So we'll just get started with the retina and systemic inherited diseases. There's another version of this like on the Moran core that I gave in person a couple of years ago, but I kind of, I wasn't that happy with it. I kind of felt like it was like the Cirque Traverse at Snowbird. So a little bit like too intense. So I tried to turn this from a black diamond into a blue square, more like the looped loop in mineral basin where you can just like look down at the black diamonds, but you don't have to go down anything really scary. So hopefully that'll that'll help because I think you just can't learn it all at once. So it's better to just start from the high yield stuff. The stuff that really sticks out that would come up on a test question or in real life. So if you guys like see something like, oh, I saw this on a test, but it's not in your lecture. Let me know because that might be something to add in here. So I just talk about how not to memorize things because when you look at this table from your BCSE on the left here, it's like incredibly overwhelming. It's just like trying to remember the names or learning how to recognize all the little brown birds. If you're a birder, it's not a good way to learn anything. So the best way to learn things is to try to group things in three to five. Try to do repetition with increasing intervals and try to explain why things happen. So humans can remember like three to four things. That's why, you know, a phone number has things grouped into like three and four digits. Unfortunately, primary children slash IC did not recognize this human limitation and they made their FID numbers have however many digits. That is all at once not broken up. So every time I have to read the FID number out loud for a time out, I get kind of stressed. Another principle for how to memorize things is to gradually increase the intervals. So at first, you might only be able to remember it for a day. But after a couple of repetitions that you can remember it for two days, then a week, then month, and that's how you kind of get things into your long term memory.  And humans remember stories. So you remember the Lorax really well and that kind of, you know, the emotions of the story and the characters a lot better than if you were to read, you know, an article about how many acres of coniferous forests were eliminated, et cetera. So trying to make a story, whether it's a patient's story or the story of how the body works and why I think will really help you memorize these like really high yield things that come up on tests because they affect the eyes and the rest of the body. So we're just going to do like four different like phenotypes, so four different categories of how the eyes or how the retinas look. One is a retinal degeneration. Another is fundus hypopigmentation. Another is a cherry red spot or vessel tortuosity kind of group those together. And the last is myopia combined with retinal detachment. So I'll start off with a case. This is a patient that I saw recently, an eight year old developmentally delayed female. She's had nice dagmas since she was little. They got a brain MRI to work her up when she was a couple of months old. That was normal. And but she's really had a lot of trouble seeing in the dark.  She used to have all the lights on. And recently she's also been feeling her way down the stairs and running into things. Her mom thinks that this could be due to her vision and her medical history. She's also congenitally deaf, but she can hear some with hearing aids, but she speaks sign language and she also had a history of hypotonia from when she was little and she has developmental delay globally. The mom said, I knew something was wrong at six months when she wouldn't sit up. But the pediatrician ignored me. I keep bringing her to all these doctors that no one will tell me what is wrong. Like, they're all these things wrong with her, but no one's put the picture together. So I asked her if she'd ever had genetic testing and she didn't know. But anyway, the reasons for that we could get into later. All right. And this is her fundus photos. I'm going to start calling on you guys, OK, in rotating order. George, what's abnormal quickly about the fundus photos? In the upper part. So in the fundus photos, I just see some speculated like bony lesions, like especially in the periphery. Yeah, they're bone spicules in here, those black things. And then there's also some sort of lesion over the macula itself. Yeah, it looks like a fairly like well demarcated area of RPE atrophy that's kind of like because this part is like paler than the rest. And then is this OCT normal? No, I would say it's not. Seems like overall pretty atrophic and especially like in the. In the RPE sort of can't really distinguish like outer retinal layers at all. Yeah, normally we have like the RPE and Brooks memory kind of right next to each other. And I think here there's still a little RPE left. But here it's the RPE is gone, but Brooks membrane is still there. And we definitely don't see that, you know, we normally see that I SOS junction, a third line, you know, above the RPE Brooks. And then the other clue that things are atrophic, like you said, like thinned and is that there's a lot of hyper transmission. So we're just seeing the coroid right or the normal, especially in the middle where there's this atrophic lesion. And the optic nerves are elevated. I frequently see this in people with inherited retina conditions. I don't know if it's like a known thing, maybe pediatric neuropomologists could tell me sometime. And then this is her flicker. So basically it's a measure of cone function because you're stimulating the retina with bright flashes that are happening so quickly that the cones have time to recover, but the rods don't have time to recover. And the amplitude is just really small. So overall, it looks like in her center macula, things are not good. And that's where most of the cones are. And then this flicker is also indicating there's a problem with the cones. But these bone spicles out in the periphery, where most of the rods are and the fact that she can't see at night, indicate that she has a rod problem. So because rods help you with a vision in the dark. So what to do next, George, what do you think we should do? Genetic testing or RP or RP related sort of syndromes. Yeah, exactly. So so as you mentioned, RP or RP related syndromes, because some of them can affect things like not only causing a retinitis pigmentosa like appearance in the eyes, but they can affect hearing and development like she has. So that's our next phenotype. So some gross generalizations about the things that cause retinal degeneration and systemic problems is that they're almost always recessive because they tend to be like really pretty bad. So they wouldn't be passed down in an autosomal dominant fashion because many times like people don't make it to the age of reproducing because of all their health problems. The other explanation for why they're often recessive is that many times these are mutations in the proteins that are enzymes. So they're breaking things down. And a lot of times for enzymes, you just need a small amount of that enzyme to catalyze thousands of reactions. So usually having half of the amount of enzymes because you've got like a dominant mutation with one good, one bad copy, one good copy, usually that wouldn't cause disease. You'd have to have like no enzyme at all. And then the other gross generalization is that most of these diseases have severe neurological problems, whether it's like on the developmental delay spectrum or they can even cause like progressive degeneration and death where kids like lose their ability to walk, talk, swallow, etc. So I like to categorize these by like what causes them. And by the critical like organelles in the in the photoreceptors. So this is the picture here. What do you think are some categories of diseases by organelle? Can you let's see, let's call on. Is it OK to call on the med students? You think this is a med student appropriate question? Where are you, Nana? Chase is nodding. Yeah. OK. OK, OK, OK.  What do you think I organelle? I was trying to illustrate by that. Yeah, I'm not really sure. But I'm going to guess mitochondria maybe. Yes, OK, you interpreted my drawing correctly. And then Brianna, the the green and the orange are like little round organelles that like degrade things. Are those lysosomes? Yeah, one of them is lysosomes is very good. And then the other critical organelle is like the cilia, which is the is this the outer? The outer of the receptors actually are modified cilium. You know, normally cilia like our move around and like help things like swim along or move along in the body. But the I think just maybe how they evolved, they were cilia. And then the other thing that degrades things is proxosomes. So we have cilia, lysosomes, proxosomes and mitochondria. So the lysosomal conditions are called lysosomal storage disorders. And then the proxosome disorders are called proxosome biogenesis disorders. OK, excellent. Oh, forgive my mess ups in my animation. So these are the ciliopathies are sometimes called like retinol blank disorders, because they frequently affect like what other organ of the body? Anyone? Your canal, your canal. Say that again. I'm guessing an inner ear canal, like the cilia in the inner ear. I don't know. Oh, they do. You know, some of them do affect hearing. Yeah, that's true. They also affect the kidneys. I'm not sure where I like, are there cilias in the kidneys? But anyway, if anyone knows, they'll free to shout it out.  It's just where the kidneys shrink and. OK, so and get scarred. I guess Nana is not able to. It's not that well. Is that like when you I can hear you, but then when you talk, I can't really like understand what you're saying. So weird. Sorry. It's OK. It's all good. OK. So can you guys name some ciliopathies that affect that cause like a retinitis pigmentosa kind of phenotype? I asked them, so you left a clue here of a brain picture where the brain stem looks like a molar tooth. Oh, I see. Thankfully, OK. Oh, OK, Nana's coming. Saving the day with his mnemonics, so jabs. Jubeir, Alstra, Bartet, Vidal and Senior Loken. Very good. Excellent. Thanks, Nana. So. All right. So I put just three of those on here thinking that maybe these are like the most high yield ones for you to memorize, like Usher syndrome, like George said, there's cilia in the inner ear, so that causes like hearing loss and retinitis pigmentosa. It doesn't usually affect like other parts of the body. And then jubeir syndrome, that's where you look at this brain stem and it looks like a molar tooth. They also tend to sometimes have ocular colobomas. And then the classic thing with Bartet Vidal is an obese kid with polydactyly. So these are the ones that really like stuck out in my mind as like maybe the most easy to remember, flash most testable. Nana's sharing more. Oh, Usher syndrome and ciliopathy have been classified separately in the BCSE. So they're saying that Usher is not a ciliopathy. Yeah, I'm not sure why. OK, OK, well. Thank you. Thank you for keeping us straight, Nana. Appreciate that. OK, so lysosomal storage disorder. So as we mentioned, lysosomes degrade things. So when you don't degrade things, things build up inside the cells and then they start all that trash building up inside the cells, make this kind of toxic. So what are some lysosomal storage disorders that cause like a retinitis pigmentosa type of issue? OK, Nana says, Fabry, question mark. So Fabry is a lysosomal storage disorder that does affect the retina. But interestingly, some of the lysosomal storage disorders cause like a retinitis pigmentosa type of phenotype. And then others cause like a cherry red spot and, you know, vascular tortuosity. I'm sure some researcher could explain to you why or someone with a deeper biochemical understanding could explain to you why. But so the ones that cause a retinitis pigmentosa like phenotype are the neuronal seroid lipofutinoses. It's also called baton disease and also the mucopolar saccharidoses. So Hunter, Hurler, Shea and San Filippo. So all these cause like retinitis pigmentosa. So I think hopefully Brianna, do you know what the inheritance of Hunter disease is? Hunter syndrome? I definitely used to, but I don't. I can't recall now. It's OK, Ivan. Excellent. OK, yeah. So excellent because I have this like mnemonic where like it's like the hunter drawing the bow or something. So what do you think the rest of these are? Brianna, what inheritance do you think they are? If you're going for a pattern, are they all excellent? They're mostly autosomal recessive. So the one that like stands out, they tend to like pick the ones that like stand out to be on tests. So like whatever is different, they tend to like test that more. And the way it might come up on a test might be kind of tricky. Like they might say, oh, this got like passed down through the family, the patients like, you know, only passes. It's only passed on through the woman in the family and only men get it. You know, so that might be like a way that it might show up on the test. So the rest are autosomal recessive because they tend to be like severe enough, especially like Shea and Hurler and neuronal steroid lipophusinosis that like people might die before they can reproduce or at least be severely disabled by that time in their life. So and the obviously the things that are building up are the oh, I have a typo here, but the muco polysaccharidosis, glycosamino glycans are building up those large carbohydrate sugars and then the steroid.  So that is what's building up in bad disease. So what are some I think we talked about like the neurodegeneration and death that can occur with these diseases? What are some other like ocular things that can come up with the muco polysaccharidosis? Anybody? OK, corneal haze, very good. And so the front of the eye can be affected by corneal haze as well as glaucoma, especially in hurler or shea. How about like in the back of the eye? It doesn't cause cataracts. I haven't heard of it causing nice diagnosis, I guess it would depend how early in life it started. But it causes optic atrophy. Or edema, so that's the key thing to remember. And then how about the rest of the body for the muco polysaccharidosis? Don't try to talk, Nana. It's not working. Maybe get closer to your mic when you're done eating. OK. OK. So the key things like about like hunter, hurler, shea, sanfilippo is that those like carbohydrates, those like glycosaminoglycans large, negatively charged long chains of carbohydrates are like building up in the face. So they cause coarse species. And then they also build up like in the liver and the spleen cause a petal splenomegaly. OK, excellent. You guys have been really great about participating. Thank you. And they can also just cause like developmental delay. So it might not necessarily be on the on the milder spectrum.  So OK. So then there's proxosomes. And they tend to be problems with the proxosomes forming. That's what biogenesis means. And the proxosomes degrade lipids, although the lysosomes degrade lipids and many other things, proxosomes are like specific to degrading lipids. Anyone name any proxosome biogenesis disorders? OK, very good, very good. So Zellweger and Neonatal Adrenal Lucidistrophy, Refsum, thanks, Nana, for filling that out. So there's kind of like they're not all referred to that as a Zellweger spectrum disorders, that there's just a recognition that these are caused by mutations in the same gene and that there's just like a range of how they present. And there's generally speaking, either develop a delay or neurodegeneration death and increased fatty acids in the blood because the body is not degrading it. And there's also like adult refsum disease, which is not a severe. And what's the one characteristic finding of that? It's ichthyosis. So like a scaly dry skin. So, Chase, do you have a guess for like what's the inheritance of the Zellweger spectrum disorders? I feel like I don't know. Well, I mean, if they're all grouped together, I feel like the Adrenal Lucidistrophy was x-linked. They're actually they're actually autosomal recessive. OK. Yeah. Because, yeah. Anyway, that's the best. Whenever you're not sure, go with the autosomal recessive for these like things that are really bad. But yeah, all right. So next we're going on. Thank you for being willing to put a guess out there, Chase. Really appreciate everyone is willing to participate. So the mitochondrial disorders are next. So what do mitochondria do? They provide energy or ATP. So along with that, there are some systemic findings. Anyone have any guess like if you don't have enough ATP, what might happen or for your eye kind of what might happen? So ATP provides energy without it, like your muscles really don't work too well. So you might have weakness. They also have hearing loss. I think that maybe the years take a lot of energy, just like the retina does. And then classic on pathology is like ragged red fibers. And then with the eyes, like the key muscles are the ones that lift the eyelids and the ones that move the eyes around. So they get chronic progressive external apothalmal plegia, which is where like you get progressive ptosis, like the eyelids are grouping and then they can't like move their eyes to the side. So those are the characteristic things. Anyone other than Nana, no any names for these? OK, well, so there's curnsayer. I think that's like the most like well-known of these. What's like a really important thing to know about like with curnsayer in terms of like their survivability? They're like cardiac abnormality. Like they don't get block. Yes, they get heart block. Very good. And then the other two are like kind of easy to remember because like they have like their their name basically describes what's happening. So there's mitochondrial encephalopathy. So the brain's like not working to all and then lactic acidosis because the muscles are not getting ATP. So they're requiring lactic acid to work and then stroke and then maternally inherited diabetes and darkness. OK, you guys are doing great. Really, the the retinal degenerations are like the biggest block of them and you have survived thus far. So thank you. So this kiddo ended up having Zellweiger spectrum disorder. It's kind of was difficult to tell the parents that, you know, she probably will be like severely disabled. And depending on where she falls in that spectrum, she may progressively like lose her her functioning and potentially even like die in her teens or her 20s. So Emily Spoth, our genetic counselor, felt that like with her presenting late, you know, not being diagnosed late until late. That, you know, that was like a good prognostic factor, but also like, you know, her did not had genetic testing due to like family not following up. And maybe she could have been diagnosed like a few years earlier, at least. OK, does she have the characteristic face? Yeah, she her I'm not sure what the characteristic face is for Zellweiger spectrum disorders, but it definitely wasn't typical. Hypertealer. Oh, yeah, she had hypertealerism. You know so much, Nana. You're really impressing me. OK, my students, once you get it, once you get to this point in in a residency, you'll know as much as Nana. I'm looking forward to that. OK, all right. So in a large forehead, yeah, yeah, I'd say that. OK, so we did retinal degenerations. The other phenotypes, fundus hypopigmentation, cherry red spot, and that's the tortuosity and myopia retinal detachment excellence. We're making good progress. So this is a five month old who got just brought to the ophthalmology clinic because he wasn't tracking, I don't know why, but we weren't able to export the photos that day. So you can see me and Glen hovering over in the reflection of the screen, taking a picture here. Chase, do you know what this finding is called? Where this part is like kind of white around the fovea and then the middle is darker. Going off of what the categorization was, maybe cherry red spot. Yeah, cherry red spot. Yeah, very good. Excellent. So this area looks kind of like red because the area around it is all whites and you can't see the coroid below. Like normally you can see the coroid through the retina. So and the coroid's kind of reddish. We've got a lot of blood in it. What other conditions can cause a cherry red spot other than the inherited disorders affecting the retina and the rest of the body? The area. George. Oh, yes. Yes, Brianna, a way to go. Yes. So a retinal artery occlusion. So with the retinal artery occlusion, like because the retinal arteries supply the inner part of the retina, whereas the coroid supplies the outer part of the retina. When you have like ischemia of the retinal arteries, then the inner retina tends to be like what swells and turns white. And then you get this cherry red spot appearance too, because in the fovea, there's not that much inner retina. So you can see the foveal pit pretty well. Okay, excellent. So and then what can we tell already about this child's prognosis prior to like getting any additional testing? This patient's doctor, Dr. Jardine was already trying to mentally like prepare the parents for what the diagnosis might be. So we can already tell that they're probably going to fall into that neurodegeneration and early death category. So all right. Well, Dr. Jardine had that conversation, not me. So some gross generalizations again, recessive is definitely the way to go for most of these, most likely, and then the neurological problems. So as we talked about when Nana brought up Fabry disease before, is that these are also lysosomal storage disorders, but instead of having a buildup of like osominal glycans or steroids, it's a buildup of sphingolipids. So they're the sphingolipidosis and then there's also the trinucleotide repeat disorders. So I think in med school, you learn about these things. I've since forgotten a lot, but there's like cerebral sides, ganglion side, sphingomyelin, but I think they basically are a lot involved in the brain. So that's why you really get that neurodegeneration. And so what are the diseases that cause cherry red spots? Neem and pick. Neem and pick. Tasex. Tasex. Tasex, good. One more. Can Gauche, oh wait, no. Yep, yep. Okay. Gauche's disease? Gauche's disease, or I don't know how to pronounce it, but so yes, very good, excellent job. You guys are impressing me. So Gauche also causes like these peripheral white spots and the brain is really not too bad. And then what was the one disease that caused the retinal vessel tortuosity? That's a lysosomal storage disorder that Nana brought up previously. It's Fabri disease. And what else does Fabri disease cause other than retinal vessel tortuosity? There's a problem with vessels elsewhere in the body. Are there kidney issues? I'm not sure if they have kidney issues. Someone Google it and let me know. But they get this angio-keratoma corporis diffusum. So potentially like on O-caps, or on boards, they might like show you a picture of the skin with you like red elevated lesions. And also corneal overtressalata is a classic finding. What other like inherited disorders cause like elevated skin things? And I think like what general category? Angio-phycomatosis or? Yeah, they are the phycomatosis. So the phycomatosis are another thing that like you should spend a lot of time memorizing. They often affect the skin as well as the eyes and show up on tests like quite frequently cause it's the kind of thing where, oh, like if I see a ERM in like a 12 year old, like this could be kind of blanking. What is it called? I'm totally blanking. Oh my goodness. What is it? Congel hammer toe, one of the red on RP. But what is the disorder, the phycomatosis that it goes along with? There's a type one and a type two. Okay. Yes, neurofibromatosis. Thank you. I was having a brain block. Thank you, thank you. So they're, you know, these are like frequently tested things. So, all right, excellent. And then Fabry is one of those that's excellent. So basically most of these disorders that we've been over so far all are all recessive, except for like which one do we discuss that was excellent? Hunter. Yeah, Hunter. And yeah, I think that was the only one. So Hunter and Fabry, remember those. Or there's different inheritance. Okay. And then there's a trinucleotide repeat disorders. What is like an example of a trinucleotide repeat disorder that doesn't affect the eyes that like we all learn about in med school? Huntington. Huntington, very good. Excellent, yeah. So what is the inheritance of Huntington's and other trinucleotide repeat disorders? Doesn't it like more likely to affect you a younger age, depending on like if your dad gave it to you or something like that, like it's your father. If your parent, yeah, if your parent gave it to you, like do you need two parents to have Huntington's nor to have Huntington's? No. Okay, so that makes it autosomal. Autosomal or recessive or dominant. Autosomal dominant, yeah. So yeah, so just having like one parent past that, you know, CAG repeat on to you is enough to like have it. So that's autosomal dominant disorder. And then the ones that affect the eyes, so I guess I only put one on here. I'm excited to cut back. There's only one on here. And it's a myotonic dystrophy and it causes some like classic eye findings like this pattern dystrophy and a Christmas tree cataract. And then it also causes chronic progressive external aphthalmoplegia. Do you guys remember where chronic progressive external aphthalmoplegia came up previously in this lecture? In Ceres. Yeah, Ceres. Yeah, and what kind of, and then what kind of retina problem did Ceres have? Like which class was that? Which category? Which we don't type. It was a life. It was just like three minutes. Mitochondria. No, it's mitochondria, thank you. Yeah, it's a mitochondrial. And then what are the eyes, what do the retinas look like in Ceres? So they look like retinitis pigmentosa. Cause like basically everything that we went over prior to now was like a retinitis pigmentosa, retinal degeneration type of thing, rod, colon problem. So current Ceres had that plus the chronic progressive external aphthalmoplegia. The other thing that myotonic dystrophy shares with, that is heart block. And when these people try to like, with myotonic dystrophy try to grab onto something they have trouble like letting go. So that's like really like characteristic thing of this disorder. Okay, got you guys are doing really great. So this kiddo got diagnosed with Tay-Sachs disease and eventually like, cause when you're five months old, like it's hard to tell someone's developmentally delay, but eventually you got diagnosed with global development of delay and then he started having seizures. And then the family decided to go with hospice and like avoid any life prolonging measures, but they're trying to do whatever they can to make his quality of life good. So that right now is just taking seizure medications. Okay, so we went through retinal degenerations and cherry red spot slash muscle tortuosity. And next we just have fundus hypopigmentation and myopia plus RD. So this is a 10 year old male with a history of nystagmus. His best corrected vision is 2100. I would love to have like a better case of this disease. So if any of you guys like come across one where the fundus photos weren't taken in like 2005 in black and white, I would really appreciate that. So please let me know. And I guess George, what's abnormal on this, on this fundus autofluorescence here? I would say maybe it's missing like the typical like pigmentation that you'd expect. Yeah, normally in the fovea, there's like this black spot because of the macular pigment blocking the lipofusion in the RPE from it's like absorbs it so it doesn't get captured by the camera. So this person is like missing the normal type of autofluorescence of the fovea. And then when you do an OCT, you can see that they have no fovea as well. So, and you can kind of see when you look at this like photo of their eye that their eyes are very blue, their eyelashes are very white. And you can kind of see it like a red reflex through their iris, which is called iris translumination. Anyone want to say what they think this is? Ocular albinism. Yes, this is albinism. There is like ocular which like only affects the eye, not the skin and hair and then ocular cutaneous albinism. I'm thinking that based on this hair color and skin color that this might be like a ocular cutaneous albinism. Okay, now to inheritance. So ocular and ocular cutaneous albinism have like different inheritance. So this is another case. Well, I guess what the two inheritances are. What are the two options? What the two things have come up mostly so far? Auto-cell and recessive and X-linked. Yeah, auto-cell and recessive and X-linked. I need to look at the next page to see which one is which. Okay, let's go to the next page. Okay, well, let's go back. Well, we'll go back to that. Okay, what are other causes of like fundus hypopigmentation? There's algeal and then wardenberg. So those are just things to like keep in mind. Every ophthalmology resident gets very familiar with algeal syndrome because they get like a million inpatient consults because like some kid is having what kind of problem and then they want you to look for what kind of problem in the eyes. Is it posterior embryotoxin? Yeah, posterior embryotoxin. So what is posterior embryotoxin? Like a thickened decimation, I think? Maybe one of you could not explain it better but there's like this white line near the limbus and I think it's, yeah, some issue with the corneal endothelium but I think isn't some layer like growing more anteriorly on the corneal than normal? I don't know. Waiting for Nana to explain it. But, okay. And then, okay, it does represent an anterior protrude, a posterior protrusion of decimates. Okay, all right. So Nana and George are on the same page there. So, and then anyone remember anything about Wardenburg?  So they're two irises are different colors. Okay. Now we're gonna, and Horner's? No. No. Okay. I was trying to talk but, okay. They both have heterochromia. Oh, alligial and Wardenburg? Okay. Waldenburg? No. Okay. I don't know. Whatever. Oh. Okay. In general, Horner's and Wardenburg both cause iris heterochromia. Ah, yes. Okay. Okay. No, I don't know where you're coming from. Okay. Thank you. No, thank you very much. Okay. I really appreciate that. Okay. And then, so since I don't remember which diseases inherited which way, we'll click on the fill in the blanks here. So the ocular albinism is X-linked and then the ocular cutaneous is also more recessive. And then there are other variants on albinism that like are frequently tested because they affect other parts of the body, Chediakigashi and Hermanski Poodlock. So those are definitely worth memorizing. So what are the key eye findings of albinism in general? We talked about iris heterochromia, foveal hypoplasia. Our patient had nice stagmus. A lot of times these, because they're foveas are not well developed, they don't fixate that wall, so they have nice stagmus. Anything else? Okay.  So a decreased visual acuity, usually the visual acuity is not normal. And then systemic findings of albinism. What are the key two things that like occur systemically that are most prominent in Chediakigashi and Hermanski Poodlock? So like if you saw someone with albinism and you want to think about like, oh, do we need to worry about these other conditions? Should we get genetic testing for them? Lots of infection, you know? Yeah, infection and bleeding. So both these disorders are characterized by those. And the P in Poodlock should help you remember that Hermanski Poodlock also has platelets, pulmonary fibrosis and it's more common in Puerto Rico, but it can also occur in other countries. Oh, yes, okay, very good. Oh, a blonde fundus. That's something I didn't even put on there because I was like so obvious to me that I forgot to say. So when you, what we mean by a blonde fundus is like people that are like very like light skins, their retinal pigment epithelium also tends to be really like lightly pigmented. So you can see their choroidal blood vessels really well. So like if we go back to this picture, it's like, wow, we can really see like every single blood vessel in their choroid versus this is like more of a normal fundus, not, I don't know, normal, but more typical fundus pigmentation where it's kind of hard to see the choroidal blood vessels. I have to say, I did a med school in New Jersey and I didn't like do any away rotations elsewhere. And when I first came to Utah and I was intern, I like asked Trent Richards, my senior resident, I was like, what is wrong with this person's eye? Cause their eye, inside their eye looked like this. And he was like, you looked and looked, he was like, he couldn't figure out like what was abnormal about the person's redness. But then eventually we just realized it never like seen the inside of a blonde person's eye before. So since I did med school in New Jersey. So anyway, if you are like just really lightly pigmented, like a lot of Utahns are, this can be normal. And sometimes the question comes up like, is this normal or is this like albinism? And that's where we just involve our experts like Erica works, I'm not an expert on that. Okay, let's, we'll keep going here. Okay, so retinal detachments in adult. Oh, yeah, we're on our last category. We're almost at the end. The end is in sight. Amazing. We do one more lecture though. But I don't know, maybe we should skip it. Okay, biopia and retinal attachments. So this kid with thick glasses and retinal attachments. So this is like what retinal attachments often look like in adults. This is actually an adult retinal attachment. But I thought I would show you a picture of like a retinal attachment in a kid. She's a teenager. She's had really thick glasses since she was age four. So four is like a really atypical age for needing thick glasses. And she, they figured out she needed glasses cause she was like holding things really close when she was in preschool.  I can't get your vision to be any better than 2070 in the right eye and 2125 in the left eye. So this right eye on this picture, on these like big circles, these are actually like macro cysts in the retina. I'll show you my drawing of it. So basically she had like an inferior retinal detachment and she had these like big macro cysts. So when you have a retinal detachment for a long time, the retina just starts like falling apart from itself and then it makes these macro cysts.  You can see up here. But basically she'd had like some little holes right over here and then the fluid had like trickled down following Linkov's roles and just like kind of filled up her eye from the bottom to the top.  I just sigh because I did not do well. It was 2070 before I operated and now it's like hand motions with hypotiny oil in the front of the eye, band carotopathy anyway. So this left eye did better. It used to be her worst eye but now it's her better eye. She had a chronic detachment and you can see these like weird pigmentary changes here. Those are like demarcation lines. So when the retinal detachment is there for a while, the retinal at their edge, the retinal pigment epithelium tends to like make some changes that can be hypo or hyperpigmentation, hyperpigmented. And then eventually the retinal detachment might progress, pass it and make like a new line. But in this case, the retinal detachment had like progressed all the way to like here. So all the way past those. And then she's got some like fibrotic bands, sub retinal bands here. And then you can see that her maculose detached on the OCT shallowly. So when the detachments are shallow, you know, they can be compatible with like pretty reasonable vision, you know, like 20, 70. So that's just the example of like a chronic detachment like in a kid. So they don't all look like that. But definitely the things that made me think, okay, there could be some syndrome going on was the fact that she'd had glasses since she was age four and she has these detachments. So I thought I would show you this video. I better share a different screen. So can you see my YouTube? Yes. So you can see here, there's like this membrane in the vitreous. And this is one thing that they, you can see in stickler syndrome is that the stickler vitreous, I would say, it's not as like black and white as people make it out to be in terms of like optically empty, but in general, it's abnormal. So it can have this membranous appearance. It can look like the vitreous of a 80 year old where instead of being like really like uniformly like scattering the light, it can have like denser fibers and then less dense areas. Let me go back to sharing my other screen. So her vitreous actually had that membranous appearance in both eyes. So then I was thinking, okay, likely to have what disease? Stickler. Yep, stickler syndrome, very good, excellent. So with the myopia and retinal detachment disorders, they're gonna be an exception to our general rules for the inheritance for these disorders. Generally speaking, these conditions that cause myopia and retinal detachment are problems with extracellular matrix proteins, structural proteins, for which having half the amount is not enough.   So what are, other than stickler syndrome, what are some other diseases that cause myopia and retinal detachment? Okay, Wagner syndrome, good. Okay, so I did, I skipped what I did there. And no block, just in the name of like, let's get the most highly tested ones on here, but those are other diseases that cause like these same phenotypes. And what are the genes that cause stickler syndrome? There are the collagen genes. So like call to A1. I don't, and call 11A1. I guess that's as far as I would go with like, the memorizing of the genes that cause stickler syndrome. Don't get too crazy. And then, so I also put Marfan syndrome and while Marchesani on here, because these can cause myopia and retinal detachment as well. So, but I would say that probably in Marfan syndrome, like the retinal detachment is not as prevalent as stickler or as young. So, but if you see, yeah. Okay, and what gene is mutated in Marfan syndrome? The FBN1 gene. Yes, very good. So FBN1, and that encodes fibrillin. Fibrillin, oh, so the collagen are major, are what make up the vitreous of the eye and then the fibrillin make up what part of the eye? That's kind of like a ligament that holds the lens in place. That when it's broken, the zonules, yes. So the fibrillin makes up the zonules. That's why when you have Marfans, you might get ectopia lentis. So, we have ectopia lentis. We talked about stickler. Oh, and the other systemic findings for stickler are PR robot, meaning like, well, I think this is something that the residents also get really familiar with, even though they've tried to shunt all the NICU consults to the peds attendings. I think you still see them. So what is PR robot? So PR robot is like when the face is not developing properly. I forget what's like the, it's like a constellation of things that all come together when things are not developing well in the lower face together. So you get like a small jaw and then the tongue sticks out. So that's like glossoptosis maxillar hypoplasia. No, that's the cheeks. But then the mid-face is kind of flat because the cheeks don't develop that well either. And then you get like cleft lip and cleft palate. So many times like when there's babies in the NICU that have like all those problems with their lower face, they might have like problems breathing, problems feeding because of that small jaw that then they might console ophthalmology and ask us to retinoscope them to see if they have like the congenital myopia. But I wonder if these days they should just like genetically test them. I don't know, it would be more high yield than rena-stoping them because you can have stickler syndrome without early onset high myopia. And then I think you guys know about Marfan syndrome while Marchesani syndrome. So I'm not gonna go into detail about the systemic findings there. Okay, we got to the end. You did amazing.


Book 16, Part 1 of the Annals by Publius Canelius Tacitus. This is the LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer, please visit LibriVox.org. The Annals by Publius Canelius Tacitus. Translated by Alfred John Church and William Jackson Broderib. Book 16, A.D. 65 and 66. Part 1, Wild Prodigality of Nero. Fortune soon afterwards made a dupe of Nero through his own credulity and the promises of Caecilius Bassus, a Carthaginian by birth and a man of crazed imagination who rested a vision seen in the slumber of night into a confident expectation. He sailed to Rome and, having purchased admission to the emperor, he explained how he had discovered on his land a cave of immense depth which contained a vast quantity of gold, not in the form of coin but in the shapeless and ponderous masses of ancient days. In fact, he said, ingots of great weight lay there with bars standing near them in another part of the cave, a treasure hidden for so many ages to increase the wealth of the present. Phoenician Dito, as he sought to show by inference, after fleeing from Tyre and founding Carthage, had concealed these riches in the fear that a new people might be demoralized by a superabundance of money or that the Numidian kings, already for other reasons hostile, might by lust of gold be provoked to war. Nero, upon this, without sufficiently examining the credibility of the author of the story or of the matter itself or sending persons through whom he might assertan whether the intelligence was true, himself actually encouraged the report and dispatched men to bring the spoil as if it were already acquired. They had triremes assign them and crews specially selected to promote speed. Nothing else at the time was the subject of the credulous gossip of the people and of the very different conversation of thinking persons. It happened, too, that the quinquinial games were being celebrated for the second time and the orators took from this same incident their chief materials for eulogies on the emperor. Not only, they said, were there the usual harvests and the gold of the mine with its alloy, but the earth now teamed with a new abundance and wealth was thrust on them by the bounty of the gods. These and other servile flatteries they invented with consummate eloquence and equal sycophancy, confidently counting on the faculty of his belief. Extravagance, meanwhile, increased on the strength of a comarital hope and ancient wealth was wasted as apparently the emperor had lighted on treasures of his wander for many a year. He even gave away profusely from this source and the expectation of riches was one of the causes of the poverty of the state. Basus, indeed, dug up his land and extensive plains in the neighborhood while he persisted that this or that was the place of the promised cave and was followed not only by our soldiers but by the rustic population who were engaged to execute the work. Till at last he threw off his infatuation and wondered that his dreams had never before been false and that now for the first time he had been deluded he escaped to grace and danger by a voluntary death. Some have said that he was imprisoned and soon released. His property had not been taken from him as a substitute for the royal treasure. Meanwhile the senate, as they were now on the eve of the quinquennial contest, wishing to avert scandal, offered the emperor the victory in song and added the crown of eloquence that thus a veil might be thrown over a shameful exposure on the stage. Nero, however, repeatedly declared that he wanted neither favor nor the senate's influence as he was a match for his rivals and was certain in the conscientious opinion of the judges to win the honor by merit. First he recited a poem on the stage. Then at the important request of the rabble that he would make public property of all his accomplishments these were their words. He entered the theater and conformed to all the laws of heart-playing not sitting down when tired nor wiping off the perspiration with anything but the garments he wore or letting himself to be seen to spit or clear his nostrils. Last of all, on bended knee he saluted the assembly with a motion of the hand and awaited the verdict of the judges with pretending anxiety. And then the city populace who were want to encourage every gesture even of actors made the place ring with measured strains of elaborate applause. One would have thought that they were rejoicing and perhaps they did rejoice in their indifference to the public disgrace. All, however, who were present from remote towns and still retained the idly of strict morals and primitive ways all too who had come on embassies or on private business from distant provinces where they had been unused to such wantoness were unable to endure the spectacle and disdain the degrading fatigue which wearied their unpracticed hands while they disturbed those who knew their part and were often struck by soldiers stationed in the seats to see that not a moment of time passed with less vigorous applause or in the silence of indifference. It was a known fact that several nights and struggling through the narrow approaches and the pressure of the crowd were trampled to death and that others while keeping their seats day and night were seized with some fatal malady or it was still worse danger to be absent from the show as many openly and many more secretly made it their business to scrutinize names and faces and to note the delight or the disgust of the company. Hence came cruel severities immediately exercised on the humble and resentments concealed for the moment but subsequently paid off towards men of distinction. There was a story that Bespasian was insulted by Phoebus, a freedman for closing his eyes in a doze and that having with difficulty been screened by the intercessions of the well-disposed he escaped imminent destruction through his grander destiny. After the conclusion of the games Popiah died from a casual outburst of rage in her husband who felled her with a kick when she was pregnant. That there was poison I cannot believe though some writers so relate from hatred rather than from belief for the emperor was desirous of children and wholly swayed by love of his wife. Her body was not consumed by fire according to Roman usage but after the custom of foreign princes was filled with fragrant spices and embalmed and then consigned to the sepulchre of the Juliae. She had however a public funeral and Nero himself from the rostra eulogized her beauty her lot in having been the mother of a deified child and fortunes other gifts as though they were virtues. To the death of Popiah which grief was a delight to those who recalled the past thought of her shamelessness and cruelty, Nero added fresh and greater odium by forbidding Gaius Cassius to attend the funeral. This was the first token of mischief nor was it long delayed. Salinas was coupled with Cassius no crime being alleged but that Cassius was eminent for his ancestral wealth and dignity of character. Salinas for the nobility of his birth and the quiet demeanor of his youth the emperor accordingly sent the senate a speech in which he argued that both ought to be removed from the senate and made it a reproach against Cassius that among his ancestors busts he had specially revered that of Gaius Cassius which bore the inscription to the party leader. In fact he had thereby sought to sow the seeds of civil war and revolt from the house of the Caesars and that he might not merely avail himself of the memory of a hated name to stir up strife but had associated with him Lucius Salinas a youth of noble birth and reckless spirit to whom he might point as an instrument of revolution. Nero then denounced Salinas himself in the same terms as he had his uncle Torquatis implying that he had already arranged the details of imperial business and setting freedmen to manage his accounts, papers and correspondence imputations utterly groundless and false. Salinas in truth was intensely apprehensive and had been frightened in decaution by his uncle's destruction. Nero then procured persons under the name of informers to invent against Lepida the wife of Cassius and aunt of Salinas a charge of incest with her brother's son and of some ghastly religious ceremonial. Volcatius Tullinus and Marcellus Cornelius Senators and Fabatus a Roman knight were drawn in as accomplices by an appeal to the emperor these men eluded an impending doom and subsequently as being too insignificant escaped from Nero who was busy with crimes on a far greater scale. The senate was then consulted and sentences of exile were passed on Cassius and Salinas. As to Lepida the emperor was to decide. Cassius was transported to the island of Sardinia and he was quietly left to old age. Salinas was removed to Ostia whence it was pretended he was to be conveyed to Naxos. He was afterwards confined in a town of Apulia named Barium. There as he was wisely enduring a most undeserved calamity he was suddenly seized by a centurion sent to slay him. When the man advised him to sever his veins he replied that though he had resolved in his heart to die he would not let a cutthroat have the glory of the service. The centurion seeing that unarmed as he was he was very powerful and more enraged than a frightened man ordered his soldiers to overpower him and Salinas failed not to resist and to strike blows as well as he could with his bare hands till he was cut down by the centurion as though in battle with wounds in his breast. With equal courage Lucius Vetus his mother-in-law Sextia and his daughter Pulutia submitted to death. They were hated by the emperor because they seemed a living reproach on him for the murder of Rubilius Plautus son-in-law of Lucius Vetus. But the first opportunity of unmasking his savage wrath was furnished by Fortunatus a freedman who having embezzled his patron's property deserted him to become his accuser. He had as his accomplice Claudius Dumanius whom Vetus, when proconsul of Asia had imprisoned for his gross misdeeds and whom Nero now released as a recompense for the accusation. When the accused knew this and saw that he and his freedmen were pitted against each other on unequal footing he retired to his estate at Formii. There he was put under the secret surveillance of soldiers. With him was his daughter who, to say nothing of the now imminent peril had all the fury of a long grief ever since she had seen the murders of her husband Plautus. She had clasped his bleeding neck in a bloodstained apparel clinging to her widowhood in perpetual sorrow and using only such nourishment as might suffice to avert starvation. Then, at her father's bidding she went to Neopolis. As she was forbidden to approach Nero she would haunt his doors and implore him to hear an innocent man and not to surrender to a freedman who had once been his colleague in the consulship now pleading with the cries of a woman now again forgetting her sex and lifting up her voice in a tone of menace till the Emperor showed himself unmoved alike by entreaty and reproach. She therefore told her father by message that she had cast hope aside and yielded to necessity. He was at the same time informed that judicial proceedings in the Senate and a dreadful sentence were hanging over him. Some there were who advised him the name the Emperor has his chief heir and so secure the remainder for his grandchildren but he spurned the notion which had clung to freedom by a final act of civility he bestowed on his slaves all his ready money and ordering each to convey away for himself whatever he could carry leaving only three couches for the last scene. Then in the same chamber with the same weapon they sundered their veins and speedily hurried into a bath covered each as delicacy required with a single garment the father gazing intently on his daughter the grandmother on her grandchild she again on both while with rival earnestness they prayed that the ebbing life might have a quick departure each wishing to leave a relative still surviving but just on the verge of death fortune preserved the due order the oldest died first then the others according to the priority of age they were prosecuted after their burial and the sentence was that they should be punished in ancient fashion Nero interposed his veto allowing them to die without his interference such were the mockeries added to murders already perpetrated Publius Gallus a Roman knight was outlawed for having been intimate with Phineas Rufus and somewhat acquainted with Vetus to the freedman who was the accuser was given as a reward for his service a seat in the theater among the tribunes officers the month two following April or Nero Nius was changed from Mayus to the name of Claudius and Junius into that of Germanicus Cornelius Orphitius the proposer of the motion publicly declaring that the month Junius had been passed over because the execution of the two Torquatai for their crimes had now rendered its name inauspicious a year of shame and so many evil deeds heaven also marked by storms and pestilence Campania was devastated by a hurricane which destroyed everywhere plantations and crops and carried its fury into the neighborhood of Rome where a terrible plague was sweeping away all classes of human beings without any such derangement of the atmosphere as to be visibly apparent yet the houses were filled with lifeless forms in the streets with funerals neither age nor sex was exempt from peril slaves in the freeborn population alike was suddenly cut off amid the wailings of wives and children who were often consumed on the very funeral pile of their friends by whom they had been sitting and shedding tears knights and senators perished indiscriminately and yet their deaths were less deployed because they seemed to forestall the emperor's cruelty by an ordinary death that same year levies of troops were held in Narbonne Gaul Africa and Asia to fill up the legions of Illyricum all soldiers in which, worn out by age or ill health were receiving their discharge Unum was consoled by the prince for a ruinous disaster by a gift of four million Cisterci's so that what was lost to the city might be replaced its people had previously offered the same amount for the distresses of Rome in the consulship of Gaia Suetonius and Lucius Telecinus Anistius Socianus whom, as I have stated, had been punished with exile for repeated satires on Nero having heard that there was such honor for informers and that the emperor was so partial to bloodshed being himself too of a restless temper and quick to seize opportunities made a friend of a man in light condition with himself one Pemennis an exile in the same place noted for his skill as an astrologer and consequently bound to many in close intimacy he thought that there must be a meaning in the frequent messages and the consultations and he learned at the same time that an annual payment was furnished him to that Antoneus was hated by Nero for his love of Agrippina and that his wealth was sufficiently conspicuous to provoke cupidity and that this was the cause of the destruction of many. Accordingly he intercepted a letter from Anteus and having also stolen some notes about the day of his nativity and his future career which were hidden away among Pemennis secret papers and having further discovered some remarks on the birth and life of Ostoria Scapula he wrote to the emperor that he would communicate important news which would contribute to his safety if he could but obtain a brief reprieve of his exile Anteus and Ostorius were he hinted grasping at empire prying into the destinies of themselves and of the prince some swift galleys were then dispatched and Socianus speedily arrived on the disclosure of his information Anteus and Ostorius were classed with condemned criminals rather than with men on their trial so completely indeed that no one would attest the will of Anteus till Tigalinas interposed to sanction it Anteus had been previously advised by him not to delay this final document then he drank poison but disgusted by its slowness he hastened death by severing his veins Ostorius was living at the time on a remote estate on the Ligurian frontier Scyther a Centurion was dispatched to hurry on his destruction there was a motive for promptitude arising out of the fact that Ostorius with his great military fame and the civic crown that he had won in Britain possessed too as he was of huge bodily strength and skill in arms had made Nero who was always timid and now more frightened than ever by the lately discovered conspiracy fearful of a sudden attack so the Centurion having barred every exit from the house he used the emperor's orders to Ostorius that fortitude which he had shown in fighting the enemy Ostorius now turned against himself and has his veins those severed allowed by the scanty flow of blood he used the help of a slave simply to hold up a dagger firmly and then pressing the man's hands toward him he met the point with his throat even if I had to relate foreign wars and deaths encountered in the service of the state with such monotony of disaster I should myself have been overcome by disgust while I should look for weariness in my readers second as they would be by the melancholy and continuous destruction of our citizens however glorious to themselves but now a servile submissiveness and so much wanton bloodshed at home fatigue the mine and paralyze it with grief the only indulgence I would ask from those who will acquaint themselves with these whores is that I be not thought to hate men who perish so tamely such was the wrath of heaven against the Roman state that one may not pass over it with a single mention as one might the defeat of armies in the capture of cities let us grant this privilege to the posterity of illustrious men that just as in their funeral obsequies such men are not confounded in a common burial so in the record of their end they may receive and retain a special memorial within a few days in quick succession Mella, Kerylius Anichius Rufius Crispinus and Petronius Fel Mella and Crispinus being Roman knights with senatorian rank the latter had once commanded the Praetorians and had been rewarded with the decorations of the consulate he had lately been banished to Sardinia on the charge of conspiracy and on receiving a message that he was doomed to die had destroyed himself Mella, son of the same parents as Galio and Seneca had refrained from seeking promotion out of a perverse vanity which wished to raise a Roman knight to inequality with ex-consuls he also thought that there was a shorter road to the acquisition of wealth through offices connected with the administration of the emperor's private business he had, too, in his son Enaius Lucanus a powerful aid in rising to distinction after the death of Lucanus he rigorously called in the debts due to his estate he spoke to an accuser in the person of Fabius Romanus one of the intimate friends of Lucanus a story was invented that the father and son shared between them a knowledge of the conspiracy and a letter was forged in Lucanus's name this Nero examined and ordered it to be conveyed to Mella whose wealth he ravenously desired Mella, meanwhile adopting the easiest mode of death than in fashion opened his veins after adding a codicil to his will bequeathing an immense amount to Tigalinas and his son-in-law Cosutanius Capito in order to save the remainder in this codicil he is also said to have written by way of remonstrance against the injustice of his death that he died without any cause for punishment while Rufius Crispinus and Anichius Carilius still enjoyed life though bitter foes to the prince it was thought that he had invented this about Crispinus because the man had already been murdered about Cerilius with the object of procuring his murder soon afterwards Cerilius laid violent hands on himself and received less pity than the others because men remembered that he had betrayed a conspiracy to Gaius Caesar with regards to Gaius Protonius I ought to dwell a little on his antecedents he passed his days in sleep his nights in the business and pleasures of life Indulence had raised him to fame as energy raises others and he was reckoned not a debauchy and spendthrift like most of those who squander their substance but a man of refined luxury and indeed his talk and his doings the freer they were and the more show of carelessness they exhibited were the better liked for their look of natural simplicity yet as proconsul of Bithynia and soon afterwards as consul he had showed himself a man of vigor and equal to business then falling back into vice or affecting vice a hero to be one of his few intimate associates as a critic in matters of taste while the emperor thought nothing charming or elegant in luxury unless Protonius had expressed to him his approval of it hence jealousy on the part of Tigalinas who looked on him as a rival and even as a superior in the science of pleasure and so he worked on the prince's cruelty which dominated every other passion charging Protonius with having been the friend bribing a slave to become an informer robbing him of his means of defense and hurrying into prison the greater part of his domestics it happened at the time that the emperor was on his way to Campania and that Protonius after going as far as Kumai was there detained he bore no longer the suspense of fear or hope yet he did not fling away his life with precipitant haste but having made an incision in his veins and then according to his humor he again opened them while he conversed with his friends not in a serious strain or on topics that might win for him the glory of courage and he listened to them as they repeated not thoughts on the immortality of the soul or on the theories of philosophers but light poetry and playful verses to some of his slaves he gave liberal presence a flogging to others he dined, indulged himself in sleep that death though forced on him a very natural appearance even in his will he did not as many in their last moments flatter Nero or Tigalinas or any other of the men in power on the contrary he described fully the prince's shameful excesses with the names of his male and female companions and their novelties in debauchery and set the account under seal to Nero then he broke his signet ring that it might not be subsequently available for imperiling others about how the ingenious varieties of his nightly revels became notorious Celia came to his mind who as a senator's wife was a conspicuous person and who had been his chosen associate and all his profligacy and was very intimate with Petronius she was banished for not having as was suspected kept secret which she had seen and endured a sacrifice to his personal resentment Mekunius Thermus an ex-priter he surrendered to the hate of Tigalinas because a freedman of Thermus had brought criminal charges against Tigalinas such that the man had to atone for them himself by the torture of the wrack, his patron by an undeserved death End of Book 16 Part 1 Book 16 Part 2 of the Annals by Publius Conelius Tacitus This is Librivox Recording All Librivox recordings are in the public domain For more information or to volunteer please visit Librivox.org The Annals of Publius Conelius Tacitus translated by Alfred John Church and William Jackson Broderib Book 16 A.D. 65 and 66 Part 2 Nero despises Thricyapitis for his virtue Nero, after having butchered so many illustrious men had last aspired to extirpate himself by murdering Thracyapitis and Barea Seranis both men he had hated of old Thracyapitis on additional grounds because he had walked out of the senate when Ekrebina's case was under discussion as I have already related and had not given the juvenile games any conspicuous encouragement Nero's displeasure at this was the deeper since this same Thracyapitis had sung in a tragedian's dress at Petavium, his birthplace and some games instituted by the Trojan Anznor On the day too, on which the priter Anticius was being sentenced to death for libel's on Nero Thracyap proposed and carried a more merciful decision Again, when divine honors were decreed to Popiah, he was purposefully absent and did not attend her funeral All this Capito Cusutianis would not allow to be forgotten He had a heart eager for the worst wickedness and he also bore ill will to Thracyapitis The weight of whose influence had crushed him while envoys from Cilicia supported by Thracia's advocacy were accusing him of extortion He alleged too, against him the following charges Thracia, he said, at the beginning of the year always avoided the usual oath of allegiance He was not present at the recital of the public prayers though he had been promoted to the priesthood of the 15 He had never offered a sacrifice for the safety of the prince or his heavenly voice Though formally he had been assiduous and unwirried in showing himself a supporter or an opponent even of the most ordinary motions of the senators He had not entered the Senate House for three years and very lately, when all were rushing fither with rival eagerness to put down Salinas and Ventus he had attended, by preference, to the private businesses of his clients This was political schism and they should not dare to do the like It was actual war Capito further added The country, in its eagerness for discord, is now talking of you, Nero and of Thracia as it talked once of Gaia Caesar and Marcus Cato Thracia has his followers, or rather his satellites who copy, not indeed, as yet the audacious tone of his sentiments but only his manners and his looks a sour and gloomy set bent on making your worthfulness a reproach to you He is the only man who cares not for your safety honors not your accomplishments the prince's prosperity he despises Can it be that he is not satisfied with your sorrows and griefs? It shows the same spirit not to believe in Popeye's divinity as to refuse to swear obedience to the acts of the Divine Augustus and the Divine Julius He condemns religious rites He annals laws The daily records of the Roman people are read attentively in the provinces and the armies that they may know what Thracia has not done Let us go over to a system if it is better than ours or let those who desire change have their leader and advisor taken from them That sect of his gave birth to the Tuberones and the Favoniii, names hateful even to the Old Republic They make a show of freedom to overturn the empire should they destroy it they will attack freedom itself In vain have you banished Cassius if you are going to allow rivals of the Brutti to multiply and flourish Finally, write nothing yourself about Thracia Leave the Senate to decide for us Nero further stimulated the eager wrath of Custunianus and associated with him the pungent eloquence of Marcellus Epairus As for the impeachment of Borea Sauronis Astoria Sobinus, a Roman knight, had already claimed it for himself It arose out of his proconsulate of Asia where he increased the prince's animosity by his uprightness and diligence as well as having bestowed pains on opening the port of Ephesus and passed over without punishment the violence of the citizens of Pergamos in their efforts to hinder Acratus, one of the emperor's freedmen from carrying off statues and pictures But the crime imputed to him was friendship with Plautus and intrigues to lure the province into thoughts of revolt The time chosen for the fatal sentence was that at which Tiridates was on his way to receive the sovereignty of Armenia so that the crime at home might be partially veiled amid rumors on foreign affairs or that Nero might display his imperial grandeur by the murder of illustrious men as though it were a kingly exploit Accordingly, when all Rome rushed out to welcome the emperor and see the king Thracia, though forbidden to appear, did not let his spirit be cast down but wrote a note to Nero in which he demanded to know the charges against him and asserted that he would clear himself if he were informed of the crimes alleged and had an opportunity of refuting them This note Nero received with eagerness in the hope that Thracia in dismay had written something to enhance the emperor's glory and to tarnish his own honor When it turned out otherwise, and he himself on the contrary dreaded the glance and the defiant independence of the guiltless man he ordered the senate to be summoned Thracia then consulted his most intimate friends whether he should attempt or spurn defense Conflicting advice was offered Those who thought it best for him to enter the senate house said that they counted confidently on his courage and were sure that he would say nothing but what would heighten his renown It was for the feeble and timid to invest their last moments with secrecy Let the people behold a man who can meet death Let the senate hear words almost of divine inspiration, more than human It was possible that the very miracle might impress even a Nero But should he persist in his cruelty, posterity would at least distinguish between the memory of an honorable death and the cowardice of those who perished in silence Those on the other hand who thought that he ought to wait at home though their opinion of him was the same, hinted that mockeries and insults were in store for him Spare your ears, they said Not only are Kosutianus and Apyrus eagerly bent on crime there are numbers more, daring enough, per chance to raise the hand of violence in their brutality Even good men, through fear, do the like Better save the senate which you have adorned to the last the infamy of such an outrage and leave it a matter of doubt what the senators would have decided had they seen Thracia on his trial It is with a vain hope we are aiming to touch Nero the shame of his abominations We have far more cause to fear that he will vent his fury on your wife, your household, on all others dear to you And therefore, while you are yet stainless and undiscraced seek to close life with the glory of those in whose track and pursuits you have passed it Present at this deliberation was Rusticus Arulanus an enthusiastic youth who, in his ardor for renown offered, as he was tribune of the people, to protest against the sentence of the senate Thracia checked his impetuous temper not wishing him to attempt what would be as futile and useless to the accused as it would be fatal to the protester My days, he said, are ended and I must not now abandon a scheme of life in which for so many years I have persevered You are at the beginning of a career of office and your future is not yet clear Way thoroughly with yourself beforehand at such a crisis as this the path of political life on which you enter He then reserved for his own consideration the question whether it became him to enter the senate The next day however two praetorian guards under arms occupied the temple of Venus Genetrix a group of ordinary citizens with swords which they did not conceal had blocked the approach to the senate Through the squares and colonnades were scattered bodies of soldiers amid whose looks of menace the senators entered their house A speech from the emperor was read by his quistor Without addressing anyone by name he censured the senators for neglecting their public duties and drawing by their example the Roman knights into idleness For what wonder is it, he asked that men do not come from remote provinces when many, after obtaining the consulate from some sacred office, give all their thoughts by choice to the beauty of their gardens Here was, so to say, a weapon for the accusers on which they fastened Cossutianus made a beginning and then Marcellus in more violent tones exclaimed that the whole commonwealth was at stake It is, he said, the stubbornness of inferiors which lessens the clemency of our ruler We senators have hitherto been too lenient to bring him to be mocked with impunity by Thricia throwing off allegiance by his son-in-law Helvidius Priscus indulging similar frenzies by Peconeus Agrippinos the inheritor of his father's hatred towards emperors and by Cirtius Montanus the habitual composer of abominable verses I miss the presence of an ex-console in the senate of a priest when we offer our vows of a citizen when we swear obedience Thus indeed, in defiance to the manners and rights of our ancestors Thracia has openly assumed the part of a traitor and an enemy In a word, let the man want to act the senator and to screen those who disparage the prince come among us Let him propose any reform or change he may desire We shall more readily endure his censure of details than we can now bear the silence by which he condemns everything Is it the peace throughout the world that victories won without loss to our armies which vex him? A man who grieves at the country's prosperity who treats our public places, theaters, and temples as if they were a desert and who is ever threatening us with exile Let us not enable such a one to gratify his perverse vanity To him, the decrees of this house the offices of state the city of Rome seem as nothing Let him sever his life from a country all love for which he has long lost and the very sight of which he has now put from him While Marcellus, with the savage and menacing look he usually wore spoke these and like words with rising fury in his voice countenance and eye that familiar grief to which a thick secession of perils had habituated the senate gave way to a new and profounder panic as they saw the soldiers' hands on their weapons At the same moment a thresher rose before their imagination and some there who had pitied Havidius too doomed as he was to suffer for an innocent alliance What again, they asked was the charge against Agrippinas except his father's sad fate since he too, though guiltless as his son fell beneath the cruelty of Tiberius As for Montanus a youth without blemish author of no libelous poem he was positively driven out in exile because he had exhibited genius And meanwhile, Astoria Sobinus the accuser of Seranus entered and began by speaking of his friendship with Rubilius Plautus and of his proconsulate in Asia which he had he said adapted to his own glory rather than to the public welfare by fostering seditious movements in the various states These were bygones but there was a fresh charge involving in the peril of the father to the effect that she had lavished money on astrologers This indeed had really occurred through the filial affection of Servilia that was the girl's name who, out of love for her father and the thoughtlessness of youth had consulted them only, however, about the safety of her family whether Nero could be appeased and the trial before the senate have no dreadful result She was accordingly summoned before the senate before the consuls tribunal the aged parent and opposite to him the daughter in the 20th year of her age widowed and forlorn her husband, Aneus Polio having lately been driven into banishment without so much as a glance at her father whose peril she seemed to have aggravated Then, on the accuser asking her whether she had sold her bridal presence or stripped her neck of its ornaments to raise money for the performance of magical rites on the ground and wept long in silence After a while clasping the altar steps and altar she exclaimed I have invoked no impious deities no enchantments nor alt-else in my unhappy prayers but only that thou, Caesar and you senators, might preserve unharmed this best of fathers my jewels, my apparel and the signs of my rank I gave up as I would have given up my life blood had they demanded it they must have seen this, those men before unknown to me, both as the name they bear and the arts they practice no mention was made by me of the emperor except as one of the divinities but my most unhappy father knows nothing and if it is a crime I alone am guilty While she was yet speaking Soranus caught up her words and exclaimed that she had not gone with him into the province that from her youth she could not have been known to Plautus and that she was even involved in the charges against her husband Treat separately, he said the case of one who is guilty only of an exaggerated filial piety and as for myself let me undergo any fate he was rushing as he spoke into the embraces of his daughter who hurried towards him but the lictors interposed and stopped them both Plais was then given to the witnesses and the appearance among them of Publius Ignatius provoked as much indignation as the cruelty of the prosecution had excited pity a client of Soranus and now hired to ruin his friend he professed the dignified character of a stoic and had trained himself in demeanor and language to exhibit an ideal of virtue in his heart however treacherous and cunning he concealed greed and sensuality as soon as money had brought those vices to light he became an example warning us to beware just as much those who under the guise of virtuous taste are false and deceitful in friendship as of men wholly entangled in falsehoods and stained with every infamy that same day brought with it a noble pattern in Cessius Esclepiodotus whose vast wealth made him the foremost man in Bithynia he had honored Soranus in his prosperity with respect which he did not cast off in his fall and he was now stripped of all his property and into exile so impartially indifferent as heaven to examples of virtue and vice Thrasia, Soranus, and Servilia were allowed the choice of death Helvidius and Peconius were banished from Italy Montanus was spared by his father's intercessions on the understanding that he was not to be admitted to political life the prosecutors Apyrus and Cossutianus received each five million Cistercius Osterius 1200 with the decorations of the quister ship then as evening approached the consul's quister was sent to Thrasia who was passing his time in his garden he had had a crowded gathering of distinguished men and women giving special attention to Dometrius a professor of the cynic philosophy with him as might be inferred from his earnest expression of the face and from words heard when they raised their voices he was speculating the soul and the separation of the spirit from the body till Dometius Cacilianus one of his intimate friends came to him and told him in detail what the senate had decided when all who were present wept and bitterly complained Thrasia urged them to hasten their departure and not to mingle their own perils with the fate of a doomed man Aria too who aspired to follow her husband's end in the example of Aria her mother he counseled to preserve her life and not rob the daughter of their love of her only stay then as he went into a colonnade where he was found by the quister joyful rather than otherwise as he had learnt that Helvidius his sudden law was merely excluded from Italy when he heard the senate's decision he led Helvidius and Dometrius into a chamber and having laid bare the arteries of each arm he let the blood flow freely and filled it on the ground he called the quister to his side and said we pour out a libation to Jupiter the deliverer behold young man and may the gods avert the omen but you have been born into times in which it is well to fortify this spirit with examples of courage then as the slowness of his end brought with it grievous anguish turning his eyes on Dometrius at this point enough much remained to be told about the last two years of Nero's reign end of book 16 end of Tacitus's Annals volume 2


So, health technology assessment is also called HDA. HDA is the systematic study of the clinical effectiveness, cost-effectiveness and social and ethical impacts of a health technology on the lives of patients and a healthcare system. This can be drugs, devices, procedures, care settings and so on. Its main purpose is to inform healthcare policy makers. Health technology assessment agencies vary but most look at the health benefit and risk of using a particular technology. HDA also looks at costs and any wider impacts that the technology might have on a population or on society.


Welcome everyone, today's session is going to be taking bias into account why introspective promise more and deliver less. Thank you and hello everyone, my name is Deepak, I am an engineering manager in Red Hat. I am very glad that I could excite you in this session. So about me, I spent five years in PTC, around ten years in Red Hat. I'm from a quality engineering background, but very recently moved into development engineering. And I am from that time when Jira was just a bug tracker. And they had not thought about putting story points in fractional numbers yet. All right, so about today's session, so what I am planning to do is I'm planning to equip you all with some of the thoughts and some of the knowledge which I have, I have read, I have researched about retrospectives. And I think, and I hope that if there is a situation where you have to probably lead or do a retrospective yourself, you can, that knowledge and that information can come handy for you. In a nutshell, today's session is going to be about rethinking retrospectives as we know them. All right, so before we start, I want to make sure that we all are on the same page with respect to definitions of some very common terms, right? So reflection is consideration of some subject matter, idea or purpose, right? For example, let's say, today morning I woke up, I had an argument with my wife. And then, which obviously I lost. And then I went to take a shower in the bathroom. And while taking a shower, I reflected on that argument, right? Without a purpose, right? I don't want to be an improved argument maker so that I can defeat my wife in the future, but just for the sake of it, right? I reflected on it. And so what were the things that I said, probably which I might have said in a better way to probably win that argument or maybe win the fair play award in that argument. But that's pretty much about reflection, where you sit and without any purpose, you reflect on things that happen in the past that matter to you. And then retrospection in our context of agile and everything is reflection in anticipation and with a purpose, right? We buy a process or in anticipation of improving something in the future. We sit and reflect on the past. That's how we do sprint retrospectives as well, right? We have a purpose to improve ourselves for the future sprints or future iterative development. OK, so in, I think, 1983, Donald A. Sean wrote a book called The Reflective Practitioner. The idea was how do people who are great in their jobs do reflection, right? And there is another book by a surgeon called Better. It's not the name of the surgeon. It's the name of the book. I don't remember the name of the author. I think it's Atul Gawande. He also says the same thing. He says that people who are experts in their field, they do a lot of reflection. And how good are they in their field depends on how quickly they get the feedback and how quickly they are able to reflect on that feedback and probably make comments on their future actions. So Dr. Sean divided reflection in two parts, reflection in action, right? So let's say during a football match between Brazil and Argentina, that is an action, right? It has a quick feedback. The result is the feedback, whether it was the win of one of the teams or it was a draw. The result is the feedback. It's a 90-minute window. And if someone is doing reflection inside those 90 minutes, that would be called reflection in action. And once the game is over, let's say Brazil won, and then the Argentinian team sits together with their coach and their staff and then they do a retrospective on what went wrong in this game and how could we beat Brazil in the next game, stuff like that. That would be reflection on action, right, after the event has passed. And when you draw parallels of this approach with working in an iterative development cycle, you'd say that the feedback comes when the software is GA or the feedback comes when you demo your sprint work to your stakeholders, right? And that is exactly when we do our actual retrospective, right, in three weeks or two weeks, whatever time. And then there is another book by this Nobel Prize winner, a psychologist called Daniel Kahneman, called Thinking Fast and Slow. And in this book, Dr. Kahneman says that there are two types of happiness, to be honest. One is in the moment, fleeting feeling, right? And then the second one is once you start reflecting on what happened in the past, right? Think about it. How you feel in your job is very different than how you feel about your job. In most of the developing economies and countries like India, work-life balance has never been a great, what do we call it, hiring incentive, right? Because people want to get into a job. They want to experience the pain, the stress and all of that. As long as they can, after one or two years, sit back and reflect on that job of three years, they know that they have queued a lot. They got promotions, they got good salary increments and all of that. And they started a good career, even after experience. In job, they were slightly unhappy because they were facing those things on a daily basis. But when they reflect on that, they feel very happy and proud that they are queued that. So the thing is that our remembering self always takes 90% of the time, takes all the decisions for us, which some of the times are not in the best interest of ourselves, right? Okay. If you remember this, that's good. This is called Deming's Field or Sheva cycle based on the guru officer, Edward Stemming, who created this in 1950 and all of the iterative development processes and continuous quality improvement processes started with this. Do, check, act and plan. The check part is where modern sprint retrospectives live, right? We do something and then we check how are the results? Did we do something wrong? And then we start acting on those results and we see that, okay, what are the changes that we need to make? But do you think that modern retrospectives work like that? They are rife with boredom, politics and even if you get some action items to work on, they might not be the best action items that your team needed. They are those action items which the most important people in that hierarchy wanted to happen, right? It's not that the team needed it. If you look at the philosophy of Agile, it means that this team has to be autonomous. They have to decide whether we want to, we made these mistakes and we want to improve them. Nobody from outside should tell them that, okay, you made this mistake and now improve it in the next sprint, okay? So John Bain and some of his colleagues in 2002 gave this framework for reflection, right? So whenever you do retrospective, you might be probably using some kind of document where people use that very common template like what went well, what went wrong and what are the things that we can improve in future, right? So if you hand over that document to me, I can clearly tell what is the level of maturity in your retrospective, right? And you can also tell that. So look at these five stages of maturity in retrospectives by John Bain. The first one is, let's say I am a developer participating in a retrospective and I write in the what did not go well section, I wrote that one of the co-developers sat on my code review for three days, which delayed my work, right? So I'm just reporting the incident. I'm not connecting the incident to my experience and feelings and thoughts. I'm not using the incident with my knowledge and everything to tell that, okay, I can understand why this happened and this is how we should be fixing it for the future. So reconstructing part is the topmost level of maturity. So if you look at, let's say there are eight people in the team and they give 20 points on the retro sheet, you can easily map them against these five maturity ratings and tell yourself that, okay, our team is at this maturity level. There are maybe one or two people who are at level five, but most of the team is at level one or two, which is wrong. You don't go to retro to just report the things, right? You go to retro to sit together and use your existing experience to tell, okay, I think this happened due to this thing and we as a team should be fixing it in this manner. Now the very important part, why do we say that we should not do retros at the end? I don't believe in doing retros at the end because of this reason. So there is a thing called recency bias. The book that I showed in last slide, this one, Thinking Fast and Slow, has a very good example of colonoscopy. They experimented that Dr. Kahneman did with two colonoscopy patients. They recorded their pain threshold during the operation. And even though patient A faced more pain collectively and had a longer procedure, but when they were asked to remember the pain, patient B said that he remembered more of the pain because in the last part of his operation was where he faced the most pain in the procedure. We say that we mostly remember whatever happened very recently. It's very common in performance management as well. So as a manager, let's say I have to give an annual bonus to one of my reportees, right? I sit and think about, reflect on what he or she did in last year. My judgment would be fully biased if I have not documented regularly, maybe monthly or every 15 days, or on certain events. If I have not journaled all these things during the year, and I'm just going to sit and reflect on what that person did for one year then assign them a bonus that would be full of recency bias. So I'll probably remember only the latest things and that can be injustice to them. And similar thing happens in retrospectives as well. And hello effect is related to, let's say we did really well in this print. And there was something which was a very minor thing if you ask the team, but for a certain stakeholder, very important person in the hierarchy, it was a major, major thing, right? So one major thing, which was not even a major thing, because it was important to some important person, takes away all the good things that we did. So the whole emphasis is now certainly on that one minor thing in the retrospectivity. So don't let hello effect alter how you think about retrospectives. And then there is lots of small numbers, right? So when we sit together, and I have seen that with mostly the Indian engineers, when we sit together in a retrospective with let's say European and North American engineers, they don't feel empowered enough to speak about the problems that they face. So law of small numbers says that if you choose a very small sample to draw conclusions about a bigger group, you are probably not getting the right indication of what has to be improved, right? And then there is some cost fallacy. Let's say the team together wrote a new logging framework for their software. And now after two or three months, they see that it's not maintainable, it's causing a lot of problems. But they don't want to get rid of it because they are emotionally invested in, because they did a lot of hard work in writing that and all of that stuff, right? So some cost fallacy says that the team is willing to drag that along and probably let their productivity hit. But don't talk about it. They don't want to talk about it because they were somehow emotionally invested in that effort, right? So as a meeting leader or a senior engineer in that meeting, or for everyone else, right, you have to get rid of those things that are not making any meaningful addition to your work. And now the takeaways, I think we just have two minutes. The takeaways, the idea is to retrospect frequently and in the moment. How do we do that? So I had mentioned one very radical idea that why not add one custom field on your tickets if it is Jira, then customize Jira to add a new field called lesson turn, right? So every time you work on a ticket and you feel something bad happened, something happened that was not good, then you go ahead and add something to that. Not in the comments section, maybe in a separate field, right? And once you start in this print and you start retrospecting, you go through those lists, collate all of them, and then think about it. That would mean that you are journaling very regularly. And your retrospecting points are not full of recency bias, right? And then reflection as a technique is a skill that can be taught. I have linked this paper in which Bail and some other researchers did a study on teachers who were learning to teach to young students. And they gave them some daily journaling activity for 30 days. And then they saw that reflection was something which could be improved by training and practice, right? We are not natural at reflection and getting purpose driven action items for future. You have to practice and learn it. And third but very important point, enable fair communication distribution in the team. As soon as you are the senior most person in a retrospecting meeting, if you are, and you see that there are only two people who are dominating and hijacking the whole discussion, then you have to make sure that everyone gets a fair chance in speaking in at least the retrospective meeting. That's very important, both for retrospection as well as for the psychological safety of the team. And I think that's pretty much it. We are at the top of time. So if you want to connect with me, this is my Twitter ID and my LinkedIn ID. In Twitter, I usually do the humor stuff. You can see a screenshot here. And in LinkedIn, I usually do the serious stuff. So yeah. Thank you, everyone.