horse with a speed of light, a cloud of dust, and a hearty high old silver, the Lone Ranger. A man's life often depended on the quickness of his draw. The local sheriffs were unable to preserve the peace, and it was not until the masked rider of the plane started his great fight for justice that law and order were brought to the lawless frontier. Return with us now to those thrilling days of yesteryear. From out of the past come the thundering hoof beats of the great horse silver. The Lone Ranger rides again. A hot, sunny afternoon at the lazy flow of life in Canyon City was startled out of its calm in the sound of a dog fight. When the townspeople saw the dogs involved, they realized it was far more than a casual encounter. They emptied their homes, towed to the plane to watch the battle. But one of the two dogs, the great black hound, was the property of old Zeb Crump, and the other, identical in appearance except for its color, was owned by Charlie Teal. For years, the two men had been rivals and bitter enemies, and everyone present was aware that this fight typified their hatred. Suddenly, old Charlie Teal, accompanied by the lumbering figure of the sheriff, pushed his way through the crowd in front of the feed store and ran toward the snarling hounds. Hi there, Lobo. Great that you hear me. Hair boy, hair boy. Lobo, come here. Hey, folks, help me break it up. Give me a hand, won't you? Sheriff, give me a hand. Lobo, stop it, you hear? Stop that fight in this minute. Pete, give me that stick you've gotten. Break it up, you loco-pitters.  Yeah, that ain't gonna do no good, Charlie. What are all you into standing around doing nothing for? Slam hot, put over the cafe there and get a pill of boiling water. That'll do the trick. You betcha. Hey, Charlie, watch out. Here comes Zeb, thought you ought to know. That old fool, he'll get his tongue to wagon from both ends again as usual, I suppose. Don't he already? No, no, no. Let me through. Come on, get out of my way. All right, if you want to get trapped below, stand aside. Hi there. What's the idea? Sicken that howl to your own mind. I'll have the law on you. I'll have you jailed. You stop them dogs fighting right now. Now, look here you get it.  I tell you to do something you do it. Hey, since when'd you get the right start giving me orders? Never mind that. Just now, hold on, Zeb. Oh, it's you, isn't it, Sheriff? Where have you been all the time? Can you hear me calling you? I was here for you. Then jail this fella. Go on, jail him. What for?  But he didn't. Charlie and me was in the feed stall when the ruckus started. You mean to tell you, Sheriff? Oh, the hot water. Well, give me that. I'll take it. Yeah, she's sure boiling all right. Well, here goes. What is something he don't take, too? Charlie's dog don't need it. It looks like the flag is done scooting for home, Zeb. When you get there, you'll likely find him waiting for you. Though both you got burnt, it plumb serves you right. Picking fights with trash. You ought to be ashamed. Who's dog you calling trash? For yours. Who just pulled? That'll be enough, you two. Charlie, you hadn't ought to have said that. Zeb, I reckon to keep the peace, you better climb in your buggy and get on out of town. It ain't safe having you both here at the same time. Can't make me go, Sheriff, unless you make Charlie too. Oh, he's running along, don't you worry. All right, then. But, Charlie... Well, there's a heap of things to be said between you and me. It's here fighting but one of them. Nothing to said that you weren't the cause of. If you weren't so all fired, jealous. Jealous? What of?  Now, not jealous. I don't want to have to keep repeating myself. I said to stop it, and that's what I meant. Now, Zeb, you get. Sure. But I just aim to tell Charlie this. What? Nobody does nothing. The folks less than they pay for it, Charlie. So far, you've been right lucky. But one of these days, you'll pay. And when you do, you'll be a mighty sorry man. Goodbye. Honest, Sheriff, sometimes I think old Zeb's clean local. Ain't he always been? I never seen you talk up to him so strong for, though, Charlie. What got into you? He ain't done no good trying to smooth things over, has it? No. Well, then why shouldn't I tell the old digit where to get off? Charlie, whatever's started all this between you two. Oh, I don't know. Ever do Zeb a bad turn? Well, not to know of. Yeah, it's a funny thing. I've been watching. It's like, uh... Well, I think you hit it right on the head. It's like Zeb was pies and jealous. And mine when you bought that dog of yours. Zeb had to have one as near like it as he could get.  And when you built your new house, you hired every hand you could find to build a biggie. When I buy saddle horse, he gets one. Even tried to bribe my foreman to come to work for him, because I claim Nate was the best common I ever seen. Yeah, yeah. Well, Charlie, I told Zeb you'd be running along, so I... I guess you bet it. All right, Sheriff. Just as you say. See you again soon, I reckon. Come on, Lobo. Yo, Sidney, you and me are going home. Yeah, wish to thunder I knew it was going to come with this. What is that you said, Sheriff? Oh, I wasn't talking to anybody just to myself. Yeah? Don't pay no attention to me, Slim. I just can't hope and it don't happen when I know dog gone well it is. Come on, Silver. Get him up, Scott. As soon as we reach the top of this hill, Tyler, you'll be able to see both places. Zebs is off to the right and Charlie's to the left. They're about five miles apart. You heard about their quarrel in town the other day, didn't you, Kimosabe? I think I mentioned it. Those two hounds, they all got into a fight. Ponto member. There's few to theirs. We'll have to be brought to an end. Maybe that'd be plenty trouble. If it's allowed to go on, I'm afraid there will be. What will Almond do, Sheriff? Everything he could, Tyler, but it hasn't been enough. And he's been at a disadvantage. Why that? Like almost everyone else in this district, he's a friend of Charlie Teals. He tries to get along with Zeb, of course, but it's difficult for him to hide his dislike. Naturally, Zeb sees that and resents it. Perhaps being strangers, we'll do better. Zeb Van Feller. He's a man whose soul has been poisoned by hatred. He knows that he's as wealthy as Charlie, if not even wealthier. His herds are as large. His range is almost limitless. He commands credit to almost any amount at the bank. And he's found that isn't enough. What do you mean? It's one of those strange quirks of personality. In spite of his wealth and power, he hasn't a real friend in the world. He knows that. Day after day, year in and year out, he's had to see Charlie secure in the respect and regard of his neighbors. While he even can't buy a surface respect. Which explains, I think, his craving to imitate Charlie in every way. Whatever Charlie does, Zeb attempts to imitate him.  When he learns that imitation can never equal the real thing.  Pull up. See, that Zeb's place over there. Now, but this way is where Charlie lives. There's a deep canyon dividing their range. If you look where I'm pointing, you'll be able to just make it out. Oh, no, what's that? Me see it. Isn't that two horsemen? Ah, them ride plenty fast. In fact... What do you think? Looks as if one were chasing the other. See, they're about 20 or 30 yards apart. They must be following right along the rim of the canyon. Listen, there's shots. Come on, Tano, we'll find out. No, look, what's up? Tano, get hit. There, in fall. Not right out of the saddle. Tano, let's go. Ah, get him up, scoundrel. Come on, let's go. Hurry, boys, hurry. Oh, there's so many foes. Oh, there's so many foes. Oh, fella. Get out of there. Hey. Easy there, old fella. Think it easy, boy. We're friends. We're not here to harm you. Watch out for that fella, Tata. He's vicious. Ah, me watch out. Now, let's see what's happened here. This is where the one fella we saw dropped from the saddle. There's his horse over there. Ah. The fella who shot him kept going. He headed into the mesquite patch there and disappeared. Not right. We don't see what we can do about picking up his trail later. The thing to do now is find out what happened to the man who was wounded. And Tata. What matter? I think I can tell you now who that man was. Who that? Look at the dog, Tata. Him black fella.  Ah, fella named Zeb. Right. I've got an idea what's become of him. Here. From the signs, he must have been just about here when he fell. Not two feet from the canyon's edge. Ah. I don't know if he was wounded badly enough. But if he went over it. You come. What is it? You look down there. Not too close to the edge, Kimosabi. Tata, careful. You look. I see nothing but those rocks below there. Yes, Tata. Now I see what you mean. Ah, what do you think? Tata, there's been murder done. Ah. That man's dead.  And it ain't to be found while wrecking. What the? Clash, man. Carol, keep your hands from those guns. What are you? This isn't a hold up. And I'm not an outlaw. I brought you news of murder. What are you? Chair of a friend of mine and I were riding toward the canyon that divides Zeb Crump's range from Charlie Teals. From a distance, we saw a running gunfight. One man dropped from the saddle. What's that? And the other man was shot. We lost his trail on that malpie over there. But the other will be waiting for you when you get there. He's dead? Yes. Masked man, who is he? We thought he'd better not be touched until you could get on the scene. You showed sense. So we didn't attempt to get down to where he was. But if I'm not mistaken... What? That man Zeb Crump. Well, you're crazy, Mr. It can't be. There it means... I know, Sheriff. I know. It would mean that he was shot by a Charlie Teal. Well, I'll be... Settle up, Sheriff. We'll take you there. There's that redhead path here. Only way to get down to the bottom of the canyon, but it's almost worse than no path at all. We're almost there. All right, tell him... Yeah, we made it. I thought I was gonna bust my neck a dozen times over. Now, which way was it, Masked Man? To your right. Come along. Lead the way. You know where you've seen him. It isn't far. Thank you. But I'm thinking of climbing up again. That's gonna be a chore. When you saw him in those rocks, you see ahead of us. Isn't that right, Hunter? That's right. Here's the place. Circle his boulder here and we... Sheriff, he's gone. What? Strange, are you sure this is the place? You sure you ain't made any mistake? Look for yourself, Sheriff. This is where he fell. Yeah. Yeah, that's so. Well, even so, Mr. You did make a mistake. Yes? You said he was done for. Well, I don't know. But he couldn't have been. How he lived through a fall like that, I don't know. But he done it all right. If he hadn't, he couldn't have got up and walked away. But, Sheriff, he didn't. I wasn't mistaken. He was killed. What makes you think that he... Read the sign, Sheriff. Look at those boot prints. Well, I'll be switched. The murderer came back and carried him away. The curtain falls on the first act of our Lone Ranger drama. Before the next exciting scenes, we have to pause for just a few moments. Now, to continue our story. When the Lone Ranger and his companions discovered the dead man had disappeared, they lost no time in starting for the top of the canyon. The difficulty of the ascent made it impossible to talk. But as they neared their rim, they heard a mournful sound. They reached them faintly at first, but gradually became clearer. You hear that, Meshman? I do. Yeah, funny thing, ain't it? That's Blackie. Old Zeb didn't have a human friend in the world. I mean animals, he was, too. But all that's something the dog just don't take into account. I mean, as Zeb was, Blackie's up there mourning and just the same as if he'd been the finest zombie ever wore outside a letter. Loyalty has bred in their nature, Sheriff. Perhaps there's a lesson in that for us. What do you mean? Maybe we should take more trouble to value men by their good qualities and less to condemn them for their bed. That's funny talk for a Meshman. Well, there's nothing to do with the problem we're up against right now. I'd suggest that just as soon as we reach the top. Rifle shots, get down, Doc. No, keep climbing. Those shots are being fired at us. We'll be safer up above. Come on, climb as fast as you can. Almost slipped. Can you climb me? We haven't much farther. Here we are. Make it. I'm all right. Up with you, Turner. Now, then, where's that hombre, huh? Where's he gone to? It's impossible to tell. If I could just get my hands on that skunker. I'm afraid you won't. But why? There's no way of telling just where those shots came from. Could have been anywhere over in there. That section's too broken up. We could spend days looking for a sign of that gunman and still not find him. That dirty Gregorch. I can't save you this. I can see how Zeb might have pestered Charlie. He just couldn't stand it no longer. But why would Charlie shoot at us? Him and me was good friends. When a man's life is at stake, he might do anything. Yeah. Yeah, I suppose that's so. But still it. Yes? I'd rather explain it by saying Charlie'd go on clean local. Didn't know what he was doing. There's the Charlie T-line who wouldn't have harmed a fly. I'm going back to town. I'll have plenty to do. You'd better send deputies to both ranches. They'll be sure their owners are missing. Yeah. And send out warrant notices for Charlie. Well, come on, mess men. Let's get back to the horses. What's the matter? What's that? Is something wrong, Turner? I mean, not no. He's uneasy about something, Sheriff. I can recognize the signs without Taddu speaking. Me watch that trail. Why, Kimosabe? I think maybe follow, follow. Following us? Do you suspect someone's following Taddu? Or do you know he is? Me not know. Keep watch, Taddu. But if we are being followed, try to do it without giving yourself away. I suppose that hombre figured if he kept on our trail, he'd get another chance to finish what he tried to start back at the canyon. It's possible. But it seems to me... Hold on. What's the matter, Sheriff? Those shots fired back at the canyon weren't fired at us. I'm certain of it. I should have known at the time. My gosh. Where were we when we heard those shots? We were climbing that path. And we're still almost 50 feet from the top. Those shots didn't come from anywhere near the edge of the canyon. We could have located them. What are you getting at? Those shots came from a point at least 300 or 400 yards back from the canyon. That's right. How could the man who fired them have been able to see us in order to aim? Well, I'll be... Mayor's men have never occurred to me at all. No, to me, Sheriff, until just now. You're right. But if he wasn't shooting at us, then who... Then he had another object. I think we can be sure that anyone wandering around in that district wasn't amusing himself in target practice. And don't talk foolish. Outside of target practice, you don't fire at an object. That isn't alive. But what other living object was around back there except ourselves? The dog. You see, Sheriff? It'll be too sure. There might have been an excellent motive, and we could just see what happened through the eyes of that fellow with a rifle. What a dog! Shootin' at a dog that wouldn't harm nobody. It wasn't bothering nobody. Well, if you could make anything out of that mess, man, then you got me licked to a phrase. I can see just one explanation. Well, let's hear it. No, for the present, it sounds too incredible. Sheriff, when you reach town, it'll be dusk. We'll ride part of the way with you. What have you got in mind? You'll go on to town as if nothing had happened out of the ordinary. And when you get there, do the things that would have been expected of you. Send deputies to both ranches. Get word around that Charlie Teal has wanted for murder. But at the first opportunity, slip away from your office without being seen. Ride just as fast as you can for the ridge. We'll be waiting for you. And then what?  All right, let's go.   Almost nine, Tyler. Sheriff should have been here. If he doesn't arrive within a few minutes, we'll have to go on without him. Wait. That horse? Maybe him now. Sheriff? That's you, man. You late? I had one dickens of a time getting away. When folks heard about Zeb being killed and Charlie turning killer, I thought they'd go crazy. I was just about to take my guns to him to get him out of the office. Well, now where are we going? Back to the canyon. I'm backing on two things. One, that the dog will continue his vigil at the point where his master met death. Oh, he likely be there all right. And two, that Tyler was correct. That someone was following us this afternoon. What's that got to do with it? He must have been the fellow who fired at the dog. And if he followed you to town, then he hasn't had time to return. You're way ahead of me, Massman. Let's hope the killer isn't way ahead of us. You want to see justice done, Sheriff? Ride like you've never ridden before. Come on, sir. You must speak softly. There's no use advertising our presence. You're the boss. That's that dog. Yes, we leave the horses here where they'll be out of sight. They'll stand. Come along. Keep to the shadows. We go this way. You take the lead, Hunter. Is where we headed now. You want to find a place of concealment as close to the dog as possible. And fella comes back, you'll have to get close himself in order to get good aim at night. And then we'll grab him. Yeah, good place. By these rocks? Get down, Sheriff. We can do nothing now, but wait. Massman. What time is it? Almost midnight. Two hours. We've been here two hours. You honestly think that hombre's going to show up? I know he will. How can you be so all fired certain? The dog's still alive.  I've got an idea that just like us, he's somewhere close. But remember, he's captured, it means his death. He's going to take every precaution to make sure he won't be interrupted again as he was this afternoon. Likely so. Be patient, Sheriff. It'll be worth it. I'm trying to. But you know Massman. What's wrong? I kind of wish I hadn't come with you. Yes? Why? I think I understand. It's the thought of arresting a man who's been your friend, having to hang him afterwards. You hit it, Massman. If I'd ever known someday I was going to have a job like this to do, I'd never run for sheriff. The lawman doesn't have an easy time of it. Oh, Charlie. The show must have gone clean out of his head. You won't. You look. What's up? What is it? Look. There. A shadow, Sheriff. Yeah, and by a target, that shadow's moving. Wait. Listen. If he continues on that course, he'll come directly between us and the dogs. That'll be the time for us to strike. Yes, you're right. Now, silence until I give the word. You stop, Massman. He's living something. He's aiming. Come on. Get that man. Stand right where you are, Charlie. You'll have to let you have it. Got that gun. Don't move. Get back. Get back. Got that gun, I said. All right. Massman. Well? This ain't Charlie. It's Zeb. Well, Massman, you've done a job to be proud of. This poor cat I got handcuffed to the saddle. Here's gonna hang. But you've kept everything so all-fired secret. Sheriff, Zeb gave himself away when he fired at the dog. And yet, if possible, the dog had to be killed. I don't savvy. It's clear enough. The murderer wanted the dog out of the way. It had to be for a reason. There was just one thing the killer was worrying about then. Discovery and capture.  We knew either Zeb or Charlie had been killed. Naturally, when we saw a black dog mourning the death of its master, we assumed that Zeb had been the victim and Charlie the murderer. That's right. But in that case, how could Zeb's dog give Charlie away? Charlie was already known to be the killer. The dog's death would have gained him nothing. That's where I was puzzled. Only one possibility remained. If Charlie had nothing to gain by the dog's death, then Zeb did. He was alive and Charlie had died. But the black dog wasn't black. His coat had been dyed. You will learn I'm right. Well, dog gone. It was a perfect plot. You would send out a description of Charlie as a murderer, not Zeb. Zeb, once he was out of the territory where he was known, would have been perfectly safe. But first, before he left... He had to get rid of the dog so I would never find out the trick he played. That's the answer, Cheryl. There's your prisoner. Come on, we may meet again. Hey, wait up! Hold on there, I want to... Clear it out. Well, Zeb, you ain't leaving. Hang on to the saddle. Your head for the Calibus.    I've just heard of the copyrighted feature of the Lone Ranger Incorporated.


I was playing a lot of Overwatch at the start of the month, but then I got pulled back into playing Stakedale Innocence, which is a game which has been on my playlist for a long time, like a long time This game has been on my list for a long time, like not even the last one Stop, I ran out of here, not even the last team sale, maybe 2 or 3 team sales Kayjan Yeah, so I haven't streamed a lot of Overwatch 2, but I haven't played that in the past maybe 2 or 3 weeks I'm gonna set my mind that let's finish this one I think I must be around 3 fourths of the way still, I'm not quite sure exactly Look at that red sun I think Wajik is working in the yard So this is quite an old game, not the sequel just came out Recently came out, Lakedale Requiem But yeah, this was a free epic game, I forget when a while back Is the lock still frozen? Yes, it's a tough winter this year Anyway, how was your nap? Feeling better? A little Did you dream of him again? Yes I'm going to prepare a special proof of Saint John's order for you That's alright Lucas, I don't need it I miss him, that's all, I have to accept that he won't be coming back Amicia Is that even like a super stealthy game? I'm going to go see the others Can you tell Melli about the just comparison? Melli is going to say something like you should just piss on it But it's way too cold for that As the mic is not coming through, that should be better Oh, it's Lakedale Requiem and DLM This is Lakedale Innocence guys How's the mic? Some people were saying that the mic was off Although it seems to be okay Sorry, let me check the audio input Okay, I just put it closer to my face Oh, is Requiem a DLC? I'm not sure To be honest, I haven't really followed that But I really dig these kind of stealthy story-driven things Oh, what are you doing here? The Hugo should have found you So this is like plot heavy The gameplay is, I mean there is some gameplay involved Yeah, it's not the reflex-oriented gameplay It's kind of more puzzle-oriented Stealthy But the stream is laggy We've never had so many apples Hugo would have made himself sick with them I think maybe I should restart Should I restart? To be fair, the PC has been on like the whole day Rodric still hasn't been able to work because of the snow Still the mic thing? Alright guys, let me take a living five minutes against the setup But okay, fine Catch me in like five minutes I'm just gonna restart everything Hopefully that clears up the GPU problems To be fair, I am running a bit of a lot of workload So, stop moniker Alright, I'm gonna just turn everything off And then I'll be back in like five minutes People are saying that the mic is weak But it should be okay But okay, alright See you in five


So I want to talk a little bit today about ROP. It's kind of, to my interest right now, are pediatrics and retina. So it's kind of a nice bridging topic for me to discuss. So kind of a generic case to start off with. Baby boy was born at 27 weeks gestation, weighing 980 grams on oxygen and NICU. When and how often do you screen these babies such as this for ROP? They do have ROP, when do you treat? And then the question also is, how do you treat? So just briefly on some of the screening guidelines. These are, people have different, there's different guidelines out there. Some are more stringent, some are a little bit more loose, but kind of the currently accepted APOS guidelines is any baby born before basically 31 weeks, regardless of their birth weight. If a baby's born 1250 grams or less, or any baby that the neonatologist deems as high risk. And then when do you screen these babies? If they're, it should be performed at 31 weeks post menstrual age and infants that are born basically 427 weeks. Or if they're born 427 weeks, then four weeks chronological age from that point on. And then there's also some criteria that suggests maybe screening at six weeks of life if they're born before 25 weeks. So once you see these babies and you say, okay, this baby looks like they have some evidence of ROP. When do we follow up? There's kind of four categories of follow up time periods. So the first is one week follow up, one week or less. These are babies that are high risk, babies that have stage one or two ROP in zone one, immature vascular or aggressive posterior ROP. Then the next category is the one to two week follow up. These are kids that had zone one ROP but are unequivocally regressing stage two, zone two, and then also just immature vascular in the posterior zone two. And then the two week follow up, these are kids again that are getting better and better unequivocally regressing ROP zone two and some still immature vascularization. And then the third category is kids that are clearly getting better that are into zone three but still have a little bit of evidence of ROP. So how do we screen these kids to know who has ROP, who's at risk for ROP? It's a really hot topic right now in research and literature. There's some different research going on on monitoring IGF-1 levels as an indicator for risk for ROP. Also monitoring VEGF levels and pigment epithelial derived factor and also erythropoietin levels. These have all shown some evidence but not a ton yet. It's still not quite clear how effective these are, how sensitive and how specific these are going to be at catching all the kids that we need to screen. So another reason it's a big topic is not every hospital with a NICU has pediatric ophthalmologists or retina specialists easily accessible to screen all these babies that may need screening. So that brings up the telurentinal imaging idea. This has been shown to be really good for clinically significant ROP but kids that have mild ROP that are in the early stages, it's not that, it hasn't shown, been shown to be great yet. People have looked at different maternal risk factors, preeclampsia, diabetes have been shown to be associated with ROP but there's a confounding effect because a lot of these babies that come from preeclampsia or diabetic mothers are born premature. And then also another way to monitor these is look for kids who have high oxygen saturation goals. There's a decent association between how high that goal is and how high risk they are for ROP. Kind of the underlying principle of those, there's nothing really beats taking a look and getting imaging hand in hand. So once we decide that a kid has ROP, there's basically three criteria for when we say, yep, we need to go ahead and treat. So zone one ROP with any stage of plus disease, zone one ROP stage three with no plus disease or zone two stage two or three with plus disease. So then it leads to the question, how do we treat? And this is probably where there's the most research and most controversy or opinion on a different camp on what the best way to do this is. So laser right now is a standard of care. Some positives about laser, we know that it improves the functional structure outcome versus kids who have no treatment. We know it's effective halting progression of ROP in most kids. There's a lot of negatives associated with it as well. We know it decreases VEGF levels in the blood, although much less significantly than with anti-VEGF treatment. There's destruction of tissue. We've lost peripheral vision, high myopia. We see these kids sometimes growing up to be minus 15, minus 20. It doesn't work for everyone and it's a very high stress procedure for these kids. A lot of stress and trauma to them. So then the other option we have is anti-VEGF treatment. So just some pictures here of some kids demonstrating the difference between laser and ROP or anti-VEGF treatment in some of these kids. So this top picture, this was before laser treatment and this is after laser treatment. You can see where the ridge was and where the laser treatment was done. Vascularization stopped there, halted the progression effectively. And this doesn't happen on every single patient but in a lot of patients, we're seeing kids treated with anti-VEGF. You can see where this ridge was and after anti-VEGF treatment, the vessels continue to progress all the way out to the far periphery. So big questions with anti-VEGF, are they safe? And if they are safe, what's the best anti-VEGF treatment? We have multiple options. And then what dose and what are the long-term side effects? A lot of questions that we're trying to get answers to. Some of the things we do know about anti-VEGF, we know that it increases anti-VEGF, increases the vascularization. There's some evidence that shows that it decreases the myopia, although it's not 100% clear at this time. It is much less invasive for the patient, much less stressful, and they develop better peripheral vision, assuming they can go ahead and progress to the periphery. Some of the negatives, we know that it decreases the VEGF levels in the blood. This is one of the biggest questions, is this safe? Then you can also see kids that get this chronic arrest of the vascularization. Kids sometimes reactivate after treatment. There's been mixed results of successful treatment for these kids.  The significance of this is unknown at this time, because these kids are still so young and it's hard to tease out how much of their abnormal vascular is from being premature versus the treatments. So here's a picture from a recent study showing this chronic arrest of the vasculature after vavacizumab injections. You can see pre-injection and post-injection didn't really progress much. So one of the big questions I mentioned earlier was the VEGF response systemically in these kids. You can see in this study by Kong et al. With laser, the VEGF level systemically did drop a little bit for a time period, not as much as the intravagal vavacizumab. But there was a drop there. And then the levels of anti-VEGF seen in this. So in the serum for eight weeks, you see a decrease in the injected eye. You see it for eight weeks. And even in the other eye, the fellow eye, you see a decrease for a couple weeks of VEGF levels. A recent study that we're actually a part of here was looking to see what dose is going to be the most effective. So basically what they did in this study was took six to one premature infants with type one ROP and I started treating them with different doses of vavacizumab. Every time a group was successful in their treatment, then the dose was cut in half. So you can see 10 out of 14 infants received 0.25 milligrams and then it dropped down to 0.125 and 0.063. And finally it is 0.031 milligrams. Basically one 20th of the current of the beat ROP dose, which is one of the bigger studies measuring how much and what medication to treat with. So this was showed to be quite successful. Some of the downsides of this study was a small study size, a short fallout period at this point, although it's still being monitored. And we didn't monitor the VEGF levels. Yeah. So what was the way to do it? That was the very last of it. We did actually measure the VEGF levels. We did, okay, I misread that. The VEGF and the serophilic, I'm sorry. No, no, please. I missed that. No, it's okay. That was my mistake. Another study recently came out called the CARE ROP study. And they looked at using Rannabisimab, or Lusentis instead of Avastin, and using even lower doses than we currently use. So they took two groups. One group had 0.12 milligrams and one group had 0.2 milligrams. And found that in both groups, the vascularization went all the way to the auricerata. The systemic VEGF was not significantly suppressed. There were a few eyes that needed retreatment in the 0.12 milligram group and in the 0.2 milligram group, one kid needed a second retreatment, so three injections total. It was interesting to note that the vascularization of auricerata was better in the 0.12 milligram group versus the 0.2 milligram group. The reason this is significant is Rannabisimab is a smaller molecule has a shorter half-life. So theoretically, if it is getting into the system, then potentially it's not having as much of a systemic effect. So some of the important points about this study. The seromente VEGF levels were monitored for up to eight weeks, longer if there's more retreatments required. And as I said, I mentioned previously, there was not a huge decrease in the systemic VEGF levels. Some of the kids did need to have rescue treatment, which basically means they didn't respond at all and needed laser within the first 28 days. And there was one kid, one child in the 0.2 milligram group that had respiratory failure that was thought to be likely to the anti-VEGF treatments. And I've not shown this slide was the kids who had the 0.2 milligram dose needed to be on oxygen for a significantly longer amount of time than the kids who received the 0.12 milligram group. So even though the anti-VEGF levels were not measurably decreased, there seemed to be some effects, which that's gonna need some more research to figure out exactly what's going on there. So overall, in all these different studies of different anti-VEGFs and different doses, there's a lot of mixed results. Aaron Bulu and colleagues found that four out of five kids improved to 14 out of 16 eyes. Ian colleagues found that in a larger study that there was good to success. Castilenos and colleagues found that six out of six kids treated with randomism map had complete resolution. But then there's other studies. One colleagues found that six eyes treated with randomism map five had reactivation of ROP and within an average time of six weeks. So in conclusion, some of the big things that we are kind of taken away from all this research is that right now it's still unknown if anti-VEGF treatment for ROP is effective, safe and effective, more research is needed. Novel screening methods are continually evolving. Nothing beats an indirect exam with imaging. Lower doses and short acting agents may be better in terms of vascularization and lower morbidity. Again, more research is needed there. Right now, laser is the standard of care but anti-VEGF is increasingly shown to have a role in treating these babies with ROP. And for now there's no FDA approval for anti-VEGF treatment for ROP. And finally, when it is decided to treat these babies with either laser or anti-VEGF it's very important to have a very detailed informed consent process to explain the risks and benefits of both these treatment because there's no perfect answer for this very, very possibly devastating disease. Any questions, concerns, yes, please. So my sense is, and I want to be corrected by retinal colleagues that even though there's still a lot of questions that the general ways of interest is moving where recently people are using VEGF inhibitors rather than lasers. Are we at the point where more than half of these kids are getting treated with VEGF? I'm not sure about that. But yes, there's greater interest. Lubee brought study, mainly in zone one, poster zone two, and the guidelines from the American Academy of Pediatrics and Ophthalmology are to treat zone one or eyes that are near death. But there's been a wave of interest in treating all type one severe ROPs of that zone two as well. And the concerns, as Chris nicely pointed to, are there. So even in the ROP-1 study, which is one of the trials that we're enrolled in, at one-twentieth of the B-prog dose, serum veg up was reduced for over a month in these babies. So the babies are developing. See, the other problem with all the studies that come up is that we tend to look at them and think that premature babies- We don't even know what we don't know for 20 years. Right, well, some of them are from India, some of them are from, and the babies are older developmental age and they're larger. So when they get the same dose of anti-vegF in a larger eye that goes into a larger blood volume, the concentration is much reduced compared to the premature babies that we have in the United States or in countries that really regulate oxygen or have the resources to do that. And in which 22 and 23-week gestational age babies are surviving. So we really can't compare the two, they're apples and oranges.  The coreroid, the photoreceptors, the circuits that develop within the cells within the retina are all developing and they may need veg up signaling. And our lab has shown that when you inhibit, so we figured out what's the optimal dose of anti-vegF. So we used a very representative model in a lab because we can't experiment on babies. And we knocked down, we figured out what cells were expressed in EGF. So Mueller cells do a lot of that. We knocked down the EGF by using a cell specific promoter and a short here pin RNA to the EGF. And so it knocked down the EGF two levels that were in the retina that were the same as a room ear rat of the same developmental age. So we felt that was physiologic. And even when we did that, we had long-term thinning of the outer nuclear layer. So what does that mean long-term? I don't know. We had some neuroprotective factors that were also released. So maybe the retina is able to respond, but the red is full term. So we really have a lot of questions we don't know. I think that what we're getting at now is that we need more than just anti-vegF. We need protective mechanisms. We need to be able to introduce methods that will allow the babies to vascularize or a vascular retina. Have protection against that compromised vascularity within the already developed vessels that occur with high oxygen. And then also allow the baby to develop and mature. And so anyway, that's where our lab is working toward looking at that and some of the recessors that might be useful in that way. Projectly those, as I go around in different places, there's more and more I sense. This is what they're doing. If you want those questions, then answer. They're moving to vegF injections rather than using them. It's so much easier to do an injection. Laser is very, it's hard as a body, you know, of the assertion. Kind of experiment on the progress which is happening in developing countries when anti-vegF treatments became available. A lot of people moved with some disastrous results to doing injections entirely, not knowing that kids would come back with fulmin and RLP. So in a lot of cases, it isn't a decision between anti-vegF and laser is becoming a combination of both where Dr. Hartman's colleagues are treating the posterior fulmin and RLP with anti-vegF. And then instead of worrying about that taking time bomb of having RLP coming back, going ahead and doing laser. So in essence the same eye is getting both treated. Thanks Chris, I think that was a really interesting talk. And kind of to Emmy's point, I just had a quick question. It's not well resolved in the literature at present what physiologic systemic vegF levels are in these preterm infants. So even though most of the studies that are done compare treated babies to babies with RLP with an alternative treatment like laser, maybe those babies have higher systemic vegF levels and that's one hypothesis that's out there and one group out of Japan has shown, in fact that's true, they have a very small sample size of course because it's so difficult to look at these babies but. And Emmy's point as well made that different populations have different age ranges in which we're seeing RLP due to the technologies and ability to administer oxygen, et cetera. But they did show that the treatment with anti-vegF while it did access the systemic circulation, it did not lower systemic vegF below what we were seeing physiologically in babies of similar gestational age. But that's one very small study and I just don't think it's well resolved in the literature. Did you get a sense of that at all in your meeting? I think that was a big point that I thought about was there's no clear resolution anywhere. A lot of big question marks, a lot of, you know, can't pull me in for directions, you know, using their database to back up, you know, the feelings they have, of course, usually, et cetera. Yeah, yeah, thanks. And I will say that RLP, I agree with you Leah, definitely. And in the RLP one study, we also measured veticism in the sample, which that Japanese study made it come as well and it was still elevated, so. The dragon stuff. Yeah, yeah. I don't think that's published very so. Interestingly though, this is becoming standard care across the country. It absolutely is. Writing at Westanger.


Under President Johnson's administration, new efforts to uplift America range from housing standards that would eliminate city tenements to a billion-dollar agency to combat poverty. These impressive breakthroughs serve to highlight the fact that even more concerted efforts to raise living and opportunity standards for millions of Americans held in poverty's grip are needed. On July 29, President Johnson established a special advisory commission on civil disorders to delve deeply into the social soul of the nation. It will be led by Illinois Governor Otto Kerner and New York City Mayor John V. Lindsay. The president reminded the commission, no society can tolerate massive violence any more than a body can tolerate massive disease, but just saying that does not solve the problem. We need to know the answer, I think, to three basic questions about these riots. What happened? Why did it happen? What can be done to prevent it from happening again and again? What we're really asking for is a profile of the riots, of the rioters, of their environment, of their victims, of their causes and effects. July closed on a nation whose social fabric was being tested as never before. Forced on the nation and the majority of people was the fact that many painful months and years lay ahead. The solution of decades-old problems had become a national imperative. And let us build something much more lasting, faith between man and man, faith between race and race, faith in each other, and faith in the promise of beautiful America. Let us pray for the day when mercy and truth are met together. Let us pray and let us work for better jobs, better housing and better education that so many millions of our own fellow Americans need so much to. Let us then act in the Congress and in the city halls and in every community so that this great land of ours may truly be one nation under God, with liberty and justice for all.


My name is Melvin Chibole, based in Nairobi, Kenya. Where would somebody want to support TechSoup? TechSoup offers a global voice. I don't think there is any organization that has the kind of network that TechSoup has. So by investing in TechSoup, we are investing in many communities that are represented by the network. And hopefully whatever we are trying to put together will end up transforming the communities that we are coming from.


The Bemidji Charter Commission has made the recommendation to switch the mayor's term from two years to four years. But after Tuesday's City Council meeting, that decision will likely be left up to the voters. The Charter Commission unanimously supported the recommendation. The amendment was presented to the council, which raised concerns over the proposal. Currently, city councilors serve four years while the mayor serves a two-year term. Some council members shared concerns about the change, possibly limiting the public's ability to change the majority on the council. I think that it is important for the public to be able to say, you know what, I don't know what this council is going on. And then you are also, you have a responsibility to listen to who's running and whether or not they're qualified and whether you believe that they're going to do a good job for you or they have your same philosophy, your same belief in the issues. So I would agree with that Nancy. The recommendation will now go back to the commission for further review. It could then submit the proposal to the voters during the next election.


Another file that I memorized is a zip file containing a single file, an agar file. That agar file is stored inside the zip file, it is not compressed, it is just stored embedded. Let me show you. So you have three records here, you have a record for the file content, a directory entry record and a record that is the end of the directory. So every record starts with pk, so that's 54b, 0304. And now here you have several fields that are words or double words. So integers that are words or double words, little engine. So first I have the version with which this was created, and that's version 14. Then I have internal flags, which are 0. Then I have the compression mode, and it is just stored, so again 0. And then I have a timestamp, also 0, and a date, which I also set at 0. And here now I have a 4 byte value, which is the CRC32 code of the file here, so the agar file. And that's 3ccf5168. And now here I have two fields, double word fields, that are the size of the compressed and uncompressed file. So that agar file is 68 characters long, so that's 44x decimal, and again here 44. And now I have the length of the filename, and I will use agar.com as a filename. It's a word, and filename I can have extra data, but here I won't have any, so that's 0, 0. And now here I can type the filename and then the content of the agar file. So let me switch agar.com, and then the string for the agar file. Okay, so that's the first record, and that size of the record is 6b, so that's okay. And now let's also check that agar string here. I calculate the hash, so 3ccf5168, so that's correct. So now I'm going to enter the second record, the one for the directory entry, so 54b, there's 102. And then again I have different fields, double word and word size fields. So first of all we have the version with which it was created, and the minimum version that is used to be able to decompress it. So again, 14, 0. Then again I have those flags that are 0. Then I have the compression method that is 0. Then I have a timestamp that I put at 0, and also the date that I put at 0. And then here again we have that CRC32 code, so 3ccf5168. And now again we have the size of the compressed and uncompressed file, so 44, 0, 0, 0, 0, 0. It's a double word, 44, 0, 0, 0, 0, 0. Then we have the length of the file name and nine characters, so 0, 9, 0, 0. Extra data field, 0. And now here so you can have a comment, and the comment, there won't be any comment, so the length is also 0. And now are a couple of more fields. So you have the disk ID field, because zip files can be spread over different disks, and that's something that dates back from floppy disks. So I just want disk and its ID is 0, so 0, 0. Then we have internal attributes, 0, 1. And then we have external attributes, those are the attributes of the flags, the flag attributes of the file. So that's a double word. And it's little union, 20, and if I'm not mistaken that is the backup attribute, so the archive attribute. And now here what rests me is again the position now, because this is an entry, this is a directory entry, and it needs to point to the record that contains the file itself. So that record is at the beginning, so that's offset 0, like this. And now finally I can type the name of the file, like this. And then to end, but we can check first. Okay, so the length here is 55 bytes, so 37 exadismals, so that's also correct. And now the last record is the end of central directory record, so that's 54b0506. And now again different fields, so there is a field for the disk, the number of disks that we have, and also which disk this is, so these are all 0, because there's only one disk. Then the number of files we have in this archive and in this disk, so that's one for each case. And now we have here the size of the different directory records. And remember there is only one record and that size was 37 exadismals, 37, 0, like this. And then we have the pointer, an offset to the first record that is the directory record. And that was 6b, remember that position, 6b00000. And then finally the zip file itself can also have a comment, but we're not going to put a comment here, so zeros. So and that is that file, so let me check, calculate a hash. And indeed here this is the hash of the zip file that I memorized. So now let me show you the decoding of those records using templates. I'm running the zip template and as you can see here, well sorry, I need to show you the templates. Template result like this, okay. And here you can see the three records. So the file record, the directory entry record and the end of central directory record here are those three records. And here are the different fields. So the signature, the version, the flags, the compression, so it is stored 0. The timestamp is 0. The date is also 0 and that results in an undisplayed date. CRC code, the compressed size, the uncompressed size, size of the file name and extra field length. And then here the file name and then we have our second record. Again signature, the version, what it was made by and the version that you need to extract it, the flags, the compression again 0, timestamp 0, date 0, CRC code, compressed size, uncompressed size. The file name length, extra field length and here the comment that is also 0. The disk number start 0, internal attributes 1, external attributes 32, the offset 0 and here the file name. And finally the end of central directory record with the signature, the disk number and the start disk number both 0. The entries on disk and the entries in this directory both 1. The size 55 or 37, 37xad, the offset 107 or 6bxad and here the length of the comment 0.