Podcasts about EF

How do you do more with Entity Framework? Carl and Richard talk to Erik Ejlskov Jensen about his work contributing to Entity Framework and creating tools to make Entity Framework easier to use. Erik talks about how EF has continued to evolve, including some significant performance optimizations. The conversation also explores code-first vs. database-first - although Erik falls firmly into the schema-first mindset. There's more coming for Entity Framework; it's worth your time to get the most from it!

Dios dio instrucciones dinmicas sobre los roles de hombres y mujeres. Dios revela que existen cinco cosas que los hombres deben hacer. Ef. 5:18-33 To support this ministry financially, visit: https://www.elsitiocristiano.com/donate/276/29

Dios dio instrucciones dinmicas sobre los roles de hombres y mujeres. Dios revela que existen cinco cosas que los hombres deben hacer. Ef. 5:18-33 To support this ministry financially, visit: https://www.oneplace.com/donate/276/29

Dios dio instrucciones dinmicas sobre los roles de hombres y mujeres. Dios revela que existen cinco cosas que los hombres deben hacer. Ef. 5:18-33 To support this ministry financially, visit: https://www.elsitiocristiano.com/donate/276/29

Dios dio instrucciones dinmicas sobre los roles de hombres y mujeres. Dios revela que existen cinco cosas que los hombres deben hacer. Ef. 5:18-33 To support this ministry financially, visit: https://www.oneplace.com/donate/276/29

The sheriff's department in mid-Missouri's Maries County is attempting to form a sheriff's posse to work in areas like search and rescue, disaster relief, weather spotting and school safety. Maries County Sheriff's Chief Deputy Scott John tells 939 the Eagle's "Wake Up Mid-Missouri" that two recent tornadoes, including an EF-2 with 122 mile-per-hour winds that touched down near Vichy, highlight the importance of having more help to go door-to-door. Mr. John also wants to have more positive role models for our community youth:

When you learn that your child has executive functioning deficits that need strengthening, it can feel confusing and overwhelming. How do you know when your child's lagging EF skills are getting in the way? What are good ways to help? In this episode, Dr. Nanika Coor explains what executive functioning is and everyday fun and useful ways to help your child improve their capacities to think before acting, mentally wrestle with relevant ideas, and respond adaptively and flexibly to their changing environment. Project Parenthood is hosted by Dr. Nanika Coor. A transcript is available at Simplecast.Have a parenting question? Email Dr. Coor at parenthood@quickanddirtytips.com or leave a voicemail at 646-926-3243.Find Project Parenthood on Facebook and Twitter, or subscribe to the Quick and Dirty Tips newsletter for more tips and advice.Project Parenthood is a part of Quick and Dirty Tips.Links: https://www.quickanddirtytips.com/https://www.quickanddirtytips.com/subscribehttps://www.facebook.com/QDTProjectParenthoodhttps://twitter.com/qdtparenthoodhttps://brooklynparenttherapy.com/ 

Welcome to The Personal Brain Trainer Podcast! In this warm and engaging episode, Erica and Darius explore the intriguing world of metacognition and executive functioning (EF). Discover how these interconnected cognitive processes shape the way we think, learn, and problem-solve. Perfect for students, teachers, or anyone with a curiosity about the human mind, this episode offers research-backed insights and practical strategies for developing metacognition and enhancing executive functioning. Join us as we dive into self-reflection, active learning, and goal-setting techniques designed to unlock your full potential in both daily life and academic pursuits. Links - What Influences Learning? A Content Analysis of Review Literature: https://tinyurl.com/46p5s7x5 - Jordan Peterson: Selective consciousness: https://tinyurl.com/3m5dbwh5 - Christopher Alexander- Morphogenic Design: https://tinyurl.com/3kmkrr86 - Mnemonics: https://tinyurl.com/ys8ysjjd - Metacognition: https://tinyurl.com/4dbtc8cw - Working Memory: https://tinyurl.com/working-memory - Inhibitory Control: https://tinyurl.com/inhibitory-control - Visualization: https://tinyurl.com/use-visualization - Inner Voice: https://tinyurl.com/inner-voices - Cognitive Flexibility: https://tinyurl.com/cognitive-flexibility - BulletMap Academy: https://bulletmapacademy.com/ - Learning Specialist Courses:https://www.learningspecialistcourses.com/ - Executive Functions and Study Skills Course: https://tinyurl.com/n86mf2bx - Good Sensory Learning: https://goodsensorylearning.com/ - Dyslexia at Work: www.dyslexiawork.com

It's been one month since an EF-3 tornado cut an 18-mile path through Fulton County. It scattered debris, felled power lines and grain bins, and swept directly through the small village of Bryant.

Ef þessi þáttur væri bolli, þá væri hann stútfullur af sjóðheitu Lavazza  kaffi. Við Tökum á ýmsu í dag: fréttir vikunnar, Launþegi vikunnar, May the 4th be with you,  Ólga vegna kostnaðar við krýningu á Kalla konung, Lénabraskari aldarinnar, AirBnb speki og meira til. Gangið hratt um gleðinnar dyr um helgina.

En este mensaje tratamos el siguiente caso de una mujer que «descargó su conciencia» de manera anónima en nuestro sitio www.conciencia.net, autorizándonos a que la citáramos: «Hace veinte años vivía con mis padres. Ellos no se llevaban bien. Mi madre estaba enferma, y yo la cuidaba. »Mi padre tenía otra familia, y me dijo que me fuera de la casa porque, si no me iba yo, se iría él. Como yo no quería que mi madre sufriera si se iba mi padre, [regresé inmediatamente al país] natal de ella.... »[Mi madre murió hace catorce años, y] ahora mi padre y su nueva y joven mujer quieren venir a vivir conmigo... debido a la situación actual [en su país]. »¿Debo recibirlos en mi apartamento? Ellos nunca han querido que yo vaya a pasar vacaciones [en su casa]... ya que yo no me llevo bien con esa nueva mujer.... [Ella y mi padre aún odian] a mi madre, [catorce años después de] su fallecimiento.» Este es el consejo que le dio mi esposa: «Estimada amiga: »... Usted no menciona por qué desea un consejo de nuestra parte... pero suponemos que es porque le importa el mandamiento bíblico que nos enseña a honrar a padre y madre.1 De ahí que quiera saber si el honrar a su padre significa que tiene que permitir que él la trate a usted como a él le plazca y luego aún poder obtener los beneficios de ser un padre digno de honra. »Nosotros creemos que el mandamiento bíblico de honrar a nuestros padres se refiere a mucho más que una relación biológica. Por ejemplo, en algunas familias los que crían a los niños son los abuelos. En otras familias, los niños han sido adoptados, por lo que sus padres no tienen ninguna relación biológica con ellos. En muchos hogares el padre biológico está ausente del todo, y la madre biológica cría sola a los niños. Por eso, el honrar a padre y madre quiere decir honrar a quienes fueron responsables de cuidarlo a uno hasta ser mayor de edad. »La Biblia también enseña que debemos ayudar en lo posible a nuestros familiares ancianos desvalidos.2 Sin embargo, no hay ninguna enseñanza que diga que tenemos que permitir que vivan con nosotros. »Para algunas personas y en algunas culturas, parece natural que un padre necesitado o enfermo sea atendido por un hijo adulto en la casa del padre o en la del hijo. Pero la responsabilidad primaria de un hijo adulto que está casado es su cónyuge y su propia familia, tal como enseñó el apóstol Pablo. El hijo adulto debe dejar a su padre y a su madre, y unirse a su esposa.3 Esa enseñanza deja en claro que el dejar a sus padres y vivir por su propia cuenta no es una forma de deshonrarlos. »Le recomendamos que honre a su padre tratándolo con respeto cuando se comunique con él. Si él necesita ayuda económica, y usted tiene los recursos para ayudarlo, envíele determinada cantidad mensualmente. A lo mejor, la otra familia de él ayudará de la misma manera.» Con eso termina lo que Linda, mi esposa, recomienda en este caso. El caso completo se puede leer si se pulsa la pestaña en www.conciencia.net que dice: «Casos», y luego se busca el Caso 745. Carlos ReyUn Mensaje a la Concienciawww.conciencia.net 1 Éx 20:12 2 1Ti 5:8 3 Ef 5:31

Hacía poco que el general San Martín había llegado al Perú con el ejército patriota y con el ánimo de acabar con el dominio español en aquella región andina. Y hacía poco que fray Matías Zapata había llegado a Chancay para ejercer las funciones de cura interino de aquella parroquia. Tan pronto se enteró de la llegada de San Martín, el padre Zapata, que era defensor de la autoridad absoluta de la monarquía española, comenzó a atacar desde el púlpito al generalísimo: «Carísimos hermanos: Sabed que el nombre de ese pícaro insurgente San Martín es por sí solo una blasfemia, y que está en pecado mortal todo el que lo pronuncie, no siendo para execrarlo. ¿Qué tiene de santo ese hombre malvado? ¡Llamarse San Martín ese sinvergüenza...! Confórmese con llamarse sencillamente Martín.... Sabed, pues, hermanos y oyentes míos, que declaro ex­comulgado vetando a todo el que gritare “¡Viva San Martín!”...» Semanas después las fuerzas patriotas ocuparon Chancay, y el infeliz franciscano cayó en poder del excomulgado caudillo. —Conque, señor godo —le dijo San Martín—, ¿es cierto que... usted... le ha quitado una sílaba a mi apellido? El atrevido fraile, ahora con temor y temblor, recurrió a la excusa de que no hacía más que cumplir órdenes de sus superiores, y ofreció retractarse públicamente devolviéndole a su señoría la sílaba. —No me devuelva usted nada, y quédese con ella —replicó el general—; pero sepa usted que yo, en castigo de su insolencia, le quito también la primera sílaba de su apellido, y entienda que lo fusilo sin misericordia el día que se le ocurra firmar “Zapata”. Desde hoy no es usted más que el Padre Pata.... «Y cuentan —concluye el popular escritor criollo Ricardo Palma en sus Tradiciones peruanas— que hasta 1823 no hubo en Chancay partida de nacimiento, defunción u otro documento parroquial que no llevase por firma fray Matías Pata.»1 En la sentencia de San Martín se cumplía el refrán que dice: «Lo que te hagan, haz, ni menos ni más», como también el refrán afín acuñado así: «Quien paga a otro en la misma moneda, saldado queda.»2 Si bien estos refranes recogen el principio de la justicia humana, rechazan el de la justicia divina. La justicia humana exige que el culpable reciba su merecido, mientras que la divina le ofrece lo que no se merece.3 Es que Dios, en su justicia sin igual, no nos paga en la misma moneda, sino que salda la cuenta de nuestro pecado en la moneda de su perdón.4 Por eso dice aquel otro refrán que sí es acertado: «El errar es humano; el perdonar, divino.» Carlos ReyUn Mensaje a la Concienciawww.conciencia.net 1 Ricardo Palma, Tradiciones peruanas (México: Editorial Porrúa, 1969), pp. 203-04. 2 Luis Junceda, Del dicho al hecho (Barcelona: Ediciones Obelisco, 1991), pp. 27-28. 3 Mt 5:38‑44 4 Ef 4:31‑32

Discovery leads to innovation. Innovation usually leads to changes in processes. But that doesn't always equate to better. Or not necessarily as a replacement.You may have seen a commercial or two for a commercial product where a walking and talking white box depicts the ease and comfort for checking for colorectal cancer at home. The insinuation is that anyone can simply send in a sample of their “#2” and find out if they have anything to worry about regarding cancer in the lower gastrointestinal tract.But at what cost is this substitute for the gold standard of colonoscopy screening actually to the patient? What are the accuracy comparisons? What to make of a positive or negative result?Ken & Eric dive in and discuss the commercial pitch for this method of using fecal DNA vs visual inspection of the colon and what actually might be overlooked for the unsuspecting patient who is trying to remain healthy.Join us on RUMBLE & LOCALS for RAW GCP! USE code GCPFREE for a month of FREE RAWHttps://kbmdhealth.com/rawHttps://kbmdhealth.com/rumbleBonus Notes covered in this episode:Does Cologuard detect polyps?Yes, Cologuard can detect polyps.  However, the detection of large polyps (the precursors to colon cancer) is less than half as accurate as a colonoscopy.Is the Cologuard test as effective as a colonoscopy?No, the Cologuard test is not as effective as a colonoscopy.  Detecting and removing polyps is critical to colon cancer prevention, and Cologuard only detects large precancerous polyps 42% of the time.  A colonoscopy detects the same polyps 95% of the time and they are removed during the same procedure.What does Cologuard detect?Cologuard can detect 92% of cancers and 42% of large precancerous polyps, the precursor to colon cancer.What does it mean if your Cologuard test is positive?If the Cologuard test is positive, it may mean that colon cancer or polyps are present. After a positive Cologuard test a colonoscopy is required for a definitive answer.  The Cologuard test has a 13% false-positive rate, which means 1 in 10 positive tests will incorrectly identify cancer or polyps.Does Cologuard detect cancer?Yes, the Cologuard test can detect cancer 92% of the time.  However, prevention of colon cancer is better than identifying it once you have it.  The best way to prevent colon cancer is by identifying and removing precancerous polyps that don't turn into cancer later.  Cologuard only finds 42% of large, dangerous polyps that can turn into colon cancer.Can patients use Cologuard instead of a colonoscopy?Cologuard is not designed to be a replacement for a colonoscopy, even though advertisements may suggest otherwise.  58% of the time, dangerous precancerous polyps are not detected with Cologuard, which is significantly less effective than a colonoscopy. However, Cologuard may be an option for some patients who insist on not getting a colonoscopy or those not healthy enough to have a colonoscopy.  Even a 42% chance of detection is better than no detection at all.References for this episode:Uptodate.com- colon cancer screening guidelinesItzkowitz SH, Ahlquist DA. The case for a multitarget stool DNA test: a closer look at the cost effectiveness model. Gastroenterology. 2017;152(6):1620–1621Johnson DH, Kisiel JB, Burger KN, et al. Multitarget stool DNA test: clinical performance and impact on yield and quality of colonoscopy for colorectal cancer screening. Gastrointest Endosc. 2017;85(3):657–665.e1.Zauber A, Knudsen A, Rutter CM, et al. Evaluating the Benefits and Harms of Colorectal Cancer Screening Strategies: A Collaborative Modeling Approach. AHRQ Publication No. 14-05203-EF-2. Rockville, MD: Agency for Healthcare Research and Quality; October 2015.Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force. JAMA 2016; 315:2595.Cost-effectiveness of a multitarget stool DNA test for colorectal cancer screening of Medicare beneficiaries Steffie K. Naber  ,Amy B. Knudsen ,Ann G. Zauber,Carolyn M. Rutter,Sara E. Fischer,Chester J. Pabiniak,Brittany Soto,Karen M. Kuntz,Iris Lansdorp-VogelaarRex DK, Boland CR, et al. Colorectal cancer screening: Recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. GI Endosc. 2017; 86(1):18-33.

April 27, 2023 marked 12 years since the devastating tornado outbreak in Alabama.  Mike Dubberly got a chance to talk with former Alabama All-American Defensive Lineman and Co-Captain Shannon Brown, who's now the principal at Liberty Middle School in Madison, Alabama.  On April 27, 2011, Shannon lost his daughter Loryn in the EF-4 tornado that hit Tuscaloosa.  The college student was pursuing her dream of attending the University of Alabama and now, endowment scholarships have been created in her honor.  Here's Shannon's conversation with Mike Dubberly. 

Llegamos al Radiojaputa número 176 con un programa especial sobre nosotras, nuestro cuerpo y el ejercicio físico. ¿Por qué hacemos menos deporte que los hombres? ¿Por qué andamos más pero hacemos menos pesas? ¿Cuánto mitos hay en torno a las mujeres y el ejercicio? Analizamos esta y muchas otras cuestiones, pero, antes, hacemos una introducción sobre las dificultades que las mujeres hemos sufrido históricamente y seguimos sufriendo a día de hoy en relación con el deporte. Nuestra primera invitada a este podcast es Sara Tabares, directora de PERFORMA Entrenadores Personales, graduada en Ciencias de la Actividad Física y el deporte y autora del libro “Ellas entrenan”. Hablamos de menopausia, de entrenamiento de fuerza y de deporte y enfermedades, entre otras cosas. Seguimos con Malu Baena, licenciada en Ciencias del Deporte, profesora de EF de secundaria y entrenadora de atletismo, además de autora del libro “Correr embarazada”, con quien resolvemos dudas y derribamos mitos sobre ciclo menstrual y deporte, y también sobre actividad física en el embarazo y posparto. Además, nos visita Ruth Cabeza, profesora de la Universidad de Sevilla, miembra de la Red Mudivi (Mujeres, deporte inclusivo y discapacidad), y directora del grupo de investigación Feminae. Con ella abordamos, entre otros, dos temazos: las quejas más comunes de las mujeres con discapacidad en relación con la práctica deportiva, así como las barreras y facilitadores, y la relación entre obesidad, deporte y gordofobia. Terminamos este especial con la sección de Lucía Martínez, “Dime qué comes”, para hablarnos sobre el papel de la nutrición en la práctica deportiva de las mujeres. Para matrocinar este espacio, puedes hacerlo en Radiojaputa. Para participar, mándanos un audio de whatsapp al (+34) 636 75 14 20. Si te han gustado las canciones, en Youtube puedes encontrarlas listadas por temporadas. Además, en nuestro Spotify las tienes también por episodios.

Dire “merci” à tout va, couper le fromage en triangles

Got ADHD? Struggle with executive functioning (EF)? What is executive functioning? How do you manage it? In this episode of Attention Talk Radio, ADHD and attention coach Jeff Copper (www.digcoaching.com) talks with Sean McCormick about executive functioning and how he helps those who are struggling to hone their executive function skills. Jeff talks about how he coaches people who struggle with EF, too. In their conversation, they make the distinction between the outcome of executive function and the EF process itself. This important distinction provides context to understand what often sounds like the same conversation but is quite different. If you have ADHD, you'll find this to be an insightful show. Attention Talk Radio is the leading site for self-help Internet radio shows focusing on attention deficit hyperactivity disorder and attention deficit disorder, including managing symptoms of ADHD in adults with ADD or adults who have children with ADHD. Attention Talk Radio, hosted by Jeff Copper, attention and ADHD coach, is designed to help adults (particularly those diagnosed with or impacted by attention deficit disorder or its symptoms) in life or business who are stuck, overwhelmed, or frustrated to help them get unstuck and moving forward by opening their minds to pay attention to what works. To learn more about attention and ADHD coach Jeff Copper, go to www.digcoaching.com. 

Ali and Mari are joined by the winner of this year's Paris-Roubaix Femmes avec Zwift, Alison Jackson. They discuss what it's like to win Paris-Roubaix, how the breakaway was able to stay alive, what was going through Alison's mind heading into the Velodrome, and of course, her famous dance moves.

kassad & vENdetta to talk about BLAST Paris Major RMRs: tech issues of Asia & Americas, VP eliminated after KaiR0N- - n0rb3r7 debacle, FaZe in the last chance bracket, other teams, format issues, and preview of Europe RMR B. ➡️ Follow us for updates: https://twitter.com/HLTVconfirmed

This week, please join author Kavita Sharma and Associate Editor Svati Shah as they discuss the article "Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction." Dr. Greg Hundley: Welcome listeners, to this April 11th issue of Circulation on the Run. And I am one of your cohosts, Dr. Greg Hundley, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Peder Myhre: And I am Dr. Peder Myhre from Akershus University Hospital, and the University of Oslo in Norway. Dr. Greg Hundley: Well, Peder, wow. This week's feature discussion, very interesting. We spend a lot of time, especially with our colleague, Dr. Carolyn Lam, on heart failure preserved ejection fraction. But this week's feature discussion, it's going to focus on some of the myocardial metabolomics in this condition. But before we get to that, how about we grab a cup of coffee, and jump into some of the other articles in the issue? How about if I go first? Dr. Peder Myhre: Let's go, Greg. Dr. Greg Hundley: Okay. So Peder, some believe that cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. And so, the American Heart Association, as you know, recently released an updated algorithm for evaluating cardiovascular health. Life's Essential 8, and it has a very nice score. So these authors, led by Dr. Lu Qi, from Tulane University, aimed to quantify the associations of the Life Essential 8 scores with life expectancy in a nationally representative sample of US adults. And the team included 23,000 non-pregnant non- institutionalized participants who were age 20 to 79 years, who participated in the National Health and Nutrition Examination survey, or NHANES, from 2005 to 2018. And whose mortality was identified through linkage to the National Death Index, from the period extending through December of 2019. Dr. Peder Myhre: Oh wow. So really, a validation of the Life's Essential 8. Greg, that's so interesting. What did they find? Dr. Greg Hundley: Right Peder, as you say, very interesting. So here are some of the data, and let's itemize them. So, during a median of 7.8 years of follow up, 1,359 total deaths occurred. Now, the estimated life expectancy at age 50 was 27.3 years, 32.9 years, and 36.2 years, in participants with low Life's Essential 8 scores, less than 50. Moderate, so Life's Essential 8 scores of greater than or equal to 50, but less than 80. And then, high scores, greater than 80. Okay? So equivalently, participants with high Life's Essential 8 scores had an average of 8.9 more years of life expectancy at age 50, compared to those with low scores. Next, on average, 42.6% of the gained life expectancy at age 50, from adhering to sort of that cardiovascular health, those recommendations, was attributable to reduced cardiovascular death. Next, significant associations with the Life's Essential 8 score and life expectancy were observed in both men and women. Next, similarly significant associations of cardiovascular health, Life's Essential 8, with life expectancy were observed in non-Hispanic Whites and non-Hispanic Blacks, but not in those originating from the country of Mexico. So Peder, finally, in summarizing all of this, adhering to the cardiovascular health lifestyle, defined by the Life's Essential 8 score, it was related to a considerably increased life expectancy. However, because of the findings from the individuals from the country of Mexico, more research is needed to be done in some of these minority groups, and particularly, those of Hispanic ethnicity, and perhaps other races. Dr. Peder Myhre: Oh, wow. Very interesting. And I would love to learn more about this subgroup analysis in future studies. So Greg, the next paper is about the hospitalization for heart failure measures. Because contemporary measures of hospital performance for heart failure hospitalization, the 30-day risk standardized readmission and mortality rate, are estimated using the same risk adjusted model and overall event rate for all patients. Thus, these measures are mainly driven by the care quality and outcomes for the majority racial ethnic groups, and may not adequately represent the hospital performance for patients of Black or other races. And in this study, led by co-corresponding authors, Mentias from Cleveland Clinic and Pandey from University of Texas Southwestern Medical Center, the authors used fee for service Medicare beneficiaries from 2014 to 2019 hospitalized with heart failure, in hospital level 30 day risk standardized remission and mortality rates were estimated using traditional race agnostic models and the race specific approach, with measures derived separately for each race ethnicity group. Dr. Greg Hundley: Ah, very interesting, Peder. So what did they find from this study? Dr. Peder Myhre: So the study included more than 1.9 million patients, comprising of 75% White patients, 15% Black patients, and 10% patients of other races, with heart failure from 1,860 hospitals. And compared with the race agnostic model, composite race-specific metrics for all patients demonstrated stronger correlation with 30 days readmissions. And that is correlation coefficient 0.78 versus 0.63, and 30 day mortality rate 0.52 versus 0.29 for Black patients. In concordance in hospital performance was for all patients and patients of Black race was also higher with race specific as compared to race agnostic metrics. So Greg, the authors conclude that among patients hospitalized with heart failure race specific 30 day risk standardized remission and mortality rates are more equitable in representing hospital performance for patients of Black and other races. Dr. Greg Hundley: Very nice, Peder. What a beautiful summary in a very elegant study. Peder, myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlining molecular mechanisms for this relationship remain unclear. Now, recent studies demonstrate, that the diabetic heart is resistant to several cardioprotective interventions, including adiponectin and pre-conditioning. The universal quote, unquote, resistance to multiple therapeutic interventions suggest, impairment of the requisite molecule, or molecules, involved in broad pro survival signaling cascades. Now caveolin is a scaffolding protein coordinating trans-membrane signaling transduction. However, the role of caveolin-3 in diabetic impairment of cardiac protective signaling and diabetic ischemic heart failure is unknown. And so these investigators, led by Dr. Xinliang Ma, from Thomas Jefferson University, studied mice fed a normal diet or high fat diet for two to 12 weeks, and subjected them to myocardial ischemia and reperfusion. Dr. Peder Myhre: Oh wow. What an interesting preclinical science paper, Greg. What did they find? Dr. Greg Hundley: Right. So the authors found that nitration of caveolin-3 at tyrosine 73 and resulted signal complex dissociation was responsible for cardiac insulin adiponectin resistance in the pre-diabetic heart. And this contributed to ischemic heart failure progression. Now, early interventions preserving caveolin-3 centered signal zone integrity was found to be an effective novel strategy against diabetic exacerbation of ischemic heart failure. And Peder, I think these very exciting results suggest that this is a new area of research and further experiments are warranted. And there's a very nice editorial by Professor Heidenreich, entitled “Pursuing Equity in Performance Measurement. Well Peder, there's some other articles in this issue, and we'll dip in this week to the mail bag, for a Research Letter from Professor Hibbert, entitled “Utility of a Smartphone Application in Assessing Palmar Circulation Prior to Radial Artery Harvesting for Coronary Artery Bypass Grafting.” Dr. Peder Myhre: That is so cool. And we also have a Letter from Dr. Kim, regarding the article entitled, “Detection of Atrial Fibrillation in a Large Population Using Wearable Devices: The Fitbit Heart Study.” Dr. Greg Hundley: Very nice. Well, how about we get along to one of Carolyn's favorite topics, heart failure with preserved ejection fraction, and learn more about myocardial metabolomics? Dr. Peder Myhre: Can't wait. Dr. Carolyn Lam: Today's feature discussion is on my favorite topic, heart failure with preserved ejection fraction, or HFpEF. But today, what we're focusing on is truly novel. We are looking at the myocardial metabolomics of human HFpEF, very, very valuable data and insights. We're so pleased to have with us the corresponding author of today's feature paper, Dr. Kavita Sharma, who's from the Johns Hopkins University School of Medicine, and our associate editor, Dr. Svati Shah, who's, of course, from Duke University School of Medicine. So welcome Kavita and Svati. Kavita, if I could start by, please put us and bring us all to the same level of knowledge, by perhaps explaining in simple terms, what is metabolomics? And what is normal versus perhaps abnormal metabolomics, in a known condition, like systolic heart failure or heart failure with reduced ejection fraction? Dr. Kavita Sharma: Sure. Well thank you, Carolyn, for the opportunity to chat around this topic. And it's great to be with you and Svati this morning. Metabolomics is a broad general study of essentially, all the chemical processes involving metabolites, or small molecule substrates, their intermediates, and even the products of cellular metabolism. This can be studied in really, any organ system, in any organ. What is really unique, I think, to this particular paper in our project is that, it has yet to have been defined or described in human HFpEF from the myocardial tissue. We call this heart failure with preserved ejection fraction, and inherent to that name in this complicated syndrome is that, there is something probably wrong with the heart, yet we have not really had much insight to what that might be from direct myocardial tissue. We are also still learning about what metabolomics looks like in, for example, the heart failure with reduced ejection fraction state. Though, there is more published in this space than in HFpEF. From the limited knowledge that we have, it does appear that heart failure with reduced ejection fraction hearts, and this is certainly seen in the plasma, which is where most of metabolomic studies have generated from, those hearts tend to utilize various forms of energy banks, if you will. Whether that's fatty acid oxidation, whether that is glucose utilization or intermediates and so on. And our primary interest was to understand, how do the preserved EF parts in patients fare in comparison? Dr. Carolyn Lam: Oh, thank you so much, Kavita. That was beautifully explained. And indeed, what's so special about your paper is, it's not just circulating metabolites but myocardial metabolites. And you have the control groups that are so important to study at the same time. So patients with HFpEF, but also those with HFrEF and versus controls. And thank you for establishing too, that if I'm not wrong, fatty acid metabolism accounts for the majority of ATP generation in the normal heart. Whereas, this declines a little in the HFrEF heart. And now, I think we're about to find out what happens in the HFpEF heart. So if you could explain what you did and what you find. Dr. Kavita Sharma: Yes, absolutely. So we examined, again, tissue and plasma metabolomics from 38 subjects with HFpEF. These are patients referred to the Hopkins HFpEF Clinic. And so they have been essentially, clinically evaluated, and have what we define as HFpEF, based on hemodynamic testing. So a right heart catheterization, often with exercise, that meets criteria for diagnosis of the syndrome. As you stated, we compared our HFpEF patient tissue and plasma samples to samples coming from patients with HFrEF, dilated cardiomyopathy, and non-failing controls. And the latter two sources were a tissue bank from the University of Pennsylvania, that is long-standing, where patients with endstage dilated cardiomyopathy are able to have tissue banked at the University of Pennsylvania at the time of explant prior to transplant. So albeit, we are comparing to fairly advanced end stage dilated cardiomyopathy, and control tissue comes from unused donor hearts, essentially. So presumably, normal heart function patients, likely in a brain death state, who for whatever reason, the hearts were not utilized for transplantation. Again, not an entirely perfect controlled state, but again, given the nature of the work, the fact that it's myocardial tissue, the closest that we have found we've been able to come to for a control comparison. We started out performing what we call quantitative targeted metabolomics. We measured organic acids, amino acids, and acylcarnitines in the myocardium. And that was totaling around 72 metabolites. And we did the same in plasma, so close to 69 metabolites. And our metabolomics work was actually completed at the University of Pennsylvania. And so, I wish to credit Dr. Zoltan Arany and Dr. Dan Kelly for their great collaboration in this study. Dr. Carolyn Lam: That's wonderful. Kavita, if you could tell us a little bit more about the patients with HFpEF. We understand it was end stage dilated cardiomyopathy, HFrEF, and donor hearts as the controls, but the patients with HFpEF, in relation to obesity, diabetes, and how that may impact the interpretation of the results. Dr. Kavita Sharma: Sure. So these are HFpEF patients that are in an ambulatory state outpatient setting. They have many of the comorbidities we know are intrinsic today to HFpEF. Out of our HFpEF population, the majority were women. So 71%, that's 27 out of the 38 we serve. And we're very fortunate to serve a African-American enriched population in Baltimore that's intrinsic to our center. And so, over half of our patients were Black. The remaining Caucasian, one non-Caucasian. Over half had been hospitalized, for example, in the prior one year. So these are certainly symptomatic patients. And all had NYHA II or greater symptoms. We do have a rather obese cohort at Hopkins. And so, our median BMI, for example, was 39, our mean is very similar. And the majority have, as we see often in HFpEF, the majority with hypertension, over half with diabetes. In fact, it was actually 70% or so. Rather few with coronary disease, and this is a trend we're seeing in general in HFpEF in the present day kind of common phenotypes, and about a third with atrial fibrillation. So really, representative, I think, of this kind of cardiometabolic as we call it, phenotype of HFpEF, that is the predominant phenotype we're seeing, at least in North America. Dr. Carolyn Lam: Oh, that's perfect. And then, maybe just a few words about the results before I bring Svati in for her thoughts. Thanks. Dr. Kavita Sharma: Sure, absolutely. So we conducted this study in a couple different stages. We first started with performing a principal component analysis and hierarchical clustering analysis, to see whether the myocardial metabolites and the plasma metabolites, respectively, would they distinguish these three patient groups? So HFpEF from HFrEF and controls. And interestingly, in the myocardial tissue, our PCA analysis and our hierarchical clustering analysis show that actually, in fact, as few as 70 metabolites in the myocardium really distinctly differentiate these three subgroups. The top contributors that separated HF from controls, for example, and HFrEF, were mostly related to amino acids, including branched chain amino acids and their catabolites, as well as medium and long chain acylcarnitines, which are byproducts of fatty acid oxidation. When it came to the plasma metabolome, on the other hand, there was far less distinguishing between the groups, and significant overlap, both in PCA and hierarchal clustering. And really, the take home there is that, the myocardial tissue and the plasma were really quite distinct for the overall metabolite analysis. But then, even as we broke it down by fatty acid oxidation, by glucose metabolism, and even branched chain amino acids, we saw this trend continue, that the plasma was quite distinct from the myocardial tissue. Now, which of the two is more representative of the disease state? Which is the one that we should be paying more attention to? I think that remains to be fully understood further. And of course, it would be really nice to replicate these findings in another cohort. But that is something that, I think, is a first, that certainly, that we have seen and important for the community. Dr. Carolyn Lam: Indeed. Oh, Kavita, we could go on talking forever, but I'd really love Svati's thoughts. Why was this paper so special? What does it tell us clinically with any implications? Dr. Svati Shah: Yeah. I just want to commend Dr. Hahn, Dr. Sharma, on this incredible work. If you can just imagine how much painstaking work this took for Dr. Sharma and Dr. Hahn. It's a very careful phenotyping of HFpEF. These are true HFpEF patients. The ability to get tissue, and to pair the tissue to the plasma, so that we can really understand. When we measure things in the circulation, and we think they're telling us about the heart, are they actually telling us about the heart? So I really want to commend this incredible work. And Carolyn, I love talking about cardiac metabolism, because the heart is an incredible organ, right? The heart is a metabolic omnivore. It'll eat many different kinds of fuels, and a lot of different things determine which fuels it uses. And as you nicely outlined, Carolyn, earlier, in the normal heart, the heart prefers to use fatty acids. But what we are not completely certain of is, what happens in HFpEF? So in HFrEF, we know that the heart switches to glucose, which is not a great fuel, actually. It's actually, a metabolically inefficient fuel. And so we know in HFrEF, that the heart has this metabolic inflexibility. All of a sudden, it's not an omnivore, and it's kind of stuck with certain fuels, which are not very healthy for it. But what Dr. Sharma and Dr. Hahn have shown, for the first time really, is what happens in HFpEF? And so, I think it's really cool that, actually, it just highlights how complex HFpEF is as a disease. So they were able to show that in some ways, HFpEF is similar to HFrEF, including that there's impairments in use of these fatty acids, which is what the normal heart does. But, they also show that HFpEF may be different than HFrEF in many ways, including, because of these branched chain amino acids. And that may be because of some of the clinical differences that we know exist in patients with HFpEF, including the obesity and diabetes, that Dr. Sharma nicely outlined. Although, I want to point out, they were very careful about trying to take these clinical factors into account when they looked at differences in the metabolites. So really incredible work, highlighting that the HFpEF heart also has this metabolic inflexibility. It also is not a metabolic omnivore like the normal heart is, but highlighting important differences, potentially, between HFpEF and HFrEF. Dr. Carolyn Lam: Oh, Svati, thank you for putting that so clearly. Dr. Kavita Sharma: No, I think that was a really elegant summary of the findings, Svati. And thank you for your kind words and support in allowing us to share our work through Circulation. I really couldn't say it better, but that's exactly what we seem to find is that, when we look at various sort of stores or banks of energy resource, what we really found is that these HFpEF hearts are energy inflexible, as Svati said, that begins with fatty acid metabolism. And so, when we look at, for example, medium and launching acylcarnitines, what we find is that these are markedly reduced in HFpEF myocardial tissue, quite similar to HFrEF. Again, both of them reduced compared to controls. And again, these are byproducts of fatty acid oxidation, and that is really responsible for almost 80% of generally what we think of energy metabolism in the normal state. In the plasma, however, again, back to that theme where we don't see that reproduced in the plasma, we find that HFpEF is actually not too dissimilar from controls for certain medium and long chain acylcarnitines, and then closer to HFrEF in some cases. And interestingly, we compared our metabolomics study to our prior report of our RNA sequencing paper, that was also published in Circulation now two years ago. And what we found is that, there is reduced gene expression of many of the proteins involved with fatty acid uptake and oxidation, when we compare them to control states. So the story is sort of, fits with what we have seen previously, and when we focus in on this group of genes. Our analysis of glucose metabolism though, did not include glycolysis or glucose oxidation intermediates. We still found that, majority of the TCA cycle intermediate, so succinate, for example, fumarate, malate, were all reduced in HFpEF versus control. It was really only pyruvate in isolation that was increased in HFpEF myocardium, compared to controls. And again, a number of genes implicated in glucose metabolism in general, we found to be lower in HFpEF versus control, including gluten 1, or SLC2A1, which is involved in glucose uptake. So again, this theme of, we have patients with significant obesity, many in the diabetic state, we would think that these hearts would utilize these energy stores, but they don't seem to be. And finally, we see distinct differences in the tissue and branched chain amino acid pathways as well. There appears to be some sort of a block between the branched chain amino acids, and then sort of byproducts, as you continue down through ketoacids and further. And we don't fully understand where those blocks are, but that was certainly notable. And then lastly, I'll say, one interest that we've had, and really, what led to much of this work in the tissue, is to pursue what we call deep phenotyping. Can these molecular signatures, whether it's gene expression, or metabolomics, or what we're working on now, which is proteomics, can these really help us identify unique subgroups within HFpEF? And so, we've tried to do that with the metabolomics, and we found that, using various sort of clustering analytical methods, in fact, there is significant overlap, as it turns out, within HFpEF, when it comes to the metabolomic signatures. And we only found, really, two subgroups within HFpEF. And even these two really did not have much that distinguished them, beyond branched chain amino acids. And so, this is the first time, at least that our group has seen, at a tissue level, that there is actually a fair bit of homogeneity now in the metabolomic signatures, compared to our RNA sequencing work. And that may be reflective of now, this increasingly cardiometabolic phenotype of HFpEF. And now, we may be seeing signs of that at the clinical and at the treatment level, where we have therapies like SGLT2 inhibitors, that are showing benefit to what seems to be a much broader spectrum of HFpEF, compared to prior therapies. So a lot of questions that have been generated from the work, and we're looking forward to exploring much of this in more detail. Dr. Carolyn Lam: And Svati, may I give you the last word? Where do you think this field is headed next? Dr. Svati Shah: I think there's so much to do, and I think Dr. Sharma and Dr. Hahn have highlighted how much work there is to do in this space. We're brushing the surface and understanding cardiac metabolism with this really important paper. But Carolyn, as you pointed out, we really need to understand what happens to these patients over time? What happens to, not just cardiac metabolism, but molecular biology more broadly, in patients with HFpEF with these various treatments? Including now, thank goodness, we have SGLT2 inhibitors as a therapeutic intervention for patients with HFpEF. And in fact, we published in Circulation a few months ago, a paper led by a very talented junior faculty, Senthil Selvaraj, where we actually showed that these acetylcarnitine levels that reflect fatty acid oxidation actually are changed by SGLT2 inhibitors, and are associated with changes in clinical outcomes in HFpEF. So we really need larger sample sizes, being able to look at these patients in a longitudinal fashion. But really, doing what Dr. Sharma and Dr Hahn have done, which is careful, careful phenotyping and multidisciplinary teams, so that we can understand the molecular biology, as well as the clinical implications. Dr. Carolyn Lam: Oh, wow. Thank you so much, Kavita and Svati, for this incredible interview. I learned so much, and enjoyed it so thoroughly, as I'm sure our listeners did as well. Well, listeners, you've been listening to Circulation on the Run. Thank you for joining us today, and don't forget to tune in again next week. Dr. Greg Hundley: This program is Copyright of the American Heart Association 2023. 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.

On Saturday (4/1/23), a supercell thunderstorm produced a violent EF-3 tornado carving a 14.3 mile path across parts of northern Sussex county in Delaware. The tornado became the 2nd strongest and 2nd fatal tornado on record in the state of Delaware, claiming one life and leaving behind a trail of destruction. Chief Meteorologist Rich Wirdzek and Meteorologist Ulises Garcia discuss the unique atmospheric setup that supplied the ingredients for a severe weather event more typical for the Midwest than for Delmarva. They also examine the damage survey data released from the National Weather Service.

A small tornado rated EF-0 with wind gusts estimated between 65 to 85 mph traveled through south Cherokee, damaging a car and a baseball complex in its path. The tornado snapped a few trees along Dreamcatcher Drive and continued eastward, causing more tree damage along Loraine Parkway and at Bell Park Drive and Bell Court. The tornado lifted as it reached Mill Creek Road. At the South Cherokee Recreational Complex, the tornado blew off the roof of a dugout, overturned bleachers, and blew over a press box. Volunteers from area youth baseball programs helped to clean up the site the following day. According to a report from SafeWise, Holly Springs has been named the safest city in Georgia for 2023, with a violent crime rate of zero incidents per 1,000 residents and a property crime rate of 2.7. Canton ranked 14th and Woodstock 20th on the list of safest cities in Georgia. The average violent crime rate in Georgia is 3.9, and the average property crime rate is 17.5. Violent crime in Georgia fell by about 3% and property crime decreased by about 13% compared to the previous year. The top five safest cities in Georgia are Holly Springs, Kingsland, Hampton, Johns Creek, and Barnesville. Student artists from the University of Georgia created three new murals in Downtown Ball Ground over the weekend. Led by Professor Joseph Norman and Cherokee County native Katie Brannen, the students added the murals to walls on the side of Ireland Restorative Dentistry and the corner of Mound Street and Gilmer Ferry Road. One mural featurse an illustration of a Native American playing stick ball, which is where the city got its name, another features a black and white photo of a group of men and Henry Calvin Farmer, the “engineer of the Amicalola Marble and Power Co. Railroad.”, and the final mural features a hand offering a glass Coca-Cola bottle. The pieces celebrate the city's history and culture. Gibbs Gardens in Ball Groundis bringing back its Twilight Concert Series after a three-year hiatus due to COVID-19. The concerts will feature local and regional cover bands every Saturday from May to October. Unlike previous years, admission to concerts is now an additional cost. Seating will be first-come, first-serve, and attendees may bring lawn chairs. The concerts will be held from 6-9 p.m. in May and June, and from 5-8 p.m. in September and early October. Boxed dinners from the Arbor Cafe will be available by pre-order, and the cafe will be selling food and drinks from their regular menu during the concerts. A new Middle School Honor Band program was recently launched by Cherokee County School District, with 100 young musicians from all seven middle schools performing together. The seventh and eighth grade students rehearsed and performed a concert at Dean Rusk Middle School under the direction of guest conductor Matt Price. The event was considered a "resounding success" by Dean Rusk Middle School band director Lloyd McDonald, who received positive feedback from students and parents. Cherokee County Superintendent Brian Hightower congratulated the students and thanked the band directors for organizing the program. A section of East Main Street in downtown Woodstock between Wheeler Street and Arnold Mill Road will permanently close the first week of April, the city announced, as construction crews start work associated with the City Center project. Construction fencing will be installed for work to extend Chambers Street from Wheeler Street to Arnold Mill Road. The former Ace Hardware parking lot will no longer be accessible. Access to the area will be available through the intersection of Fowler Street and Main Street during this phase of construction. The Chambers Street extension is expected to be completed this fall. An Etowah High School instructor has been named the Cherokee County School District's Teacher of the Year. Science teacher Lara McDonald is CCSD's 2023 Teacher of the Year, the district announced Thursday night at its Legacy Makers CCSD Teachers of the Year Celebration. Other educators were also honored during the event. The Legacy Makers event, held at the Northside Hospital Cherokee Conference Center in Canton, honored the Teacher of the Year for every CCSD school, including four finalists who were announced in February.   And now, as we get closer to the start of the 2023 Masters, Times-Journal Incorporated sports editor John Bednarowski joins the show to continue to take us on a tour of Augusta National presented by Ingles. #CherokeeCounty #Georgia #LocalNews           -          -          -          -          -          -          The Cherokee Tribune Ledger Podcast is local news for Woodstock, Canton, and all of Cherokee County. Register Here for your essential digital news.             This podcast was produced and published for the Cherokee Tribune-Ledger and TribuneLedgerNews.com by BG Ad Group     For more information be sure to visit https://www.bgpodcastnetwork.com/    https://cuofga.org/   https://www.drakerealty.com/   https://www.esogrepair.com/           See omnystudio.com/listener for privacy information.

This week, please join authors Tatsuhiko Naito and Kosuke Inoue as well as Associate Editor Wendy Post as they discuss the article "Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Study." Dr. Greg Hundley: Welcome listeners, to this April 4th discussion of Circulation on the Run. I am one of your co-hosts, Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Peder Myhre: And I'm Dr. Peder Myhre from Akershus University Hospital and the University of Oslo in Norway. So Greg, today we have the feature paper, discussing the genetic risk of primary aldosteronism and its contribution to hypertension. So this is such an interesting topic and av very important cost on hypertension. And in this paper, they use cross-ancestry meta-analysis from GWAS studies to assess this very interesting discussion. But first, Greg, I have a paper that comes to us from the DELIVER trial, and it is about dapagliflozin to patients with HFpEF, and assessing the association with the duration of the heart failure. So Greg, it is important to understand how the effects of new treatments vary by the duration of heart failure. Because on one hand, physicians may think that a patient who has longer standing heart failure represents a stable survivor where new treatment is unnecessary. On the other hand, the view has been expressed that patients with long-standing heart failure may have more advanced disease, and there may come a point where they no longer respond to or tolerate the addition of new therapies, particularly because of hypotension, kidney dysfunctional and electrolyte abnormality. So the investigators from the DELIVER trial, led by corresponding all author John McMurray from University of Glasgow, therefore, aimed to assess the efficacy and safety of the SGLT2 inhibitor dapagliflozin, according to the duration of heart failure with EF above 40%. So that is mildly reduced or preserved. Dr. Greg Hundley: Wow, Peder, very timely, very timely article. So what did they find? Dr. Peder Myhre: So Greg, the authors categorized patients by duration of heart failure, one category less than six months, and then six to 12 months, and then one to two years, two to five years, and finally, more than five years. And longer duration heart failure patients were older, and more comorbid with worse symptoms, and the rate of the primary outcome increased with heart failure duration. And so, the benefit of dapagliflozin was consistent across heart failure duration categories with hazard ratios 0.67, 0.78, 0.81, 0.97, and 0.78. And that gives a P4 interaction of 0.41. So the absolute benefit was therefore since there was no P4 interaction, greatest among those with highest risk, and that it was the longest duration heart failure. So there was a number needed to create for heart failure above five years of 24, versus 32 for those with the shortest duration of heart failure. And the authors therefore conclude, that even in patients with long-standing heart failure and generally mild symptoms cannot be considered stable, and it is not too late for such patients to benefit from an SGLT2 inhibitor. Dr. Greg Hundley: Ah, very practical information, Peder, beautiful description. Well Peder, this next paper comes to us evaluating low density lipoprotein cholesterol. And as you know, low density lipoprotein cholesterol is an important causal risk factor for atherosclerotic cardiovascular disease. However, a sizable proportion of middle-aged individuals have not developed coronary atherosclerosis as assessed by the presence of coronary artery calcification. Now whether the presence of coronary artery calcification modifies the association of LDL cholesterol with atherosclerotic cardiovascular disease risk, well, that's unknown. So these authors, led by the corresponding author of Martin Mortensen from Aarhus University Hospital, evaluated the association of LDL cholesterol with future atherosclerotic cardiovascular disease events, in patients with and without coronary artery calcium, from 23,132 consecutive symptomatic patients evaluated for coronary artery disease, using coronary commuted tomography angiography, or CTA, that were included in the Western Denmark Heart Registry, which is a semi-national multi-center based registry with longitudinal registration of both patient and procedural data. Dr. Peder Myhre: Oh, that is so important, Greg. So we're looking at LDL cholesterol and the association with ASCVD in patients with and without coronary artery calcification. So what did they find? Dr. Greg Hundley: Right, Peder. So during a median follow up of 4.3 years, 552 patients experienced a first cardiovascular disease event. In the overall population, LDL cholesterol per 38.7 milligrams per deciliter increase, was associated with cardiovascular disease events during the follow-up period. Now, when stratified by the presence or absence of a baseline coronary artery calcium score, LDL cholesterol was only associated with a cardiovascular disease event in the 47% of patients with a coronary CAC score greater than zero. While no association was observed in the 53% of individuals with a coronary artery calcium score equal to zero. Now similarly, very high LDL cholesterol, so greater than 193 milligrams per deciliter, versus an LDL cholesterol of less than 116 milligrams per deciliter, was associated with a cardiovascular disease event in patients with a CAC score greater than zero, but not in those without coronary artery calcium. Next, Peder, in patients with coronary artery calcium equal to zero, diabetes, current smoking, and low HDL cholesterol levels, were associated with future cardiovascular disease events. This principle finding was replicated in the multiethnic study of atherosclerosis. And so, Peder, LDL cholesterol appears almost exclusively associated with a cardiovascular disease event over the ensuing five years of follow-up in middle-aged patients with versus without evidence of coronary atherosclerosis, as identified by coronary artery calcium scores. This information is quite valuable for individualized risk assessment among middle-aged patients. Dr. Peder Myhre: Oh, that is so important, Greg. So really, LDL seems to be more predictive of atherosclerotic cardiovascular disease than those with calcium in their coronaries, while there was no association in those with no calcium in their coronaries. Very interesting. Dr. Greg Hundley: Absolutely. And there's a very nice editorial by Professor Sniderman entitled, “Cholesterol Coronary Calcification and Cardiovascular Prevention: Lessons We Can Learn from the Western Denmark Heart Registry.” Dr. Peder Myhre: Thank you, Greg, that was a beautiful summary. And we are going to stay in clinical science, but we're going to move to aortic disease and look at gut microbiota. Now, Greg, large scale human and mechanistic mouse studies indicate a strong relationship between the microbiome dependent metabolyte, Trimethylamine-N-oxide, abbreviated TMAO, and several cardiometabolic diseases. And in this study, which comes to us from corresponding author Philip Owens from University of Cincinnati, the investigators aim to assess TMAO's role in the pathogenesis of AAA and targeting its parent microbes as a potential pharmacologic intervention. Dr. Greg Hundley: Ah, very interesting, Peder. So what methodology did they use? Dr. Peder Myhre: So Greg, this is one of those fantastic studies combining clinical and preclinical science. And the investigator measured TMAO in two independent patient cohorts, with a total of 2,129. And in addition, they used the murine AAA model, and fed the mice a high choline diet, which is a diet that markedly augment plasma levels of TMAO. And these mice were then treated with broad spectrum antibiotics, targeted inhibition of a gut microbial enzyme with fluorometer chloroquine, called FMC, or utilizing mice genetically deficient of Fmo3. Dr. Greg Hundley: Very nice. So what did they find, Peder? Dr. Peder Myhre: So the authors found that elevated TMAO was associated with increased AAA incidence and growth in both patient cohort studies. And dietary colon supplementations augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad spectrum antibiotics. In treatment with FMC ablated TMAO production attenuated colon augmented aneurysm in the initiation, and halted progression of an established aneurysm model. And additionally, the Fmo3 knockout mice had reduced plasma TMAO, aortic diameters, and were protected from AAA rupture compared to wild type mice. So Greg, in conclusion, this study defined a role for gut microbiota generated TMAO in AAA formation, and additionally, increased microbiome derived TMAO may serve as a novel therapeutic approach for AAA treatment where non currently exists. Dr. Greg Hundley: Beautifully described, Peder. And another one of their articles in Circulation that, as you indicated, very nicely complying the world of preclinical and clinical science. Well, we've got some other articles in the issue, and how about we jump into some of those? So first, there's a very nice Letter to the Editor from Professor Wong entitled, “Frailty and Age Correlation in Clinical Trials.” And there is another reply to a prior Letter to the Editor from Professor McMurray entitled, “Efficacy and Safety of Dapagliflozin According to Frailty in Patients with Heart Failure, a Pre-specified Analysis of the DELIVER Trial.” And then next, Peder, Michelle A. Albert has a very nice synopsis of the American Heart Association Presidential Address, entitled, “Economic Adversity and Healthcare.” Dr. Peder Myhre: Nice. And finally, there's a Research Letter from Dr. Baggish entitled, “Association Between Concussion Burden During Professional American-style Football and Post-career Hypertension.” Dr. Greg Hundley: Very good, Peder. Well, what a packed issue we have this week, and how about we jump next to that feature discussion with our colleague Carolyn? Ah. Dr. Peder Myhre: Let's go. Dr. Carolyn Lam: Primary aldosteronism, or, we're going to say PA for this discussion, is one of the most common causes of secondary hypertension, and it is also a particularly morbid form of secondary hypertension. So identifying this subgroup of hypertensive patients with primary aldosteronism, again PA, would allow us to perhaps, direct more aggressive management to their cardiometabolic risk. Now, is a genetic approach the way to do it? Well, we're about to find out in today's very special paper. We're very honored to have the first author, Dr. Tatsuhiko Naito, from Osaka University Graduate School of Medicine, and his second and co-author Dr. Kosuke Inoue, from the Graduate School of Medicine in Kyoto University, as well as our associate editor, Dr. Wendy Post, from Johns Hopkins University School of Medicine, here to discuss this very important paper. Perhaps I could start with you, Dr. Tatsuhiko. Could you please, perhaps, tell us a little bit about what made you do this study, what you did, and what you found? Dr. Tatsuhiko Naito: I would like to thank you for inviting us to present the information from our paper. In terms of genetic, germline genetic factors behind the development of PA has not been isolated. And in addition, the PA is the cause of hypertension, but the genetic relationship between hypertension and PA has not been discussed previously. That is why we conducted a genome-wide association study, GWAS, of PA here. Our GWAS consisted of three defined cohorts of our Japanese cohort, UK Biobank, and FinnGen. In our Japanese cohort, we collected samples in Hiroshima University, and we used controls from Biobank Japan, which is the largest Japanese biobank. And we also used two publicly available biobanks, UK Biobank and FinnGen. So they can be used upon registration. By utilizing these resources, we conducted a cross-ancestry, meta-analysis of GWAS. Dr. Carolyn Lam: Thank you. And the results, please? Dr. Tatsuhiko Naito: In the meta-analysis, we identified five genetic loci that were significantly associated with the risk of PA satisfied in the genome world significant threshold. The strongest association was observed at WNT2B, which is located in chromosome 1. And in addition, we identified one near the genome-wide association locus CYP11B1 and B2, which is located on chromosome 8. So CYP11B2 is the key enzyme that acts in producing aldosterone in the adrenal gland, thus, we consider that resource. This locus would be also our PA risk associated locus with a high probability. Of interest, these loci were reported to be associated with hypertension, but we thought this results is resemble, because PA occupies around five to 10% of causes of hypertension. Does the PA associated loci could be reported as hypertension associated loci in previous GWAS with large sample size? So to support our assumption, we compared the risk effect of these genetic loci between PA and hypertension. So if there are risk effects who are coming from PA, these loci should present higher effect on PA than on hypertension. And expectedly, these loci presented significantly higher effect on PA here. And lastly, inspired by these results, we hypothesized that some of other loci, that had been reported to be associated with hypertension, might come from the primary effects on PA. To investigate this, we picked up blood pressure rated genetic loci from previous GWAS of blood pressure, and compared their risk effects between PA and hypertension. The result was that, 66.7% presented a higher risk effect for PA than for hypertension. And two strictly demonstrates the result. We also performed the adjustment of blood pressure values, and even in this adjustment, 61.9% showed a higher effect on PA than on hypertension. So considering the prevalence of PA among hypertensive individuals, this result is little bit surprising, we think. So PA may explain an unexpectedly large amount of genetic background of hypertension, we think. Dr. Carolyn Lam: Wow, thank you so much, Tatsuhiko. So first, genome-wide evidence for genetic predisposition to PA susceptibility, and then, revealing that two thirds of previously established BP associated variants were in fact a higher risk effect for PA than for hypertension. Wow. So Wendy, could you help us put these findings into perspective, please? Dr. Wendy Post: Thank you, Carolyn. Congratulations to the authors. This was a really interesting paper that we enjoyed discussing in our meetings. We were especially interested in the clinical potential, clinical implications of your study. We all see patients with hypertension, whether we're cardiologists, or endocrinologists, or primary care physicians. And so, trying to understand more about what is potentially the underlying causes for hypertension, from a biological standpoint, that might help us to identify and treat our patients appropriately, is really so important. And so, I was wondering, Kosuke, if you could tell us, from your perspective as an endocrinologist and a researcher, how you interpret these studies in a way that our readers might be able to use these results to think about the next patient we're seeing in our clinic with hypertension? Dr. Kosuke Inoue: Yeah. Thank you very much for asking this important point, Wendy. We're, first of all, I'm very pleased that our research is published in Circulation, and thank you very much for your consideration. And I think there are two major implications of our findings, treatment and a diagnosis. First of all, for treatment, well, our findings advance our current state of knowledge about PA pathogenesis. Like Wendy said, what is the causes? And what is the genetic causes of primary aldosteronism ? And particularly, it'll be helpful for better precision medicine in the future. And therapy involving genetic information, this may not be the clinical practice tomorrow, but this would advance our clinical practice in the future. And the second point is diagnosis. Well, primary aldosteronism is really important to diagnose, because treating only blood pressure, or hypertension, is not enough for patients with primary aldosteronism. Like Tatsu said, aldosteronism itself has a direct effect on organ damage beyond blood pressure, elevated blood pressure. So diagnosis of primary aldosteronism is critical, and our findings showed 10%, the current percentage of 10% primary aldosteronism, may not be fully diagnosed patients, given that 67% of PA associated variants presented higher alteration for the PA. So I think, we needed to be more careful about diagnosing primary aldosteronism. So for those who have a resistant hypertension, or who are suspected to have primary aldosteronism, we needed to screen more for such patients. Dr. Wendy Post: Thank you, that was really helpful. Can I ask you a little bit more about what you recommend in clinical practice? I've been asking around, we actually just had our American College of Cardiology meeting in New Orleans, and I knew this paper had just been published online, and the editorial is about to come out. And so, I noticed that there's a lot of variability in practice, as to whether we screen for PA, or just treat with aldosterone blocking medications, such as spironalactone. So can you tell me a little bit more about what you recommend? And maybe your practice is different as an endocrinologist, but should we just presume people have primary aldo, and aldosteronism, and treat them for that? Or should we be searching for aldosterone producing adenomas, and surgically removing them? If you could, tell us a little bit more about what you recommend. Dr. Kosuke Inoue: Thank you very much for asking this, Wendy. So to be honest, I don't think we can conclude something only from our result, of course. But what I can recommend is, from our findings, it is better to always thinking about primary aldosteronism when treating patients with hypertension. So those may have and those may not have that. I think thinking about primary aldosteronism is important, and if there's a possibility they have, or if their clinicians have trouble treating hypertension, then I would recommend screening for such patients about primary aldosteronism. Dr. Wendy Post: In order to find an adenoma, is that the purpose of the screening? Dr. Kosuke Inoue: I think, whether they have an adenoma or, there are two types of primary aldosteronism, aldosteronism producing adenoma, and BAH bilateral adrenal hypocardia. And rather does not have adenoma itself, but they have a hyper aldosteronism in their blood. So we cannot tell whether they have a PA or BAH. But anyway, we needed to think about whether they have excess level of aldosterone, and if they have, we needed to think about the proper treatment, such as medication therapy or surgical treatment. Dr. Wendy Post: Thank you. So if they have bilateral adrenal hyperplasia, then medical therapy. Dr. Kosuke Inoue: Yes. Dr. Wendy Post: If they had an adenoma, you might consider surgical excision. Dr. Kosuke Inoue: Generally, yes. Dr. Wendy Post: Thank you. Dr. Carolyn Lam: Wendy, I love that clinical focus, because much as PA is a highly morbid cause of secondary hypertension, it's also sometimes seen as potentially curable, or at least targetable with specific medical therapy. And thank you for inviting that beautiful editorial, I'd love to quote from it. Because the final sentence of it really does say that this paper really reminds everyone treating hypertension, to maintain a high clinical suspicion for PA, and hopefully, such a high clinical suspicion will lower the threshold for biochemical testing. Will motivate the pursuit of localization studies, to determine if a surgical cure is possible. And at minimum, allow for early initiation of mineralocorticoid-receptor blockade. How beautifully put, huh? So thank you for inviting that editorial. And if I may, are there any final take home messages from anyone? May I start with Dr. Tatsuhiko? Any take home messages or next steps you'd like to mention? Dr. Tatsuhiko Naito: Okay. Yeah. I think the future advances in this study first, as Kosuke said, of PA is mainly classified into aldosterone producing adenoma and bilateral adrenal hyperplasia. However, we couldn't identify subtype specific risk associated loci, due to the lack of statistical power. And specifically, we know that histopathological features of aldosterone producing adenoma are reported, vary depending on the causative somatic mutations. So further insights may be obtained by investigating the genetic risk of aldosterone producing adenoma, according to the causative somatic mutations. But anyways, we are happy to present the genome-wide association genetic loci that associated with PA in the cross-ancestry cohort for the first time. Thank you. Dr. Carolyn Lam: Thank you. Kosuke? Kosuke Inoue: Sure. So I totally agree with what Tatshu said, and also, aldosterone is a nasty hormone. So as a clinician, I would recommend, for all clinicians who treat patients with hypertension, please always consider aldosterone, and whether their aldosterone should be treated or not. And thank you. Dr. Carolyn Lam: Wendy? Dr. Wendy Post: I also wanted to get back to your statements, Kosuke, about precision medicine. And this was a genetic study, and you did mention how this could potentially lead to precision medicine, practical approaches to identifying patients who might be treated with specific therapies, based on their genetics. And of course, we're not there yet, but thanks for helping us to get closer to that vision in the future. Dr. Carolyn Lam: Indeed, thank you so much for publishing this very important paper in Circulation, and for coming online to discuss it today. You've been listening to Circulation on the Run. Thank you listeners for joining us today, and don't forget to tune in again next week. Dr. Greg Hundley: This program is copyright of the American Heart Association 2023. 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.

New YouTube Channel - https://www.youtube.com/channel/UCKjWKXfpjtNL0oL2R6MKSxwToday's Sponsors:Brad Reynoldshttps://thinkbrad.com/Bowtie Barber Clubhttps://www.bowtiebarberclub.com/Nash NewsNWS confirms 3 severe tornadoes in Tennessee, Arkansas; damage surveys ongoinghttps://www.tennessean.com/story/news/local/2023/04/02/nws-confirms-tornadoes-in-tennessee-arkansas-assess-damage/70073443007/Protesters Storm Tennessee Capitol Demanding Gun Control https://www.dailywire.com/news/protesters-storm-tennessee-capitol-demanding-gun-controlMarch for Our Lives "walk-out" planned to mark one week since The Covenant School shootinghttps://www.newschannel5.com/news/march-for-our-lives-walk-out-and-metro-schools-walk-in-planned-to-mark-one-week-since-the-covenant-school-shootingSpecial Segment Damage From the Tornadoes over the weekend. At least 18 dead after tornadoes rake US Midwest, Southhttps://www.newschannel5.com/news/tornadoes-strike-arkansas-illinois-7-dead-dozens-injuredMap of Tennesseehttps://geology.com/county-map/tennessee-county-map.gifAt least 15 dead after storms in Tennessee, TEMA confirmshttps://www.wsmv.com/2023/04/02/least-15-dead-after-storms-tennessee-tema-confirms/NashSevereWxhttps://twitter.com/nashseverewxWeather Service confirms EF2 Tornado in Wayne and Lewis Countieshttps://www.newschannel5.com/news/weather-service-confirms-ef2-tornado-in-wayne-and-lewis-countiesSevere storms cause freight train cars to overturn in Marshall Countyhttps://www.newschannel5.com/news/severe-storms-cause-freight-train-cars-to-overturn-in-marshall-countySevere weather destroys homes and businesses across Rutherford Countyhttps://www.newschannel5.com/news/severe-weather-destroys-homes-and-businesses-across-rutherford-countyCleanup begins after an E-F-3 tornado hits Hardin Countyhttps://www.newschannel5.com/news/cleanup-begins-after-an-e-f-3-tornado-hits-hardin-countyLocal Artist FeatureNashville Daily Artist of the Day Playlisthttps://open.spotify.com/playlist/51eNcUWPg7qtj8KECrbuwx?si=nEfxeOgmTv6rFUyhVUJY9AFollow us @ XPLR NASHWebsite - https://nashvilledailypodcast.com/YouTube Channel - https://www.youtube.com/c/xplrnashInstagram - https://www.instagram.com/xplr.nash/Twitter - https://twitter.com/xplr_nashNASHVILLE & XPLR MERCH - https://www.xplrnash.com/shopMedia and other inquiries please email hello@xplr.life

Nearly 12 years ago, On April 27, 2011, the U.S. Storm Prediction Center (SPC) counted 219 tornadoes in the United States, breaking a previous record of 147 which was set in 1974. There were 317 fatalities that day alone, and a record-breaking 4 EF-5 tornadoes cut huge swaths through Alabama, Mississippi, and Tennessee, while many other huge tornadoes swept through 16 states over a 4 day period, leaving behind a path of devastation claiming over 340 lives and costing over 11 Billion dollars. Our Shows: all available at www.1001storiespodcast.com ... #TORNADO #STORM CHASER #2011SUPER OUTBREAK Get all of our shows at one website: www.1001storiespodcast.com REVIEWS NEEDED . My email works as well for comments: 1001storiespodcast@gmail.com SUPPORT OUR SHOW BY BECOMING A PATRON! www.patreon.com/1001storiesnetwork. Its time I started asking for support! Thank you. Its a few dollars a month OR a one time. (Any amount is appreciated). YOUR REVIEWS AND SUBSCRIPTIONS AT APPLE/ITUNES AND ALL ANDROID HOSTS ARE NEEDED AND APPRECIATED! LINKS BELOW... Open these links to enjoy our shows! APPLE USERS Catch 1001 Heroes on any Apple Device here (Free): https://podcasts.apple.com/us/podcast/1001-heroes-legends-histories-mysteries-podcast/id956154836?mt=2  Catch 1001 CLASSIC SHORT STORIES at Apple Podcast App Now: https://podcasts.apple.com/us/podcast/1001-classic-short-stories-tales/id1078098622 Catch 1001 Stories for the Road at Apple Podcast now:  https://podcasts.apple.com/us/podcast/1001-stories-for-the-road/id1227478901 NEW Enjoy 1001 Greatest Love Stories on Apple Devices here: https://podcasts.apple.com/us/podcast/1001-greatest-love-stories/id1485751552 Catch 1001 RADIO DAYS now at Apple iTunes!  https://itunes.apple.com/us/podcast/1001-radio-days/id1405045413?mt=2 Catch 1001 Ghost Stories & Tales of the Maacabre on Apple DevIces here: https://podcasts.apple.com/us/podcast/1001-ghost-stories-tales-of-the-macabre/id1516332327 Catch 1001 Sherlock Holmes Stories (& Arthur Conan Doyle) on Apple Podcast Here: https://podcasts.apple.com/us/podcast/1001-sherlock-holmes-stories-best-sir-arthur-conan/id1534427618 Catch 1001 History's Best Storytellers (interviews) here: https://podcasts.apple.com/us/podcast/1001-historys-best-storytellers/id1483649026 ANDROID USERS- 1001 Radio Days right here at Player.fm FREE: https://player.fm/series/1001-radio-days 1001 Classic Short Stories & Tales at Spotify https://open.spotify.com/show/6rzDb5uFdOhfw5X6P5lkWn 1001 Heroes, Legends, Histories & Mysteries: https://castbox.fm/channel/1001-Heroes%2C-Legends%2C-Histories-%26-Mysteries-Podcast-id1323418?country=us 1001 Stories for the Road on Stitcher https://www.stitcher.com/show/1001-stories-for-the-road Enjoy 1001 Greatest Love Stories on Stitcher here: ​​https://www.stitcher.com/s?fid=479022&refid=stpr.  1001 Ghost Stories & Tales of the Macabre on Spotify: https://open.spotify.com/show/5P4hV28LgpG89dRNMfSDKJ 1001 Sherlock Holmes Stories (& Tales from Arthur Conan Doyle) :https://www.podparadise.com/Podcast/1534427618 1001 History's Best Storytellers: (interviews) on Stitcher https://www.podparadise.com/Podcast/1534427618 Catch ALL of our shows at one place by going to www.1001storiesnetwork.com- our home website with Megaphone. Learn more about your ad choices. Visit podcastchoices.com/adchoices

In this episode, Erica and Darius discuss the importance of time management and ways to evaluate and improve this skill. They share practical techniques like creating a schedule, prioritizing tasks, time blocking, delegating tasks, and managing distractions. They also recommend a variety of apps for tracking time and improving productivity. Tune in to learn how to manage your time more effectively and efficiently. Links: -The Checklist Manifesto - https://tinyurl.com/3p6bzxvd -Tony Buzan - https://tonybuzan.com/ -Dan Sullivan - Strategic coach: www.StrategicCoach.com -Kanban Method: https://kanbanize.com/ -Google Keep: https://keep.google.com/ -Google Calendar: https://calendar.google.com/ -The Right Brain Time Manager: https://tinyurl.com/3cj9mbec -Planning, Time Management and Organization for Success: https://tinyurl.com/ydx7vazp -EF activities: https://tinyurl.com/yeytwn7v -EF and Study Skills Course: https://tinyurl.com/3brpf52j -Executive Functioning Assessment: https://tinyurl.com/48ywprbx -Time Management Assessment: https://tinyurl.com/5yvtzdyf - Forest, Rize, Serene, Habitica, Toggl Track, HourStack, Timely, TrackingTime, RescueTime  - BulletMap Academy: https://bulletmapacademy.com/ - Learning Specialist Courses:https://www.learningspecialistcourses.com/ - Executive functions and Study Skills Course: https://tinyurl.com/n86mf2bx - Good Sensory Learning: https://goodsensorylearning.com/ - Dyslexia at Work: www.dyslexiawork.com

Í þessum þætti kíkja Villi og Fjölnir á nokkra hluti. Hluti sem okkar kynslóð horfir á með nostalgískum augum. Hvað er það sem er að láta tiktok kynslóðina dýrka Blossa? Af hverju viljum við, þúsaldarkynslóðin, fá að djamma á Astró? Ef hlutir eru slæmir, verða þeir alltaf að vera þannig? Kíkjum aðeins á þetta!

The following question refers to Section 9.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.  The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Duke University cardiology fellow and CardioNerds FIT Ambassador Dr. Aman Kansal, and then by expert faculty Dr. Anu Lala. Dr. Lala is an advanced heart failure and transplant cardiologist, associate professor of medicine and population health science and policy, Director of Heart Failure Research, and Program Director for the Advanced Heart Failure and Transplant fellowship training program at Mount Sinai. Dr. Lala is deputy editor for the Journal of Cardiac Failure. Dr. Lala has been a champion and role model for CardioNerds. She has been a PI mentor for the CardioNerds Clinical Trials Network and continues to serve in the program's leadership. She is also a faculty mentor for this very 2022 heart failure decipher the guidelines series. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #13 Mrs. Hart is a 63-year-old woman with a history of non-ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 20-25%) presenting with 5 days of worsening dyspnea and orthopnea. She takes carvedilol 12.5mg BID, sacubitril-valsartan 24-46mg BID, empagliflozin 10mg daily, and furosemide 40mg daily and reports that she has been able to take all her medications. What is the initial management for Mrs. H? A Assess her degree of congestion and hypoperfusion B Search for precipitating factors C Evaluate her overall trajectory D All of the above E None of the above Answer #13 Explanation The correct answer is D – all of the above.   Choice A is correct because in patients hospitalized with heart failure, the severity of congestion and adequacy of perfusion should be assessed to guide triage and initial therapy (Class 1, LOE C-LD). Congestion can be assessed by using the clinical exam to gauge right and left-sided filling pressures (e.g., elevated JVP, S3, edema) which are usually proportional in decompensation of chronic HF with low EF; however, up to 1 in 4 patients have a mismatch between right- and left-sided filling pressures. Hypoperfusion can be suspected from narrow pulse pressure and cool extremities, intolerance to neurohormonal antagonists, worsening renal function, altered mental status, and/or an elevated serum lactate. For more on the bedside evaluation of heart failure, enjoy Episode #142 – The Role of the Clinical Examination in Patients With Heart Failure – with Dr. Mark Drazner. Choice B, searching for precipitating factors is also correct. In patients hospitalized with HF, the common precipitating factors and the overall patient trajectory should be assessed to guide appropriate therapy (Class 1, LOE C-LD). Common precipitating factors include ischemic and nonischemic causes, such as acute coronary syndromes, atrial fibrillation and other arrhythmias, uncontrolled HTN, other cardiac disease (e.g., endocarditis), acute infections, anemia, thyroid dysfunction, non-adherence to medications or new medications. When initial clinical assessment does not suggest congestion or hypoperfusion, symptoms of HF may be a result of transient ischemia, arrhythmias, or noncardiac disease such as chronic pulmonary disease or pneumonia,

6 people killed inside a Nashville elementary school, more than 20 people killed after an EF-4 tornado devastated Mississippi, chaos in Israel as crowds get PM Netanyahu to delay his plan to weaken the judicial system, a Florida plastic surgeon is charged with murder in connection to a missing attorney, and the inspiring stories of hope amid the destruction in Mississippi.

On this week's episode of Inside Outside Innovation, we sit down with Tom Daly, founder of Relevant Ventures. Tom and I talk about the challenges big companies have when trying to navigate technology and market changes. And what you can do to avoid some of the common obstacles and barriers to innovation and transformation. Let's get started. Inside Outside Innovation is the podcast to help new innovators navigate what's next. Each week we'll give you a front row seat into what it takes to learn, grow, and thrive In today's world of accelerating change and uncertainty, join us as we explore, engage, and experiment with the best and the brightest, innovators, entrepreneurs, and pioneering businesses. It's time to get started.Interview Transcript  with Tom Daly, Founder of Relevant VenturesBrian Ardinger: Welcome to another episode of Inside Outside Innovation. I'm your host Brian Ardinger, and as always, we have another amazing guest. Today we have Tom Daly. He is the founder of Relevant Ventures. Welcome Tom. Tom Daly: Thank you very much, Brian. Pleasure to be here, speaking with you. Brian Ardinger: I'm excited to have you on the show. You have had a lot of experience in this innovation space. You worked with companies like UPS and ING and I think most recently, Coca-Cola and a lot of the innovation efforts around that world. So I am excited to have you on the show to talk about some of the new things you're doing and I think more importantly, some of the things you've learned over the years.Tom Daly: I started doing this work before people called it digital transformation or innovation. The Earth cooled, at about the same time I began getting my head around this. I'm an advertising guy to begin with, and I can't prove it, but I think I created the world's first dedicated 30 sec TV commercial to a website. UPS. In that process, I picked up some vocabulary and I learned some things about how websites, quote unquote work, so that when people started calling, you know, back in the mid-nineties wanting to talk to somebody about the web or the internet, the calls came to me. And it was during that process where I started to build new networks within UPS, learn about new things going on at UPS and discover some of the opportunities. It's been a while. Brian Ardinger: You talk a lot about this ability to turn big ships in small spaces. Talk a little bit about what that means to you and, and what the challenges really are for corporations in, in this whole innovation space. Tom Daly: The idea of turning big ships in small spaces actually goes back to my boss's boss at UPS who noticed I was toiling. UPS has a reputation as a conservative company. A little bit unfair, there's some truth to that, but not quite what people think.It's actually a very, very innovative company and has been for its entire history, but it is collaborative. There's a lot of debate and a lot of discussion. So getting new things done, driving new ideas that my boss to encourage me, you'll get there, Tom, but it's like turning a battleship in the Chattahoochee.So, I don't know where listeners are, but imagine a pretty darn small body of water and a really big ship that you're trying to turn. So, a lot of back and forth, a lot of kissing babies, shaking hands, and just getting, you know politics, but in a good positive way to kind of really understand interests and concerns and build a better program, a better idea.So that's the idea, and it was encouraging to me. So, this notion of turning big ships in small spaces, it seems to be, to the degree I have any superpowers, that's the one I'm able to kind of figure out how to help larger organizations figure out how to extract value from, you know, kind of what's coming up around the corner.Brian Ardinger: Obviously you've seen a lot of changes, whether they're technology changes or business model changes that have happened over the years. Where do companies typically run into the problems when they see something on the emerging horizon and they're saying, we've gotta do something about this. What goes through their mind and what can they do to better prepare for some of these drastic changes?Tom Daly: The thing companies can do to help themselves most be prepared for big ships in the world that we all live and compete in, is, you know, the twin keys of openness and acceptance. Being open to an idea is really important, but it is only half the battle. Being accepting of the implications of those ideas is really key and the classic example would be Kodak. You know, Kodak early in, open to the idea of digital photography. But equally unaccepting of its implications. So they didn't jump in, they didn't do the things they needed to do, and as a result, very different company Blockbuster would fit in that category.Certainly, they understood the implications of streaming technologies and the web and the ability to distribute content. Given the retail heavy business, the land heavy business, they just weren't accepting, or at least not accepting fast enough to be able to secure position in the next evolution of how people consumed content. So those two ideas, being open and accepting both in equal measures is critical to getting yourself in a good spot. Brian Ardinger: Well, you touched on an interesting point. You read about the stories of companies failing or being disrupted, and from the outside it looks like, well, they didn't pay attention, or they didn't know what was going on.But it seems like, from the stories and the people that I've talked to, it's not that they weren't aware of what was going on. Or the fact that it was going to have a major impact or that they should do something about it. It was more to that line of it, like you said, acceptance of, well, how do we actually do this knowing that we're going to have to change our business models, change the way we make money, change everything about what we currently do to make this radical shift. And it's that classic innovator's dilemma. Are you seeing that changing nowadays, now that people are kind of more familiar with the concept of this and, and as more and more changes hit corporations, so you're getting faster at having to adapt to this. Are you seeing the world changing or are you still seeing the same problems exist?Tom Daly: You know, anybody in this space, Brian, doing what I've been doing for as long as I've been doing it, you need to be an optimist. You need to believe that, you know it's all going to happen. That said, the conversations I'm having today in 2023 are pretty darn close to the conversations I was having in the middle, you know, of the nineties, right?So, whether it was the dawn of, you know, this graphical overlay on the internet, the web, and when browsers enabled, or the introduction of now advertising and marketing opportunities on the web, which didn't really happen at the beginning of the browser era, that followed a little bit later. Or the introduction of mobile phones and then smartphones and all the, it's the same conversations. And they all come from a place of gaps.I won't say a lack because in some places there is confidence and acceptance and alignment with what's going on. But it's not uniform within organizations. Right. Then there are pockets of people within departments, IT people, marketing people, salespeople. They see the same opportunities. But there are also folks who do not see the future in the same way. And that's where that acceptance problem comes in. So I ask questions, I do a little survey. And I ask people really fundamental questions, one of them having to do with innovation. Now, where do you put your company in terms of new technologies and how quickly they would be used. Like you see yourself among the first to use emerging technologies?I'm asked almost around 2000 people this question. And interestingly, overall, 16% of people would say, yes, our company is among the first. But if you drill down into that, you see CEOs of the C-suite at 36% believe they are the first to use technology, but only about 19% of VP and director level. So that gap needs to be studied.It could be that CEOs are both open and accepting, but just can't bring their organization along with them. And get people to the same head space. Or it could be that the, you know, VP director level folks see something different. We're not among the first, and it's this overconfidence among the C-suite, who happen to believe, but it may not be the reality of what you don't see it. What you're looking at C-Suite is really not what's going on. Regardless of how you interpret that gap, there is a gap. And understanding it, managing it, dissecting it, interrogating it is kind of what's really important. Brian Ardinger: You know, a lot of this change and the, the ability to accept change and, and adapt to it comes down to incentives. What are you seeing or what have you seen that's worked when it comes to incentivizing teams or even the C-Suite to put new things into place and to react and adapt to new changes? Tom Daly: It's going to happen; it's going to change. My technique, it may be more patient than others. I don't know how to make it go super-fast. I just know that lots of back and forth. You know, I think that the thing to do is demonstrate that this is real. I'll tell you an example, a little technique that I used back before the advent of mobile payments. Before people using their phone to buy things was really as prevalent as it is today. It was possible, but not a part of many people's experience.So, at the time I was at Coca-Cola, our products were sold in a lot of retail environment where these capabilities were being slowly introduced. But I was also working among a group of people, none of them are ignorant, they just didn't believe it was happening. I organized what I called a mobile payments safari.I got a local little tour bus. And planned out a route to Coca-Cola Company customers. Dunkin Donuts, local Burger Joint, Home Depot. All of these companies using Mobile payments in one way, shape, or form. And I made everybody kind of get the appropriate app, sign up for the appropriate services. They paid early days of Square. I didn't pay for this bus ride out of my own budget. I had each participant use Square to see how that worked. Took them to Dunkin Donuts to go get their coffee or Coke and donut. Talk to the counter, see customers, so on and so forth throughout the day. Now, by the end of the day, it wasn't Tom's opinion, my language I gave everybody the same inputs that I had. With the benefit of those same inputs. They reached the same output. They reached the same conclusion, alignment gaps closed. People started to realize, oh yeah, that's, it is happening in the world, you know where I live. Brian Ardinger: That's a great exercise, and I think more and more folks need to pay attention to that. You know, we talk a lot about the customer discovery process and that. Especially when we're working with startups, because at that early stage, they're trying to figure out who their customers are. Is their market and everything else. I think the challenge when you get to a kind of an established company is they think they know who their customers are or they, you know, read about it or hang out with the same competitors. And so, there's a natural tendency to think they know what's going on in the world and that ability to step outside the office and see what's really going on. And, you know, firsthand knowledge I think is so important for whether you're launching a new product or just trying to, like you said, understand a new technology set and how that's impacting or could impact your current business. Tom Daly: Brian, I think there's a lot to that and it's incredibly helpful, but the other thing that you need to be able to do is tell the stories around that and help people understand it in a way that's digestible. Before I organized this local payments safari, I circulated a couple of case studies, one of which super impactful I think you know, that again, back to a square example, the, Salvation Army, you know, that famous red kettle collecting coins around the holidays. There was a early and really interesting experiment where Salvation Army was using Square to accept payments. Why? Not because everybody was using their phone to buy stuff, but they were using credit cards. They were not using cash. So, they didn't have change in their pockets, and you know, felt bad in the Red Kettle. So, they said, well, we got to find a way to get some money. You know, the storytelling that I created was, you know that the coins that go on the kettle in December, are the coins that go on a vending machine in July.And if people don't have the money to put into that red kettle, they're going to be the same dilemma. And we just got to catch up with us. So, we have to find ways to remove that payment friction. Then I happen to be focused on mobile technology at the time. The point is the storytelling and finding ways to connect these trends and whether it's super easy. Nope, no language, no technical stuff. You didn't have to understand just, oh yeah, I get it. No coins. Brian Ardinger: So, I'd love your insight into how important it is to get buy-in across the organization, or how difficult is it for the average manager within a company to help push the transformation agenda forward. Versus having corporate buy-in and, and everybody aligned. Can you talk a little bit about what are the skill sets, tool sets, things that people need from a manager level to make this stuff happen? Tom Daly: I wish I had the one silver bullet to tell you some new blinding revelation. I don't. It's the usual suspects, Brian. You know, you need to be informed. You kind of need to know a little bit about how the watch is made. Not just sort of the superficial part of kind of what you saw. This, your technologist is probably more likely to understand a little bit of the underlying technology, but you may not have the language or experience or vocabulary to talk about how that interacts with people. If you're a marketing person, you probably have the skillset to talk about the stories and the like, but you don't have the technical knowledge. Whether you're coming at innovation, regardless of the perspective that you're coming at an innovation discussion or transformation discussion knowing both is important. You can't just kind of say, oh yeah, and well payments, you kind of have to know a little bit about how the watch is made. So certain amount of curiosity, critical, tenacity, perseverance. You know, we've captured my personal style, that big ship, small spaces constantly creeping towards the destination.Other people will have different styles at different techniques. But it is all captured by the same notion of perseverance, tenacity, persistence, et cetera, et cetera. So, no unique, I do have a couple of resources though that would be helpful for folks. You know, first thing folks might want to do is wherever they buy their books, great book written by a fellow named Kumar Metta, who wrote something called The Innovation Biome. And the Innovation Biome is a book capturing case studies from cultures of innovation, big companies. You know, Amazons of the world, Apples. What do they do culturally to enable these environments? You know, you'll use a reference, a culture will Yes, within Amazon. So it's not the manager's job to say no. Sort of the manager's job to say, okay, but yes, but let me help you get this through so you can get the information that you need.So, you know, I've worked with folks in the past, you know, who facilitate meetings that allow executives to get together, break out of the day-to-day. Some of the techniques we've already touched on, talk to customers, walk around where people are living and doing their day-to-day thing to see where your ideas fit. Where there are problems that you can solve. Simple stuff. But if you don't do it and you spend your time looking for that silver bullet, you're gonna miss it. Just do it. Brian Ardinger: Absolutely. The last topic I want to talk about is, obviously again, you've been in a lot of different industries and that. You pay attention to a lot of the trends that are going on. Obviously in the, in news this week, in, in the past few weeks, the whole AI movement and chat, GPT-4, and I'm, I'm talking to a lot of different companies saying hey we see this thing coming, we have no idea how to attack it or use it or whatever. What are you seeing when it comes to the AI trend and what is your input for helping companies try to navigate that early stage? Tom Daly: We would agree. A generative AI overall kind of a a big deal. Going be super transformative. This book that I mentioned, the Innovation Biome. The author Kumar Metta talks about the fallacy of the next big thing, and he picks apart you know, the first fallacy is that, you know, it's the next thing. So generative AI is here. But it's like day one, right? I mean, not literally, but you know, broadly speaking. So, what it will truly become, who knows, right? I mean, so don't get too fixated on it as a thing at this moment in time. Allowing yourself to just project forward and imagine scenarios down the road of what a future could look like, because eventually it will get there. Lots of folks you know, back in the day of 56 K modems. Nobody will ever buy you anything. Music won't ever happen. And this blockbuster streaming thing. Well, 56 became 124. 124 became EF whatever. And you know, here we are on our phones doing things that were unimaginable really not that long ago. Generative AI is only important if it turns into a billion-dollar idea for you.If you set that standard, you're going to miss it. Right. Think about small, quick little wins things that you can do today. Learn the technology. Introduce it into your organization. Become familiar with it, and don't worry about the long ball, right? Singles and doubles. Three yards caught. Where are your sports? Whatever you're thinking. Start with what you can do and don't despite what I just said about learning how the watch is made, you'll be overly focus on a specific thing, right? Chat Gpt, GPT-4, whatever it is, open up the aperture. Think more broadly about where these things, what's the real root essence of it? Not a specific manifestation of it. If you give yourself that latitude, it's important to you even if it only saves two seconds a day for somebody. If it saves two seconds for somebody, maybe it saves two seconds for everybody. A company that matters. It'll magnify itself if it's real.Brian Ardinger: I also find that you mentioned opening up the aperture, and I think a lot of times when I'm talking to C-suite folks or team leaders and that they oftentimes think that they have to have all the answers. And especially in larger organizations, you have a lot of people in the depths of the organization that I believe are curious and restless in and around these particular topics. And sometimes all it takes is opening that up and saying, hey, who else in the organization has access or information or insight or a desire to help us figure this kind of stuff out?And if you opened up the conversation, I think that sometimes takes the pressure off of the lead team to have to have all the answers or figure it out all themselves. I think what you'll find is there are people and pockets within the organization that can help you move faster if you just allow them to help you do that.Tom Daly: Brian, that's what I was trying to get to with the kissing babies and shaking hands and politics isn't a bad thing. It's not a bad word. It's people. It's sitting down, grab a cup of coffee with your colleagues, you know, share your idea. Why you might be enthusiastic or excited about a particular opportunity, but be open and, and listen when they tell you why that might work.Big organizations, a lot of specialized skills and capabilities and these are intricate machines built over a long time and my clever little idea looks like a bit of grit. No, it's just going to come up the work style. They'll do it. Tell me why. Partner? Why is it going to go up the works? That'll help me think about it more deeply.Come back to you and say, well, I think I've solved that problem. What's next? Oh, okay, you have. Good now. Hey, let's go rope in this other person. And then you just build that consensus. Now again, in smaller organization, that cycle goes faster. But the principles say if you just show up with an idea when you went home on Friday, we did it this way.Here we are Monday morning. We're doing it a totally different way. Gaps in alignment, confidence and trust are going to come back and bite you. My analogy is turning a big ship. That's the rocks. Those are the rocks that are going to sink you. You're going to get stuck. It's just a lot more work to get unstuck. And had you just charted the course a little bit more methodically?For more informationBrian Ardinger: Makes a lot of sense. Well, Tom, we live in fascinating times. I appreciate you coming on and, and sharing your thoughts and insights over the past couple decades of how to navigate this changing world that we're living in. If people want to find out more about yourself or about relevant ventures, what's the best way to do that?Tom Daly: Best way would be just to visit relevantventures.com website. Of course, you'll find me, you know, a couple of Slack channels here and there. You'll find me on LinkedIn. I am wide open to sharing these ideas. It's how I learn and how I get better. And I hope someone has an idea that they want to discuss, because I love to share what I've learned along the way.Brian Ardinger: Sounds great. Well, Tom, thanks for bringing on Inside Outside Innovation. Looking forward to continuing the conversation. Tom Daly: Thank you. Brian Ardinger: That's it for another episode of Inside Outside Innovation. If you want to learn more about our team, our content, our services, check out InsideOutside.io or follow us on Twitter @theIOpodcast or @Ardinger. Until next time, go out and innovate.FREE INNOVATION NEWSLETTER & TOOLSGet the latest episodes of the Inside Outside Innovation podcast, in addition to thought leadership in the form of blogs, innovation resources, videos, and invitations to exclusive events. SUBSCRIBE HEREYou can also search every Inside Outside Innovation Podcast by Topic and Company.  For more innovations resources, check out IO's Innovation Article Database, Innovation Tools Database, Innovation Book Database, and Innovation Video Database.  

The Final Four is set for the Men's NCAA Tournament and no one expected these matchups this far into the tournament. And Dave was happy to see his LSU Tigers make the Final Four in the Women's Tournament.  Over the weekend, Dave's family celebrated the 4th anniversary of his oldest granddaughter's "Gotcha" day.  Bill was on catsitting duty last week and keeping tabs on one of the cats was a bit more work than he anticipated.  An EF-4 tornado hit Mississippi on Friday night,...

Natural disasters are one of the most unpredictable, but expected forms of destruction that humanity can expect to happen anywhere and at any time. Unfortunately, many types of disasters result in the loss of life, in addition to wide-scale devastation. When it comes to educational facilities like schools, there's a certain type of disaster response that communities will need in the aftermath of one. The city of Joplin, Missouri, which experienced a deadly tornado in 2011, would come to terms with this when a disaster occurred on a high school's graduation day and caused the death of seven students and a staff member.Natural disasters are unavoidable, but how can preparedness, particularly in schools, assist in response efforts to them? And what did Joplin School officials learn from it?In the latest “School Safety Today” podcast, host Michelle Dawn Mooney interviewed Dr. C.J. Huff, an Education Consultant and Disaster Recovery Expert and the former superintendent of Joplin Schools. Dr. Huff discussed how the tornado impacted the district's students, families, and staff and what he learned from the urgent needs Joplin needed immediately after.Mooney and Huff also talked about …1. How the Bright Futures framework assisted in Joplin Schools' recovery and rebuilding efforts following a devasting EF-5 tornado2. Strategies to build local leadership and resource capacity 3. Lessons learned that are applicable to the day-to-day crises school communities face“One of the primary lessons learned and where Bright Futures really comes into play, is the idea that relationships matter. You have to have relationships in your community, across your community, and across your region, in order to be able to be successful in that long-term recovery effort,” said Dr. Huff. “Because all disasters start at low point, have a lot of resources pouring into your community initially, but the next disaster comes along, those resources go away to address that next disaster, and you kind of find yourself relying on those resources you have there locally or regionally, and the thing that Bright Futures did for us in Joplin, prior to the disaster, was allowed us that opportunity to build those connections, relationships across the community, put support structures in place to meet the needs of our kids, identify those resources, create systems that would allow us to get those resources quickly to our children, so that we can stabilize our lives to the greatest degree possible as we dealt with poverty issues and other issues that surfaced that so many of our kids are faced with, and then leverage those partnerships and relationships to create new opportunities for our kids.”Dr. C.J. Huff is an educator, an Education Consultant and Disaster Recovery Expert, and the former superintendent of Joplin Schools. He led his district's disaster response strategy, and he has over two decades of experience as an educator. Dr. Huff is also the founder of Bright Futures USA.

Ha descubierto que ser un cristiano es un duro trabajo? Usted NO puede vivir la vida cristiana por medio de esfuerzos humanos. El secreto consiste en estar consciente y continuamente llenos del PODER del Espritu Santo. En este mensaje el pastor Adrin Rogers nos muestra cmo podemos dar al Espritu Santo acceso a cada rincn de nuestra vida. Ef. 5:18 To support this ministry financially, visit: https://www.oneplace.com/donate/276/29

Ha descubierto que ser un cristiano es un duro trabajo? Usted NO puede vivir la vida cristiana por medio de esfuerzos humanos. El secreto consiste en estar consciente y continuamente llenos del PODER del Espritu Santo. En este mensaje el pastor Adrin Rogers nos muestra cmo podemos dar al Espritu Santo acceso a cada rincn de nuestra vida. Ef. 5:18 To support this ministry financially, visit: https://www.oneplace.com/donate/276/29

Ha descubierto que ser un cristiano es un duro trabajo? Usted NO puede vivir la vida cristiana por medio de esfuerzos humanos. El secreto consiste en estar consciente y continuamente llenos del PODER del Espritu Santo. En este mensaje el pastor Adrin Rogers nos muestra cmo podemos dar al Espritu Santo acceso a cada rincn de nuestra vida. Ef. 5:18 To support this ministry financially, visit: https://www.oneplace.com/donate/276/29

Ha descubierto que ser un cristiano es un duro trabajo? Usted NO puede vivir la vida cristiana por medio de esfuerzos humanos. El secreto consiste en estar consciente y continuamente llenos del PODER del Espritu Santo. En este mensaje el pastor Adrin Rogers nos muestra cmo podemos dar al Espritu Santo acceso a cada rincn de nuestra vida. Ef. 5:18 To support this ministry financially, visit: https://www.oneplace.com/donate/276/29

Domingo IV Semana Tiempo de Cuaresma De verdad que si fuésemos conscientes de quienes somos otra sería nuestra historia... los textos de hoy desde la simbología del Bautismo nos enseñan a enfrentar la vida con esta plena conciencia de ser Ungidos De Dios. Lee los textos y renueva tu Bautismo en Fe... 1 Sam 16, 1.6-7.10-13 Sal 22, 1-6 Ef 5, 8-14 Jn 9, 1-41

Íslenskir flakkarar hafa ekki alltaf verið heitið fyrir einhverja grunsamlega tækni sem þú getur keypt í næstu raftækjabúð. Þessir flakkarar komu til þín, og voru kallaðir ýmsum nöfnum, en þó flestir kallaðir Gvendur.Ef þið viljið vita hvað það þýði að "dúlla fyrir aðra", þá verðið þið að hlusta á þennan þátt.

Episode 386 of the Lens Shark Photography Podcast   Featured: Fashion and portrait photographer, Jai Mayhew   In This Episode If you subscribe to the Lens Shark Photography Podcast, please take a moment to rate and review us to help make it easier for others to discover the show. Show Opener:Fashion and portrait photographer, Jai Mayhew. Thanks Jai! Sponsors: - Fujifilm's Create With Me program.  Build Your Legacy with Fujifilm - Since 1957, the legends at Roberts Camera. Also, unload your gear with UsedPhotoPro.com - Great 25% OFF savings on sweet Nanlite gear at NanliteUS.com- Sweet 25% OFF savings on sweet Shimoda gear at ShimodaDesigns.com - More mostly 20% OFF codes at LensShark.com/deals. Stories: Canon's roadmap for RF-mount glass, not EF. (#) Why the “Safety shot” is a good idea. (#) Sirui's Dragon is bendy and cool. (#) A photographer wins with the CCB. (#) Lensrentals has another top list. (#) Canon's EOS R5 Mark II, and EOS R1 may be delayed. (#) Leica's 100-400mm. (#) We may not see the Canon Speedlite EL-5 for awhile. (#) Edelkrone's revamped StandPLUS. (#) Hints of a useful AI-based wearable camera from Humane. (#)   Connect With Us Thank you for listening to the Lens Shark Photography Podcast! Connect with me, Sharky James on Twitter, Instagram Vero, and Facebook (all @LensShark).