Podcast appearances and mentions of Bradford Hill

Bilginin korkunç bir hızda aktığı zamanlardayız. Teknoloji ve sosyal medyanın gelişimi sayesinde bilgiye ulaşmak, hiç bu kadar kolay olmamıştı. Fakat iletişimin bu kadar kolay olmasının bazı olumsuz etkileri de var elbette. Örneğin post-truth, yani gerçek ötesi kavramı... Artık bir bilginin doğru veya yanlış olduğunu anlamak eskisi kadar kolay değil. Hatta yalan olduğunu içten içe bildiğimiz bazı bilgileri büyütebiliyor, o duvara bir tuğla da biz koyabiliyoruz. 111 Hz'in bu bölümünde post-truth çağında doğru bilgiye nasıl ulaşabileceğimiz üzerine düşünüyoruz. Yalan haberlere ya da bilgilere neden inandığımızı ve bunlara karşı nasıl önlemler alabileceğimizi araştırıyoruz.Sunan: Barış ÖzcanHazırlayan: Özgür YılgürSes Tasarım ve Kurgu: Metin BozkurtYapımcı: Podbee Media------- Podbee Sunar -------Bu podcast, getirfinans hakkında reklam içerir.getirfinans iyi faizi vade beklemeden günlük kazandırır. Kredi faiz oranı düşüktür. Aidatsız kredi kartı sunar. Para transferinden ücret almaz. Sen de getirfinanslı ol.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Send us a textCan you provide feedback on my podcast (what you like?  what you want more of?  length?  Please answer a few questions here.  Can a simple habit like flossing really reduce your risk of stroke? In this episode, Dr. Bobby unpacks the headlines sparked by a recent presentation at the American Stroke Association's International Conference that claimed regular flossing could reduce stroke risk by 20–50%. Dr. Bobby begins with a refresher on the importance of stroke prevention. From there, he explores the biological plausibility of a connection between oral health and cardiovascular events. While Americans are fairly diligent about brushing (with 90% brushing once daily and 60% brushing twice a day per YouGov data), flossing habits lag significantly (NIH Oral Health Study—highlighting a clear opportunity if the flossing-stroke link is real.Dr. Bobby dives into the study behind the headlines, a new analysis from the long-running Atherosclerosis Risk in Communities (ARIC) study, which tracked over 6,000 individuals for 25 years. The preliminary finding: regular flossers had significantly lower risk of ischemic and cardioembolic strokes (Study Abstract). Surprisingly, brushing and dental visits showed no significant benefit in this analysis.So why isn't this flossing-stroke connection headline a "five-alarm fire" in medicine? Dr. Bobby explains the limitations: the results were shared via a conference abstract, not a peer-reviewed journal article. Without full access to the data or understanding how many other hypotheses were tested from this large dataset (which has already generated over 2,300 publications), we risk falling into the trap of correlation being mistaken for causation.To further evaluate the credibility of this association, Dr. Bobby introduces the Bradford Hill criteria—nine principles to assess causality in observational studies. While the biological plausibility is strong and the effect size notable, the study fails on criteria like replication, dose-response, and publication rigor (Bradford Hill Overview).In closing, Dr. Bobby affirms the benefits of flossing—not necessarily for stroke prevention, but for better oral health, which is valuable in its own right. He shares his personal oral care routine, including flossing nightly and using a water jet, while reminding listeners to stay evidence-informed in their health decisions.Takeaways Flossing likely improves oral health, but its role in stroke prevention remains unproven. Be cautious with headlines drawn from unpublished conference abstracts—they're a starting point for inquiry, not a reason to change behavior just yet."How to Live Long and Well" at DrBobbyLiveLongAndWell.com.

Avsnitt 444 handlar om Jacobs topp 7 saker de flesta bör fokusera på för en bättre hälsa. Efter att ha funderat kring en fråga från en följare i några timmar så kom Jacob fram till en lista för de saker som han tror är viktiga för en god hälsa. Han har dessutom funderat kring hur stor betydelse han tror att de har i förhållande till varandra och hur stark evidensen verkligen är för de olika sakerna. På Tyngre Träningssnacks instagram kan du hitta bilder relaterat till detta och tidigare avsnitt. Hålltider (00:00:00) Intro - värme när man inte alls är värmeanpassad (00:02:37) Wille har börjat läsa böcker den senaste tiden (00:08:42) Det vi tror är viktigast för god hälsa - och hur säkra vi känner oss på det (00:13:29) Listan gäller saker som berör befolkningen - för vissa individer kan andra saker spela större roll (00:15:20) Plats 1 - Sämst för hälsan är Rökning (00:17:38) Bradford Hill kriterinerna för kausalitet via observationsstudier (00:29:38) Plats 2 - Bär inte runt på för mycket fettmassa (00:43:24) Plats 3 - Alkohol har tappat en plats jämfört med för några decennier sedan (00:50:54) Plats 4 - Regelbunden träning och motion (00:57:43) Plats 5 - Tillräcklig och fullgod sömn (01:03:55) Plats 6 - Bättre mat påverkar hälsan för sig själv utöver effekter på vikten (01:09:36) Plats 7 - Gemenskap och ett känsla av ett socialt sammanhang (01:13:30) Stress får vara med som en bubblare (01:16:38) Saker som inte är med på listan

A Rebelião Saudável nasceu da união de diversos profissionais de saúde que pensam diferente e cujo foco é promover saúde e bem estar, com comida de verdade e sem medicamentos. Semanalmente a Rebelião se reune no app Telegram para discussão de tópicos importantes relacionados a Nutrição Humana e Qualidade de vida. Nessa semana, a Rebelião discutiu sobre Os Critérios de Bradford Hill Fonte: HILL AB. THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION? Proc R Soc Med. 1965 May;58(5):295-300. PMID: 14283879; PMCID: PMC1898525. Você também pode participar da discussão e da Rebelião. Toda Segunda feira, às 7:00, estaremos ao vivo no Telegram, basta acessar o nosso canal: https://t.me/RebeliaoSaudavel. Se você gosta de nosso trabalho, deixe um review 5 estrelas e faça um comentário no seu app de podcast. Essa atitude é muito importante para a Rebelião saudável e vai ajudar nosso movimento a chegar a cada vez mais pessoas. Você também pode nos acompanhar no instagram, http://www.instagram.com/henriqueautran. E em nosso canal do YouTube: https://youtube.com/c/henriqueautran.

The guys open the show discussing the early slate for Week 2 of College Football. Lifshatz addresses the comments from Bradford Hill and the Mass State Gaming Board. 2 PP's

Travelogue Series: I start a multi-episode travelogue exposition in 2022, by visiting North Carolina and the Yadkin Valley. In this multi-part series on North Carolina, we’ll explore the Yadkin Valley, meet with producers, and feature several interviews for the YouTube portion of the show with those producers. We will feature Finger Lakes producers in between, and ultimately also explore The Hill Country in Texas, and the wine-growing regions of Idaho. Please excuse errors in the text, this was dictated and gently edited.North CarolinaWhen I moved to the Finger Lakes a decade ago, I was hungry to find as much information as possible about the region. I wanted to find books magazine articles, podcasts, and nearly anything that would shed light on the history of the region that I was moving to. At that time, there really weren’t very many publications. At the very least, I couldn’t seem to find a short history of how the finger Lakes and become one of the most discussed emerging regions in the United States. There was of course the wonderful book, Summer in a Glass, by Evan Dawson, in which he follows a number of different winemakers through the growing season 2009 in the Finger Lakes. In the absence of such a book, I set out to write one of my own, with much more of an eye towards content marketing for our new winery, and dug into all of the old journals, periodicals, and textbooks on American wine I could find. I published A Sense of Place in 2014, and have been able to use it as a great tool to help educate customers and even tasting room associates. I wasn’t able to find anything quite like that on North Carolina, and realized a lot of the lessons I would learn would have to be done on the ground.The Yadkin Valley is vast, covering more than 1,300,000 acres. With such a large span of land, I knew that there was going to have to be variation in the topography, and even the climate to a certain extent, within the AVA. I was a bit surprised flying from my layover in Atlanta into Greensboro, to see a dusting of snow covering the ground. For the cold climate winemaker, I just assumed that North Carolina would be significantly warmer than the finger Lakes I had left behind. I was surprised at the temperature spread on the ground that morning was only about 10°, with a balmy 31°F when I landed. Setting out from the airport, and passing through Winston Salem, more than anything else I just wanted to get a feel for the lay of the land. Whenever I arrive in a new place, in order to get my bearings in a sense for what the place looks and feels like, I’d like to just go for a drive. It gives me a better understanding of where the towns are that get referenced in conversation, what some of the local historical landmarks are, and even where the politics of a place takes place. Knowing that I was in the Yadkin Valley, and heading west from Winston Salem towards Yadkin County, and the Yadkin River, I figured why not plug Yadkinville into my GPS.I had broken up my trip into visiting the southern portion of the EVA for the first day and a half, and the northern portion of the AVA on the second and third days. Highway 218 seems to cut the AVA in half so it was a good working point to begin to discover some of the different wineries I had a particular interest in tasty.To choose just a few wineries in an emerging wine region is an extraordinarily difficult job. In a sense it’s kind of a gamble, you rely on reputation, customer reviews, and references from people who are much more expertise in the region and then yourself, but so much of wine still comes down to personal taste, and aesthetics. What I had decided I wanted to do, in pursuing a slightly deeper understanding of the AVA, was to look at oneThat was an anchor in terms of the history of the region, to look at a winery that was relatively new, but small and focused on extraordinary quality, and to look at one of the biggest producers in the AVA with an extraordinary offering of a variety of different ones. I figured I would have a chance to taste several other wineries along the way and include them in this report.Because in so many ways this was a last minute trip many of the people I reached out to likely hadn’t even opened their inbox by the time I was heading out of town. It was the period just after New Year’s, and often times it’s pretty slow start in the new year in the wine industry. I had however, gotten replies from Shelton, that winery that I referenced as a pioneer in the AVA, and really one of the reasons why there is a Yadkin Valley a View today. I had received word back from Childress, the the winery name and founded by Richard Childress, of NASCAR fame. North Carolina is NASCAR country, and Richard Childress has built one of the largest brands, in fact one of the few I had heard of before traveling to North Carolina, while making wine in New York. I also received word from Diana Jones, of Jones Von Drehle, one of the wineries at the northern end of the AVA, and one that had come extremely highly recommended.  Some of the wineries on my shortlist included Ray Lyn, Raffaldino, Shadow Springs, and a handful of others. I guess from the perspective of somebody who is trying to discover a new wine region, one of my only frustrations was not having more direct links to members of winery staff where I could email or contact them directly. I realize this is a problem on my own website, and after experiencing this, something I’ll be change. Sometimes the ease of having an inbox that serves as a catch-all becomes a crutch for us small business owners, but as someone who is seeking some very specific answers to some very specific questions, it can make sense to ensure that those individuals with deeper questions can reach winemakers directly.In any event, I arrived in Yadkinville, crossing the Yadkin River, and decided to head to town where I could pick up some bottled water and a couple snacks and see what the town offered. Yadkinville is a small town, there doesn’t seem to be much of a culinary scene, and it really is just the county seat. It’s where you go to get permits, and like we have your county planning board meetings. There wasn’t much by way of a presence of wine in the town, but I did notice when I stopped in to the local grocery store, Food Lion, and realized this was a state that sells wine in grocery stores, and they had a small selection of some of the local producers, with Childress being one of them. The wines on offer were very basic, emphasizing the muscadine production of sweet wines from local producers, but there were a few dry reds and whites included on the shelf. Since Yadkinville marked in the center of the AVA, and it was getting to be towards the middle of the afternoon, I figured I would enter wineries into my GPS to see if any were open, and get back on the road. Leaving the main highway I drove beautiful winding roads and very gentle hills in what was largely agricultural countryside. I drove by a winery called Bradford Hills, which was a very small tasting room and an out-building, a small but well manicured vineyard, and it look like a fantastic place to visit on a beautiful summer day. It didn’t look like it would be open until after my flight was departing on Friday, and I quickly realized that I likely would not have a chance to taste many of the wineries that I hadn’t made contact with, during the middle of the week. This meant that a lot of the small producers, wineries about my own winery’s size and smaller, would have to wait for another trip.After taking some pictures I set back out onto the road, looking at my GPS and seeing what wineries I would be passing on my way to Lexington, where Childress is located and where my hotel room was booked. I noticed that RayLyn could be reached with a small detour. From my research it was a winery that I really wanted to taste at, and I noticed they were open, so I made my way. Even though it is winter, there’s still more sun and warmth then we get in the finger Lakes. The grass was still green, though the trees were bare, and the bare trees opened up the countryside even more so that you could see the hills and buildings, that were off in the distance. Making my way from Bradford Hill winery, the landscape became less dramatic, slightly flatter, but retaining the same intrinsic quality. Passing fields that had recently been ploughed, the deep tones of brick and garnet that marked the clay that is found all throughout this region, was everywhere. My GPS led me to RaeLyn Vineyards, and upon entering I was impressed. The site was easily accessible from many of the main highways, and from that perspective, it seems to be ideally situated to attract a steady flow of customers. One of the things I’ve learned as a producer, especially one in an emerging region, is how important it is to be able to attract customers in as convenient of a location as possible. When so much of your business depends on people knocking on that cellar door, you want that door to be easily accessible. RayLyn was marked with a beautiful gate as an entrance, and a a gentle drive through the vineyards towards the tasting room in winery. I passed a small new planting of strawberries and several young rows of blueberries. I particularly like when wine wineries are able to integrate other forms of agriculture into their farms. Whether they are used for any sort of wine production, I think it encapsulates this idea of our responsibility to the soil and to the earth. It also reminds us of the other forms of agriculture that we can be excited about. I’ve begun integrating more produce at our winery, planting cucumbers and tomatoes, peppers and squash, and hope to grow this out in the future.Approaching the parking lot at Ray Lynn, there’s a very nice outdoor tent that they seem to be able to use for banquets or weddings, and likely overflow for the tasting room if the weather is inclement. At this point in the afternoon the temperature had risen to about 41°, but with that southern sun shining bright, the fresh air combined with the warmth felt wonderful on my skin. And it wasn’t just me, there were a couple folks sitting out enjoying the day on some picnic tables outside the tasting room with a glass of wine. They were polite and smiled and gave me a small raise of the glass as I walked by. I entered the tasting room was read it immediately. People in North Carolina are friendly. I spoke with the tasting room staff, explained I was a winemaker and operated podcast, and had wanted to feature RayLyn on the shelf. This was one of the emails that had gotten lost in my expedited travel plan, and so without an appointment I took a gamble. It was a great choice. The tasting room staff was excited, informed me that her husband was from Watkins Glen, and eagerly brought up the names of some of my favorite producers in the Finger Lakes, folks that they have close personal relationships with. Being from Watkins Glen, of course the Stamp family at Lakewood, received some of the highest praise. She offered to taste me through the portfolio and I happily agreed, this would be my first taste of North Carolina wine In North Carolina.This winery offers a full suite of different wines, emphasizing dry veneer for a red and white wines, they also offer a beautiful Charmat style rosé, of course some of the sweet wines that have built this region made from the Muscadine grapes, and canned wine as well. We worked our way through the Chardonnay, Sauvignon Blanc, and the dry rosé. Review my notes to include some of the specifics about each wine here. Fortunately, the tasting room also had available detailed notes on the chemistry of the wines, the harvest date, and the components that were in most of the blinds. It’s interesting in the finger Lakes, our growing season doesn’t really kick off until May, and that means that most varietals won’t begin harvest until September. Of course there are some hybrid grapes that are harvested much sooner, but those don’t tend to be any of the bridals that I work with. With harvest starting in September, there have been vintages where we are harvesting all the way through early November, and that doesn’t include wines that we are making as light harvest wines, where we can be harvesting all the way to Thanksgiving, or ice wines which may be picked in January or February of the next year. It seems to me, that much of harvest will begin in August here in North Carolina and be ramping up by the end of September. It also struck me that that works very well for those people who enjoy wine country visits in October, during the fall when the air begins to cool and the excitement of all the dressings of fall are in the air. As a wine maker in the finger Lakes, Columbus Day marks our busiest weekend of the year. It also marks one of those weekends where we are fully in mashed in all of the seller activities, and that means I rarely get a chance to spend time with customers during harvest. It would be great to have the opportunity to spend more time as a wine maker with customers just as harvest is wrapping up and tourism is peeking. Though I love both red and white wines, my desert island wine will generally consist of a white. For me white wines offer a transparency into Vineyard practice and seller practice that edge out reds. Consequently I spend a lot more time thinking about white wine, I spend a whole lot more time making white wine in the finger Lakes, and I find that I drink or white wine. All of the whites offered at RayLyn were wonderful, some with a small component of Muscat Canelli, which added some wonderful aromatics.  Add a little bit of the history from the website of RaeLyn here. While tasting Rachel, one of the owners and daughter of the founder, and the ray of RaeLyn stop by to say hi. She made sure that I was enjoying my tasting, and trying to help me make contact with Steve, their winemaker. He had been in Asheville that day and wouldn’t be arriving until later in the week. She gave me his email address and I hope to have him on in the future in a long distance long-form interview. From everything I’ve heard, he’s one of these towering pioneering figures in the Yadkin Valley and someone who is clearly taking their wines to great heights. The Reds were equally as compelling as the whites, and in someways perhaps even more so. You can get the sense when you’re at a winery, what is the family who makes these wines prefer to drink, and I did get that sense here. One of the bottlings, had what I assumed with some modern art on it, but upon looking closer and receiving the explanation understood That it was actually the Doppler radar of a hurricane. Yes one of my questions has been immediately answered, hurricanes can be a factor here in the Yadkin Valley, though they are nowhere near the factor that people who live closer to the coast have to deal with.  Discuss this wine.After a really wonderful visit at RaeLyn, I ordered a case of wine, had it shipped back to our winery in New York, and set off for Lexington. Again with no familiarity of any of these towns or cities, I chose Lexington because it is the closest town to Childress vineyards. Lexington is nestled in the far south eastern portion of the AVA and most of the city isn’t included in the AVA itself. The town itself is it fairly nice downtown area, and it does feel like there is a small foodie movement emerging, with some local cafés and a Piedmont cheese shop. But in many ways it remains in agricultural and industrial, southern town that I can picture with time and investment has the potential to grow itself into a hub of Wine and food centrality.Just outside the fenced in property for Childress Vineyards was the Holiday Inn and adjoining plaza.  There weren’t really any shops in the small but nice strip mall that is next to the Holiday Inn, but it is all designed in a very similar fashion to Childress itself. The hotel has one side that looks out at the vineyards which I imagine would be a wonderful way to wake up. I was booked on the highway facing side, but the room is quiet and clean and a nice place to eat my takeout Mexican dinner for the night.So much of my philosophy is based on the specifics and the importance of place, and tied up with that philosophy is the notion that small is often better. Most of the time, most of the restaurant and dining options I observed, or chains that work cute in to specializing in any notion of local cuisine. Out here it wasn’t even real common to find a lot of barbecue joints, which I half expected to see almost everywhere. Again maybe I wasn’t looking in the right places, but I do have the sense that restaurant and food entrepreneurs will likely have a huge market to tap into if that’s the direction they would like to go in partnering with this growing wine country.My appointment with Mark Friszolowski was at nine the next morning, and so after getting a good nights sleep and waking up fairly early, I headed over to Childress Vineyards. I was said to meet him in the lobby and as a military man, who retired as a colonel and between his active and reserve duty spent 37 years in the army, I knew that on time was to be 10 minutes early. Driving into Childress which was literally just around the corner from the parking lot of the hotel in through the gates, you pass through a wonderfully manicured vineyard.  The varietals are all identified by signs with the trademark Richard Childress logo, and varietals like Maulbeck and Cabernet Sauvignon and Merlot, and multiple Ciano I’ll stand out. There were signs marking planned plantings of Chardonnay and Pinot noir, which I’m particularly interested to see how they do with the North Carolina heat. The tasting room and winery set a top of hill which can be seen from almost any point of the drive into the wineries grounds. It is a beautiful Modern take with an Italian 18. It is the sort of Tuscany inspired building but you’ll find Americans like to build. It sets the tone for the romantic visions that we have of European, and especially Italian, winemaking culture. I know that there are some people who don’t like this form of architecture, they don’t like the sense that it calls out and emotive response that she would find somewhere else in the world but with modern building materials and aesthetics. I’ll be honest, I liked it. I think that they put a lot of effort into creating a beautiful building and grounds with a nice setting that makes you feel like that The winery you’re entering is making some special wines, they put in a lot of effort to set a tone and that tone carries through from the heat and painted murals on the wall of scenes of grape harvest, to the indoor fountain, to the seated tasting room with string lights and doors. This is not the Olive Garden experience, this is something much nicer and with such warm staff, more personal too. The entire tasting room experience was wonderful, The seller tour, The tour of the grounds in the bonded warehouse, explanations on infrastructure projects, a peek inside the restaurant and banquet facility, were all greatly appreciated. Mark was a wonderful host, who poured some great wines. We focused on their vinifera wines,tasting Sauvignon Blanc and Chardonnay, as well as Montepulciano, and some red blends. Mark’s personal history, from his time helping out at Dry Creek Vineyards in California, managing operations at Pindar on Long Island, and ultimately moving to North Carolina to help found Childress. Mark is one of the first winemakers in the country to collaborate on creating the Meritage Alliance, and therefore creating Bordeaux based blends.  The specific vintage of Meritage we tried, the 2015, is a well aged current release. It carried many of the things I love about older Bordeaux, the hints of cedar, the forest floor. It was it both times bolder than what you’ll find in many offerings in the Finger Lakes, but leaner than what you would find in California. And struck a nice middle ground, and was a sort of sweet spot of bold but not overly dramatic red blends that I personally like, and that I think complement food quite well. I’ll be spending an entire feature in an episode with Mark on Childress, so for now we’re going to continue with our travelogue and look at the rest of us the experience here in the Yadkin Valley._____ In crafting the short travel log, I wanted to make sure that it wasn’t strictly about wine. Most of the time when we travel, there are other things on our quotation mark to do quotation mark list. There are a couple of really interesting tourist activities here in the Yadkin Valley, but deal both with history, pop-culture, and the wonderful natural surroundings. Mark was so generous with his time, but I found myself leaving the winery later than I had expected. I certainly wasn’t disappointed and I had made sure to leave a good window of time to spend at this landmark property. I figured I would spend the rest of the afternoon exploring some of those other offerings, and found my way to highway, and I headed up for the town of Mount Airy.Mount Airy sits on the North Carolina Virginia border. It is like so many other hill and mountain towns in America, a quintessential snapshot of life in both modern and past American societies. Mountains and hills can I think we people to be a bit more hearty sometimes a bit tougher but always genuinely very nice. The town itself is built around its historic Main Street. And coming in to Mount airy do you understand what that history is all about.  The name of the highway even changes and becomes the Andy Griffith Parkway, and that of course is named after the famous television show an actor that for seven seasons captured the aspirational qualities of American small-town life. With its classic whistling introduction, it’s sensitive skipping Stones and safety and security, of good old fashion morals and values and being raised in small-town life, Mount Airy was the inspiration for the Andy Griffith show fictional town of Mayberry. Mayberry is the corner stone upon which so much of the towns character now rests. You see signs for Aunt Bee’s café, you see the Mayberry antique shops, the Mayberry museum, ice cream shops meant to look like they were preserved from the 1930s, and a sense of pride that their town was once the basis for this dreamscape of Americana. Some of that dreamscape feels a little rough around the edges now, who knows if it was then if that’s what it’s always been, or if the changing times or loss of industrial base, of structural changes to our economy, and even the opioid epidemic that we face in this country, have added a touch of tarnish to the shine. In all, it’s a great place to be, a wonderful old historic town and I’m happy I made a detour.As you leave Mount Airy and head south on the highway back towards a more central location of the AVA you pass a geological wonder, an outcropping called Pine Mountain. It dominates the skyline and can be seen from many many miles away when you’re on top of hills. Driving past it, and without enough time to drive to the park and visit the mountain personally, I realize that this will be on the top of my list when I have a chance to return with my family and my children. I used to love walks through areas like this when I was a child and I can’t wait for Andrew And Audrey to have that experience with me. I found out, it isn’t the only fascinating geological wonder to explore, as there’s also Stone Mountain, which figured prominently in my second visit on my third day on the ground in the Yadkin Valley.For that evening I had made reservations in a small town called Elkin, or rather just outside of it, in the adjoining town of Jonesville. Jonesville is the classic sort of truckstop town, that offers some heavy industry, but largely consists of some gas stations, hotels, a Cracker Barrel, fast food restaurants, and a grocery store that serves the locals. It did have a Mexican restaurant, this one called Margaritas, which I took advantage of both nights of my stay in the Hampton Inn.Arriving at the hotel, it was a little older, but the staff was exceptionally accommodative, the room was perfectly clean, and the setting itself was quiet. When you were on the road there are very few other things that you actually need. Warm cookies were waiting for us as we checked in, and I unloaded my bags and all of our equipment in my room before I set out for the town to see what was available. Before I set my sights on dinner, I wanted to see Elkin itself. For my own personal aesthetic tastes, this portion of the AVA felt like it matched my desires more closely than the south eastern portion of the AVA. Elkin was quaint but beautiful. As the sun was coming down, the Yadkin River roared not too far away, the train tracks cross run adjacent to the main street, and the town itself seems well put together. Large murals adorn some of the older brick buildings, many featuring grapevines, and the town features a wonderfully restored old theater. Elkin felt nicer than Mount Airy in someways, not to denigrate Mount Airy at all, but it struck me that Elkin is the sort of town that could deal with in Oakville grocers type of concept, some interesting fine dining that features many of the local wineries strongest efforts, and some other cultural activities. Again it’s the off-season and perhaps there is that sort of activity that is going on that I’m simply not aware of, but I feel like the future for Elkin is bright. There aren’t a lot of accommodations right around downtown, but with all of the hotel options in Jonesville, Elkin will be able to maximize the heads in beds that is so important for wine country tourism. Interestingly Elkin and Jonesville, where you reach Jonesville by crossing the Yadkin River, are in different counties. I’m not sure if any of the development has anything to do with that, but in my own experience, especially when you’re dealing with the county and town level, so many of the decisions on what can happen and how well a town or region grows, are based on the local politics and the bureaucratic decisions that are made. I’d have to be there for a lot longer to know if any of this is in play.I picked up some carnitas and pollo asado street tacos, and headed back to my room for another great night sleep. The next morning I had appointments with two different wineries, Shelton Vineyards, and Johns Von Drehle.I woke up early the next morning, spent some time on my computer making sure that I had transferred all of my photos and videos, refreshing some of my notes from my previous day’s visit, and set out for Shelton Vineyards. Any of my initial skepticism‘s on the beauty of the countryside, how this wine region will grow and what its potential is, we’re set aside as I visited Shelton. Shelton is located in the town of Dobson.The exit from the highway for Shelton Vineyards also leads you to Surrey Community College. Surrey Community College was constantly a subject of discussion with most of the people in the wine industry that I met. It is a community college with a vineyard and enology program, and one that was largely initiated and funded by the Shelton Brothers the founders a Shelton Vineyards.  Similar to my emphasis in the finger Lakes on the finger Lakes community college Viticulture program, the Surrey community College program helps to introduce and train up the next generation of viticulture lists knickers. The college itself has a program and a 10 acre Vineyard where students can learn. Against that backdrop of both philanthropy and history, I was excited to have the chance to meet with Ethan Brown, winemaker in Shelton in Vineyards. Ethan had been there for four years, and in a way that completes the circle of the importance of programs like the one at Surrey community college, he attended the program many years ago. Ethan was a young organized dynamic guy, and he wasted no time in showing me around the winery tasting room, and providing a little bit of context for the history of the place. Currently the largest vinifera vineyard in the state of North Carolina, Shelton farms 80 acres of grapes with plans to plant a lot more. Exceptionally manicured, with beautiful old fashion light posts lining the long driveway from the highway to the winery, Shelton truly transports you to a different world. The gentle rolling hills adorn with a backdrop of the mountains, which on clear warm days, I can imagine, inspires you to find your own piece of beautiful grass, and enjoy a glass and some cheese with someone you laugh. For those wine club members who want the best of views, you can climb up to the gazebo that rests surrounding vineyards and truly has the best features of the entire valley.Built in 1999, Shelton Vineyards really isn’t showing it’s age that much. It speaks to the efforts of the staff to ensure maintenance is done regularly and things are taken care of. The cellar itself is built into a hillside which means most of it is underground. The barrel rooms are probably 20 feet high but at least 2/3 of that being underground meaning temperature control from both cold and heat is a lot easier and done with much less energy.  Producing around 25,000 cases a year, this is a Winery that has seen the baton passed from the founding Shelton brothers to the next generation. With that transition is an intention to grow their programs and initiate new ones. With the recent purchase of a break tank and a small hand bottling counter pressure system the winery seeking to do more charmat style sparklings. Ethan also talked about expanding cock and re-instituting their traditional methods Sparkling Wine program. I tasted a Sauvignon Blanc, a dry rosé based on Merlot, Petit Verdot, and a Petit Verdot/Cabernet Sauvignon blend.. All of the wines were exceptionally crafted, showing what I had begun to discern as something that speaks to the North Carolina fine wines that I tried. The whites and the reds are both fuller bodied than what we find in the Finger Lakes, they have generous acid ,but lower than what we have in truly cool climate winemaking; and the reds weren’t overly extracted. They spoke of great fruit, they were well balanced, and their alcohols were generally about 13%. I also tasted a great Tannat. My wife and I have visited Madiran in southern France, I’ve had a lot of experience with the French version of the varietal. We visited a number of producers large and small in Madiran, and I love those wines, there just aren’t that many American Tannat’s that I have fallen in love with. Of course the wines of Jenny McCloud of Chrysalis have been wonderful, and I’ve been lucky enough to cellar those for many years. This North Carolina Tannat, my first experience with a varietal in the terroir, makes sense for the region. There are some very strong Virginia Tannats that are growing, and with this particular vineyard in North Carolina, I renewed my love of the varietal. As with Childress, and the winery I’ll be talking about next, Jones Von Drehle, Shelton will have its own feature in the podcast, as I sat down with Ethan Brown to discuss his own experience, Shelton Vineyards, and where the region and the winery is going. As Ethan and I wrapped up, and he was generous enough to spend several hours and taste a lot of wines with me, I headed off for my last visit of the day to Jones Von Drehle. The roads grew less crowded, the bends and winds and hills became more dramatic, and I started to wonder where in the heck was this place. I arrived early, about an hour or so, and took advantage of the opportunity to do just a little bit of driving and perhaps find something to eat. I typed in food nearby and the nearest place was the Stone Mountain General store. It wasn’t too far from the Stone Mountain State Park entrance, and so I figured I’d head over there and see what was available. The general store itself feels plucked from time. An old rustic wooden building, but offers inside a few knickknacks, necessities for campers such as para chord, fire starters, and offers a few small food items for the weary traveler camper. Simple offerings like a hamburger or cheeseburger, or a housemaid turkey or ham sandwich were available. The turkey sandwich tasted like home, although it was on white bread. Turkey, American cheese, lettuce, tomato: all for $2.95. It wasn’t the most glamorous meal I’ve ever had in wine country, but it filled me up, tasted just fine, and was certainly marked as my cheapest option I’ve ever had on the road. I took advantage and drove around the park a bit, didn’t have a chance to see Stone Mountain itself but just like Pine Mountain, this will be on my itinerary for the next visit, one I hope to take with the family.Heading back down the hill I arrived at my appointment just on time at Jones Von Drehle, and boy was I impressed. The Vineyard itself has two entrances, a service entrance and a guest entrance. I can tell it was an extremely quiet day but I wanted to have the standard customer experience, and so I entered the other guest entrance. Driving down the crusher run you are snaked through the vineyards, pass the retention ponds, as the tasting room and winery, and brand new amphitheater open up before you. It is an impressive and beautiful experience. The slope of the hills hug you to your right as you wind your way around the vineyards on one side nature on the other and approach your final destination. The hills jumped in different directions the vines bear open up the view to see row after row in this well-kept vineyard. The amphitheater itself is gorgeous. Recently finished it’s part of the philosophy of the owners to incorporate wine music in food into living a good life. The tasting room is not extraordinarily elaborate in it’s design, but it’s well thought out and well appointed inside. The most impressive feature, is the immersive feeling you get when you walk in turn to your right and look out the windows in the back of what is the tasting room. The slopes feel even more dramatic here from the vineyards, and with the trees bare of their foliage you can peer through the trunks to see the steep incline of the Granache and the Malbec and other varietals.  Well lit, and open, without any sense of clutter, the tasting room invite you to a horse shoe shaped bar in the middle were the tasting room attendant who was very nice and gracious, and the new to the wine industry expressed an amazing thirst for knowledge, that is extremely inviting. Diana Jones was waiting for me, and informed me that her husband Chuck was on his way back from Charlotte where they had been delivering some wine. This 6000 case winery is centered around 30 acres of a estate vineyard. They do not have a distributor, and unfortunately don’t ship to New York state right now, but when they get that license, I can assure you I’ll be ordering more wines. Everything was wonderful and unique. From their Grenache rosé, to their Chardonnay - both stainless steel and barrel fermented, to the real interesting Petit Manseng, which carries a fairly heavy alcohol, but is it so well balanced on the pallet that it is neither distracting nor over the top. It is well balanced and full bodied, and a wine that they described as being extremely popular at restaurants who have received James Beard‘s nominees and nods, as a “buy the glass” pour. Tasting through their Grenache rosé, this dry rosé echoed Provence with its own North Carolina flair. It was a wonderful wine and one I decided I had to take one home. Their red offerings were equally as compelling. Cabernet Franc, Merlot, Petit Verdot and Cabernet Sauvignon blend - all were well-crafted, clearly brilliantly grown, and offered everything I could hope for. Their winemaker, cut his teeth in California, spending decades in the industry until he finally decided he wanted to have a small farm himself and, with land prices in California being what they are, realized the East Coast offered his best opportunity to become a farmer himself. He took over the reins at Château Morissette in Virginia, and this large production oriented winery did well for him for sometime. As he sought to become more ingrained in a small production oriented facility, he had heard about the efforts of these two crazy couples from Atlanta Georgia with original roots in North Carolina, that had planted an estate vineyard in the middle of the hills just south of Stone Mountain. It’s been a match made in heaven and with Dan’s experience, and the attention to detail in Vineyard, the wines are truly top-notch. The way the Vineyard is set up, many of the worst things that you deal with in the Yadkin Valley AVA, are ameliorated naturally. Water naturally runs down the clay hill slopes, with the help of some drain tile. The intense humidity and moisture that you deal with in North Carolina, is marginalized by the fact that the steep hills along with the fact that the mountains are in the distance, create an almost constant airflow which helps to dry the canopy and the fruit during crucial periods of the year. Additional measures such as the first cordon being 42 inches high instead of 36 inches from the ground help reduce ground moisture from impacting the fruit. The whole property is fenced to keep our critters. The wind also helps to protect the vines from early-season frosts, which often compromise buds, particularly the primary buds where the majority of the fruit is located, and get them through very treacherous periods where the temperatures will impact that year‘s harvest. And overall just the amount of effort that the team here puts into their vineyards, the philosophy that fine wine comes from extraordinary vineyards rings true. We go even deeper into Jones Von Drehle in our long-form interview, which is slightly shorter than the long form interviews I do from the studio, but nonetheless will give you a much deeper picture of this winery it’s history and it’s increasingly prominent role in the North Carolina wine industry.Returning to Elkin for the evening, I had wished I brought an extra bottle to enjoy that evening. Instead I did what we winemakers often do and grabbed some local beers, picked up another to go order of Mexican food from Margaritas, and spent some time recapping the visits with my wife, enjoying the shrimp chipotle that I filled into some fresh corn tortillas, and then headed to bed. The next morning I would be leaving the Yadkin Valley, and any initial apprehension that I had as to where this wine region was, was disappearing. When it came to food, Diana Jones had mentioned that Asheville and Raleigh were truly astounding foodie towns. With that as a basis, it won’t take long for some enterprising young chef or cook who wants to do their own project, to find their way to one of the small towns and make it work during the busy tourist seasons.Yet again, I woke up early worked on my computer for a bit, and double checked my itinerary checking in to my Delta flight. I realized at this pace, I may not have time to taste at any other wineries, but I could at least take a peek at the landscapes in the settings that the region had to offer. I took a drive out to a winery that I had really wanted to visit, but in this trip just couldn’t make it work.  Raffaldini is widely regarded as not just an important landmark in North Carolina wines, but a house that is making some truly stellar North Carolina wines.  From all my research, it is the sort of aspirational wine story that is bred in a man who worked hard and made a great deal of money in another field. Using those resources, he has poured them in to building a truly astounding estate. You can look at pictures on the Internet, you can watch videos on YouTube, but with some properties you don’t understand just how special they are until you actually visit them. And so setting Raffaldini in my iPhone map, I headed in the direction of the winery.  Driving down the highway, North Carolina has done such an excellent job in featuring the different wineries throughout the state with these large highway adjacent signs, that I quickly realized this was a pocket of the AVA I should’ve explored right away. Instead of one or two wineries indicated there were multiple. And not only were there multiple, they were all wineries that in my research into the region, come vaguely familiar with. Wineries like Laurel Gray, Shadow Springs, Raffaldini Vineyards, Piccione, and several others. That last winery was one that I heard mentioned multiple times when I was tasting in different tasting rooms and talking with local proprietors of every sort.  If there is a small pocket of fine wines, with multiple wineries working towards the same goal, emerging in North Carolina, this may be the place. There are of course a lot of people doing a lot of great work throughout the entire region. But one thing I have understood in my research of, particularly American wine, is that like the person who wants to start a gas station, the very best place you can locate a new gas station is across the street from an existing gas station. The logic may seem counterintuitive, but if people start to think of that intersection as a place to get gas, then that is where they will get gas. Likewise in wine, tourists often don’t take the extraordinary measures of researching soil types, property histories, winemakers, and all of the other factors that lead to a specific winery making great wines. They look for the clusters where numerous proprietors are working on their own, sometimes in concert with their community, to pull the best fruit from their land and produce the best wines from their grapes. If there is an early nucleus that we can expect the North Carolina wine country in the Yadkin Valley to flourish from, my sense was, this might be it. With that said, I did not have an opportunity to taste any of these wines.For those listening who are interested in exploring North Carolina wines, I would certainly say that visiting any of the wineries I have mentioned is a prerequisite. But I think that in my next visit, I will certainly start in this particular part of the AVA. I will likely visit Raffaldini, Piccione ,and many of the other surrounding wineries. I would not miss out on visiting either Shelton or on Jones Von Drehle Vineyards Winery or Childress. But I think that this particular corner of the AVA is fostering a sort of spirit that seems to be building upon itself. There are no restaurants nearby, there are no hotels within a 1 mile drive most of these places. For the entrepreneurs listening, I would expect that to change, because this seems to be where some of the energy for the AVA seems to be admitting from.I guess as a closing retrospective, there is an immense amount of differentiation within the Yadkin Valley AVA. From topography, to culture, to wine styles produced by the different wineries. When I landed, and first began to explore the very core of this viticultural area, I will admit to feeling a little underwhelmed. That feeling began to dissipate upon visiting RayLyn, and after tasting at Childress I was excited. The entire focal point of the trip changed as a ventured outside of the south east quadrant and moved into areas that, admittedly, felt a little bit more familiar. Call it a personal bias, call it a personal preference. My conclusion is this… The Yadkin Valley AVA is vast, it includes so many different specific tear wars, that it’s difficult to call it one region. From the wind and hills at Jones Von Drehle, to the gentle slope‘s just south west of the northern reaches of the AVA, to the flatter more populated areas in the south east corner of the viticultural area.  What I can say is this, each producer I visited produced all level of quality that far surpassed any of my expectations. Too many regions I visit , Or rather have visited in my life, think of themselves as Napa in the 1970s. This is not Napa in the 1970s, because this is not America in the 1970s. This is North Carolina in 2022, and it is full of surprises, and beauty, and wines that will surprise at every turn. Is this a region worth visiting question?  If you are an American who loves wine, this is a region you must visit. You will fall in love with many of these wines. I don’t know what your personal preferences, I don’t know if you like red or white, or lean or bold, or salty whites or tannic reds, but you will love it. You will find wines you love and you will want to taste these wines the rest of your life. In vino Veritas, and in North Carolina, there is indeed, great wine.________Visit our website at www.VitiCulturePodcast.com, and don’t forget to share with your friends via all major social media platforms @VitiCULTUREPodVisit Bellangelo Winery and Missick Cellars at www.Bellangelo.com and www.MissickCellars.com.You can watch the interview on our YouTube channel here: Get full access to The Viti+Culture Podcast Newsletter at viticulturepodcast.substack.com/subscribe

My sources for this podcast are Dr. Peter McCullough and Dr. Joseph Mercola. In this podcast, Dr. McCullough reports on the toxicology reports paper and the Kostoff analysis revealing the dangers associated with the mRNA VAXX shots. He goes on to explain the Bradford Hill criteria for causation and talks about the need for early treatment in Covid-19 cases.  www.freedomfromaddiction.libsyn.com. 

Is Marijuana use associated with psychosis and schizophrenia or does marijuana actually causes schizophrenia? What about Suicide? Dr. Christine Miller has meticulously studied the medical literature and the Bradford Hill criteria. The Bradford Hill criteria is the standard used to prove causation. This methodology was used to prove tobacco smoking causes various health effects. This interview was recorded November, 2020. Christine L. Miller, Ph.D. Christine L. Miller received her B.S. degree in Biology from the Massachusetts Institute of Technology and her Ph.D. in Pharmacology from the Neuroscience Training Program at the University of Colorado Health Sciences Center. Her academic career with the University of Michigan and Johns Hopkins University, was devoted to researching neurobiological mechanisms that underlie psychotic disorders. Now retired from academia, she volunteers her time as a science advisor for Smart Approaches to Marijuana www.learnaboutsam.org and Moms Strong www.momsstrong.org, educating the general public and legislators about the causal link between marijuana use and serious mental health impacts, including psychosis and suicide. Dr. Miller has continued to author scientific papers and reviews, most recently book chapters entitled “The Impacts of Marijuana on Mental Health”, published by Oxford University Press in 2018 and “Marijuana and Suicide: Case-control Studies, Population Data, and Potential Neurochemical Mechanisms”, published by Springer Press in 2020. Dr. Miller reviewed the Bradford-Hill Criteria for epidemiological causation verses association as it related to marijuana and psychosis. A strong association A dose-response relationship Timing of the association Administration of THC in the clinic Drug-seeking behavior risk does not seem to explain the impact Quitting the habit resolves psychosis (in 50%) Plausible biological mechanism You can find more details on the Bradford Hills Criteria on the IASIC website library under Psychosis, the International Academy on the Science and Impact of Cannabis. Dr. Miller's Marijuana Psychosis Facts: 5x risk chronic psychotic disorder for heavy marijuana users 7 x increase risk suicide attempt in Caucasians who begin using in teens Recovery of a psychotic break from marijuana occurs 50% of the time compared to recovery other drugs 70% – 95% recovery Risk of violence in any drug induced psychosis is 9-fold increase compared to those with psychosis has nothing to do with drugs Violence risk is 18-fold from marijuana induced psychosis compared to controls Psychotic individual who are not using drugs and taking medication are very unlikely to commit violence Dr. Miller is honored by the introduction in this podcast, but wishes to make clear her knowledge is based on the meticulous work of renowned epidemiologists, for which she can take no c

Dr. Bradford Hill, molecular biologist at the University of Louisville Diabetes & Obesity Center speaks about 'Cardiac Metabolism in Health & Disease'. This talk was given at the online 'Bench Talk Live' session organized by the Kentucky Academy of Science on January 21, 2021. Use this link to watch the entire session: https://zoom.us/rec/play/FpLQHcw7km7SfUqrDOgNyw2YMRMRdivzu4cJsexDsEx18hBd56YoWoNCxGUWOAzDusnchV62wtACRBMb.des11_zo_B8TLCGI?continueMode=true&_x_zm_rtaid=hhd4lytATzKuGGcU4YzvAA.1627166823352.89357fcec411b535425e4427cf384f13&_x_zm_rhtaid=733. To see the Powerpoint slides for this talk go to https://www.kyscience.org/bench_talk_live.php and scroll down to the January 21st session. Bench Talk is a weekly program that airs on WFMP Louisville FORward Radio 106.5 FM (forwardradio.org) every Monday at 7:30 pm, Tuesday at 11:30 am, and Wednesday at 7:30 am. Visit our Facebook page for links to the articles discussed in this episode: https://www.facebook.com/pg/BenchTalkRadio/posts/?ref=page_internal

In this episode of the Grounded Excellence show, we are joined by special guest & family - Bradford Hill. Bradford is a graduate of North Carolina A&T SU & University of North Carolina at Pembroke. He is a licensed mental health counselor & operates his own company dedicated to that. He is also a Academic Success Coordinator at North Carolina State University. Tune in as we discuss the benefits of strengthening our minds & other great information! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

This conversation brings up a lot for discussion in terms of not just current and retired players of the AFL but society as a whole and how head trauma can be the catalyst of the downward spiral in mental health. Peter and I also discuss how head trauma might affect children as young as 6 years of age, who are playing impact sports that result in head trauma. All of these have wide implications how we look at and treat mental health and often the extension of that, domestic violence. To say this is an important conversation is a gross understatement. In this episode we discuss: · Neurological impairment as a result of brain trauma · The four pillars by which we measure brain impairment · The concussion rule in the AFL · Women playing AFL · Children and brain trauma As a parent and grandparent, and an avid supporter of AFL this conversation has left me questioning if I have truly evaluated the risk versus rewards of contact sport. And as Peter says, are we treating the brain with the respect we should, when we have three weeks off with a hamstring injury and just 12 days for a brain injury? Show Notes: 1.28 – When Peter's career of managing AFL players began 4.38 – Managing negotiations of Nicky Winmar's contract 7.23 – Concussion rules in the AFL 8.17 – The four pillars by which to measure brain trauma – mood, behaviour, cognition and motor skills 9.07 – Neurological impairment 9.43 – Staggering statistics in former AFL players who are showing symptoms of brain trauma, including structural damage 12.01 – Dylan Grimes and does delayed concussion exist 14.44 – Primary testing prior to playing AFL 18.44 – Danny Frawley and Shane Tuck 19.46 – CTE and how it is diagnosed 22.23 – Shaun Smith's record payout and the Bradford Hill causation paradigm 25.00 – Children playing AFL and the research of Vicky Anderson into children's brain trauma 26.40 - Prevention and mitigation strategies 28.06 - Nick Riewoldt's comments in regard to players being able to make their own decision on playing after a concussion 30.09 – Player education on brain trauma 29.45 – Insurance policies not being fit for purpose 32.26 – Women in AFL – the dose rate of brain trauma as a result of concussion is lower in women than in men – Jacinda Barclay 33.30 – Maggie Varcoe 37.40 – How do we make the game of AFL safe? You can find Peter here: https://www.pjaaccountants.com.au You can find Tanya here: www.rawheartandsoul.com www.integritychiropractic.com.au Instagram: rawheartandsoul

On this week's episode of the pod, we discuss the history of epidemiology. We kick things off with a definition of the term and clarify that epidemiology is not specific to infectious disease but rather all diseases, as well as their risk factors. We take a trip down memory lane and revisit the different eras of epidemiology including the sanitary era, the infectious disease era, the risk factor and black box epidemiology era, and what many call the eco-epidemiology era of today. We dig into some epidemiological case studies of yesteryear, including the famous case of John Snow and the Broad Street Cholera outbreak of 1854. We also highlight some other key players in the evolution of epidemiology as a science and the critical roles they played. We also briefly discuss Hill's causal criteria and their use (still today!) in strengthening our confidence in attributing a causal link to an association. We hope you enjoy!

  Aaron Freiwald, Managing Partner of Freiwald Law and host of the weekly podcast, Good Law | Bad Law, is joined by Philosophy Professor Carl Cranor, of the University of California, Riverside, to discuss toxic chemical exposure and the legal challenges in proving when a dangerous chemical or substance causes harm.   In today’s conversation, Aaron and Carl delve deep into the intersection between law and science. The author of numerous books and articles on today’s topic, Carl’s areas of interest include legal and moral philosophy, specifically issues concerning risks, science and the law, the regulation of carcinogens and developmental toxicants, and the use of scientific evidence in legal decisions. Carl and Aaron talk about a variety of things throughout this episode, ranging from tort litigation to the Trump administration. Aaron and Carl explore the differences between regulating pharmaceuticals and pesticides in comparison to toxins as well as what tools we as a society have to establish whether or not something is in fact safe or harmful. Statistical significance, the role of Judges, the EPA, philosophical values and ethics, toxicology and epidemiology, and the notion of “certain science” are all topics Aaron and Carl touch on. Are we in the middle of an assault on science?   A graduate of both UCLA (Ph.D.) and Yale Law School (M.S.L.), Dr. Cranor is a Distinguished Professor of Philosophy and a Faculty Member of the Environmental Toxicology Graduate Program at UC Riverside. Professor Cranor has focused much of his career on the morality, legality, and justice of exposure to toxic molecules that could threaten the public’s health. He has written widely on philosophic issues concerning, risks, science and the law, the use of scientific evidence in legal decisions for regulating carcinogens and developmental toxicants, the idea of acceptable risks, protection of susceptible populations, and how society might approach the regulation of new technologies and toxicants to better protect the public’s health. At the undergraduate level he has taught courses on ethics, political philosophy, law and society, legal philosophy, environmental ethics, justice and utilitarianism, among others. At the graduate level seminars have included, philosophy of the tort law, legal philosophy, and the idea of acceptable risks. He has served on science advisory panels as well as on Institute of Medicine and National Academy of Sciences Committees. Professor Cranor was the National Romanell-Phi Beta Kappa Professor in Philosophy for 2014-2015.   Listen in to learn more!   To learn more about Professor Cranor, and to see a full-list of his publications, please visit his bio page here. To check out Tragic Failures: How and Why We Are Harmed by Toxic Chemicals, please click here. To read Professor Cranor’s co-authored article, “The Use and Misuse of Bradford Hill in U.S. Tort Law,” please click here. To read Professor Cranor’s article, “Milward v. Acuity Specialty Products: Advances in General Causation Testimony in Toxic Tort Litigation,” please click here.   Host: Aaron Freiwald Guest: Carl Cranor   Follow Good Law | Bad Law: YouTube: Good Law | Bad Law Facebook: @GOODLAWBADLAW Instagram: @GoodLawBadLaw Website: https://www.law-podcast.com

In this episode Mary Jacob joins us to discuss the Space Force, her career in journalism, and the ongoing pandemic!   Links:   https://en.wikipedia.org/wiki/Koch%27s_postulates   https://en.wikipedia.org/wiki/Bradford_Hill_criteria https://schoolsucksproject.com/this-is-a-test-part-one-with-darrell-becker-podcast-655/ https://schoolsucksproject.com/this-is-a-test-part-two-with-darrell-becker-podcast-656/ https://en.wikipedia.org/wiki/L._Fletcher_Prouty https://en.wikipedia.org/wiki/National_Security_Act_of_1947 https://en.wikipedia.org/wiki/Copts https://en.wikipedia.org/wiki/Virtuous_circle_and_vicious_circle  

Scottish doctor, writer, speaker, and outspoken cholesterol sceptic Malcolm Kendrick is back on the podcast this week. He continues to challenge the widespread use of statin medications, despite being targeted personally and professionally by those opposing his message. Since we last talked he has authored a new book, A Statin Nation: Damaging Millions in a Brave New Post-health World, elucidating his position against mainstream medicine’s rampant cholesterol-lowering tactics.  On this podcast, Dr. Kendrick describes in detail exactly what he believes drives the process of cardiovascular disease, informed from 35 years of research on the subject.  He explains specifically why cholesterol has been misunderstood, and how medicine got it wrong. We discuss corruption in medical research and the money supporting the status quo, and Dr. Kendrick shares some of the best ways to avoid heart disease (which have little to do with diet!). Here’s the outline of this interview with Malcolm Kendrick: [00:00:07] Our first podcast with Malcolm Kendrick: Why Cholesterol Levels Have No Effect on Cardiovascular Disease (And Things to Think about Instead). [00:00:30] Book: A Statin Nation: Damaging Millions in a Brave New Post-health World, by Dr. Malcolm Kendrick. His previous two books: Doctoring Data and The Cholesterol Con. [00:02:00] Causes vs processes. [00:03:40] History behind his journey and questioning authority. [00:07:30] Articles written by Elspeth Smith. [00:09:00] Karl Rokitansky’s paper discussing an alternative way of looking at CVD: A manual of pathological anatomy, Vol. 4. Day GE, trans. London: Sydenham Society, 1852:261; in print here. [00:09:06] Rudolf Virchow, researcher who pointed to cholesterol in artery walls. [00:10:55] Researcher Nikolai N. Anichkov: fed rabbits a high-cholesterol diet and cholesterol appeared in their arteries (sort of). [00:12:07] Ancel Keys; blaming saturated fat. [00:14:11] France - highest saturated fat consumption, lowest rate of CVD. Georgia - lowest sat fat consumption, highest rate of CVD.  See graph, here. [00:15:16] International Network of Cholesterol Skeptics (THINCS). Study: Ravnskov, Uffe, et al. "Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review." BMJ open 6.6 (2016): e010401. [00:16:50] Pleiotropic effects of statins. [00:17:29] Movie: 12 Angry Men (1957). [00:20:30] Robert Ross - response to injury hypothesis; Study: Ross, Russell, John Glomset, and Laurence Harker. "Response to injury and atherogenesis." The American journal of pathology 86.3 (1977): 675. [00:20:40] TV show: Stranger Things. [00:22:31] Infectious disease hypothesis. [00:22:52] Analogy of rust in the paint of a car; Sickle Cell Disease as an example. [00:27:12] 14-year old boy with Sickle Cell and atherosclerosis; Study: Elsharawy, M. A., and K. M. Moghazy. "Peripheral arterial lesions in patient with sickle cell disease." EJVES Extra 14.2 (2007): 15-18. [00:28:57] Endothelial progenitor cells, produced in the bone marrow, discovered in 1997. [00:29:31] Pig study of endothelial turnover: Caplan, Bernard A., and Colin J. Schwartz. "Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta." Atherosclerosis 17.3 (1973): 401-417. [00:31:48] Vitamin C's role in maintaining collagen and blood vessels. [00:33:08] Lp(a) molecules - patching cracks in the artery walls. [00:33:42] Depriving guinea pigs of vitamin C caused atherosclerosis; Study: Willis, G. C. "The reversibility of atherosclerosis." Canadian Medical Association Journal 77.2 (1957): 106. [00:34:24] Linus Pauling - said CVD was caused by chronic low-level vitamin C deficiency. [00:35:53] What else damages endothelial cells? Many things, including smoking, air pollution, high blood sugar, Kawasaki disease, sepsis/infection. [00:41:19] Glycocalyx; Nitric oxide. [00:43:30] Health benefits of sun exposure. [00:44:26] Biomechanical stress (blood pressure) - atherosclerosis in arteries but not in veins. [00:47:57] Things that interfere with repair: steroids, vascular endothelial growth factor (VEGF) inhibitors. [00:55:00] The effects of stress on the cardiovascular system. [00:57:55] Red blood cells are what brings cholesterol into blood clots. [00:58:59] Cholesterol crystals in atherosclerotic plaques come from red blood cells. Study: Kolodgie, Frank D., et al. "Intraplaque hemorrhage and progression of coronary atheroma." New England Journal of Medicine 349.24 (2003): 2316-2325. [01:00:55] Very low-density lipoproteins (VLDLs) are procoagulant; High-density lipoprotein (HDL) is anticoagulant. [01:03:46] Familial hypercholesterolemia (FH); Factor VIII. [01:08:15] Cholesterol-lowering pharmaceuticals; Repatha. In the clinical trial, the total number of cardiovascular deaths was greater in the Repatha group than the placebo group. Study: Sabatine, Marc S., et al. "Evolocumab and clinical outcomes in patients with cardiovascular disease." New England Journal of Medicine 376.18 (2017): 1713-1722. [01:09:34] David Deamer, biologist and Research Professor of Biomolecular Engineering. [01:10:05] Karl Popper, philosopher. [01:10:28] Bradford Hill’s Criteria for Causation. [01:13:52] Michael Mosley, BBC journalist. [01:16:40] Statin denialism - an internet cult with deadly consequences? [01:19:18] The money behind the statin and low-fat industries. [01:20:06] Margarine; Trans-fatty acids, banned in several countries. [01:24:37] The impact of food; The focus on food to the exclusion of other pillars of health. [01:26:38] Dr. Phil Hammond; CLANGERS [01:28:21] Avoiding internet attacks. [01:32:00] ApoA-1 Milano. Original study: Nissen, Steven E., et al. "Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial." Jama 290.17 (2003): 2292-2300. [01:33:05] The Heart Protection (HPS) Study in the UK: Heart Protection Study Collaborative Group. "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial." The Lancet 360.9326 (2002): 7-22. [01:33:36]  Scandinavian Simvastatin Survival Study (4S) Scandinavian Simvastatin Survival Study Group. "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)." The Lancet 344.8934 (1994): 1383-1389. [01:33:49] West of Scotland Coronary Prevention Study (WOSCOPS): Shepherd, James, et al. "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia." New England Journal of Medicine 333.20 (1995): 1301-1308. [01:34:21] National Institute of Health’s ALLHAT-LLT trial: Officers, A. L. L. H. A. T. "Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)." JAMA 288.23 (2002): 2998-3007. [01:34:50] 2005 - Regulations guiding clinical trials changed. [01:35:14] Negative antidepressant studies not published; Study: Turner, Erick H., et al. "Selective publication of antidepressant trials and its influence on apparent efficacy." New England Journal of Medicine 358.3 (2008): 252-260. [01:37:11] Minnesota Coronary Experiment (MCE): Analysis of recovered data: Ramsden, Christopher E., et al. "Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)." bmj 353 (2016): i1246. [01:39:44] Why Most Published Research Findings Are False: Ioannidis, John PA. "Why most published research findings are false." PLoS medicine 2.8 (2005): e124. [01:39:55] Richard Horton, editor of the Lancet: half of what is published is not true: Horton, Richard. "Offline: What is medicine’s 5 sigma." Lancet 385.9976 (2015): 1380. [01:41:11] The problem with reproducibility; a database of clinical trials that cannot be challenged or reproduced. [01:42:37] Editors of prominent journals losing faith in published research: Marci Angell, Richard Smith [01:44:55] Parachute study: Yeh, Robert W., et al. "Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial." bmj 363 (2018): k5094. [01:46:01] Benefits that are major are obvious; no randomized clinical trial necessary. [01:48:33] Preventing vs. screening. [01:51:42] Podcast: Movement Analysis and Breathing Strategies for Pain Relief and Improved Performance with physical therapist Zac Cupples. [01:51:59] Analysis of women who died in various ways, examining breast tissue; found that a high % of women had what you could diagnose as breast cancer. Study: Bhathal, P. S., et al. "Frequency of benign and malignant breast lesions in 207 consecutive autopsies in Australian women." British journal of cancer 51.2 (1985): 271. [01:53:34] Screening programs not associated with reduced CVD or death; Study: Krogsbøll, Lasse T., et al. "General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis." Bmj 345 (2012): e7191. [01:54:26] Coronary Artery Calcium (CAC) scan. Podcast: Coronary Artery Calcium (CAC): A Direct Measure of Cardiovascular Disease Risk, with Ivor Cummins. [01:54:46] Cardiologist Bernard Lown.  [01:58:38] People who had measles/mumps less likely to get CVD; Study: Kubota, Yasuhiko, et al. "Association of measles and mumps with cardiovascular disease: The Japan Collaborative Cohort (JACC) study." Atherosclerosis 241.2 (2015): 682-686. [02:00:55] Life expectancy in US and UK is now falling. [02:06:46] Physical health doesn't exist without social health and psychological health. [02:07:40] Negative Twitter messages correlate with rates of heart disease; Study: Eichstaedt, Johannes C., et al. "Psychological language on Twitter predicts county-level heart disease mortality." Psychological science 26.2 (2015): 159-169. [02:09:58] People who take statins believe they’re protected so they stop exercising. Study: Lee, David SH, et al. "Statins and physical activity in older men: the osteoporotic fractures in men study." JAMA internal medicine 174.8 (2014): 1263-1270. [02:11:45] Simple changes: make friends, have good relationships, speak to your kids, exercise, eat natural food, sunshine. [02:16:53] Blood sugar measurements following funny lecture vs. boring lecture; Study: Hayashi, Keiko, et al. "Laughter lowered the increase in postprandial blood glucose." Diabetes care 26.5 (2003): 1651-1652. [02:18:08] Dr. Malcolm Kendrick’s blog.

Can we ever know what causes a chronic disease? In this episode, I’m joined again by Dr. Shoshana Herzig to finish a three-part miniseries on Bradford Hill and Doll’s attempts to prove that smoking caused lung cancer. We’ll talk about the first prospective cohort trial in history, 1960s “Fake News” from tobacco companies, public spats with the most famous statistician of the 20th century, and the development of the Bradford Hill Criteria, a guideline, however imperfect, that gives doctors a blueprint to finally figure out what causes diseases. Sources: Crofton J, The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10): 531–534. Daniels M and Bradford Hill A, Chemotherapy of Pulmonary Tuberculosis in Young Adults, Br Med J. 1952 May 31; 1(4769): 1162–1168. Dangers of Cigarette-smoking. Brit Med J 1, 1518 (1957). Doll, R. & Hill, B. A. Lung Cancer and Other Causes of Death in Relation to Smoking. Brit Med J 2, 1071 (1956). Doll, R. & Hill, B. A. Smoking and Carcinoma of the Lung. Brit Med J 2, 739 (1950). Hill, A. The Environment and Disease: Association or Causation? J Roy Soc Med 58, 295–300 (1965). HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931). Keating C, Smoking Kills: The Revolutionary Life of Richard Doll. 2009. Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012). Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999). Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973). Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004). Phillips, C. V. & Goodman, K. J. The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives Innovations 1, 1–5 (2004). Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006). Wynder, E. RE: “WHEN GENIUS ERRS: R. A. FISHER AND THE LUNG CANCER CONTROVERSY”. Am J Epidemiol 134, 1467–9 (1991).

In this episode, I have the honor of discussing Hill's Causal Guidelines with Dr. Maria Mori Brooks, a professor at the University of Pittsburgh Graduate School of Public Health. We go through the guidelines step by step, comment upon their practical applications, and discuss the pragmatic use of statistical analysis.Hosted by Sarah Morgan.Twitter: @nagrom_harasFor text and quote sources, visit badmedicinepod.blogspot.com.Twitter: @badmedicinepod1Patreon: patreon.com/badmedicinepodcastGmail: badmedicinepod@gmail.comBlog: badmedicinepod.blogspot.comEmail the Gmail to be entered into the book giveaway!Support the show (http://patreon.com/badmedicinepodcast)

In this episode we talk to Ed Boyer about Kratom, pharmacology, legal status, and discuss recent reports of adverse effects. Boyer et al Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth) FDA response to Kratom Bradford Hill Criteria [...]

Hilary and Roger talk about building data science products that provide a good user experience while adhering to some kind of ground truth, whether it’s in medicine, education, news, or elsewhere. Also Gilmore Girls. Show Notes: HIll’s criteria for causation: https://en.wikipedia.org/wiki/Bradford_Hill_criteria O’Reilly Bots Podcast: https://www.oreilly.com/topics/oreilly-bots-podcast NHTSA’s Federal Automated Vehicles Policy: http://www.nhtsa.gov/nhtsa/av/index.html Support us through our Patreon page: https://www.patreon.com/NSSDeviations Roger on Twitter: https://twitter.com/rdpeng Hilary on Twitter: https://twitter.com/hspter Get the Not So Standard Deviations book: https://leanpub.com/conversationsondatascience/ Subscribe to the podcast on Apple Podcasts: https://itunes.apple.com/us/podcast/not-so-standard-deviations/id1040614570 Subscribe to the podcast on Google Play: https://play.google.com/music/listen?u=0#/ps/Izfnbx6tlruojkfrvhjfdj3nmna Find past episodes: http://nssdeviations.com Contact us at nssdeviations@gmail.com

Wed, 05 Apr 2017 06:53:04 +0000 https://evidenzbasierte-pharmazie.podigee.io/40-sonderfolge-evidenz-geschichte-n-austin-bradford-hill-oder-warum-wir-randomisierung-brauchen c122ad2b74d60ae4046e0a4e4eafb15b Hier kommt die nächste Folge der Evidenzgeschichte(n): England nach dem 2. Weltkrieg: Tuberkulose gehört zu den wichtigsten Todesursachen bei jungen Menschen. Wie zuverlässig hilft Streptomycin? Das untersucht der Medizinstatistiker Austin Bradford Hill mit äußerst knappen Mitteln und einer neuen Methodik: einer randomisierten kontrollierten Studie. **Unsere Quellen** Wikipedia-Einträge zu - [Austin Bradford Hill](https://de.wikipedia.org/wiki/Austin_Bradford_Hill) - [Tuberkulose](https://de.wikipedia.org/wiki/Tuberkulose) Wo ist der Beweis? [Unverzerrte prospektive Zuteilung zu verschiedenen Therapien](http://de.testingtreatments.org/tt-main-text/6-faire-tests-von-therapien/vergleiche-von-therapien-mit-maessigen-aber-wichtigen-effekten/) James Lind Library - [Die veröffentlichte Studie zum Streptomycin-Versuch und Erinnerungen von Bradford Hill und D'Arcy Hart](http://www.jameslindlibrary.org/medical-research-council-1948b/) - Bradford Hill, [Principles of medical statistics](http://www.jameslindlibrary.org/hill-ab-1937b/) - [Hintergrundinformationen zum Streptomycin-Versuch](http://www.jameslindlibrary.org/articles/the-mrc-randomized-trial-of-streptomycin-and-its-legacy-a-view-from-the-clinical-front-line/) Weitere Quellen - [Die Randomisierung im Streptomycin-Versuch](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114162/) Den Podcast Evidenz-Geschichte(n) kann man auch separat abonnieren - am schnellsten über unsere Seite bei Podigee. 40 full no

  ULTRAMAN X THE MOVIE © 2016 UX FILM PARTNERS   In this special episode, Jessica and Chris chat with William Winckler and Bradford Hill, the duo behind the new English Dub and theatrical release of the Ultraman X the Movie and Ultraman Ginga S double feature. Listen to how Ultraman made his way to the big screen in the West in 2017 William Winckler copyright William Winckler Productions Inc Bradford Hil   Notes; copyright William Winckler Productions Inc US Theater Listings Alamo Drafthouse Laredo (Laredo, Texas) Alamo Drafthouse Westlakes (San Antonio, Texas) Alamo Drafthouse One Loudoun (Ashburn, Virginia) Alamo Drafthouse Winchester (Winchester, Virginia) Alamo Drafthouse Lakeline (Austin, Texas) Alamo Drafthouse Kalamazoo (Kalamazoo, Michigan) Alamo Drafthouse Kansas City (Kansas City, Missouri) Alamo Drafthouse San Francisco (San Francisco, California) Alamo Drafthouse Yonkers (Yonkers, New York) Alamo Drafthouse Mason Park (Katy, Texas) Alamo Drafthouse Dallas Ft. Worth (Dallas, Texas) Alamo Drafthouse Littleton (Denver, Colorado) Music Box Theatre (Chicago, Illinois) Loft Cinema (Tucson, Arizona) Capitol Theatre (Cleveland, Ohio) Keystone Cinemas (Mt. Washington, Kentucky) Hollywood Theater (Portland, Oregon) Additional dates added! Studio Movie Grill Tampa (Tampa, Florida) Studio Movie Grill College Park (Indianapolis, Indiana) Studio Movie Grill Pearland (Houston, Texas) Majestic Cinemas (Meridian, Idaho and Walla Walla, Washington) Grand Cinemas Yakima Valley (Sunnyside, Washington) Yelm Cinemas (Yelm, Washington) Grand Cinemas Walla Walla (Walla Walla, Washington) Beartooth Theatre (Anchorage, Alaska) Hollywood Blvd. Cinema (Woodridge, Illinois) Maple Theater (Bloomfield, Michigan) Los Angeles Comic Book & Sci-Fi Convention Screenings (Los Angeles, California) * Special 40th Anniversary 2-Day Event, Grand Ballroom Theater Mahoning Drive-In Theater  (Lehighton, Pennsylvania May 12th ~ 13th spring-time drive-in screenings) Royal Theatre (Toronto, Ontario, CANADA) UPDATE: Additional theaters included as of January 11, 2017: The Screening Room Cinema (Amherst, New York) The Carolina Theater (Durham, North Carolina) Mayfair Theater (Ottawa, Ontario, Canada) Rio Theater (Vancouver, British Colombia, Canada) Gateway Theater (Columbus, OH) Jean Cocteau Cinema (Santa Fe, NM) Melba Theater (Batesville, AK) Eclipse Theaters (Las Vegas, NV) US Ultraman X trailer https://www.youtube.com/watch?v=39l15x79WGQ Bradford Hill on Twitter William Winckler on Twitter Interview with William Winckler from Los Angeles Premier   Listen to us on Stitcher: Or download us on Itunes Feedback on either would be appreciated Let us know what you think by emailing us at The.Kaiju.Kingdom.Podcast@gmail.com Check us out on Twitter @TheKaijuKingdom Facebook: https://www.facebook.com/TheKaijuKingdomPodcast And on Tumblr as well http://thekaijukingdompodcast.tumblr.com Also check out our other podcasts and follow the Panzer Crush Podcast Network on Twitter: @Panzercrush As well as Facebook And if you like what you hear, please pass it along to a friend.  We always welcome feedback as well.

Hilary and Roger talk about building data science products that provide a good user experience while adhering to some kind of ground truth, whether it’s in medicine, education, news, or elsewhere. Also Gilmore Girls. Show notes: HIll’s criteria for causation: https://en.wikipedia.org/wiki/Bradford_Hill_criteria O’Reilly Bots Podcast: https://www.oreilly.com/topics/oreilly-bots-podcast NHTSA’s Federal Automated Vehicles Policy: http://www.nhtsa.gov/nhtsa/av/index.html

What a show!  First Elan loads our skeptical rifles with the Bradford Hill Criteria.   Next, special guest Julian Janes gives us an excellent overview of the dark art of cold reading.   Lastly, Darren asks does the earth really orbit the sun?

[intro music]   Host – Dan Keller Hello, and welcome to Episode Fourteen of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features part two of an interview with Professor Gavin Giovannoni about the role of Epstein-Barr virus in MS. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   We've published a blog post from Christine Granfield, the founder of HealthCare Journey. Healthcarejourney.org is a website designed to help MS patients easily navigate the expanse of information about MS. In the blog post, Ms. Granfield says that HealthCare Journey is not meant to replace the doctor-patient relationship but instead provide a place where patients can find answers to questions with accurate, up-to-date information when their physician might not be available.   We published another blog post written by our intern, Cynthia McKelvey, on how to interact with the news media. News about science is often sensationalized and over simplified. But that’s all the more reason for researchers and clinicians to be media-friendly. In her post, Cynthia offers 13 tips on how to talk to reporters so you can be sure the best and most accurate information gets to the public.   Last week we interviewed Dr. Alan Thompson of the International Progressive MS Alliance about the difficulties of researching progressive MS. We published more information on the Alliance, its goals, and a full list of the 22 recipients for their first round of funding, totaling 22 million euros. To view the article, visit msdiscovery.org and visit our News Briefs section under the News and Future Directions tab.   [transition music]   Now to the interview. Professor Gavin Giovannoni from Queen Mary University in London is one of the worlds most prolific and most visible MS researchers and clinicians. He's also on the scientific advisory board for MSDF. Two weeks ago we featured the first part of my interview with him about the potential for a cure in MS. This week we’re going to discuss the roll of EBV in MS.   Interviewer – Dan Keller Professor Giovannoni, where does it come in? How has it entered the thinking?   Interviewee – Gavin Giovannoni We have a causal theory. We don't just switch on a light switch, and we've got a call that said it evolves over time. And if there's one particular thing that looks like it's got the top candidate for being a cause of MS is Epstein-Barr virus. And I think the original observation is epidemiological. People with infectious mononucleosis, which is delayed EBV infection that is symptomatic, have a higher risk of developing MS, and that's been reproduced now across many, many studies as a risk factor. But EBV infection in itself is a risk factor because if you're not infected with the virus, in other words people who don't have the virus, have a very, very low risk…it's almost a zero risk of getting the disease. So in terms of its negative predictive value – that's the strongest value we have – people don't get MS if they don't have EBV. So it looks like it’s an essential component of the causal pathway. How it's acting in the causal pathway? We don't have any idea. We just do know that if you do get EBV infection or infectious mono it's a risk factor throughout life. So in the Danish study, it shows the risk remains even when you go into your 40s, 50s, and 60s, which is interesting.   And EBV is a complex biology. We don't know where it's acting. We know it resides as a latent infection in the B cell. And what it's doing to B-cell biology is incredibly complicated. It hijacks B-cell biology, and it affects its antigen-presenting function, it affects its survival, etc. So people are targeting the B cell; I think the B cell is important. And the reason why I think the B cell is important when you look at all the most effective therapies in MS, when you put them on a chart with all the cells they affect, the only common cell to all of them is the B cell. And the link that the B cell may be the Epstein-Barr virus. And how EBV triggers autoimmunity haven't a clue. We originally thought well maybe the link between infectious mono and MS was related to HLA susceptibility. But we did a study on university students in the UK, and we showed that the HLA type that predisposes you to infectious mono is not the HLA type that predisposes you to MS. So we don't think it's at the HLA level that EBV is interacting with MS susceptibility; it's somewhere else.   The other risk factors are smoking. And when you start putting smoking and EBV and low vitamin D, which is the other environmental factor, together it looks like there's some interaction of all three components. But how they're working at a biological level that's where research needs to be done. So some people are … I think there's mimicry between EBV and myelin proteins, and there is some data that there are some antigenic epitopes in the EBV proteins and [?] antigens, which is why a lot of people are focused on CD4 cells as being the link. I'm not sure if it is the CD4. Others are focused on the CD8 cells as being the link. Michael Pender in Brisbane, Australia, thinks that Epstein-Barr virus is acting as the innate stimulus, the danger signal, that just upregulates innate immunity that then allows autoimmune responses to occur on top of that. And he thinks that's occurring in the central nervous system. That's his theory. And he thinks that people with multiple sclerosis have a deficiency of cytotoxic CD8 cells that keep the EBV virus in check. So he's now testing the strategy of trying to boost the CD8 response against EBV and kill the Epstein-Barr virus to lower the innate activation and reduce autoimmunity. That's his theory.   I wish I could tell him my theory. All I know is that the epidemiological observations are pretty standing. And you know, we probably should be doing a vaccine trial to test the hypothesis. There is a vaccine for EBV, but it's been discontinued. So GSK developed the vaccine. It wasn't that effective in stopping EBV infection, but it was very effective in preventing infectious mono. So what it did was it raised your immunity to a level that stopped you getting infectious mono, and that may be enough for MS prevention. You know, when they sold the EBV vaccine program to MedImmune, and I heard about six months ago that maybe they had stopped the program. There is no EBV vaccine program occurring in the pharmaceutical arena. There's been a recent meeting in Oxford around Epstein's anniversary because it's 50 years since he discovered the virus. And the, Harold Varmus was there, and there's a big push now for the NIH to fund a vaccine study – interesting not to prevent MS but to prevent the secondary malignancies linked to EBV. Because EBV is linked to a whole lot of hematological malignancies. So the idea there would be if you could prevent people getting Epstein-Barr you prevent a whole lot of lymphomas particularly. I'm personally a little worried about that strategy because EBV is one of our most co-evolved viruses. At a population level, it's part of our immune systems. So I actually think at a population level EBV must be doing something good for society and the population. I think it may be a link to B-cell memory or something like that.   So if we stop people getting EBV, we may be storing our problems at a population level. But until we do the trials we won't know. So we need a vaccine, and that's the way to test is EBV causal? Coming away from it, it may just be the trigger, or it may be driving the disease continuous. If that's the case, then we need to have anti-EBV drugs. And there is one being tried right now; it's called ocrelizumab. It's an anti-CD20 drug. Itself hasn't been tested as an anti-EBV drug, its predecessor, which is rituximab, is licensed as an anti-EBV. It's actually the only drug that's licensed to treat EBV. It's licensed to treat EBV associated lymphoproliferative disease, which occurs in transplant patients. It's pretty effective at switching off on that condition, and the EBV levels just plummet. A company that's developing ocrelizumab, which is Genentech Roche, wouldn’t like for me to say that it's an anti-EBV drug, but that's exactly how it may be working in MS; it may be targeting EBV. The obvious thing is to test antivirals that target EBV. There are no specific ones that have been designed for EBV, but we've got a particular drug that we would love to test against EBV because it has some activity. Trying to get the funders convinced that we should do a trial of an anti-EBV drug in MS has been difficult. I think we shouldn't ignore the EBV hypothesis, though, because the data out there is pretty compelling that it's causal. And as a community, I think we have a responsibility to test whether or not it is causal. And the only way we can do that is intervention studies – vaccines and targeting the virus with antibiotics.   MSDF It seems the geographic distribution of MS may actually be opposite say the distribution of Burkitt’s lymphoma. And what is EBV doing and how does it do it in different regions? And I wonder if that brings in the vitamin D hypothesis again.   Dr. Giovannoni MS prevalence pretty much matches infectious mono prevalence. So infectious mono has also got a gradient. The Burkitt's lymphoma thing probably that follows patterns of parasitic infection, particularly in malaria. So I think EBV probably interacts with other infectious agents, and that's one of the theories about EBV; it's not working on its own; it's working as a coinfection with another virus. The other virus that we need to talk about are the family of the HERVs, human endogenous retroviruses. Because the EBV is a potent transactivator of these viruses. In the big body of literature on HERVs being involved in MS, a lot of us think it's associative. In other words, inflammatory response triggers transactivation of HERVs in what we see as an epiphenomenon. But there are people who think it may be linked to the cause of the disease. Again the only way we can test this hypothesis is by treating people with drugs that target EBV and HERVs. Because HERVs are drugable; they are retroviruses, and you've got a whole arsenal of therapy that could target the various components of HERV biology. We should be doing trials in that as well.   Coming back to the vitamin D, there has been one small study that needs to be reproduced showing that if you do get EBV infection when your vitamin D levels are low your antibody responses are much more marked. And so there may be some link between low vitamin D and infection, but nobody has actually studied that formally, and I think it's something we tried to do with our epidemiological tools to see vitamin D deficiency or low levels makes it more likely that you're going to get infectious mono, that maybe they are interacting with each other. I don't think it's going to be as simple as that, though, to be honest with you. I think they're probably going to be working in an immunological level. I'm not sure if they're going to be causal; I think they may be associated with each other. EBV triggers a mess of lymphoid proliferation, which consumes vitamin D levels. So if you find someone with infectious mono and they have low D levels, it could be the infectious mono is reverse causation rather than the other way of causation. So we need to do that prospectively, and it's a difficult study to do.   But I think also the other thing you've got to look at is when they're starting to put all of these risk factors together in studies, and this has been mainly been done in the Scandinavian databases – and you start putting the HLA-DR15 in, the protective HLA-A2 in, the history of infectious mono, serum levels of anti-EBV antibodies, put smoking in, start putting vitamin D levels in – you're beginning to see relative up about 40. So that's a big signal to me because the doyen of causation theory, Bradford Hill, said that when you start getting relative risks above 40 that you should be thinking causation. So I'm beginning to see a causal pathway where all of these factors now are giving relative risks that are very high compared to the background population. And so, those factors must all be in the causal pathway. And the question is which one can you intervene in? And there's a few you can intervene in. But EBV is the obvious one. If you take it out of the causal pathway, you may be able to prevent this disease.   So I'm lobbying – and whole lot of us are lobbying – that we really need to get the public health community and the MS community and the virology community together so we can start thinking about prevention trials. Around about 5 to 10% of the adult population are EBV negative. But that group of people don't get MS. So that's the important factor is those people don’t get MS.   MSDF But the flip side is 90% of the population has been exposed to EBV, and most of those people don't get MS. So do you think it's all of these other cofactors you've mentioned? Whereas EBV sort of lights the fire if the fuel is there?   Dr. Giovannoni Yes, I think that's true. And Bradford Hill, I mean he developed his theory for causation around common manifestations or re-exposures. Like asbestosis is one of the examples he always used that if you had asbestosis, which is quite of a rare exposure, the chances of getting mesothelioma, which is a rare cancer, was almost 200 times background. So that's easy to understand. But EBV is such a common exposure, and MS is a relatively rare manifestation. So in that situation, the relative risks come down. So even though the relative risk of getting MS is only about 2.2 to 2.5 with infectious mono, it doesn't mean to say it's not causal. It could still be causal. So I'm not worried that the relative risks are low. But I agree with if it's EBV infection on top of something else the genetic susceptibility, the low vitamin D, or all those other factors that then triggers the autoimmune response.   But if EBV is a pivotal factor and you stop it, those other factors are irrelevant. That's why we need to do prevention studies. We need the vaccine, though. The original vaccine strategy was developed to prevent EBV completely; that's in terms of oncoprevention. But in terms of MS and autoimmunity, you may not have to prevent Epstein-Barr virus. Maybe what you need is to make sure you're vitamin D replete and get wild-type infection when you're very young. That may be sufficient to lower the risk of MS. You may not necessarily need a lifelong protective immunity against Epstein-Barr, but maybe you just need to be infected at a young age when your immune system can deal with it. It doesn't fertilize the field for autoimmunity later on in life; that may be the strategy.   MSDF Does it get into the possibility of tolerance?   Dr. Giovannoni Yes.   MSDF To EBV?   Dr. Giovannoni If we knew about the biology of EBV, I mean I'm not a virologist. And when I delve into the complex biology of Epstein-Barr virus, how it's fooling the B cell into surviving longer and bypasses B-cell signaling pathways, it's a credibly cleaver virus. And there's a lot of biology there that needs to be picked apart in the MS field. So there may be pathways in the EBV biological pathway that could be targeted rather than just targeting the virus itself. So I think there's lots of research to be done. This is why we, as an MS community, really need to bring virologists into the community as much as possible. And at the moment, that doesn't seem to be happening a lot. There's very few virologists interested in MS. You can count them on one hand to be honest with you that are really interested in MS. Most virologists are working on other diseases. And when you go to them, it's hard to get them interested in MS because MS is something on the periphery of their thought. They're usually targeting obviously infectious diseases. But most of the EBV virologists are working in oncology, lymphomas.   MSDF Very good. Thank you.   [transition music]   MSDF Thank you for listening to Episode Fourteen of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]