The measures of inequality, the genie coefficient for economists in many U.S. cities is much worse than it is in developing nations overseas. Los Angeles, Miami, other cities have higher measured inequality than places like Costa Rica or Zimbabwe. So there's terrible inequality and it continues within cities. There's also inequality between cities. And economists thought both of these things would be competed away by the market, that within the city skills would equalize and incomes would come down, and between cities expensive places would be too expensive and capital and labor would move. But they haven't. That hasn't happened. Neither of those inequalities has diminished significantly. I'm Rick McGayhee. I'm an economist at the New School. I used to work here at INET. I have a lot of public policy experience working as Senator Kennedy's economic advisor and also time at Foundations at the Ford Foundation on Urban Economic Development. My book is Unequal Cities, published by Columbia University Press in January of 2023. America is an urban economy. As most modern economies are, 90 percent of our GDP comes from metropolitan areas. So you would think, well, that's great. We must honor. We must take care of cities. We must promote them. But the history of the United States and contemporary practice is, in fact, to treat cities badly, to underfund their needs, to strip their political power, and to make them unequal. This is deeply rooted in American history. It goes all the way back to the revolution and the Constitution, and has not—it's changed, but I would say cities are still at a significant disadvantage from where they should be economically. So the book has three case studies, New York, Detroit, and Los Angeles. Those are all cities that tried pretty much on their own to fight inequality, to institute social policies and housing, employment, economic civil rights. And by and large, I'm sad to say they all largely failed because they faced several structural challenges. One is the hostility of the federal government to cities. Second, and a bit of a surprise to me when I was writing the book, is how hostile state governments are to the cities, and the power of the states in our political economy really disadvantages these three areas. The third major factor is structural racism, that the concentration of non-whites, especially blacks, in the core cities in the metropolitan region from housing segregation and economic discrimination, really gave the cities most of the region's problems and much less of the resources they need to combat them. This goes way, way back. Thomas Jefferson said cities are a pestilence on the body politic. I'm paraphrasing this one, but when Yellow Fever epidemic hit, he said, well, it may be—it'll have some benefits.  Now, you might think, OK, this is an 18th century slaveholder, and you would expect those views, but it's pretty built into our system, this hostility. States start with the electoral college. Rural states have much more power to elect people. The U.S. Senate, I think a person from Wyoming has something like 70 or 80 times the representation that a citizen of California has. Each state has two senators. And then within states, states have the ability to set voting rights, to set their legislative districts or gerrymander them, as they often do. And the combination of those factors, both federal and state, puts cities at a real disadvantage. It's heightened in America in a lot of ways. If you look at London, for example, people think, well, there's something natural about the formation of the cities we have. The New York economy has over 750 municipal governments in it, three state governments, a bunch of regional boards, water boards, planting boards. You could say, well, it's just so big it had to sprawl out that way. But the city of London, Westminster, the little pocket aside, is run by one mayor. Now they delegate authority to the regional areas. And then think in square miles, it's about the same size as New York's smaller population. So it's not anything that's natural or just occurs because of the way the economy works. It's driven by policy. So economists, mainstream economics has a very partial view of cities, but it's improved some in recent years. It used to be that it was just models of household choice. How do people decide where to live and trade off commuting versus work costs? That's a truism, but not really the driver. The revival of mainstream urban economics really came by paying attention to cities as hubs of innovation and hubs of growth. Ed Glazer at Harvard is a big proponent of this work and has done a lot of good empirical work on it. The theoretical work is problematic in my view. It actually draws on Jane Jacobs, the famous urbanist, who was a big believer in cities as innovators. And that's been the real energy that's come into mainstream urban economics in the last couple of decades. Cities as innovators bringing together innovative forces and those innovations in term drive economic growth for the whole economy. So what to do about this problem? And I am somewhat skeptical about our ability within the current political structure to solve this city problem. I was inspired by looking at some geographers who did a study of what economists call commuting zones and just what are the mapped patterns of where people go to work and where they live. And they were able to map almost 90 plus percentage of commuting trips in the lower 48 states to about 50 pockets all centered on metropolitan areas. And I look at that map, I thought, well, what if those were the states instead of the states we have? They would be centered on cities. Some would still be Republican or more conservative but probably not as strongly as the states that we have. And so I thought, well, let's return to city states. Let's just get rid of the states in the United States, make the political map look a lot more like the economic map so we can align those interests and cities wouldn't be harmed so much. It's a thought experiment. It makes you think about why the political arrangements that we do have are so disadvantageous to cities, which are the things that give us prosperity. So there's two types of inequality that I look at in the book. One is within the cities that the cities are very unequal places. The measures of inequality, the genie coefficient for economists in many new US cities is much worse than it is in developing nations overseas. Los Angeles, Miami, other cities have higher measured inequality than places like Costa Rica or Zimbabwe. So there's terrible inequality and it continues within cities. There's also inequality between cities. And economists thought both of these things would be competed away by the market, that within the city skills would equalize and incomes would come down. And between cities, expensive places would be too expensive and capital and labor would move. But they haven't. That hasn't happened. Neither of those inequalities has diminished significantly. And a lot of that's due to the policy structure that we have. The, again, states are empowered over cities. Cities are creatures of states legally, not the federal government. They, and cities can't do anything if their states won't let them. And so to the extent that you have a non-progressive state, which is a lot of them, they block cities from doing anything. One quick example, state of Missouri has two big cities, Kansas City and St. Louis. Both cities passed a city-wide minimum wage increase, not a statewide but a city-wide. The Missouri state legislature overturned both those laws and then passed a law saying that neither city could enact a minimum wage increase on its own. It had to have state approval. This is because cities are legally creatures of states in America. So another great example of the difference between politics and economics in states and cities, the Texas Triangle. So at the top, it's Dallas-Fort Worth, San Antonio, Austin and Houston. That triangle is about 75% of Texas GDP. It's not cows and oil. It's those cities driving the economy, about 65% of the state's population. Yet they are totally disempowered in terms of state politics. If you look at Texas, what it passes, it's not anything that those cities support. And that's because the state has gerrymandered heavily and unequally and controlled. This summer during the heat wave, the state legislature passed a law forbidding those cities to mandate heat breaks for workers when the temperature was routinely over 110 degrees. Because the cities wanted to pass those laws and the states were able to prevent, Texas was able to prevent them from doing that because, again, cities are creatures of states in America. Most of the working from home, it's not people moving from one metro to another. Most of the moves working from home are within the same metropolitan area, but people not commuting into the central business district. Let's take New York for an example. The reduction of trips into the central business district has hurt cities' tax revenue, has hurt the low-income workers, food service, janitorial services, office cleaning, security guards that depended on a vigorous central business district for their jobs. So that the suburban workers who already disproportionately benefit from the urban economic effects created in a metropolitan area but live in exclusive suburbs where non-whites aren't allowed to live and there's no multi-family housing, by staying home or expanding out a little bit further into their metro have made it even harder in the short run for New York and cities like it to deal with inequality. So I was surprised when I was writing the book. I knew the federal government was bad on cities because of the support to states. What really surprised me was how hostile historically states have been to cities and how I think that continues in most or many American states. The power of state governments to control cities entirely, this was a legal battle that was fought out in the late 19th century, oddly over railroad financing, but states won and the prevailing rule now is that states can block cities from doing almost anything and they often do. At the same time, those cities and metropolitan structures within those states, I gave an example of Texas earlier, think about New York. The New York metro area is by far the largest contributor of revenue to New York state but yet the state controls a large number of things that the city has allowed to do and constrains it in policy terms. So the cities, you also see this between states that more metropolitan states send revenue through the federal government to more red rural Republican states. They benefit greatly from the economic prowess of cities but the fiscal and tax returns aren't nearly equivalent. Of my three cities, Los Angeles I think has done the most consciously around cities. After the Rodney King riots where a black motorist was beaten almost to death by the Los Angeles police department, a group of people got together and tried to bring together different, call them progressive, but different groups in the population who hadn't worked well together and those were labor unions and some economic developers and the second is communities of color who wanted jobs but had been excluded by unions and also by traditional economic development. And the third were environmentalists who often or sometimes take anti-development position and by harnessing those three groups together through a process of intense organizing and constant meeting and constant talking to each other. This isn't a magic thing where suddenly everybody gets enlightened. You have to work out those interests but they did that. My best example of how they were successful in 2008 in the middle of the global recession depression, Los Angeles passed a tax increase, a sales tax increase on the ballot to build the metro system and in California it takes a two-thirds vote to pass a tax increase as a legacy of Proposition 13 and they did it. They got a two-thirds vote in the middle of one of the worst recessions we've had since the depression and they did that because the metro appealed to the environmentalists for those reasons. They had a vigorous jobs program for people of color, particularly young men, to get into unionized construction jobs and it created unionized construction jobs and new opportunities for economic development. So that triangle of forces I think is the best hope I've seen for cities to move forward in a progressive way. Even, this is a controversial thing for some progresses, but even market rate or luxury housing helps everybody and we have a lot of good empirical evidence now. One of the good things about the new twist in mainstream economics is they do a lot of good empirical work. The theoretical stuff is you don't need to look at the empirics and there's very good empirical work that shows that housing supply lowers rents and lowers prices and doesn't lead to the displacement and gentrification of people legitimately fear, but you just can't find it statistically. I'd make those housing jobs unionized if I could and also make sure that the communities of color got their share of that work and it would have mandatory affordable housing in it, but housing would be where I'd start. One thing that's important to always remember, and this is true of lots of issues in the United States, is that you can't understand what's happened to cities and what's happening to them without thinking about structural racism. It permeates really everything about the city experience. So in the post-World War II period when these mostly white suburbs grew, they grew with federal support in transportation and mortgage lending. At the same time that blacks were legally barred from owning houses and buying them, Levittown, the famous suburban Long Island outside of New York, had explicit clauses in contracts saying that houses could not be sold or resold to someone who wasn't white. And you see those all across the country. I grew up in Kansas City and the main developer there, J.C. Nichols, was a pioneer of these racial covenants. So it really shaped the political form that as the suburbs are politically independent from the city and the city can't get the tax revenue. It also blocked city residents, particularly black and poor residents, from moving to places with higher tax bases and better schools and perpetuates this inequality. So there are a lot of factors that go into this, but it's I think very important to understand how racism is an integral part of it and remains part of it now. I've always been interested in cities and I'm an economist and I read a lot of urban economics and it wasn't satisfying to me, but it goes back for that. I grew up in an all-white suburb of Kansas City and cared a lot about civil rights, but there was nothing happening in the civil rights movement when I was growing up. And I've always wondered why things were so unequal and so both economically and racially unequal. When I was in high school when Martin Luther King was assassinated, there were violent disturbances in downtown Kansas City. Three miles from my high school, I was in a high school of 2,100 people that had two people of color, exchange students from abroad. And that level of segregation and inequality has just always, I've never understood it really. And so I think the book is an attempt many years later to try and really understand it, but also understand the economics of it.


I have something to confess. We have worked hard on this session to have five countries represented on this session, included all three South Caucasian states. But for various reasons, it was not, unfortunately, possible. But we have two best speakers with us. Our now very good friend, Roman Vasilenko, he was with us last year. And our new guest, Vahan Kostanian, Deputy Minister of Foreign Affairs of Armenia. And you know, Mr. Kostanian, last year, after our session, the first question coming from our audience was about Nagorno-Pakarabakh. But unfortunately, we did answer it as we could. But this year, we have a real opportunity to know more about the situation today and the perspective from the first hand. But I would like to start with the question about what we have just heard by the Minister of Foreign Affairs, Mitra Kuleba. I would have your reaction to what Minister Kuleba said. How do we see the current situation in Ukraine, on the ground, the current and common risks? What if the West no longer has the will to support Ukraine because of Ukraine fatigue and the multiplication of tensions inside conflict and wars outside included Middle East? What can be the end of the war in Ukraine and what if Ukraine lose the war? The question is not the taboo now. What consequences, what impact on your country, on your region and on global balance? We will start with Mr. Vasilian Kadeyputi, Minister of Foreign Affairs of Kazakhstan. Thank you very much. Is it working? No. Not sure? No. It is working now. Yes. Thank you very much, and I'm delighted to be here again. Thank you for inviting us. Well, I had a friend for many years, a journalist, and he told me to never answer a question that begins with, what if? Because, I mean, speculating is an ungratifying kind of job. But what I would like to say is that, of course, it is an extremely sorrow and painful thing to watch and to feel in your heart. It's a tragedy that is taking place, that continues to take place for more than a year and a half now. We, as Kazakhstan, a peace-loving country, a country that doesn't have problematic relations with any country, we naturally want the solution as soon as possible. We are prepared to help to serve as a negotiating platform if Russia and Ukraine would want our services. We maintain relations with both Russia and Ukraine, so we keep the bridges open, keep the doors open. We think the solution can be only found on the basis of the United Nations charter and the respect for the fundamental principles of this charter, including the respect for the territorial integrity and sovereignty of states, including, in this case, Ukraine. Yes, thank you very much. Thank you. I believe, first, we should understand what happened and when it started. The very principle of use of force was violated. And it was not violated first time back in February 2021. The international community, we, the South Caucasus, witnessed the violation of this very principle, yet a year ago before the war in Ukraine started in 2020 in our region in Nagorno-Karabakh. And unfortunately, back to that time, many of the international partners were silent and they were both sided, let's say, when it came to the situation and not putting clear and direct calls that the use of force is not acceptable. And this became a precedent. And if something can be tolerated in case of one country, probably the others can think or interpret the situation as a green light for them to act in violation of UN Charter as well. Nobody knows better the horror of the war than us who we witnessed it in back in the 90s. We witnessed it in 2020. We are still witnessing the consequences of it, of the recent military aggression of September 19, 2020, at the result of which Nagorno-Karabakh and 100,000 people were forced to the place and basically Nagorno-Karabakh is ethnically cleansed. But we do believe that at some point the word order should be established in a way that the principles can be equally projected to everyone and everyone should adhere to these principles. And violation of principle without any geopolitical calculations should be equally raised and should be equally rejected by international community. OK. Thank you.


Welcome to Kent. They say the fallen whirlwind was worse than the collapse. How many more do I need? Just four. Wow, this has been a farm. Well, grinds aren't really farming much, because I ain't getting much. This game's going to go bad already. I can just feel it. I can just feel it. Getting them mooch, my mother, my motherfuckers. Getting them mooch, my mother, my mother, my motherfuckers. People really need to use the minimap. Just use the minimap. You'll see all those moots around you. I don't know if you're in. OK, you got this. That's me full. Oh, dear. Oh, my Rambo.  I see you, boy. Well, have you just hit me with this? It was hard. That's what you do, you just run away. Run away. You're not exactly playing it safe, aren't you?  I'm dead. I'm so dead.  Oh, I'm a fail.  Oh, my days.   Well, this is a loss. My days, we're just getting battered. You've got 15 moats, mate. It's gone bank, and why are you still trying to collect them? This is the teammates I get the worst, my PVP teammates.  Moats, they're so lagging.  You can come back. This is going to be the ultimate combat. This is going to be the ultimate combat. Oh, OK, maybe not. Well, I can't do anything, can I? What can you do? What can you do there, people? There's not much you can do. We're so done. This makes you feel like you don't want to play. I'm telling you. Oh, man. I'm this far too long.  Let's go back over. Just trying to slow him down. That's the goal here, slow him down.  Oh, I'm so dead. Oh, no. He's bad. Oh, he's so bad. Oh, yeah, I will use my super because I don't need it. Who are you trying to chase as well?  Sit down. We got these lads. We have got these lads. Nobody can't hear me. So little gambits, just bad gambit. We got this. We got this. Oh, my teammates. Whoa, I'm going back, people. Wow. I need to kind of get a kill, to be honest. Slow him down a bit.  I'm done. I ain't doing nothing here.  Just might be wasted a super. That's good. You ain't using that on the bus, and that's good. That's good. I'm just going to evade. I'm just going to evade. Slow him down, make them waste their supers. Done too so far, people. Too so far. It's going to be the greatest comeback in the history of anything. Oh, yeah. That's what I like. This is what I like. Oh, yeah. OK, sneaky. I'm about to get nothing here. I'm about to get nothing here.  Oh, I failed it. I ruined it. I messed it up. I messed it up. That could have been the best comeback ever. Moist George and moist old. Oh, we've got a prime. We've got a prime evil.  Yo, I'm going back. We've got these people. We've got these people. I need to get kills here. I need to get kills. Bitch, sit down. Look at this. Oh.  I can't see him.  Come on. Anybody else? Four seconds, three seconds, two. We've got this stuff. We've got this. Keep shooting. Keep shooting. Wow. Oh, why couldn't that have been a bottom dollar? That would have been ultimate. That would have been the best. Wow. What a comeback. I know I'll come back because I lost 15 moats. I killed seven guardians. That's what it was all about. Wow. All my days.


Hi. So I'm a postdoc in the Redslap at the Sloan Kettering Institute, and I will be showing you some really cool results of our analysis on the TCGA data, where we're trying to take a pan-canned view on alternative splicing. So let me give you a little bit of a motivation here. So this is a figure from a paper, a nature review paper from 2012, and it shows you how, if you have alternative splicing, you can have a few genes where you have alternative three prime ends, exon-skips, which may change certain domains in the gene and can in fact change the function of the gene. You can switch from having pro-apoptotic to anti-apoptotic functions, and you can also change function from being angiogenic to anti-angiogenic. So there's a certain motivation to look into these things as potential targets for cancer treatment. So we set out, therefore, with the following gods. So we want to identify cancer-specific splicing patterns based on the TCGA RNA-seq data. So we're also interested in identifying variants regulating splicing in the same genes. So trying to find cis-associations, essentially, and then also trying to find variants regulating splicing in other cancer genes. And so the TCGA data is particularly suited because it has RNA-seq data and the matching exome data. For the RNA-seq, we will find and quantify the splicing events, and the exome data does in fact cover enough of the flanking regions into the introns to actually have variant codes there and try to find cis-associations. However, there's one problem with this. Unfortunately, the TCGA data has not been uniformly processed, and so we set out to do the following, and this was quite a major effort on our side. We have basically gone back, re-analyzed all of the raw sequencing data. We have gone, taken all the exome data and the RNA-seq data and designed our own pipeline to remap everything and do a joint variant calling using the Unified Genotyper, but also trying to find somatic variants using Mutec. And then we have done a splicing quantification using Splatter. It's a tool developed in the Ratch Lab to actually find alternative splicing events and add towards the annotations of the already known existing splice events. So let me walk you through our approach of finding new splicing events. So we basically start off with building a splice graph from the known splice annotations, and then using the RNA-seq data, we're trying to find new splice junctions if you have support for new events. We will then count the amount of reads supporting, and this is an example of an axon skip, so in this case, we will try to find the reads supporting this alternative axon and then basically normalize it across the reads covering the whole region, and this gives us something we call a splicing index or the percent spliced in. And so here you can see an overview of our efforts. On the very left you can see that these are already annotated splice events broken down to the different types. Here is what we have filtered down to, this is actually a very stringent filter towards a set of events where we have high confidence and based on the data we have seen, and this is what we have generated using splatter, again filtered with the same thresholds, adding a lot of new splicing events towards already existing annotation. And so in order to find cancer-specific splicing events, you can see here a little bit of a map where we have broken down the splicing events into specific tumor types and sorted them. So each color here represents a little bit of the fraction of samples which support a specific axon skip, and on the left you can see a comparison to whether we see that particular event in the encode data or in the amount of normal RNA-seq data available from the TCGA. Unfortunately, there is not much of the match normals available, so you have to take this with a sort of grain, but you can definitely see a bunch of cancer-specific, in some cases possibly tissue-specific events of alternative splicing. So basically, this gets us to our first goal. So we basically have gone and analyzed the RNA-seq splicing events. We detected new splicing events that occur frequently in specific cancer type. Of course, we still need some more independent validation, but they are very interesting cases which may be suited as potential targets for treatment. So let me go to the next goal, which is trying to take a statistical genetics view on finding variants associated with alternative splicing. Here you can see on the left what people have done so far in the statistical genetics field and doing QTL analysis on next-generation sequencing data, with GEOVAD as being one of the most recent one. But if you're looking on the right, different colors represent the heterogeneity in the cancer, the different cancer types, but you have quite a large data set available already to do this type of analysis. So it is perfectly suited to understand tissue and cancer-specific specificity of splicing as well as finding cancer association, which has been very limitedly possible due to the lack of power in previous projects. However, there's a problem if you're doing this on this type of data. Of course, it's noisier, you have heterogeneity, you have purity of the samples, and the many rare events due to the somatic mutations definitely cause a problem. I won't be talking much about rare variant analysis. We have done this as well. Come talk to me if you're interested in this. But I want to focus here more on the common variant analysis, where we're basically taking the typical linear regression approach, but we are going a step further and doing something which is called a linear mixed model. So you're basically just looking for a correlation between an exon skip here and a variant you observe in your data. But what often is a problem is something we call a population structure, where your data set is composed out of patients from different populations, and you have a lot of population-specific variants. And if you're doing a PCA on the germline data, you can see how your population nicely separates. Doing this on the somatic variants, actually, you don't get that type of separation, but nevertheless, the structure in cancer requires you to actually account for it. And if you're actually now coloring this PCA based on cancer types, you can see a little bit better how your cancer types cluster based on the somatic variants, which is quite interesting, and we believe that it is necessary to account for this in doing an association analysis. So let me show you an example here. This is a cis-association in SNERB-C. It generates a protein which is essential for the formation of the spliceosome. So this is why it's particularly interesting. On the bottom here, you can see the gene structure with the three exons. This is the exon which is being skipped. You can see on the top right the different splice indices. You can see how the inclusion of the exon goes down from the alter, or respectively up from the reference to the alternate allele. This is all your sample sizes we have in the TCGA data. And here you can see on the left, you can see the P-values, right? So you see the SNPs and the associated P-values. Each color represents a cancer type here. And you can see how you have a nice cis-association right around the splice junction, which is associated with the change in using this in the exon usage for the data we have seen. And so if you're actually doing this across multiple cancer types, you get actually to this nice plot here. So this is basically just a plot on a set of cancer census genes. And we have tried to indicate here on the left the different cancer types. And each blue dot marks its cis-association within the cancer type of a particular gene. So this is particularly remarkable, MMAB, where we can replicate the cis-association in each of the cancer types just using a subset of samples. On the right side you can see this on doing the same thing on splicing-related genes. You can see here some of the interesting ones, like RBM-25. And we can replicate a lot of these cis-associations over across different cancer types. So this is all across 5% FDR, just to show. So we also look at trans-association. And this is a little bit of an example. This is an interesting gene. It's directly related to P53-mediated apoptosis. And we find if you're looking actually at trans-association at the same FDR threshold of 5%, we find various other factors connected to this, to alternative splicing in this gene. And here you can see obviously the loop itself indicate cis-association. And you can see we found some other links in the datasets supporting several trans-associations. And this is a subset of what we have found so far. We find several trans-associations in various genes. Of course, most of them will be cis-association. It's simply where you have the most power for, and most of the signal is coming from that. And we certainly don't believe that all of them are right. And they definitely still need some confirmation. There's a certain error rate associated with it. But the truth will probably be lying somewhere in the middle. So let me go to conclusions. So basically we have developed a new resource for novel and known alternative splice events. So we will try to make this available to the community as soon as we can. We identified cancer-specific isoforms that appear rarely expressed. You have seen that in the heat map. We have a slightly updated version now where we actually accounting for the existence of tissue specificity. So we performed common variant associations to map splicing phenotypes.  Again, not all of them may be functional, but maybe correct. But some of them certainly will. And so we're definitely looking further into that some of them still need some validation. And again, particularly in trans, they are usually hard to find. And there certainly may be some previous associations. So let me acknowledge particularly this group which has been working with me on this project. Particularly, I want to emphasize Andre here. He has been particularly helpful in handling the next generation sequencing data. We have been working with the 3,000 sample. And it has been a huge amount of work. It's a relatively small group for this scale of a project. And with that, thank you. And I'm taking this. And two questions. One is, do you see what's the frequency or prevalence of those kinds of specific splicing? In other words, do you see a small group of gene that has high enough frequency in tumor that could be novel therapeutic targets?  So yeah, these are two questions. So first, we're definitely looking into trying to filter down these events. Right now, we're just looking at the subset of genes, which seems to be cancer-less tissue-specific. We're trying to particularly sort out what's tissue-specific and what's cancer-specific using the normal data available. Towards doing somatic variant association, we are working on doing a rare variant association using the somatic SNPs, but we have also associated all the common somatic variants available in the data set.  But for the common somatic, it's already available and the rare variant is currently in progress. So I think on your first slide, you talk about recalling all the somatic mutations as well as splicing events using the same pipeline pancancer. So how important, in your opinion, is that versus a lot of people that are using individual calls from different working groups? It depends on what you want to do. We particularly are interested in also looking across cancer types. And if you're doing that and using QCs, which are done separately for each cancer type and you're looking across various cancer types, there's definitely a difference. Particularly if you're looking at mutation calls, you can sometimes see that there's an increase of calls in certain cancer types. For example, all your lung cancers are hypermutators, right? And sometimes the thresholds have been more stringent, but you want to have sort of uniform thresholds to actually analyze this. So I think for that type of analysis, it's important. It's not necessary for any type of analysis. It really depends on what you do. Are you guys going to make those mutation calls available? We can make the somatic variant calls available. The germline call, however, is a hip-power rate. Okay, Aaron. Next speaker is Dmitri Gardinian from NIEHS, and he will talk to us about pancancer analysis of apobec mutagenesis.


I have horrible problems with anxiety, horrible, and as I went through my 20s, it got worse and worse and worse and worse, and in my thinking and pictures, which is available in the UK in all formats, I described my experiences with antidepressant medication, it saved me. It stopped horrible colitis attacks, horrible, health was just a mess. I'm sorry to hear about that.    I can do it. And for me, my sense of identity is career. And I'm saying a lot of, and some of the most fun stuff I ever did was in construction. Funnest stuff we ever did. You see, that's friends who shared interests. I was bullied horribly in high school, horribly, called all kinds of names like tape recorder. People don't even know what a tape recorder is now. Big thing with reels like this that you record on. And they called me that because I would keep using the same phrases. So I'd walk across the cafeteria and they'd go tape recorder and it was horrible. And the only places I was not bullied was horses, model rockets and electronics.  Do you think that there was some, like, what do you think? Because personally, for me, I have quite severe depression and anxiety that was caused by the bullying and isolation that I experienced at secondary school. And the issue was for me is that I have always had, even from a very young age, a really, really, really big interest in other people, you know, the psychology of people, how people work and how to get on with them and make friends. And I've done quite a lot of work in my time on things such as cognitive empathy, reading, reading people. And I've had a lot of practice sort of out there in in group situations, in at parties, talking to people that I don't know and chit chatting and stuff.   OK, there's quite a few people on spectrum that are good at that. That's good. Yeah. And my mom, my mom has always been really great. She's always introduced me to different different hobbies and stuff and different, you know, within those hobbies, you have other people that you can talk to about the things and sort of slowly build those social skills up. Well, and I did a lot of things like that, too, and the friends who shared interests. And fortunately, when I was in elementary school or what you'd call primary school, my third grade teacher when I was eight years old, really good teacher, explained to the other students that had a disability that was not visible like a wheelchair. Yeah. And that's called peer mediated intervention, actually the fancy name. And so I managed to not be bullied in elementary school or primary school, but went by the 14, 15, 16 years old secondary school.  And and and the only places I was not bullied was the friends who shared interests, forces, electronics and model rockets for another child.   But where things have been good or a whole lot better is when there's a lot of there's a shared activities they can do. It is a really big issue, bullying and. Oh, it's terrible. It's absolutely terrible. Like even rates of severe mental health and and suicidality, even even at a very young age is something that occurs way too regularly.  Well, no, it's completely terrible. And the thing that saved me is even in a career. OK, to sit around the shop, there's two things you do.  Now, I have the managers, but the thing that saved me was friends who shared interests. Same thing at work. You know, we would talk about animal behavior research, stuff like that. That's making up new studies to do an animal behavior. Like I did study 25 years ago, my student did it. I thought it up. And I said, well, I think cattle, they jump all around when you handle them, they're going to have lower weight gain. People thought I was crazy. Well, that's been replicated a whole bunch of times now. Yeah. But you see that that, again, is career related and and I'm. Where I've had, you know, this is a book different, not less. This is 18 people in the US. Well, actually, it's one in the UK. Actually, there's a veterinarian where getting diagnosed later in life gave them insight into their relationships, you know, and why they weren't getting along. And I edited this book that wrote in their own words. I learned a lot from this, too, about how I think differently. It's my main emotion is fear. OK, I'm. OK, yesterday, for example, OK, I went to Canada and I've been out of the country for two and a half years. Sure. Now, I'm not going to say I freaked out as we approached customers, but I mean, I'm going to be just fine. You know, it's it's I'm fear is my main emotion. Yeah. Yeah. And and there's like an emotional complexity that most people have that I don't have. And it kind of sounds like because I do a lot. I've done a lot of reading into a concept called a lexaphymia, which I think is I don't know what that is, because you tell me what it is. Sure. It's the ability to to recognize and categorize your own emotions. And it's it's something that is very, very highly correlated with autism.  So it's so for, for example, if you have a threshold of anxiety from zero to one hundred, one hundred being complete meltdown, complete, can't do anything. And most most people, their their threshold for noticing when the anxiety sort of increases would be like maybe 20, 30, 40 percent. Whereas for autistic people, our threshold is a lot higher. So it takes, you know, it takes a lot, a lot more time for us to notice or a lot more strong emotions to notice them. And, you know, that that, you know, you think, well, the other thing I find a lot of my problems is that a lot of problems I don't have any processors.  This car I got, it's got proximity sensors. Then I take the seatbelt off to try to reach the thing, to stick the credit card in it that didn't work. So now I get the seatbelt thing going on, proximity sensor going off, going to get the machine to work. And and that kind of stuff on, you know, it loads my processor. Yeah, I like to use a computer analogy. I'm an Intel 286, but I got the cloud warehouses full of servers for memory. And you see it just all those going ding, ding, ding, ding, and it's making some other noise. And I couldn't reach the machine. And and then if I get closer to it, then the proximity sensors are made another alarm and that kind of stuff. If you want to tired, I'm so I go to the gate with the attendant. But the attendant gate wasn't open that night. So I just want to avoid that problem. So I just, I go to the gate that's got the person in it. Yeah, yeah.  Like you experience those complex background emotions in your behavior. So it's a thing, you know, complex emotions. I get scary easily. But then there's things where I used to be afraid of airplanes. Terrified. Yeah. Well, you know how I got over that? You make them interesting. Yeah, you just make them really interesting. I got the ride in a cockpit back in the 70s, a big airplane hauling halfers. That was really interesting. I'm not afraid of airplanes anymore. It's sort of like you learn more about COVID. What I did with COVID is I read all these scientific articles about COVID, OK, there's all this controversy about medications. I won't discuss them. That is too controversial. Yeah. But let's put it this way. I went deep into the scientific literature and I was pretty sure if I got COVID, I could save my life. Let's just leave it at that. Yeah. And having that knowledge reduced the fear. So it's so having the knowledge reduced the fear. So I am a scientist. I was going very deep into the literature, scientific literature, way further than 99.9 percent of doctors. So. I spent hours online, hours online, on scientific databases, doing that. Yeah. That's how I dealt with my fear. Now, I can also be really happy. And I've learned I got when I was in teenager, I got in trouble for anger.  Yeah. So then when I get in some situation that's upset and cry because you don't get in trouble for crying, you get in trouble for hitting. Yeah. So you have to, you know, get rid of that and I can be sad. And I can tell you the things that make me sad. I have to give you a specific example. I read about a scientist in the Ukraine who was studying whale fossils and he couldn't take his fossils with him. And so he photographed everything and he had a single portable hard drive. It's not like I think about the size of this block. Yeah. With his life work on it. And that's so it's a fragile thing. It could break so easily. His whole life's work was in a hard little hard drive box. And I start to get upset just talking about that. Yeah. He was doing everything he could save his life's work, trying to download it to France over slow internet connections. I'm going then finally went on a train with it. And I'm going, what would I do with that hard drive? It'd be right here under my shirt, tucked in with a jacket over it. Yeah. I'm I wouldn't even have it in a bag. Yeah. And the cords would be under my shirt, too. You see, but preserving his life's work, I can't even talk about that without getting upset. I can't even look at a hard drive now, without a portable hard drive, practically, not without getting upset because I think about that. And this gets back to what identity is. The scientist's identity was what was in that hard drive box. And he wanted to get it safely downloaded somewhere else. You could drop it in a puddle. You see, I'm a visual thinker, not the end of his life's work. I get I get upset about that. You see, and that's I'm I'm not saying the path I've taken is a path that everybody should do. But having interesting career, interesting stuff to do. I had to have a COVID project. So I worked on this book on visual thinking. I went deep into scientific literature on that. Because I had to have stuff to do. Yeah. On. And then the knowledge I had of medical stuff. Well, now I'm quite brutal vaccinated and I'm not worried about it now. Good.


Let's uncover the mystery of what I'm going to be reading in August. So cheesy. My channel and welcome to another episode of TBR Cluedo! This is my TBR game if you don't know inspired by Super Cluedo and we have all the different rooms but they are genre themed. I'll link the full playlist down below where in the first video you can go through all the rules. But essentially it picks six books that I read as a prompt and genre rooms is essentially the idea. I don't have an explanation for you and you may not get one. How are we all doing? I am so excited for August. August I have some of the most exciting videos coming, some of the most exciting reading coming. I literally can't wait like I literally can't be contained. Today we're going to be seeing how kind TBR Cluedo was in allowing me to fit in while I was already excited to read in August or whether I'm having to read other stuff entirely. We're going to find out together and yeah I'm just very excited for August. I feel like we're on an upswing. I feel like life is great. Let's all be positive. You know life's great.  Let's just get straight into the roles. I'm really really excited for this month. Okay time for roll one. Person number five which is white over here in magical realism. Let's see how many we roll. I've got a four and a three. I'm just going to go one, two, three. That is number 12 which is a favorite author. That's going to be tricky. Roll one was in the magical realism room which I can also read like fabulism. Anything kind of along those lines. And the prompt was a favorite author and I have picked Switch by ASKIG. This is one of the releases that came out last year that I have just been so excited to read. I can't believe it took me this long to get round to. ASKIG is one of my favorite authors. Dig and please ignore Veeradids are some of my favorite kind of fabulism books that I've ever read. I am just so excited to get to this. I literally can't wait. So time has stopped. Our kind of protagonist lives in a house with a switch that no one ever touches. A switch her father protects every day by nailing it into hundreds of progressively larger boxes. But she's got a crowbar and one way or another she's going to see what happens when she flips the switch. It's crazy. It's crazy. I think this is crazy. It's told in a lot of like really short, you can't really see like really short sections with these kind of headers to it. And here's the thing. I said this before ASKIG either give five stars or 2.5. This is going to be one of them. Like this is going to be literally known between. I know with ASKIG I either love or don't really like her books. So it's I will just say the video I'm reading this for this month it is funny that I got this prompt. I will just say that. I will just say that it's funny that I got this prompt. I'm very excited to go into the mind of ASKIG. Just the craziness that is ASKIG's mind. And I always have a fun time reading her books even if I don't like them. They're just they're just something different something interesting. So I'm very excited to read this this month. Roll number two person number three which is red over here in historical. Let's see how many we roll. Okay we've got a six and a three. Can I get into mystery with that? But quite a few mysteries I would like to read. One, two, three, four, five, six, seven, eight, nine. There we go. That is number 16 which is a book with four or more words in the title. Next is a mystery and you just heard the prompt but I haven't written it down. I knew what book I wanted to read straight away for it. Is it four or more words in the title? I'm pretty sure it was.  Are you ready to scream? Are you ready to scream? The book that I'm reading for this prompt, The Man Who Died Twice by Richard Asen. I'm excited for reading this. If you watched some of my videos you'll probably know that Thursday Made a Club was one of my favorite books I read last year and I just can't wait to read this. I've been waiting for the perfect time and the perfect time is now. I'm just so excited. So this is a Murder Mystery series following this group of friends who live at retirement village and every Thursday they had a murder club where they would try to solve cold cases. That was kind of their hobby but then a murder happens on their doorstep. It's kind of like mainstream cozy mysteries. I wouldn't say it's like a pure cozy mystery. Do you know what I mean? Like something like the Lady Hardcastle mysteries which I love are but it's got this coziness and this quaintness and this uniqueness to it that I really love. I loved the writing. Usually I'm quite against celebrities you know becoming mainstream authors and taking over the book chart. I love David Rylian. It's like I don't really like it but I will make an exception for Richard Osman. Usually I'm quite against you know celebrities getting these massive advances when authors other authors are struggling but I really feel like Richard Osman can write and can write really well. He's the kind of person that I thought would always kind of want to write a book and I just loved the first one so much and so many people have said this one is so much better it made them cry. The first one made me cry. So if this one made everyone else cry what is awaiting me? I'm really nervous.  Maybe I'll cry. This is one of my most anticipated books to read. I am just so excited and yeah I'm finally gonna be reading it. I'm actually reading this next after I finish my current read and I just can't wait. Okay next roll. Oh number six which is yellow here in Thriller. Let's see how many we roll. Whoa. Shit. Not the destruction that just reaped. Let's just go one which is number four which is a book that I bought because of a booktuber. Roll three was a thriller I bought because of another booktuber and this is a round that I gave to my patrons to vote on so if you don't know my patrons get to vote on one round of tbrcuda every month and then that book becomes a book club pick which we have a live show for and I do an exclusive reading vlog over there for. So the options were Sleep by C.L. Taylor which was my vote. I'm not gonna lie I'm very excited to read this. I bought this because of Mara from Books Like Woe. Never Saw Me Coming by Vera Kurian. I bought this I think because of Mara as well. I heard Good Things. The Whisperman by Alex North which I feel like I can't find my copy of it. It's somewhere back there but I feel like not a lot of people ended up liking this but I bought it because a lot of booktubers hold it. I think like Kayla and Chandler and then Final Girls by Riley Sega. I would say I've just bought because of like wider booktube love for Riley Sega but people like Gabby I think has read it. I actually liked it. I can't remember but I just you know you hear people talk about it a lot so you get it. And the vote was super close. It kept changing. I think Crystal one of my pictures actually commented like this poll is giving me anxiety because every time I come back it's different. Like the poll kept going up and down but the one that ended up winning the vote was Final Girls by Riley Sega. I'm very excited. This is my final backlist final. This is my last backlist Riley Sega that I have to read. Why did a whoopee Goldberg blurb this? She said it was fantastic. I just wasn't expecting that. Yeah this is my last backlist Riley Sega so I'm very excited to get to it. After this I'll only have his new release House Across the Lake which I haven't read. I'm so excited to read this everyone. I feel like we're gonna get some really fun discussions and really interesting discussions so yeah this will be our book club pick. Oh the font is much smaller than I expected. So yeah if you want to come join us come join my Patreon come read this with us. There'll be an exclusive reading vlog of me reading this over there and discussion live show which always so much fun. I sometimes get some of my patrons to come onto the live as guests. We have like a really good discussion so yes very very excited to read this for the book club. Next one roll four person number five which is white over here. See how many we roll. Whoa a three and a five. Okay I think I'm gonna go into fantasy. Let's go one two three four five six seven eight which is number two which is a series I'm partway through. Next was a fantasy that is part of a series that I'm partway through. This is probably I'm very nervous. I've been putting this book off for a long time. I actually can't believe I'm finally reading this. We're gonna be reading The Dragon Republic by Ivequan. Yes we are. This is a reason to celebrate. So I read Poppy Poppy War probably was it in 2020? It was in 2020. I read the Poppy War in 2020 and then I've been putting off finishing the series. My dad has read the whole series. He loved it and it's time. It's time now they're very long. I am a bit nervous about that but I feel like the kind of books you read really fast. The only thing is I don't like, I don't know why, I don't like the audiobook narrator for these. I don't have anything against it but I'm listening to the audiobook narrator. I don't dislike her but then I've gone back and I look back at all the books I've read that she narrated and I rated them low so I don't know what's going on there so I can't listen to the audiobook to help it make it quicker for me. Yeah I'm you know excited to be back with Rin. Obviously a lot of you all know the Poppy War is this Asian-inspired fantasy where it's set during a war. I forget what's a spoiler or what's not. Rin is very morally gray as a character and I'm just so excited to see where the series goes. And obviously Babble is coming out by Ivequan I think in September. I have it pre-ordered I'm very excited so I'd be really happy if I can finish her other books and then get to Babble. Okay roll number five. Person number one. Let's see how many we roll. A one and a three. Okay so I can't go very far so let's just go one two three which is number 26 which is a book I've been scared to read. Roll five was a fantasy another fantasy that I've been scared to read. Dragon Republic can work for that as well but I'm gonna be going with King of Scars by Libar Dugo. I told you I've read in some heavy hitters in August. I'm sorry this is making me so excited. Isn't life great you guys? Isn't life great? Isn't it only blessed? I've been scared to read this because I loved Six of Crows on Crook Kingdom so much. I really did. I gave them I think a 4.5 and a 5 star. I really enjoyed them. I've been scared to continue because I don't want this to be Shadow and Bone season Storm Ruin and Rising vibes. I want it to be Six of Crows' Crook Kingdom vibes and I'm scared as to which direction is going to go in. Yeah I'm scared that I don't know like the Grisha verse I'm scared to enter it again but I am excited. This is another obviously a geology that I'm starting so I will have to try and finish it um this year hopefully but yeah I'm excited to be back with these characters but I'm scared because they are majority of the characters from I think Shadow and Bone trilogy versus Six of Crows. I think it's Zoya, Nikolai and Nina so obviously one from Six of Crows two from Shadow and Bone. I'm scared but hopefully I am going to enjoy it and love it and fingers crossed everyone pray for me. Okay final roll person number six which is yellow again over here let's see how many we roll oh my god a two and a three uh let's just go one two three which is number 22 which is a book which has a title with three words in the title and then our final roll was a thriller with three words in the title and I just need everyone to take a moment okay we're all ready we're gonna be finally reading I'm the Girl by Courtney Summers this is an arc I have of it it comes out in September I think towards like the end of September and I'm finally gonna be reading it this month I'm so excited you know this is one of probably my most anticipated release for this year I love Courtney Summers so much she's an icon she's a legend and she is the moment now come on now I've loved Sadie and the project for Courtney Summers which I've read so I am so excited to get to this Courtney Summers has pitched us as being inspired by the Jeffy Epstein case following three girls one girl is murdered she's 13 and this other girl and the girl who's been murdered sister team up to try and figure out what's going on and I think you know it's a story about power about money about control I'm just really excited to enter the world of Courtney Summers again I'm ready for my heart to be broken it's very nerve-wracking I feel pretty sick thinking about it but I am really excited to enter this world again and to just fall in love with this book even the font the Courtney Summers font like looking at that stars up a feeling in me I don't think you understand like it makes me feel a certain kind of way so yeah I have no doubt I'm probably gonna give this five stars I already feel like that like if this isn't five stars there's a bit a shift in the world's balance do you know what I mean that's generally how I feel so very very excited to read this I absolutely can't wait and we will see what I think of it so there we have it oh my god the books are sliding around but that is my tbr for August I want you guys to start getting excited because I've got some really exciting videos coming this month I'm just I just can't wait I feel like there's a lot of good ticks in here a lot of good variations so I am so excited if you got into the end what should we comment or comment the dragon emoji comment the dragon emoji for dragon republic comment that if you got into the end thank you guys so much as always watching and I will see you very soon in another video bye