Cool. Right. Can everyone hear me? Is the mic working? Oh, just for the recording. Oh, just for the recording. Gotcha. Cool. Thank you for coming everyone. This is, I'm going to try and stand here mostly because my beeper is not working. Unfortunately, I can't do anything except laser you with it. So I'm going to talk today about Homebrew 2.0. Starting point, who's heard of Homebrew? Anyone in the room? Cool. A few people. Who uses Homebrew? Again, probably the same. Who here has submitted a pull request to Homebrew ever? Nice. Who here maintains Homebrew? Hey, there's more than just me today. Exciting. Thank you. And anyone submit a PR to Homebrew and had it rejected by me? Hey, only maintainers. That's okay. That's fine. Cool. And then we also have, who likes our new logo? In fact, no. A tougher question. Who can tell the difference between our new logo and our old logo? It's basically the easy way to tell in case you're wondering if you've got a vintage logo sticker on your laptop, is the new logo has a straight beer glass sides instead of overly curved one. We have one of the Homebrew cost-maintenors full-time job as a designer. In fact, is Vitor in the room? There, Vitor. Hello. We've not met before. Hello. Yeah, so he sent me a list of corrections of why their old logo didn't meet standards. So, like, now we have a nice new logo with more accurate beer glasses so you don't get confused and think that you're drinking when you're homebrewing or vice versa or whatever. Anyway, so, who am I? My name is Mike McQuade. Thank you very much for having me here. My worlds collide often because I both work at GitHub and work on Homebrew. My job at GitHub is not to work at Homebrew. That's a kind of happy side effect. And as a result, like, I'm often telling people, sometimes diplomatically, sometimes not, in GitHub, everything that I kind of want GitHub to do better for open source and then vice versa, kind of sometimes defending stuff that GitHub has done to kind of homebrew maintainers who are grumbling about it when it happens. But yeah, so if you want to talk to me about Homebrew or open source stuff or whatever, you can get me on Twitter. You can find my email address on my website and stuff like that. And I'm always happy to talk more about this type of stuff. I've been working on Homebrew for about 10 years. This year, I guess, 10 calendar years at least. I'm working for GitHub for about five. So, yeah, I was a happy GitHub user before I worked there. So I'm somewhat less biased than I might sound. We released Homebrew 2.0 yesterday, like I was sitting in the... Thank you very much. In the cafeteria, which was nice. It was kind of felt satisfying to actually tag the commit and submit it whilst here. So, yeah, I wasn't sure when we were going to release this. So because I did it yesterday, I figured we could do in this talk some of the things that my top 10 features, I guess, that we've shipped in Homebrew 2.0. Some of these things are not... So the difference between 1.9 and 2.0 were relatively minimal, but it was all... Most of these things were all things that I kind of wanted to see us do before we would call ourselves 2.0. It's kind of fun, because I guess this time, two years ago, I was doing the same talk about Homebrew 1.0, which had been released a few months before. So it was a fun little game going back and comparing the notes from a few years ago and seeing what we've done in that time period and what things we've changed and what we haven't and all this type of thing. To make it more of an adventure, what I'm going to do is I'm putting up pictures that are loosely related to the features and then we're going to see if you can guess what the feature is. Homebrew maintainers, you are not allowed to guess. Right, so the first one... Anyone guess... Support, yes. So that is a picture of a... I know it looks like it's an actual photograph, but I did modify that myself. That is a picture of a mountain line, which was RSX 10.8 and it is crying because it is no longer able to run Homebrew. So it's a little bit weird, it's like a feature, but the main thing I guess many of you here work on software projects or open source software projects yourselves and that allowed us to delete enormous amounts of legacy code because versions pre-mounted line and below ship with like now really with the old compilers that don't support C++11, don't support C++14 and stuff like that.  So the next one... Yes, so the options. This has been a little bit contentious recently, I don't know if you've noticed. So in the Homebrew core repository we now don't provide options on packages. Again, this seems like a weird thing. I'm starting with the horrible features that aren't really features for anyone except maintainers first and then we'll build into the nice stuff later. But anyway, so with the options stuff basically we've had a long running battle with options much like this dog here, the options did not want to behave. So the way Homebrew started out is a little bit of history if anyone hasn't been using it for a very long time or whatever. Homebrew started out as being a from source package manager for Mac. The only shipped for I think OSX 10.5 was the version that we were at when it shipped. So people were using it, people were building stuff from source pretty much like the expectation was that everyone who worked on Homebrew and was submitting stuff to Homebrew were the people using Homebrew and vice versa. There wasn't a long tail of users who didn't know how to kind of modify Homebrew it was pretty much like everyone who was using Homebrew was the ones contributing to it at the same time. And obviously over time the tool becomes more popular and more and more people use it and what ends up happening eventually is we end up getting bigger, we end up getting more support requests and we end up getting more bugs that people find with the software. And one of the biggest causes of bugs and you will sympathize if you run a from source like Linux distribution as well is the weird things people have on their system weird things they have set up in their dot files or their editors or whatever can like subtly break build processes really easily. So we ended up having binary packages for more and more stuff eventually binary packages for literally everything that is compiled. And then we've got to a point where we notice that effectively all our support issues are coming from a very small number of people who are doing from source builds of things and that made us want to use binaries more and then the problem with the options is we have the way it was working until recently well it still works this way if you're running a third-party repository but in the main repository you would have a package and it would have say four or five different options in it and because we don't have the CI infrastructure we couldn't test that all those options actually work correctly. So each option you add to a formula you add my math is not great but if I've understood correctly it's a factorial increase in the number of option combinations someone who knows math is nodding at me so I believe them. So basically you have a dramatic number of combinations and some of the options didn't work and then some of them only worked when in combination with other options. So you end up in a situation where we're shipping a bunch of software that we know is going to break we know people are going to file issues like tough this is broken you can't do anything about it particularly when you end up with more and more homebrew usage being stuff like you know guides on the internet saying hey you want to encode this YouTube video just copy and paste this line to install homebrew copy and paste this line to you know install ffmpeg with 40 different options and then there you go. So what we've done now is we've made homebrew core have no options in it so the binary packages are always the same for everyone and what we're trying to do instead now is say something like ffmpeg we're trying to build it with a sensible default of things that people can use and when people ask for something basically we're generally adding as much as we can to provide as much support. So what we don't want to do is provide three different open jmpag encoders but we can have a discussion about what's the best one and then we can make that default. But yeah so basically this is this may be if you're if you haven't bumped into this yet this may be a couple of month hiccup this may be annoying for you and I apologize for that but longer term this is going to make it much easier to actually run the project and have it be sustainable. So next feature oh I forgot this wasn't working right so this is some counter strike reference I didn't really understand that I think it's about tapping the mouse or something but this is this is some loose google image searching this morning so I apologize so this reference is the fact anyone want to guess oh sorry no you started and then I gave it away yes so we now have one main tap which is homebrew core previously a couple of years ago we had inside the homebrew organization a bunch of like third party repositories which was sort of official and sort of not now the issue came about with that that like some of these taps were fairly well maintained but would do things differently and then some of them were like completely like literally no one had committed to them for years at a time and the problem is is because they're all under the homebrew umbrella it looks like these are all official and they should all work and so what we've done now is we've tried to move as much stuff as possible that actually works and meets our requirements into the main tap and then we're trying to make it as easy as possible for other people to create their own taps so I realized who doesn't know what a tap is anyone yep awesome at least one person stuck their hand up so a tap is a third party homebrew repository which effectively means if you're used to other package managers it's just a way of having a collection of packages in one place and what you can do is you can use the brew tap command to add more more of these so that you can install stuff maintained by other people other than the main homebrew maintainers so the default tap is on github.com slash homebrew slash homebrew core and then any other tap is generally shortened to be so for example the Linux one which I'll talk about later would be linuxbrew homebrew core and again that's like a short version of describing where it is on github you can also have taps that are not on github or not using git or whatever but that's kind of a longer tail that's talked about in the man page right so the next thing this is very niche so this is like literally probably no one cares about this except me so I'm not even going to ask but homebrew core now is all or should be at least all open source software so this is something that's come up I guess in a few talks I've heard over this weekend where we're having an interesting time in open source where we have some companies the one that kind of jumps to mind but they're not the only company being like mongerdb who are releasing open source software which they claim to be open source software and which other organizations such as in mongerdb's case I believe fedora debian and the osi currently claim to not be open source software so this puts us in a tricky situation because we are part of software freedom conservancy and one of the agreements of our terms is being part of that is our repository is all open source software so basically what we decided to do is punt the work onto someone else which is the osi and we're basically saying what the osi says is open source is what we consider to be open source and everything in hubrew core should be open source under that definition so we'll see what happens with licenses for various things in future but it has meant we've had to do stuff like raw mongerdb back to the last version I can't remember what it is off the top of my head that was released under a osi license rather than their new SSPL thing but yeah this is going to be interesting to see what happens in the next few years I think because there's a lot of companies who are doing kind of open sources of business type thing who are moving in a direction which some might say is away from open source principles and putting additional restrictions which are certainly not certainly prohibit them being considered free software anymore and may or may not stop them being considered open source software so we'll see what happens right the next thing is this anyone recognize this where you might see a page like this no but that's a good question a good suggestion so we have a site now which is formulae.brew.sh which is a like there was a site previously called Browmeister did anyone use that so yeah so that was like a kind of package online package browser for homebrew and this was sort of like an import of that that then got kind of a bit of a rewrite and then it's now running on github pages basically just because I'm cheap and don't want to pay for infrastructure but I would recommend when you look at the github pages source like you close one eye at a time because like because it's doing things like rendering a JSON API like static JSON files like using liquid and things like the syntax highlighter is like looks really looks like it's crying blood so it's it's not happy times but it's kind of cool like how it works and that gets updated on each push so that also means that as well as all the information you can get about a given formula that's double you get there and this is all basically like JSON and information that we're then representing nicely there's also a we document on the formula which provides like an API doc so you can now use that to kind of query JSON information about formula and about their analytics data as well if you look at the very bottom you can see installs 30 days so this is the nice thing we've kind of got to through this as well and I'm going to talk about there so in fact talk about that now so I don't know if anyone has seen this output ever again this is relatively niche and a new command but this is the output of brew info analytics so that's like when we introduced Google Analytics a few years ago one of the concerns that people had was they said it would be nice for the community to be able to access all the information the maintainers access and we're kind of uncomfortable with there being a sort of an information imbalance and I can say as of the last few days there are only two Herber maintainers who have access to anything more than what the rest of the public have and that's purely for just administrative reasons because that's how the information is generated and the rest of it you can get all the information on formula.brew.sh and then you can use this brew info dash dash analytics which does a JSON call and pulls that data off formula.brew.sh and basically what that's giving you is like the install counts and the balances for each of these kind of formula here so here you can see an example of what I was talking about before of like the option removal over time so like the options are diminishing there so such that you get to 99.9% at the top and 99.88% at the bottom and again hopefully that illustrates the point that even back when a year ago when there was all these options these were being used by what 0.12% of the people who were installing WGAP but yeah so this is a really nice tool both for the maintainers but then also if you want to kind of I find it interesting it's got cast analytics up there now as well if you kind of almost just want to discover new software kind of based on popularity it's kind of interesting to just kind of click through and see what stuff is there and what it's being used for and you can kind of single click to the home page and the formula and all this type of stuff any guesses on this one? Linux support, hooray! so Homebrew and Linux which is also known as Linuxbrew is officially supported now I don't know how many of you are Linux people in here but there is sometimes some confusion as to why one would want to run Homebrew on a system which has in my humble opinion almost always a much better package manager than Homebrew installed on it and a common use case I've heard or one of the best use cases I've heard is there's quite a lot of people I believe some of the Linuxbrew maintainers for example have nice Linux machines like in high performance computing environments for example which they have access to the machine they have access to a compiler say but they do not have root access on that machine so because Homebrew itself you can actually technically install it anywhere we recommend you install it on the default location because then you get all the binary packages but because you can install it anywhere on Linuxbrew that means that you can basically have a fully working package manager just in your home directory which you can use without anything other than just a compiler basically so this has now been merged the projects are still somewhat separate in that we have our formula like the package descriptions are separate but then the Linuxbrew-brew like package manager repository the bits that are actually kind of running the code rather than just the formula descriptions those repositories have now been merged and we're kind of collaborating together as a team more than we were yeah so the tap there is a Homebrew dash Homebrew core tap which is for all the macOS packages the Linux-Homebrew core which is the Linuxbrew equivalent but you can more and more third party taps are providing support for both mac and Linux so the stuff you could install for example if you installed Linuxbrew on your own machine in the home directory you can in theory run any package that can be used with Homebrew there's no underlying technical differences it might just be that they don't work because they need to specify more dependencies but they tweak the install or whatever but again yeah if you were working on mac and Linux it's relatively easy to create your own formula that can be in sync and work on both yes yes right again you can see you can definitely probably get a theme of the ones where I spent longer on Google image search trying to find something that was tenuously related so this is basically Homebrew previously had things called more later bottles so that was a way that we allowed people to declare that a binary package by default the binary packages on Homebrew are just built for the macOS version that they're running on so if you're on the latest version of Mojave previously that would have been you only can get binary packages that are built on Mojave because again like Apple don't guarantee they guarantee a reasonable amount of backwards compatibility but certainly not forwards compatibility so we couldn't build them on one version and assume they would work now after a fair bit of testing over the years and doing some tweaks to make sure the stuff works we now do this by default which will probably not be noticeable or make anyone particularly happy right now but when a new version of macOS is released if you're running the betas we generally have a bit of a frantic run to try and rebuild everything on the new version so this won't be necessary now we will still rebuild them for the new version to get more optimized binary packages but you will be able to use all the binary packages from the old versions on the newer version which should make life a little bit nicer so this is another one the clue for this one is right at the bottom any guesses yeah so we now actually verify if you're past so previously if you passed an invalid option to like a homebrew command you may have noticed we just silently ignored it because we just checked for did you specify this particular option string but we now actually use a proper option parser which validates the options for the formula which validates the options for the command and the nice thing with this as well is it lets us all the manually curated previously like output for all the help commands and stuff like that is now generated from the options so that we know that the documentation and the options we actually check are one to one in sync so the next one which is the last and biggest change which you should be aware of is that now homebrew will run clean up by default and automatically you can opt out of this behavior but and some people may be inconvenienced by this and I apologize but we've had basically years and years of people on twitter and in person being like oh I never knew about boot clean up and then I ran it and I saved like 20 gigs of space on my machine and to me others may disagree to me that strikes me as a really bad default when people need to go and search the man page to find something that they are expected to run periodically by themselves so now brew clean up is run automatically every 30 days like in full and then whenever you install or upgrade a package it will basically like clean up the old versions behind itself as it does that so as I say there is an opt out if you check the man page for that but that's basically like a new thing which will hopefully mean that it's a little bit easier for you to kind of keep your homebrew up to date so the goal with this now is that because I guess with 1.0 we had brew update would be run automatically so now you should be able to run for example just like brew install brew upgrade and never actually need to worry about running other commands so that is a fine workflow basically if the only command you ever run are install and upgrade then you can still use homebrew quite well now which is hopefully getting us down to a nice minimal subset of commands that you need to know about in order to kind of have homebrew work nicely for you so that's the last of the features I wanted to run through and I have time for a couple of questions seven minutes so yes yeah so homebrew cask for anyone who's not oh sorry repeat the question says the thing on the bit of paper so the question was about what is the status of homebrew cask upgrades so homebrew cask for anyone who's not aware that's a way of installing basically like binary and proprietary software such as say something like Google Chrome that you want an automated and repeatable way of installing that rather than going to the website manually downloading it click click click and it allows you to use a homebrew basically more or less identical interface to homebrew as part of homebrew itself now to install that software so the question was about upgrading brew casks and what's the status with that now you can basically I'm looking at brew cask maintenance when I say this to make sure I'm not saying anything wrong but my understanding is you can now upgrade brew casks but that some of them that have weird versioning semantics or don't provide upstream versions like may behave slightly differently is that a fair description yeah so some casks the latest ones may need to have a forced upgrade but otherwise that's how they work now cool next question oh what's next what for homebrew I don't know so yeah yeah so I mean that's one of the fun things that we're doing which is why there's a bunch of maintenance in the room so we've been kind of building up our kind of funds and donations over the last few years and we're actually spending some money now so we have I think 14 homebrew maintainers who are going to be at a meeting in Brussels tomorrow in which we're kind of going to plan some of the kind of future roadmap for the project both on the organizational side and kind of maybe talk about some features we want to build and stuff like that so yeah basically so from my personal viewpoint I guess in terms of the features that I build like there's nothing really big that I'm like I feel like homebrew kind of needs now and like most of the really big things I feel like we've addressed in the last few years so my personal priorities are more around stuff like our CI system is like something that is a bit of a bus factor of one situation and I want to stop that being the case anymore and so that I in case I get hit by a bus so yeah like no big things on the horizon but just trying to make things better and make the community work better any other questions yes good question how do you get involved with homebrew so yeah if you go to the hub repository that's the best bet and that's linked from the home page as well that can describe some easy ways to get stuck in I would say I mean homebrew has 7000 plus contributors at this point I would say it's probably one of the easiest projects to get involved with certainly if you use it because there's loads of stuff which kind of works fine but you need slightly tweaked or cleaned up and we have quite strict kind of linting tools there's one called brew audit which will go and basically like complain about various minutiae packages that aren't quite how we want them so that is a really good way to get started if you can run brew audit on packages that you already have installed and you already use and then you have a bit of a scratch or an itch type situation going on then you can submit a pull request to do that another command that's useful for that is there's a brew bump formula PR command which literally lets you upgrade a homebrew formula to a new version in a single commit and then we'll create the pull request for you so that's like literally the easiest way to get started with homebrew development and then you can kind of see how that goes and then you can get a first commit on homebrew without even having to know how to commit and create a pull request yourself so thank you good question well I think we're question list now so thank you everyone for coming and thank you for using homebrew yeah sure thank you John yeah see you later I don't know what you're asking but I can file 12 blocks off, have you? I've been playing this oh yeah have you seen it? I don't know


Hello everyone, I'm Andrew Joyce, EKB sports director and football fan. Welcome to our season premiere of Armchair Quarterback, a weekly high school and college football show spotlighting local high school and college football in the mountains. Each week, we'll display our local athletes' outstanding plays, we'll bring you highlights from area games, and we'll release our Sports Guys Super 7 rankings. We'll have interviews with players, coaches and maybe a fan or two, and we'll preview the week ahead. Yes, we'll pack all of that into a half hour. We've got a great show tonight with a preview of the Community Trust Magpie Catty Bowl and all the games around the region. Highlights from last week and coaches' interviews and of course those Super 7 rankings. And it's all presented by Jimmy John's Gourmet Sandwiches at Pikeville Commons. Let's get it started as we'll each week with some interesting tidbits from the first week of the regular season. Kentucky Class Triple A appears to be loaded at the top, Belfry, Corbin, Lexcath, Boyle County, E-Town and Louisville Central all took highly competitive wins last week. Big scores in week one, 17s eclipse 60 points and the blowout of the week was Shelby Valley 66-0 win over Jenkins, while the biggest output was Mason County's 68 points. First win for Floyd Central, they celebrated the program's first win in school history and five first year coaches got wins, including Sean Hager at Floyd Central, Dudley Hilton who's back at Bell County for the third time, and Louisville Central, new head man Marvin Dantzler. And the old ball coach, Steve Spurrier, the former Florida and South Carolina coach. His grandson is the starting quarterback at South Moron, Gavin Spurrier, a junior through for 263 yards and two touchdowns. He's the son of Steve Spurrier Jr., who's now the quarterback coach at Western Kentucky. From the high school football scoreboard, last week Perry Central wins a shootout over McCreary Central, 64-58 in four over times. It was Knox Central, 27-20 over Letcher Central. East Carter dropped McGuffin County, 36-6, while Paintsville rolled over Estle County, 41-14, and Floyd Central defeated Harlan, 28-12, Dylan Cottle with 135 yards rushing and two touchdowns. Stay tuned, more highlights and interviews from week one coming up along with the preview of the 33rd annual community trust bank, Pike County Bowl. This week's Super 7 rankings and the area schedule. It's armchair quarterback presented by Jimmy John's gourmet sandwiches in the Pikeville Commons. Here's some football inspiration to take you to the break. Ability is what you're capable of doing. Motivation determines what you do. Attitude determines how well you do it. From Lou Holtz, former college coach. We'll be right back. And this has been my definition of fresh since 1983. Good folks at Howard Family Pharmacy grew up right here in Eastern Kentucky. They know this town just as well as they know their customers. You want to be greeted by a friend and a pharmacist you know and trust. Come see Wes Howard, Tiffany Jacobs, and Lauren Mullins at Howard Family Pharmacy. Located at Eastern, near Allen Central High School, call or visit howardfamilyfarmacy.com. These insurance plans are accepted, late hours and open on Saturday too. Howard Family Pharmacy. If you're looking for a fun, safe, friendly atmosphere to achieve your fitness goals, be sure to check out Heavenly Strong, a Christian fitness group that supports your physical and spiritual journey to wellness. Call<PHONE_NUMBER> for more information. No matter where you are on your journey to physical and spiritual wellness, Heavenly Strong is here for you. It's the high school football game of the week, presented by Paul Howard Jr. Attorney at Law and the Golden Corral Restaurant in Plankville. The Floyd Central Jaguars play their first home game ever, taking on the Bobcats from Betsy Lane. The game of the week airs Saturday at 7 and Sunday at 4 and 8.30 only on EKB-TV.  It's time to look at last week's action. The Pikeville Panthers opened the 2017 season welcoming Covington Holy Cross to the Hambly Complex. That welcome turned sour quickly. The Panthers blew this game open in the first quarter rolling to 37 opening stands of points. Here's how they did it. First quarter, Zach Roberts with a two yard run. After a big run down the far side line, Roberts will punch it in from just two yards out and the Panthers take an early 7-0 lead after the extra point. After the free kick, the Panthers will get a long run back. How about Jackson Hensley, 65 yard return on the free kick. The Panthers score quickly. That free kick coming after a safety that the Panthers defense had put up, Pikeville goes on top. Now Peyton Boyd Blair. We'll look down the far side line, 24 yard pass to Seth Pugh and the Panthers are rolling. Still in the first quarter and there's still plenty more points to come in that opening quarter. Zach Roberts, you'll hear that name. He goes down the near side line, cuts back, gets a block, gets another block and then just out runs at Covington Holy Cross defender, a little stiff arm and into the corner of the end zone. 50 yard run for Roberts, continuing with first quarter action, Christian Billitner. You'll see the ball pop loose on the ground, a scramble, Billitner will pick it up and he does what he does best, he's an athlete, he can run, he outruns everyone to the end zone. 25 yard fumble return. Panthers up 37-0 running clock as we go to the second quarter, Connor Wright.  At the half, Pikeville on top, 44-0. Then in the third quarter, Zach Roberts, he finished with nearly 200 yards on the night, a 75 yard run. Good blocking at the point of attack and downfield and then Roberts just outruns and breaks the tackle, Panthers go on top by 51. The final, Pikeville 51, Covington Holy Cross 14. Zach Roberts, 193 yards rushing, three touchdowns, next up the Panthers will take on Lexington Christian in the Pike County Bowl this weekend, Saturday night. Panther coach Chris McNamee shared his thoughts on the opening win. Well, I was really happy with the way our guys came out, both teams us and Holy Cross didn't have a lot of experienced players returning, but I thought our guys came out and got on them early and forced them into some bad situations and were able to get up by a few points early. Well, I thought we got to the ball well, I thought we played aggressive, forced a few turnovers, scored defensive touchdown, also got a safety and punt return, so I scored a lot of different ways, but defensively I was happy with the way our guys got after it. And the Letcher Central Cougars hosted Knox Central Friday night at Whitesburg, it was a beautiful night early. Letcher Central dressed in the blue quarterback, Nick Sergent passes to Nathan Short, will hurdle a defender for a five yard game. In the red zone, Sergent hands off to Hunter Campbell, Campbell five yard touchdown run into the end zone and Letcher Central with the lead early in this one. Then Knox Central quarterback, Levin Campbell, and off to Ethan Mills, simply a ten yard game, but Knox Central able to move the football.  Knox Central will get the ball back, quarterback, Levin Campbell fakes the gift, completes the pass to Jacob Barnard, twelve yard game. Knox Central able to move the football all night in the red zone, looking to punch it in, Mills takes the hand off, comes up short, he'll fall to the two yard line. He'll play, Campbell to give to Jermell Carleton, he'll walk into the end zone untouched. Cougars with the ball, hit their own territory after a little celebration by Knox Central. Sergent will get the ball out to Blake Rashiers, thirteen yard game and the passing attack moving the football for Letcher Central. That drives stalls and Knox Central with the football. They'll drive downfield, Campbell completes the pass to Nick Martin, twenty yard pick up. Knox Central again, looking to score, Campbell with the quarterback keeper, scrambles to the side line, he'll lose the football and the Panthers recover for a thirteen yard game. Knox Central spoils opening night for the Cougars in the end, Knox Central twenty seven, Letcher Central twenty. Stay tuned, more highlights and interviews from week one coming up along with the preview of the thirty-third annual Community Trust Bank Pied County Bowl, this week's Super Seven rankings and this week's schedule. It's armchair quarterback presented by Jimmy John, Gourmet sandwiches and Pied Pocombs. And this has been my definition of fresh since 1983. If you're looking for a fun, safe, friendly atmosphere to achieve your fitness goals, be sure to check out Heavenly Strong, a Christian fitness group that supports your physical and spiritual journey to wellness, call<PHONE_NUMBER> for more information. No matter where you are on your journey to physical and spiritual wellness, Heavenly Strong is here for you. Folks at Howard Family Pharmacy grew up right here in Eastern Kentucky. They know this town just as well as they know their customers. You want to be greeted by a friend and a pharmacist you know and trust. Come see Wes Howard, Tiffany Jacobs and Lauren Mullins at Howard Family Pharmacy, located at Eastern near Allen Central High School. Call or visit howardfamilyfarmacy.com. Most insurance plans are accepted, laid hours and open on Saturday too. Howard Family Pharmacy. Eastern Kentucky, beautiful, green, peaceful, friendly, but there's a darker side to these mountains. When crime is committed, sometimes cases go unsolved. Occasionally, the perpetrators even get away with murder. On our latest news segment, The Scene of the Crime, I'll be working with local law enforcement to help find justice for victims and their families. The Scene of the Crime, Fridays during the EKB news at 6 and 10, starting August 25th. Welcome back everyone. This armchair quarterback presented by Jimmy John's Gourmet Sandwiches in Pikeville Commons. Last week, Shelby Valley was playing without running back, Seth Johnson, Tico Field at Robinson Creek was the scene as the Jenkins Cavaliers traveled US-23 to battle Shelby Valley. The Wildcats took control early. Mason Lane, you'll hear that name often tonight, Lane had a huge night. Shelby Valley quarterback Clay Morgan gives the ball off to Jordan Little, 20-yard gain. And again, Morgan takes the snap. This time gives to Mason Lane around the opposite end, 22-yard touchdown. That's where it got started. Wildcats are driving down the field when Morgan connects with wide open Dylan Newsom, 30-yard Shelby Valley touchdown. Valley in the red zone looking to punch it in. Mason Lane up the middle. He'll come up just short near the one-yard line. Jenkins now on offense pushing the ball downfield. The quarterback finds a wide open receiver down the sideline, 35-yard gain. Jenkins in business. The Cavaliers still looking for their first four. The quarterback scrambles to his right, dumps it off to a receiver down the sideline, makes a man miss, 22-yard gain for the Cavaliers. That drive will stall. Wildcats are back inside the tent. Guess who? Mason Lane takes the handoff, gets around the edge, 7-yard touchdown and medical leader sportsman Teddy Painter getting some air time. The final Shelby Valley 66 Jenkins, nothing. Next up, Twin Valley will be at Jenkins Friday. Shelby Valley faces Pike Central Saturday in the Pike County Bowl at Pikeville. Let's travel to Betsy Lane where the Sheldon Clark Cardinals open the season on the hill facing the Betsy Lane Bobcats. Sheldon Clark quarterback Drake Muncie will give the ball to Zach Priest up the middle. Sheldon Clark rolling 14-yard gain. Very next play, Muncie hands off to Brent Burke around the end. He'll run over a defensive back and dives for the 15-yard gain. Cardinals now in the red zone. Brent Burke takes the give up the middle and punches it in. That's an 8-yard score for Sheldon Clark. The Bobcats now looking to make a drive. Quarterback Bradley Woods gives off to Quentin Adkins. He has the ball knocked loose and Austin Borden's recovers the fumble for Sheldon Clark. D. Liman gets his hands on the ball. Happy guy. That fumble recovery puts the Cardinals in the red zone. Zach Priest brings the ball around the end looking for the end zone. Big hit knocks him out of bounds. Into the camera man. He crosses the plane for a touchdown. 10 yards and Sheldon Clark puts 6 on the board. Back deep to the return. The kick for the Bobcats, Jacob Williams. He gets a nice return. A couple of big blocks and on his own he'll have a 25-yard return. Betsy Lane now on the move looking to score. Quentin Adkins takes the handoff. That's a 17-yard gain before he's pushed out of bounds. Again, Woods takes the snap and he'll give off to Quentin Adkins. 15-yard gain for Betsy Lane. This game back and forth, the Bobcats in the red zone looking to punch it in. Woods takes the snap. Quarterback Keeper. Down to the near side. Goes around the edge. 12-yard touchdown. Bobcats with the lead. The final however, Sheldon Clark, 26, Betsy Lane, 24. Next up, Sheldon Clark is at non-central. Betsy Lane goes to Floyd Central. It's our EKB-TV game of the week. Stay tuned to preview of the 33rd annual Community Trust Bank Pike County Bowl this week's Super 7 rankings and the area schedule. Next arm-chair quarterback presented by Jimmy John's Gourmet Sandwiches in the Pikeville Commons. And this has been my definition of fresh since 1983. Appalachian Wireless and the stations of East Kentucky Broadcasting present the long, hot summer of cold hard cash. And while summer is indeed winding down, you still have plenty of opportunity to win big. Register at your local Appalachian Wireless location every week. You'll give away $500 in cold hard cash every Friday till Labor Day. The more you enter, the more chances you have to win. No purchase necessary. All entries stay eligible for the $3,000 grand prize to be given away Friday, September 1st. You can also like and share our cold hard cash post on Facebook for a chance at the grand prize. You may be just as lucky as last week's winner. My name's Ollie Rowe. I'm from Mealy, Kentucky and I just won $500 from Appalachian Wireless. The long, hot summer of cold hard cash. Exclusively on the stations of East Kentucky Broadcasting and Appalachian Wireless. And this has been my definition of fresh since 1983. Welcome back to Arm-Chair Quarterback presented by Jimmy John's Gourmet Sugs in Pikeville Commons. The unofficial kickoff of the season takes place this weekend with the 33rd Annual Community Trust of Bankpike County Bowl to be played at CAM Stadium at Belfry and Pikeville's Hamley Complex. The Community Trust of Bankpike County Bowl has seen 32 years of success with over $812,000 being returned to the schools. While a financial success and fan favorite, Belfry head coach Phillip Paywood, who has coached in all 33 bowls, shares his thoughts on what the bowl means to high school football in our region. It's always a good atmosphere, you know, we have huge crowds for the bowl game. It's something our kids look forward to and it's something that over the years has really been good for us because it brings in some big named teams from way back when from the Fort Thomas Highlands, Louisville Mail and people like that from all across the state have come to play in this bowl. So it gives us some good name recognition and it lets people know about the programs here in eastern Kentucky and in our case Belfry High School and you can make a huge difference by coming out and being in those stands and letting these kids see you in the stands when they come out on the field on that Friday night. But it's been a great bowl game and great thanks to Community Trust Bank and the bowl committee and all the things that they've done and the original guys that came up with the idea because it's been such a good thing for football in this area. While Panther head coach Chris Magnamy has not coached in each of the bowls, he has been a player, coach and coach of a visiting team in the bowl. Coach Mac tells us why the bowl is special. Well I just think for eastern Kentucky in general I think it's a good thing. I think football in our part of the state has come a long way and you know since we started this bowl years and years ago but you know we get we get a chance to bring some good teams in here and and see what they've got and also for them to see what what we have to offer here and I think you know hosting at Belfry in here at Pikeville to the best programs around and I know our kids look forward to it every year. Well I think you're gonna see a good football team in Lakeston Christian coming in. I know they'll bring they'll travel well. I know our people will come out and it's just you know and got a good first game before us with Chevy Valley and in Pike Central two close teams so it's always packed here big time atmosphere for this early in the season and I'm hoping that everybody comes out and supports their local teams. The bowl kicks off at 635 at Belfry's Cam Stadium with the Eastridge Warriors battling the Phelps Hornets and the four-time defending state champion Belfry Pirates taking on Huntington High at 835. Saturday's Pike County Bowl a line up includes Pike Central and Shelby Valley at 630 in the opener and Pikeville hosting Lexington Christian at 835 at Hillard Howard Field. Saturday night one of eight Pike County Bowl Queen candidates will be crowned Pike County Bowl Queen and the 2017 Bowl legend honoree will be presented. This year's Pike County Bowl legend is former Pikeville and UK lineman Bob Shurtliffe. And week two of the Kentucky high school football season has some great matchups. Things get started with the 33rd Pike County Bowl Friday at Belfry's Cam Stadium Phelps Eastridge at 635 Belfry Huntington High at 835. Radio coverage on 93.1 WDHR 103.1 the Rock and Z1075 and the first home game ever for Floyd Central kicks off at 730 Friday with the Jaguars hosting Betsy Lane. Mingo Central will be at Point Pleasant again. You'll hear on 965 WXCC and Sherman is at Tug Valley. In other action, Tulsa goes to Wayne. Painesville visits Harlan. Harlan County is at hazard in a big matchup. Capital West Virginia travels to Johnson Central. Sheldon Clark is at Nont Central. MacGuffin County goes to Lawrence County. North Laurel will visit Prestonsburg. And on Saturday schedule, Pike Central Shelby Valley 635 at Pikeville's Hamley Complex in the bowl and Pikeville facing Lexington Christian at 835. You can catch complete coverage of the Pike County Bowl on WDHR 103.1 the Rock, Z1075 and hit City 98.1 FM. And the college football season kicks off tonight. The University of Pikeville Bears are on the road at Campbellsville. Bears coming off of Mid-South Conference East Division Championship look to open the season where it left off with the win. Kick off is at 7 in Campbellsville. Complete coverage on EKB's 107.5, Z107.5 and online at Z1075.com. That's going to do it for the season premiere of Armchair Quarterback. Thanks so much for tuning in. We hope you've enjoyed the show and join us again each week at this time. I'll leave you with this very true quote and thought about football and something that relates to life. Something to ponder. Winning is not a some time thing. It's an all the time thing. You don't win once in a while. You don't do things right once in a while. You do them right all the time. Winning is a habit. Unfortunately, so is losing from the great Packers coach, Vince Lombardi. Have a great week, everyone. Armchair Quarterback is a presentation of EKB Sports and brought to you by Jimmy John's Gourmet Sandwiches, Pikeville Commons. Thanks for tuning in.


I'd like to thank the TCGA and the organization for giving me the pleasure of presenting the results that we've been collecting with Mike Lawrence on the pan-cancer data that's being analyzed by the TCGA right now. So many of you have probably seen this slide and it just goes to the basic notion of how genome and exome data is analyzed in many of these sequencing projects. So the tumor and the match normal extracted from a patient and they're compared against each other to come up with the, to characterize the most important somatic genetic alterations that we tend to look at nowadays, which is a single nucleotera variance, indels, copy number alterations, translocations, etc. And then when we combine these we get cohorts of patients either in the same tumor type or now as you will see across tumor types to look at, to perform statistical analysis to see which genes are, which events are most recurrent, significantly recurrent in the population and then see what are these genes, what are the pathways and what is the selection that they provide to tumor genesis. So this is a little bit of overview of the data that has been collected due today and us the TCGA have contributed to a large portion of it and as you can see we cover about 20 to 25 tumor types with about 500 tumor normal pairs for each and you can see that we have many types of data for each. We have whole exome sequencing, we have whole genome sequences, RNA-seq, SNP arrays and methylation data and as you can see the ICGC is also contributing for a huge amount to up to 50 different tumor types with 500 tumor normal pairs for each. So this in a nutshell says that there is a huge amount of data and this is a flood that we have to handle and we have to take advantage of the power that it gives us and also we have to deal with the complexity that it actually represents when we add so much data together and the way this data is processed and this is something that Mike Noble will go over in his talk. So basically going from sequencing data to a BAM file which is the line data against the reference genome and then going through quality control and then going to the characterization pipelines that are all in fire hose at the brood and they detect all of the genetic alterations that we try to look for which is mutations, indels, characterizing purity of sample, copy number, rearrangements and pathogens in tumor data. So this is the overview of the pancancer data set so we have eight different tumor types so it's breast, colon, glioblastoma, kidney, lung squamous, ovarian, rectal and endometrial to a total of 2,143 patients and also that amounts to 436,755 mutations, coding mutations. So that's an extremely large amount of data and we can see here the spread of the different mutation frequencies across tumor types so we can see that they can vary and the lung has a significantly higher mutation frequency than the rest of the tumor types and we can see that within tumor type we have variable mutation frequency. Also we can see the different mutation categories on the bottom panel and the C2A changes are the ones that are prevalent in lung squamous and those are the typical signature for smoking and also we can see that C2T transitions are prevalent across all tumor types and those are largely the C2G context mutations which are contributing to the high amount of the background mutation rate. So in order to deal with the 400,000, approximately 400,000 mutations and figure out what are the recurrent genes, we have been working on the pipeline music for several years now and at this point in time this algorithm takes into account multiple factors so it calculates sample-specific, gene-specific and context-specific background mutation rates so this is for each gene, we try to estimate the background model just based on the number of mutations that are there and so then we look at the base level evolutionary conservation of the events, we look at the positional configuration along the CDNA to see where are the mutations located and are there particular hotspots that they cluster in and we also have a separate metric for truncating mutations. This is an overview below of all the different tumor types that we analyzed and we see that the number of significant genes varies from a couple of dozen to only a few significant genes and we see that in pan-cancer we actually detect a lot more and we'll go into the details one by one so I'll present all of these published studies one by one in the chronological order in which they were published, we can go over some of the genes that we find and then we'll see how that actually is represented once we combine all these data sets together. So this is Glioblastoma and this was published a long time ago already 2008 and we can see that here we find most of the genes that were published at the time that are characteristic for GBM like EGFR mutations, PTEN mutations, RB1 mutations, PIC3R1 mutations and then soon after this paper was published also IDH1 was published and we see that the mutations here are clustered in two hotspots in two sites and there's 15 of them so I'm going to go over what the columns mean of this table. So basically in this table we have a list of genes, we have a number of mutations, number of patients, number of sites and then we have the different P values that the algorithm outputs so we have the background model P value, we have the clustering P value, we have the P value for conservation and then we have a P value after we combine all of these different metrics together. So this is for Glioblastoma and then we see that IDH1 is up on the list and we have GABR1 and integrin alpha might be also interesting because it's clustered and also well conserved. And so also for Varian we see the basic highlight that most patients have P53 mutations and also by performing clustering and conservation analysis we managed to pull up SARC which is I'll be on low recurrence, there is only four mutations and four patients but they're in two sites that are well clustered and well conserved. So for colon we have as you've seen in the published data we have the two major pathways the wind pathway and the TGF beta receptor pathway, we have FBXW7, we have APC, we have FAM123B and then for TGF beta receptor we have SMAT2, we have TGFBR2, we have SMAT4, then we also have some PIC3CA mutations, we have BRAF mutations V600E that also cluster and they're very well conserved as you can see here. So we managed to get most of the genes that were published in an order on the top of the list, so the same two pathways are implicated in rectal tumor as well as you can see here. For lung squamous we also managed to get a lot of the genes that were published in the manuscript and one of the most important ones are Nf2O2 and KEEP1 which are binding partners, then we have notch one loss of function mutations that are similar to the head and neck paper that also came out with the similar type of mutations, we have RB1, we have MLL2, so as you can see we're getting the same mutations that were published and these are important pathways and they're important to their respective tumor types. For breast we also get all the genes that were and even though we lose in this case we use different algorithms we get largely the same genes that were published, so we get the genes from every different each subtype of breast cancer, luminal A, luminal B, basal, etc. So we get GATA1, RUNX1, we get AKT1, we get MLL3, we get P10 and also we also very interestingly we get SF3B1 which was published in a chronically lymphocytic leukemia paper in New England and also it was also implicated in MDS and it's a splicing factor that it's still being largely researched to see what the target that it's misplicing is, so for kidney cancer we have the two important genes that were just talked about in the previous talk, PBRM1, VHL and VAP1 and so here we have a much lower recurrence of P53 and also there is an interesting gene here, DNH9, which is clustered and conserved with 20 mutated sites. So with endometrial the most interesting genes here apart from the ones that are in the known pathways that we know about are NFV202 which is implicated in lung cancer and also we have SPOP which is important in prostate cancer and NFV202 is also clustered and conserved the same way it is in lung squamous but we don't see its binding partner here so it would be interesting to investigate exactly how this pathway functions in endometrial tumors. So now after putting all of these data sets together we have a lot more power to detect genes that are not significant in any of their respective tumor types because there is not enough power to detect them in them but now once we combine everything together we'll see that apart from the genes that we get that are significant and they're hallmark genes for each separate tumor type we as we go down the list we see genes that we can only detect by combining tumor types. So here on the top of the list this is 150 genes so there is five parts of this table and the top part shows the older genes that I just went over and they're all from the different tumor types that we described and they're all hallmarks of each respective tumor type up until we start getting to this part of the list where we have MTM1 and HCN1 which are new and then we have NFV202 and then we go forward to see another family member of hyperpolarization activate cyclic nucleotide receptor and then we have beta 2 microglobulin so we have a lot of genes that we wouldn't be able to find if we were doing all of these tumor types separately also ATM is a famous it's a it's a famous tumor suppressant gene it was found to be significant in CLL in the New England Journal paper where SF3B1 was found as well but we didn't find it as significant in any of these tumor types that we analyzed and also ERB2 is significant and and other genes as well on this list so and here we have different transcription factors like E2F1 which is a very well clustered and well conserved and we have also DCF7 and STK3 which is a serine 3 and in kinase which is not very recurrent in the set but it's really well clustered and well conserved so here is a here here are the genes represented as a percent maximum number of percent mutated for for the respective tumor type so we can see in this in this table that that the genes that order in the way that they were so we see most genes that we found significant by analyzing the tumor types separately so we have TB53, APC, P10, KRAS, PIC3CA so we have all of the genes that we've talked about in all the papers that we published so far and this this this represents summarizes the the recurrence of the results when we analyze all the tumor types separately and so when we combine the datasets together we get a table where there's where they're sorted by percent recurrence in the overall dataset the pancancer dataset and so here we we we see the same genes up on top that we get in all the papers but now we get genes that we think they're significant in one tumor type but they're also muted it in every other tumor type and that's DNA, DNAH9, we have FAT4, we have MLL2 and and then we have we have certain genes that we have to see if they're real or not like EYS and and so on NFE2L2 is only in lung but so so so to summarize these results as I said we have a different number of significant genes per tumor type and we have a lot of significant genes on the pancancer dataset and and we have a lot of new genes that come up and I only talked about a few of them but you see that there is a big list and and here are some of them that I just mentioned that are family members that might be important and then we have beta 2 microgoblin which is an immune immune pathway an antigen marking pathway and then we have MTM1 which is a muscle cell differentiation molecule and we know that that differentiation is an important mechanism in cancer but there are still genes that are part of it that we haven't found yet and and so so to conclude I think that when combining tumor types together there's two things that we have to keep in mind combining tumor types give us the significantly more power to detect putative driver genes that we're under power to detect in each tumor type separately and on the on the flip side it also dilutes the power to detect driver genes that are potentially important in the respective tumor types so genes that are found on the bottom of the significance table that are barely recurrent enough to actually be noticed by by the analysis team in the respective tumor type will not make it in the in the final list once we once we combine all the datasets together but here are some future steps that we need to consider when we combine datasets because this is a pretty complex problem so there's a couple of things we can do we can incorporate other information for potential functional role apart from conservation so there is polyphen 2 there is mutation assessor and there is chasm and racial cartoon we'll be talking about those things in the next talk and then we have we can we can perform the significance analysis on curated gene sets which we have done before for different tumor types and then we can extend this analysis to look at correlation and mutual exclusivity with MIMO within and across tumor types and we can take into account the variable background mutation frequency across the genome and by taking the variable mutation rate across the genome we can also look at pathways by performing significance analysis and out there gene subnetverse by working with hotnet and and paradigm as well so it's important to collaborate with these groups together and also the other thing that's really important this is as the previous speaker mentioned is that integrated analysis has not been done yet especially on these on these huge gene huge huge data sets where we get genes that are that are new and that are not significant in the respective tumor types so with that I would like to conclude and thank first of all gattie gets with being spearheading this pan cancer effort at the Broad and then Matthew Myers and Stacy Gabriel Levi Levi Eric Linda and Todd who are you know the leaders of the Broad who help a lot with this analysis and and bringing about these ideas and also I'd like to thank our analysis team and our collaborators thank you so how often two related questions how often do these look like gain of function versus loss of function these these rare ones that you're pulling out do you see second sort of corollary do you see particular point mutations at particular amino acids showing up in in multiple cancers very infrequently or these are more often very loss of function in many different ways so for for certain genes that we found in the in the last table that I showed we have we have an investigative there are really loss of function but we have both cases for DNA H9 for example we have hot spots and for beta 2 microgoblin we have to see if if if there are loss of function or not but we haven't really looked at these genes closely they're just you know just fresh out of the computer and we have to go through them so just two more questions then we'll have to move on hi I'm Angela from Harvard I have a question on since you've done the pan cancer analysis now can you comment on which pathway had the most mutated genes of from all the different tumors you've analyzed and my second question is are you look going to look at the promoter regions in your whole genomes to look for significantly altered regions so for the first question I think from from what I've been noticing and the the most implicated pathway seems to be you know the tg of beta receptor and the and the wind signaling pathway mutations that are on top of the list but we also have to look and see if we can place the other genes that we just discussed that are more rare into different pathways and for the second question I'm not exactly sure how many whole genomes we have to analyze this but we can use the flanking regions and the coverage in the flanking regions to see if there is any promoter mutations yeah basically so I'd like to know that if you have the percentage information or mostly for this mutation are they like site specific mutations or they are this most related to the alternative splicing like related to that also and I'd like to know that what kind of software you use when to identify these kind of mutations thank you excuse me can you repeat what type of mutations the first one yeah so my first question is asking and you you have any information related to these gene mutations are they mostly like a site specific mutations or are they like you mean the clustering yeah bake changes like alternative splicing so so the so the first question is about the cluster mutations right yeah related to the so we have so we have an add-on to the mutic algorithm that looks at jointly looks at the conservation and and the clustering and then we combine that metric with the with the p-value that we get for the for the different covariates that build the background model and so that way we can pull up genes that are not as recurrent in the data set but are well clustered and have some sort of conserved hot spot that might be important in a pathway and that that's how we can get genes like SF3B1 with a canonical site which is a splicing factor and then we can get other mutations like a lot of different kinases this way okay thanks thanks and uh one more speaker


Our culture is obsessed with the checklist and diagnoses. And if we're witnessing psychopathic behavior, we can call it psychopathic behavior because it is psychopathic behavior. There's a weird trend in our culture where we need to find labels and checklists as if all of us fit into some kind of Excel spreadsheet somewhere. People are all different. And I think it's a critical oversight that really undermines our understanding of psychopathy and it favors simplistic flawed labeling system that gives us a placebo of feeling like we understand something about the messy truth of just human life in general. The psychopath checklist is a model. And as Mark says, all the time all models are wrong. Some models are useful.