Podcast appearances and mentions of Nicholas Smith

How likely is an asteroid to impact Earth? Neil deGrasse Tyson and Chuck Nice sit down with planetary scientist Rick Binzel, the creator of the Torino Scale, to discuss asteroid hazards, the results of the asteroid sample return, and the search for Planet 9.NOTE: StarTalk+ Patrons can listen to this entire episode commercial-free here: https://startalkmedia.com/show/asteroids-headed-towards-earth-with-rick-binzel/Thanks to our Patrons Euclid A LoGiudice, Todd Thedell, Girolamo Castaldo, Scott E Mann, Stephen Luick, Lou Perreault, Tom Womack, jonas dravland, Carla Garner, Matthew Smith, Marcy Hansen, Dale Schurman, David LoMonaco, Manoj Chugh, Lynn Cade, James Dudley, Gaterdog44, Ally Whitchurch, George Pipe, Collin Brumm, Amanda Phillips, George Murray, Daniel Persaud, Jason Bennett, Damon, Dutt Bobba, Gregorio Sanford, Dre Adamenko, rohit chaudhary, Krys Kap, Lukasz Kosturek, Nicholas Smith, Martin Wegner, kaley knowles, SciFiGriffin, Lucas Sanjuan, Jacob Hodges, BRET ANDERSON, Irina Cher, R B, Norway man, Wayne Gosson, and Fireworks for Buddha for supporting us this week. Subscribe to SiriusXM Podcasts+ to listen to new episodes of StarTalk Radio ad-free and a whole week early.Start a free trial now on Apple Podcasts or by visiting siriusxm.com/podcastsplus.

Nicholas Smith, managing partner of Smith Fence – a third-generation, family-owned Florida business – covers a lot of ground with host Owen LeFave in this conversation that explores how a company can innovate successfully in a competitive industry, all while staying true to its roots. Nicholas shares the origin story of Smith Fence, tracing the business back to his grandfather, who entered the fence industry after World War II. Much has changed since then, and today the company has evolved and modernized, utilizing AI to improve efficiency in a labor-intensive industry where paperwork and project complexity have steadily increased. Discover how Nicholas and his leadership team leverage technology and embrace innovation without sacrificing their family-first culture, deep sense of community, and focus on building strong relationships.   The Bank of Tampa | Member FDIC

Listen to our talk with artists Andy Butler and Nicholas Smith on their new works presented as part of 'Future Remains: The 2024 Macfarlane Commissions'. This podcast was recorded as part of an Artist Talk at ACCA on Saturday 13 July 2024.

September 20, 1994. Los Angeles, California. Alfredo Newball returns to his apartment and discovers that his 32-year old pregnant wife, Cecilia Newball, and his six-year old stepson, Rene Perez, have vanished without a trace and Cecilia's Jeep and all of their personal possessions have been left behind. Even though Cecilia is only two weeks away from giving birth, Alfredo is soon mailed a typewritten note in which Cecilia reveals that she and Rene have run off with a doctor from Honduras. Prior to her disappearance, Cecilia had been contacted by a woman who wanted to arrange a meeting to show her some baby furniture on the day she went missing, but she cannot be identified and Cecilia and Rene are never found. February 21, 1991. Las Cruces, New Mexico. 35-year old Edyth Warner, an art student at New Mexico State University, leaves her class and does not return, and 11-year old Nicholas Smith, Edyth's son from a previous marriage, also seems to go missing at the same time. According to Edyth's current husband, Henry Warner, Edyth took Nicholas and went to stay at a friend's house and never came back, but she inexplicably left behind the couple's three-year son, Andrew. Investigators eventually come to believe that Edyth and Nicholas were the victims of foul play, but no suspects are named and the case is never solved. On this week's episode of “The Trail Went Cold”, we explore two unsolved missing persons cases in which a mother and son disappeared together. Additional Reading: https://unsolved.com/gallery/cecilia-newball-rene-perez/ https://unsolvedmysteries.fandom.com/wiki/Cecilia_Newball_and_Rene_Perez_Jr. https://charleyproject.org/case/cecilia-elizabeth-newball https://charleyproject.org/case/rene-perez-jr https://www.latimes.com/archives/la-xpm-1994-09-29-me-44410-story.html https://web.archive.org/web/20130718060712/http://www.lacountymurders.com/wanted/099-00062-3199-011.pdf https://charleyproject.org/case/edyth-ann-warner https://charleyproject.org/case/nicholas-vincent-smith https://www.latimes.com/archives/la-xpm-1991-10-30-vw-653-story.html https://www.newspapers.com/image/431536244/ https://www.newspapers.com/image/997619150/ “The Trail Went Cold” is on Patreon. Visit www.patreon.com/thetrailwentcold to become a patron and gain access to our exclusive bonus content. “The Trail Went Cold” is going to be appearing on podcast row at Crimecon UK” in London on September 21-22, 2024. To get a 10 % discount on the purchase of tickets to either event, please use our specialized promo code, “COLD24”, by visiting Crimecon.com or Crimecon.co.uk. “The Trail Went Cold” will be appearing at the True Crime Podcast Festival, taking place at the Denver Marriott Westminster in Colorado on July 12-14, 2024. To get a 15 % discount on tickets, please use our specialized promo code, “TRAIL”, by visiting https://truecrimepodcastfestival.com. The Trail Went Cold is produced and edited by Magill Foote. All music is composed by Vince Nitro.

September 20, 1994. Los Angeles, California. Alfredo Newball returns to his apartment and discovers that his 32-year old pregnant wife, Cecilia Newball, and his six-year old stepson, Rene Perez, have vanished without a trace and Cecilia's Jeep and all of their personal possessions have been left behind. Even though Cecilia is only two weeks away […]

Financial derivative products can be a complex topic. There are several types of products and concepts to understand before investing. In this episode, we explore the basics to bring clarity to what can sometimes seem like a challenging topic to new investors. Nicholas Smith, VP of Sales at Eurex joins Cassidy Clement, Senior Manager of SEO and Content to discuss.

On this episode of Our American Stories, Nicholas Smith, author of Kicks: The Great American Story of Sneakers, takes us for a journey through American history... through the lens of the sneaker! Support the show (https://www.ouramericanstories.com/donate)See omnystudio.com/listener for privacy information.

150 Years Ago (February 1874) Ingersoll Lockwood, the 6-foot-4 former U.S. consul to the Kingdom of Hanover [which became part of Germany in 1871] and the nephew of Cold Spring resident Nicholas Smith, spoke at the Baptist Church about women's faces, both ancient and modern, to benefit the Sunday School. William Garrison, who represented Philipstown on the county Board of Supervisors, proposed that the town be split so it would have two representatives. He noted that, with six supervisors, the votes were often ties, and that Philipstown had a third of the county population but only a sixth of the vote. The pastor of the Baptist church, the Rev. Benjamin Bowen, wrote a long letter to The Cold Spring Recorder in which he offered to pay the salary of the highest-paid teacher in Philipstown for one year if anyone could show him in the Bible a mention of infant baptism (which Baptists do not practice), or where someone had received communion before being baptized, or any documentation of infant baptism before the middle of the third century. While Charles Warren was delivering milk, someone stole $10 [about $250 today] from the cash box on his wagon. Alfred Little painted advertising "business charts" at the post office and railroad station with notices for 13 local merchants and mechanics. While walking on the railroad track at Constitution Island, Arthur Naylor of B Street saw a fox walk out of the woods. He drew his revolver and fired; the trophy was on display at Mosier's oyster and fish store on Market Street. Bernard Daley of Kemble Avenue lost a pig when it was struck by the No. 7 express train. Bystanders with buckets filled at a nearby municipal pump managed to contain a fire at Mrs. McArthur's newsstand on Main Street. S.B. Truesdell was circulating a petition to ask the state to extend the ban on shooting robins from Aug. 1 to Oct. 1, to allow the birds more time to mature. The Recorder reported that, after a snowball fight in Nelsonville got out of hand, a boy complained to his father. The father confronted the first boy he encountered, which resulted in a lawsuit. A farm dog belonging to B.A. Yonmans that followed the horses to church was found dead the next day in the churchyard. It was supposed he had been poisoned. The Recorder reported that 8,100 men, 1,375 boys, 581 horses and 41 steam engines were employed along the river securing the ice crop. One crew managed to get 2,700 cakes into an ice house in a single day. Thomas Avery and William West of Cold Spring, who had announced they would embark on the manufacture of paper bags in the village, were dissuaded by the high rents and instead leased a structure in Fishkill that was built to order. The Wappingers Chronicle claimed that it was common to see men walking in Cold Spring stop suddenly, place their hands on their knees and groan. In response, The Recorder noted that "Cold Spring whiskey is stronger than that to which some visitors are accustomed." The county school commissioner condemned the District 8 schoolhouse and estimated it would cost $800 [$20,000] to build a new one. William Bennett of Nelsonville lost several toes after a 500-pound casting fell on his foot. Members of the Ladies Aid Society and the Presbyterian Church held a masquerade with cakes and coffee at the West Street home of William Coleman. 125 Years Ago (February 1899) At 10 p.m. on a Wednesday, young men walking the tracks from Garrison came upon four teenagers, ages 13 to 15, crying from hunger and cold. One of the boys told Officer McCaffrey that they had been playing at the freight yard near their homes at 32nd Street and Seventh Avenue in New York City when they climbed aboard a freight car for a ride to Spuyten Duyvil. But the train was going too fast for them to jump off and they had to wait until it stopped at a switch near Garrison. The Recorder noted that a bill had been introduced in the state Legislature to allow women to vote in villages and towns concerning matters of tax...

We hear about the influence of data and science in sports every day. You can't watch an NFL game without hearing “the analytics say this is the right decision.” So it should come as no surprise that the world's best swimmers work with experts to find speed anywhere possible. Enter Nick Smith and the field of “movement science.” He's worked with Cam McEvoy in his ascent to the top of the sprinting world, as well as other Aussie swim stars like Ariarne Titmus and Shayna Jack to name a couple, with the objective of understanding how the body moves through water, where in the race there is room to improve, and helping craft that improvement. Nick Smith is an expert and is part of why Cam McEvoy told us in Episode #150 about his target time to 15m being a huge priority and how he was able to achieve it en route to his World Championship title in the 50m Freestyle. Check this one out to learn how Nicholas Smith, Queensland Academy of Sport and Team Australia are leveraging science to achieve results in the pool. Enjoy!

On this episode of Our American Stories, Nicholas Smith, author of Kicks: The Great American Story of Sneakers, takes us for a journey through American history... through the lens of the sneaker! Support the show (https://www.ouramericanstories.com/donate)See omnystudio.com/listener for privacy information.

Evan Campelli-Melody, runs SneakerDealer.ie and Nicholas Smith, Author of "Kicks: The Great American Story of Sneakers"

A torn letter exposes the lonely lives and cruel deaths of the mysterious Tipperary couple Nicholas Smith and his wife Hillary. Shane Phelan Legal Affairs Editor at Irish Independent joined Pat on the show this morning with more on this.

On this episode of Our American Stories, Nicholas Smith, author of Kicks: The Great American Story of Sneakers, takes us for a journey through American history... through the lens of the sneaker! Support the show (https://www.ouramericanstories.com/donate)See omnystudio.com/listener for privacy information.

This week, please join author Sunil Rao and Guest Editor and Editorialist Gregory Lip as they discuss the article "A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction" and the editorial "Factor XIa Inhibition: Is It a Novel Alternative Antithrombotic Strategy for High-Risk ACS Patients?" 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 co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, today's feature paper is about the factor XI inhibitor asundexian. It's the trial that we've been waiting for the PACIFIC-AMI trial. You really have to listen to it because these factor XI inhibitors are super interesting. What? We're going to tell you about the other papers in today's issue first. Aren't we, Greg? Do you want to go first? Dr. Greg Hundley: You bet, Carolyn. Thank you so much. Carolyn, did you ever consider the genetic underpinnings of venous thromboembolism? Well, as you know, venous thromboembolism is a complex disease with environmental and genetic determinants. And in this study, this large investigative team represented by Dr. Nicholas Smith from the University of Washington in Seattle, and their colleagues present new cross-ancestry meta-analyzed genome-wide association study results from 30 studies with replication of novel loci and their characterization through in silicone genomic interrogations. Dr. Carolyn Lam: Wow. Sounds like a really large effort, Greg. What did they find? Dr. Greg Hundley: Right, Carolyn. In the author's initial genetic discovery effort that included 55,330 participants with venous thromboembolism: 47,000 were European, 6,000 African, and a little over 1000 Hispanic ancestry. They identified 48 novel associations of which 34 are replicated after correction for multiple testing. In their combined discovery replication analysis, so that's 81,669 venous thromboembolism participants and ancestry stratified meta-analyses from the European, African and Hispanic ethnic groups. They identified another 44 novel associations, which are new candidate venous thromboembolism associated loci requiring replication. And many of the replicated loci were outside of known or currently hypothesized pathways to thrombosis. Carolyn, in summary, these findings from this very large GWAS analysis highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of anti-thrombosis treatments with reducing the risk of bleed. Dr. Carolyn Lam: Wow. Super interesting and very related to that feature paper that we just discuss. But nonetheless, this next paper I love as well, if I may say so myself. It deals with frailty and as we know, frailty is increasing in prevalence. And because frail patients are often perceived to have a less favorable benefit risk profile, they may be less likely to receive new pharmacological treatments. And so, we and led by Professor John McMurray from the University of Glasgow, decided to investigate the efficacy and tolerability of dapagliflozin according to frailty status in the DELIVER trial. Dr. Greg Hundley: The DELIVER trial. Carolyn, tell us about the DELIVER trial? Dr. Carolyn Lam: Sure. In deliver dapagliflozin compared to placebo, reduced the risk of worsening heart failure events or cardiovascular death and improved symptoms in more than 6,000 patients with heart failure and mildly reduced and preserved ejection fraction, so ejection fraction above 40%. Now in this pre-specified analysis, we examine the efficacy and safety of dapagliflozin according to frailty status. That was determined using the Rockwood cumulative deficit approach. And so, what we found was that greater frailty was associated with more impairment of health status and worse clinical outcomes in patients with heart failure and ejection fraction of 40%. The beneficial effects of dapagliflozin compared to placebo on clinical outcomes were consistent regardless of frailty class. But interestingly, the improvement in symptoms, physical function and quality of life were larger in the frailest patients. Adverse events were not more common in individuals randomized to receive dapagliflozin compared to placebo irrespective of frailty class. And so, the take home message is the benefit risk balance related to frailty in patients with heart failure with mildly reduced and preserved ejection fraction is favorable for dapagliflozin. And so, these findings should challenge any clinical reluctance to introduce dapagliflozin in patients perceived to be frail. Dr. Greg Hundley: Wow. Carolyn, really interesting. You could see with the diuretic effect in someone that's frail, the potential hesitancy, but very interesting study results in this world of frailty and the use of dapagliflozin. Well, Carolyn, this next study is very interesting and it comes to us from the world of preclinical science that takes a very interesting approach to a scientific question. Now, as you may know, RNA-binding proteins or RBPs are master orchestrators of genetic expression regulation. They regulate hundreds of transcripts at once by recognizing specific motifs, thus characterizing RBPs targets is critical to harvest their full therapeutic potential. However, such investigation has often been restricted to a few RBP targets, thereby limiting our understanding of their function. Carolyn, these investigators led by Dr. Grégoire Ruffenach from UCLA were interested in assessing pulmonary arterial hypertension and they turned to the world of cancer research. Carolyn, in cancer, the RNA-binding protein hnRNPA2B1, and we're going to abbreviate that as A2B1, promotes a pro proliferative anti-apoptotic phenotype. The same phenotype is present in pulmonary arterial smooth muscle cells and is responsible for the development of pulmonary arterial hypertension. However, the A2B1 function that's never really been investigated in pulmonary arterial hypertension. Dr. Carolyn Lam: Oh, Greg, that's not only fascinating, but so beautifully described. Thank you. What did they find? Dr. Greg Hundley: Right, Carolyn. These authors found that A2B1 expression and it's nuclear localization are increased in human pulmonary arterial hypertension, pulmonary arterial smooth muscle cells. Using bioinformatics, they identified three known motifs of A2B1 and all mRNAs carrying them and demonstrated the complimentary non-redundant function of A2B1 motifs as all motifs are implicated in different aspects of the cell cycle. In addition, they showed that pulmonary arterial smooth muscle cells and A2B1 promote the expression of its targets. Additionally, in vivo A2B1 inhibition in the lungs rescued pulmonary hypertension in rats. And so, Carolyn, through the integration of computational and experimental biology, this team study revealed the role of A2B1 as a master orchestrator of pulmonary arterial smooth muscle cells in pulmonary hypertension and that phenotype and its relevance as a therapeutic target in pulmonary arterial hypertension. Dr. Carolyn Lam: Wow, that's super, Greg. Thanks. Shall we go through what else is in today's issue? Dr. Greg Hundley: You bet, Carolyn. There's a Research Letter from Professor Mustroph entitled, “Empagliflozin Inhibits Cardiac Late Sodium Current versus Calcium Calmodulin‐dependent Kinase II.” Dr. Carolyn Lam: There's also an exchange of letters between Doctors Omarjee and Diederichsen regarding vitamin K2 and D in patients with aortic valve calcification: [an] absence of evidence might not be evidence of absence? And finally, there's an On My Mind paper by me and Scott Solomon and it's entitled, “Delivering Therapeutic Efficacy Across the Ejection Fraction Spectrum of Heart Failure.” But let's go on now to talk about the Factor XI inhibitor, shall we, Greg? Dr. Greg Hundley: You bet. Well, listeners, welcome to this feature discussion on October 18th at a very special article today. And we have with us the lead author, Dr. Sunil Rao from NYU in New York City and also our associate guest editor as well as editorialist, Dr. Gregory Lip from Liverpool. Welcome, gentlemen. Sunil, we'll start with you. Can you describe for us some of the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Sunil Rao: Yeah, great. Thanks so much, Greg. It's a real pleasure to be here with you. The background of the PACIFIC-AMI study is really rooted in the fact that patients who have acute myocardial infarction are really at risk for recurrent thrombotic events, even after their event. And this risk continues despite the fact that we have evidence based therapies that are really around targeting the platelet as well as aspects of the coagulation cascade. There have been studies that have looked at the use of dual antiplatelet therapy plus an anticoagulant or single antiplatelet therapy plus an anticoagulant. And those studies have shown a benefit. However, their clinical use is limited because of the bleeding risk. Factor XI is an interesting target, because factor XI is likely involved in the amplification of thrombin generation after plaque rupture. But it really doesn't play much of a role in hemostasis. And so, as a target in reducing events after acute coronary syndrome, activated factor XI is a very attractive one. And so, the hypothesis of this study was that a highly bioavailable oral, direct, selective activated factor XI inhibitor called asundexian would be safe and effective in the treatment of patients who experience acute coronary syndrome at reducing adverse events. Now, this is a phase two study, so it really wasn't powered for clinical events. It was really a dose-finding study, so it was really looking at adverse events and sort of bleeding complications. Dr. Greg Hundley: Very nice. Asundexian, a new factor XI inhibitor. And Sunil, can you describe for us your study design and then maybe a little bit more about the study population, how many subjects? Dr. Sunil Rao: Sure. Again, this is a phase two study. It was a randomized, double-blind, parallel-group design where patients, who were admitted with acute coronary syndrome were randomized to three different doses of asundexian and or placebo in a one-to-one to one-to-one fashion. Patients who met criteria for enrollment were: patients who were admitted with a diagnosis of acute MI; if they were older than or equal to 45 years of age; they were hospitalized in acute coronary syndrome that did not occur in the context of revascularization, so it was not a type 4 event; and they were planned to be treated with dual antiplatelet therapy after hospital discharge. Dr. Greg Hundley: Sunil, thank you for describing this very interesting study design. Now, how many subjects did you include and could you just describe for us the study population? Dr. Sunil Rao: We had a total of 1,601 patients that were randomized at 157 centers in 14 countries between June 2020 and July 2021. And in order to be eligible for enrollment into the study: patients had to be admitted with a diagnosis of acute MI, they had to be greater than or equal to 45 years of age, and be hospitalized with that acute MI that did not occur in the context of revascularization, so type 4 MIs were excluded. The other inclusion criteria was that they had to be planned to be treated with dual antiplatelet therapy after hospital discharge. Now, we allowed randomization up to five days after hospital admission and randomization occurred after patients were clinically stabilized and any planned PCI was performed. We included both patients with STEMI as well as non-ST segmental elevation ACS, but we capped the number of patients with STEMI that were included to no more than 50%. Now, the main exclusion criteria were things that you would expect for a phase two trial. Obviously, hemodynamic instability at the time of randomization, active bleeding or bleeding dialysis, severe renal dysfunction, planned use of full-dose anticoagulation. Dr. Greg Hundley: Very nice. And so, we have several doses of this new factor XI inhibitor. Describe for us your study results? Dr. Sunil Rao: Again, this was a phase two trial that was really looking at safety and adverse events as you would expect. The study groups were pretty balanced across all of the dosing arms. When we looked at the pharmacokinetic and pharmacodynamic data, we found something really interesting, which was that there was a dose relationship between the dose of asundexian and the factor XIa activity. Factor XIa is activated factor XI. The higher the dose, the more suppression of factor XI activity. In fact, the highest dose nearly eliminated factor XI activity. The drug clearly works in the way that it was intended. Now again, the clinical data, it wasn't powered for clinical data. But when we look at the bleeding results, we found that there was in fact an increase in bleeding as the dose of asundexian increased. The overall rate of bleeding in the highest dose of asundexian was in 50 milligrams was 10.5% with type 2 or 3 or 5 BARC bleeding, a placebo is about 9.02%. Again, the efficacy outcomes, very, very low rates of overall events. Again, not powered to show a difference. Essentially, very similar across all the arms. Dr. Greg Hundley: And did you find the same results for the men and the women? And what about older individuals and younger individuals? Dr. Sunil Rao: Yeah. We did look at some subgroups. And you had to be a little bit cautious because again, the trial itself is relatively small. I mean, we didn't notice any significant patterns across these subgroups. And the overall interaction p-values were really non-significant. But I think what this does show is like a phase two trial that the drug works as in the way that it's intended. Overall, safety was as expected. And I think it really sets up data for a larger study. Dr. Greg Hundley: Well, listeners, what a fantastic presentation. And now, we're going to turn to our guest editor and editorialist, Dr. Gregory Lip from Liverpool. Greg, I know working for circulation, you have many papers come across your desk. What attracted you to this particular paper? And then maybe secondly, can you help us put the results of this study in the context of other studies that have been evaluating these factor XI therapies? Dr. Gregory Lip: Thanks, Greg. Well, I think this is an important paper, because it is a phase two trial with a novel, orally bioavailable inhibitor factor XI. And this is intriguing because factor XI efficiency in humans and experimentally in animals is associated with a reduced risk of thrombotic events like stroke or venous thromboembolism. But spontaneous bleeding is rare and also bleeding in response to trauma or surgery is much milder. Really it's the holy grail of trying to get an anticoagulant that reduces thrombosis but doesn't cause an excess of bleeding. Now, this was the quest with different anticoagulants. And I think it was very exciting to see this particular paper in the patients who've had an acute coronary syndrome, because there was a lot of interest in the use of anticoagulants, particularly in combination with antiplatelet therapy from trials such as ATLAS and COMPASS, where there was certainly a reduction in adverse cardiovascular events. But a downside with those drugs and when using combination, was an excess of bleeding by the combination of the available anticoagulants now plus antiplatelets. The factor XIs agents offered the possibilities we might have combination therapy to reduce cardiovascular events but not causing an excess of bleeding. Dr. Greg Hundley: Well, listeners, what a wonderful discussion that we've had here. Let's circle back with both individuals. Sunil, we'll start with you. What do you see as the next study to really be performed in this sphere of research? Dr. Sunil Rao: I think that factor XI is a very attractive target in patients with acute coronary syndrome. Again, the rationale for why we did this phase two trial was to show that inhibition of activated factor XI should result in a low rate of ischemic events without a significant increase in bleeding. This phase two trial was really to try and decide which doses result in potent inhibition of factor XIa and potentially which doses should be carried forward into a larger study. What we found in the PACIFIC-AMI trial was that the doses of asundexian and the factor XIa inhibitor were very, very well tolerated with a low rate of adverse events. It resulted in a dose-dependent near complete inhibition of factor XIa activity without a significant increase in bleeding and a low rate of ischemic events. I think, again, it's a very attractive target in patients with ACS and this really provides support for a larger adequately powered clinical trial in patients with acute coronary syndrome that is really looking at clinical events such as MACE as well as bleeding. Dr. Greg Hundley: And Greg as an editorialist, what did you see with this paper? Maybe some unanswered questions that we'd like to pursue further? Dr. Gregory Lip: Well, I think this does raise a lot of questions in the sense that it'll be interesting because as a phase two trial, it's a relatively moderate sized trial. It's not like a phase three large outcome trial and phase two trials also testing different doses of the novel agent. We need to see the definitive phase three trial and to look at the magnitude of benefit versus potential for bleeding if in the large phase three trial and obviously, the net clinical benefit and importantly are some of the subgroups: ST elevation, myocardial infarction, undergoing primary PCI, for example, those with renal impairment. And I think particularly intriguing would be looking at the patients in this scenario who get the new antiplatelet drugs such as ticagrelor and prasugrel. And the reason I say that is what we have with warfarin or Coumadin and from the current DOACs or NOACs, depending on the risk side upon. We refer to them, that's the direct oral anticoagulants or non-vitamin K antagonist or anticoagulants. Well, if you give a more potent antiplatelet like prasugrel or ticagrelor, the risk of bleeding not surprisingly is higher. Hence, the guidelines recommend that if you use an anticoagulant or a DOAC, you use it with a P2Y 12 inhibitor clopidogrel as opposed to the more potent ones. If this new class of drugs, the factor XI inhibitors can work well in combination with one of the more potent antiplatelets without causing an excessive bleeding, again, this is going to be a substantial advance. Well, with these new class of anticoagulants, will be really interesting to see the phase three trials when applied to other chronic conditions. For example, stroke prevention and atrial fibrillation. And the other category of patients would be those who've had an embolic stroke of uncertain source or ESUS or in old terminology cryptogenic stroke. With the ESUS group of patients, they're currently treated with aspirin because the trials which tried a NOAC or DOAC, they were not showing a positive result. They'll be interesting again with the factor XI inhibitors, whether we are going to see this benefit with the reduction in recurrence stroke with no excessive bleeding. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Sunil Rao from NYU in New York City and Dr. Gregory Lip from the University of Liverpool for bringing us this study highlighting that in patients with recent acute myocardial infarction, three doses of asundexian when added to aspirin plus a P2Y 12 inhibitor resulted in dose-dependent near complete inhibition of factor XIa activity without a significant increase in bleeding and a low rate of ischemic events. And certainly, the data from this study support the investigation of asundexian at a dose of 50 milligrams daily in an adequately powered clinical trial of patients following acute myocardial infection. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

A collection of this week's Witness History programmes, presented by Max Pearson. The guest is Nicholas Smith, author of "Kicks: The Great American Story of Sneakers" and Presenter of the BBC's "Sneakernomics" podcast. He explains how footwear revolutionised sport and became high-fashion. In 1948, two brothers from a small German town called Rudi and Adi Dassler created the sportswear firms Puma and Adidas. Reena Stanton-Sharma hears from Adi Dassler's daughter, Sigi Dassler, who remembers her father's obsession with footwear and talks about her fondness for the rappers, Run-DMC, who paid tribute to her dad's shoes in a song. We also hear about one man's mission to castrate Pablo Escobar's hippos, the unpredictable rule of Kenya's former President, Jomo Kenyatta, the 'Japanese Schindler', and the raising of the 400-year-old Mary Rose. (Photo: Adi Dassler. Credit: Brauner/ullstein bild via Getty Images)

Dr Nicholas Smith is a Doctor of Physical Therapy and is a certified strength and conditioning coach who helps grapplers own their injuries, develop explosive strength, and build relentless conditioning.Being that the knees are the number one injured area in jiu-jitsu, I wanted to talk specifically with the doctor about knee injuries. According to many studies it is the joint most likely to get hurt while training, sparring, and competing.So, in this episode we explore why that is, why knee injuries are so common, what you can do to give yourself the best shot of preventing knee injuries, how to train around them, and the steps to take if you actually do sustain a knee injury.It's a phenomenal conversation that I hope will help any of you out there dealing with knee problems or will at some point in your BJJ career.In This Episode We Discuss:Why knee injuries are so common in BJJWhy the meniscus is frequently injured in BJJWhat you can do to avoid surgery if you tear something in your kneeTests you can do to determine if you have a knee tearExercises to strengthen the muscles that support the knees to reduce injuriesHow the Doctor determines if surgery is necessaryHow to speed recovery after knee surgeryThe pros and cons of having knee surgeryAlternatives to surgery and things you can try before going underThoughts on PRP or Plasma Rich Platelet injections for healingHow to train around knee pain to continue making progressGetting ahead of injuries and aging to prolong your time on the matHow to structure a good warmup for BJJ to reduce injuriesThe Doctor's favorite supplements for injuries and BJJGet the full show notes here.

The relics of St. Bernadette Soubirous are travelling throughout the United States with a stop in St. Louis. Msgr. Michael Witt gives us a brief of St. Bernadette. Fr. Nicholas Smith speaks with us regarding the veneration opportunities. Dr. Scott Hahn wraps up his reflections on the Holy Eucharist. Learn more about Covenant Network Catholic Radio at www.ourcatholicradio.org . 

A community in Tipperary has been thrust into the spotlight for all the wrong reasons after the deaths of Hilary and Nicholas Smith. The small village of Cloneen has been reeling since the bodies were discovered, and it now looks like they could have been dead for 18 months. Criticisms have been levelled at the locality for not keeping an eye on them, Sean was joined by Fine Gael Cllr Mark Fitzgerald owns The Thatch Pub in the village, to discuss if that criticism is unfair.

A community in Tipperary has been thrust into the spotlight for all the wrong reasons after the deaths of Hilary and Nicholas Smith. The small village of Cloneen has been reeling since the bodies were discovered, and it now looks like they could have been dead for 18 months. Criticisms have been levelled at the locality for not keeping an eye on them, Sean was joined by Fine Gael Cllr Mark Fitzgerald owns The Thatch Pub in the village, to discuss if that criticism is unfair.

On this episode of Jury Duty: The Trial of Kyle Rittenhouse, host Kary Antholis is joined once again by Abbe Smith who serves as Professor of Law and Director of the Criminal Defense and Prisoner Advocacy Clinic at Georgetown University. Together, they discuss the final witness testimonies in the State's case against Rittenhouse, as well as the testimony of the first Defense witness, Nicholas Smith.Looking to listen to Jury Duty ad-free? Become a patron on our Patreon page! In addition to ad-free content, you'll receive exclusive access to the full Crime Story Media catalog—including our Storyteller Interview Series featuring Kary Antholis' conversations with ground-breaking, award-winning storytellers like David Simon, George Pelecanos, Vince Gilligan, and David Chase; all of our Amanda Knox Project opinion and interview pieces; and Judge Katherine Mader's INSIDE THE ROBE.You can also find out more information about each of the trials covered by Jury Duty at CrimeStory.com.Or at these dedicated links...The Trial of Kyle RittenhouseThe Killing of Ahmaud ArberyThe Trial of Robert Durst See acast.com/privacy for privacy and opt-out information.

Do you realize that you have giant potential but aren't quite sure how to unlock it? Nicholas Townsend Smith is a performance coach and author of the book, The Giants and the Smalls and cofounder of the Wake Up With Giants program. He joins me on this episode of Solopreneur Money to teach us how we can all live a giant life.  Nick helps individuals see the gaps in their performance and create a clear path to change. By helping leaders and individuals navigate twelve journeys, he has taught them to unlock unlimited growth to live a Giant life.  You will want to hear this episode if you are interested in... How Nicholas got started with the life he lives today [1:22] How the book is written [10:26] Journey of unconsciousness [13:43] How depression can increase your awareness [17:56] Trust your vision [26:32] Collaboration increases our capacity [30:25] Abundance feeling good and giving back [35:36] The money questions [40:24] Resources & People Mentioned Steve Hardison BOOK - Who Moved My Cheese? By Spencer Johnson  BOOK - The Ultimate Coach by Alan Thompson and Amy Hardison BOOK - The Happy Pocketful of Money by David Cameron Gikandi BOOK - The Black Swan by Nassim Nicholas Taleb BOOK - Man's Search for Meaning Victor Frankl BOOK - Yes to Life by Victor Frankl BOOK - Dare by Barry McDonagh Connect with Nicholas Smith BOOK - The Giants and the Smalls by Nicholas Smith  The Giants and the Smalls on YouTube Tribe of Giants on Facebook Wake Up with Giants TV on Facebook The Giants and the Smalls on LinkedIn Connect With Gabe Nelson BOOK – The Solopreneur's Money Manifesto by Gabe Nelson www.GabeNelsonFinancial.com/contact FREE Downloadable Resources at https://www.gabenelsonfinancial.com/resources/ EMAIL: Gabe (at) GabeNelsonFinancial.com Follow Gabe on LinkedIn Follow Gabe on Twitter: @GabeNelsonCFP Follow Gabe on Facebook Follow Gabe on Instagram: @GabeNelsonCFP Subscribe to Solopreneur Money Audio Production and Show notes by PODCAST FAST TRACK https://www.podcastfasttrack.com

What would AYBS be like if it was filmed in Los Angeles instead of London?? The Unanimous loved The Unanimous Episode! And we'd still love to hear from you if you didn't get on the podcast. Get well soon folks who have COVID. Blackface verses Drag: comparable or not? Are you a drag queen? We'd love to hear your thoughts about what drag means to you. There's only one recording of “Beane's of Boston” (and that's probably for the best…). Beanes of Boston was filmed between seasons 6 and 7 of the original AYBS in the UK. “Healthy” Kentucky Fried Chicken?! Beane's was broadcast once on May 5, 1979 during the old “Good Times” time slot on CBS. Theme songs: a pilot episode in music. Beane's of Boston is like an American Grace Brothers… kinda. Frank Beane (“Old Mr. Grace”) played by Tom Poston (who guest starred on every sitcom in the 70/80s). Mr. Brandon's brain is AYBS and nothing else. Old Mr. Beane is a dirty old man like Young Mr. Grace. Harrold Bennet's YMG was somehow sweet while being a dirty old man; Frank Beane not so much. We love bumbling Mr. Rumbold played by Nicholas Smith. How did “pilot season” effect the actors in Beane's of Boston? “Miss. Brahams” feels like an airhead from “Three's Company”. Remaking films/TV shows is such a tricky thing since audiences will naturally compare the new product to the classic one. Why couldn't American audiences watch the original UK TV series? American censors couldn't handle sexual jokes or overtly gay characters? Check out Steven Capsuto's Youtube channel about LGBT TV history at https://www.youtube.com/channel/UCT-uzyA8-dkyNpMBKXb8mZw We meet Alan Sues who plays Mr. Humphries (Sues was gay but not out for his career). John Hillerman plays MISTER Peacock and carries it off very well. Charlotte Rae plays Mrs. Slocombe without her famous tinted hair. Was blue hair only a UK phenomenon? Slocombe does the “are you free?” line! Did American audiences know about AYBS? Repetition of classic AYBS jokes- “German Week” episode set up. “Well there goes my ride home” = a bold gay joke for American TV in 1979. The first black AYBS-related actor is Don Bexley who plays Mr. Johnson (like Mr. Harmond in maintenance). The German week jokes didn't get any laughs from the American audience. Mrs. Garrett from “The Facts of Life”! The Trans-Atlantic accent: the world's completely artificial accent in 1930s Hollywood films (think Catherine Hepburn). Drunk Mrs. Slocombe singing Marlene Dietrich! Comparing the German Dance Slap Fight with the original just isn't fair. The American experiment failed but it's a great way to compare and construct BoB with AYBS. Generation gaps made the original UK show so funny and relatable: by 1979 in the US, that just didn't work. Treat yourself to some That Does Suit Madame merch at our Bargain Basement podcast shop at imfree.threadless.com for t-shirts, mugs, tote bags, and more! Leave the show a voicemail at the Peacock Hotline: (662)-PEACOCK (662-732-2625) and find us on Twitter @DoesSuitMadame and #AYBS #AreYouBeingServed #ImFree #Britcom #comedy #MrHumphries #ThatDoesSuitMadame #GraceBros #podcast #LGBT #BlackLivesMatter #BBC

Nicholas Smith The newest gallery on the Sydney scene opened during Sydney's 2021 COVID lockdown – N Smith Gallery. Director Nicholas Smith is optimistic for the potential for the gallery to make a lasting impact because of his belief in the artists he represents. He speaks openly about his journey from sceptical science student to contemporary art gallery owner. Visit the Gallery's website for all the info on Nicholas' artists, https://www.nsmithgallery.com/ For other episodes go to our Instagram page @FineArtFiona.

In this episode of the Perspectives on Healthcare Podcast, Rob Oliver interviews Nicholas Smith. Nicholas is a millennial (a member of generation Y) and provides a pediatric psychology postdoctoral fellow's perspective on healthcare. He is located in Tampa Florida and worked with Johns Hopkins Hospital. Here are 3 things that stood out to me from the conversation with Nicholas Smith: · A psychologist is a behavioral health provider (not just someone you talk to about your feelings) · Mental health affects not just the patient but also the providers · Assessing some of the social determinants of health You can connect with Nicholas Smith through LinkedIn: Linkedin: https://www.linkedin.com/in/nicholas-david-w-smith-ph-d-6a1649a5/ To connect with the show on social media use the links below: Twitter: http://twitter.com/yourkeynoter Facebook: http://facebook.com/yourkeynoter Instagram: http://instagram.com/yourkeynoter Linkedin: http://linkedin.com/company/yourkeynoter YouTube: https://www.youtube.com/channel/UC9ub8CjRQAmXsOEA4s9AYbw We would love to hear from you. Visit the website and use the “Contact Us” form: https://www.perspectivesonhealthcare.com/ On the website are more Perspectives on Healthcare!

In this episode of the Perspectives on Healthcare Podcast, Rob Oliver interviews Nicholas Smith. Nicholas is a millennial (a member of generation Y) and provides a pediatric psychology postdoctoral fellow's perspective on healthcare. He is located in Tampa Florida and worked with Johns Hopkins Hospital. Here are 3 things that stood out to me from the conversation with Nicholas Smith: · A psychologist is a behavioral health provider (not just someone you talk to about your feelings) · Mental health affects not just the patient but also the providers · Assessing some of the social determinants of health You can connect with Nicholas Smith through LinkedIn: Linkedin: https://www.linkedin.com/in/nicholas-david-w-smith-ph-d-6a1649a5/ To connect with the show on social media use the links below: Twitter: http://twitter.com/yourkeynoter Facebook: http://facebook.com/yourkeynoter Instagram: http://instagram.com/yourkeynoter Linkedin: http://linkedin.com/company/yourkeynoter YouTube: https://www.youtube.com/channel/UC9ub8CjRQAmXsOEA4s9AYbw We would love to hear from you. Visit the website and use the “Contact Us” form: https://www.perspectivesonhealthcare.com/ On the website are more Perspectives on Healthcare!

This month on Episode 25 of Discover CircRes, host Cindy St. Hilaire highlights the topics covered in the June 11th Compendium on Peripheral Vascular Disease, as well as discussing two original research articles from the May 28th issue of Circulation Research. This episode also features an in-depth conversation with Drs Eric Small and Ryan Burke from the University of Rochester Medical Center about their study Prevention of Fibrosis and Pathological Cardiac Remodeling by Salinomycin.   Article highlights:   Ghosh, et al. IAP Overexpression Attenuates Atherosclerosis   Dörr, et al. Etelcalcetide for Cardiac Hypertrophy   Compendium on Peripheral Vascular Disease   Cindy St. Hilaire:        Hi and welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to be highlighting articles presented in our May 28th and June 11th issues of Circ Res. I'm also going to speak with Drs Eric Small and Ryan Burke from the University of Rochester Medical Center about their study Prevention of Fibrosis and Pathological Cardiac Remodeling by Salinomycin. Cindy St. Hilaire:        The first article I want to share comes from the May 28th issue and is titled Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis. The first author is Siddhartha Ghosh, and the corresponding author is Shobha Ghosh, and they're from VCU Medical Center. The Western diet is a colloquial term that is used to say a diet that is high in fats, sugars, refined grains, and red meat. A diet consisting of these foods can cause intestinal inflammation, which weakens the gut lining and facilitates transfer of the bacterial toxin lipopolysaccharide, or LPS. Once in the blood, LPS causes systemic inflammation. Cindy St. Hilaire:        Patients with diseases such as diabetes and atherosclerosis, in which inflammation is a major contributor, have increased levels of LPS in the blood. In the gut, the enzyme, intestinal alkaline phosphatase, or IAP, is a critical barrier for the intestine. It regulates the integrity of epithelial cell junctions and helps to detoxify LPS, both of which limit intestinal inflammation. Clinical trials of oral IAP have hinted at its potential to treat patients with ulcerative colitis. In this study, Dr Ghosh and colleagues investigated whether over-expression of IAP can reduce systemic LPS and help to prevent atherosclerosis. They fed atherosclerosis-prone mice engineered to over-express gut IAP, a Western diet for 16 weeks and found that the animals had improved gut integrity, reduced plasma levels of LPS, reduced gut lipid absorption, lower body weight, and decreased aortic plaque burden as compared to normal controls. Together, these results indicate that improving gut barrier integrity by boosting IAP, either by diet choices or pharmacologically, may help to slow atherosclerosis. Cindy St. Hilaire:        The second article I want to share is titled Randomized Trial of Etelcalcetide for Cardiac Hypertrophy and Hemodialysis. The first author is Katharina Dörr, and the corresponding author is Rainer Oberbauer, and they're from the Medical University of Vienna. In chronic kidney disease, or CKD, loss of renal function leads to systemic mineral imbalances. These imbalances trigger further physiological problems, such as the excess production of parathyroid hormone and growth factor, FGF23. The former can cause muscle and bone weakness, and the latter has been implicated in left ventricle hypertrophy. Hyperparathyroidism can be treated with calcimimetics or with vitamin D, but while both approaches lower parathyroid hormone levels, calcimimetics also lower FGF23. Cindy St. Hilaire:        This study investigated whether CKD patients treated with a calcimimetic, etelcalcitide, had any measurable improvements in left ventricle mass, as compared to patients given a vitamin D analog, alfacalcidol. In a single blind randomized study, 32 CKD patients were treated with etelcalcitide and 30 were treated with alfacalcidol for a year. At the end of the study, left ventricle mass measured by magnetic resonance imaging, was found to be significantly lower in the etelcalcitide group. FGF23 levels had also declined in this group, but had risen in the alfacalcidol group. The results indicate that calcimimetics reduce the risk of cardiac hypertrophy, as well as treating hyperthyroidism, and thus, might be a preferable treatment option in CKD. Cindy St. Hilaire:        The June 11th issue of Circulation Research is the Peripheral Vascular Disease Compendium, and in this compendium, we have 14 articles that are written by the leading experts who present an update on the state of the field of peripheral vascular disease research. They discuss current research and also current therapeutic options. Drs Nick Leeper and Naomi Hamburg serve as the guest editors of this compendium. Drs Derek Klarin, Phil Tsao, and Scott Damrauer discuss the genetic determinants of peripheral artery disease. Drs Kunihiro Matsushita and Aaron Aday present a Review on the epidemiology of peripheral artery disease and polyvascular disease. Cindy St. Hilaire:        The potential of leveraging machine learning and artificial intelligence to improve peripheral artery disease detection, treatment, and outcomes is covered by Drs Alyssa Flores, Falen Demsas, Nicholas Leeper, and Elsie Ross. The benefits of walking as exercise therapy and its benefits on lower extremity skeletal muscle is presented by Drs Mary McDermott, Sudarshan Dayanidhi, Kate Kosmac, Sunil Saini, Josh Slysz, Christiaan Leeuwenburgh, Lisa Hartnell, Robert Sufit, and Luigi Ferrucci. Drs Marc Bonaca, Naomi Hamburg, and Mark Creager discuss medical therapies currently available to improve outcomes in patients with PAD. In a similar vein, Drs Joshua Beckman, Peter Schneider, and Michael Conte cover the recent advances in revascularization for peripheral artery disease. Cindy St. Hilaire:        Racial and ethnic disparities in PAD is discussed by Drs Eddie Hackler, Naomi Hamburg, and Khendi White Solaru. Drs Tom Alsaigh, Belinda Di Bartolo, Jocelyne Mulangala, Gemma Figtree, and Nicholas Leeper present their thoughts on optimizing the translational pipeline for patients with peripheral artery disease. New directions and therapeutic angiogenesis and arteriogenesis in PAD is covered by Drs Brian Annex and John Cooke. Drs Esther Kim, Jacqueline Saw, Daniella Kadian-Dodov, Melissa Wood, and Santhi Ganesh review sex-biased arterial diseases with clinical and genetic pleiotropy, focusing in on multi-focal fibromuscular dysplasia and spontaneous coronary artery dissection, which have a much higher prevalence in women. Cindy St. Hilaire:        Drs Matthew Fleming, Ling Shao, Klarissa Jackson, Joshua Beckman, Anna Burke, and Javid Moslehi cover the vascular impact of cancer therapies and focus on how cardiac and vascular sequelae of novel targeted cancer therapies can provide insights into cardiovascular biology. Epidemiology and genetics of venous thrombosis and chronic venous diseases is presented by Drs Richard Baylis, Nicholas Smith, Derek Klarin, and Eri Fukaya. Dr Stanley Rockson reviews advances in our understanding of lymphedema and the compendium concludes with an article by Drs Yogendra Kanthi, Meaghan E. Colling, and Benjamin Tourdot, which reviews, inflammation, infection, and venous thromboembolism. This comprehensive compendium on peripheral vascular disease is found in our June 11th issue. Cindy St. Hilaire:        So today, Drs Eric Small and Ryan Burke from the University of Rochester Medical Center are with me to discuss their study Prevention of Fibrosis and Pathological Cardiac Remodeling by Salinomycin. This article is in our May 28th issue of Circ Res. So thank you both for joining me today. Eric Small:                  Thanks Cindy, for having us. Excited to talk about our research with you. Ryan Burke:                Yeah, thank you very much for having us. Cindy St. Hilaire:        Absolutely. So fibrosis, it's essentially a wound healing mechanism, it's where connective tissue replaces the innate tissue of the organ system that it's happening in. It's really a component of many disease states. As far as I know, treatment options are pretty limited or really non-existent except in a couple rare cases, and in particular, your study, as it's in Circ Research, is focused on cardiomyopathy and the fibrosis related to that. But before we dig into your findings, which is really focused on a great therapeutic angle, I really want to take a step back and ask about what we know about fibrosis or the fibrotic process itself, maybe in the context of the heart, and despite why it's relatively common, it's been so difficult to target in terms of either therapies or really just understanding some of the basic processes. Eric Small:                  Sure, I'd be happy to discuss this. So as you know, and you alluded to already, pathological fibrosis contributes to progression of many debilitating human diseases. So in injury response in many tissues or organs, including the heart, kidneys, lungs, even the skin, leads to a wound healing process and that wound healing process is meant to repair the tissue and that includes an inflammatory response and secretion of extracellular matrix that fortifies the structural integrity of the tissue. But you can imagine in the context of a heart, that has to beat 60 plus times per minute, any alterations to the biomechanical properties of that tissue can alter the function. Eric Small:                  So extracellular matrix, which is meant to improve the structural integrity of an injury, even in the heart, ultimately can lead to reduced cardiac function. So this extracellular matrix, and in the context of disease, this extracellular matrix is called fibrosis, can reduce the contractility and the relaxation of the heart. The relaxation of the heart is actually an important aspect in insufficient relaxation called diastolic dysfunction, is becoming a more prevalent disease phenotype and it is called heart failure with preserved ejection fraction. What we're finding and what some investigators are alluding to is that fibrosis is a major component of this disease, and so understanding how extracellular matrix is secreted, why it is deposited in the context of injury, especially in the context of the heart, why does that process not stop sufficiently and revert once the injury is repaired, is a really important basic science and clinical question. Cindy St. Hilaire:        So why, specifically, has fibrosis or cardiac fibrosis been so difficult to target therapeutically? Eric Small:                  From my point of view, one of the reasons that fibrosis, organ fibrosis in general, and especially within the heart, is hard to target is because I think we're understanding now that one of the major cellular sources of extracellular matrix in disease is the fibroblast. This cell type has been sort of underappreciated for many years and is coming to the forefront now of biomedical research. So fibroblasts until maybe 10 or 15 years ago were thought to be more of a structural component. Of course, they contribute to wound healing, but it was thought that they contribute mostly to structural integrity and homeostasis of the injury. It's becoming more apparent now that resident cardiac fibroblasts contribute to extracellular matrix deposition in disease. But these cell types are really plastic, phenotypically plastic cell, they respond to a lot of biomechanical stimuli, especially that are induced in the context of tissue injury or disease, and so they respond to mechanical stretch or cellular deformation, and they can respond to many secreted factors, especially the canonical factor that has been studied extensively, TGF-beta. Cindy St. Hilaire:        Which itself is extremely complicated, to say the least. Eric Small:                  Absolutely, and so it does so much, and they respond to factors that are really high up on this hierarchy, that do so many things that I think obviously targeting TGF-beta is not going to be really an efficacious therapeutic option. So understanding what's more downstream and much more specifically related to the fibroblast, I think is really important to come up with new therapeutics. Cindy St. Hilaire:        So in your quest to identify novel therapeutics, or even really understanding that below the surface signaling you just talked about, you developed a high-throughput screen. I think this is a term that we often use, but we don't really know the details of that term, like what does high-throughput actually mean when you're doing it with cells and disease models? Dr Eric Small:             Sure. So I think in our case, we really let the science lead the way when it came to the high-throughput screen. So I'm not a chemical biologist, I have never, before now, developed a high-throughput screen and the science just pointed me in this direction. So the basic science research related to fibroblast plasticity and what induces fibroblasts to secrete extracellular matrix in the context of disease, all culminated in this one reporter that I thought would be good for the assay. So maybe as a way of a little bit of background, one difficulty in understanding fibrosis and fibroblast plasticity is that there are no really unique specific markers for an activated fibroblast. So most of the markers that people say are myofibroblast markers, which is the term for an activated ECM-secreting fibroblast, are expressed in other tissues or cells. Probably the most used and best characterized marker of a myofibroblast, is the smooth muscle alpha-actin gene, which encodes the smooth muscle actin protein, which is highly up-regulated in myofibroblasts, but obviously is expressed in a lot of other cell types, including smooth muscle cells. Eric Small:                  So it is a good marker of a myofibroblast, but it's not unique to myofibroblasts. But, this smooth muscle alpha-actin gene allowed us to make inroads into better understanding how fibroblasts respond to different stimuli. So what we did was, in the lab, one of the earlier things that we did when I set up my lab as an independent investigator, was to try to develop a stable cell line that expressed this reporter in a way that we could easily assay. So we could do it with GFP or a luciferase reporter or something like that. We made a luciferase reporter of this smooth muscle actin myofibroblast, alpha-actin gene. So one important aspect of a screen is, especially in our screen, which we were looking for chemicals that would inhibit our reporter, that we would hope would be anti-fibrotic Eric Small:                  Our hope was that this reporter would actually, in some cases, lead to an anti-fibrotic compound, but an important aspect of this screen, which was, I think the original question, was to not come up with factors that would just kill fibroblasts, but come up with factors that would specifically inhibit smooth muscle actin and myofibroblast activation without being too toxic. We don't want to inject a toxic chemical into a person; we want to inject a chemical that would be specific to an activated myofibroblast. So that was the first consideration, is to make sure that these were not toxic compounds, but were acting specifically on the smooth muscle actin report. Cindy St. Hilaire:        So with this system, you were able to screen over 2000 compounds, it was like 2300 or something like that. From that 2000 compounds screen, you zeroed in on salinomycin and two other compounds that are in the same family, I think, of chemicals like polyether ionophores they were called, I think it was the top three were all this similar class. So that's probably unsurprising that similarly-structured chemicals have a similar function or phenotype, but it's also intriguing. So I'm wondering, what's known if anything, about this class of chemicals, have they been used in therapy or is there some kind of naturopathic history to salinomycin or these other compounds that maybe if we read more carefully, we would have got a hint before? Ryan Burke:                Salinomycin has a pretty storied history in the literature, but it's an odd history. It's a veterinary antibiotic. So it's actually used primarily in livestock management and it had really no approach in human science at all. Then it was discovered that salinomycin, its earliest contribution, was that it is a compound that is actually very selectively targeting cancer stem cells. So salinomycin has a very extensive literature in cancer. It affects a lot of relevant signaling pathways, it's actually where we got a lot of our insight as to what we should be evaluating in fibroblasts. Both, in terms of ... This is probably going to be a charged statement; but there's a lot of similarities in how ... Cancer cells, when they're metastasizing and activating and moving around, there's a lot of EMT involved in that, there's a lot of things that are very analogous to how fibroblasts activate in heart failure. Ryan Burke:                I'm not saying they're the same, that's the charge portion of it, but the pathways are often conserved. What we found is that salinomycin had been studied extensively in various models of both solid and blood tumors, and it was found that it was affecting a whole ton of signaling pathways and sparing others, which was actually some of the insight that we had about AKT signaling. In the heart, it seemed very easy to just apply that and say, "Well, activation of fibroblasts is largely dependent on signaling pathways like SMADs and p38 signaling, so let's see what salinomycin does to these pathways in fibroblasts," and it turned out that that wound up being a very fruitful avenue for exploration, because it does behave very similarly in fibroblasts to the way it behaves in cancer cells. We didn't really find a lot of discordance in those results. Ryan Burke:                This study was very iterative, right? So do the high-throughput screen, find the drug, then try a preclinical model in animals. Then when it worked quite well in the angiotensin, hypertension-induced remodeling, that's a pretty mild model, right? Give the mouse an MI, see if it works in that, because that's a much more serious remodeling and when it performed well there, it's like, "Wow, you really actually probably have something here." Cindy St. Hilaire:        Yeah, and that's a perfect segue for my next question really, was I wanted to ask about these different murine models. Like you identified this compound, now you want to test it. Could you maybe give us a little brief background on why you chose the models you did and the treatment regimens that you also tried? Ryan Burke:                Sure. When we began, we began with angiotensin infusion because it's a fairly mild remodeling. You get some hypertrophic remodeling of the heart, you get some proliferation and some mild fibrosis in the mouse model. We figured this would give us the best chance to see a signal versus noise. It turned out that the results were really striking. Even the mice that were given the condition that we expected to see nothing in, is the drug with a saline infusion, even that had effects that were consistent with the effects that were seen. Consistent in direction in terms of the overall morphology and function of the heart, consistent with what you were seeing with the normalization of that hypertrophic remodeling in the angiotensin model that also got the drug. So that was really interesting to us. It was just consistent all the way through. Ryan Burke:                We wound up having a meeting about it and we were like, "All right, we've done the preventative regimen. We've preloaded them and then run them through with the drug. Now let's see if we can reverse established remodeling." So we did that study and when that worked out okay, there was yet another discussion where it was like, "All right, are we doing this?" And it was a myocardial infarction study. Myocardial infarctions, that's really extensive remodeling with huge changes, both the macro and microstructures of the heart. There's a lot more of an inflammatory component involved in that. Ryan Burke:                So we weren't sure how this would perform and it turns out that it performs exactly as it performs in pressure overload. You see normalization in physiology. I think that's part of the power of this study is that you're looking at non-ischemic and ischemic heart failure models, you're looking at preventative and interventional regimens, and it's just consistently performing at a level. We wanted to check all of our boxes, really, with this. Cindy St. Hilaire:        Sure. Yeah, maybe salinomycin's going to be the new aspirin we pop when we're over 50. Ryan Burke:                I doubt it, it's worth $7 a kilogram. I very highly doubt anyone's licensing that. Eric Small:                  But I think it's interesting you say that because understanding the mechanism after you understand that it's efficacious is sort of a similar idea here. We don't necessarily know precisely what it's targeting to act as an anti-fibrotic in this case, and so there's a lot of work to be done on this compound. I'd like to reiterate something that Ryan actually said is that really interesting, at least in cells and in the animal models, that salinomycin doesn't have a huge impact on the heart or on cultured fibroblasts in the absence of, for example, TGF-beta stimulation or a disease mechanism. It's really when we have a disease that salinomycin blocks the activation of the myofibroblasts and prevents that from contributing to the disease. Cindy St. Hilaire:        Interesting. So that can really, at least in the case of maybe cardiomyopathy, would help target it to the heart. Eric Small:                  That would be the hope, yeah. Cindy St. Hilaire:        Yeah, that's great. Wow. Speaking of the heart, and you mentioned this in that first answer that you had about the fibroblast being kind of the forgotten child of the heart and the focus is really more the cardiomyocyte, but did this drug have any impact on the cardiomyocytes itself that are also probably exposed to this TGF-beta signaling, in the context of an injury? Eric Small:                  So this is where we have some interesting, but not anticipated, results. So we obviously performed a screen in fibroblasts to look for specific anti-fibrotic compounds and when we put this into animals into ischemic or non-ischemic models, especially in the ischemic model, we found a much better outcome than we would have expected from simply an anti-fibrotic. So for example, we saw that pretreatment of mice with salinomycin prior to myocardial infarction, almost completely abrogated, not completely, but highly significantly abrogated necrotic tissue formation. So when Ryan went back and looked at the percentage of heart that became necrotic, or ischemic, after myocardial infarction, it actually reduced the necrotic core significantly. So we do think it's acting on cell types other than the fibroblasts in the context of ischemic remodeling, and it does seem to induce potentially protective signaling pathways in cultured myocytes. So that's definitely an area that we'd be interested in pursuing in more detail. Ryan Burke:                So of course the question there is, and this is a totally fair question for people to evaluate, we're looking at an organ in which all the cell types are talking to each other. We know we've affected the fibroblasts in a certain way, and we know to a certain extent, from what we found, what we've done for the fibroblasts, and we know what that looked like as a result in myocytes, but who initiated that, right? Did we affect the myocyte and then fibroblasts changed? Or did we affect fibroblasts and myocytes changed? But those are important type questions. We've shown the changes, but how do we show the connections? I think that's the really interesting work that we're still doing. We even extended it a little bit to endothelial cells in the heart, because we were showing that there was sort of a preservation of vascularization in the MI model that was associated with salinomycin, and we wouldn't rule out that we were affecting endothelial cells as well. I mean, I think this is a subject for discussion in the field, in the future. Groundwork is there, it's time to move forward. Cindy St. Hilaire:        Yeah, that is so exciting, and it's also I guess the classic chicken and egg question of science. What's causing what? That's excellent. So what's next for this project? I mean, you just highlighted some other angles, endothelial cell, but is there plans to translate it to a clinical setting, especially because it's already used in humans, so there's all that safety data out there? What's the plan? Eric Small:                  So that's a really interesting question. So our collaborators here at the University, Colin Woeller, Patricia Sime, Rick Phipps, they have been involved in the study with us and they are interested in fibrosis in other aspects as well. So they're interested in lung fibrosis, idiopathic pulmonary fibrosis, ocular eye fibrosis, and they've found that in other situations, salinomycin can inhibit fibrotic disease remodeling, for example, in the eye and in the skin. So branching out into other animal models of fibrotic disease is one area that we'd like to pursue. One area that I'm really interested in looking at salinomycin would be, for example, in models of HFpEF to see whether salinomycin might be efficacious in limiting the progression of animal model HFpEF. These are now becoming more prevalent and so it'd be great to test that there. Eric Small:                  So I think probably with some of these small animal studies, it would lay the groundwork for larger animal studies as collaborations or with other investigators. Absolutely, I think that's where this could definitely go next. Ryan Burke:                Also, it's a high-throughput screen, right? It wasn't the only hit and so extending the screen outwards both ... So the screen was designed to pick up both anti and pro-fibrotic drugs. So pro-fibrotic drugs have applications in wound healing. It also gives us a hint as to if a drug has some unexpected side effects in large clinical populations, then we can look at that and say, "Oh, maybe we have mechanistic understanding of why this might be the case." I think you'll see some future explorations down that path as well in that study. Cindy St. Hilaire:        Well, I look forward to seeing all of them. This was a wonderful study. I'm more vascular biologist, but obviously being on Circ Res, I'm learning so much more about the heart, but this one, I just particularly love that you started with this crazy complex question of what the heck is going on and this high-throughput screen was just designed in such a way that it really narrowed down what was a huge amount of options to start with. So it was really elegantly done and I just love the story, so congrats to you both and I look forward to future publications. Eric Small:                  Thank you. I'm especially proud of this one because as a basic scientist and as a trained in graduate school as a developmental biologist, I was following the science and when this opportunity arose to try to make this high-throughput screen work, I mean, this was as clinically relevant as I could ever have imagined my lab becoming. I'm really proud that we're able to do that. Cindy St. Hilaire:        Absolutely. I know, it's something we always talk about, and this research can be translated to humans eventually, and you're almost there. That's great. Well, congrats again. Thank you both for taking the time today and I look forward to your future studies. Eric Small:                  Thank you, Cindy. Ryan Burke:                Yeah, thanks Cindy. Cindy St. Hilaire:        That's it for the highlights from the May 28th and June 11th issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DiscoverCircRes. Thank you to our guests, Drs Eric Small and Ryan Burke. This podcast is produced by Ashara Ratnayaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most up-to-date and exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association, 2021. The opinions expressed by the speakers of this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.  

How celebrity began to change the face of sport, and how boards went from surf to street. Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 5 Cast: Paul . . . . . Gunnar Cauthery Steve . . . . . Aaron Gelkoff Tony . . . . . Arun Blair-Mangat Bill . . . . . Nathan Osgood Barbara . . . . . Jane Whittenshaw Shoji . . . . . Daniel York Loh Phil . . . . . Trevor White John . . . . . Mark Edel-Hunt Doug . . . . . Joseph Balderrama Rob . . . . . Wilf Scolding Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Walt Frazier, Art Simburg, Tony Alva, Steve Van Doren, Jeff Johnson, Julie Dixon, Bob Woodell, Peter Moore, Russ Gater, Cindy Yoshimura, Patricia James, Clare Ewing and Jamie Larsen.

Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 6 Cast: Horst . . . . . Mark Edel-Hunt Kathe . . . . . Jane Whittenshaw Reporter . . . . . Gunnar Cauthery João . . . . . Joseph Balderrama Rob . . . . . Wilf Scolding Phil . . . . . Trevor White Adriaan . . . . . Roger Ringrose Secretary . . . . . Cecilia Appiah Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Michael Dassler, Sigi Dassler, John Boulter, Patrick Nally, Sonny and Pam Vaccaro, Julie Dixon, Angelo Anastasio and Andrew Jennings.

Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 7 Cast: Ron . . . . . Ed Gaughan Nurse . . . . . Charlotte East Frank . . . . . Martins Imhangbe Phil . . . . . Trevor White Rob . . . . . Wilf Scolding Bob . . . . . Joseph Balderrama Jeff . . . . . Ian Dunnett Jnr. Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Russ Gater, Jeff Johnson, John Boulter, Mike Deegan, Gary Aspden, Neal Heard, Julie Dixon, Peter Moore, Nelson Farris, Joan Benoit Samuelson, Gina Millson, Clare Ewing and Jamie Larsen.

Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 8 Cast: Rob . . . . . Wilf Scolding Michael . . . . . Martins Imhangbe Phil . . . . . Trevor White Sonny . . . . . Joseph Balderrama Cheryl . . . . . Cecilia Appiah Paul . . . . . Ed Gaughan Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Julie Dixon, Sonny and Pam Vaccaro, John Boulter, Joe Foster, Angel Martinez, Professor Akilah Carter-Francique, Jeff Johnson, Bob Woodell, Nelson Farris, Peter Moore, Dr Todd Boyd, Paul Litchfield, Victoria Purcell, Michelle Apodaca, Clare Ewing and Jamie Larsen.

Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 9 Cast: Rob . . . . . Wilf Scolding Phil . . . . . Trevor White Waitress . . . . . Cecilia Appiah Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Peter Moore, Julie Dixon, Nelson Farris, Sonny and Pam Vaccaro, Paul Litchfield, Anna Bryher, Rob Harrison, Mimmy Kowell, Matt Powell, Sebastien Kopp, Angel Martinez, Bob Woodell, Sigi Dassler, Michael Dassler, John Boulter, Joe Foster, Joe Franklin, Gary Aspden, Clare Ewing, Adam Gibbons and Simon Ward.

How two shoe-making brothers played a part in altering German history. Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 2 Cast: Sepp . . . . . Roger Ringrose Joe . . . . . Aaron Gelkoff Rudi . . . . . Joe Sims Adi . . . . . Gunnar Cauthery Horst . . . . . Mark Edel-Hunt Fritz . . . . . Ian Dunnet Jnr Eckel . . . . . Stefan Adegbola Charles . . . . . Trevor White Clarissa . . . . . Jane Whittenshaw Chuck . . . . . Joseph Balderrama Bill . . . . . Nathan Osgood Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Joe Foster, Sigi Dassler, Michael Dassler, Abe Aamidor, Charles Slack, Angelo Anastasio, Patrick Nally, John Boulter, David Jones, Michael McKnight, Helmut Fischer, Kerstin Neuber and Victoria Purcell.

The sibling rivalry that spawned two of the world's biggest sports brands. Trainers? Sneakers? Whatever you call them - they are amongst the most iconic cultural objects of our time. But their evolution is a story rarely told until now. Sneakernomics is a close encounter with the visionaries who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. It's 100 years since salesman Chuck Taylor joined Converse and the Chuck Taylor All-Star was born, perhaps the most iconic trainer of all time. Across nine episodes, we trace the extraordinary transformation that has happened since, telling the origin stories of some of the world's biggest brands and how leisure evolved into a multi-billion-dollar industry. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be No. 1 tore families and friendships apart, divided towns, and sometimes even distorted sporting ideals. Presented by Nicholas Smith, (author of Kicks: The Great American Story of Sneakers) and 1Xtra presenter Ace, with drama written by multi award-winning playwright and screenwriter Al Smith. Episode 1 Cast: Adi . . . . . Gunnar Cauthery Rudi . . . . . Joe Sims Jesse . . . . . Arun Blair-Mangat Kathe . . . . . Charlotte East Friedl . . . . . Ceciliah Appiah Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Mike Holt, Angelo Anastasio, Dr Todd Boyd, Michael Dassler, Sigi Dassler, David Jones, Joe Foster, Professor Akilah Carter-Francique, the Adi & Käthe Dassler Memorial Foundation, Helmut Fischer, Kerstin Neuber and Victoria Purcell.

How an Oregon track coach ignited the running boom in America. Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 3 Cast: Bill . . . . . Nathan Osgood Phil . . . . . Trevor White Jeff . . . . . Ian Dunnett Jnr Shoji . . . . . Daniel York Loh Dale . . . . . Wilf Scolding Carolyn . . . . . Cecilia Appiah Bob . . . . . Mark Edel-Hunt Truck Driver . . . . . Joseph Balderrama Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Jeff Johnson, Bob Woodell, Angel Martinez, Julie Dixon, Nelson Farris, Peter Moore, Jamie Larsen, Clare Ewing and Jeffrey Johnston.

How the shoe wars and the Dassler family rivalry reached their peak in Mexico 1968. Sneakernomics is a close encounter with the visionaries, artisans and journeymen who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. Across nine episodes, Sneakernomics tells the extraordinary origin stories of some of the world's biggest brands, and how sponsorship deals and celebrity culture redefined our relationship with products. It's also a business story – how leisure has evolved into a multi-billion dollar industry; a sports story – how games became organised and grew into a global spectacle; and it's a story of invention – how enthusiastic hobbyist-pioneers often took extraordinary risks that changed the course of sport and fashion. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be number one tore families and friendships apart and divided towns. Above all, this is the story of the people behind the shoes. What you'll hear is a mix of interviews with many of the key individuals who've played their part in that extraordinary story, interlaced with moments of fiction inspired by their testimonies and our research. Written and presented by Nicholas Smith, with 1Xtra presenter Ace. The drama is written by Al Smith. Episode 4 Cast: Bud . . . . . Joe Sims Tommie . . . . . Arun Blair-Mangat John . . . . . Stefan Adegbola David . . . . . Gunnar Cauthery Sepp . . . . . Ian Dunnett Jnr Michel . . . . . Hasan Dixon Inspector . . . . . Joseph Balderrama Horst . . . . . Mark Edel-Hunt Concierge . . . . . Cecilia Appiah Other parts . . . . . Charlotte East & Trevor White Production Trainee: Marithe Van Der Aa Assistant Producer: Ben Hollands Sound: Peter Ringrose Producer: Sasha Yevtushenko Special thanks: Art Simburg, David Jones, Sigi Dassler, Professor Akilah Carter-Francique, Dr Todd Boyd, Michael Dassler, John Boulter, Patrick Nally, Michael McKnight, Helmut Fischer, Harry Blutstein, Professor Kevin Hylton and Kerstin Neuber.

Trainers? Sneakers? Whatever you call them - they are amongst the most iconic cultural objects of our time. But their evolution is a story rarely told until now. Sneakernomics is a close encounter with the visionaries who've made, and been made, by trainers. We'll follow in the footsteps of mavericks, hustlers and dreamers, and hear their tales of boom and bust, fame and infamy, hope and heartbreak. It's 100 years since salesman Chuck Taylor joined Converse and the Chuck Taylor All-Star was born, perhaps the most iconic trainer of all time. Across nine episodes, we trace the extraordinary transformation that has happened since, telling the origin stories of some of the world's biggest brands and how leisure evolved into a multi-billion-dollar industry. The sneaker story is characterised by fierce competition and rivalry. We explore how the quest to be No. 1 tore families and friendships apart, divided towns, and sometimes even distorted sporting ideals. Presented by Nicholas Smith, (author of Kicks: The Great American Story of Sneakers) and 1Xtra presenter Ace, with drama written by multi award-winning playwright and screenwriter Al Smith.

Nicholas V. Smith joins Bret on the latest episode of Titans of Nuclear. 1) From the Football Field to Electrical Engineering (1:54-17:05) 2) Nuclear’s Role in Grid Stability (17:05-24:52) 3) National Reactor Innovation Center Projects (24:52-35:33) 4) ZPPR and EBR-II Modifications (35:33-47:19) Find more episodes on iTunes, Spotify, and on our Titans of Nuclear YouTube. You can follow us on Twitter at @NuclearTitans.

Summary: Our guest CJ Casciotta is a well-known speaker, author, and Tedx alum. Today we talk about what it means to be weird and how embracing that can propel your business into a truly purposeful venture. Everything you do can be knocked off, but your unique weirdness, cannot. At college in Southern California during the birth of YouTube and the Twittersphere, CJ started out helping people develop their brands. Now he’s a brand consultant and has turned his specialities of leaning into purpose on himself- the result is Ringbeller Studios. Today’s episode is going to dig into CJ’s unique value proposition, how embracing his weirdness has turned business into passion, and how you can apply this same technique in your agency.   Top 3  Curtain Pulls in this episode:  Lean into your own personal weirdness- the thing that makes you unique and stand out from the crowd is what is going to propel you life and in business (contrary to what we are taught growing up). Everyone is uniquely suited to serving others around them in an authentic way, and getting to that core means embracing your weirdness! Don’t be ashamed of having fun doing what you do. When you’re creating content and driving creativity for your brand, it can sometimes come with a feeling of guilt or shame about having fun while you work. Resist that feeling. Having fun increases your creativity, helps you create a better product, and well… it’s fun, so enjoy it for goodness sakes! Being weird isn’t a license to be obnoxious or unkind. Lean into your uniqueness with the goal of making the works better for everyone. Don’t live trying to PROVE something to the world. Live trying to GIVE something to the world.   For more tips, discussion, and behind the scenes: Follow us on Instagram @AgencyPodcast Join our closed Facebook community for agency leaders   About our Guest:  CJ Casciotta: Founder of Ringbeller Studios, author of Get Weird, and overall brand-building specialist, CJ resides in Franklin, TN after moving from Southern California. He is the innovative brain behind educational and kid-driven content that does a great job of teaching skills that kids can use every day. His childhood love of the Muppets and Mr Rogers Neighborhood planted a deep desire to create positive change and teach kids kindness and creativity in a way that was palatable for them, meeting kids where they are at, both in the classroom and at home.   Check out more on CJ: https://www.cjcas.com/ Grab his book: Getweirdbook.com Connect with him on LinkedIn: https://www.linkedin.com/in/cjcasciotta   About The Guys:  Bob Hutchins: Founder of BuzzPlant, a digital agency that he ran from from 2000 -2017. He is also the author of 3 books. More on Bob:  Bob on LinkedIn twitter.com/BobHutchins instagram.com/bwhutchins Bob on Facebook Brad Ayres: Founder of Anthem Republic, an award-winning ad agency. Brad’s knowledge has led some of the biggest brands in the world. Originally from Detroit, Brad is an OG in the ad agency world and has the wisdom and scars to prove it. Currently that knowledge is being applied to his boutique agency. More on Brad: Brad on LinkedIn Anthem Republic twitter.com/bradayres instagram.com/therealbradayres facebook.com/Bradayres Ken Ott: Co-Founder and Chief Growth Rebel of Metacake, an Ecommerce Growth Team for some of the world’s most influential brands with a mission to Grow Brands That Matter. Ken is also an author, speaker, and was nominated for an Emmy for his acting on the Metacake Youtube Channel (not really). More on Ken:  Ken on LinkedIn Metacake - An Ecommerce Growth Team Growth Rebel TV twitter.com/iamKenOtt instagram.com/iamKenOtt facebook.com/iamKenOtt   Show Notes: [1:00] Brad introduces today’s guest, CJ Casciotta of RingBeller Studios. They met back in Santa Monica, CA several years ago and both wound up in Franklin, TN.  Quotes CJ’s book “What if we live as though we had something to give instead of as though we had something to prove?”  Brad asks CJ for a recap of the last 10 years since they last connected in California.  [5:15] CJ talks about his late college years when YouTube and Twitter first got big and how quickly that changed the landscape. He worked as a freelancer and media producer as a natural flow from college and eventually honed in on branding as a speciality.  “I loved getting into people’s message, their identity, what they cared about, what made their heartbeat as a company, as an organization… really going deeper and leaning into those conversations that I was already naturally having with clients.”  Now he’s transitioned over to a brand consultant, which feels strange because 10 years ago there was no such thing- but ultimately he is passionate about helping people find that core essential value that makes you unique and ultimately, makes you weird.  He started a podcast called “Sounds like a Movement” where they got to interview a lot of really interesting people all around the world who were using their brand and unique message in a really great way to make a difference in people’s lives.  [7:18] CJ continues: “Then at some point I kind of woke up and realized I like doing this, but what is my core purpose? What’s my unique point of contributing to the world? And I realized I wasn’t leaning into my personal weirdness…”  “What if I started doing all these things, teaching people what made them unique and how to express that. And how to make a positive impact on their community.”  He shares that with Ringbeller, he was able to merge his love of uniqueness and with the creativity he craved- rooted in a childhood love of the Muppets and Mr Rogers Neighborhood. They create educational, fun videos for kids.  Now the focus has been on scaling that in a sustainable way to help as many people as possible.  His puppets have been able to interview big names such as Ira Glass, Seth Godin, and Nicholas Smith.  [10:05] Bob talks about how The Guys have extensive careers in branding and creating unique visions for their clients, but often the hardest client is yourself when it comes to branding. A quote we mention often at Agency Exposed “The cobblers kids have no shoes.” He asks CJ about the process of moving from clients to himself as the focus.  [10:49] CJ: Says he will probably always be iterating what that looks like- but starts with knowing when to invite people in and what to invite them in on. Perspective can get narrow, so it’s important for him to know what ONLY he can do and maintaining that balance has been the struggle.  [11:45] Brad asks about CJ’s theme of “weirdness” in his business and why he values the weird so much in a business sense.  [12:15] CJ talks about the wakeup call of realizing that the need to fit in and measure up that we are taught as kids no longer applies- in reality, it’s what makes us stand apart from others that will bring real growth. This is truly the cornerstone for branding for any brand and business.  “On a personal level… I was a weird kid… I loved things that weren’t your standard idea of what it meant to be a kid.”  [13:55] CJ “The great danger is that we are educating our kids and conditioning kids to really neglect the thing that will help our society move forward and innovate and be the environment that we are all really long for and wish for.”  [15:27] Bob asks “Would you say that you’re taking the word unique… and figuring out what’s your unique selling proposition? Are you saying that, are you taking the word unique and exchanging it for weird, or would you define them as different things?”  [15:55] CJ responds that yes they are being used synonymously. “It drills down to how you position the business, how you create a team culture, etc.”  [16:46] Bob says that being “unique” or “different” is one thing, having a different angle to approach a sale. But truly being “weird” is a bit more vulnerable, a bit more human.  [17:31] CJ talks about another litmus test for weirdness versus your run of the mill unique selling proposition- it comes from your people, the humans and make up your organization- not just a product set apart from other products.  [18:18] Ken asks CJ for more info on his current business model. “Do you have clients? Do you create products?”  [18:31] CJ responds. V1 of an app for Ringbeller is in being built. They are building more interactivity and games for ways to turn kids into the media creators. This is being filtered through a school product but also a family product.  Creating a product that parents/teachers can trust with the social, emotional wellbeing of their child is the end goal. Especially in light of changes in the academia industry since Covid-19, there is tremendous opportunity here.  [20:46] Ken says that he feels this need, as a dad trying to help his kids through the delicate learning stages they’re at right now.  [21:23] CJ says that Ringbeller is focused more on soft skills, on social and emotional learning. There is a lot of content out there that focuses on these things, that are very touchy feely, but Ringbeller has created an archetype of an 8th grade boy that may not have resources or support, that would find these videos attention-grabbing and laugh-inducing, to then teach him important life skills that he needs.  The name Ringbeller comes from a Roald Dahl book, The BFG. A ringbeller is a really great dream that kids have. [24:11] Bob asks CJ what his ringbeller is, what his Why is behind the company.  [24:32] CJ says “I don’t think Mr Rogers ever intended to have his successor… his entire career and purpose was about helping us be a little version of what he was teaching… I really do think it’s not going to take one sort of individual leader, it’s up to a lot of little micro decisions and choices from each of us to live out that message.”  [26:35] Ken talks about how businesses should and could change lives, some are explicitly in that space. Some awesome realization that don’t think they have a deep reason for existence to realize they do, then use that influence to help the world is THE way to go.  [28:15] Ken highlights the pain points of creating a brand for yourself after you’ve spent so much time creating brands for your clients. How do they start creating their own media that has a meaning and purpose? [28:36] CJ says that for him, creating new content has always resulted in getting a new client along the way. It’s the one area where you don’t have the restrictions of your clients preferences. It might seem like playing, like too much fun to be work, but at the end of the day it is! It’s work and it’s investing in your brand and your vision.  [30:26] Ken can sympathize with this shame and guilt, as Metacake has created YouTube videos and books.  “I believe that you have to be intentional about exploring, and it’s kind of a never-ending thing… some people are born and they know their purpose but I think that’s rare.” [32:25] Brad asks CJ: “How do you communicate about your business to your employees so that they understand what the big picture is and what you’re really there to do- what’s the ethos of the company?”[33:00] CJ talks about being aware of the majority and minority micro culture that exist within every company. He gives the example of a brand he’s worked with, a young, creative, surfer kid-led company that constantly butted heads with their finance department. This was a great thing ultimately, as both play an important part of knowing the culture and maintaining the balance of authenticity.  “To safeguard against their creative culture going off the rails and being unproductive and unprofitable, they need to have a cultural minority sort of checking their balances so that they have a certain amount of weirdness and encourage a certain amount of weirdness.”  When an organization knows their culture, hands down, it makes things a lot easier.    “So if you are somebody that is in the cultural minority, you go, okay I am here to push back to a degree, but I know that I have chosen a role in an organization that values X versus Y and so at the end of the day I shouldn’t be frustrated and I shouldn’t be disenfranchised when they choose X over Y.”    [35:20] Brad asks CJ if a little bit of weirdness is necessary for the leaders to be able to get their employees to think outside of the box. [35:22] CJ: There is a difference between a company that defers to whatever the competition is doing versus a set of people who are free to create their own path to differentiate from the competition. He says there needs to be a little bit of that rebellious attitude in this regard- sort of like “We’ve gotta carve our own path, zig where everyone else is zagging.”  [37:38] Brad: “Knowing what makes you weird is the best thing you can offer your art, your business, your friends, your family, and yourself. It’s the essence of creativity. It’s the stuff of movements and the hope of humanity.”- this is a quote from CJ’s book!  [38:42] CJ plugs his book and platform! Getweirdbook.com and ringbeller.com  [39:53] The Guys reflect on their talk with CJ. Bob says that the feeling of shame that we all struggle with when it comes to creativity and the fun that comes along with it is important to talk about. With so many voices speaking into the void about how to do YouTube the “right” way, how to motivate your clients to click, it’s easy to lose sight of everything that CJ is talking about.  [40:28] Ken talks about how marketing is contributing to the lack of mental health in the population SO much. For example, going into Q4 as an ecommerce brand doesn't mean stress is innate in everything you do. Shame-based marketing, super urgent marketing, etc are contributing to the detriment of people’s mental health. “I think marketers should realize that weight.”  [41:55] Ken: “In my opinion, I think finding purpose is the best business strategy. It’s the only one that people can’t rip off.”  As a society, we’re scared of being different. But that truly is the only thing that is going to make you stand out- your weirdness is the ultimate differentiator.  [44:37] Brad talks about the commercials that he’s seen since Covid-19 took over the news and culture. Instead of ads for cars, the ads were about human triumphing, the human spirit, and more of an emotional connection.  [46:41] Ken says that when you’re the leader of the company, when you’re developing the company ethos and pedigree that will be trained into your employees and passed on, at some point you have to come out about what your purpose is. If that doesn’t happen, it’s highly unlikely that your wins are going to have the impact that they could have otherwise.  [48:06] Brad talks about how weirdness may not do favors on Wall Street, but it’s what keeps people’s eyes on you and what truly draws value to you in the end.  [52:50] Bob says that speaking with Calvin Nowell of C’Mon Media is a great example of leaning into what makes you different and even weird, by some standards. It sets him apart and makes him memorable.  [53:46] Brad quotes CJ once again “What if we lived as though we had something to give instead of living as though we have something to prove.” 

Nicholas Smith explains how we all came to get our kicks from the ubiquitous sneaker. Conor Heffernan on the specter of the 97-pound weakling and the rise of bodybuilding in the US.

Now, more than ever, the world is moving at a breakneck pace. Companies and businesses need to be able to change with it if they want to stay relevant and still be a part of it in the future. But being able to remain relevant is only part of it. One also needs to be […]

Now, more than ever, the world is moving at a breakneck pace. Companies and businesses need to be able to change with it if they want to stay relevant and still be a part of it in the future. But being able to remain relevant is only part of it. One also needs to be sustainable to cope with so many product and material shortages and an increasing demand for eco-friendly products. Joining Tom Hazzard and Tracy Hazzard on the show today is Nicholas Smith, the Director of Operations for HP, Inc. Nicholas gives an eye-opening view of 3D manufacturing sustainability and supply chain management, production, and planning to create business sustainability. He also talks about HP’s initiative to innovate a better way to print, publish, and produce while lowering the environmental impact of printing. More About HP: Capture and Create with Z by HP, Inspiring you for your next creative breakthrough with the Z portfolio designed and built to improve the way you create. Discover the latest Z Book to help you with your latest creative project. Experience your design with HP Multi Jet Fusion technology and solutions reinvent design and manufacturing, unlocking the full potential of 3D printing and bringing down the barriers of 3D printing adoption across industries through materials innovation. For more details about Multi Jet Fusion technology click here. Join the WTFFF?! 3D Printing movement today: 3DStartpoint.com Facebook Instagram LinkedIn Twitter YouTube

This podcast is possible due to the donations of its supporters. Donate here if you believe in what we do: https://anchor.fm/sportsasajob/support We are joined by Nicholas P. Smith. He is an Instructor and Internship Coordinator of Sport Management in the College of Arts, Sciences, and Education in the Department of Counseling, Recreation, and School Psychology at Florida International University. He received his Master of Arts from the Department of Kinesiology and Health Studies at Southeastern Louisiana University. Mr. Smith received his Bachelor of Arts degree in political science from Louisiana State University. Smith also completed his internship at St John's University Athletics in New York, New York. Mr. Smith currently teaches sports management undergraduate courses, both traditional and online. He comes to FIU with over a decade of experience in various management positions with ASM Globals formally SMG / Mercedes Benz Superdome / Smoothie King Center / Champions Square. Along with teaching at FIU, Mr. Smith volunteers with the Greater New Orleans Sports Foundation, Sunbelt Conference, Orange Bowl Committee, Atlanta Super Bowl Host Committee, and is on the recruiting volunteer committee for the 2020 Miami Super Bowl Host Committee. Smith has also managed events for Louisiana State University Athletics, Tulane University Athletics, University of New Orleans Athletics, New Orleans Babycakes, and Landmark Event Staffing Services over the years. Let’s learn how to “Apply Yourself” with Nicholas Smith! Episode Timestamps: 1:34: Nicholas shares with us his background and 13 years of practical experience. 7:30: We dive into his 13 years of experience starting with being hired at the famous Superdome. There is a moment that Nicholas does not get the job he originally applies for. 13:25: Nicholas is now an instructor and internship coordinator. How much does his previous experience play into what he emphasizes to his students? 15:00: Are you thinking about going back to school or switch majors? Hear about what a great sport management program looks like and the importance of it. 22:38: What is any trends that Nicholas thinks will be big in the future? You can follow Nicholas Smith on Twitter @nicksmithMA and on LinkedIn here. Send us your feedback and send us questions on our Social Media Platforms: Twitter @sportsasajob Instagram @sportsasajob Facebook @sportsasajob LinkedIn: Sports As a Job Visit our website www.sportsasajob.com Intro Music credit to ABAPO Music Studios: https://www.youtube.com/channel/UCwF1OqcNsQEOd0iNu0Yjitg Go sign up for #1 job sports focused job board online and be part of their network. https://www.jobsinsports.com/ make sure TO LET THEM KNOW YOU HEARD OF THEM FROM THE PODCAST. I want them to know we got industry leaders and future stars in this community!

Good morning, RVA! It’s 61 °F, and rainy. But! Later today the rain should stop and the temperatures should head all the way up into the mid 70s. If things work out, we could have some good porch-sitting weather this evening.Water coolerAs of this morning, the Virginia Department of Health reports 10,998 positive cases of the coronavirus in the Commonwealth, and 372 people in Virginia have died as a result of the virus. VDH reports 1,379 cases in and around Richmond (Chesterfield: 402, Henrico: 718, and Richmond: 259). The data bad news from yesterday: 732 new positive cases marks the most ever reported in a single day. The data good news from yesterday: 3,740 tests is the second most ever reported in a single day. Now we just need to keep it up and, like, quadruple the number of tests we’re doing. Here’s the chart of new cases and new tests that I keep updating, and here’s the chart of the seven-day rolling average of new tests per 100,000 people that I stole from the NYT. Again and always, I don’t think any of these data indicate the true number of folks infected with the coronavirus. They’re just lots of context for folks who don’t know how to process any other way than building spreadsheets.On the testing tip, the Richmond Times-Dispatch says the Health District will provide walk-up testing in three of Richmond’s public housing neighborhoods: Hillside Court, Gilpin Court, and Creighton Court. This is great to see, and I hope folks take advantage of it. More of this everywhere!Remember however many virusweeks ago when the Governor announced that he had signed a contract with a private company to wrangle the supply chain and get healthcare workers in Virginia the gear they need? Kate Masters at the Virginia Mercury has the details on that contract, and, whoa, what a weird world we are living in. What states must go through to get critical supplies—simultaneously battling each other and the worst parts of capitalism—seems…suboptimal.The Virginia Employment Commission’s weekly update continues to show massive numbers of new folks filing for unemployment—but massively fewer than the last couple of weeks. 82,729 people submitted initial claims for unemployment insurance for the week ending in April 18th, but that’s “a decrease of 21,890 claimants from the previous week.” This particular graph shows how the Commonwealth has passed a clear peak in new claims filed while the number people continuing to file for unemployment insurance keeps climbing (297,993). Since this crisis began, food service workers have made up 20.2% of all initial unemployment claims. That’s wild, and I’d love to see how the occupations groups of folks filing has changed as we’ve progressed through the stay-at-home order. As with a lot of pandemic-related things, these numbers would be way more interesting if they weren’t about actual folks’ livelihood.I enjoyed this piece by Louise Lockett Gordon over at Bike Walk RVA about what the coronavirus has revealed about biking and walking in the region. I can’t agree with this more: “In this moment, opening neighborhood streets to biking/walking activity only can be done on a less grand scale, simply affording people nearby the opportunity to be active in a car-free environment.” The City should follow Oakland’s lead and close 10% of its streets to through traffic. That doesn’t mean emergency vehicles and residents no longer have access, it just means prioritizing our neighborhood streets for people to have safe places to move around outside of their home. This type of open/slow street policy is one of the easiest and cheapest things the City could do to make Richmonders’ lives better during the coronacrisis, and I’m not sure why we haven’t done this yesterday!Parks & Rec in Richmond announced that the Manchester Climbing Wall is now closed. I don’t know why people would want to put their sweaty virushands right where other folks’ sweaty virushands have been, but sure. Also, Parks closed Chimborazo Park to cars, which is maybe as close to a slow street as we’ve gotten!Roberto Roldan at VPM reports on something I’d not even thought of: Collecting signatures to get on the ballot while adhering to social-distancing requirements is…hard?…impossible? While getting on the ballot locally doesn’t require a huge number of signatures—just 125 for City Council—I can see how the tried-and-true ways of gathering signatures like attending large events or door knocking just aren’t going to work. I’m not opening my door for anyone these days, I tell you what.My pal Nicholas Smith resumed his Virginia General Assembly newsletter right before the GA’s reconvened sessions yesterday. He had a lot of questions that are now answered, but you should still tap through to read his thoughts on the Land Value Tax. Richmond now has access to another (progressive) form of tax! This is rare and wonderful and we should totally get to implementing it as soon as possible. I doubt “hey let’s do a new tax” is on any councilmember’s agenda—especially right before elections—but maybe we start putting the pieces together next year?At 10:00 AM this morning, ChamberRVA will host a virtual town hall with the Director of the Richmond and Henrico Health Districts, Dr. Danny Avula. I’m sure Dr. Avula is incredibly busy at the moment, so this is a rare opportunity to see him in a setting other than giving coronavirus updates from behind a podium.This morning’s longreadThe Hunt for Planet NineNerds on an adventure is one of my favorite genres of story.If the planet they’re looking for exists, it is likely six times the mass of Earth, with an atmosphere made of hydrogen and helium covering its rock-and-ice core. What makes it hard to find is its likely location: at least 400 times further away from the sun than our own planet, and 15 to 20 times further out than Pluto. As a theorist Batygin feels that he’s already mathematically proven its existence. But it’s generally accepted that for a planet to be considered discovered in the field of astronomy, the theory must also be accompanied by a photograph. This is where the Subaru telescope comes in. They know that Planet Nine is somewhere in between the constellation Orion and Taurus, but that’s about as exact as they can get, and they’ll need good weather to locate it.If you’d like your longread to show up here, go chip in a couple bucks on the ol’ Patreon.

Good morning, RVA! It’s 47 °F, and temperatures today will head right up into the mid-to-upper 60s. I dunno, we might could even see 70 °F! Expect a pretty temperate first week of February.Water coolerRichmond Police are reporting that a driver hit and killed a person walking along the 5200 block of Hull Street over the weekend. Police are still looking for the driver and the vehicle—which may be silver or gray in color with heavy damage to the front end. If you have any information you can call the RPD’s Crash Team Investigator (804.646.1665) or contact Crime Stoppers at 804.780.1000 or at 7801000.com.Remember when Republican freshman delegate Wendell Walker submitted a bad-faith bill to remove the Harry F. Byrd statue from the Capitol grounds? Byrd, a Democrat, was Virginia’s head segregationist, and I guess Walker thought that present-day Democrats would recoil at the thought of taking down a monument to an actual racist who happened to be one of their own. Well, that plan to own the libz has severely backfired as Democrats are pretty stoked to vote for Walker’s bill, which he has now requested be removed from consideration. Turns out, that’s not how things work, and the House Rules Committee has asked Walker to come to the front of the class and explain, why, exactly, he submitted the bill in the first place and why he now wants it killed. These sort of time-wasting bills that exist solely to prove a point (bread and butter for folks like Sen. Tommy Norment) work a lot better when you’ve got control of the legislative body—otherwise own the libz quickly turns into a very public self own.Speaking of bills that won’t die, Nicholas Smith’s latest edition of VAGAries gets into the particulars of how bills do or do not die. Tap through to read the thrilling tale of what exactly happened with Del. Bourne’s bill to redirect some of the State’s sales tax to help pay for Richmond’s proposed new downtown arena—it’s an absolutely bananas chain of events. The tl;dr is that almost no one knows if Bourne’s bill is actually all dead or if it’s still slightly alive (big difference). We’ll learn more at a Finance subcommittee meeting today at 8:00 AM, but I’m leaning toward the whole thing being a series of unfortunate events—you know, assume incompetence before you assume malice.Samuel Northrop at the Richmond Times-Dispatch says that Richmond Public Schools have sold the empty Moore Street School to VCU for $1. VCU has plans to turn the building into a child development center and will hold a third of the slots—at no cost!—for kids living in Carver and Gilpin Court. If this turns into anything like the VCU Health Family Care Center at Northside, it’ll be a pretty great addition to the neighborhood. I do, however, think, of all entities in the region, that VCU could afford to at least pay the assessed value of the property (I’d look that up, but the City’s parcel mapper appears to be down this morning). It’s awesome that VCU will hold space for kids in the community but, like, no need to just give property away when the school district has so many financial needs.What does it mean when legislators or bills say things are “in the public interest?” Sarah Vogelsong at the Virginia Mercury explains it all, in this edition of Virginia Explained. You’ll learn a bunch about legislative process but also how it applies to Virginia’s renewable energy economy.Today is your final opportunity to weigh in on the Amelia Street School renaming, which you can do at 6:30 PM (1821 Amelia Street). I think this is the final public engagement session for school renamingthat RPS plans to do, so we should soon see a report or a PDF or something with suggested new names for George Mason Elementary, E.S.H. Greene Elementary, the Amelia Street School, and the new middle school on Hull Street.via /r/rva, I kind of love this beer (or soda!) bottle cap map of Virginia.The 2020 Iowa Democratic caucuses take place today, and you can follow along in a million different ways, even right on Wikipedia! This means we’ve got just a single month until Super Tuesday, when Virginia’s primary rolls around.This morning’s patron longreadNightmares on wax: the environmental impact of the vinyl revivalSubmitted by Patron Jeanna. Everything comes from somewhere, including vinyl records. Keep reading though, because streaming music comes from somewhere too, and the environmental impact of massive data centers is certainly nonzero.While it is far exceeded by revenues from streaming, the vinyl market keeps growing – Americans now spend as much on vinyl as they do on CDs, while there were 4.3m vinyl sales in the UK last year, the 12th consecutive year of growth. So, if you’re one of the millions of people to re-embrace vinyl records, it’s worth knowing where they come from and how they’re made. There are containers called hoppers at each pressing station, brimming with the lentil-like polymer pellets that get funnelled down into the machinery, heated and fused to form larger biscuits that resemble hockey pucks, and squashed to make records.If you’d like your longread to show up here, go chip in a couple bucks on the ol’ Patreon.

Good morning, RVA! It’s 16 °F, but highs today will head up out of the frozone and into the mid 40s. Expect plenty of sunshine as temperatures continue to warm throughout the week.Water coolerI know it’s only January, but last night marked the official kickoff for the 2020 Budget Season! Over at the School Board meeting, Superintendent Kamras introduced his FY2021 budget (PDF), and, I swear y’all, it is the most readable and approachable budget document I think I’ve ever seen. They’ve got proposed expenditures broken down by categories from the strategic plan (Dreams4RPS(PDF)), which is so smart. For example, RPS wants to spend $489,000 more on adding six social workers, which falls under Priority 3, Safe and Loving School Cultures. Honestly, right away I feel a weird sense of protective ownership in this budget (??) since we all collectively spent so much time working on the strategic plan a couple summers ago. However, it all comes down to money and the extremely tiny amounts of it we have available, so what’s the total cost? $39 million more dollars. That’s a lot, but it should surprise exactly zero humans as RPS has been exceedingly clear and upfront with their budget needs moving forward over the next couple of years. The School District plans to pick up $18 million more from the State, should the Governor’s budget pass as is, so that leaves $21 million on the City’s tab. It’s been awhile, but do you remember how I kept talking about restoring the real estate tax to pre-Recession era levels because schools—not to mention transit or public housing—needed tens of millions of dollars of immediate investment? Well, City Council decided not to do that, so here we are with a big, not-unexpected request from Richmond Public Schools. I’m very interested to see how the Mayor and City Council deals with it. BUCKLE UP IT IS BUDGET SEASON.Schools don’t have a monopoly on budgets, and GRTC’s CEO introduced a FY20–22 Capital Blueprint (PDF). This budget document is…not as heartwarming as RPS’s—but that’s a high, high bar. C. Suarez Rojas at the Richmond Times-Dispatch breaks down some of the details, which include articulated buses and a Park and Ride for the Pulse.Over the long weekend, Richmond Public Schools Superintendent Jason Kamras decided to close schools this coming Monday, January 27th because “it appears that nearly 700 (about a third) of our teachers will be taking personal leave to participate in the VEA rally” for increasing state-level education funding. First, that’s kind of rad—good for those teachers. Second, my family is in the very privileged position of easily being able to absorb a day off from school with only a week’s notice. Many folks are not and will have to scramble to figure out childcare, meals, and a bunch of other logistics. I’m sure that was a tough call to make, but it feels like the right one. Also, where are you going to find 700 substitute teachers?Graham Moomaw at the Virginia Mercury has the update on the fate of Republican gun bills down at the General Assembly. Did you know Republicans had gun bills? They do, or, well, more accurately, they did. Unable to read the room, Republicans submitted some pro-gun violence bills, including one that would have allowed concealed carry without a permit. These bills did not make it out of subcommittee.Speaking of the General Assembly, I really recommend you check out my pal Nicholas Smith’s VAGAries email. Yesterday, he had a great bit about the proposed shopping cart bill (a real bill that definitely exists) and a couple days ago he had some nuanced thoughts on whether or not we should make Election Day a holiday. Sure, it’s nice to know about big-picture items like the ridiculous Republicans gun bills dying in subcommittee, but what I’m really after is slower, more thoughtful writing about what the heck stuff down at the GA means. This newsletter fills a hole in my politics-nerd life for sure!The impeachment trial of Donald Trump got underway in earnest yesterday. Lots of stuff happened! Or, at least, it took Republicans in the Senate a long, long time to vote NO on many, many things and to establish the rules for the next steps of the process. Now the arguments portion of the trial begins, which means it is definitely the time to subscribe to impeachment.fyi if you haven’t already. I mean, who wants to spend their own time watching hours and hours of public meetings drag on into the middle of the night? Just kidding! That sounds awesome, and, if I had the time, it is exactly how I’d spend my evenings over the next week or two. But, since I definitely do not have that kind of time, I will read the impeachment.fyi each morning and feel plenty informed.This morning’s longread“Flood the zone with shit”: How misinformation overwhelmed our democracyI loved this Vox article—even though it deeply bums me out—about our media and our very brain’s inability to deal with this present moment.We’re in an age of manufactured nihilism. The issue for many people isn’t exactly a denial of truth as such. It’s more a growing weariness over the process of finding the truth at all. And that weariness leads more and more people to abandon the idea that the truth is knowable. I call this “manufactured” because it’s the consequence of a deliberate strategy. It was distilled almost perfectly by Steve Bannon, the former head of Breitbart News and chief strategist for Donald Trump. “The Democrats don’t matter,” Bannon reportedly said in 2018. “The real opposition is the media. And the way to deal with them is to flood the zone with shit.”If you’d like your longread to show up here, go chip in a couple bucks on the ol’ Patreon.

In this episode, Robbie interviews Nicholas Smith, a fitness expert on how to get the absolute most out of your workouts and spend less time at the gym while making way more gains… Show Notes: Stronglifts, crossfit, HIIT, whats your workout routine and which is best? The biggest enemy to any workout protocol... (02:40) Things [...]

In this episode, Robbie interviews Nicholas Smith, a fitness expert on how to get the absolute most out of your workouts and spend less time at the gym while making way more gains… Show Notes: Stronglifts, crossfit, HIIT, whats your workout routine and which is best? The biggest enemy to any workout protocol (02:40) Things […] The post 126: 6 Easy Workout Hacks to Reach Your Fitness Goals Faster appeared first on Inner Confidence.

In this episode, Robbie interviews Leverage Tribe Leader, Nicholas Smith, a Chiropractor by trade and lifelong student of sales and persuasion, who has been party to over 100,000 interactions with patients; helping them to achieve a healthier back and spine. This podcast takes a deep dive into the strange but all-too-common phenomenon of why people often [...]

In this episode, Robbie interviews Leverage Tribe Leader, Nicholas Smith, a Chiropractor by trade and lifelong student of sales and persuasion, who has been party to over 100,000 interactions with patients; helping them to achieve a healthier back and spine. This podcast takes a deep dive into the strange but all-too-common phenomenon of why people often […] The post 123: Start w/ No, The Secret To Persuasion & Negotiation appeared first on Inner Confidence.

The Energy Department's Idaho National Laboratory has established a new innovation center to focus on a new generation of commercial reactor technologies. Heading up that office are Ashley Finan and Nicholas Smith, laboratory director and deputy director, respectively, who joined Federal Drive with Tom Temin to talk more about their work.

Dr. Nicholas Smith has worked with athletes in the NFL, NHL, MLB, AMA Supercross, as well as patients with more typical "office jobs". Nick dives in deep on the importance on mentors, and how they helped get him to where he is today. We also spoke about content strategies, and how we are both approaching tiktok. Thanks for tuning in!20AT20 - facebook - instagram Dr. Nick Smith - facebook - instagram - website - twitter - YoutubeBryce Betts - facebook - instagram - website - twitter - linkedin

In this podcast,  Dr Nicholas Smith and I talk about MUSCLES.  How to build muscle, how to prevent muscle atrophy, the best way to balance muscles, how to create a strengthening program and so much more.    We discuss how to develop muscle strength, muscle endurance, muscle power, and muscle tone to prevent injury and perform activities with confidence.  Aging causes our muscles to become smaller and slower, which is why consistent strength training is essential to age well.  Dr Smith explains the important elements of exercise intensity, frequency, duration, and consistency to meet your personal goals.  He gives a few tips that will help you stay motivated with exercise. Tune in to this episode to make your workouts better and more efficient.  You won’t want to miss this one! Watch the podcast on Balanced by Beth YouTube Channel.  Nicholas Smith PT, DPT, OCS, CSCS Movement Links Certified Clinician Owner of Smith Forged S&C -  www.SmithForgedSC.com Active on IG, YouTube, Twitter @smithforgedsc Beth Teran, PT, DPT, CSCS Host of Balanced by Beth Podcast Creator of 30 Day STRONG Programs Follow Balanced by Beth Instagram Account www.balancedbybeth.com  Thank You to Be Seen Co for your excellent and quality production of the Balance by Beth Podcast and YouTube Video.  www.beseenco.com If you are someone who directly benefits from this podcast and want to be a supporter to keep this content coming, please visit Beth’s patreon page and give as little as $1 a month. Your support is extremely valuable to this podcast. Thank You!  www.patreon.com/balancedbybeth  --- Support this podcast: https://anchor.fm/balancedbybeth/support

Moderator: Tyler Silverman, DPM, AACFAS Panelists:  Kelly Pirozzi, DPM, FACFAS; Nicholas Smith, DPM, FACFAS Release Date: December 15, 2018 Run Time: 37min 04sec

In this episode, Hall interviews Nicholas Smith of Southern Methodist University. Nicholas was selected for SMU Maguire Energy Institute's "Spindletop Fund" Investment Program 2017-2018, and is one of 30 students that analyze, track, pitch, and invest part of the SMU Endowment in energy equities each year.

Listen up. No, seriously. I had some people make this request and I thought it was a good idea. So, here’s an audio version of the recent article, Chad Reed: Against the Current. Read by the author, edited by Nicholas Smith. I’m working on creating a podcast channel for these on iTunes and Stitcher, etc. The post Ep. #1 Chad Reed: Against the Current appeared first on We Went Fast.

Fun episode recorded at Ahh Sushi in downtown SLC before the Ahh HaHa Comedy show. Ben and I are joined by comedians Christopher Stephenson, Nicholas Smith, and Michael Schooley stops by for a surprise visit. We talk about suicide, the health benefits of smoking, why Bob Marley is a cool name, and the uplifting tunes of Will Smith.

Floods in Cumbria; Donald Trump; Personal stories; Nicholas Smith; Tyson Fury; Prepare, Prepare, Prepare; Always move forward, never back; It's all in the delivery; An interview with Dale Irvin; Music from David Knopfler

This week on Stupid questions Nicholas Smith joins Jason Harvey and Natashia Mower to talk about the anniversary show of Dungeons and Comedy. After talking D&C they play some D&D. We had a lot of fun recording this episode, hope you have fun listening. http://earwholemedia.com/wp-content/audio/stupid-questions/008-stupid-questions.mp3 The post STUPID 008: “I Hope Blood Clots Are Flammable” appeared first on Utah Podcast Network.

Dr Adam Smyth (English, Oxford) Doing things with errors Nicholas Smith and Colin Clarkson (University Library, Cambridge) Practical printnig Abstracts Doing things with errors ‘God helpe the man so wrapt in Errours endlesse traine,’ laments Edmund Spenser’s Una in he Faerie Queene. But what can we, as readers and critics, do with errors in printed books? This paper suggests that the history of the Renaissance book is also a history of error, and proposes that we need to learn how to treat typographical slips seriously, or, at least, that we need to think more about their hermeneutical potential. The paper suggests two ways of proceeding: first, to treat errors as moments when, in breaking down, the book briefly but often vividly reveals the processes of its production; and second, to read errors and errata as literary forms that shaped the literary imagination of authors such as Spenser and Milton. Practical printnig This paper describes the practical difficulties and potential pitfalls associated with the stages in the production of a printed work in the hand press period: composition, imposition and presswork. The speakers will bring along some type, composing sticks and other exhibits to illustrate this process, and will also demonstrate on a tabletop printer, which, while rather different from those used for book work, will give some idea of what is involved. They will show a short film made to accompany the “Private lives of print” currently being exhibited at the University Library.

Great episode featuring Lamar Kellywood and Nicholas Smith. We talk about being a Pilgrim parent, tough guys and E-cigarettes, and how hard it must have been to paint pictures of Jesus. Recorded at the Complex in downtown Salt Lake City before and during the Comedy Roadkill show. Ben and I get two other comics together and do some joke writing. Not sure if we wrote a joke but we had fun doing it. Enjoy.

A panel discussion with Prof. Michael Dukakis, Prof. David Kaye, and MA candidate Nicholas Smith, co-sponsored by the Burkle Center and the Undergraduate International Relations Society (UIRS).

A panel discussion with Prof. Michael Dukakis, Prof. David Kaye, and MA candidate Nicholas Smith, co-sponsored by the Burkle Center and the Undergraduate International Relations Society (UIRS).