly to our ego. If we win, ego boost. If we lose, ego bruise. What will others think?? Maybe it is worth making a shift. Nelson Mandela said, "I never lose. I either win or I learn." When you don't win, you can learn! Great shift. "Losing" is an opportunity for learning. When you don't win, there is an opportunity for growth, for learning... for being better. But it is still bound by ego. What if it isn't even the win? But the learn? Then, we either learn... or we learn. Listen to this episode for more on winning/losing versus learning/learning. RELATED RESOURCES What I learned in Jiu Jitsu More I learned in Jiu Jitsu Even MORE I learned in Jiu Jitsu Trial-And-Error Mindset Three Growth Mindsets Showing UP Book: Thrive Principles Book: The Immutable Laws of Living ... And show some love with a tweet by CLICKING HERE.
Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your cohosts, I'm Dr Carolyn Lam, associate editor from National Heart Center and Duke National University of Singapore Dr Gregory Hundley: And I'm Greg Hundley, associate editor from the Pauley Heart Center in Richmond, Virginia at VCU Health. Our feature article today really invokes thought regarding LVAD bridging to heart transplantation. I really look forward to the conversation with Dr Veli Topkara from Columbia University, the corresponding author and our associate editor, Dr Mark Drazner from UT Southwestern. And it's regarding the outcomes from their study, evaluating patients waiting for transplant that are bridged with an LVAD versus not. But before we get to that, let's dive into some of our other original articles with our little coffee chat. Do you have an article that you'd like to discuss? Dr Carolyn Lam: You bet I do Greg and I have my coffee here. Have you ever wondered, does microvascular disease, in any location in the body, increase the risk of lower limb amputation? Well, this was looked at in the paper that I chose first today. It's from Dr Beckman from Vanderbilt University Medical Center in Tennessee and his colleagues, and they basically examined 125,674 participants in the Veterans Aging Cohort Study from 2003 to 2014 and analyzed the effect of prevalent microvascular disease defined as retinopathy, neuropathy and nephropathy and peripheral artery disease status on the risk of incident amputation events, of which there were 1,185 amputations over a median of 9.3 years. Dr Gregory Hundley: Wow, Carolyn. What did this study find? What did Josh and his colleagues find? Dr Carolyn Lam: They found that the presence of microvascular disease increases the risk of amputation significantly in the absence of peripheral artery disease. As many as one in six below knee amputations may result from microvascular disease, even without peripheral artery disease. Microvascular disease also potentiates the amputation risk in persons with peripheral artery disease to more than 20-fold, compared to persons with neither peripheral artery disease nor microvascular disease. Further research is really needed to understand the mechanisms by which this occurs. And in the meantime, clinicians should bear this increased risk in mind when screening for and managing lower extremity disease. Dr Gregory Hundley: Ah. Well Carolyn, my first paper is somewhat related because we're going to talk about triglycerides. And this paper is from Zahid Ahmad from UT Southwestern Medical Center. He's the corresponding author. And can you imagine Carolyn an antibody that could correct elevations in serum triglycerides? Dr Carolyn Lam: Tell us about it, Greg. Dr Gregory Hundley: Well, I'm going to give you a little background first. Low levels of triglycerides and other lipids are observed in individuals with loss of function mutations in angiopoietin-like protein 3 which inhibits lipoprotein lipase activity, increasing triglycerides and other lipids, and providing a rationale for development of a monoclonal antibody therapy. Dr Carolyn Lam: Interesting. What did this study do Greg? Dr Gregory Hundley: It evaluated evinacumab. They looked at the safety of this. This is a fully human angiopoietin-like protein 3 antibody, and it was compared with placebo, with no serious treatment emergent adverse events, no events related to death or treatment discontinuation was reported. They did two phase one studies evaluating single and multiple ascending doses. In addition, substantial and sustained percent reductions from baseline versus placebo were observed and triglycerides with absolute levels reaching about 50 milligrams per deciliter for several of the evinacumab doses at specific time points in both studies. And therefore, the data from these two phase one studies in this one paper support further clinical evaluation of this new antibody in larger studies of hypertriglyceridemic individuals. Dr Carolyn Lam: Definitely a space to look out for. Well Greg, my next paper is a basic paper. Genome wide association studies have identified chromosome 14 Q32 as a locus for coronary artery disease. The disease associated variants fall in a hitherto uncharacterized gene called Hedgehog Interacting Protein Like 1, or HHIPL1. the function of this gene and its role in atherosclerosis has previously been unknown, well, until today's paper. But Greg, here's your quiz. What do you know about the hedgehog proteins? Dr Gregory Hundley: Well, I know hedgehogs are friendly little animals and I know they must have great proteins because they're so friendly. Dr Carolyn Lam: Why did I expect that? Oh, let me tell you a little bit about them. The mammalian hedgehog proteins like sonic hedgehog, desert hedgehog, and Indian hedgehog are secreted molecules that exert a concentration and time dependent effect on target cells following binding and complex signal transduction pathways. They induce the transcription of target genes, primarily involved in cell proliferation, survival, and fate specification. Now in adults, the hedgehog signaling is involved in the maintenance of adult vasculature and ischemia induced neovascularization, including after myocardial infarction. Today's authors, however, including Tom Webb from University of Leicester and colleagues, report the first experimental investigation of HHIPL1 and the present evidence that it is a secreted proatherogenic protein that regulates smooth muscle cell proliferation and migration. So, that's novel. Through a series of experiments involving coronary artery disease, relevant human cells and mouse models, they showed that HHIPL1 is a secreted protein that interacts with sonic hedgehog and is a positive regulator of hedgehog signaling. In murine models, HHIPL1 deficiency attenuates the development of atherosclerosis by reducing smooth muscle cell proliferation and migration. The clinical implications are two-fold. First, this study supports HHIPL1 as the causal gene at that 14 Q32 coronary artery disease locus that we did not really understand previously. And secondly, HHIPL1 is a promising therapeutic target that affects a pathogenic mechanism not addressed by current mechanisms for coronary artery disease. Room for novel development. Dr Gregory Hundley: Very interesting Carolyn. Well, I've got another basic science paper, and this is from Dr Kenneth Walsh at University of Virginia and it's going to look at the role of neutrophils, not necessarily macrophages but neutrophils and their role in pressure overload induced cardiac dysfunction. While the complex roles of macrophages in myocardial injury is widely appreciated, the function of neutrophils in nonischemic cardiac pathology has received relatively little attention. This study examined the regulation and function of neutrophils in pressure overload induced cardiac hypertrophy as mice underwent treatment with Ly6G antibody to deplete neutrophils and then subjected them to transverse aortic constriction or TAC. Dr Carolyn Lam: Huh? What did they find? Dr Gregory Hundley Caroline, the study revealed that neutrophils played a critical role in the hypertrophy of the left ventricle that results from pressure overload in this murine model of heart failure and identified that a non-canonical Wnt protein is essential for the recruitment of neutrophils to the injured myocardium. Dr Carolyn Lam: Hmm. What do you think are the clinical implications of this? Dr Gregory Hundley This study demonstrates how neutrophils contribute to the hypertrophy of the left ventricle under conditions that do not involve ischemia or myocardial necrosis. Also, since cardiac hypertrophy is a risk factor for the development of heart failure, this study implicates WnT5a mediated neutrophil infiltration as an early step in the progression of this disease. Dr Carolyn Lam: Wow, thanks Greg. That was so cool. But let's hurry on to our feature discussion, shall we? Dr Gregory Hundley You Bet. Dr Carolyn Lam: Bridge to transplant with left ventricular assist devices is a mainstay of therapy for heart failure in patients awaiting heart transplantation. The criteria for heart transplantation listing does not differ between patients medically managed versus mechanically bridged to heart transplant. However, are there differences in post-transplant outcomes between medically managed and mechanically bridged patients? Well, today's paper provides important data to address this question. So pleased to have with us the corresponding author, Dr Veli Topkara from Columbia University Medical Center, New York Presbyterian as well as Dr Mark Drazner, associate editor from UT Southwestern. Welcome gentleman. Veli, this is an important question. Could you please tell us how you addressed it and what you found? Dr Veli Topkara: We decided to visit an old question of whether bridging with LVAD confers at risk for post-transplant mortality. Because the field and pump technology has been rapidly changing. There has been a significant increase in utilization of devices nationwide to the extent that more than 50% of patients already have an LVAD in place by the time they receive a heart transplant. And patients also wait much longer on these pumps before they could get a heart. Currently, available devices provide continuous flow and patients essentially live without a pulse for many months to years waiting for a heart. And with this unique physiology, they also have unique complications such as RV failure and there has also been pre-survey reports including one from our center suggesting an increase in the primary graft failure rates after heart transplant. And mostly seen in patients who were bridge to transplant with an LVAD. To address some of these questions, we took advantage of the UNOS database, which is the largest prospective transplant data registry in the United States. We were able to identify more than 14,000 patients who are either medically or mechanically bridged to transplant. We then derived a cohort from patients who were LVAD baseline by propensity score and we looked at their outcomes. And what we found was that patients who were mechanically bridged to transplant with an LVAD, had 9.5% mortality at one year, compared to 7.2% in patients who were medically bridged. And this is more than 30% increase in relative risk of death for LVAD patients. When we looked at the specific cause of death at one year, LVAD patients had a higher number of cardiovascular death secondary to primary graft failure, confirming findings of the recent studies at a larger scale. Next, we looked at whether mortality risk factors were similar in the mechanical versus medical bridged patients. And this is a very important question clinically because the criteria for transplant listing do not distinguish between the two patient cohorts. For example, at my center age cutoff transplant listing is less than 72 years of age and that is whether or not patients are on VAD support. And same applies for example, GFR cutoff for renal function or PVR cutoff for pulmonary hypertension. And all the cutoffs that are utilized are essentially identical for transplant candidates irrespective of the bridging strategy. But what we found in this paper, however, what's quite different that if we apply the same thresholds for mechanical versus medical bridged patients, for some of these risk factors, you end up having outcomes that are remarkably different. For example, for patients with a normal renal function, the mortality risk is similar going into transplant with or without an LVAD, but for patients with borderline renal function observed mortality has more than doubled for those going into transplant with an LVAD, as opposed to medical therapy. And we also observed similar trends for recipient age, BMI and PVR, in which numerical increase in these factors would translate to high risk of mortality in LVAD patients going into heart transplant. Despite the limitations of this large registry analysis, I think these findings suggest that we may need to think of it differently when it comes to listing or transplanting patients who are on LVAD. And there seems to be a group of patients who are perhaps maybe better served by staying on an LVAD as opposed to moving on to heart transplant and we need to better identify who these patients are. Dr Carolyn Lam: Oh Wow. Veli, thank you. First, congratulations on a very important paper and also how you beautifully summarized. Mechanically bridging patients associated with a higher risk of early post-transplant mortality and even providing data on the cause and risk factors associated with that mortality. Mark, could I bring you in here? Not just as AE (associate editor), but as a doc[tor] who manages many of these patients. What were your perspectives? Dr Mark Drazner: As I step back and as Veli said, there's an increasing number of patients who are being bridged with a VAD, so the question clearly is important, and we don't really have any randomized data available to us in terms of how the bridging strategy may impact outcomes. When you look at the groups of patients who are supported with VADs or not, they're very different and so you need to do some statistical manipulation which here they did propensity matching, to try to come up with equal groups as you look at their outcomes. That was nicely done. And then theoretically I think you could argue there may be reasons why patients bridged with VADs may do better or they may do worse. They may do better because you may restore their functionality, you may improve renal function and, but they may do worse because they have coagulopathies, the VAD itself may lead to complications and so it's a question you can't really answer just logically. You really need some data which is I think the best study that's been brought forward so far as the one we're discussing today. Veli, let me ask you because the obvious question then is why do you think the outcomes are worse among the patients who are bridged? Dr Veli Topkara: I think they are doing worse for multiple different reasons. Having an LVAD is clearly an additional surgery which technically makes the second transplant surgery more complicated. But when we looked at the risk factors for primary graft failure at our institutions, the predictors of primary graft failure in LVAD patients were also very similar to factors we identified in this nationwide analysis which included renal failure, RV dysfunction, as well as trans-transplant and increased time on device support. I think it's clear that some subset of LVAD patients who have these risk factors are at higher risk for increased post-transplant mortality for some of the mechanistic reasons are unclear at this point. Dr Mark Drazner: Do you think their continuous flow exposure is part of it? Dr Veli Topkara: That's clearly one of the hypotheses that we have been talking about because as we discussed, these patients are exposed to continuous flow for a long time and one of the concerns is whether they lose their peripheral arterial venous-reactivity over time. And this could potentially also be the reason why patients who are on pump support for longer times are at higher risk for PGF. That's a possible underlying mechanism. But in this data set, we didn't have fair data with regards to pulse pressure and pulsatility, which could have helped answering this question. Dr Mark Drazner: And just for clarification for the listeners, this was pre-HeartMate 3 data, is that correct? Dr Veli Topkara: Yes. This analysis doesn't include any HeartMate 3 patients. Dr Carolyn Lam: And Mark, if you don't mind, could you also clarify for the listeners why you specifically pointed out HeartMate 3 in the setting of the pulsatility? Dr Mark Drazner: There is some degree of pulsatility reintroduced with the HeartMate 3, whether that has any physiological consequences is not yet known. Certainly, in terms of the impact of transplants. But as Veli said, the dataset available didn't yet include the HeartMate 3 so that's, remains an unanswered question for us currently, but certainly an important one. Dr Veli Topkara: We would probably be able to do this analysis now that we have accumulated more patients with HeartMate 3. At the time of the study we didn't have any HeartMate 3 patients in the registry. In terms of primary graft failure, we have implanted over 160 patients with HeartMate 3 at my center, but we still see primary graft failure in HeartMate 3 patients going into heart transplant, but that would clearly be an interesting follow up project. Dr Mark Drazner: Yeah, for sure. Another point that people, as they looked at your paper and asked me, is in terms of the impact of the VAD complications, whether the patients who are doing worse or those who, because they are patients who had VAD who have had complications and then went on a transplant and the impact of that, in terms of your findings. I know you did some analyses on that. Could you just clarify that for our listeners as well? Dr Veli Topkara: Sure, so we wanted to look at for the LVAD patients, if there were any VAD related factors that would impact the posttransplant mortality and one of the things that we looked at was, their specific complications on LVAD support and were able to pull that data by looking at their reason for 1A upgrade status which clarifies the complication pipe. And when we looked at, based on complication type, we didn't see any impact of complication on the post LVAD mortality. In other words, the other patients who are transplanted with an infection or they were transplanted because of device thrombosis, they did not have any difference in terms of their posttransplant mortality. We also compared patients who were supported by axial flow devices versus centrifugal flow devices and again, there was no significant difference in terms of posttransplant mortality. One factor that we found that was significant was the duration of the LVAD support and patients who stayed on the LVAD for longer times clearly had increased higher risk of posttransplant mortality. And this is also something that we had found in our institutional data. Dr Mark Drazner: And Veli that would potentially speak to the impact of the continuous flow if duration of VAD is a risk factor. Dr Veli Topkara: That's our hypothesis Mark. And I think we all tend to think that continuous flow is not natural, and we have pulse style flow for a reason. Now it's possible that if our bodies and end organs and vessels are exposed to continuous flow for a long time, that may be potentially a reason for, increased risk of PGF or raise of PGF after heart transplant. But I don't think we have enough data yet. Dr Mark Drazner: Veli, one of the other interesting findings was the lack of impact on long-term outcomes. I'd be interested in your thoughts about that, why there was an impact on the first year but not long term. Dr Veli Topkara: Absolutely. And that was a critical part of the findings and when we looked at our survival, when we visually looked at the curve, it seemed like the curves really separated early on and they sort of remain parallel to each other after one year. And for that reason, we did a conditional survival analysis starting from one year and then we compared starting for one year. There was actually no difference between the LVAD versus medical group. Again, confirming that the adverse impact of survival was really early, within the first year after transplant and I think that really has to do with primary graft failure as well as vasoplegia which are, typically seen early posttransplant. And I think the reason the VAD support is increasing mortality is most likely through increasing risk of PGF as well as vasoplegia. Now that's my read on the early risk rather than the late impact. Dr Mark Drazner: Do you think that speaks to maybe not as big an impact on the immunological milieu of VADs as one might anticipate? Dr Veli Topkara: Certainly, I mean the immunology, one thing we know is that LVAD patients have higher HLA sensitization going into transplant. However, primary graft failure is typically very early after transplant. And in general, we don't find, obviously we don't see any rejection in these patients. The mechanism is not related to HLA mediated rejection. Dr Mark Drazner: That's interesting. Dr Carolyn Lam: Well Mark and Veli, thanks so much. This is such an important and interesting discussion. Could I wrap it up now by asking each of you, you've already covered possibly the important areas for future research including the pulsatile devices, but what should clinicians take home right now? Veli, if I could start with you, because you had already said earlier that perhaps these patients need to be more carefully considered. What do you mean by that? What's the take home for now? Dr Veli Topkara: I think the question is whether we should be listing or transplanting LVAD patients who are high-risk, and I think the research should focus on developing tools to better identify LVAD patients who are too high-risk for transplant. In this project, we only worked with a limited number of variables that were available in the UNOS registry, but there may be more specific clinical risk factors or even biomarkers predicting outcome in this unique cohort of LVAD patients potentially transitioning into transplant. I think that's an important question to figure out. And another important question is whether we should be using identical cutoffs for listing patients with or without LVAD and if not, what would be the ideal cutoff for each one of these risk factors? Because what I read from this paper is that, a creatinine level of 1.8 may signal a different risk in an LVAD patient versus another patient on a minor trump. That's another important question. And also, since October of last year, the new heart allocation policy has been in place, which now defines LVAD patients to appear status three or four based on their complication profile. And it will be interesting to see how the new allocation system would impact patients are on LVAD support waiting for an organ. And it's possible that these patients may end up waiting longer compared to patients who are with cardiogenic shock and are assigned to higher tier status. And if LVAD patients wait longer as we see from this data, they will have worse posttransplant outcomes. It's going to be very interesting to see how the new allocation policy impacts. Another point I want to make is that with the recent MOMENTUM-3 trial patients receiving HeartMate 3 LVADs, had a 13.4% mortality risk at one year and this is actually lower than 17.6% mortality at one year in high risk LVAD patients in our study. Again, questioning transitioning from LVAD to transplant in high risk patients. Dr Mark Drazner: I might take a step back even further. It's an important, it touches on a critical question in my mind, which is if you have a patient who needs to go into transplant and they're not crashing and burning. I'm assuming if they're crashing and burning, you need to go onto an LVAD, the following comments won't apply to that group. If you're a patient who's relatively stable, is it a better strategy to try and get them to transplant directly? Or is it better to go through and VAD and then transplant them? And ultimately that strategy question I think would require randomization to really answer that. But the data that we have discussed today, I think are opening that question and touch upon that in terms of the strategy of the impact of bridging people with VADs itself, which is why I think this is such an important question. Dr Carolyn Lam: Thanks again, Mark and Veli. That was an amazing discussion. Thank you, audience, for joining us. You've been listening to Circulation On The Run. Don't forget to tune in again next week. This program is copyright American Heart Association 2019.
July 30, 2019 There are fewer and fewer compliments being given face-to-face. Why is that? Shark Week continues on Discovery Channel, so why not add a new breakfast cereal? (Huh?) What are the most overrated places to visit? We have a few to mention… Find out what’s wacky out there with our wacky stories of […] The post Mason On Demand: Fewer Compliments Being Given, Over-rated Places To Visit appeared first on Q105.
Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your cohosts. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: I'm Greg Hundley, Associate Editor of Circulation, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr Carolyn Lam: Greg, guess what? We are going to be talking later about non-inferiority trials. Now, you're going to go like, "Huh? What?," but then we see more and more non-inferiority cardiovascular trials. And do we really know the advantages and limitations of this type of trial design? Which is so important to understand, because we need to understand the factors that may impact our confidence and interpretation of these results. So, that's going to be a really important feature discussion, coming up right after our coffee chat. Greg, what are your papers? Dr Greg Hundley: Thanks Carolyn. Boy, I can't really wait to get to that feature discussion. That's something that we deal with all the time, and I look forward to that explanation and that discussion. I'm going to talk a little bit of basic science, with two papers right in a row. And the first one involves catecholaminergic polymorphic ventricular tachycardia through inhibition of calcium/calmodulin-dependent kinase II. The lead author is Dr Vassilios Bezzerides from Boston Children's Hospital. Carolyn, this paper focuses on treatment of catecholaminergic polymorphic ventricular tachycardia, an underlying diagnosis in at least 12% of pediatric patients who present with unheralded cardiac arrest. ICDs, as you know, are frequently implanted, but are problematic because of increased complication rates in pediatric patients, failure to convert ventricular arrhythmias, and the risk of fatal ICD-induced electrical storm. Modulating CaM Kinase II within the heart shows promise to treat this, but CaM Kinase II is essential in other tissues, most notably the brain. Dr Carolyn Lam: How interesting. So, what did the study show? Dr Greg Hundley: Well, the investigator used adeno-associated viral gene therapy, which is proven to be a safe and efficient vector for sustained gene transfer into many cell types to selectively inhibit CaM Kinase II in cardiomyocytes. They were able to express the specific CaM kinase II inhibitory peptide AIP in cardiomyocytes without significant extra cardiac expression, and an inhibition of CaM Kinase II effectively suppressed ventricular arrhythmias in a murine model of catecholaminergic polymorphic ventricular tachycardia after a single therapeutic dose. So thus, in animal models, delivery of a CaM Kinase inhibitory peptide by AAV represents a novel single dose gene therapy for catecholaminergic polymorphic ventricular tachycardia. How about that? Dr Carolyn Lam: Wow. You've got a second paper? Dr Greg Hundley: I sure do. So now we're going to jump into, again, looking at polymorphic VT from engineered human heart tissue. And this article is from Kevin Parker at Harvard University, "Modeling of Human Arrhythmias Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes has Focused on Single-Cell Phenotypes." With this said, it is important to realize that arrhythmias are emergent properties of cells assembled into tissues and the impact of inherited Arrhythmia mutations on tissue level properties of human heart tissue. And therefore, newer technologies are needed to develop more satisfactory therapeutic interventions. Ones that encompass all of the tissue, not just single cells. Dr Carolyn Lam: Interesting. So, what did this particular study do? Dr Greg Hundley: So, Carolyn, in this study, the investigators report on an optogenetically-based human-engineered tissue model of catecholaminergic polymorphic VT, which as we have discussed in the previous article is promoted by mutation of the cardiac ryanodine channel 2, which is promoted by mutation of cardiac ryanodine channel and triggered by exercise. They developed a human IPSC cardiomyocyte-based platform to study the tissue level properties and investigated pathogenic mechanisms in polymorphic VT by combining this novel platform with genome editing. The authors found that engineered heart tissue, fabricated from human pluripotent stem cell derived cardiomyocytes, effectively modeled catecholaminergic polymorphic VT caused by dominant mutations in the cardiac ryanodine receptor, including induction of arrhythmias by conditions that stimulate exercise. Using selective pharmacology and genome editing, the authors identified activation of calcium/calmodulin-dependent kinase II, or CaM Kinase II, and CaM Kinase II mediated phosphorylation of ryanodine at Serine 2814 as critical events that are required to unmask the latent arrhythmic potential of catecholaminergic polymorphic VT, causing ryanodine mutations, highlighting a molecular pathway that links beta adrenergic stimulation to arrhythmogenesis in this disease. Dr Carolyn Lam: Wow Greg! So, two very interesting and important linked genetic papers. Well, we're going to switch tracks a little bit and talk about, well, my favorite topic: heart failure with preserved ejection fraction and the whole complex issue of the diagnosis of this syndrome. Now we know that the diagnosis is kind of complex and there is currently no consensus but several proposed definitions. So how do the clinical and hemodynamic profile of patients vary across the different definitions of HFpEF? So, this question was answered by Dr Jennifer Ho from Massachusetts General Hospital and her colleagues, who examined consecutive patients with chronic exertional dyspnea and an ejection fraction above 50% who are referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. They applied societal and clinical trial HFpEF definitions and compared the clinical profiles, exercise responses, and cardiovascular outcomes by these different definitions. So, of 461 patients, 416 met the ACC/AHA definition, 205 met the ESC definition, and 55 met the HFSA criteria for HFpEF. The clinical profiles and exercise capacity varied vastly across the definitions, with peak oxygen uptake averaging 16.2 for those with the ACC/AHA definition and down to 12.7 in those satisfying the HFSA definition. Dr Greg Hundley: Wow. What a difference from these societies. Dr Carolyn Lam: Mm-hmm (affirmative). Dr Greg Hundley: So Caroline, it sounds like they looked at all comers with exertional dyspnea. Now how about those that had hemodynamic evidence of heart failure with preserved ejection fraction? Dr Carolyn Lam: Yeah, good question Greg. So, you caught me telling you that all these patients had hemodynamic cats as well, and a total of 243 had hemodynamic evidence of HFpEF, which was defined as an abnormal rest or exercise feeling pressure. Of these, 222 met the ACC/AHA criteria, 161 met the ESC criteria, and only 41 met the HFSA criteria. Over a mean follow-up of 3.8 years, the incidents of cardiovascular outcomes range from 75 for the ACC/AHA criteria to 298 events per thousand-person years for the HFSA criteria. The application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication. So in summary, the authors demonstrated significant diversity in the number of patients meeting HFpEF criteria. And using different HFpEF classifications variably enriched for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure really highlighted the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF sub-grouping to test therapeutic interventions. Now, these are all discussed in an important accompanying editorial by Michele Senni, Sergio Caravita, and Walter Paulus. Dr Greg Hundley: Wow Carolyn. It appears, depending upon the definition, we could really classify patients drastically differently. Dr Carolyn Lam: Yeah, an important paper indeed. And again, I would strongly encourage everyone to read that editorial as well. For my second pick, we're going to switch to CPR in children. So these authors, now led by Dr Rohan Khera from UT Southwestern, examined the prevalence and predictors of survival of children who progress from bradycardia to pulselessness in in-hospital cardiac arrest despite cardiopulmonary resuscitation. So they looked at almost 5,600 pediatric patients age more than 30 days to under 18 years of age, who received CPR at hospitals participating in the Get With The Guidelines - Resuscitation during 2000 to 2016 each CPR event was classified as bradycardia with pulse, bradycardia with subsequent pulselessness, and initial pulseless cardiac arrest. And the authors assessed for risk adjusted rates of survival to hospital discharge. Dr Greg Hundley: So Carolyn, what did they find? This is really interesting. Dr Carolyn Lam: Well, among hospitalized children in whom CPR was initiated, half had bradycardia with poor perfusion at the initiation of chest compressions and nearly one third of these progressed to pulseless in-hospital cardiac arrest despite CPR. Survival was significantly lower for children who progressed to pulselessness despite CPR compared to those who were initially pulseless. So, these findings suggest that pediatric patients who lose their pulse despite CPR are at particularly high risk and require a renewed focus on post resuscitation care. Dr Greg Hundley: Very interesting, Carolyn. Dr Carolyn Lam: Well, that wraps it up for our discussion. Let's go onto the featured discussion. Shall we, Greg? Dr Greg Hundley: You bet. Dr Carolyn Lam: Non-inferiority cardiovascular trials are increasingly being published and in the highest impact journals. Yet how much do we really know about these designs of the trial, of the non-inferiority trials? Well, I have to admit not much in my point of view, and I was so pleased to see our feature discussion paper really published in this week's journal, which really digs deep into non-inferiority trials and talks about time trends and perhaps some lessons that we should all bear in mind when we look at these. I'm so pleased to have the first author, Dr Behnood Bikdeli, to tell us about the study. And he is from Columbia University Medical Center, New York Presbyterian Hospital, Yale Center of Outcomes, Research and Evaluation Core, as well as the Cardiovascular Research Foundation in New York. We also have Dr Naveed Sattar, associate editor from the University of Glasgow. Behnood, could you tell us, so what made you look at this question and what did you find? Dr Behnood Bikdeli: For a while we've been very interested in profiling the cardiovascular trials, trying to understand a little better, what are the specific characteristics of the major child that we rely upon for research but also for clinical practice? Years ago, we did some studies for surrogate outcome trials and this, let's just say subsequent piece, where we tried to look into a randomized cardiovascular trial that use a non-inferiority design. We had a series of features in terms of quality metrics and methodological metrics that we wanted to look into. The over eight almost 27-year period, we identified 111 of these trials. Reassuringly, most of these trials inherited several important quality and methodological metrics that we were looking into. However, we also saw a significant room for improvement. There were quite a few quality or methodological metrics that some of these trials were not adhering to and we think it's important because ultimately for the design reporting and last reading of these trials, knowing these pluses and minuses would help inform people. Dr Carolyn Lam: That's great, Behnood. Now for those of us listening who don't think about this every day, could you give us some examples of the top errors perhaps to look out for? Dr Behnood Bikdeli: For example, in the typical superiority trials, when we want to test an intervention a versus intervention B, all that matters is we do a very good and adequately sized trial and rest of it is up to the study and how it goes to see whether or not something panned out. There was a significant difference between the new intervention versus the older ones, but in non-inferiority trials we have something called the non-inferiority margin and that's very highly relevant when it comes to the outcome that you're assessing when it comes to the ultimate results of the trial. If the investigators choose a very lenient y non-inferiority margin, they may end up calling an intervention non-inferior. They may give it a pass. While in reality the intervention has quite a lot of a risk or harmful profile compared with standard of care. But in the other side, as a clinical example, we have several interventional tools at hand, like transcatheter aortic valve replacement. Most of the indications where it's currently used came from large bell designed non-inferiority trials. Where they showed that it was almost as good as surgery, in some cases better, but also it had a lot of ancillary advantages. Dr Carolyn Lam: Thanks, Behnood. And you know here, I just want to call out to the readers. You have to look at this paper. Look at the tables and figures which are really so helpful. And Naveed, can I bring you in on this now? I mean, I just love this paper. It's such an important topic and I've never seen it addressed like this before. Could you tell us a little bit about what the editors discussed when we looked at this? Dr Naveed Sattar: I've been involved in a few non-inferiority trials and some of the factors that many of us discuss and some of course associated, sort of our clinical trials, and I've been involved normally in superiority trials, but increasingly we have cut our teeth in non-inferiority trials. So, some of the points that the paper picks up resonated well with us in terms of, one of the examples was Behnood and his team found that around about 40% of trials didn't even justify what their non-inferiority margin was. And that's something I've actually had detailed discussions involved in various trials with. And that's a really important point, but it isn't a, you have to be able to justify why you choose particular margin and what that margin would mean to the community. Otherwise you potentially could just pick something out there which really doesn't allow you to make a really strong non-inferiority claim. And I think that's one of the factors that you found, Behnood. Is that correct? Behnood Bikdeli: Absolutely. And that's a great point. Thank you. To us, there were two things about it. One was whether or not they provided any detailed justification for it exactly as you said, not that they're just picking up something because that's the sample size that they could achieve or that's the number that they felt comfortable with. But also the second piece of it, a respective of how they calculated or came up to the number, their readers have a right to know how this was calculated or were this came from, so it's the reporting part of it. Sometimes they reported both in the published paper and a study protocol or a design paper. Sometimes it was only in one of them. Sometimes as you mentioned, it was not mentioned in either, which puts the reader in a very difficult situation. So we think, and these were the best of the best trials in the highest impact journals. Probably if we look high and low elsewhere it's going to be even more challenging. So, we think there's a lot of room for improvement for the readers to expect cleaner, more comprehensive papers to come, but also for the trialist to report them with more clarity. Dr Naveed Sattar: And going forward, issue a nice figure that shows that the trend is that we are going to see more of these trials probably because you've got lots of better treatments now. So, you know it's getting harder, in the sense, in many areas of cardiovascular medicine to show superiority. So, there is a need for more trials which actually show benefits beyond just perhaps the main outcome in ways that you've explained in the particular paper. Do you think the FDA does enough in this particular area in terms of this helping investigators decide what the non-inferiority margins are? Or is that something in terms of the quality of the trials that needs a bit more investigation? I think your papers partly are pushed to say, "Actually we need to do these better. We need to justify them better. We need to look at them better." Because actually they do have a greater influence going forward. Dr Behnood Bikdeli: First, I cannot agree more. We are going to see a lot more of non-inferiority trials sort of, maybe because we have reached a ceiling effect when traditional intervention for superiority, but there's a lot of room to find interventions that are at least as safe or as good but have a lot of side advantages and ancillary benefits that's happened with some of the anticoagulants among other therapies available. In terms of the regulatory aspects, one of the things we were fortunate about was within our team, we had people with expertise on the trialist side while communicating with the regulatory bodies and also from people who were consulting to the FDA for assessment of non-inferiority trials. So, we were fortunate to look into several of the methodological or quality metrics that were being thought of and we consulted with the in-source guidelines and FDA guidelines. That said, I completely agree that, for example, the suggestions that you provided in one of the tables could hopefully help shape some of these trials in a more rigorous way. Or at least a reporting, which is also an important piece, would be more transparent ultimately for the readership. Dr Naveed Sattar: Absolutely. And transparency is really pivotal so that the readers completely understand what was done, what was predefined, and what was found so that they can make a proper judgment. And probably the final question I have in terms of, you make a good point that actually if the trials are not done well and there's a bit of slippage either in terms of loss of data or methodological issues, that then really pushes a trial towards a "no", in a sense you get a false reassurance of non-inferiority, but partly because the methodology wasn't robust enough. And it's really very critical for these trials, perhaps at least as critical as they are in superiority trials, but perhaps even more so. Is that a fair judgment? Dr Behnood Bikdeli: No, no, no. You're absolutely right. That's another very important point in the typical superiority trial, if any bias drives the results toward no difference. Investigators are naturally guarding against that because it's going to be very problematic in non-inferiority trials. Depending on the effect measure that they choose, it could actually falsely favor the intervention of interest because it might show a false assessment of non-inferiority, and there are ways to work around it. There are ways to correct for it, such as choosing both absolute and relative effect measures, which practically addresses this concern. Again, gets back to the importance of appropriate design and appropriate transparency to report the results in a robust way, both intentions to treat and has treated or per protocol, both relative effect measures and absolute effect measures. Dr Naveed Sattar: My sense of and getting back to you, but I think this will be a really seminal paper for the community to look at and really help us as a community to improve our conduct of such trials in the future because there will be more of these coming forward. Dr Carolyn Lam: And I couldn't have said that better, Naveed. I think the take home message is right there. Pick it up, have a look and especially have a look at those tables and figures. It's really going to help you read many, many journals. Thank you so much, Naveed and Behnood. Thank you audience for joining us on Circulation on the Run. Talk to you next week. This program is copyright American Heart Association 2019.
Download MP3 留学早々、Momoはさっそく大学の宿題に取り掛かろうとしています。そんな彼女を悩ませるのが、爆音で音楽を聴いている大学寮の隣人。堪りかねたMomoは隣人のドアをノックし、静かにしてもらうようお願いします…。 「アメリカ★は愉快だ」は、英語は上達したいけど少し苦手…という方々を対象にしたシリーズです。シャドウイングの練習もありますので、しっかり聞いて、しっかり声に出して練習してみましょう。 5: Dorm Friends (Momo and Carson) W: Ugh, the neighbors have been blasting music for over an hour now! I hate confronting people, but I really wanna get started on this homework. (knocks on door, but no answer) Um, excuse me… Hello? HELLO? M: (turns music down, opens door) Huh? What’s up? W: I, uh… Sorry to bother you, but… I’m trying to do some homework, and you’re being kind of loud. Could you turn your music down a little? M: Oh dang, my bad, dude! Yeah, for sure, I’ll turn it down. W: Um… OK. Thanks. See you. M: Hey, wait! Since we’ll be living next to each other for a year, we should probably know each other’s name! I’m Carson-- yeah, (sarcastic) haha, like Carson City, the capital of Nevada. My parents hate me. W: Oh. I’m Momoko, but you can call me Momo. M: Right on. Nice to meet you, Momo. So, where are you from, Momo? W: I’m an exchange student from Japan. M: Whoa, great! W: Anyway, I’ve got to get back to my homework now… M: It’s only the first week of school, how much homework can you have? … Well, see ya around! (Written by Jazmin Boulton)
Download MP3 留学早々、Momoはさっそく大学の宿題に取り掛かろうとしています。そんな彼女を悩ませるのが、爆音で音楽を聴いている大学寮の隣人。堪りかねたMomoは隣人のドアをノックし、静かにしてもらうようお願いします…。 「アメリカ★は愉快だ」は、英語は上達したいけど少し苦手…という方々を対象にしたシリーズです。シャドウイングの練習もありますので、しっかり聞いて、しっかり声に出して練習してみましょう。 5: Dorm Friends (Momo and Carson) W: Ugh, the neighbors have been blasting music for over an hour now! I hate confronting people, but I really wanna get started on this homework. (knocks on door, but no answer) Um, excuse me… Hello? HELLO? M: (turns music down, opens door) Huh? What’s up? W: I, uh… Sorry to bother you, but… I’m trying to do some homework, and you’re being kind of loud. Could you turn your music down a little? M: Oh dang, my bad, dude! Yeah, for sure, I’ll turn it down. W: Um… OK. Thanks. See you. M: Hey, wait! Since we’ll be living next to each other for a year, we should probably know each other’s name! I’m Carson-- yeah, (sarcastic) haha, like Carson City, the capital of Nevada. My parents hate me. W: Oh. I’m Momoko, but you can call me Momo. M: Right on. Nice to meet you, Momo. So, where are you from, Momo? W: I’m an exchange student from Japan. M: Whoa, great! W: Anyway, I’ve got to get back to my homework now… M: It’s only the first week of school, how much homework can you have? … Well, see ya around! (Written by Jazmin Boulton)
MEME SEASON. Happy December, the season of the holiday memes. Huh? What’s a meme, and what’s it got to do with the holidays? A meme is an element of culture or system of behavior that is passed from one individual to another by imitation. This episode explores the beliefs and “festive” images that bombard you during the December holidays. They are meant to cheer you up. But they can play havoc with your emotions if you are not mentally prepared for them. Here’s some of the fun stuff you’ll hear and learn about as we undress the holiday memes: The origin of the word meme How things we hate can become things we love overnight Why all beliefs are made up stories The media holiday traps to avoid if you want to feel good The 5 biggest memes guaranteed to spoil you holidays Why no one is better off than anyone else Plus, you will discover 12 “weapons of mass empowerment” that will lift you spirits high during the upcoming holiday season, In fact, they can empower you for the rest of you life.
The Vikings loss to the Bills will go down as the day the Vikes lost the season, but it sure was fun being at the Colesium Thursday night! I didn't expect a Vikings win, but the game was much more entertaining than I expected. Both defenses ate shit, but the Rams made a couple more plays, and got the W. Can everybody who counted the Patriots out (again) eat a shit sandwich? This is the same record the Pats sat at after the "We're on to Cincy" game vs the Chiefs, and I see the same end-of-season-result.. a Super Bowl. They get Edelman back this week to go along with Gordon, Gronk, White, Michel, Hogan, and Mr. Brady. Fuck all of you who wrote them off (again). Please pump the brakes on Patrick Mahomes. I love the kid, but I just saw someone on TV ask if he's the best QB in the NFL. Huh? What fucking world are we living in? The kid's played 4 games, and we're putting him in the HOF? Let's see how he does this week vs Jacksonville, and then (not really then) we can talk.
If you read the title of our podcast this week and thought, "Huh? What does politics have to do with parenting," you aren't alone! Elle asks this too after Abigail gets an email about parenting feeling "radical." Do we mean marching for rights, or championing parenting causes? Not exactly. We are talking about the change you are making in the world every day. Through parenting. What Does My Parenting Have to Do with The World? Did you ever feel life got, kind of, small, after you became a parent? Elle and Abigail talk about how easy it was for them to get caught up in the daily grind of parenting - the cutting up the quesadillas, the back and forth between school and activities, the constant tidying toys and checking schoolbags - and the negative impact that can have on us as parents. What changed all that for them was realizing that when a parenting approach fits with our true selves, our ideas and philosophies, we can marry our before-parent selves with our now-parents selves. That does seem a little, well, radical! But there's more. In showing up, day after day, in allowing your child's feelings, in responding with empathy, and in making decisions for and with our kids, our role as parents can have a bigger footprint. For sure, it starts small, in the playground, or at the park, when another parent notices you responding playfully, or sitting quietly supporting a child as they cry, but it soon moves out. Perhaps it's your child next time that sits with another while they cry, and then later, it's your child sitting with their child, your grandchild, and their friends noticing. The circles spread. That, to us, feels like making a difference, making an impact. All the small decisions you bring to raising kids can have a big, good impact - and it's an idea worth remembering the next time you slice a quesadilla. Join us this week and feel brighter about your everyday role as a parent. Help Hand in Hand Make Positive Change For 29 years, Hand in Hand Parenting has inspired change. Please help us keep that change going. Your gift today helps us provide free resources, programs, and support to parents in communities that need it most. The 29 stories Elle mentions today are here - also the place you can give a gift too! Join the Hand in Hand Community We’d love to hear about your parenting challenges. You can follow Hand in Hand on Facebook, Twitter, Pinterest, and Instagram. Be sure to drop Elle and Abigail a message Sign up for our Monthly Newsletter
Many questions are being asked about the future of several coaches in the SEC, meanwhile Alabama and Auburn continue to improve. Huh? What?! All of this and more from a fan's perspective. Online at www.FansDownSouth.com
#71: Roger Whitney is known as the "retirement answer man." "All I think about, all day long, is how to make that [retirement] transition successfully," he says. But he holds a dirty little secret. "I don't believe in retirement. And the most successful clients that I work with ... technically they're retired, but they're still working." Huh? What does that mean? In today's episode, Whitney and I discuss the nuances of 21st-century modern retirement -- and how this ain't nothin' like the traditional retirement that you've been taught to expect. Enjoy! ______ For the "WTF?" -- Vocabulary guide from this episode - visit http://affordanything.com/episode71
You yell "barracuda", everybody says, "Huh? What?" You yell "shark", we've got a new episode of Diminishing Returns on our hands, in which Calvin Dyson, Sol Harris and Allen Turing talk through the Jaws movies, culminating in 1987's infamous Jaws: The Revenge, before pitching how they'd continue the franchise.
Sometimes what you think about God reveals something about what you think about yourself or the world around you. In this passage, a petulant God plans to rage destruction upon the Hebrew people but Moses gets God to change God’s mind. Huh? What might we learn about God—and ourselves—from that. Dive in with Brian and Fr. Shay and let’s unpack it […]
In this episode of the Cultural Wormhole podcast it's do-over time once again for DC Comics as Antony, David, and Paul take a look at the first crop of books from the DC Universe: Rebirth. The Cultural Wormhole Grading Scale! 1. Yes! Enthusiastically on board! 2. Liked it. Will give it a three issue test drive. 3. Meh. Didn't rock my world. 4. Huh? What the hell is going on here? 5. Garbage. DC Universe: Rebirth - DC Universe: Rebirth #1, Batman: Rebirth #1, Green Arrow: Rebirth #1, Green Lanterns: Rebirth #1, and Superman: Rebirth #1.
Photo credit: Aviation Herald/Google Earth The crew for this week's episode: Captain Jeff, Dr. Steph, and Captain Nick Airline Pilot Guy App - Android Airline Pilot Guy App - iPhone/iPad 32R Aviation Apparel Promo code APG gets you 10 percent off! Nick’s chat with Mike Young of Aircrew Interviews - http://www.aircrewinterview.tv/ This week's Plane Tails by Captain Nick is entitled "An Interview with WWII Pilot Andy Anderson - Part Three" NEWS EgyptAir 804 Crash "Aviation Expert" Flowchart Multiple Failures Put Learjet 35A into the Atlantic SERIOUS INCIDENT Boeing 757-224, N41140 80 NM Southwest of Dublin, Ireland 20 October 2013 FEEDBACK Kevin - Problems at the Gate Tim Van Raam - Fatal Crash involving FA-18 Big data Ken - China To Build 66 New Airports Over The Next Five Years Larry Gregory - Speed Enforced By Aircraft Mark in Ottawa - RCAF C-130 Flies into History Chattanooga TIM - August 21 2017 500 days away Mike - Exposure to jet fuel, not just noise, contributes to hearing problems. Huh? What did you say? Zach - Student Pilot Certificate and Solo Flight on 16th Bday Adam - Feedback on Concorde ops Jake - Frozen Door Kevin - QF32 Nev - Pilot Fatigue Richard - Feedback Adam - LAX by Hot Snakes (Aviation Themed Songs) Will - Fear of Flying Conquered! Bill - Wind Shear Alerts Matt - Anti-skid Braking Captain Al - Papal Plane Feedback The Guru - New Grab App for ordering food at the airport APG Fak Checkers! #4 Ham Radio Jim - APGS Cure: Bourbon! James - Military to Civilian Transition Episode 216---from "Blaster" Bill Jason Wu - Oral Hygiene, Physical Requirements Nicnacjak - Looking For Podcast Host! Nicnacjak's email: nicnacjak@gmail.com VIDEO Audible.com Trial Membership Offer - Get your free audio book today! Give me your review in iTunes! I'm "airlinepilotguy" on Facebook, and "airlinepilotguy" on Twitter. feedback@airlinepilotguy.com (304) 99-PILOT (304) 997-4568 airlinepilotguy.com ATC audio from http://LiveATC.net Intro/Outro music by Tim Brown, BrownHouseMedia, iStockphoto.com Copyright © AirlinePilotGuy 2016, All Rights Reserved
From The Oakland Police Department via Nixle The Oakland Police Department would like to apologize for the recent press release addressing traffic safety enforcement during the Cinco de Mayo holiday. We acknowledge that the language in the message sent was completely insensitive to the cultural holiday. We have worked extensively to build trust with all our communities and value the amazing cultures that make up the heart of our City. We are taking appropriate steps to insure that this does not happen again. Our intentions were to raise awareness about drunk driving and notify the community of traffic safety during the important holiday. As for every holiday and celebration, we want to remind everyone to celebrate responsibly and safely. "We acknowledge that the language in the message sent was completely insensitive to the cultural holiday."...HUH??? What in the world did the OPD say????? “Cinco de Mayo has become synonymous with festive fiestas and salty margaritas,..." Well that's true. I don't understand why police leaders feel the need to apologize because someone gets offended over something that is not offensive. The statement, the press release, the stats.....everything was informational, not confrontational and didn't single out a class, culture or group. A group on Facebook were the ones offended. Literally saying that the police were targeting Latinos What??? Oh come on. Yes, someone put their own words into the release and that's what the police apologized for. Then....I saw it. What led to the reversal and apology. A Facebook Group posted it and there were 14 comments and 51 reactions. Oh the horror!!! And not all the comments were against it! Oakland City Councilman Noel Gallo says the police department’s warning about the dangers of drinking and driving during Cinco de Mayo twisted the holiday’s rich cultural history into a caricature. No it didn't!! Taco Bell has done that along with every other marketing company that is trying to gain market share on social media for the 5th of May. Leaders lead.
Almost immediately after the March Fed meeting, the FedHeads began speaking to talk up the next hawkish point of view. Why? They were worried about sounding too dovish in the March meeting statement. Huh? What happened to the good ole' days where there was little transparency and they did not care. Investors were better because they worried about less. Listen in and let us know!
Vani makes her living making food companies angry. She challenges them on the chemicals they use to make manufactured food more addictive, longer-lasting and as cheap as possible to produce. And she’s not quiet about it. Is she alarmist? Unabashedly, yes. Her headlines are notoriously, um, cloying at times. (Did you catch the infamous “Do You Eat Beaver Butt?” post?) ...And it would be easy to write her off as an obnoxious headline-grabber who is just looking to generate a following by making big companies like Kraft, Starbucks, Kellogg, and General Mills look bad. Except, isn’t there something backward here? Vani Hari receives death threats on a regular basis because she is telling the world what food manufacturers opt to put in our food supply. Huh? What’s wrong with this picture? From her site: Back when Congress gave the FDA authority over food additives (in 1958), there were about 800 additives. Today, the number of known ingredients has swelled to more than 10,000 and continues to grow. Even the FDA’s Deputy Commissioner, Michael Taylor, recently said: “We simply do not have the information to vouch for the safety of many of these chemicals… we do have questions about whether we can do what people expect of us”. - Washington Post Additional resource: “Food additives on the rise as FDA scrutiny wanes” - Washington Post Well, maybe that isn't as scary as it sounds, because apparently new food ingredients are commonly approved by the manufacturer themselves, and not by the FDA. So, that's helpful, right? [What the ???] So, what does this mean to you? Why should you care? Here are a few reasons:- hyperactive children- asthma- diabetes- cancer- eczema- digestive disease- premature aging- obesity- lethargy…are all on the rise. Like, WAY. ON. THE. RISE. And, according to some experts, 70% of the average American diet now comes from processed food. Interestingly, a research review of 172 clinical studies published in the Journal of American Clinical Nutrition concluded that "virtually all chronic diseases are partially caused by our modern diet of engineered foods." Related? You decide. And isn't that the point? Do you have to like the Food Babe? Nope. Do you maybe want to listen to the information that she’s making public, then decide for yourself whether you opt in or out of the chemical s&^% storm that makes up the majority of processed foods? Uh, yeah. Please do. And, if you’re not a little riled up after hearing this episode, then you weren’t listening. All of the resources mentioned in today's show can be found at www.OnAirwithElla.com And....join the Ella's "Fellas & Bellas" on Facebook for updates, photos, tips and resources that you won't find anywhere else!
'used to' for past habits The text is called ‘Guys used to wear hats’ and this talks about – yep, you guessed it – how people used to wear hats once upon a time, but it seems this is no longer true. But first let’s talk about the grammar, used to. You know how the past tense talks about a finished or competed action that we also know when it happened, like I ate cereal for breakfast? Well, used to talks about past routines or past habits or past situations that were regular but that don’t happen anymore now. So,’ I used to wear short pants when I went to school (but I don’t anymore)’. Or ‘I used to work out every Saturday (but I don’t anymore)’. Used to shows the difference between the past and the present, saying that something was regular but it stopped. You can make this clearer by adding a negative phrase like ‘I don’t now’, or ‘I don’t anymore’.  You can also use it to talk about states that are no longer true, like ‘I used to be fat but then I went on this great exercise program’. To make it is pretty simple – just add used to in front of the base form of the verb like this – ‘I used to love her’. To make the negative, just put didn’t in front of used to, like ‘I didn’t used to love her’ what does this mean? It means I do now! You can also use never instead of didn’t for the same meaning, so ‘I never used to love her’. A quick warning about spelling for negatives – the past in used to is ed, in the negative it loses the d and the past is shown in the didn’t, so negatives with didn’t lose the d. But…with never, used to keeps the d. Why is that? Because it still shows the past. To make questions just put did in front of used to, so ‘When you were a kid, did you use to play with the other kids or stay at home?’ One interesting point (well, for saddoes like me, anyway) is that you can use would instead of used to for nearly exactly the same things except for one exception. So for example, you can say ‘I would wear shorts to school’. But the problem is that you can only use would when it is a regular, repetitive action, NOT a state. Huh??? What’s the difference? Well, we can say ‘I used to’ or ‘I would’ or ‘I’d wear shorts’ because it is an action. But what about a state? We can’t use would here. Try this one – ‘I used to be happy before I met you’, then change it with would. ‘I would be happy before I met you.’ Nope, it doesn’t work. So, would can be used in most places where used to can be used except for state of being. Gotta love all the little exceptions in English. OK, so to summarize, we can use used to to talk about routines and habits that are no longer true. Watch out for the spelling in the negative and the question form as it drops the d. Lastly, watch out you don’t confuse it with two verbs that sound similar but have different meanings. These are, get used to doing something, and be used to doing something. Now, on to the comprehension text. This little text talks about how in the past people had a regular habit of wearing hats but now – yep – just look around you, they don’t seem to wear hats so much. Now, why is that? Listen to the text and find out. And don’t forget to download the transcript from our website, New English Academy.com and check out the great online learning activities and games and tests. Guys used to wear hats There was a neat little article on NPR the other day about how, in the past, men always used to wear hats, but now they don’t. I know my grandfather had some ideas about fashion and what men should wear. For example, he thought gentlemen shouldn’t show their braces (the elastic things that hold your pants up) in public. And he especially felt that going out without a hat was like walking around in the nude. People used to think that way, once upon a time. If you look at old movies and pictures of until about 40 years ago, you can see that guys always used to wear hats. People used to have hats for different occasions, so you had a collection. For example, you used to have a going-to-church-type hat, a going-to-work-type hat, a working-in-the-garden-type hat, etc. In fact, there even used to be a TV commercial in the UK for beer where a middle-aged wife wants to know where her husband has gone so she looks at the hat rack by the front door. His fishing hat is missing so she assumes he has gone fishing. The commercial ends of course with our hero sitting in a pub, drinking his favourite beer and wearing his fishing hat! The NPR article gave various reasons for why hats used to be popular and why men no longer wear them. Obviously, they keep your head warm and dry and protect you from the sun. And that was fine when people used to spend a lot of time outdoors, either travelling to work or working outside. But nowadays people drive to work, and it is pointless and even uncomfortable to wear a hat in your car. I guess people don’t go outside as much as they used to. Also, we have good sun-glasses now to protect our eyes. Another reason why men don’t wear hats so much these days is that hair-style is more important than it used to be. Wearing a hat gives you hat-head, where your hair is all mussed up. Lastly, a hat is an extra thing to carry around, something else to worry about when we don’t need extra hassle. Often things these days are designed to be functional but pocket-sized. I haven’t seen a good-looking hat you can get in your pocket yet. The only guys I see who still regularly wear hats are blue-collar American men, with their bill-caps or baseball caps. They wear them wherever they are, outside, when they are driving, or indoors. At sports events they all stand up and remove their caps and place them over their hearts when they hear the national anthem. They each probably have just the one cap which they wear day in, day out. Perhaps like my grandfather they feel naked if they go out without their cap.  I have to wonder, how will our world change? What do we take for granted now that will disappear in the future? Will our grandchildren look at movies and pictures of us now and talk about what we used to do that they don’t do anymore? What will change, do you think?Â
Huh? What happened to episode 2, you say? Long story short is that it’s locked away on broken computer, but should hopefully get recovered. In the meantime, we went ahead with episode 3, going over an old panel about international reinterpretations of … Continue reading →
We're back from a one-week break! Did you miss us? We certainly missed you! Now we've got lots of catching up to do, so let's skip the topical discussion this week and jump straight into the games we've played. First up, we finally get our grubby paws on Ni No Kuni: Wrath of The White Witch for PS3 and everybody's got an opinion on that. Then Joel discovers Minecraft anew on an OMGeek Tekkit Lite server, Dave gets creative with DrawQuest, and Lisa gets destructive with Little Inferno. Let's also talk Gaming News. How about that PS4 announcement, huh? Huh? What do you think about that feature-packed controller? Do you want your console experience to be more social? And what about those exciting upcoming games: Deep Down, The Witness, Watch Dogs and Diablo III? Okay, maybe not Diablo III. Tell us what you think by writing to us at hello@staringatscreens.org! In other news the perennial Plants Vs. Zombies is free for a limited time on iOS! Finally we want to give a big shout out to all our new listeners and those who found us via our Swagathon or via our 15 minutes of fame on /r/Gaming. Welcome, Redditors, and we hope you like what you hear enough to stay. Forever. Some links: Didn't wake up early to watch it live? Here's the PS4 Announcement Abridged to get you caught up quick. Okay, that was a joke, but here's a serious article about mitigating your PS4 expectations despite the post-announcement euphoria. Indie Royale Chosen Bundle where you can get the short but very funny DLC Quest (Not long to go! 2 days left at the time of posting.)
Level 6 Lesson 12 / What do you mean? What does that mean? / 무슨 말이에요? In the previous lesson, we introduced how the phrase “I mean...” can be translated into various Korean expressions. In this lesson, let’s take a look at how to ask someone in Korean, “what do you mean?”, “what does that mean?”, or “what’s that suppose to mean?” when you can’t believe what you’ve just heard or when you don’t understand someone’s remark or point very well. 무슨 말이에요?[mu-seun ma-ri-e-yo?]= What do you mean? = What’s that supposed to mean?= What does that mean? = What are you talking about?무슨 [mu-seun] means “what kind of” or “which” and 말 [mal] means “word” or “language”. Therefore, 무슨 말 [mu-seun mal] means “what word” “which word” or “what kind of things (to be said or written)” 무슨 말이에요? literally means “what word/language is it?”, but it is more correctly translated as “What do you mean?” You can use 무슨 말이에요? when you are in disbelief after you hear someone say something or when you have not clearly understood what they mean. Ex)A: 카메라 팔 거예요. ( I’m going to sell my camera.)B: 무슨 말이에요? 카메라도 없잖아요. (What do you mean? You don’t even have a camera!) 무슨 소리예요?[mu-seun so-ri-ye-yo?]무슨 소리예요? is the same as 무슨 말이에요? but it is less formal and less polite. Therefore, it is not advised to use it to someone older than you or someone you’re supposed to be polite to. This is because 말 means “words”, but 소리 means “sounds”. You don’t want to refer to the words of the other person as mere “sounds”. You can use 무슨 소리예요? more safely, however, when you are literally saying “What’s that sound?” 무슨 말씀이세요? [mu-seun mal-sseu-mi-se-yo?]In Korean, there are many ways of making a phrase “honorific” and one of the ways is to use “honorific” nouns. 말씀 is the honorific version of 말. How to literally ask “What does this mean?”As we’ve introduced in the previous lesson, when you want to LITERALLY ask what a certain expression means, you can use the expression “무슨 뜻이에요? [mu-seun tte-si-e-yo?]”Sample Sentences1. 네? 그게 무슨 말이에요?[ne? geu-ge mu-seun ma-ri-e-yo?]= What? What do you mean? = Huh? What does THAT mean?2. 그만둘 거라고요? 갑자기 무슨 말이에요?[geu-man-dul geo-ra-go-yo? gap-ja-gi mu-seun ma-ri-e-yo?]= You are going to quit? What do you mean all of a sudden?3. 무슨 말이에요? 제가 왜요? [mu-seun ma-ri-e-yo? je-ga wae-yo?]= What do you mean? Why (do) I (have to …)? = What do you mean? Why me?4. 무슨 말인지 잘 모르겠어요.[mu-seun ma-rin-ji jal mo-reu-ge-sseo-yo.]= I’m not sure what you mean.= I don’t know what you are talking about.5. 무슨 말인지 알겠어요. [mu-seun ma-rin-ji al-ge-sseo-yo.]= I know what you mean.= I understand what you are saying.
Level 6 Lesson 12 / What do you mean? What does that mean? / 무슨 말이에요? In the previous lesson, we introduced how the phrase “I mean...” can be translated into various Korean expressions. In this lesson, let’s take a look at how to ask someone in Korean, “what do you mean?”, “what does that mean?”, or “what’s that suppose to mean?” when you can’t believe what you’ve just heard or when you don’t understand someone’s remark or point very well. 무슨 말이에요?[mu-seun ma-ri-e-yo?]= What do you mean? = What’s that supposed to mean?= What does that mean? = What are you talking about?무슨 [mu-seun] means “what kind of” or “which” and 말 [mal] means “word” or “language”. Therefore, 무슨 말 [mu-seun mal] means “what word” “which word” or “what kind of things (to be said or written)” 무슨 말이에요? literally means “what word/language is it?”, but it is more correctly translated as “What do you mean?” You can use 무슨 말이에요? when you are in disbelief after you hear someone say something or when you have not clearly understood what they mean. Ex)A: 카메라 팔 거예요. ( I’m going to sell my camera.)B: 무슨 말이에요? 카메라도 없잖아요. (What do you mean? You don’t even have a camera!) 무슨 소리예요?[mu-seun so-ri-ye-yo?]무슨 소리예요? is the same as 무슨 말이에요? but it is less formal and less polite. Therefore, it is not advised to use it to someone older than you or someone you’re supposed to be polite to. This is because 말 means “words”, but 소리 means “sounds”. You don’t want to refer to the words of the other person as mere “sounds”. You can use 무슨 소리예요? more safely, however, when you are literally saying “What’s that sound?” 무슨 말씀이세요? [mu-seun mal-sseu-mi-se-yo?]In Korean, there are many ways of making a phrase “honorific” and one of the ways is to use “honorific” nouns. 말씀 is the honorific version of 말. How to literally ask “What does this mean?”As we’ve introduced in the previous lesson, when you want to LITERALLY ask what a certain expression means, you can use the expression “무슨 뜻이에요? [mu-seun tte-si-e-yo?]”Sample Sentences1. 네? 그게 무슨 말이에요?[ne? geu-ge mu-seun ma-ri-e-yo?]= What? What do you mean? = Huh? What does THAT mean?2. 그만둘 거라고요? 갑자기 무슨 말이에요?[geu-man-dul geo-ra-go-yo? gap-ja-gi mu-seun ma-ri-e-yo?]= You are going to quit? What do you mean all of a sudden?3. 무슨 말이에요? 제가 왜요? [mu-seun ma-ri-e-yo? je-ga wae-yo?]= What do you mean? Why (do) I (have to …)? = What do you mean? Why me?4. 무슨 말인지 잘 모르겠어요.[mu-seun ma-rin-ji jal mo-reu-ge-sseo-yo.]= I’m not sure what you mean.= I don’t know what you are talking about.5. 무슨 말인지 알겠어요. [mu-seun ma-rin-ji al-ge-sseo-yo.]= I know what you mean.= I understand what you are saying.
Every television show has a "showrunner" -- one person who sits at the nexus of the writers, directors, cast, crew, and studio and network executives and call the shots. As the showrunners for Stargate SG-1 and Stargate Atlantis, executive producers Brad Wright and Robert C. Cooper make the series happen. GateWorld recently sat down with Wright and Cooper at their home base -- the famed Stargate production offices in Vancouver, British Columbia! Thanks to the generous gift of their time and candor, we are pleased to present the complete interview in this 3-part series. For the first time ever, you can sit in on a conversation about the past, present, and future of the Stargate franchise inside the offices of the shows' creators. In part one of our interview, the executive producers reflect on the two shows' accomplishments in Season Eight and Atlantis's first year, and setting up a new enemy and a new environment for telling stories in Season Nine. (Beware of some minor spoilers for the new season's first three episodes.) They also talk about the very real necessities of science fiction television production, about which viewers are often unaware. GateWorld's interview with Brad Wright and Robert Cooper is available in MP3 audio format for easy listening. Part one about 15 minutes long, and is also transcribed below. You can also download the interview to your MP3 player and take GateWorld with you! Continue to Part 2 >> GateWorld: What is your overall opinion of Season Eight now that it's in the history books? Brad Wright: Season Eight? Robert C. Cooper: I don't remember ... it's a blur! GW: Let me just say that the second half, especially "Reckoning" through "Moebius," is fantastic. We loved it. RC: Thanks. I'll tell you, we felt like we ended the show. We felt like it was the closing of a chapter on Stargate SG-1. BW:: We thought we ended it three times even before that. RC: But this was the real ending! And in fact so much so that in discussing whether we were going to come back and do SG-1 Season Nine or a new show or whatever, we basically -- and the decision was made to do Season Nine -- we decided that regardless of the fact that we're continuing the same series, we're done ending things. We're not going to write another season that leads up to another ending. Season Eight brought startling revelations and conclusions to many storylines, including Anubis, Oma, and Daniel's ascension in "Threads." That's over! Ending the show is over. Because, quite frankly, it seems as though the show will never end. So instead what we decided is we're going to start beginning again. This new season, Season Nine, is much more about opening all kinds of new doors and starting fresh -- not just for the characters but with the storylines. BW:: The truth is it had to be done anyway because the Goa'uld are defeated and because there've been some big cast changes. RC: There's a certain point at which, yes, for some really developed fans who've followed the show from the beginning, "Reckoning" and "Threads" and "Moebius" really paid off a lot of things for the characters and for the plots and made you feel like watching the show for so long was really a satisfying experience. All these things were coming to a nice head and culminating. But also, Season Eight -- again, I think if there was anything wrong with it was it was a little bogged down in all the wrapping up in having to service storylines that had come from before. [It] in some ways alienated a new audience who may have been coming to the network, SCI FI, to watch Atlantis for the first time, tuning into SG-1 and going "Huh? What's going on? Who are those people? What's this storyline?" We couldn't do a long enough "Previously On" at the beginning of every show to explain to new viewers what was happening in this particular episode. GW: They seemed to be getting longer and longer. RC: Well,
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