Podcast appearances and mentions of Peter Campbell

Peter Cambpell has worked with the Donegal Democrat since 1977. Starting out in their printing office, he took up a journalism role with them in 1990. He was sports editor between 2004-2021 and in recent years , has retired and but continues to work part time. A respected voice who has seen so much down through the years, and I reflect with him on some of the finest moments he has covered including Donegal's Sam Maguire wins in 1992 and 2012. Elsewhere I chat to Peter about other aspects of life, including his own time playing underage and senior gaelic football with St Nauls and his love of golf which sees him being a member of the Bundoran GC. There's also a full preview of the upcoming club championship matches this weekend Sept 14th/15th in Donegal..Support the show

This week's episode of the Be More Today Show features Captains Keron Alleyne and Peter Campbell from Black Men Run NYC. Join our conversation as we discuss the healthy brotherhood, how running has helped to reverse generational health disparities in the BIPOC community, and why sharing the legacy of Ted Corbitt is so important. For more information about the club follow them on IG @blackmenrunnyc or email them at blkmenrunnyc@gmail.com. For all other questions visit www.bemoretoday.com and check out our YouTube page for the show as well at https://www.youtube.com/@bemoretoday --- Support this podcast: https://podcasters.spotify.com/pod/show/bemoretoday/support

This episode explores the story of Peter Campbell, the owner of Red Wagon Pizza, who brings his pizzas to events with his mobile catering service. He offers practical advice on efficiencies to optimize his busy summer season. Highlights: Humble Beginnings: Peter started by making and selling pizzas at his kids' school fundraiser. Taking the Leap: Encouraged by positive feedback, Pete decided to turn his passion into a business. However, he faced the fear of quitting his stable job and the financial risks involved. Building a Plan: Pete didn't have a traditional business plan, but he researched and learned from resources like Live Plan and books on starting a business. Step-by-Step Growth: Pete started small, participating in farmer's markets and mobile events. He gradually reinvested his earnings in equipment and grew his operation. The Importance of Commitment: Pete emphasizes the importance of full commitment when starting a business. He highlights the risks involved and the need to be prepared to go all in. Scarcity as a Marketing Tool: Pete highlights the power of scarcity in marketing. By limiting his availability at events and initially focusing on mobile operations, he created a sense of demand for his pizzas. Multiple Revenue Streams: Pete discusses the benefits of having additional revenue streams beyond just the restaurant. He gives the example of his pizza classes and frozen pizzas. Check out Peter Campbell here: https://www.redwagon-mpls.com/ Follow Peter Campbell here: https://www.instagram.com/redwagonpizza/?hl=en Thank you to our show sponsors: Corto Olive Oil: https://shareasale.com/r.cfm?b=1808352&u=2800064&m=112748&urllink=&afftrack= Ooni Pizza: https://shareasale.com/r.cfm?b=2430866&u=2800064&m=82053&urllink=&afftrack= Bacio Cheese: https://www.baciocheese.com/?utm_source=Influencer&utm_medium=Podcast_Social_Web&utm_campaign=Whats_Good_Dough&utm_content=Bacio DM @whatsgooddough https://www.instagram.com/whatsgooddough/ email me: eidref@whatsgooddough.com Topics: Bacio Cheese Mobile Catering Pizza Catering Business starting a pizza business turning a hobby into a business pizza business tips mobile pizza business farmers market pizza business

The most enthralling conversation I've ever had with anyone on cancer. It's with Charlie Swanton who is a senior group leader at the Francis Crick Institute, the Royal Society Napier Professor in Cancer and medical oncologist at University College London, co-director of Cancer Research UK.Video snippet from our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with audio links and many external linksEric Topol (00:07):Well, hello, this is Eric Topol with Ground Truths, and I am really fortunate today to connect us with Charlie Swanton, who is if not the most prolific researcher in the space of oncology and medicine, and he's right up there. Charlie is a physician scientist who is an oncologist at Francis Crick and he heads up the lung cancer area there. So Charlie, welcome.Charles Swanton (00:40):Thank you, Eric. Nice to meet you.Learning from a FailureEric Topol (00:43):Well, it really is a treat because I've been reading your papers and they're diverse. They're not just on cancer. Could be connecting things like air pollution, it could be Covid, it could be AI, all sorts of things. And it's really quite extraordinary. So I thought I'd start out with a really interesting short paper you wrote towards the end of last year to give a sense about you. It was called Turning a failing PhD around. And that's good because it's kind of historical anchoring. Before we get into some of your latest contributions, maybe can you tell us about that story about what you went through with your PhD?Charles Swanton (01:26):Yeah, well thank you, Eric. I got into research quite early. I did what you in the US would call the MD PhD program. So in my twenties I started a PhD in a molecular biology lab at what was then called the Imperial Cancer Research Fund, which was the sort of the mecca for DNA tumor viruses, if you like. It was really the place to go if you wanted to study how DNA tumor viruses worked, and many of the components of the cell cycle were discovered there in the 80s and 90s. Of course, Paul Nurse was the director of the institute at the time who discovered cdc2, the archetypal regulator of the cell cycle that led to his Nobel Prize. So it was a very exciting place to work, but my PhD wasn't going terribly well. And sort of 18, 19 months into my PhD, I was summoned for my midterm reports and it was not materializing rapidly enough.(02:25):And I sat down with my graduate student supervisors who were very kind, very generous, but basically said, Charlie, this isn't going well, is it? You've got two choices. You can either go back to medical school or change PhD projects. What do you want to do? And I said, well, I can't go back to medical school because I'm now two years behind. So instead I think what I'll do is I'll change PhD projects. And they asked me what I'd like to do. And back then we didn't know how p21, the CDK inhibitor bound to cyclin D, and I said, that's what I want to understand how these proteins interact biochemically. And they said, how are you going to do that? And I said, I'm not too sure, but maybe we'll try yeast two-hybrid screen and a mutagenesis screen. And that didn't work either. And in the end, something remarkable happened.(03:14):My PhD boss, Nic Jones, who's a great guy, still is, retired though now, but a phenomenal scientist. He put me in touch with a colleague who actually works next door to me now at the Francis Crick Institute called Neil McDonald, a structural biologist. And they had just solved, well, the community had just solved the structure. Pavletich just solved the structure of cyclin A CDK2. And so, Neil could show me this beautiful image of the crystal structure in 3D of cyclin A, and we could mirror cyclin D onto it and find the surface residue. So I spent the whole of my summer holiday mutating every surface exposed acid on cyclin D to an alanine until I found one that failed to interact with p21, but could still bind the CDK. And that little breakthrough, very little breakthrough led to this discovery that I had where the viral cyclins encoded by Kaposi sarcoma herpes virus, very similar to cyclin D, except in this one region that I had found interactive with a CDK inhibitor protein p21.(04:17):And so, I asked my boss, what do you think about the possibility this cyclin could have evolved from cyclin D but now mutated its surface residues in a specific area so that it can't be inhibited by any of the control proteins in the mammalian cell cycle? He said, it's a great idea, Charlie, give it a shot. And it worked. And then six months later, we got a Nature paper. And that for me was like, I cannot tell you how exciting, not the Nature paper so much as the discovery that you were the first person in the world to ever see this beautiful aspect of evolutionary biology at play and how this cyclin had adapted to just drive the cell cycle without being inhibited. For me, just, I mean, it was like a dream come true, and I never experienced anything like it before, and I guess it's sizes the equivalent to me of a class A drug. You get such a buzz out of it and over the years you sort of long for that to happen again. And occasionally it does, and it's just a wonderful profession.Eric Topol (05:20):Well, I thought that it was such a great story because here you were about to fail. I mean literally fail, and you really were able to turn it around and it should give hope to everybody working in science out there that they could just be right around the corner from a significant discovery.Charles Swanton (05:36):I think what doesn't break you makes you stronger. You just got to plow on if you love it enough, you'll find a way forward eventually, I hope.Tracing the Evolution of Cancer (TRACERx)Eric Topol (05:44):Yeah, no question about that. Now, some of your recent contributions, I mean, it's just amazing to me. I just try to keep up with the literature just keeping up with you.Charles Swanton (05:58):Eric, it's sweet of you. The first thing to say is it's not just me. This is a big community of lung cancer researchers we have thanks to Cancer Research UK funded around TRACERx and the lung cancer center. Every one of my papers has three corresponding authors, multiple co-first authors that all contribute in this multidisciplinary team to the sort of series of small incremental discoveries. And it's absolutely not just me. I've got an amazing team of scientists who I work with and learn from, so it's sweet to give me the credit.Eric Topol (06:30):I think what you're saying is really important. It is a team, but I think what I see through it all is that you're an inspiration to the team. You pull people together from all over the world on these projects and it's pretty extraordinary, so that's what I would say.Charles Swanton (06:49):The lung community, Eric, the lung cancer community is just unbelievably conducive to collaboration and advancing understanding of the disease together. It's just such a privilege to be working in this field. I know that sounds terribly corny, but it is true. I don't think I recall a single email to anybody where I've asked if we can collaborate where they've said, no, everybody wants to help. Everybody wants to work together on this challenge. It's just such an amazing field to be working in.Eric Topol (07:19):Yeah. Well I was going to ask you about that. And of course you could have restricted your efforts or focused on different cancers. What made you land in lung cancer? Not that that's only part of what you're working on, but that being the main thing, what drew you to that area?Charles Swanton (07:39):So I think the answer to your question is back in 2008 when I was looking for a niche, back then it was lung cancer was just on the brink of becoming an exciting place to work, but back then nobody wanted to work in that field. So there was a chair position in thoracic oncology and precision medicine open at University College London Hospital that had been open, as I understand it for two years. And I don't think anybody had applied. So I applied and because I was the only one, I got it and the rest is history.(08:16):And of course that was right at the time when the IPASS draft from Tony Mok was published and was just a bit after when the poster child of EGFR TKIs and EGFR mutant lung cancer had finally proven that if you segregate that population of patients with EGFR activating mutation, they do incredibly well on an EGFR inhibitor. And that was sort of the solid tumor poster child along with Herceptin of precision medicine, I think. And you saw the data at ASCO this week of Lorlatinib in re-arranged lung cancer. Patients are living way beyond five years now, and people are actually talking about this disease being more like CML. I mean, it's extraordinary the progress that's been made in the last two decades in my short career.Eric Topol (09:02):Actually, I do want to have you put that in perspective because it's really important what you just mentioned. I was going to ask you about this ASCO study with the AKT subgroup. So the cancer landscape of the lung has changed so much from what used to be a disease of cigarette smoking to now one of, I guess adenocarcinoma, non-small cell carcinoma, not related to cigarettes. We're going to talk about air pollution in a minute. This group that had, as you say, 60 month, five year plus survival versus what the standard therapy was a year plus is so extraordinary. But is that just a small subgroup within small cell lung cancer?Charles Swanton (09:48):Yes, it is, unfortunately. It's just a small subgroup. In our practice, probably less than 1% of all presentations often in never smokers, often in female, never smokers. So it is still in the UK at least a minority subset of adenocarcinomas, but it's still, as you rightly say, a minority of patients that we can make a big difference to with a drug that's pretty well tolerated, crosses the blood-brain barrier and prevents central nervous system relapse and progression. It really is an extraordinary breakthrough, I think. But that said, we're also seeing advances in smoking associated lung cancer with a high mutational burden with checkpoint inhibitor therapy, particularly in the neoadjuvant setting now prior to surgery. That's really, really impressive indeed. And adjuvant checkpoint inhibitor therapies as well as in the metastatic setting are absolutely improving survival times and outcomes now in a way that we couldn't have dreamt of 15 years ago. We've got much more than just platinum-based chemo is basically the bottom line now.Revving Up ImmunotherapyEric Topol (10:56):Right, right. Well that actually gets a natural question about immunotherapy also is one of the moving parts actually just amazing to me how that's really, it's almost like we're just scratching the surface of immunotherapy now with checkpoint inhibitors because the more we get the immune system revved up, the more we're seeing results, whether it's with vaccines or CAR-T, I mean it seems like we're just at the early stages of getting the immune system where it needs to be to tackle the cancer. What's your thought about that?Charles Swanton (11:32):I think you're absolutely right. We are, we're at the beginning of a very long journey thanks to Jim Allison and Honjo. We've got CTLA4 and PD-1/PDL-1 axis to target that's made a dramatic difference across multiple solid tumor types including melanoma and lung cancer. But undoubtedly, there are other targets we've seen LAG-3 and melanoma and then we're seeing new ways, as you rightly put it to mobilize the immune system to target cancers. And that can be done through vaccine based approaches where you stimulate the immune system against the patient's specific mutations in their cancer or adoptive T-cell therapies where you take the T-cells out of the tumor, you prime them against the mutations found in the tumor, you expand them and then give them back to the patient. And colleagues in the US, Steve Rosenberg and John Haanen in the Netherlands have done a remarkable job there in the context of melanoma, we're not a million miles away from European approvals and academic initiated manufacturing of T-cells for patients in national health systems like in the Netherlands.(12:50):John Haanen's work is remarkable in that regard. And then there are really spectacular ways of altering T-cells to be able to either migrate to the tumor or to target specific tumor antigens. You mentioned CAR-T cell therapies in the context of acute leukemia, really extraordinary developments there. And myeloma and diffuse large B-cell lymphoma as well as even in solid tumors are showing efficacy. And I really am very excited about the future of what we call biological therapies, be it vaccines, an antibody drug conjugates and T-cell therapies. I think cancer is a constantly adapting evolutionary force to be reckoned with what better system to combat it than our evolving immune system. It strikes me as being a future solution to many of these refractory cancers we still find difficult to treat.Eric Topol (13:48):Yeah, your point is an interesting parallel how the SARS-CoV-2 virus is constantly mutating and becoming more evasive as is the tumor in a person and the fact that we can try to amp up the immune system with these various means that you just were reviewing. You mentioned the other category that's very hot right now, which is the antibody drug conjugates. Could you explain a bit about how they work and why you think this is an important part of the future for cancer?Antibody-Drug ConjugatesCharles Swanton (14:26):That's a great question. So one of the challenges with chemotherapy, as you know, is the normal tissue toxicity. So for instance, neutropenia, hair loss, bowel dysfunction, diarrhea, epithelial damage, essentially as you know, cytotoxics affect rapidly dividing tissues, so bone marrow, epithelial tissues. And because until relatively recently we had no way of targeting chemotherapy patients experienced side effects associated with them. So over the last decade or so, pioneers in this field have brought together this idea of biological therapies linked with chemotherapy through a biological linker. And so one poster chart of that would be the drug T-DXd, which is essentially Herceptin linked to a chemotherapy drug. And this is just the most extraordinary drug that obviously binds the HER2 receptor, but brings the chemotherapy and proximity of the tumor. The idea being the more drug you can get into the tumor and the less you're releasing into normal tissue, the more on tumor cytotoxicity you'll have and the less off tumor on target normal tissue side effects you'll have. And to a large extent, that's being shown to be the case. That doesn't mean they're completely toxicity free, they're not. And one of the side effects associated with these drugs is pneumonitis.(16:03):But that said, the efficacy is simply extraordinary. And for example, we're having to rewrite the rule books if you like, I think. I mean I'm not a breast cancer physician, I used to be a long time ago, but back in the past in the early 2000s, there was HER2 positive breast cancer and that's it. Now they're talking about HER2 low, HER2 ultra-low, all of which seem to in their own way be sensitive to T-DXd, albeit to a lower extent than HER2 positive disease. But the point is that there doesn't seem to be HER2 completely zero tumor group in breast cancer. And even the HER2-0 seem to benefit from T-DXd to an extent. And the question is why? And I think what people are thinking now is it's a combination of very low cell service expression of HER2 that's undetectable by conventional methods like immunohistochemistry, but also something exquisitely specific about the way in which HER2 is mobilized on the membrane and taken back into the cell. That seems to be specific to the breast cancer cell but not normal tissue. So in other words, the antibody drug conjugate binds the tumor cell, it's thought the whole receptor's internalized into the endosome, and that's where the toxicity then happens. And it's something to do with the endosomal trafficking with the low level expression and internalization of the receptor. That may well be the reason why these HER2 low tumors are so sensitive to this beautiful technology.Eric Topol (17:38):Now I mean it is an amazing technology in all these years where we just were basically indiscriminately trying to kill cells and hoping that the cancer would succumb. And now you're finding whether you want to call it a carry or vector or Trojan horse, whatever you want to call it, but do you see that analogy of the HER2 receptor that's going to be seen across the board in other cancers?Charles Swanton (18:02):That's the big question, Eric. I think, and have we just lucked out with T-DXd, will we find other T-DXd like ADCs targeting other proteins? I mean there are a lot of ADCs being developed against a lot of different cell surface proteins, and I think the jury's still out. I'm confident we will, but we have to bear in mind that biology is a fickle friend and there may be something here related to the internalization of the receptor in breast cancer that makes this disease so exquisitely sensitive. So I think we just don't know yet. I'm reasonably confident that we will find other targets that are as profoundly sensitive as HER2 positive breast cancer, but time will tell.Cancer, A Systemic DiseaseEric Topol (18:49):Right. Now along these lines, well the recent paper that you had in Cell, called embracing cancer complexity, which we've talking about a bit, in fact it's kind of those two words go together awfully well, but hallmarks of systemic disease, this was a masterful review, as you say with the team that you led. But can you tell us about what's your main perspective about this systemic disease? I mean obviously there's been the cancer is like cardiovascular and cancers like this or that, but here you really brought it together with systemic illness. What can you say about that?Charles Swanton (19:42):Well, thanks for the question first of all, Eric. So a lot of this comes from some of my medical experience of treating cancer and thinking to myself over the years, molecular biology has had a major footprint on advances in treating the disease undoubtedly. But there are still aspects of medicine where molecular biology has had very little impact, and often that is in areas of suffering in patients with advanced disease and cancer related to things like cancer cachexia, thrombophilia. What is the reason why patients die blood clots? What is the reason patients die of cancer at all? Even a simple question like that, we don't always know the answer to, on death certificates, we write metastatic disease as a cause of cancer death, but we have patients who die with often limited disease burden and no obvious proximal cause of death sometimes. And that's very perplexing, and we need to understand that process better.(20:41):And we need to understand aspects like cancer pain, for example, circadian rhythms affect biological sensitivity of cancer cells to drugs and what have you. Thinking about cancer rather than just sort of a single group of chaotically proliferating cells to a vision of cancer interacting both locally within a microenvironment but more distantly across organs and how organs communicate with the cancer through neuronal networks, for example, I think is going to be the next big challenge by setting the field over the next decade or two. And I think then thinking about more broadly what I mean by embracing complexity, I think some of that relates to the limitations of the model systems we use, trying to understand inter-organ crosstalk, some of the things you cover in your beautiful Twitter reviews. (←Ground Truths link) I remember recently you highlighted four publications that looked at central nervous system, immune cell crosstalk or central nervous system microbiome crosstalk. It's this sort of long range interaction between organs, between the central nervous system and the immune system and the cancer that I'm hugely interested in because I really think there are vital clues there that will unlock new targets that will enable us to control cancers more effectively if we just understood these complex networks better and had more sophisticated animal model systems to be able to interpret these interactions.Eric Topol (22:11):No, it's so important what you're bringing out, the mysteries that still we have to deal with cancer, why patients have all these issues or dying without really knowing what's happened no less, as you say, these new connects that are being discovered at a remarkable pace, as you mentioned, that ground truths. And also, for example, when I spoke with Michelle Monje, she's amazing on the cancer, where hijacking the brain cells and just pretty extraordinary things. Now that gets me to another line of work of yours. I mean there are many, but the issue of evolution of the tumor, and if you could put that in context, a hot area that's helping us elucidate these mechanisms is known as spatial omics or spatial biology. This whole idea of being able to get the spatial temporal progression through single cell sequencing and single cell nuclei, all the single cell omics. So if you could kind of take us through what have we learned with this technique and spatial omics that now has changed or illuminated our understanding of how cancer evolves?Charles Swanton (23:37):Yeah, great question. Well, I mean I think it helps us sort of rewind a bit and think about evolution in general. Genetic selection brought about by diverse environments and environmental pressures that force evolution, genetic evolution, and speciation down certain evolutionary roots. And I think one can think about cancers in a similar way. They start from a single cell and we can trace the evolutionary paths of cancers by single cell analysis as well as bulk sequencing of spatially separated tumor regions to be able to reconstruct their subclones. And that's taught us to some extent, what are the early events in tumor evolution? What are the biological mechanisms driving branched evolution? How does genome instability begin in tumors? And we found through TRACERx work, whole genome doubling is a major route through to driving chromosome instability along with mutagenic enzymes like APOBEC that drive both mutations and chromosomal instability.(24:44):And then that leads to a sort of adaptive radiation in a sense, not dissimilar to I guess the Cambrian explosion of evolutionary opportunity upon which natural selection can act. And that's when you start to see the hallmarks of immune evasion like loss of HLA, the immune recognition molecules that bind the neoantigens or even loss of the neoantigens altogether or mutation of beta 2 microglobulin that allow the tumor cells to now evolve below the radar, so to speak. But you allude to the sort of spatial technologies that allow us to start to interpret the microenvironments as well. And that then tells us what the evolutionary pressures are upon the tumor. And we're learning from those spatial technologies that these environments are incredibly diverse, actually interestingly seem to be converging on one important aspect I'd like to talk to you a little bit more about, which is the myeloid axis, which is these neutrophils, macrophages, et cetera, that seem to be associated with poor outcome and that will perhaps talk about pollution in a minute.(25:51):But I think they're creating a sort of chronic inflammatory response that allows these early nascent tumor cells to start to initiate into frankly tumor invasive cells and start to grow. And so, what we're seeing from these spatial technologies in lung cancer is that T-cells, predatory T-cells, force tumors to lose their HLA molecules and what have you to evade the immune system. But for reasons we don't understand, high neutrophil infiltration seems to be associated with poor outcome, poor metastasis free survival. And actually, those same neutrophils we've recently found actually even tracked to the metastasis sites of metastasis. So it's almost like this sort of symbiosis between the myeloid cells and the tumor cells in their biology and growth and progression of the tumor cells.Eric Topol (26:46):Yeah, I mean this white cell story, this seems to be getting legs and is relatively new, was this cracked because of the ability to do this type of work to in the past everything was, oh, it's cancer's heterogeneous and now we're getting pinpoint definition of what's going on.Charles Swanton (27:04):I think it's certainly contributed, but it's like everything in science, Eric, when you look back, there's evidence in the literature for pretty much everything we've ever discovered. You just need to put the pieces together. And I mean one example would be the neutrophil lymphocyte ratio in the blood as a hallmark of outcome in cancers and to checkpoint inhibitor blockade, maybe this begins to explain it, high neutrophils, immune suppressive environment, high neutrophils, high macrophages, high immune suppression, less benefit from checkpoint inhibitor therapy, whereas you want lymphocyte. So I think there are biomedical medical insights that help inform the biology we do in the lab that have been known for decades or more. And certainly the myeloid M2 axis in macrophages and what have you was known about way before these spatial technologies really came to fruition, I think.The Impact of Air PollutionEric Topol (28:01):Yeah. Well you touched on this about air pollution and that's another dimension of the work that you and your team have done. As you well know, there was a recent global burden of disease paper in the Lancet, which has now said that air pollution with particulate matter 2.5 less is the leading cause of the burden of disease in the world now.Charles Swanton (28:32):What did you think of that, Eric?Eric Topol (28:34):I mean, I was blown away. Totally blown away. And this is an era you've really worked on. So can you put it in perspective?Charles Swanton (28:42):Yeah. So we got into this because patients of mine, and many of my colleagues would ask the same question, I've never smoked doctor, I'm healthy. I'm in my mid 50s though they're often female and I've got lung cancer. Why is that doctor? I've had a good diet, I exercise, et cetera. And we didn't really have a very good answer for that, and I don't want to pretend for a minute we solved the whole problem. I think hopefully we've contributed to a little bit of understanding of why this may happen. But that aside, we knew that there were risk factors associated with lung cancer that included air pollution, radon exposure, of course, germline genetics, we mustn't forget very important germline variation. And I think there is evidence that all of them are associated with lung cancer risk in different ways. But we wanted to look at air pollution, particularly because there was an awful lot of evidence, several meta-analysis of over half a million individuals showing very convincingly with highly significant results that increasing PM 2.5 micron particulate levels were associated with increased risk of lung cancer.(29:59):To put that into perspective, where you are on the west coast of the US, it's relatively unpolluted. You would be talking about maybe five micrograms per meter cubed of PM2.5 in a place like San Diego or Western California, assuming there aren't any forest fires of course. And we estimate that that would translate to about, we think it's about one extra case of never smoking lung cancer per hundred thousand of the population per year per one microgram per meter cube rise in the pollution levels. So if you go to Beijing for example, on a bad day, the air pollution levels could be upwards of a hundred micrograms per meter cubed because there are so many coal fired power stations in China partly. And there I think the risk is considerably higher. And that's certainly what we've seen in the meta-analyses in our limited and relatively crude epidemiological analyses to be the case.(30:59):So I think the association was pretty certain, we were very confident from people's prior publications  this was important. But of course, association is not causation. So we took a number of animal models and showed that you could promote lung cancer formation in four different oncogene driven lung cancer models. And then the question is how, does air pollution stimulate mutations, which is what I initially thought it would do or something else. It turns out we don't see a significant increase in exogenous like C to A carcinogenic mutations. So that made us put our thinking caps on. And I said to you earlier, often all these discoveries have been made before. Well, Berenblum in 1947, first postulated that actually tumors are initiated through a two-step process, which we now know involves a sort of pre initiated cell with a mutation in that in itself is not sufficient to cause cancer.(31:58):But on top of that you need an inflammatory stimulus. So the question was then, well, okay, is inflammation working here? And we found that there was an interleukin-1 beta axis. And what happens is that the macrophages come into the lung on pollution exposure, engulf phagocytose the air pollutants, and we think what's happening is the air pollutants are puncturing membranes in the lung. That's what we think is happening. And interleukin-1 beta preformed IL-1 beta is being released into the extracellular matrix and then stimulating pre-initiated cells stem cells like the AT2 cells with an activating EGFR mutation to form a tumor. But the EGFR mutation alone is not sufficient to form tumors. It's only when you have the interleukin-1 beta and the activated mutation that a tumor can start.(32:49):And we found that if we sequence normal lung tissue in a healthy adult 60-year-old adult, we will find about half of biopsies will have an activating KRAS mutation in normal tissue, and about 15% will have an activating mutation in EGFR in histologically normal tissue with nerve and of cancer. In fact, my friend and colleague who's a co-author on the paper, James DeGregori, who you should speak to in Colorado, fascinating evolutionary cancer biologists estimates that in a healthy 60-year-old, there are a hundred billion cells in your body that harbor an oncogenic mutation. So that tells you that at the cellular level, cancer is an incredibly rare event and almost never happens. I mean, our lifetime risk of cancer is perhaps one in two. You covered that beautiful pancreas paper recently where they estimated that there may be 80 to 100 KRAS mutations in a normal adult pancreas, and yet our lifetime risk of pancreas cancer is one in 70. So this tells you that oncogenic mutations are rarely sufficient to drive cancer, so something else must be happening. And in the context of air pollution associated lung cancer, we think that's inflammation driven by these white cells, these myeloid cells, the macrophages.Cancer BiomarkersEric Topol (34:06):No, it makes a lot of sense. And this, you mentioned the pancreas paper and also what's going in the lung, and it seems like we have this burden of all you need is a tipping point and air pollution seems to qualify, and you seem to be really in the process of icing the mechanism. And like I would've thought it was just mutagenic and it's not so simple, right? But that gets me to this is such an important aspect of cancer, the fact that we harbor these kind of preconditions. And would you think that cancer takes decades to actually manifest most cancers, or do we really have an opportunity here to be able to track whether it's through blood or other biomarkers? Another area you've worked on a lot whereby let's say you could define people at risk for polygenic risk scores or various cancers or genome sequencing for predisposition genes, whatever, and you could monitor in the future over the course of those high-risk people, whether they were starting to manifest microscopic malignancy. Do you have any thoughts about how long it takes for the average person to actually manifest a typical cancer?Charles Swanton (35:28):That's a cracking question, and the answer is we've got some clues in various cancers. Peter Campbell would be a good person to speak to. He estimates that some of the earliest steps in renal cancer can occur in adolescence. We've had patients who gave up smoking 30 or so years ago where we can still see the clonal smoking mutations in the trunk of the tumor's evolutionary tree. So the initial footprints of the cancer are made 30 years before the cancer presents. That driver mutation itself may also be a KRAS mutation in a smoking cigarette context, G12C mutation. And those mutations can precede the diagnosis of the disease by decades. So the earliest steps in cancer evolution can occur, we think can precede diagnoses by a long time. So to your point, your question which is, is there an opportunity to intervene? I'm hugely optimistic about this actually, this idea of molecular cancer prevention.An Anti-Inflammatory Drug Reduces Fatal Cancer and Lung Cancer(36:41):How can we use data coming out of various studies in the pancreas, mesothelioma, lung, et cetera to understand the inflammatory responses? I don't think we can do very much about the mutations. The mutations unfortunately are a natural consequence of aging. You and I just sitting here talking for an hour will have accumulated multiple mutations in our bodies over that period, I'm afraid and there's no escaping it. And right now there's not much we can do to eradicate those mutant clones. So if we take that as almost an intractable problem, measuring them is hard enough, eradicating them is even harder. And then we go back to Berenblum in 1947 who said, you need an inflammatory stimulus. Well, could we do something about the inflammation and dampen down the inflammation? And of course, this is why we got so excited about IL-1 beta because of the CANTOS trial, which you may remember in 2017 from Ridker and colleagues showed that anti IL-1 beta used as a mechanism of preventing cardiovascular events was associated with a really impressive dose dependent reduction in new lung cancer primaries.(37:49):Really a beautiful example of cancer prevention in action. And that data weren't just a coincidence. The FDA mandated Novartis to collect the solid tumor data and the P-values are 0.001. I mean it's very highly significant dose dependent reduction in lung cancer incidents associated with anti IL-1 beta. So I think that's really the first clue in my mind that something can be done about this problem. And actually they had five years of follow-up, Eric. So that's something about that intervening period where you can treat and then over time see a reduction in new lung cancers forming. So I definitely think there's a window of opportunity here.Eric Topol (38:31):Well, what you're bringing up is fascinating here because this trial, which was a cardiology trial to try to reduce heart attacks, finds a reduction in cancer, and it's been lost. It's been buried. I mean, no one's using this therapy to prevent cancer between ratcheting up the immune system or decreasing inflammation. We have opportunities that we're not even attempting. Are there any trials that are trying to do this sort of thing?Charles Swanton (39:02):So this is the fundamental problem. Nobody wants to invest in prevention because essentially you are dealing with well individuals. It's like the vaccine challenge all over again. And the problem is you never know who you are benefiting. There's no economic model for it. So pharma just won't touch prevention with a barge pole right now. And that's the problem. There's no economic model for it. And yet the community, all my academic colleagues are crying out saying, this has got to be possible. This has got to be possible. So CRUK are putting together a group of like-minded individuals to see if we can do something here and we're gradually making progress, but it is tough.Eric Topol (39:43):And it's interesting that you bring that up because for GRAIL, one of the multicenter cancer early detection companies, they raised billions of dollars. And in fact, their largest trial is ongoing in the UK, but they haven't really focused on high-risk people. They just took anybody over age 50 or that sort of thing. But that's the only foray to try to reboot how we or make an early microscopic diagnosis of cancer and track people differently. And there's an opportunity there. You've written quite a bit on you and colleagues of the blood markers being able to find a cancer where well before, in fact, I was going to ask you about that is, do you think there's people that are not just having all these mutations every minute, every hour, but that are starting to have the early seeds of cancer, but because their immune system then subsequently kicks in that they basically kind of quash it for that period of time?Charles Swanton (40:47):Yeah, I do think that, I mean, the very fact that we see these sort of footprints in the tumor genome of immune evasion tells you that the immune system's having a very profound predatory effect on evolving tumors. So I do think it's very likely that there are tumors occurring that are suppressed by the immune system. There is a clear signature, a signal of negative selection in tumors where clones have been purified during their evolution by the immune system. So I think there's pretty strong evidence for that now. Obviously, it's very difficult to prove something existed when it doesn't now exist, but there absolutely is evidence for that. I think it raises the interesting question of immune system recognizes mutations and our bodies are replete with mutations as we were just discussing. Why is it that we're not just a sort of epithelial lining of autoimmunity with T-cells and immune cells everywhere? And I think what the clever thing about the immune system is it's evolved to target antigens only when they get above a certain burden. Otherwise, I think our epithelial lining, our skin, our guts, all of our tissues will be just full of T-cells eating away our normal clones.(42:09):These have to get to a certain size for antigen to be presented at a certain level for the immune system to recognize it. And it's only then that you get the immune predation occurring.Forever Chemicals and Microplastics Eric Topol (42:20):Yeah, well, I mean this is opportunities galore here. I also wanted to extend the air pollution story a bit. Obviously, we talked about particulate matter and there's ozone and nitric NO2, and there's all sorts of other air pollutants, but then there's also in the air and water these forever chemicals PFAS for abbreviation, and they seem to be incriminated like air pollution. Can you comment about that?Charles Swanton (42:55):Well, I can comment only insofar as to say I'm worried about the situation. Indeed, I'm worried about microplastics actually, and you actually cover that story as well in the New England Journal, the association of microplastics with plaque rupture and atheroma. And indeed, just as in parenthesis, I wanted to just quickly say we currently think the same mechanisms that are driving lung cancer are probably responsible for atheroma and possibly even neurodegenerative disease. And essentially it all comes down to the macrophages and the microglia becoming clogged up with these pollutants or environmental particulars and releasing chronic inflammatory mediators that ultimately lead to disease. And IL-1 beta being one of those in atheroma and probably IL-6 and TNF in neurodegenerative disease and what have you. But I think this issue that you rightly bring up of what is in our environment and how does it cause pathology is really something that epidemiologists have spent a lot of time focusing on.(43:56):But actually in terms of trying to move from association to causation, we've been, I would argue a little bit slow biologically in trying to understand these issues. And I think that is a concern. I mean, to give you an example, Allan Balmain, who works at UCSF quite close to you, published a paper in 2020 showing that 17 out of 20 environmental carcinogens IARC carcinogens class one carcinogens cause tumors in rodent models without driving mutations. So if you take that to a logical conclusion, in my mind, what worries me is that many of the sort of carcinogen assays are based on driving mutagenesis genome instability. But if many carcinogen aren't driving DNA mutagenesis but are still driving cancer, how are they doing it? And do we actually have the right assays to interpret safety of new chemical matter that's being introduced into our environment, these long-lived particles that we're breathing in plastics, pollutants, you name it, until we have the right biological assays, deeming something to be safe I think is tricky.Eric Topol (45:11):Absolutely. And I share your concerns on the nanoplastic microplastic story, as you well know, not only have they been seen in arteries that are inflamed and in blood clots and in various tissues, have they been seen so far or even looked for within tumor tissue?Charles Swanton (45:33):Good question. I'm not sure they have. I need to check. What I can tell you is we've been doing some experiments in the lab with fluorescent microplastics, 2.5 micron microplastics given inhaled microplastics. We find them in every mouse organ a week after. And these pollutants even get through into the brain through the olfactory bulb we think.Charles Swanton (45:57):Permeate every tissue, Eric.Eric Topol (45:59):Yeah, no, this is scary because here we are, we have these potentially ingenious ways to prevent cancer in the future, but we're chasing our tails by not doing anything to deal with our environment.Charles Swanton (46:11):I think that's right. I totally agree. Yeah.Eric Topol (46:15):So I mean, I can talk to you for the rest of the day, but I do want to end up with a topic that we have mutual interest in, which is AI. And also along with that, when you mentioned about aging, I'd like to get your views on these two, how do you see AI fitting into the future of cancer? And then the more general topic is, can we actually at some point modulate the biologic aging process with or without help with from AI? So those are two very dense questions, but maybe you can take us through them.Charles Swanton (46:57):How long have we got?Eric Topol (46:59):Just however long you have.A.I. and CancerCharles Swanton (47:02):AI and cancer. Well, AI and medicine actually in general, whether it's biomedical research or medical care, has just infinite potential. And I'm very, very excited about it. I think what excites me about AI is it's almost the infinite possibilities to work across scale. Some of the challenges we raised in the Cell review that you mentioned, tackling, embracing complexity are perfectly suited for an AI problem. Nonlinear data working, for instance in our fields with CT imaging, MRI imaging, clinical outcome data, blood parameters, genomics, transcriptomes and proteomes and trying to relate this all into something that's understandable that relates to risk of disease or potential identification of a new drug target, for example. There are numerous publications that you and others have covered that allude to the incredible possibilities there that are leading to, for instance, the new identification of drug targets. I mean, Eli Van Allen's published some beautiful work here and in the context of prostate cancer with MDM4 and FGF receptor molecules being intimately related to disease biology.(48:18):But then it's not just that, not just drug target identification, it's also going all the way through to the clinic through drug discovery. It's how you get these small molecules to interact with oncogenic proteins and to inhibit them. And there are some really spectacular developments going on in, for instance, time resolved cryo-electron microscopy, where in combination with modeling and quantum computing and what have you, you can start to find pockets emerging in mutant proteins, but not the wild type ones that are druggable. And then you can use sort of synthetic AI driven libraries to find small molecules that will be predicted to bind these transiently emerging pockets. So it's almost like AI is primed to help at every stage in scientific investigation from the bench all the way through to the bedside. And there are examples all the way through there in the literature that you and others have covered in the last few years. So I could not be more excited about that.Eric Topol (49:29):I couldn't agree with you more. And I think when we get to multimodal AI at the individual level across all their risks for conditions in their future, I hope someday will fulfill that fantasy of primary prevention. And that is getting me to this point that I touched on because I do think they interact to some degree AI and then will we ever be able to have an impact on aging? Most people conflate this because what we've been talking about throughout the hour has been age-related diseases, that is cancer, for example, and cardiovascular and neurodegenerative, which is different than changing aging per se, body wide aging. Do you think we'll ever changed body wide aging?Charles Swanton (50:18):Wow, what a question. Well, if you'd asked me 10 years ago, 15 years ago, do you think we'll ever cure melanoma in my lifetime, I'd have said definitely not. And now look where we are. Half of patients with melanoma, advanced melanoma, even with brain metastasis curd with combination checkpoint therapy. So I never say never in biology anymore. It always comes back to bite you and prove you wrong. So I think it's perfectly possible.Charles Swanton (50:49):We have ways to slow down the aging process. I guess the question is what will be the consequences of that?Eric Topol (50:55):That's what I was going to ask you, because all these things like epigenetic reprogramming and senolytic drugs, and they seem to at least pose some risk for cancer.Charles Swanton (51:09):That's the problem. This is an evolutionary phenomenon. It's a sort of biological response to the onslaught of these malignant cells that are potentially occurring every day in our normal tissue. And so, by tackling one problem, do we create another? And I think that's going to be the big challenge over the next 50 years.Eric Topol (51:31):Yeah, and I think your point about the multi-decade challenge, because if you can promote healthy aging without any risk of cancer, that would be great. But if the tradeoff is close, it's not going to be very favorable. That seems to be the main liability of modulation aging through many of the, there's many shots on goal here, of course, as you well know. But they do seem to pose that risk in general.Charles Swanton (51:58):I think that's right. I think the other thing is, I still find, I don't know if you agree with me, but it is an immense conundrum. What is the underlying molecular basis for somatic aging, for aging of normal tissues? And it may be multifactorial, it may not be just one answer to that question. And different tissues may age in different ways. I don't know. It's a fascinating area of biology, but I think it really needs to be studied more because as you say, it underpins all of these diseases we've been talking about today, cardiovascular, neurodegeneration, cancer, you name it. We absolutely have to understand this. And actually, the more I work in cancer, the more I feel like actually what I'm working on is aging.(52:48):And this is something that James DeGregori and I have discussed a lot. There's an observation that in medicine around patients with alpha-1 antitrypsin deficiency who are at higher risk of lung cancer, but they're also at high risk of COPD, and we know the associations of chronic obstructive pulmonary disease with lung cancer risk. And one of the theories that James had, and I think this is a beautiful idea, actually, is as our tissues age, and COPD is a reflection of aging, to some extent gone wrong. And as our tissues age, they become less good at controlling the expansion of these premalignant clones, harboring, harboring oncogenic mutations in normal tissue. And as those premalignant clones expand, the substrate for evolution also expands. So there's more likely to be a second and third hit genetically. So it may be by disrupting the extracellular matrices through inflammation that triggers COPD through alpha-1 antitrypsin deficiency or smoking, et cetera, you are less effectively controlling these emergent clones that just expand with age, which I think is a fascinating idea actually.Eric Topol (54:01):It really is. Well, I want to tell you, Charlie, this has been the most fascinating, exhilarating discussion I've ever had on cancer. I mean, really, I am indebted to you because not just all the work you've done, but your ability to really express it, articulate it in a way that hopefully everyone can understand who's listening or reading the transcript. So we'll keep following what you're doing because you're doing a lot of stuff. I can't thank you enough for joining me today, and you've given me lots of things to think about. I hope the people that are listening or reading feel the same way. I mean, this has been so mind bending in many respects. We're indebted to you.Charles Swanton (54:49):Well, we all love reading your Twitter feeds. Keep them coming. It helps us keep a broader view of medicine and biological research, not just cancer, which is why I love it so much.******************************************The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informativeVoluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff tor audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Local artist Peter Campbell, and his mate Barney on the bass, come into the studio and give us their take on a an 80s Country Music classic by George Strait, "Amarillo by Morning"!See omnystudio.com/listener for privacy information.

How do ChatGPT and other large language models (LLMs) work, and how might ophthalmologists harness their power for use in clinical practice? Drs. Peter Campbell and Travis Redd join host Amanda Redfern to discuss the advent of generative AI and its current and future implications for the practice of ophthalmology.  For all episodes or to claim CME credit for selected episodes, visit www.aao.org/podcasts.

FOLLOW UP: CONTINENTAL FINED $107M FOR DIESELGATEContinental, the automotive parts supplier, has been fined €100 million for its part in the dieselgate scandal. The fine was such due to the full cooperation of the company and changes they have subsequently made to their compliance structures. There are six weeks for Continental to pay the fine. Click this Reuters article for more information. STELLANTIS LASHES OUT AT EV MANDATESCarlos Tavares criticises the current UK EV mandates as “terrible”. He has met with the Transport Secretary, Mark Harper, to discuss the situation and suggest alterations that will make it more workable for the industry. We are finding out that you cannot just manufacture demand, when reviewing the monthly SMMT registration figures. You can read more, via a Peter Campbell thread here. For another article, click here to view an Autocar article. LOTUS CHIEF COMMERCIAL OFFICER IS LEAVINGMike Johnson, who is the chief commercial officer of Lotus and the public facing executive for the brand, will be leaving the company after only 18 months in role. He is said to be staying in automotive, but we will have to wait to find out where and when. If you wish to read more on this, click the Autocar article link here. RANSWOMWARE ATTACK IMPACTS STREET LIGHTSA ransomware attack on Leicester City Council has led street lights to “misbehave”. This should cause great concern as more and more systems are linked and accessible remotely. Hopefully, more important and safety critical systems are being looked at across the country so there is not a serious impact from such incidents. Click this BitDefender story link here, to read more.MERCEDES EACTROS 600 CHARGES AT 1MWMercedes-Benz are preparing for the Megawatt Charging System (MCS), that is due to be finalised in 2025, and have successfully charged an eActros 600 prototype at 1MW for the first time. Not details were given on how long the vehicle charged or even how long at 1MW. You can read more, by clicking this electrive article link here. SAMSUNG TEASES FASTER CHARGING LONG LIFE BATTERYAt the 37th Electric Vehicle Symposium & Exposition, in Seoul, Samsung revealed that they will start production of a new electric vehicle batteries that will charge to 80% in nine minutes and some will last 20 years. The plan is for production to start in 2026, but it being fitted to cars in 2029. That's all a little way off, hopefully this isn't like solid state batteries and just far enough ahead for us to forget the last date that was declared. Click this article link from The Register for more. If you like what we do, on this show, and think it is worth a £1.00, please consider supporting us via Patreon. Here is the link to that CLICK HERE TO...

2024-02-25 - Peter Campbell

17, Peter Campbell - Let Me Ride by Warm

Learn more about your ad choices. Visit megaphone.fm/adchoices

Learn more about your ad choices. Visit megaphone.fm/adchoices

Welcome to episode three of the all-new, five-part Autocar Business Power List 100 Podcast, produced in partnership with automotive experience platform Keyloop.Throughout the series, we'll be inviting industry experts to discuss the biggest names, companies and topics outlined in the Autocar Business Power List 100 – a ranking of the 100 most influential people in the automotive industry.In this episode, Mark Tisshaw, editor of Autocar, and Peter Campbell, global motor industry correspondent at the Financial Times, sit down with Jacqui Barker, global OEM director at Keyloop, to discuss Chinese car makers and the impact they're having on the global automotive scene, their industry-leading battery technology and why Chinese cars are becoming ever more desirable for European consumers. Hosted on Acast. See acast.com/privacy for more information.

Peter Campell is the Chef and Owner of Red Wagon Pizza Co. in Minneapolis. Peter started making pizzas at the age of 2 with his grandfather. He grew up working in kitchens and continued to do so through college. After a long time working with banks and in the world of real estate, he started making pizzas on Friday nights for friends and family. He started his business in 2012, doing pop ups in farmers' markets. In 2014, he opened his brick and mortal restaurant, Red Wagon Pizza Co.  Success quote/mantra:  "Don't fear failure." Today's sponsors: Owner.com, One Degree Coaching, Restaurant Systems Pro, and Tater Kegs Contact info:  Instagram: @redwagonpizza

Welcome to episode two of the all-new, five-part Autocar Business Power List 100 Podcast, produced in partnership with automotive experience platform Keyloop.Throughout the series, we'll be inviting industry experts to discuss the biggest names, companies and topics outlined in the Autocar Business Power List 100 – a ranking of the 100 most influential people in the automotive industry.In episode two, Mark Tisshaw, editor of Autocar, and Peter Campbell, global motor industry correspondent at the Financial Times, sit down with Megan Harvey, chief alliances officer at Keyloop, to discuss the top automotive disruptors – including Elon Musk and Tesla's game-changing approach to carmaking, Uber's wide-reaching mobility ambitions and whether tech giants like Google, Apple and Amazon will ever foray into automotive manufacturing. Hosted on Acast. See acast.com/privacy for more information.

Peter Campbell: Why are EV Sales Slowing Down? Learn more about your ad choices. Visit megaphone.fm/adchoices

When a group of nine people went out for a meal in Rob's Ranch House in Wexford, they got a big surprise! Restaurant owner Peter Campbell told us all about it.To hear the full chat, press the play button on this page.

Professor Lucy Blue speaks to Dr Lisa Briggs and Dr Peter Campbell from the University of Cranfield who have been searching the deep waters of the Straits of Sicily using micro-AUVs - autonomous underwater vehicles.  Deployment of these small, agile vehicles has enabled the team to map large areas of this busy maritime highway of the Mediterranean.  The team aim to locate historic remains and ancient shipwrecks, and have consulted local fisherman for potential targets as they trawl the seabed and often snag remains in their nets, even including statues.  These mini autonomous underwater vehicles (AUVs) can be deployed in multiples, thus covering large areas of the seabed.  They are relatively cheap to purchase and easier to use and programme than larger AUV's.  Fitted with cameras might they become a principal tool not only for maritime archaeology, but also other disciplines such as marine biology. Learn how these vehicles have democratised survey previously limited to researchers with much larger budgets.  

Britain's biggest steelworks is to receive 500 million pounds in government support - but at a cost of thousands of jobs. Ian King is joined on the programme by Gareth Stace, Director General of UK Steel. The Financial Times' Motor Industry Correspondent, Peter Campbell discusses the walkouts among US car makers in one of the sector's biggest pay disputes in decades. And - a takeover of Everton FC has been announced.

Drs. Michael Chiang, R. V. Paul Chan, and J. Peter Campbell, members of the Imaging and Informatics in Retinopathy of Prematurity (i-ROP) Research Consortium, discuss the latest advances in ROP screening, treatment, and management. For all episodes or to claim CME credit for selected episodes, visit www.aao.org/podcasts.

Luke Ferrari is a horseman, log home builder and rancher from Saskatchewan. Luke's horsemanship journey began when he met his long time friend and mentor, Peter Campbell. Topics discussed include developing horses, how to help others learn, and the lasting impression Peter had on Luke's life.

*This event is presented in partnership with Baylor University* About the Lecture Is American politics and foreign policy being militarized? Is the health of American civil-military relations being compromised? With former military officers occupying traditionally civilian political positions and retired officers stepping into the partisan political fray, these dangers cannot be dismissed out of hand. One danger, some argue, is an increased chance of war because the military mind is too focused on using force to solve problems. Others see the military mind as inherently parochial, always seeking more resources, prestige, and autonomy for its organization, even at the expense of sound strategy and foreign policy. To understand the full implications of increased military influence in American politics, strategy, and foreign policy, we need a more complete picture of the military mindset. Peter Campbell argues that this can be accomplished by using the theory of Military Realism to identify some of the underappreciated tendencies of the military mind. When considering the use of force, the military realist focuses on the interactive nature of violence, the ever-present frictions in war, and the uncertainty generated by the use of force for political ends. Campbell argues that President Ulysses S. Grant's approach to foreign policy was informed by a Military Realist perspective. At times, Grant's military realism and political inexperience were a liability in foreign policy. Overall, however, Grant's military realist outlook tempered calls for the use of force in foreign policy during his administration. Along the way, Campbell shows that Grant was a preeminent strategic thinker and that unique aspects of his character also shaped his leadership and foreign policy. When we appreciate the military realist perspective, we can better assess the potential implications of military influence on American politics, strategy, and foreign policy in the future. About the Speaker Dr. Peter Campbell is an Associate Professor of Political Science at Baylor University. He holds an M.A. in war studies from King's College London and a Ph.D. in political science from the University of Notre Dame. He is the author of Military Realism: The Logic and Limits of Force and Innovation in the U.S. Army (University of Missouri Press, 2019). His areas of research include national security decision-making, civil-military relations, strategy, international relations scholarship and policy relevance, insurgency and counterinsurgency, the just war tradition, and cyber warfare. Learn more about IWP graduate programs: www.iwp.edu/academic-programs/ Make a gift to IWP: interland3.donorperfect.net/weblink/Web…31090&id=18

FOLLOW UP: BRITISHVOLT BOUGHT BY RECHARGE INDUSTRIESThe troubled British battery startup has been bought by Australian firm Recharge Industries, but that means a pivot to battery storage and away from automotive - at least for the moment. Click here to read the main BBC story and click here for the thread by Peter Campbell of the Financial Times.STELLANTIS POSTS RECORD PROFITSStellantis has posted record profits while also recording a 41% rise global EV sales. Is this because of supply chain constraints forcing them to focus on building their most profitable models?Click here to read the Autocar story.CITROEN BOSS STEPS DOWNIn a surprise move, Citroen boss Vincent Cobée has left the company.Click here to read the Motor1 story.SONO STYMIES SOLAR SIONGerman solar panel startup Sono has ended its project to produce the Sion solar-augmented EV, instead it's going to focus on producing solar cells suitable for vehicles through its existing partnerships.Click here to read the Move Electric story.MOBILITY APP SHOWS CO2 COST OF BUSINESS TRAVELA new app can help calculate the total CO2 cost of employee business travel across all modes and can help benchmarking against similar organizations.Click here for the full Autocar story.ENERGY STORAGE SYSTEMS TO HELP EV MOTORWAY CHARGING National Highways is planning an £8million investment in containerized battery EV chargers for some high demand English service stations with limited electricity supply.Click here for the full Motoring Research story.More funding for Councils to expand ev chargingSome English councils have won a share of £56million to expand their local EV charging networks.Click here for the move Electric Story.Firms greenwashing their products face steep finesNew rules will prevent companies from selling their products and services on claims that may be false or impossible to prove.Click here for the Guardian article.Bentley W12 reaches the end of the line in the BaturBentley's W12 engine will bow out in 2024 in the limited-production Batur.Click here for the Autocar article.If you like what we do, on this show, and think it is worth a £1.00, please consider supporting us via Patreon. Here is the link to that

Four blocks apart in South Minneapolis, two families have developed into a culinary powerhouse. Broder's built a Little Italy at the corner of 50th & Penn beginning with a market in 1982, growing to a pasta bar and a wine bar. Now the next generation is running that business - we speak with the matriarch Molly and one of her kids, Charlie. At 54th & Penn, Peter Campbell and his wife Jackie started with a pizza oven at farmers markets, and gained a national following thanks to appearances on Guy Fieri's Diners, Drive-ins and Dives as well as Guy's Grocery Games. He talks about pizza as well as the growth in CBD-infused drinks at his restaurant.

Peter Campbell's Red Wagon Pizza has come a great distance in the last decade plus. Starting out making pizza with friends, followed by serving at farmers markets, then building a beloved Minneapolis restaurant, and now shipping nationwide on Gold Belly-- Pizza Pete has seen it all. And now his time has come to join LFE and tell Charles & Quam all about that PIZZA LYFE, in addition to discussing:

FOLLOW UP: DFT WITHDRAWS APPEAL AGAINST FOI REQUESTDr Greg Marsden has confirmed that the Department for Transport has withdrawn their appeal over the Freedom of Information requirement for the justification of the Government's plans for decarbonisation of transport. He has even been supplied with the answers to his three questions. Click here to see his Tweet about this. Now we wait on the analysis of said information. FOLLOW UP: BRITISHVOLT RESCUE PACKAGE SLASHES VALUATIONBritishvolts has entered administration, you can find out more by clicking this link to Peter Campbell's Twitter thread. Just last year Britishvolt was valued in excess of $775 million, now there are rescue packages which state the company is worth $39 million. There are, reportedly, two consortiums bidding. To read more, click this Automotive News Europe article here. For more context around battery factories and how the UK appears to be sinking behind others, click this article from The Guardian. ENVIRONMENT AUDIT COMMITTEE RECOMMEND IEA PLAN TO UKThe Environment Audit Committee, from Parliament, has recommended the UK Government implement the ideas from the International Energy Agency (IEA)'s ten-point plan to reduce oil usage. Some of the suggestions are reducing the speed limits by at least 10km/h, allowing cars to enter cities on alternate days of the week, encouraging working from home and more. Click here to read the article on Autocar. For the IEA plan, click this link here. FUEL STILL TOO EXPENSIVEWhilst the wholesale price of oil has dropped, particularly in December, the retail price has not matched the same pace. This comes as no surprise to anyone, mind you. There has been seemingly constant calls on the big retailers, including supermarkets, to drop their prices more than they have, but to no avail. Click here to learn more, from a Motoring Research article. POTHOLE DAMAGE UP 34% SINCE 2016In another piece of news that is not surprising in any shape or form, we find out that damage to cars from potholes has risen 34% since 2016. The suggestion is that due to the cold and the wet, which this winter has treated the UK to, the quality of roads will deteriorate further, meaning even more claims. Sunday was ‘National Pothole Day', as promoted by Admiral insurance. Click here for more, from Motoring Research. UNMARKED SPEED CAMERA VANS TRIALEDNorthamptonshire Police are trialling the use of unmarked speed camera vans, in an effort to see if they deter excessive speeding and phone use behind the wheel. The force are at pains to explain they do not financially gain anything, bar an admin fee, for any tickets issues. They also explain that drivers do change behaviour when they see marked...

GOVERNMENT BUDGET STATEMENTThe Chancellor of the Exchequer announced that electric vehicles will, from 2025, be required to pay Vehicle Excise Duty (VED) for the first time. This will be £20 in the first year, if brand new, then rising to £165 per year after that. The extra charge for cars over £40,000 will also come into force at the same time. Fleets will also be impacted, not just via the introduction of VED but at the Benefit in Kind rate is changing. They will rise 1% from 2025 to 2028. Added to this, there are changes to National Insurance contributions, charging costs and workplace charging point installations. These are all protected to some degree, but home charging will not be as the Government is reducing the help it gives households, from April next year. To read more, click this Autocar article. For more context, click the Autocar article from Alex Grant here. THIERRY BOLLORÉ TO LEAVE JLRThierry Bolloré has announced that he will be leaving Jaguar Land Rover, after only a couple of years in charge, due to “personal reasons”. The news is on the back of another round of losses, albeit much less than previous results. To read more, click this link from EVO. For some context around his departure, click this Autocar link to read what Steve Cropley has to say. And, if you fancy it, you can find more context with Peter Campbell and his tweet here. MAZDA EXITING RUSSIAN MARKETMazda has sold their part of the joint-venture operations to Soller, for €1, with a three year buy-back clause in place. They are the latest manufacturer to make such a move. Click this MSN article link, to learn more. DfT ORDERED TO RELEASE FORECAST BEHIND NET ZERO PROJECTIONSThe Information Commissioner has ordered the Department for Transport to release traffic level forecasts, which are behind the Net Zero projections. Professor Greg Marsden of Leeds University, submitted the Freedom of Information request as he states transport professionals and the public need to know what choices are behind the scale of change required to meet targets. Click here to read the TransportXtra article, for more on the story.If you like what we do, on this show, and think it is worth a £1.00, please consider supporting us via Patreon. Here is the link to that CLICK HERE TO SUPPORT THE PODCASTWRC: DRIVER MUSICAL CHAIRSNow is the brief window between a season ending and the next starting in Monte Carlo, early next year, for WRC. That means it is silly season, where there is a scramble for drivers and teams to get seats filled. The not so unexpected news came from M-Sport, announcing that they'd parted ways with Craig Breen.

FOLLOW UP: MORE BAD NEWS FROM ARRIVALArrival announced that it has a cash problem, as in not enough to get it through to the end of next year. They are looking at cutting more costs, which is rumoured to include large layoffs in the UK as it focuses the operation in the US. To read more, click this article here from Yahoo Finance.FOLLOW UP: PORSCHE CLASS ACTION SETTLED IN USIn diesel gate news we find that a US judge has approved a settlement of $80 to $85 million for the class action brought against Porsche over emission tampering and misleading fuel economy information. Porsche also have to pay $25 million legal fees. There is also an extra $250 per vehicle that has Sport+ fitted. Further information can be found by clicking this Automotive News article link. EURO 7 ENGINE RULES ANNOUNCEDIf both manufacturers and environmental groups are both unhappy with the new regulations for Euro 7 internal combustion regulations, does that mean they are pretty close to being right? Manufacturers are shouting it is too tough and the environmental groups are screaming it is too weak. Click here to read the Autocar Business article about the proposals. For some more context, on one of the trickier parts, is a thread from Julian Rendell discussing the constant monitoring tech that does not exist, which you can read by clicking here. More context can be found in this excellent article from Emission Analytics, who talk about the balance the regulations have hit. Click here to read that. JLR REDUCES LOSSES IN LAST QUARTERThanks to the new Range Rover and Range Rover Sport, Jaguar Land Rover reduced their losses to £175 million, when £302 million the previous year. Sales were up to £5.3 billion, a jump of 36% on the three months previous and 20% on the same period last year. To read more about this click the BusinessLive article here. For some extra context, click the Tweet from Peter Campbell. CONTINENTAL DATA STOLEN IN HACKContinental, the Tier 1 supplier to much of the automotive and mobility industry, has been hacked by the group called LockBit. The group claims to be selling 40 terabytes of the company's data to anyone willing to stump up $50 million. Continental stated it was hit in August this year but it had “averted” the attack, yet also confirmed to Handelsblatt business newspaper that data had been stolen. Not a great look when you desperately need to get your customers to trust you and your systems. This is potentially very bad for a wide range of mobility and automotive related areas due to Continental having a lot of fingers in a lot of pies. To read more about the incident,

As Naomh Conaill make their Ulster senior club championship entrance this weekend, Conor Breslin is joined by Peter Campbell and Michael McMullan (Gaelic Life) to look ahead to Sunday's clash with Antrim champions Cargin in Belfast.

FOLLOW UP: BRITISHVOLT TEMPORARY REPRIEVEBefore we had even published last week's show the news about Britishvolt had changed from receivership to saved. More details are now available, as Glencore have given the company a five week lifeline. Britishvolt has again asked the UK Government for an early release of £30 million in funding. To learn more about what has happened, click this Move Electric link here. Peter Campbell has produced a Twitter thread with more context and information, click here to read. The Guardian has an article asking if the Government is doing enough for the car industry, click here to read that. FOLLOW UP: ARRIVAL IN TROUBLEArrival, the EV light goods vehicle company, appears to be in more trouble than some thought. There has been a fire in one of their vans, there are reports of low moral and a company wide email from the CEO expressing his anger at leaks to the Financial Times. On top of that, some really silly management decisions such as thinking of opening an office in Mauritius and trying to develop an electric jet plane. For more click another Peter Campbell Twitter thread here. GHOSN'S RESCUE TEAM SENT BACK TO USThe father and son team who helped Carlos Ghosn escape from Japan have now been sent back to the US, where they will serve the remainder of their sentence. To read more, click this Bloomberg link here. NEW CAR REGISTRATION FIGURES OCTOBER 2022The SMMT has released data on the New Car Registration figures for October 2022. They have risen 26.4% over 2021, but that was an appalling month. Battery electric vehicles were a big portion of the spike. Added to which the just announced canned Fiesta finally makes it back in the Top 10 Most Registered vehicles for the month, at No.1, pipping the Nissan CashCow by two! To read more about this, click here for the SMMT article link. ASTON MARTIN DOWNGRADES OUTLOOK FOR 2022CEO Amedeo Felisa has stated that supply issues and logistics are at the core of their problems that have led to them cutting back on forecasts for margins and deliveries in 2022. However, he went onto say that the steps being taken mean 2023 onwards will be much better. Share prices dropped on this news. Click here for the BusinessDay article to learn more. BENTLEY DOUBLES PROFITS IN FIRST QUARTERBentley has announced that it increased profits in the first quarter, thanks to sales improving in the US, Europe and the UK. These more than offset the drop in China, Middle East and Africa. New model derivatives and personalisation are the reasons why, according to the company. Learn more by clicking this BusinessLive link here. SAUDI...

FOLLOW UP: BRITISHVOLT IN RISK OF RECEIVERSHIPThings are moving quickly at Britishvolt. A week or so ago we were talking about them seeking funding, as of Monday's news, they could well have been in receivership by the time you listen to this episode. They had sought to draw some of their funding from the Government early but have been rebuffed as they decide not to risk more public money. However, it appears they do have some short and medium term funding secured, but we don't know from where. To get an idea of what has gone spactacularly wrong, click this Twitter thread link from Peter Campbell. To learn how they have found some funding click this BBC News article link. EU BANS NEW ICE CARS FROM 2035The 27 countries of the EU have agreed to ban all new internal combustion engined cars, powered by fossil fuels, from 2035. There is also an increase in the reduction of CO2 emissions from 2030, up to 55% reduction on 2021 engines, where previously it was 37.5%. There are some exemptions though, for smaller production numbers. Those registering between 1,000 and 10,000 will be exempt until the end of 2035, whilst those registering less than 1,000 cars do not need to comply. Autocar has more information, which you can get to via their link here. FORD AND MERCEDES THE LATEST TO LEAVE RUSSIABoth Ford and Mercedes have sold their Russian facilities to in-country partners as there is no end in sight to the current geo-political instability, thanks to the invasion of Ukraine. Ford have paid a “nominal” fee and have a nice year buy-back clause agreed. We know very little of the details of Mercedes's deal. Click here to access the Reuters article about the Ford story. For more on the Mercedes news, click this Reuters link. FORD AND VW PULLING THE PLUG ON ARGO AIArgo AI is an autonomous vehicle technology company founded in 2017. Ford and Volkswagen were their major investors but are now pulling their funding meaning that the company is closing. Argo AI were the only AV company who produced a safety case for their work, unlike all others in the industry. However, statements by Ford CEO has made it clear this would never succeed as board members still have no real understanding of what is and is not autonomous and automated tech. You can find out more by clicking this TechCrunch article link. GEORGE HOLTZ QUITTING COMMA AIGeorge Holtz, who rose to fame claiming he could write autonomous vehicle software until the US Government told him to stop experimenting on public roads, is leaving his company Comma AI. Recently he pivoted the business to target driver assistance technology and started to call those still attempting to create AVs as con artists. He stated that he is not the right person to now lead the company as it needs to be led, to ensure it is successful. More can be learnt about this, by clicking this The Verge link here.TESLA FACING CRIMINAL PROBE OVER SELF-DRIVING...

What is the effect of laser prophylaxis in patients with Stickler Syndrome, and just how effective are buckles in patients with GRT detachments? Yoshi Yonekawa, MD, PhD, is joined by Peter Campbell, MD; Karen Jeng-Miller, MD; and Prethy Rao, MD, to review two recent contributions to the literature, during which they probe the papers' findings and explore their limitations.

Peter Campbell has been a force in the Minneapolis food community for several years. When he opened Red Wagon Pizzeria in SW Minneapolis, he immediately tackled the issue of sourcing heritage grains for his dough. The result has been nothing less than spectacular. Combining that artisan dough with creative toppings has put Red Wagon in a class by itself.

What changed in the most recent iteration of the International Classification of Retinopathy of Prematurity? And what do new data tell us about how ROP patients fare in adulthood? To find out, Yoshi Yonekawa, MD, PhD, is joined by Peter Campbell, MD; Karen Jeng-Miller, MD; and Prethy Rao, MD, to break down the latest literature, examine the papers' limitations, and offer pearls for surgical management of adults with history of ROP. 

Paddy McGill brought the tent and sleeping bag with him for the weekend's club championship games. Top analysis from all four quarter-finals as well as reaction from Brian McCabe and Peter Campbell to Sunday night's semi-final draw...

Conor Breslin is your host this week - and the chat centres on Thursday's reports that Malachy O'Rourke is out of the running to be the next Donegal manager. Peter Campbell and Ryan Ferry reflect on that - along with a lookahead to Sunday's decisive round four senior club championship games as the scramble for quarter-final places reaches a climax.

We are two weeks into the 2022 Donegal Senior Club Football Championship, which has still to catch fire. This week's host Ciaran Cannon is joined by Peter Campbell and Danny O'Donnell to assess the team prospects ahead of this weekend's round 3 games - as well as examining whether any 'new blood' have put their hands up for county consideration when the eventual new Donegal bainisteoir starts his job...

A bonus episode featuring my highlights and personal analysis of Elon Musk's keynote appearance at FT Live in London. Musk appeared via video link with fellow Tesla co-founder, and former Chief Technical Officer,  JB Straubel on stage. They spoke about the history of the company before Elon answered questions from Peter Campbell, Global Motor Industry Correspondent. 

Sunday was a good day for Donegal in Clones - with both the men and women's gaelic footballers securing Ulster final places. Paddy McGill looks back on an entertaining men's semi-final in the company of Ryan McHugh, Derry's Conleith Gilligan, Tyrone's Kyle Coney, along with journalists Peter Campbell and Jason Byrne.

Conor Breslin chats to former Donegal 1992 All-Ireland winner Joyce McMullin, and journalist Peter Campbell about how one win has apparently transformed expectations in the county. There's a look-ahead to the Cavan semi-final - and there may a few words too about a certain 30-year reunion at the Armagh game....

Interview with J. Peter Campbell, MD, author of Cost-effectiveness of Artificial Intelligence–Based Retinopathy of Prematurity Screening. Hosted by Neil Bressler, MD.

Interview with J. Peter Campbell, MD, author of Cost-effectiveness of Artificial Intelligence–Based Retinopathy of Prematurity Screening.  Hosted by Neil Bressler, MD.

Glenavon captain James Singleton is my latest guest on the podcast. We discuss the Lurgan Blues season so far, how starlets Peter Campbell and Matthew Fitzpatrick are pulling up trees and chat about life at Mourenview Park. James is a massive Chelsea fan so we discuss the influence of players such as Ashley Cole and Frank Lampard have had on his own career. James was part of two Irish Cup winning sides and we chat about those memories and working with current manager Gary Hamilton. We finish up by discuss former and current team mates, karaoke singing with Sean Ward and battles with Gavin Whyte.

The battle of the Egadi Islands - or the Aegates - is one of the most significant naval battles of the ancient world. On 10 March 241 BC the mighty naval powers of Rome and Carthage met off the coast of Sicily. The Carthaginian fleet was ambushed by the Romans in a well-planned and brilliantly executed trap leading to a decisive Roman victory. This was the battle that ended the mighty First Punic War which had dominated both Roman and Carthaginian history for two generations; it marked a turning point in the histories of both empires; it was the moment that marked Rome as having the potential to be far more than a local power in the Mediterranean; and it is the ONLY naval battle that archaeologists have managed to identify. The finds raised from the seabed across this enormous battle site are unique and astonishing. To find out more Dr Sam Willis speaks with Peter Campbell, an archaeologist who has been involved in the project to survey and excavate the battle site for many years. See acast.com/privacy for privacy and opt-out information.

Paddy McGill digests Donegal's dramatic 2-10 to 0-12 victory over All-Ireland champions Tyrone in Division 1 of the Allianz Football League on Saturday night in the company of Mark McHugh and Peter Campbell - with postmatch contributions from manager Declan Bonner and Ciaran Thompson.

Today we Explore BioSpiritual Focusing.  The founders of Biospiritual Focusing are Peter Campbell and Edwin McMahon. These men had been trained in the spiritual tradition of Saint Ignatius of Loyola, founder of the Jesuits.  With this common background they could appreciate the evolutionary spirituality of the two Jesuits, French Theologian Pierre Teilhard de Chardin and German Karl Rahner, considered to be one of the most influential theologians of the 20th century.  Focusing, in itself, is inherently a body practice and this was not lost on the men who started BioSpiritual Focusing. It is the human body which provides our most grounded spiritual link, both to the details of daily living as well as the mystery of an evolving universe.  Our body, which we so identify with mortality, is itself our conscious bridge into immortality! It is our precious “link” to the universe as a whole–and beyond!

Today we Explore BioSpiritual Focusing.  The founders of Biospiritual Focusing are Peter Campbell and Edwin McMahon. These men had been trained in the spiritual tradition of Saint Ignatius of Loyola, founder of the Jesuits.  With this common background they could appreciate the evolutionary spirituality of the two Jesuits, French Theologian Pierre Teilhard de Chardin and German Karl Rahner, considered to be one of the most influential theologians of the 20th century.  Focusing, in itself, is inherently a body practice and this was not lost on the men who started BioSpiritual Focusing.   It is the human body which provides our most grounded spiritual link, both to the details of daily living as well as the mystery of an evolving universe.  Our body, which we so identify with mortality, is itself our conscious bridge into immortality! It is our precious “link” to the universe as a whole–and beyond!

Nothing illustrates the conditions at Markievicz Park on the opening Sunday of the league than the TG4 camera shot.. Paddy McGill squelched his way through Sunday's 0-11 to 0-11 draw between Mayo and Donegal, in the company of TJ Kilgallon, Eamonn O'Hara, Michael Murphy, Peter Campbell and Mike Finnerty.

About the lecture: As a general, Ulysses S. Grant was often dismissed as a butcher of men and no strategist. This reputation is undeserved, however. Ulysses S. Grant's memoir of the Civil War is a treasure trove of insights for the strategist. In its pages, Grant invites his reader to contemplate with him the constant struggle to reconcile military means with political ends, the way military maxims crumble under the weight of the reality of war, and, most importantly, the vital role that character and personality play in the design and execution of military operations and strategy. About the speaker: Peter Campbell is Associate Professor of Political Science at Baylor University. He holds an MA in War Studies from King's College London and a Ph.D. in political science from the University of Notre Dame. He is the author of Military Realism: The Logic and Limits of Force and Innovation in the U.S. Army (University of Missouri Press, 2019). His areas of research include national security decision making, civil-military relations, strategy, international relations scholarship and policy relevance, insurgency and counterinsurgency, the just war tradition, and cyber warfare.

Peter campbell was bron in Tipperary in 1780 and is credited as the founder of the Uraguayan Navy

Peter Campbell, chef and owner of Red Wagon Pizza Company stops by to talk about how he got into the restaurant business, his philosophy on what his actual product is, and what running a restaurant during a pandemic is like. Really cool conversation about a food everyone loves. Supported by Manscaped (https://www.manscaped.com/) Use Promo Code “MSFU” for 20% off and FREE shipping!