Right? So again, good morning to everybody. Welcome to our discussion on hematology 2. So last meeting on our last video, we talk about your, we talk about an overview on your hemostasis. Now, we're going to talk about your megahariocytopoasis. So your megahariocytopoasis will be a two-part discussion for today. So a two-part discussion and I divided it will be first talking about platelet production, the megahariocytopoasis part, the production of your megahariocyte and your platelet shedding. And the second part of our discussion will be talking about your platelets alone. So your platelets alone meaning to say we're going to talk about the ultrastructure and also the function of your platelet. Now let's get started with our discussion. So first and foremost, let's talk about your megahariocytopoasis. Some of you are wondering through, is there a difference if I call it megahariocytopoasis or megahariopoasis? There's none. I just wanted you guys to get familiar with the megahariocytopoasis because I guess you are much familiar with the megahariopoasis, but nonetheless, both of them are the same. Now moving forward, megahariocytopoasis is actually the production and the development of megahariocytes. Let me just reiterate that part first. This isn't the production of platelets yet. This is the production of your megahariocytes. I have to clarify that part because later on, we'll be talking about your platelet shedding and platelet shedding is known to be your thrombocytopoasis. This is now the actual production of your platelets and they are now being shed into your bloodstream.  Similarly, just like your hematopoasis, your megahariocytopoasis also happens within your bone marrow. Let's just have a quick review. You're seeing a diagram of the hematopoietic stem cell, your pluripotent stem cell.  Now we're going to talk about in more detail, your megahariocytopoasis. Last time, during our orientation, one of the few questions I asked you guys is that from what progenitor cell did your megahariocyte came from? There are actually two lineage that we all know. The common myeloid progenitor, let me just pull out my laser, your common myeloid progenitor and your common lymphoid progenitor. Between the two, your common lymphoid progenitor only give rise to three types of cell, your T cell, your B cell, and your natural killer cells, which are to be discussed in our immunology serology discussion. Now let's focus our attention to the common myeloid progenitor.  It will also give rise to your erythrocytes and most importantly will give rise now to your megahariocyte that will also produce now your platelet. Now let's focus our attention to your megahariocyte erythrocyte progenitor. Remember that your common myeloid progenitor is being influenced by a lot of your interlukin. In this particular part, when it comes to your common myeloid progenitor, it will commit itself to become a megahariocyte erythrocyte progenitor. Remember that your CFUGMM will influence your common myeloid progenitor, now that it will now start to differentiate and to commit, excuse me, one moment please. Now moving back, your megahariocyte erythrocyte progenitor will now commit itself to either produce your platelets or to produce your erythrocytes. So depending on the hormone that will be produced, so if it is an EPO, your erythropoietin, it will be committing to become, it will be influenced and it will eventually commit to produce erythrocytes. If your thrombopoietin is the one that is produced then it will be influenced, therefore will commit to produce your platelet. Remember that your hematopoietic stem cell, ladies and gentlemen, can make copies of themselves to maintain the stem cell pool and they do possess the ability to generate cells of all lineage. That's why we call it pluripotential. So this stem cell give rise to multipotent myeloid and lymphoid progenitor cells. We say multipotent because they can become a granulocyte, a monocyte, a basophil, eosinophil, megahariocyte, erythrocyte. Even your lymphoid progenitor is also considered to be a multipotent. Why? Because it can become your T cell, your B cell or your NT cell. So ultimately the progenitor cells are restricted only to specific lineage. So that's why I have to clarify and reiterate to you the difference between the common lymphoid and the common myeloid progenitor. So with appropriate cytokine stimulus, appropriate hormone, stimulus, the committed progenitor cell will undergo proliferation to a recognizable precursor of that specific cell they committed to become. Similarly in our life, if you want to become a medical technologist in the future, you commit to yourself with all the stimulus, the academic, and also extracurricular stimulus that will help you proliferate, that will help you differentiate to a recognizable meditech in the future. Similarly to your megahariocyte, that's also what happened. They will also differentiate and mature and therefore become a mature end stage cell. So this stem cell and progenitor cell, always remember, cannot be morphologically differentiated. What I'm trying to say is that lahat sila magtapa mukha. Let's say in English, all of your progenitor cell, including your hematopoetics stem cell, all of them looks the same. They are morphologically indistinguishable. So all of them look like the same cell. So how do we differentiate them later on? We'll be talking about that shortly. So since we cannot classify them by their appearances, by their morphologic appearance, what we use now are your CD. I mentioned it immediately, your CD or your cluster of differentiation. So your cluster of differentiations, these are protein markers specific to a specific type of cell. But think for example, you have identical triplets. So these are three individuals, all look the same, but there are distinguishing marks that will enable you to identify who is this person. If this is A, B, or C. So similarly, with the use of your cluster of differentiation or your CD proteins, we're also able to classify them. That is only through CD or cluster of differentiation. Never through morphological or microscopic differentiation. So let us note that I wrote down our discussion to your megacaryocyte. Remember that your megacaryocyte of poesis happen in your bone marrow and most of your megacaryocyte. The differentiating in your mature megacaryocyte usually are localized in the abluminal or the non-blood surface of the sinusoid lining in the telial cells. So as you can see, they are not within the blood surface. So they are just near or they are localized. They are residing on the lining of your endothelial cell. This is in preparation for their bupid into the blood stream. They just reside near so that at any given time, once that they are ready to shed the platelets, they can already deliver it directly to the blood. Directly to your blood. So since we're already talking about your megacaryocyte to poesis, let's talk about now the progenitor cells of your megacaryocyte. So when we say progenitor cell of your megacaryocyte again, similarly to your hematopoietic stem cell, they are indistinguishable. So there are three stages of megacaryocyte progenitor. So from your megacaryocyte eretrocyte progenitor, remember it will become your CFUGMM will give rise to your megacaryocyte eretrocyte progenitor. So once that there are cytokines like your megacaryocyte colony-stimulating factor or your MEG-CSF together with your interleukin-3, now with also the influence of your thrombopoietin, your CFUGMM will now be differentiating into becoming your burst forming unit megacaryocyte or your BFU megacaryocyte. Your BFU megacaryocyte is capable of producing or proliferating into forming hundreds of BFU. That's why you call it BFU because these are burst forming units. They can undergo mitosis. So eventually this burst forming unit will eventually become now your colony forming unit megacaryocyte. Your colony forming megacaryocyte, your CFU will now form a differentiated and a more mature megacaryocyte. Remember that in your BFU meg and your CFU meg, burst forming unit megacaryocyte and colony forming megacaryocyte, both of them are still capable of the normal mitosis. I say normal mitosis because once that your CFU and your BFU meg become now your LD CFU megacaryocyte or your light density colony forming unit megacaryocyte, it is no longer capable of the normal mitosis. It is only capable of endo mitosis. Before I explain to you guys what is endo mitosis, remember that your BFU meg CFU meg and your LD CFU meg, all of them looks the same. They cannot be differentiated from one or the other. All of them looks the same. You guys might look at it as something smaller, but your BFU meg, these are actually all BFU megs. These are all BFU megs. These are all CFU megs. We are just trying to give you an idea how much, how much mitotic activity do they have. So your BFU meg can form hundreds of BFU megs and then it will differentiate to become your CFU meg and then it will become your LD CFU meg. So again, between among the three, LD CFU meg is the one not capable of normal mitosis, not capable of normal mitosis. What is it capable of? It is capable of what? It is capable of endo mitosis. So what is endo mitosis? So let me explain what endo mitosis is. Endo mitosis is a form of mitosis that lacks your telophase and your cytokinesis. So as you all know, your mitosis has four important phases, your prophase, metaphase, anaphase, and telophase. So those are the five phases or the phases of your mitosis. Now when it comes to endo mitosis, it is not similar to the usual one that our cells underwent every now and then because your endo mitosis lacks your telophase. So there is no cytokinesis, there is no cell separation, there is no production of two daughter cells. Instead what happened is that your megacaryocyte just continually just continue to grow. Your megacaryte will just continue to grow. Your megacaryocyte will employ their multiple DNA copies. The DNA will continually replicate and the nucleus will continually enlarge. But at the same time, it will also synthesize abundant cytoplasm. Magproduce abundant cytoplasm because ultimately that is where your platelet will come from. So in a more technical aspect, remember that you have your gata one or it stands for your globine transcription factor one and your FOG gene, which is a friend of gata, a friend of gata one. That's why it is FOG one. So what happened is that these two are the one that facilitates or ensure your mitosis. But once that it enters your LBCFU peg, your gata one and your FOG one will now start to slow down being expressed in your cell. Once that nawala or these two are no longer expressed, the one that will be expressed now, the one that will control the mitosis inside your megacaryocyte are your RNX1 or your RNX1 gene. This is a gene that will now initiate your endomitosis. So once that your RNX1 is the one responsible for the mitosis, it will become now your endomitosis. Endomitosis in the sense that there will no longer be cell division. There is technically a cell division and I hope you get me guys now. But there is no longer a telophase and a cytokinesis part in the cell division that's happening. And that is what we call your endomitosis. Where do we see endomitosis? We see that in your LD CFU meg of the three megacaryocyte progenitor. Three megacarycyte progenitor. Again, reiterate to everybody the stages are your BFU meg, your CFU meg, and your LD CFU meg. So your BFU meg is the least mature one of the three progenitor, meaning to say, ito yung pinakabata, least differentiated, followed by your colony farming unit megacaryocyte, which has at this time, since this is still normal mitosis, it's still deployed. It produces deployed. It participates still in your normal mitosis until we go to your LD CFU meg, which is the one more mature of them all. Among the three, your LD CFU meg is the most mature. Aside from that, your LD CFU meg, aside being the most mature progenitor of your megacaryocyte, it also loses its capacity to divide. Again, that is your endo mitosis. That is your endo mitosis. It lacks your telophase and your cytokinesis. So there is no separation now of your daughters. So all of these three, again, resembles like a small lymphocyte in your bone marrow. If you prepare a bone marrow, a bone marrow smear. So remember that all of these three that we're discussing cannot be differentiated morphologically. That's why we're saying that these are morphologically indistinguishable from one another. Now, the question is, sir, how do we identify them now? So the way to identify them is through immunologic test or cytokemical state. I guess you guys are familiar with cytokemical stain from your histopathology last semester and also hematology one, specifically when you talk about your white blood cells. When you did talk about your white blood cells. So there are immunological tests that uses your flow cytometry that will allow us to identify what specific cell are we dealing. So there are different markers that we can use. So you can use your MPL.  So as you can see, as you can see guys, the bar that you can see meaning to say the marker is present in that particular specific. The marker is present on that specific type of cell. So now I want you guys just to focus first on your BFU meg until your LDCFU meg because they are indistinguishable morphologically. So like for example, you look at the microscope. You will not know if this is BFU meg, CFU meg, or LDFU meg unless you look at the microscope. Unless you look at the microscope. Now how are we going to differentiate BFU meg? BFU meg can be differentiated because it does have all of them. So let me just try to erase the high things that I did. So here, how do we differentiate your BFU meg from all the others? Remember that when you use MPL, all of them does have MPL. So check. They do have MPL meaning to say we cannot use MPL to differentiate them because they all have the same. Now when we talk about CD4, that's also problematic because all of them does contain CD34. So we cannot differentiate that. We cannot differentiate the three using that. Now we can differentiate your BFU meg from your CFU meg and your LDCFU meg using your CD34. Why? Because your BFU meg do not contain your CD41. So if the cell contains MPL, CD34, but does not have your CD41, that means that it is a BFU megacarouside. Now let's go to another story. How about CFU meg and LDCFU meg? Sure. If we're going to do immunologic test, if we're going to do immunologic test, they're almost the same. They're almost the same. So how will I be able to differentiate one from the other? To answer your question, the ultimate differentiating factor between your CFU meg and your LDFU meg is to identify if there is endometosis or not. If there is no endometosis, walang endometosis, then that is probably your CFU clinical carouside. But if it has, okay, if it has your endometosis going on, then that will give you an idea now that what you're looking at, what you're seeing or what you are counting are your LDCFU megacarouside. So again, please remember how to differentiate them. Your BFU meg can be differentiated using your CD41 between the two CFU meg and LDCFU meg, how to differentiate them by identifying which one has your endometosis. Okay? Which one has your endometosis? So please, again, remember that. Okay? And do not forget that in our succeeding discussion. Now, okay, we are finished talking about the non-identifiable stages of megacarouside progenitor, which are your BFU meg, your CFU meg, and your LDCFU meg. So do not forget that, do not forget these three. So these are the first three progenitors of your megacarouside. After that comes now your morphologically identifiable. When we say morphologically identified, we can now identify them under the microscope, okay? So we have your MK1, your MK2, and your MK3.   And now finally, okay, we also have your blast that is your megacarouside, which is the mature one now, okay? So to further give you their identifiable or their distinguishable characteristic, so let's go on. Your MK1 or your megacarouside blast, they contain your, you can see plasma blebs, blunt projections, okay, sorry for the typographical error. So they have plasma blebs, blunt projectors, okay? So their plasma blebs or these are blunt projections from the margin that resembles your platelet, okay? At the same time, you can already see your demarcation system. So this is very important. Your demarcation system, these are like lines, okay? If this is your cell, okay? These are already lines, okay? Or cutouts. It looks like cutouts within the cytoplasm and that will now be shed off as a mature platelet, okay? A mature platelet. So there, you have cutouts or these are demarcation lines. Yan matatanggal, okay? Kapag nag shed off yan, that is now an entire platelet, okay? So aside from that, we also have your MK2 or your pro megacarouside. So they have lobulate nucleus. So aside from, they do have lobulate nucleus. So you have to see lobulation on their nucleus already, okay? And lastly, okay? Lastly, we have your MK3 or your megacarouside. Intensely, they are observable by having your intensely lobulated nucleus already. So between the two, you can differentiate pro megacarouside from megacarouside depending on the lobulation and their nucleus. Aside from that, if you're reading your product, the latest edition, you can also differentiate them and you can specifically identify your megacarouside by identifying the ploidy level, okay, the ploidy level using your propodium iodide, okay? Using your propodium iodide. So this is what we use, okay? This is what we use so that you'll be able to what? You'll be able to identify your platelets or rather, your megacarouside. Now, okay? To give you a summary, okay? So remember, so this is a terminal megacarouside differentiation stage. So we can differentiate them according to their diameter. But most importantly, what I want you guys to remember when it comes to the difference to the megacarouside differentiation stages, your MK-123, when it comes to my tosis, all of that, MK-123, it's already absent. When it comes to endometosis, in your megacario blast, it's still present, okay?  And already absent in your MK-3, in your MK-3. And lastly, your demarcation system is present in all of them. Similarly with your alpha granules and also your dense granules. Much about your alpha dense granules in your demarcation system once we reach your ultra, the platelet ultra structure. Now, we're nearing the end of our discussion. So now that we already know, there are three progenitor cells of your megacarouside, your BFUMeg, CFUMeg, LDCFUMeg.  Now, we will now talk about your megacarouside. So this is not the end of your megacarouside to poesis. Your megacarouside is the largest cell in the bone marrow. So we have less than 0.5% of all, we have less than 0.5% megacarouside of all bone marrow cells. So, with multiple chromosome copies because of their polyploid, because of their polyploid, we can reach up until 128 ploidy, 128 ploidy, again, because of endo, mitosis. So we can identify them, okay, we can study them using your bone marrow aspirate and stain them using your right gym sustain. And when we measure it, it's around 30 to 50 micrometer. So their nucleus is multi-lubulated, intensely-lubulated. Because this is already your MK3, your megacarouside. So, when you're looking under the microscope, you can see around 2 to 4 megacarouside per 10 times LPO, okay, per LPO field. So 2 to 4 megacarouside per LPO. So, that's now how your megacarouside are produced. So from the hematopoietic stem cell, okay, from the hematopoietic stem cell, it becomes your CFU GEMM. Influenced by your TPO, your megacarouside-stimulating factor, colony-stimulating factor. And then your interleukin 3, becoming now your BFU meg, CFU meg, LDCFU meg. And then, becoming now your megacarouside pro-megacarouside. And then eventually your megacarouside, which we have now like this, okay? This is now your megacarouside, okay? This is now your megacarouside. Now, once your megacarouside are mature enough, okay? Sabi natin kanina, they will be residing on the endothelial lining of your bone marrow. They will now be ready for platelet shedding. Okay? Your platelet shedding, also known as thrombocytopoiesis.  Okay, this is your megacarouside. And this one, okay, a pro-platelet projection. Okay, a pro-platelet projection. As you can see, they are now releasing. Okay, they are now shedding. Rather, they are now shedding your platelet. So, one megacarouside, okay, one megacarouside can produce around 2,000 to 4,000 platelets. So, maybe you're wondering how are they being released or how they are being shed. That is through your demarcation or your demarcation system, the one that I'm talking about moments ago. So, your demarcation system are like cutouts in the cytoplasm that will be where your platelets shed or be released. So, they undergo fragment the cytoplasm of your megacarouside undergo fragmentation where your platelets are now being released. Now, the platelets are formed at the end of your pro-platelets and are released by micro tubular action. Okay, I'll show, I think I have a picture later. I think I was able to delete the picture here. Here na lang. This one, okay, this is your pro-platelet. It's an extension. It's like an extension of the cytoplasm where your platelets are being shed. Excuse me.   So, your thrombocytopoiesis leaves behind a megacarouside nuclei to be consumed by your bone marrow macrophage. So, remember, okay, like what I was mentioning tanina, okay, like what I was mentioning tanina, your megacarouside even though they do not divide, okay, even if they do not physically divide, they grow their platelet, they grow their cytoplasm because that is where your platelet would come from. Now, the cytoplasm will completely be fragmented and all will become platelet. Around 2,000 to 4,000 platelet will be produced. Leaving us now in noclius, that is exposed and will now be consumed and engulfed by your macrophages, okay, your macrophages. Now, remember, the pro-platelet, the one that I showed you tanina, that is a pseudo-podial extension, okay, a pseudo-podial extension of your megacarouside where your platelets are being released, okay. Now, we finish your megacarouside, we finish, they already undergo thrombocytopoesis or platelet shedding. Now, for the last part of the discussion, let's talk about your platelets or commonly known as your thrombocytes. These are inocliated cells. The only they are inocliated cells, okay. They are inocliated cell, so they are around 2.5 micrometer, so when it comes to their mean platelet volume that is around 8 to 10 femtoliter, so they are the normal range or the reference value for your platelet in a normal individual that is 150 to 400 times 10 to the 9 10 times 10 to the 9 power per litter. It's slightly lower at both sexes over 65 years old and your platelets are technically higher in women. So 30% of your platelets or one third of your platelets are found in your spleen. They are deposited in your spleen and two thirds of your platelets are circulating. So one third or 30% are stored in your spleen that is your resting platelets and two thirds or 70% of your platelets are circulating platelets. Okay, they are circulating platelets. Again, the 30% that is yours that is your resting platelets this are your circulating platelets. So platelets per oil immersion field in your peripheral blood smear a normal one normal when you look at it under the microscope it would have around 7 to 21 7 to 21 platelets per oil immersion field. So your platelets are the one that could trigger your primary hemostasis your primary hemostasis remember your primary hemostatic is your platelet blood. Okay, now to end our discussion let's just talk about a few things before we end this discussion and that is about the different hormones and cytokines of your mega cario cytokines of your mega cario cytokines So the first one are the one that in the most important hormone in your mega cario cytokinesis because they induce stem cell differentiation they induce proliferation and platelet release and these are your drogopoietin ladies and gentlemen are found in your kidney similarly with your erythropoietin although they are also found in your liver and in your smooth so kidney, liver and smooth muscle majority are coming from your liver now it circulates in your plasma your drogopoietin circulates in your plasma and for individuals that has problem producing drogopoietin and would now lead to drogopoietin there's a recombinant drogopoietin that can be used so that as a therapy we can trigger or we can elicit a production of platelets in those patient so aside from that aside from drogopoietin I also mentioned some cytokines a while back and these are your interleukin 3 that is involved for the early differentiation of your stem cell remember your megakaryocyte colony forming colony stimulating factor or your MEG-CSF your MEG-CSF together with your interleukin 3 and your TPO they allow the differentiation of your stem cell to become your BFU megakaryocyte aside from that we also have your interleukin 6 and interleukin 11 to enhance endometosis remember what Jean was responsible for endometosis that is your run X1 your run X1 so endometosis and then eventually megakaryocyte maturation and platelet release and platelet release so finally finally I already showed you this ano na I already showed you this picture a while back this is how we different this are the different hormones and cytokines that control your megakaryocyte so remember your TPO interleukin 3, 6 and 11 so interleukin 3 and TPO is for the differentiation of your progenitors BFU meg until LDCF for the differentiation of your megakaryocyte we have TPO interleukin 3 and interleukin 11 for late maturation your TPO interleukin 6 and interleukin 11 for trombocytopoiesis the platelet shedding we only need your interleukin 6 and interleukin 11 so with that thank you so much everyone for listening so I hope you have an idea now how your megakaryocyte to poiesis is happening inside our body now for the second part of our discussion on our next meeting we will be talking about the ultra structure of your platelets with that thank you so much for listening so if you have any questions or gratification please send me a message through TLC or through my email and I'll be happy to answer you as soon as I can so thank you so much for listening with that thank you so much you can now leave the platform and do not forget to read your book okay to read your book so that you'll be able to have an idea of the entire context of what we just discussed today so again thank you so much and I'll see you on our next discussion goodbye


Hello, everybody, and my name is Davide. I'm a production engineer at Facebook, and I'll be talking for a bit about what we've been doing with SystemD for the past year or so. I've given versions of this talk before, and hopefully every year there's something new that's interesting. I'll start with a quick recap of the story so far. I'll talk for a bit about what we're doing for deployment, and how that ties into the development workflow we use for SystemD. I'll quickly go through a few new features, and I'll try to close with some case studies if there's time. So without further ado, as I said, I'm a production engineer. I work on the operating systems team. My team is responsible for maintaining CentOS on the Facebook fleet. We have a lot of machines, as you might imagine. We have a lot of physical machines. All of these machines run CentOS. All of these machines run SystemD. We're on CentOS 7 on the fleet. We're starting to prep for Cent8, but right now everything is on Cent7. And by now we've been doing this for a while. We've been running SystemD for at least three years on a wide scale. And it's said to the point where it's pretty much everywhere. It's been quite interesting seeing internally how things moved and how people reacted to it. When we started doing this, people were fairly skittish. We had to do a lot of work explaining people why we were making the effort to move to SystemD when we're doing CentOS 7. And now it's at the point where it's the opposite. We have people reaching out to our team and to other teams fairly frequently with ideas they have for new features they want to build that might tie into SystemD or how they might leverage new SystemD features for what they're doing. And at the same time, we've also started doing a lot of development ourselves around SystemD and its ecosystem, contributing both to SystemD proper and to tools around it. And I'll go over some of these. So how do we get SystemD on the fleet? We deploy SystemD with Chef from RPMs. We don't run the SystemD as in CentOS. We build it from GitHub because we want to be able to track what AppStream is doing. So at the end of last year, we were on 239. When 240 was released, 240 was a pretty big release. It took us quite a long time to qualify, so we ended up skipping it for deployment. We were on 239, 241, and then 242, which is what's running now as of today on 98-ish percent of the fleet. We started playing with 243. It's not in wide deployment yet, but we have it running in some places. That's probably what I'm going to start working on when I get back from this conference. The back port we use is based on the Fedora packaging. You can find it there if you're interested. In general, these processes work pretty well. We've been doing this for a while. We don't have any major issues with it itself. The main pain point here is that the long tail is annoying, and the long tail is pretty small, it's 2% of machines, but when you have a lot of machines, 2% is still quite a bit. And there are too many reasons for the long tail. One reason is that sometimes you just have broken machines, and broken machines sometimes don't run Chefs, sometimes there are PM databases corrupt, sometimes things happen and systems don't get updated, and for one reason or another, they stick in production, and it takes a while for them to go away. I don't care about those that much, because eventually they'll go away, and they're broken, so who cares? The thing that's more annoying is that sometimes when we do a release, we have to put in place exceptions because we will find, either we will find a change in upstream or a bug or something that affects a specific customer in a way that they can't quite update right now, and at the same time we don't wanna stop the whole rollout just for them, so we'll pin them to the previous version and then we'll go on. Or sometimes we'll find that something changed and something our customer was doing was either wrong or doesn't fit quite well with the model. So you end up tracking these around, we have four or five of these in place right now. I think the oldest goes back to 2.39. We are fairly diligent at cleaning this up, but sometimes you have to deal with that. Now, as I said, the release process works fairly well, but it does take a while. Oftentimes, from the moment when the system, the upstream, cuts the release to when we deploy it in production, the actual manual work of prepping the RPMs for testing is a couple of days of work maybe, but it can take quite a while from getting it to the point where we feel safe rolling it on the fleet. Part of the reason here is because when we go from one release to another, we don't generally do much testing with what's happening in between. We will follow what's going on upstream, but we do deployments on the fleet between major releases. So there can be quite a lot of changes that accumulate and that can lead to last-minute surprises for people. The other thing is that there's basically two people doing this, which is me and Anita, so if one of us ends up under a bus, that's not ideal. What we'd really like to be able to do is do the development and testing concurrently. Most of the time when people do feature developmental systems, they'll do it on master, then they'll end up reporting the patch internally and testing it on whatever release we have deployed. This isn't too bad, but it is friction. We would also like to be able to do more and faster integration testing, having better ways to find issues early on and have a fast-figure process, both for our developers and for upstream developers. So I started looking at what we could do there and we ended up building a little CICD pipeline for this. This is not open source, mostly because it ties into internal stuff. It's also not particularly rocket science. We take the Fedora packaging. I have a horrifying shell script that replaces the tarbol in there with a tarbol made from Gitmaster. It runs every day at 10 a.m. It builds the RPM, it runs the test suite as part of the build. If that passes, it deploys the RPM on a small number of machines and we have a daily running on a small number of machines. We are working right now on getting this hooked up also with the container testing infrastructure because one of the main customers we have of SystemD is the container infra. So this way, we can find issues early on. Now, this is something pretty simple and yet these letters already find a significant number of issues way before our release. And when we cut 243, when we cut 242 and later 243, this was a lot faster. We had this running since March. It led to filing maybe about 10 GitHub issues between GitHub issues and PRs for various things we found throughout it. One thing I want to add soon is integration testing of bare metal as well. I've also started looking at there's a test suite on GitHub that Red Hat uses for doing the CI based on CentOS hooked to the upstream repo. I want to start looking to see if we can run those tests internally as well to have better coverage there. So that's on the deployment side. On the development side, as I said, we would like to be able to do faster, faster iteration and faster development. And we would also like to be able to leverage the internal tooling we have for doing code review, for doing CI. Right now, the way people do code review for system D changes tends to be, they make a pace being equivalent of what their patch is and one of us looks at it, which is not ideal. We also already know how to do this, because if you look at it, this is kind of like the kernel development process. So the current plan is to basically do what the kernel team does. So we are putting together an internal system repo that will be just a read-only mirror of what's on GitHub with the same branches, same tags. People will branch off master for future branches, so if they're working on a thing, they branch off master, work on their, mirror their PR, hopefully they'll build a thing, cut from it and test it before they make a PR, but you know, this way, at least they can get signal on what's going on. When we make releases, we'll branch releases off, release, after they release tags, cherry pick from the future branches, cut the release. This has also the benefit that we can get rid of the hairy pile of patches we use right now with the RPM packaging and we'll just have a simple script to grab patches from the Git tree. This is exactly what the kernel team does. We think it might work and make life easier for us and hopefully lead to having better and faster feedback outside as well, but we'll see. And I'd actually be interested to hear if other folks here do internal development for system D, what development process you use, or if you build tooling around this. Now, let's go over quickly a few new features that landed recently. I'm not gonna spend too much time on this because there's been a lot of other talks from Facebook people on things and I'd rather have them talk about what they work on. Once in it hasn't come up yet, that is pretty cool and ended up in 243 is that condition. Exact condition is something that Tanita developed. It's kind of a hybrid between condition and exact start pre where it run a commands before the unit is started, actually before the prescripts run and depending on the execute of the command, it can pass, so it will keep running the unit, it can fail, mark the unit has failed or it can skip execution kind of when a condition fails. Now, why would you want to do this? Well, I can tell you why we want to do this. The reason we want to do this is that we want to gently nudge people to do continuous deployment of their tools. So we want to have a tool that checks the binary and if the binary is too old, just refuse to start the service and then do a bunch of other things but that's one of the main reasons and this is a fairly simple and straightforward way to do it. There's a possible improvement where we could maybe have a percent specifier so we don't have to copy the name of the binary there but that's just sugar. This is actually a pretty good example of I think feature development that goes well because we came up with the idea of maybe we should do something like this before Christmas internally. We discussed it, we played with a few ideas. We were in Bernot in February for DefConf, we met with assistant developers, we discussed this with them, we brainstormed on possible designs and we ended up with, oh yeah, doing like this seems to be simple enough and it could work and then it was coded in the months afterwards and it landed in 243. I think this is pretty much the ideal way you want development to go. On the resource management front, there's already been several talks. Teju and Dennis talk cover resource control in general. Dana and Anita talked about UMD. Ioannis is gonna talk later today about Senpai. Two things I wanna raise, there's disabled controllers that landed for transient units as well. Disabled controllers is quite handy because it allows you to turn off specific controllers without having to rely on kernel command line flags so without having to reboot the box. The other thing that landed is a number of UM specific control for the kernel UM, not the user space UM around C-group 2, notably UM policy, so you can apply UM settings to specific C-groups. Something else we've been working on for a while is Python D. Alvaro did a Lightning talk on this yesterday. So Python D is available there. It's a thin-size-on wrapper on top of SDBus. It wraps the SDBus API with the idea of making it easier to interact with system D, but it also allows you to pocket D-Bus in general. Right now, this supports pretty much all the D-Bus properties exposed by system D. It's been working quite well. We've been very happy with it and we've started building quite a lot of tooling around it internally. I would like to see this more used in general because at least in my experience, it's one of the most stable ways to interact to D-Bus from Python. Once in the landing recently, it's also socket support, so you can do fairly neat or terrifying things, depending on your point of view, where when you, that's just an example, you can import to try it, but what that does under the hood is that it makes a transient socket, makes a transient service, then forks off and a little Python web server and it ends up being managed as a proper service with a proper socket, which is nice. I mentioned before, we have for config management. We have a code book called FB system D for managing system D, some GitHub, it's been there for a while. We, there was quite a bit of work on these in the last half or so, mostly internals. One thing that's interesting is when you write on this system unit, you generally end up doing that using templates. Using templates for managing overrides is what we were doing before. It's really annoying because you end up writing the same boilerplate code which is make the directory, make the template, then delete the directory, clean up the template, reload system D is obnoxious. So I wrote a little customer resource in Chef that lets you drop an override and internally it figures out where should it go, it cleans it up when it needs to be cleaned up, it did, reload system D when it needs to be reloaded. This is pretty useful and it's straightforward enough and the syntax is about the same as the upstream system D unit resource in Chef. Then one more thing that Chris down has been working on. Lately is a linter for system units. When people use system D, they find about a lot of features that system D has and they start using them. Some of these features are great. Some of these features, we'd really rather than not use them. Like one example is people using kill mode equal process and not really understanding what it does or people using interesting settings for namespacing without really understanding them. So all of these are things that are well suited for linting. There's already a bare bones, it's not really a linter, it's more of a consistency checker built into system D that's analyzed. This is meant more of a general purpose. Linting tool where you can define a policy for the things you care about and then it can surface them. We have this running internally, it exists and it works. We would like to open source it by the end of the year. It's a standalone tool so there's nothing Facebook specific in it. Hopefully people will find it useful and maybe it will help other companies and folks prevent issues there. Okay, I have a couple of horror stories on the same theme of implicit dependencies. So on this one we had a bunch of machines where after we rolled out a new system diversion, I don't remember if it was 241 or 242, we started seeing that NTP was not starting on boot. After considerable digging, we discovered that the NTP service in CentOS uses private temp, which is fine, except private temp internally takes a dependency and implicit dependency on temp.mount, which I did not know and only found out after digging through this. This would be great except on these machines for because of the way they were set up, people didn't really notice that the way they were set up was that they would boot, temp mount would start and do this thing, but then we would mask temp.mount in Chef. So you would end up with this unit that would be both active and masked, which is probably not something that's supposed to work. And in fact, while this works in 239, in the sense that by works I mean it doesn't complain, from on later versions, system view will hard fail and refuse to start a unit that happens to have a dependency on a thing that is both active and masked. So yeah, this was not great. This was actually one of the things I mentioned before where we had to pin this fleet to 239 for a while while we figured this out. It took us probably a week working on it on and off because it wasn't really a showstopper. We could keep it running just fine when it was back on 239. So yeah, implicit dependencies are kind of annoying. We had another case like that where we had some hosts where some directors just were on their own boot. After digging, we found that the temp file was not being created because the temp file setup never ran. And since the temp file setup depends on local FS, it depends on swap. Except one of my colleagues was working on this code book called FSwap to do encrypted swap and a bunch of other things. And he added a whole bunch of masks to the unit as the dependency of swap.target, which makes the whole thing fail so the entire thing gets prone, it doesn't exist anymore, and you end up with no temp files. The way we debug this, by the way, both of these problems, but these ones specifically, was you use system.deanalyze, system.deanalyze just to really hand the commands, plot and dot, one will give you a butcher-style plot of the boot, the other will give you the octopus-style dependency graph. The dependency graph is completely useless in our case because it ends up being this gigantic thing, but you can tell it to only show you a subset of it, which is very helpful. You can also enable debug logging in PID-1 either by killing it with a special signal or by passing a command-line flag. This is actually how we found this out because we ended up seeing the debug message that said these three is getting prone because this thing doesn't exist anymore. And that's all I have. Questions? You mentioned that you are starting to think of debugging system.deanalyze, like debugging the kernel. Developing. Developing the kernel, but also, I guess developing involves debugging. Can you elaborate a little bit more on that analogy between kernel-level stuff? Are you bisecting things? Are you the whole range of what that would mean? So I meant that primarily in terms of development workflow. More than specifically on the debugging side. In terms of development, we have a fairly well-honed process where we have an internal kernel tree. We use exactly that, the feature branches and the release branches model. We have automated testing for the kernel. We have CI. We have automated deployments. We have very good way to understanding either via CI or via AB testing whether a specific change is going to impact things and how it's going to impact them. And we would like to bring that to system.de as well and eventually to other system software we work on. For debugging-specific issues, I mean it ends up becoming... It's very different, actually, I think, than developing the kernel in the same senses. And it tends to be very hit or miss. What I personally do is play with the debug logging, play with tools available on the box, surprisingly oftentimes tracing PID-1 ends up being very useful for understanding what's going on. We had a couple of cases when we ended up with PID-1 that locked or in bedstays. I talked about them last year, actually. And in those cases, tracing was how we found out what the hell was going on there. We had interesting and tricky interactions between kernel and user space sometimes, especially when there's API mismatches or things that change. But I say that doesn't really happen that often nowadays. We got pretty good at that. I would assume that at Facebook you are logging a lot of stuff. Do you use JournalD or do you have a different logging system? Are you logging remotely or locally? We run JournalD on every machine in the fleet. We run, by default, we run JournalD with a 10 megabyte volatile journal. And then we run RC's log on all the machines and RC's log ships the logs off somewhere. I don't know what happens afterwards, actually. There is a lot of collection infrastructure managed by the security team for that. The reason we do this is because people really like being able to grab VALUG messages and stuff like that. And there's some amount of tooling that also does automation sometimes based on that. We've been trying to move people towards the journal because usually what happens is that they give up training internally on this and people realize the journal is nice and they would really like to use it and they find out all the journal city documents they could use and then they ask me if they can deploy it. It's kind of difficult to have both the journal and RC's log running concurrently because you end up double writing and causing a lot of extra IO. And we have applications that can be extremely chatty in terms of logging. So if you end up writing three gigabytes a second of logs that's not great. One thing that will help, we've been looking at ways, right now the journal is a bit all or nothing endeavor because either it's entirely volatile or it's entirely on disk. We've been looking at ways that we could have a per unit setting here and that would have transitions things over because in a lot of cases it would be one application team that would really like to use the journal but maybe everybody else not quite yet. I think this is one of the things that I might play with when we start rolling out the next CentOS release and see if we can couple with that rollout maybe not gym people to use this more. Have you looked into like using our SysLog and GE because it has modules to slurp up the journal D and as well as SysLog entries and other things together such that those who want grabbing our SysLog they can and those who use journal they can and you're writing once and storing once. Well, you can do that, but you still end up writing twice though, don't you? Sure, but then when you run Journal CTL you only get the small buffer you have because that's kind of the problem there, yeah. We actually have our SysLog setup that way right now. I think it uses the module to get the IMK journal or something, yeah. Yeah, that's kind of the problem because if you only have a small volatile buffer then if you actually want to use journal CTL or if you do system CTL status on something you see no more logs and that's a bit annoying. Regarding the linter tool, so I'm wondering since you mentioned it's more than just linting maybe analyzing too. Why not integrate it into system de-analyze and then if not, why not and then also then with the versions of system de-changing and the unifile being different, how do you manage that? So some of the things that we wanted to do in the linter actually ended up in analyze. One thing specifically was parsing time specs and validating the time specs like we do on calendar or something were correct. That ended up being implemented as a feature in analyze itself. I think implementing the whole linter as part of analyze is something that will probably be possible. I think it will maybe be kind of out of scope for analyze itself, especially because we want to specifically this to be pluggable in terms of policy and have maybe the ability to have more complex policies. I don't know how well that will fit there. Chris is actually there and he can answer that more usefully than I can most likely. Thank you. So another reason is because if you look inside the system de-source like one of the things we have is kind of, we have a lot of little bits of unit state. We have a lot of little bits of like go look for this thing and store it somewhere. You don't really have a way to kind of homologate that back to here is how the unit file looks or here is how, you know, you can get something in system CTL show, but it's hard to map that back to like here is how we got to that outcome. And that's often the thing we need to know is like how do we get here? So currently it's hard to just make it part of system CTL analysis because I mean you would, you can do it, but you would again have to kind of re-implement a unit parser and do all kinds of other stuff. And I think it doesn't make a whole lot of sense. That thing is, thank you Daniel for your talk. We got a quick five minute break. Sorry.


Welcome to the functional group update general. I'm your host, Sid. And today we're gonna talk about these things. And if I say strange words to refer to customers, it is because of our organizational code names. I wanna have a try at making this call fit for public consumption. However, if you wanna ask something that is not fit for the general public, please do not hesitate because the last thing I want is people not asking certain questions. Some of the good stuff that happened. We made our revenue goal for January. Q1 is looking good. We're more likely than not to exceed our goal. However, it is dependent on some large deals. So that's the thing with large deals. They can happen, they cannot happen. It can have a big difference. Tone, yes, Chad is still confidential. And look, Tone, if you wanna ask a question that is confidential, go ahead, just do it, and then we'll just not publish this call. So don't worry too much about it. Just want to, I wanna make sure that we, as a company, can publish even more materials. And if we work with code names, we can do that. So that's why I want to get everyone used to that. And thanks Yop for linking to the code names in the chat. Another great thing, the pipeline for Q2 is looking good. We have a few more millions to go, but the team, especially the SDR team, is producing really well. We added two million in a week of incremental of additional pipeline. So that's going very well. So we're gonna meet two times pipeline coverage. And that's the minimum for Q3. We're gonna look at three times pipeline coverage, but still it's an improvement. And we're hiring at a rapid pace. Now, hiring is not a goal in itself. Like we hire people because we need them, but when we need people, and we decided we'd need a lot of extra people, it's great that we're able to get them. And I'm just seeing really, really qualified candidates the whole time. And I'm impressed by the quality of people. We can attract them, wanna especially call out like the SDR team, we needed a lot of extra SDRs and the people that are joining us are just really, really good. So thanks to the SDRs that joined us, but also thanks for the team for reaching out to people and finding them. Cortland says, I'm feeling like buying a car. Yeah, the code names are all based on car models. And it is so when you see a car model, you realize that it's a code name. At least that's the idea. So that you're like, oh, what is this strange car? Oh yeah, cars are code names. Some concerns, the move of GitLab.com to Impressa is being delayed from March to April. So that's not fun. But I think the team is doing good job considering the circumstances. We're not actively sourcing for old vacancies that need it. We're hiring 100 new people in a quarter. That is just a very, very rapid pace. And it is a big stretch for the recruiting team to do that. So they're working as fast and as hard as they can, but it's just a whole lot of vacancies to fill. In the future, hopefully we hire slightly slower and we have an even more efficient process than we can have active sourcing on all the vacancies that need it. And another concern is that Fable, one of our largest customers might churn. These churning happens from time to time. It's not fun and me and Hayden, we had a call for example yesterday, we're doing everything we can to prevent that and we'll see many times if you fight for it or if you work for it, great things happen. And Scott mentions in the chat, like we welcome all referrals. Yeah, it's not just the recruiting team that does the recruiting and the sourcing, it is everyone, especially the hiring managers, but everyone, if you have a great referral or if you know someone who's great, please, please do help. Someone mentioned that I might be a bit overzealous with code names. So, and then you kind of give away the code name. So that's a lesson for me. Philips, there's what's the trend for the coming months regarding recruiting? I think that, so Q1, we're adding 100 people, then the whole rest of the year, we're adding another 100 people. So it's slowing, you could see it as slowing down by a factor of three. Now in Q4, it's gonna be a bit harder to hire anyway and we might have some kind of leftover things from leftover vacancies from Q1 that we didn't manage to fill and have to fill in the rest of the year and we might change how many people we hire if we adjust that upward. So don't count on it slowing down by a factor of three but a factor of two should be, is something I do expect. So James makes a good point we might have to kind of revolve code names at some point. And James, I must say many of these code names, I don't think that the customers that we mentioned like mind that much, it just, we have to be a bit on the careful side but it's, I know that some of the customers even tweeted that they use us. So it's not the end of the world. Gabriel says that we should probably use more obvious car names that make sense or highlight the words. So that's a good idea. I can make them bold when I use them. Scott has a metric. We're doing about 20 hires per month. Yeah, Marcus reminding the sales team. I'm happy to join on customer prospects calls. I love that. I love being in touch with customers. So like whenever you put me in touch with a customer you're doing me a favor. Victor, a rotating code names. Yes, good idea. One-time pad, less of a good idea. But I do think there's something to be said for rotating a code name every once in a while, especially if it comes obvious after the fact. Paul Schieber asks what skill sets are we hiring? Paul, I think it would be good to look on our jobs page about getland.com slash jobs. So you can see the different vacancies we have. Mark Punsek has UBK based code names. Well, Mark, speak up if you can explain how that works. Clements. I was hoping Victor's rotating keys. If you want to really secure, you have to press the UBK every time you want a new code name. Yes, we're going to have public private code names. Very sure. It's going to be one-way hash code names. We'll just put the hash in there. Clemente asks what inspired the code names idea because the problem is sometimes we want to talk in an issue about like this organization needs something and it's really hard. Now we solve that a bit by just linking to Salesforce, which works exceptionally well, but selling presentations like this, like having a Salesforce link in there feels a bit weird. So that's why we had the code names idea. And it also feels a bit cool, I must admit. It's using a code name not already hint. Yes, it kind of is. And Philippe, it doesn't have to be perfect, this whole code name stuff. And Scott mentions that everything on our job page is something that is a priority and we're hiring for. And Mario, thanks for adding the URL here. Cool. Some plans really early. We're starting on time this time with the OKRs for the second quarter. So really early OKRs that haven't even been this, that basically come from me and not from the executive team are on the OKR page. Another plan is to get BizObs running. Today is the plan, but I wanted it down to this week, but with Brian Flood and the rest of the teams made some good progress there and we're figuring out what we wanna do, what we don't wanna do. And I look forward to kind of the first graphs in our data warehouse this week. Hiring a CRO this quarter, interviewing we have three great candidates that we're now doing extended interviews with. I'm really excited about external repositories in 10.6. This used to be called CI only, but we thought we focus on kind of what we support and as a support, we add support for having your repository outside of GitLab. So I think that's a great naming suggestion. I think it was Williams. And I'm very excited about this because this means that we open up GitLab to a whole new world. I think it's gonna help a lot on SaaS especially where people can now like, they don't have to move from GitHub straightaway, but they can use like the best CI and CD system in the world. So I think it's a big thing. We're gonna do our best marketing it and I'm really excited about it. Yop corrects me. It's the eGroup, not the team. Thank you, Yop. Still getting used to that myself. Fabio links to the external repositories issue, Fabio, but thanks for linking. And then the partnership launch in Q2. I'm also excited about that. I think it's a great partnership. I think we're betting on the public cloud that is gaining ground, gaining traction and that is very much aligned to what we are doing. Now, some top of mind things and I am running out of time. So I'll just let you read those, but I'd love to talk about them. It's gonna be according to questions because I'm out of time. Can you specify what changed on the team structure table? So the team structure table, the fact that we have one is basically what changed. So let me see if I can click through to this. So we kind of now have a word for every layer in the company and then it's something I've never seen before, but now that we made it, I think it's a very useful thing. You kind of have a management group and a reporting group. So the management group is that layer and everything up.  And then the reporting group is that layer and everybody below. And I'm sorry about this above and below nomenclature. I tried to kind of switch around the order but most people think of an org chart top down, kind of like a pyramid. So it ended up being this.  So unless you wanna speak up, consider muting yourself. So the reporting group is that layer and everyone below. So on a manager, that would be the team. So a team we refer to kind of the smallest possible, it's just a combination of individual contributors and their manager. And then on a director level, you'd call it the department. And on a VP or C level, you'd call it a function in the company. Robert, do we really need to tell people to scroll a page? Yeah, I don't like it. I would rather have our org chart under aboutgitlab.com slash team slash chart, for example. Now, the whole team doesn't work anymore in that URL too, but I'd rather have it on a separate page and then keep this page for describing the structure and I have the chart for the chart itself. And that way we can just refer to another page. I think that's better than scrolling, but I didn't have the time to move this thing. So if anybody else can, please help. Brittany, does that answer your question? Yes, the only question I had was, I know that the nomenclature changed where we had band and crew versus using team. Did that adjust as well with this iteration? Yeah, so the band thing, Martin said it didn't work. He tried it for three weeks and it didn't work. So I think that's the strong data. He actually tried it and it didn't work. Okay, great. So we should change that. And he said the team was the best term for that. So I'm like, okay, let's roll with that. Let's have team for the manager and reports, but then we needed other terms for the whole rest. The crew thing is still a thing. It's not based on success, but that is still a thing. So if we assemble a group of people to temporarily work on an issue, we can refer to that as a crew, because we don't wanna use the word team for that because that might be confusing. Cool, thank you. Thanks for asking. Abby says crew seems strange. Yes, it's strange, but I love for an alternative. This is the best I could come up with. So I'm open to suggestions. So Sid, what are some of your thoughts on consistency of demos? Thanks for asking, John. I think right now what I'm seeing, I'm seeing our solutions engineers give good demos. So yay, that's great. That's awesome. However, I don't see changes to our official demo page. So it seems that people are just doing kind of one-off demos. They kind of learn the product and then they give a demo. And a reason might be like the idea to production is a really long demo, but I much rather have a couple of demos on this page and then be able to discuss upfront, like what demo are you gonna give? Like, is it gonna be the demo that involves the prototype and framework that we made? And after that look at, I think like whatever we do, I think it's good to kind of have a name to refer to it and do it the same way. So that's not happening. So I'd really love for the solution engineers to start making contributions on this page. I checked this page out. I think the number five contribution is like five months ago from Mark. That can be the case. We're giving demos every day. So we should be improving and we should be contributing to it and we should have a way to do a demo. It shouldn't be something that we just give over from person to person. It should be something documented because if it's documented, it's easier to learn from each other. Oh, the other person gives it this way. I tried this other way. I think it's better. Let's change it and let's have everyone do it that way. And we're gonna get there eventually because product marketing is gonna kind of organize these things and we're hiring for a product marketing manager. It is a technical specialist that can help with this. But in the meantime, I'd love for solution engineers to contribute to this page and describe the different demos that they're giving. It's fine if we have like five flavors of demos. I just think it should be something that we document instead of something that everyone has to figure out by themselves. What do you think, John? I think you're right. I know the essays are talking a lot about creating like plug-and-play demos because a lot of the demos are structured around the pain points that were discovered during an earlier discovery call. So we try and craft the demos to show how we solve their pain points. So I think that's why you might be seeing a greater variety of demos. They are typically based around the I2P demo. Yeah, I think it makes sense that we have different demos. I just think we should kind of document them better. And yeah, William, you made an issue to create a stock demo. We have a stock demo. It's on this page. So let's figure out what we need to add to this page instead of creating a new page that has our stock demo. Like just describe the different variants. Don't start from a vacuum and then have a problem of having to integrate it with this demo. Just make this one better and make different versions of this. And naming the demos is like the hardest thing. So I think, for example, on this page, and I apparently stopped sharing my screen at some point. I'm not sure why that was. But on this page, it should have the idea to production demo and then there's a CI CD deep dive, but there should also be a CI CD overview demo. And it could say, like, hey, this is do the same thing as the I2P demo, but start at test and end at production. Like that's totally valid. And then we have a way to refer to the demo because now if I have a call with a customer and I know they need a certain demo, I cannot ask a solution engineer, give that demo. Because there's no word for it. If there are no other questions or suggestions, thanks everyone for joining. Have a great day and maybe see you at the team call.


How's everybody doing? Is that Storm? Wake you guys up? No. No. It's just me. I'm Rachel DeCrube. I'm one of the retina attendants. So we're supposed to cover retinal vascular occlusions. And it's two parts. So today we're going to do kind of vascular occlusions. And then I come back in a few weeks and we'll talk about some less common entities. So hopefully, since it's a small enough group, you guys can just ask questions. Hopefully there's a fair amount of participation. I could talk about the images and kind of what we're thinking. But we'll just get started. So the first picture. Oh, wait. Oh, this one. That's right. Okay. So anybody? What do we have? This is pretty straightforward. Yeah. So there are some patches of white in the reds. Yeah. What part of the retina, which retinal layer is affected by a continental spot? Yeah. So it's a nerve fiber layer infarct. So nerve fiber layer infarcts. It's caused by a retinal arterial obstruction. Usually they'll fade over a couple of months. So back ahead on differential for a continental spot. Does anybody have anything else that they would keep in mind for continental spots? HIV retinopathy. Vasculitis, leukemia. This patient I actually saw a couple weeks ago, and this was radiation retinopathy. She'd had optic nerve meningioma that had been treated with radiation. So that's the big thing with continental spots. They're really never normal. You see a continental spot. You're not just going to say, oh, that's nice. You've got to really investigate a continental spot and figure out why they got a continental spot. But it's typically hypertension, diabetes. Keep in mind HIV retinopathy, anemia, radiation retinopathy, sickle cell disease, which we hardly ever see here, but it does exist. And leukemia, vasculitis. So investigate a continental spot if it shows up in your clinic. Okay. What about this picture? See, like retinal whitening along what looks to be like maybe retinal artery. It's like a branch retinal artery occlusion. Exactly. So that's the branch retinal artery occlusion. So it's a block of different retinal artery and you'll get this edematous pacification that can happen within hours. And then this is another example of a branch retinal artery occlusion. This was a 44-year-old woman I saw in my clinic a few weeks ago that had this branch retinal artery occlusion. And this... So what kind of embolus? Does anyone know what kind of embolus we call that? I think platelet fiber and embolus, yeah. So it's usually several disc diameters in weight that completely occlude the arterial. She came in complaining of this banana-shaped defect in her vision that had been there for a few days. And this was her OCT... Oh, sorry. I'm doing two computers, so... Does anybody see this OCT finding before? Rachel. It's like PAM. It's PAM, yeah. So it's paracentral acute middle maculopathy. And do you know which retinal layer it's? So it's the... the... internuclear, like, typically, but, yeah, it does look like it's affecting the outer plexiform layer. Sometimes it can be a little more patchy, but it's this diffuse hyperreflective band here in the internuclear layer. And it's been described mostly in vascular disease, but it's also videopathic. And you can see the arterial obstructions. Okay. Next one. See this on call? Ever? Okay, so... Yeah, so this is kind of our classic cherry red spot right there. And you have this edematous kind of whitening of the posterior pole. What kind of finding are we seeing in the blood vessels? Does anyone know what we call that? Box carving. Yeah, so you can see this kind of segmental opening of the blood vessels from the occlusion. And then this picture is interesting. I think... I just got a note from Dr. Tabin. I think I'm seeing this patient next week. Can you guys tell me what it looks like is happening here? It's kind of blurry. I just screen-grabbed that off-axis. I guess that's not the best way to do it, huh? She has the fellas. Anyway, so right here, what does that look like? A little plaque, an embolus there. Some plaques in the blood vessels here. You have edema and a pacification of the posterior pole with the cherry red spot. But what's happening here? Yeah, so there's that silio-retinal artery that's perfusing this little area. And the OCT is pretty cool, actually. Because you can see on the OCT, so kind of the typical findings of an OCT and a QR, arterial obstruction, is this kind of diffuse hyper-reflectivity. You lose the cellular details and the cellular layers. But in the area... Can you guys see the pointer? I can't really see it. It's so tiny, isn't it?  But over where the area of the silio-retinal artery, you can see the normal cellular layers pretty nicely. So that is a CREO. Most of the retinal sparing. And then this patient actually had a ultrasound, too. And you can see the plaque in the central retinal artery. Oh, yeah, that's a really tiny dot. All right, so that's the B scan that Dr. Harry did. So for causes of arterial occlusions, what's the most likely cause? Were you looking? Embolic, yeah. And where's the most likely sources of embolic? Exactly, that's where you've got to look, is the carotids in the heart. That's about 90%. What's the less likely cause of arterial occlusion? I think it's... Yes, giant cell arteritis. So that's what you've got to keep in mind. Especially if you don't see an embolus, you really want to keep giant cell arteritis in mind and you've got to roll that out, especially in elderly patients. Less likely causes are going to be trauma, sargulophates, collagen vascular disease, bushets, leukemia. So those are the most likely sources, causes. Okay, this... So these are just pictures of different embolic sources. So usually we have cholesterol plaques, platelet-fibrin plaques, which we showed you a picture of calcific plaques, which are coming from the heart. And those are usually kind of this chalky white plaque. And that one's a calcific plaque. Yeah, this one looks like a calcific plaque and it's kind of chalky white. I think the biggest thing to emphasize is you see the plaque, it's not really a highly predictive value to determine if it's heart or cardiac. You've got to look at both. You can't just say, oh, yeah, that's chalky white. Yeah, that's the heart. Really, you've got to have a pretty aggressive workup and figure out where it's coming from. Less common causes of emboli are fat talc and you can also see corticosteroids that can travel through the arteries and cause emboli. So here's some more examples of different embolic photographs that really aren't showing up that well. Sorry about that. So for the hole-in-horse plaque, usually you'll see it kind of lodging at a bifurcation of an artery. And the hole-in-horse plaque, usually it doesn't occlude the flow. It doesn't really cause an arterial obstruction very well. Very often, usually kind of the blood will travel around it. But the calcific embolus, you'll see it often at the optic nerve head and it will occlude flow. And usually a calcific embolus doesn't fade away. That will be there forever. But a hole-in-horse plaque can fade over time. And then this is an example of the platelet-fibrin embolus. And that'll just fill the whole vessel, cause an arterial obstruction. It can be several dyspneamiders in length. So the most common symptom for a central artery occlusion is patients that come in with sudden vision loss, no pain, they can't see it all. They'll often have episodes of amirosis perceiving it about a quarter of a time. And on exam, you'll see this cherry red spot. Does anybody know what the cherry red spot's from? Why we see the cherry red spot? It's like the underlying core. So you don't have like the pigment in that area? Exactly, cause the ganglion cell layers that are there and then your fibro-layer layers that are there. So you're seeing the normal corporeal vasculature and everywhere else is edematous and opaque from ischemia. Mule, that edema in the cherry red spot will fade over a month and then you're left with a really pale nerve, really slurotic-continuated blood vessels. Initially, you'll see that box-carrying of the vessels where you see kind of the blood flow. On Fluorescena angiogram, you'll have a delay in arm-de-retina time, often, you know, 40 seconds until you're getting flow through the retinal arteries and then delay in the AB transit as well. So for a central retinal artery occlusion, basically the thrombosis gets... Sorry. There's a thrombosis, or an embolus, sorry, not a thrombosis, but an embolus just right at the lamina corposa and you'll get irreversible retinal damage after 90 to 100 minutes. This is why it's hard to do any treatments or trials or studies because patients don't usually present that quickly. You know, you guys probably see them quicker than I do, usually I see them after they've already had their work up, to be honest. What's happening in this picture, couldn't even tell? It looks like retinal edema. Yeah, so this is actually a siliorretinal artery occlusion in the setting of a central retinal vein occlusion. So the most common cause of a siliorretinal artery occlusion is actually a CRBO. And so the idea is that there's a thrombosis at the CRBO side that leads to stasis in the siliorretinal artery and leads to an occlusion. What's something else to think about for a siliorretinal artery occlusion? That is the answer. Siliorretinal artery. So yeah, consider GCA. So the siliorretinal artery is coming from the posterior ciliary vessel so it's not coming from the central retinal artery. About a third of eyes will have a ciliary retinal artery and in about 15% it'll supply the macular circulation. So in this photograph this is kind of a cherry red spot right here with the central retinal artery occlusion and then there's a siliorretinal artery here that's perfusing this little tiny area of the macula. Unfortunately, it didn't go a little further over. So people have tried a lot of different things to restore vision from a central retinal artery. Nothing's really been shown to be that efficacious. But people have tried to lower the pressure doing AC taps. I've tried it. If they come in quick enough or massage you'll put like a contact lens on the eye and try and massage the eye. The idea is to dislodge the embolus allowed to move downstream and restore blood flow. I've seen patients that have had hyperbaric oxygen treatment. People have tried to do inter arterial TPA and capitalize the ophthalmic artery but that's a pretty high morbidity and mortality associated with it. I've seen people present trying to yag the embolus and restore blood flow that way. But nothing really works out well because they have irreversible ischemia after an hour and a half, 100 minutes. So it's hard to restore vision. About 15% of eyes will develop neovascularization and it typically will occur within one month. So it happens pretty quickly. I think that the biggest thing that we need to do for arterial occlusions is recognizing them and then doing the systemic work up and doing an expedited work up through neurology often. There's been a movement to start calling this acute retinal ischemia and to really push it into the neurology kind of stroke world. So people take it seriously. There's been a lot of studies that have shown that ophthalmologists and optometrists do see these and I don't think here but I have seen it in the community where we don't get that expedited work up to look for cerebral infarcts and the underlying cause. A few months ago I had a patient that was referred in for an arterial occlusion just a B.R.A.O. And they, I don't know, I guess the referring doctor didn't recognize the urgency of it and by the time they got to me three or four weeks later they'd had a massive stroke. They'd crotted into our rectum and I think that if we would have recognized the arterial occlusion and started the work up, got the C.E.A. before they had the stroke they would have had a better outcome. So there's a pretty high rate in central retinal artery occlusions of finding cerebral infarcts on MRI scans. So kind of the policy here and whenever I've had to coordinate this I found it to work pretty well with the inpatient stroke team but if it's been, if they've had vision loss less than seven days you're supposed to coordinate an expedited inpatient stroke work up and typically I call this stroke team on call and they usually admit them and get everything going and I really haven't had an issue. If it's been longer than seven days then the policy is that we're supposed to start the work up into the stroke team after that and kind of the work up you guys know the work up right what are they going to do? Chronic ultrasound they'll get like basic lab work echo yeah they'll do the bubble study and they'll rule out GCA and typically they'll start aspirin and a statin if it's not contraindicated oh I guess I should I wish I could do this live like a Bluetooth to there that would be cool we're not at that point are we? okay so that is the work up that we were just talking about but I found whenever I called the stroke neurology team I think they're really receptive to this have you guys had issues on call? yeah yeah it's been really usually we have a patient that comes in and I had two French red artists and they page you and then the neurology team pages me because they are like in the TPA especially they're in the TPA window yeah yeah I found him to be this is just a patient of mine I saw a couple weeks ago this was his initial of CT a year ago from his CREO and you can see that hyperreflectivity the edema lost the cellular details and then over a year this is what the OCTO look like and so it becomes really atrophic and then less commonly I actually don't know if I've ever seen an ophthalmicardic occlusion that I was trying to think if I've ever seen one I really don't think I have but their vision is worse than a CREO it's usually light perception or no light perception there's no choroidal or retinal feeling on the FA and the ERG will show an absent A and B way there's no cherry red spot the most common thing to cause this would be a giant cell but you could also see it with the internal carotid dissection mucor or complications of surgical intervention okay any questions on artery occlusions what do we have Cerebio what else would be in your differential for a Cerebio for sure the other things you want to consider d retinopathy often that will be bilateral ocular ischemic syndrome the difference with ocular ischemic syndrome is that typically the vessels aren't quite as dilated and tortuous and the hemorrhages are usually kind of deeper retinoletic layers and then this is a BRBO segmental hemorrhages at an AV crossing site typically you can often see cotton wool spots as well and then later stages of a BRBO and this isn't showing up as well but the big thing you know when you look and do an examination you can see these kind of what we call collateralization across the median ruffe so you'll see these blood vessels that start to cross over here and this is allowing another drainage site an outflow site this patient also had neobascarization of the disc with that attenuated vessel and you can kind of see here the sectoral PRP that was done for the neobascarization so a BRBO is basically compression of the retinal vein at the AV crossing site and there the arteries overline the vein in this common adventitial sheath and that thickened arterial wall the vein leads to turbulent flow into little damage and then the thrombosis you want to consider an inflammatory cause if it's not associated with an AV crossing site the most common quadrant that's affected in a vein occlusion is in a branched vein occlusion is superior temporal about 60% of the time and so this is kind of a typical BRBO superior temporal at this but you can see up at that AV crossing site you can see the artery in the vein where the occlusion starts so it does come it's kind of finicky so what are some risk factors for a vein occlusion the biggest thing is age, hypertension glaucoma diabetes is not an independent risk factor and that comes from the eye disease case control studies a little crop of bun O-cap so diabetes is not an independent risk factor for a branched vein occlusion but it is for central renal vein occlusion the vision loss acutely you'll see macular edema, hemorrhages ischemia that can lead to vision loss and then long term chronic vision loss can be related to sub renal fibrosis pigmentary changes it can develop epiretinal membrane formation glaucoma, vitreous hemorrhages so the outcome really depends on the severity often the resolution of the macular edema is associated with these formation of those collaterals and this floor scene shows pretty well this collateralization that's happening in the chronic BRVO and so these collaterals just allow another outflow system for the macular edema and improvement and vision so those patients actually do better if they have that collateral formation in a central renal vein occlusion the collaterals occur off the optic nerve and you'll see these collateral shunt vessels in a CRBO you're getting compression of the renal vein at the lamino crevosa and they get this increased renal capillary pressure with associated macular edema and renal hemorrhages just to compare the risk factors for a CRBO versus a BRVO the one kind of thing to keep in mind is diabetes was an independent risk factor for the renal vein occlusion when do we work up these patients so do you guys know when we typically would work up a CRBO or a BRVO what about like an age cut off usually if they're younger than 50 we do a work up to figure out why they had a vein occlusion if they're older than 50 ages a bit of this risk factor for a CRBO we kind of break it down into the non ischemic and the ischemic CRBOs so for the non ischemic CRBO they usually have better vision they have less ischemia they have a better visual outcome for an ischemic CRBO it's 10 disc diameters of non perfusion that you'll see on fluorescent angiography they'll often have an adherent pupillary defect and the ERG will show a reduced lower flat B wave does anyone know what this is hemirentinal vein occlusion so would we classify hemirentinal vein occlusion as a CRBO or a BRVO CRBO so what's happening in a hemirentinal vein occlusion it's basically an anatomic variation where the superior and the inferior draining retinal veins actually meet posterior to the lamina crevosa so it's actually happening at the optic nerve head behind the lamina crevosa and it actually has a higher risk of neobascular complication than a CRBO or a BRVO so we kind of manage a combination of the two but it is considered a CRBO so instead of these retinal veins meeting here at the optic nerve head they meet behind the lamina crevosa and you get an occlusion there behind the lamina crevosa and that leads to hemirentinal vein occlusion so things to consider so vein occlusions when they come to our clinic most of us will start check the blood pressure right away often it's high kind of with a primary care doctor to control the blood pressure evaluating for glaucoma working with the glaucoma doctor primary eye position and then like I said under 50 do a workup I think the other thing that we'll see a lot of kind of younger women they're often on either estrogen or contraceptives or hormone replacement therapies I think that's an important thing to keep in mind and see if that's something they're able to come off of because that can increase their risk of vascular or occlusion disease this is kind of like a starting point for doing a hypercoagulable workup obviously but protein C protein S homeless esteem CBC cholesterol panel and then if you really aren't getting an answer I've ended up referring patients to HEMOC to help do a workup too if I can get to the bottom of it so I think the hardest thing about vein occlusions is the studies and these are always going to come up on OCAPs and it's trying to keep them straight and what they are right so there's really like the three main these are like the landmark vein occlusion studies that you've got to know I'll tell you how I remember them I don't know if it'll help you guys but the oldest study is the one that got the BVO and the CBO in the name right it's the oldest study so the oldest thing we were doing for vein occlusions laser so those are the laser studies so they got the name, they're the laser studies they're from like the 80's and 90's so that's how I remember the BVO and CBO score does anyone know what score is in the name like core corticosteroids that's how I remember it that's the corticosteroids study so that's how I remember it and then Bravo and Cruz, does anyone it's anti-vegeta it's randomism map and so I remember it B for BRBO, R for randomism map C is CRBO, R randomism map so that's the first kind of anti-vegeta those are the ones that tend to crop up on the test the most because they're the landmark studies so BVOS this was in like the mid 80's and there was two questions basically is there a reason to do macular grid for macular edema due to a BRBO and then the second question a benefit to PRP for neobascular disease so basically they found that macular grid improved two lines of vision in the majority of patients and treated like eyes were more likely to have vision better at three years they started the laser treatment at three months after presentation and then for PRP sectoral PRP reduced the risk of hemorrhage and neobascular complications after the development of neobascular disease so we don't do it for the ischemia but once neobascular disease develops like here then we would start sectoral PRP so that's the BVOS CBOS same questions it was like five or six years later early 90's photo coagulation reduced neobascular complications and then macular grid does that help macular edema from a CRDO they also will follow the natural history so from the CBOS macular grid really didn't help improve vision so that's why often we don't do grid laser for a CRDO it did PRP did help after neobascularization develop so we don't treat just ischemia but we treat neobascularization so BVOS BRBO you'll treat macular edema with grid this was our gold standard until the next studies came out treat neobascularization after develops from the CBOS no macular grid laser for macular dema and a CRDO so the score study this is a corticosteroid study and it compared standard of care which was laser versus one milligram and four milligrams of IVT so for the score BRBO study basically there was no difference between the three groups and the steroid groups were more likely to have complications like high pressure and cataract formation so after the score BRBO study we didn't change much what we were doing we kept doing macular grid and that remained the standard of care this was different from the score CRBO so before steroids we were just doing laser for neobascular complications we weren't really doing much for these patients at all because macular grid laser didn't work we didn't have antipagefs so these patients were really just two different doses of steroids versus observation and the steroids did better than doing nothing so for BRBO grid laser remained the standard from score and CRBO do steroids don't do nothing and then BRABO so this was our ranivizumab study and this led to ranivizumab getting an FDA approval for BRBOs and the ranivizumab patients did significantly better than sham so just remember this is ranivizumab where antipagefs became kind of our standard of care crews same thing patients did better with antipagefs than nothing at this point like we weren't even really doing steroids so they were able to just do sham so it's like two doses of ranivizumab versus sham and obviously the ranivizumab patients did better so really the big drawback to the antipagefs is that we just have to keep doing it ongoing I have CRBOs that I've been treating for seven years and I try and spread them out one week beyond 11 weeks they get macular edema they lose vision and we go back it's just crazy but we just can't just keep doing it so there's other treatments we do obviously now they're studies for these also but they're not kind of the key core landmark studies in vein occlusions the Azardex study was called Geneva I think the big thing to remember is the ILP speak with Azardex occurs more around eight weeks where IVT you see it usually around a month but the Azardex patients did really well and then ILEA had to get to do their studies to get their FDA approval as well and those are called Galeo and Copernicus for CRBOs and the Vibrant study for BRBOs but those don't tend to get tested on quite as much so really kind of our standard that you'll see us do for vein occlusions is start with anti-begeuffs monthly then try and treat and extend we'll add in steroids whether that's IVTs or Azardex and then we can add in laser grid if we're unable to extend or also if we're worried about poor follow-up as far as veneovascular complications this can be pretty complicated to treat we're lucky here to have really good glaucoma colleagues to help us with some of these neovascular complications in the retina clinic we're usually using a combination of anti-begeuffs with pan-retinal photocoagulation often they'll go on to need Ahmed valves or tubes to control the glaucoma or perhaps even a diode laser the nice thing about the anti-begeuffs is you can see the effects very quickly but the PRP will give you your longer duration of effect to control the neovascular complications so I think kind of historically people have tried to do a lot of other things for vein occlusions that have been pretty interesting not anything has worked really as well as anti-vegeuffs or steroids but they're kind of historically interesting so I mentioned that people did pretty well if they developed those collateral either across the ROFE or the optociliary shunt vessels so people have tried to surgically create these anastomoses and people have tried to do really hot laser burns in each quadrant to stimulate the retina to create these anastomoses or people will surgically go in and basically just kind of use a blade to create an incision at the venous congestions to allow an anastomoses it didn't work very well and it's pretty high risk people have also tried to go in with a retinal vein occlusion and I mentioned how the occlusion happens at that sheath where the AV crossing site is so people would go in and try to open up that sheath and allow outflow sheath and allow outflow and then also there's been reports of people using robotic surgery to cannulate the central retinal vein and allow an improvement in outflow and this is an interesting surgical procedure that people did and obviously this was before anti-vegeta before steroids but you have these horrible central retinal vein occlusions that you couldn't control and people would basically go in and I did this when I was a fellow so it's not that old but they did not do well but basically you do have a tractomy you take your MBR blade and then you go in at the optic nerve and take your MBR billiard and stab it into the optic nerve to the level of the laminate crevosa and making a big incision and the idea is just to allow drainage you have so much blood you gotta turn up the pressure really high but then they would end up having a lot of hemorrhage in the eye afterwards as well and we didn't really have anti-vegeta to control it, it was just crazy but I did do that when I was a fellow so I don't do it anymore I don't even know but those patients probably aren't around anymore they were do you guys have questions about vein occlusions, the vein studies are you gonna keep them straight? does that help at all? what was the way you remembered the BVOS and CVOS? so I figure like that's practically the name of the disease right? so it's B-O-B-O, C-R-B-O they got the name of the disease so it's the oldest study and the oldest treatment was laser so it's the oldest study, they got the name so that's how I remember it I don't know if that helps I think that's like the worst part of writing a book is just all the freaking studies studies I know but I feel like those three and they're like so old, we don't hear so anymore it's true, but the BVOS and CVOS was important because it kind of was in the natural history for us but I just remember because it has the name of the disease and the title so it's the oldest one and then score for quarter costeroids and then Bravo crews they have the R in their name for randomism I know, but it is a hard thing about the retina book is all the studies you know, marine, anchor, but that's what you know, I don't think you need to remember like Geneva, that's not as critical as score okay you guys look tired but I bore you to death with the retina I have a few questions, let's see if you know these, or if you paid attention I don't know so what has the highest rate of neovascularization of the iris hemirentinal vein occlusion but then after that it's CRBO but I mean we don't see hemirentinal vein occlusion that much when does the neovascularization occur after CRBO yeah and then what about a CRBO one month okay, you did listen does anyone know, I didn't say this does anybody know what this is oh, susan yes you get consults for it all the time do you really?  I saw it I've seen one patient that would say tally's patient oh yeah, I think I've seen my tally's patient that has it yeah, we've probably lost okay, see I'm an old patient, central retinal artery occlusion you can't see an embolist yes okay, most common quadrant for a BRBO yes super temporal, about 60% of the time okay, laser treatment for retinal vein occlusions, landmark study BVO yes, yeah just group yeah, group them together okay, CRBO what part of the ERD B-wave, ophthalmic artery occlusion yes yeah, AMB wave that's absent A waves okay, how many minutes perfect okay, you guys listen even though you look so tired she's so tired face that sucks, the 7am lecture well, that's a little bit because you have so many lectures I'm sorry yeah so after you have like a branch retinal vein occlusion or how long does it take before like findings in the retina like go away or what will I see like after the patients had one second so we had a patient in clinic yesterday actually that presented a little bit late but she had an episode of hypertension of the lidocaine occlusion over like 200 systolic and then about like the next week she noticed that her retina was blurry all over she'd already been dilated so I could check for an APB chest, robotic meridus so it was like 6 weeks later that I saw her so I was like thinking I was like I don't know the progression of like a resolution well, if she didn't have any treatment you know, so if it's a mild vein occlusion it could resolve over almost several months but usually there would still be some findings you could also have hypertension written off of these that could cause more acute hypertensive changes that could resolve what's resolution of blood pressure did you, you didn't have any findings on exams? no, so I didn't find anything so I was like looking and I was like and I checked her, she had an optic meridus in the eye so she had normal color vision and no red g-sat, no pain and then her vision was just a little reduced and she had a slight visual acuity to compare to so Dr. Lange just thought it was her cataracts but I was like, wondering about I mean, usually if it's been 6 weeks and they had her true ischemic event vein occlusion, you would see something you know, you would see sheathing of the vessels some retinal hemorrhages you know, long term a severe BRBO I mean, I'll look in a retina you'll see that collateralization across the median refabe to develop though and you can see that and you'll be like oh, they had a vein occlusion years ago and I'll still look in an eye and you can tell based on the shump vessels that it did happen unless it was a really mild event it wouldn't resolve that quickly I wouldn't think, usually there's something I mean, because I'll see those like dot hemorrhages from PDPs that you can treat and they're still there so next time I'm supposed to talk about oh, yeah, this is what we're supposed to talk about but I'm supposed to talk about ocular ischemic syndrome hypertension, sickle cell coats, macriannurisms do you guys want me to just prepare the lecture and we just talk and do some questions I mean, I know we're supposed to be doing this like flipped classroom, do you want to do it where we break it up and do some cases or what's better for you guys I favor ounce format okay okay we'll do it that way so you guys don't want to repair it yeah, I'll look I mean the hardest ones to find is going to be the sickle cell I'm going to have to take those from Julia I'm sure she has one I know that's the hardest but yeah, okay, we'll do a more like cafe round something good and go around and talk about cases is everybody okay with that all right cool, thanks guys