Llywodraeth yw'n rhoi'n amlwg am y dyfodol i'r Llyfrgell yng Nghaerdoeddfa Roedd yn Cymru. Mae'n rhoi'n rhoi'n rhoi'n rhoi'n rhoi. Rwy'n rhoi'n rhoi'n rhoi, rydyn ni'n mynd i'ch bod fy ychydig yn un o'r ei chyfeu'r ysgol. Fe fyddai'n mynd i fydda i yw, bod yw'n rhoi'n rhoi fydda i'r llwyddoeth, felly rydyn ni'n rhoi'n rhoi'n rhoi'n rhoi'n rhoi'n rhoi'n rhoi'n rhoi. Can you all stand up? Thank you. If you've... Okay, remain standing if you've heard of a particle accelerator before. Remain standing if you've heard of a particle accelerator before. Okay, remain standing if you've ever heard of a particle accelerator being used for something other than particle physics. So if you think that particle accelerators are just particle physics, can you sit down for me? Okay? Good. Find a question. Remain standing if you think that you can explain even just vaguely or briefly how a particle accelerator works. Can you remain standing if you think... If you think I'm not going to make you? Promise? Oh, a couple, a couple, a couple. Okay, okay, thank you. You can all sit down again. Thank you. So let's start then because a lot of you weren't able to say what it was or what they used for. With this question, what is a particle accelerator? Well, most of you have heard of them and probably for most of you, the one that brings us to mind is this image here. Can anyone put their hand up and tell me what the name of this machine is? Have you recognised it? Just shout it out up here. Thank you very much. This is the Large Hadron Collider. It's the world's biggest particle accelerator. It's 27 kilometres in circumference. It's buried about 100 metres underground near the border between France and Switzerland near Geneva. And we'll hear a little bit more about that. But that's only one particle accelerator. There are actually over 26,000 of them in the world. Hopefully later on we'll find out a little bit more of where they use. But to start with, let's quickly go through. I won't make those people who are left standing do this for me. I'll tell you very briefly how they work. So we need a few ingredients. And the first thing we need is some particles. And by that I mean subatomic particles. Or even atoms themselves perhaps. So here's a little quiz for you. Four different types of particles. Electrons, neutrons, protons and gold atoms. Can you put your hand up if you think that you know or think you can tell me that one of those you can't put in a particle accelerator. Can anyone suggest which one you think you can't put in an accelerator? In the centre here? Can you say it a bit louder? A neutron. Do you know why? Because it isn't charged. Thank you very much. You can't put a neutron in a particle accelerator because it doesn't have an electric charge. Now there's another one there that jumps out at me that might not have an electric charge. Can someone tell me which one it is? The gold atom. Can anyone suggest a way to get that gold atom into a particle accelerator? Up the back there? You can ionise it. So to ionise a gold atom you can rip the electrons off or add more electrons on or whichever way round you want to do it, give it an electric charge and then we can put it in a particle accelerator. So that's the kind of particles we need. Now the next thing we want to do with those particles is to give them some energy. That's the basics of how an accelerator works. You just take these particles, you give them some energy and you do something with it. So I've got a machine here called a vanagraph generator which does that on a slightly bigger scale. Building up charge, actually building up voltage is the key to giving particles energy in a particle accelerator. So if I just switch this one on then, now some of the first particle accelerators were actually genuinely using this mechanism of having a belt and some rollers and building up lots of voltage. They were called vanagraph accelerators. They still exist. I've worked on one actually. So this isn't actually that far fetched. But if you pretend that these are some particles which are charged, so if they're the same charge they get repelled and there's a force there, they're pushed away and they gain some energy, which in that case just pushed them up in the air. But in the case of an accelerator, we'll get our particles up going faster and faster and faster towards the speed of light. To make that a little bit more realistic, I have a demonstration here which is the simplest particle accelerator I could make, which is in a giant salad bowl. Can I have the visualizer on someone up there? Let me just put that under here. There we are. So you can see in that bowl that there are some metal strips and they cross over in the centre. And the four in the centre that cross over are going to be connected to the high voltage part of the vanagraph generator. Now the other four strips, those ones like that one are connected to ground or zero volts. So I'm just going to connect that up. OK, so in this case, my bowl is actually going to be the particle. It's covered in a conducting paint, so again it will be charged in the accelerator. And well, I'll pop it in there and see what happens. If I just switch this on, hopefully we'll be able to see up on the screen there. There we go. OK, so what's happening here is that when it goes over the charge strip, it picks up the same charge and it gets repelled just like the metal cups were repelled and it gets pushed along. Then it hits the grounded strip and it dumps all of that charge, but it keeps its momentum, it keeps rolling around. So then it's able to approach the next charge strip without getting decelerated or slowed down. So every time it goes over one of those four that crosses in the middle, it gets a kick or gets accelerated and it gains energy again and again and at the moment it's actually circulating in the bowl just outside of your field of view there and it's limited in how far it can go up this bowl by friction and by gravity in this case. Slow it down again.  So this is a pretty simple particle accelerator and I think you'll recognise that it's not really how a proper one works. There's a few reasons it's not how a proper one works. The first one is that in this demonstration the ball has to change charge and fundamental particles don't change charge. So while in this case my voltage is constant and my particle changes charge, in a real accelerator we have a constant charge particle and that means that we have to change the voltage really, really quickly in time with the particles coming around to get them to accelerate. So I'm going to switch that one off. Right, so that's approximately how we're going to give some particles some energy. The next ingredient is how to control them and for that we use magnets. Hopefully some of you will know that if you put a current or a beam of charge particles through a magnet it will actually bend around a corner so that's how we achieve control and then there's no point getting these particles up to a huge energy if you're not going to do something with them so I'll call that collision and there's no point doing all that great science unless you can see what you're doing. The final ingredient that I put in the list of things we need for an accelerator is a detector which in this case was our eye but in other cases they can get a little bit more complicated and this is an example of an image from one of the Large Hadron Collider detectors of two beams of protons smashing into each other and creating loads and loads of different particles which you can then see in the detector. That's actually a simulated one, not a real one but they'll look pretty much identical. But this talk isn't about accelerators. We now know how they work. The talk is about five things you should never do with a particle accelerator. So, I'm sure when you heard the title of that you thought, oh, you probably shouldn't do this so can someone give me an example of something they think you probably shouldn't do with a particle accelerator? What do you think? There's lots of things, they are mostly silly so please do say them. Anyone? Up there? Put a live animal... You're onto something there because do you know what? That's number one. I did not plant that, I promise. Right, so the first one. Do not try to accelerate a pet. I don't know why as humans we automatically think I've got this crazy machine, I'm going to put a bunny in it. Anyway, so can anyone think? I mean, mostly through this talk we're going to have some crazy ideas but I want you to try and use your brain or physics to think, why couldn't you do that? Why couldn't you put your pet in a particle accelerator? Up here, yep. It's not magnetic and it's also not charged. It doesn't have an electric charge. Okay, so we could strap two of these to the bunny and charge him up and then he'd be charged but he's slightly too big and the other thing that might happen is he's going to be affected by the vacuum in the pipe of the machine. At least I suspect he would. So, unfortunately, well, we had this little marshmallow man who was kind of already parked over here but I'm going to demonstrate to you what might happen. Can we get the visualiser back up please? What might happen?   That's amazing! Sorry, we haven't tested this. I didn't realise it was going to be this good. Oh, okay, and he's gone past. So what was happening there is I'm just going to switch it off while he looks a bit sad.  Now, in this case, a marshmallow is stretchy so he grew to a pretty good size there actually and then once it went past the point of the marshmallow being elastic, that's when he kind of died and shriveled back down again. Is it possible to slowly let the air back in and just to let the air back in? Yeah. Thank you. Can you give Andy a big round of applause for helping me with that demo? Okay, so that's one reason why you probably shouldn't accelerate your pet.  Would your head freeze because of the cryogenics? So minus 271 degrees in some accelerators not all of them but take the large Hadron Collider for example there, you know, the magnets are pretty cold or would the heat from the beam make your head explode? Or would your head explode from the ultra-high vacuum?  So I'm going to say one, two, three, four and I want to show off hands for which one you think would get you first. So one, who goes for one? Who goes for your head freezing from cryogenics? Oh, only a couple people. Who goes for number two? Who thinks the heat from the beam? Oh, a few people at the top think the heat from the beam. Okay. Who thinks the head would explode in the ultra-high vacuum? It's convincing, isn't it? It is, yeah. There's quite a few people who like that one. Okay, and who thinks you would die from the radiation dose? Who thinks you would die from the radiation dose? Interesting, okay. So what is the answer? Well, I had a bit of a think about it. And the answer is it depends which accelerator we're talking about but let's consider the large Hadron Collider. First of all, let's think about the cryogenics about that really cold temperature. It's minus 271 degrees. That's very cold.  This is a picture of one of the 15-metre-long dipole magnets, one of the bending magnets in the machine, and they are cooled down to this temperature, but it's extremely difficult to get your head in there.  You'd stick it in somewhere easier in a bit that wasn't cooled down to minus 271. So the likelihood is that wouldn't get you first. What about the ultra-high vacuum? Well, it's kind of the same thing with the marshmallow man before.  But people have done studies in outer space of astronauts and how they could survive in the vacuum of outer space. Now, I don't actually know how the two vacuums compare, but that information says that you could survive in outer space with your space suit open for about 10 seconds before you were ripped apart by the vacuum. So I don't think that's going to get you first. So what about heat from the beam? Well, this is a challenge, actually. Heat from the beam is an interesting one because it's actually incredibly difficult to stop the beam, and if you put your head in the way of the Large Hadron Collider beam, unlike what some of these people in the video thought, it would actually go straight through and out the other side. In fact, it has enough energy to go through your head and out the other side about 100,000 times before it loses all its energy. And that's actually one of the issues they had to deal with when designing the machine, is how do you stop the beam? And we want to stop it occasionally, intentionally because we're done with that particular fill of the beam or because we think there might be a problem somewhere so we want to get the beam out and dump it. So they had to put a lot of effort into designing what they call the beam dump, a big block of a very dense graphite which absorbs the energy. But even then, there's so much energy that they can't just dump it directly on it or the thermal shock would make the thing explode. So they actually have to paint the beam in sort of a swirly pattern in order to spread out the load of the heat from the beam on this huge graphite block. If you just put this beam onto a massive block of copper, you could actually melt 600 tonnes of copper from solid to liquid, just using the large hadron collider beam.  Radiation effects. Quite a few of you were keen on this one. Yeah, it's happened. So there's this guy, Anatoly Bogulski, who, once before the days of such strict health and safety, somehow managed to bypass a safety mechanism on an accelerator and stick his head in a 76GV proton beam. Now that's quite a lot lower in energy than the large hadron collider beam. But the amazing thing is that he just saw a really bright flash and he didn't feel any pain at all, which is interesting. Most people think, well, this beam has got lots of energy, it will just destroy you. That's not quite what happened.  At the time he was studying for his PhD and he went on to get his PhD, his didn't put him off. He worked as a scientist for many years and he's actually still alive in Russia, living in relative obscurity. I'd love to know really what he's up to now. A journalist interviewed him a few years ago and went to see him. Because the side of his face that the beam irradiated was paralysed because of the dose of radiation, and he hasn't been able to move the skin on that side of his face for so many years, that side of his face looks like it was pretty much the day that this accident occurred. When I first read this, I was like, Miracle cure for aging! Paralyzed face is probably not a miracle cure for aging, but there you go. He looks like he did 19 years ago on one side of his face. You can actually put your head in the beam of an accelerator and survive it. He's not the only one to have done it. In the days of Cockroft and Walton when they were first developing particle accelerators, they didn't know about the dangers of radiation. One of the ways that they counted the events or what was happening in some of their nuclear physics experiments was actually to sit under the thing, under the beam. The beam would come down, some nuclear reaction would happen, and then they'd have this fluorescent screen that would light up every time what they were looking for happened, and they would sit there and count each time it lit up, sitting underneath the beam being irradiated. Now, actually, these people lived relatively healthy lives and Cockroft and Walton got a Nobel Prize for their work, which doesn't justify it, but there have been people who have stuck their heads in particle accelerators. Nowadays, you wouldn't want to do that voluntarily and you wouldn't want to do it without understanding the consequences, but there are some situations that you might want to do it in. There's a very good reason for that because if you take a much lower energy beam than the Large Hadron Collider beam and you put it into water or to the human body or into tissue and you start it with the correct amount of energy, it will actually slow down and stop and deposit almost all of its dose or its energy in one spot, and we call this the Bragg Peak. Now, the radiation dose that the LHC beam could give you could kill you 76,000 times over, but the radiation dose you'd receive from a beam of say 200 MeV, a relatively modest proton beam is much lower and can actually be used to treat cancer. We use this in something called proton therapy, which we're getting in the UK. We did actually pioneer it, and then it hasn't quite come back onto the NHS yet, but in cancer therapy usually you like to direct a dose of radiation exactly where you'd like it, so in this case, this is a child with their spine that needs irradiating. The tumor removed from the base of the skull and they need to irradiate the spine in order to stop the cancer spreading down the spine to save that child later in life. Now, with X-rays, with usual X-ray radiotherapy, the dose distribution there is the best that we can do using all modern techniques. You can see that underneath the spine in the sort of stomach area there is quite a lot of radiation dose that we might not want to be there. If you use protons instead, you can actually get a much better defined distribution of the dose, and this is really a fantastic treatment. It is more expensive than X-ray radiotherapy, but based on the basic physics of how a beam reacts inside the body or inside tissue, I think it's a fantastic treatment and one that we should look forward to using in the future. So look it up if there's anything else.  Moving on, number three, don't use a particle accelerator as a death ray. Now, when I was putting together this lecture, I asked a question to my colleagues, my very esteemed colleagues, has anyone ever tried to develop an accelerator as a weapon? And they said, oh mumble mumble, cold war, space, star wars, something rather, no, that was their conclusion. They were wrong. People in the US didn't think about building a particle accelerator, called a neutral beam accelerator, that they would launch into space, that's the first bit, which is a bit wacky, and then they would use it to shoot down satellites and shoot down missiles and destroy anything that they didn't like because they were going to have this super powerful beam in space. Well, they quickly realised that this was crazy and that they were never going to be able to actually make a weapon out of one of these machines, mostly for the reasons that I explained before. Even if you had the Large Hadron Collider in space, I have no idea how you'd get up there, but even if you did, it would actually be difficult to do damage with it, mostly because the beam would just go through things and out the other side. But they did, in fact, one of the interesting things I discovered, they did put a particle accelerator in space, which I think is fantastic. They developed this machine, which was only about this big, and they used ultra-light weight materials and only weighed about 50kg. Compare that with a 27km long ring. 50kg was only low energy, but they just built it, they sent it up in a rocket and they actually tested it in space and then they brought it back down to Earth and they tested it again on the Earth and it still worked, which I think is an incredible feat of engineering. People really haven't heard of this experiment before, so I thought I'd point you towards it. If you're interested, it's called The Bear Project in 1989, and I have a contact who worked on it if you really want to find out more. We can't use them as a weapon. No deployed weapon has ever used this technology. What could you do, though, if you took particle accelerators and you made them really powerful? This is something that I work on, is taking proton accelerators of relatively low energy, putting more and more particles in and getting a really high beam power. One of the reasons we want to do this is because we want to drive something called an accelerator-driven, subcritical reactor. This is where you take a nuclear reactor, a fusion reactor. In the core, instead of having uranium, it has an element called thorium, which is actually much more abundant and you don't have to refine it. You can use all of it. Hook up to the reactor, a particle accelerator, a very high-power proton accelerator. The protons come in and they smash into a heavy metal target and create neutrons. It's those neutrons, then, that drive the reaction in the reactor. Without the accelerator there, the reactor is subcritical. It doesn't produce energy. It doesn't sustain a chain reaction. Once you add in the accelerator, you can continue to drive the reaction and generate energy. That's why we're using nuclear waste into something much shorter lived and much safer. There's some really interesting applications of accelerators way outside of the realm of particle physics that we're starting to get a handle on. The only problem is the accelerator for this is about ten times more powerful. The requirement is about ten times more powerful than the ones that we can currently make. There's lots of challenges for people like me who design accelerators to try and come up with ways of making them more and more powerful for a reason. We can't use it as a weapon of mass destruction. This was another one that someone told me that the thing they shouldn't do with a particle accelerator is you shouldn't eat it, which is true.  That's probably a bad idea. There's this guy called Montsuim Monchtoo, who is a Frenchman, who, according to Wikipedia, ate all of these crazy things.  I just want to give you a very quick... Yeah, there's an aeroplane there, and 400 metres of chain. Let me just give you a very quick reminder of radiation. What is radiation? It's energy in the form of moving particles, or waves, emitted by an atom or another body as it changes from one energy state to another. That's the official definition. You can have two main types of radiation, which are ionising or non-ionising. Ionising radiation is the stuff that does us damage. There's three types which you're probably familiar with, called alpha, beta and gamma radiation. Just to remind you of alpha radiation won't go through your hand.  There you go. You've been reminded of what radiation is. Can you put your hand up for me if you think that radiation is scary? I'm going to put my hand up. If it's a fearful... If it's a thing to be afraid of. Less people than I thought. OK. Not so scared of radiation. Can I have a volunteer, please? One of those people who said they were afraid of radiation, could you come down for me? Do you want to come down? Can I have another volunteer who's not afraid of radiation, please? Do you want to come down? Thank you. If you would like to stand on this side and you can hold this thing with the radioactive symbol on it. There you are. Don't lick it. You can hold some bananas. Can you stand to the right over there? Thank you. OK. Is the thing that you're holding radioactive? What do you think? Yeah, it probably is. Ah, radioactive bananas. I'm guessing it is. You're guessing it is? That one's pretty easy. The interesting thing about radiation is it's naturally present in most of the things around us. Who's now slightly afraid of the bananas over there. How many bananas do you think you'd have to eat to get a dose of radiation that would make you sick, even? Well, just from eating them, you'd get sick after eating about 50. OK, but they are actually radioactive. You might not have known. It's a potassium in the bananas. It contains potassium. A very small percentage of potassium is naturally radioactive. But you'd actually have to eat 5 million bananas in one sitting to get sick.  That thing that you're holding there is radioactive. They're called thoriated rods and they're used in welding. You can actually just buy them. This thing I'm holding here is called a Geiger counter. It will tell us whether or not these things are radioactive. So, just to show you. Can you hear that? Yep. So, there is something coming off there just to demonstrate that the bananas are really only very mildly radioactive. We can't pick them up with a Geiger counter. So, when we're thinking about radiation and radioactivity, it is worth keeping in mind that just the fact that something is radioactive does not mean it's harmful to us at all. Can you put those down? Can you thank my two volunteers? This is a naturally radioactive food. There are foods which are naturally radioactive. But most of us would like to think we've never eaten food that's actually been in a particle accelerator. Right? That sounds a bit crazy. So, surely we don't eat anything that's been in a particle accelerator. Well, in the UK, we don't eat many things that have been in a particle accelerator. But things like herbs and spices or other things occasionally go through a process called cold pasteurisation or electronic pasteurisation which uses electrons from a particle accelerator to treat the food. Now, it is legal, not illegal in the UK and in the EU and it's fully authorised and there's a number of foods that you can find which have been irradiated and that goes all the way through from bananas so sometimes they're treated with this process to slow down the ripening process so that they can stay greener for longer so they'll have a longer shelf life and as you increase the amount of radiation that these things are treated with you go from some grains, seafood to killed bacteria, herbs and spices are a more common one and then even sometimes higher doses on things like poultry to kill salmonella. Now I tried to go in the supermarket and find things which said that they'd been irradiated because according to EU law it has to be labelled on the packaging to say that it's been irradiated and I couldn't find anything that had been irradiated in the UK supermarket so I think in the UK we don't get much of this even these things that I'm holding actually this is not a brand advertisement even herbs and spices I couldn't find any that had been irradiated but it's quite common if you travel or if you go to other parts of Europe or the US to find things which have been irradiated and in the US if you see this green symbol on your food that doesn't mean it's organic it means it's been irradiated which is a little bit misleading if you ask me but never mind but one of the things I want to point out to you is that this is not a dangerous process in fact it's a really really useful process to kill the bacteria in our food and make it healthy for human consumption and just because we've irradiated it does not mean that it becomes radioactive so there's a distinct difference here between a naturally radioactive food or something that's actually could genuinely be harmful to me about ate it and food which has been irradiated because it's only gone through that process to treat it to make it fit for human consumption and there's one place that I can think of that well maybe you might get to go eventually that you really really wouldn't want bacteria or you wouldn't want food poisoning and that you would probably elect to say yes if I'm going there I want my food irradiated before I go but the worst place I could think of to get food poisoning is when you're in one of those and a lot of astronauts food is irradiated before they send it up so that they really really aren't going to get sick from it so yes you probably have eaten something that's been through a particle accelerator but perhaps you're more or less concerned about that than you are about eating horse meat I don't know so the final thing I think you probably shouldn't do with a particle accelerator is you probably shouldn't destroy the earth with it now I don't know why I need to say this even but people seem to think that when we design new massive particle accelerators that are going to have particles that are huge energies that we've never created before in the lab that somehow that we just built it for the lulls and that we're going to destroy the earth with it and that we haven't quite thought it through and that we're not quite sure what we're doing and yes have you if you're at all concerned please go to hasthelarjhadroncollider destroytheworldyet.com and well you can tell me what you find there but answer to some of the questions that we had a few years ago when the large hadroncollider started up of you know could it destroy the world the answer and the most convincing answer to me as to why it couldn't is because we have particles in outer space from cosmic rays and things like that at much much higher energies than we could ever dream of creating in the lab and so far they haven't done anything catastrophic to us and we're perfectly fine so in terms of just reaching a higher and higher energy I think it doesn't really matter what we do in the lab that we should be safe on earth from these high energy particles and if we start creating things like many black holes which we may or may not they will pop out of existence so quickly that they wouldn't have time to suck any matter in and the interesting thing the interesting message that I take from this is that these machines are built so infrequently you know 25, 30 years between these big accelerators every time it happens I'm told by my sort of retired colleagues this happens every time this scare story that we're going to destroy the earth with it because it's so long between them that people actually forget the media hype that happened last time around so I'm tasking you with the job when you're older, if one of these machines starts up and people start going oh it's going to destroy the earth that you think uh-huh I've heard this before it's not really going to happen so I just like to finish by saying that sometimes some of our craziest ideas and I've been through some pretty crazy ideas of things that you could do with a particle accelerator here but sometimes they turn out to be surprisingly good ones if you do them in the right way and these machines are not just useful for particle physics they're useful for all sorts of other things like cancer treatment like killing bacteria in food and other things I haven't discussed like carbon dating and imaging down to the atomic scale and all sorts of other things and I just like to leave you with my advice in choosing your career for what it's worth and that is to find something that makes you sit up and think this is really important or this is fascinating or this is what I'm passionate about and it can be in any area really something like space might get you or climate change might be a concern you might really love astronomy or you might be more passionate about world hunger injustices in the world the availability of water, energy, health aging, anything like that think about it and do something about it that's all really you need to do and make a career out of doing something about it because if you do something that you're passionate about and you're really, you know, you love you're not going to even feel like you're going to work each day you're just going to feel like you're getting up and you're doing what it is that you're passionate about and while you do that don't be afraid to challenge yourself don't shy off doing something just because you think it's hard it's when we do something hard that we really make a difference so dig deep and don't be afraid to dream and I will leave you with some photographs of some of the places that my career in physics has taken me so far and I hope to add many more to this list in the future so that's five things you should never do with a particle accelerator thank you


All right, let's see. Where should we start? OK, this talk is about super happy fun times, or happy fun times, depending on the complicated thing. So let's get right to it. Let's see. I still never remember how to switch things in. Pull out your phones. Connect to the Wi-Fi. Happy Wi-Fi fun times. If you have iOS, if you're lucky, just be patient. If you're on Android, yeah, it'll be like 20, 30 seconds. If you're on Android, once you're connected, go to Chrome and go to h.com. Is there sound for the computer? Does anybody have sound for this thing? OK, so I don't know what it is about your guys' projection system, but it should be 60 hertz. Is that something you can set over there? Both the sound and the refresh rate. It's HDMI, but it's going to the adapter, right? So you're probably losing it. Can I just plug it in there and plug it in my computer? Hold on, maybe I can just set the sound. All right, sorry, hold on, hold on. Sound. Output. Internal speakers. Oh, sound. So this is happy fun times. It's a system for making multiplayer games in your browser, or installations, or giant ads you want anybody to interact with. People connect immediately. They don't want to do anything. They connect and they're in. I apologize for the speed. This is the first time I've been somewhere where the projection system doesn't have a good frame rate. Every place else has been 60 hertz.  It's going fast here. This is actually a virtual game console. So you guys are all playing this game. I'm going to switch games. So you're all back in. Those are just controllers. This is a Bomberman. We've got 41 players. I've had 92.  But when you die, you'll be on the edge and you can throw bombs in. Somebody just died. These games are actually in JavaScript and WebGL, just because I used to work in the Chrome team. I know that stuff pretty well. It was easy for me to get started with JavaScript. So if you're on the side, you can throw bombs in. You can actually collect the power-ups to make your bombs bigger, even when you're dead.  If you're on the outside and you hold the button down, oh, someone won. Player 24. All right. OK, another game. This game I made five years ago. Before I built the system, I built this game. And then I just sat on it for four years thinking, I should probably turn this into a library. And so this is an example of when you design games like this, you have to take into account how many players. So the way it works is only six people are up there. And all the rest of you are in this waiting list. And you collectively control the ghost ship, which is over there. So if you all press to the right, it'll go to the right.  This is also an example of the system is communicating to your phone. So if you die, your phone will actually make explosion sounds. And if you have your sound up, your shots only last. You only get three shots.  But the point about the limited players is that if I let all 40 of you guys up there, it would just be bullet hell.  So you have to really take that into account. The same with Bomberman, like 20 players, maybe you can play, but when I had 92 players, you guys had 41, it's almost impossible to find out where you are when it starts. And so if you're going to make a game, you have to design something around that. If any of you just have player, you can click the little gear box in the top corner, and you can change your name. So I'll show you a couple others. This is the worst game ever, but I wanted to show that I could take the orientation from your phone. So if you can find the color on your screen and you can find the matching color with 41 people that's nearly impossible, then you should be able to tell that as you tilt your phone, it changes that thing to orient that way. People have actually used this to make a Google Glass game, not Google Glass, Google Cardboard games, where everybody out there is in Cardboard, and they're all playing a network game. A couple others I'll show you. Here is one that just moves the dots around. So you slide your finger, and if we don't erase, then where I can ever read? Don't have it here, do I? Paint, there it is. If I don't erase, then you can all paint. Of course, this brings up another problem with group games. Maybe not in Singapore, but certainly in America, somebody will draw a penis, or they'll name themselves penis. So you have to take that into account when you make a game. Let's see. There's also I have Unity plugins. So if you want to make the games in Unity, you can do that.  I need to do work on the camera. The camera will at some point just zoom out, and you won't be able to see anything. But you can't see it's working. All right, there it goes. Yeah. All right. Where did it go? Is there anything else I want to show on here? Yeah, that's a bit different now. So a couple of things I want to show are, let's see, should have prepared this. So these are a couple of games that were made last year. This game is from last October. And it's six screens long.  And this is again, that's actually six machines each running Chrome, running a game in WebGL, going through the system. So it's all JavaScript. So you'll see those three guys jump off the screen and walk on the next screen. And I actually asked them for 20 monitors. I'm glad they only gave me six, because making content for six was enough work. I had some luck. A couple of friends helped out. One of them, his son, is only 16, did all the graphics. So then also last year, UCLA has a game lab. And they used it to make some games. So this is one game that they made. The players are using their phones to control those bunnies. And they are trying to shoot the magic hat. There's a guy under the magic hat using elite motions to control the gloves and like shoo away the bunnies. It was a student project. It was the end of the season project for them. So you can see him standing there using his hands to move the gloves. But that's the kind of thing you can do with a system like this very easily, let people interact with some giant art installation. Another game was this one, which is a risk type of game that some other students made at a game. They started at a game jam. And so you can see they have a giant map. And this is an example where they actually, because they made these maps and they wanted to support multiple players, they actually made a map for four players, a map for five players, a map for six players, all the way through 12. But at some point, that's a lot of work. And they didn't have to come up with some auto map generating system. They also had to make flags and all that kind of stuff. So that became work. It's showing the results of the last moves. And then when the moves are over, the phone screen will change to say, OK, what move do you want to make next? And then everybody makes their move. It's also an example of design problems that since they made it a jam, they didn't have a lot of time to iterate. And so there it is saying, what moves do you want to make? I'm saying, I want a stockpile. Yes, do you really want to do that? And then it goes back for waiting for everybody to make their moves. But what you have with the moves is that people get tired of waiting for other people, like, who hasn't made the move yet? I'm tired of waiting. And then they kind of just leave. So that's one of the things you have to take into account, design your game around people coming and going, or make sure people always have something to do. That's actually what happened in the Bomberman game. It used to be when you died, you had to wait until the round was over, and people would just stop playing. And so, OK, I'll put you on the edge so you can throw bombs in and keep playing. So yeah, a couple of other things. Oh, this isn't going to work anymore, is it? I don't think I can make it. I can't go presentation because I'm offline. That is a bug in, yeah, presents just great out. So one thing that's easy is that the phones are just controllers. So at least at one level, it's much easier to write a game using this than, say, something like, than a normal network game.  From the game's point of view, it just gets button presses. I mean, you can do more than that.  And this one, there's only one view. And so that makes that easy to get something started. Another thing that I mentioned, players can disconnect at any time, so you need to take that into account. A lot of students at UCLA tried to make games that required poor people for the entire game. And if somebody, like, got a message from their friends and picked up their phone, well, they're out of the game. And then the game was waiting for them to play. You need to do something about that situation if you're going to make a game. And as I mentioned before, if players have nothing to do, they're going to leave. So if you're going to have rounds, give them something to do while they're waiting for the round to end. You can have too many players. That's Barman Man with 413 players. Not actually 413 players. It's just, like, made up some simple AI just to see it work. But it works. Another thing which you haven't done a lot is just using the system to do unique things. So the games that I showed you are mostly what I call low-hanging fruit. They're just an old game, like some 30-year-old games, with more players. And really nice to explore things that people haven't done, kind of like the bunny game maybe that you saw. There was another game I mentioned that people did stuff with Google Cardboard, and that was a team-based thing. So one person's looking at the Cardboard, and they're telling the teammate a little bit to the right, and they're doing something a little bit like, no, a little bit down, and a little bit down, and their team's competing. And that's something you couldn't do in an old system just with more controllers. So this is an example like maybe you could put all the phones down and just turn to one big controller and use the system to coordinate them. Another example is making team games. If you look at what's actually on the screen on these shots, like the blue and the green guys are clearly on the same team, because the blue guys got to press them in the green guys' phone, the green guys got to press them in the blue guys' phone, you'd have to be creative in your design so they can't just shout across them, hey, blue, press this, right? But maybe it's big enough. Or even in real games, like if you play a card game with real cards, people can cheat, but they don't. So hopefully people will just participate. Another example is maybe making some of the games where you put an image on people's phones, then you go find people to have the same color background, and they all have to arrange their phones to make some image. And once they've arranged them, there's something they have to trace or something they have to do. They have to navigate something across. I would like to explore that. Other things you can do is because you can have sounds from the phone, you can make things where they put their headphones in, and you give them private instructions for only that person. Or you can make asymmetric controls where every person in the room has different controls. That's something I'd like to explore. There's a few games out there, like if you ever played Space Team, it kind of does asymmetric controls. The controls are just web pages. That's how you didn't have to install any software to play. So that makes them easy to make. The bad thing is, they're web pages, so you have problems like as a iOS 8, if you press anywhere in the top, like quarter inch to the bottom, or the top center, or the bottom center to the screen, these bars pop up, they never disappear. And so those are issues. Android, you can go full screen, and so once you go full screen, you can control that stuff. Hopefully, maybe iOS 9 will add something to fix that. Because of that issue, I noticed that almost all the games I've made have used landscape mode, but it might be easier sometimes to do a portrait because it feels like you have more space. So that's just one thing to be aware of. The last thing is, last month, I was at a game jam, and I was making this work with a friend's game system, which you guys would check out. It's called Pico 8, and it kind of emulates an 8-bit computer, and he's got like a sprite system and a map editor built in, and he limits how much you can do, and the cool thing about it is that because you're so limited, it's very quick to make something really cool very quickly, because you don't have like skies to limit. And so I made, we worked together, and we made Happy Fun Times work with this, and that turned into, I made a HTML5 gamepad API. So what that means is that with one line of code, you can take any HTML5 game engine out there, and if you're supporting the gamepad, it will run through, you can just add one script line, and then you can use your controllers, and you don't have to change your code, it'll just do the gamepad API.  You're gonna have to design something around that, like a one D-pad and two buttons, or just a couple buttons, but I have options to get all the orientation and stuff that through that, so that's an easy way to get started. And that's basically it. It's all open source, it's on GitHub. You can probably start there and find your way to it. There's an app you can install, so if you want to, not an iOS and Windows app, so if you just wanna play it at somebody's house, you can just have them installed on their PC, and they just have people connect to their home network, and they can connect automatically. They don't have to configure their, this is like, the way I have it set up today is kinda like installation mode, where it will auto-connect. In that case, you go to Happy Fun Times on your phone, and it'll redirect you to the local game that's playing. And so, we tried to make it set up so that people could very quickly get, play some games, you made them. So yeah, that's Happy Fun Times. What kind of server space did you use to support simultaneous connections from multiple people? Because I tried doing that with a live audience as well, and just told, I was using all this in free local. Could you talk a little bit about the server space? Okay, so Happy Fun Times itself is just written in Node, JS, and it's just basically a web server to serve the web pages, and then web sockets to pass the messages. And then your game can be in any language, as long as it can speak web sockets to the Happy Fun Times server, and it relays those to the phones and the phones' messages back to the game. And that's basically what it's doing. Of course, that's easy. That took like a day to get working, right? Can you host your servers? No, their servers is running here. Oh, and you have a laptop, and multiplayer can just connect. Yeah, they're going through this. So you guys are all connected to this router, and it's sending them to the server. I wish to host specifications, whether I'm a Rock or either. Well, so it's not really the kind of thing that you would host remotely, right? Because people need to look at one screen. So if you're gonna, they're all gonna be looking at one screen, you can put a computer near that screen. You can run on any device you want, but that's not really the point. It's really like local people playing on one screen. I mean, you also have your screen on your phone, but that's the unique thing about it, right? I guess it's kind of unique. So you can have latency issues when you have it? You do have, I mean, the more people you get, the more latency you're gonna have. If you have a really crappy router, like the router at the apartment that I'm at right now, even though the router's only about as far away as that monitor, there's a wall and it's just horrible. We're gonna ask that question, right? Don't we have connectivity issues when you suddenly get most of the people? Well, so you do have an issue that there's a limit on the number of people that connect to one router. You can connect more routers like you would at an office, right? I also have this router. You guys have probably seen these TP-Link routers. They're like $15 or maybe 20 SG or something. And they only support, well, I don't know if you hack them, but the firmware that's in it only supports 15 connections. So that's like this and four more, but I can just plug it in directly with no power, just powering it off the notebook and I've induced small parties like our, you know, small presentations. So I carry that with me and for testing as well. You can also test through the simulator locally and you can just open up a browser window and just go to a local host and it'll pop up with the controller. So you have the game over here and the controller over there. Yeah, do you have any other questions? Do you have any other questions? I'm not, I'm just visiting, but I know Jason and he was like, hey, here's all these meetups that are happening.  And he wants to see it. He's like, yeah, okay. But I'm here from time to time because Jason's here with some other friends. What was that? I was about to place the website as part of the WebRTC. Yeah, so the problem with WebRTC is it doesn't exist on iOS. And when I come to a place like this, I don't know about Singapore, but in the States like 70% of the room will be iOS. Okay, so that's, and there's another issue with going to WebRTC is that it's not reliable. So like if you need to tell the controller, turn to this thing, and they didn't get that message, you're screwed, they're not on the right place. So that means you have to, instead of just coding, you don't have to decide, is this message important? Use this path. If it's not important, okay, I can use that path. And you have to decide that for every message. Right, if the guy's setting his name, you need to know what his name is. But if he's only pressing left to right, you don't care, right? Okay. I know because like I know guys on like the Diablo team, and they all went UDP, and at the end of the day, they said they basically wrote all of TCIP because they needed to be reliable in the end. But they can't do WebRTC as well. Yeah. Well, I don't need to carry a router anyway. I can use the router here, just fine. It just, it has to be NAT because they all have to be, from the point of view of to get them all connected, you have to have some round of the server somewhere, right? Well, so the server can be on the internet whereas actual connection. Right. I already have that set up. So I have a round of the server that works for this. So if you're on a regular internet, as long as you're all connected to the same router, it will route you to each other. Anyway, yeah, I'd love to see WebRTC in there as well. Any other questions? Is the game logic in a browser or around in the middle? The way the game logic is in the browser or whatever game engine you want. I have a C++ library for CIG engines. I have a C-sharp library that I'm using in Unity. That yeah, the whole point is that from the point of view of the game, it's just a game with lots of controllers plugged in. I mean, there's more options because you can send commands back to the controller to say switch the screen or change the color or whatever you want to do. It's your, you write a web page and you receive the message and you choose what happens here. But at a basic level, if all you want to do is a simple controller, it just looks like a controller to your game. So, right? You don't, it's not. You write the game any language you want just as long as you have WebSockets. Anything else? All right. Thanks.


Why am I not surprised? This breaking news comes to us via Project Veritas, who were contacted by an FBI whistleblower, who provided them with a leaked Domestic Terrorism Symbols Guide on, quote, militia-violent extremists that lists things like the Gadsden flag, the Betty Ross flag, revolutionary war imagery, in other words, our founding history. And they even list the Second Amendment itself as an example of violent domestic extremism and terrorism. Oddly, there's no reference at all to violent left-wing groups like BLM and Antifa, nor are there symbols and flags listed at all, such as the Hammer and Sickle flag and the Antifa flag. These groups openly perpetuate and threaten violence. We've seen years' worth of it. For example, those Democrat rioters that attacked the White House on May 28th, 2020 and injured over 200 secret service agents had all their charges dropped.


At the beginning of 2022, the media brought us the news of a truly remarkable bit of technology which allowed a paralyzed man to walk again after a severe spinal injury. The implant is able to restore the connection at the site of injury by sending electrical currents to the neurons below the spinal cord injury. So far, nine people have received the implant and regained the ability to walk. The development of this life-saving device was made possible by studies in rats and monkeys. This device that can restore movement to people who are paralyzed from the waist down is a prime example of scientists working over a long period of time, in this case 30 years, towards a life-changing medical device. Next we have another breakthrough research story from January of 2022 where for the first time in history, a genetically modified pig heart was transplanted into a human patient at the University of Maryland School of Medicine. The transplant was considered a success despite the patient dying two months after his surgery. The doctors involved in the patient's care made it clear that this experimental surgery always presented a risk and it was only approved as a final treatment option for the patient with their full consent. Xenotransplantation, which is the transplanting of organs from an animal to a human, is a goal that scientists across the world have been working towards for decades.  Scientists hope that further investigations will improve the outcome of this surgery and determine the next steps in this critical research to solve the global shortage of available organs for transplanting. Another story from early in the year reported that a six month old baby had become the first person in the world to receive a combined heart and thymus transplant. Born with a weak heart and problems with his immune system, the child spent time on life support and needed numerous heart operations and treatments for infections. So how did animal research contribute to this life saving transplant? Well it was research in mice that originally provided the evidence that transplanting a small piece of thymus tissue from the heart donor can help the body accept the foreign heart and therefore prevent organ rejection. Every week in the UK, 12 people under the age of 35 die of an undiagnosed heart condition very often caused by cardiomyopathy, which is a genetic heart disease. Scientists have developed a cure that works in animals. It silences the faulty genes using a precise genetic technique. This gene therapy, if successful in the next stage of human trials, will be a once in a generation opportunity to relieve families of the constant worry that they will develop heart failure and need a transplant. Epstein bar virus is a type of herpes virus commonly spread via saliva and it is present in over 90% of the population. The virus causes glandular fever, which our American friends will also know as mono, and it is associated with multiple sclerosis, lymphoma and stomach cancer. In 2022, researchers developed a vaccine to protect against the virus that has shown promise in tests with mice, ferrets and rhesus macaques, a species of monkey. After receiving the vaccine against Epstein bar virus, 17% of genetically engineered mice with a human-like immune system became infected, compared to 100% of mice that did not receive the vaccine. None of the vaccinated mice developed lymphomas, compared to half of the unvaccinated mice. Human trials are expected to start in 2023. If proven successful, the vaccine could be administered to children and prevent Epstein bar-related conditions. Lung cancer is the third most common cancer in the UK. There are around 48,500 new lung cancer cases in the UK every year, which equals more than 130 cases every day. Scientists have confirmed the link between car fumes and lung cancer that helps explain why so many non-smokers develop the disease. The findings in mice and human tissues outline how fine particulates contained in car fumes awaken dormant mutations in lung cells and tip them into a cancerous state. At least 2.6 million people in the UK have narrowing of the arteries around the heart, which can lead to a heart attack, angina, or both. Researchers have showed in genetically altered mice that this build-up of plaque can be reduced by increasing chaperone-mediated autophagy, a process that keeps cells functioning by selectively degrading cellular proteins. For the first time, a robot successfully carried out keyhole surgery on the bowels of pigs with limited intervention. In this scenario, the robot was used to join two ends of the intestines after a section was removed, on four pigs with limited human intervention. One week after the surgery, the results were significantly better than those achieved by human surgeons. Robots used in human operations are generally used on small, rigid parts of the body that do not change shape, such as bone. Automated surgery on soft tissue is extremely difficult due to the movement of the tissue. Brain organoids are grown to study human disease, but they have limitations. To create more accurate models of the brain, researchers transplanted human stem cell-derived cortical organoids into the brains of newborn rats. Here, the human organoids developed mature cell types that integrated into sensory and motivation-related circuits. The implanted cells extend axons throughout the rat brain. Researchers were able to see the implanted cells responding to sensory inputs, such as air being blown across the rat's whiskers. How you behave when you are sick has been shown to play an important role in recovery from an infection. Animals and humans tend to eat, drink and move less when they are fighting an infection and feeling unwell. By provoking immune responses in mice, researchers demonstrated that a specific population of cells in the brain stem induced three telltale sickness behaviors. Inhibiting these neurons blunts each of these behavioral elements of the sickness response. The findings directly link information to neural pathways regulating behavior, offering insight into how the immune system interacts with the brain. That concludes our top 10 animal research news stories for 2022. As always, more information can be found on each of the stories we have covered on our website and via the links in the caption below. Thank you for listening and don't forget to subscribe to keep up to date with the most recent animal research news stories.


Let's talk about proteins since I was already in my Google slides. I just decided dude I'll show you the subunits for proteins right now Proteins all of them are made from amino acids There are 20 amino acids that are used to build the proteins in our body And you can think of it almost as if there's an alphabet of or there's 20 different Legos that you can use to build all the things all the muscle things all the receptor things all the hormone things all the neuron things I Mean it'll be really interesting to see what you think at the end of the class when we get all the way through it Which of these bio molecules did we talk about the most? I'm gonna throw down some money that says we're gonna talk about proteins the most At the very least I'll throw down right now for physio We definitely talk about proteins the most in physio and all of them are built from these amino acids Now I am gonna go back to my notes and one more time I am totally punting on that chart So you go back and fill in that chart based on but I just don't have enough room for what I want to say here our proteins the subunits are amino acids and If we talk about the Function of proteins we could spend a million years just talking about What they do? Um, and the shape and maybe this is the thing that just this is the take-home message the shape of of a protein determines its function And this is something I'm just gonna take a second to Put little hearts around this and tell you we'll draw and maybe a flower So that you remember this fact The shape of a protein its structure determines its function I don't know if I've said this already in this class But if I haven't it's not the last time you're gonna hear this in all of your biology classes. It's a theme of the biological sciences that the Structure of the thing the structure of the organ the structure of the molecule Determines its function its shape Let's it do the thing it's gonna do and proteins They're sensitive little critters and they're powerful little critters and I say they're sensitive because guess what? pH Hydrogen ions what who knew that one little proton could be so powerful hydrogen ions can change the shape of a protein and in Can make it not work anymore That's why your pH in the human body is actually maintained between like I don't know 7.38 to 7.42 Not seven 7.38 to 7.42. So if you go down to 7.3 you are considered Too acidic your blood is too acidic and your proteins start to change shape Your proteins start to change shape and you stop functioning the way that you are supposed to function Which is bad? You don't want that to happen. So pH is super important because of proteins now let's talk about the structure because there are four levels of protein structure Primary structure of a protein is just the sequence of Amino acids so remember that list of 20 amino acids I had you could just throw those out in a line and the sequence that you tell me is the primary structure of that protein all Proteins have a primary structure. They have a sequence of amino acids that they're made of Some part like the biggest protein is a protein called Titan and it's in your skeletal muscle organs and It has like I had 30,000 amino acids in one protein like it's absurd how huge that protein is hemoglobin Very important protein. I think it's hemoglobin. Oh, no, it was insulin insulin is a protein hormone a peptide hormone and it has 51 amino acids that make it up if we listed out all 51 We'd have the primary sequence of the primary structure for insulin if we listed out all 30,000 We'd have the primary sequence for Titan Don't worry. We won't be doing that your secondary structure your secondary Structure of a protein is actually okay, and this is really interesting. So you imagine a string of amino acids well, sometimes those amino acids are attracted to each other and the the string sort of folds and it can fold in like little accordion shapes or a little helix shape But the actual string Does these little folds and that is your secondary structure? I'm just gonna write alpha helix or Beta pleated Sheet that doesn't mean a whole lot to me except those are some examples of the ways that that sequence of amino acids can fold To create that secondary structure Well, your tertiary structure. I'm gonna write that one out because I would not think that worked tertiary structure is That secondary structure folds on itself again Folds on itself again, I Do have a hard time. Maybe I'm out of practice for writing and talking at the same time. I Have a hard time I go, okay alpha helix beta pleated sheet We pleated and we helixed and then we fold those up and I am and then I Create a thing that has even more sort of globular Structure and that would be my tertiary structure and there is a quaternary structure and that's when more than one protein subunit Combine So you can end up with and this is hemoglobin has multiple subunits And that's a protein that carries oxygen in your blood cells red blood cells when those different subunits those different tertiary folded Strings of amino acids combined together and have a new structure. That's quaternary structure of the proteins Now you might be like, oh my god, seriously like what why do we need to know all of that? Well our next biomolecule is nucleic acids and Hopefully you've heard of DNA DNA provides the instructions for building all the proteins in your body and those proteins. I'm telling you All the other stuff is cool. I mean I got a little of the fat along with everything else, but protein That's what that's what's doing the work of being alive Carbs are providing the fuel to make it happen. That's are storing it and keeping us waterproof. Thank you very much But proteins those guys are doing all the work. So let's look at our last category of biomolecules and then we're going to say good night


Okay, so we'll go into the second half here. I've got a lot of slides so I'll go relatively quickly, but feel free to stop me at any point here. Hopefully everybody got a chance. First off I'd like to thank the entire family, Tiffany, Lisa, and Rose for coming today and being a part of this. We really do appreciate it and the photos don't really do justice to what we see, so we appreciate that you're able to come in. But you will see a lot of photos, and everything I put up here also is just from reading the notes, so if it's wrong I apologize. So we'll get going here. So I have to put this disclaimer on everything that I do. These are my views, these are not Department of Defense, Department of Navy policy views, or otherwise related to anything Department of the Defense. So, and that's a carrier strike group, which is by far the most dangerous weapon in the world. Alright, so we'll just get right into it. So our case presentation is a case that recently we did surgery on, and so that's the one I'll start with here. It's a 34-year-old female with a history of cavatary disc anomaly who presented with six days of blurry vision in her left eye, which was her good eye. She noted sudden central distortion and significantly decreased vision. She didn't have any pain and she states that this is similar to what happened in her right eye many years ago. Okay, hold on one second here, I just got to make sure I've got something. So, she had no other significant ocular review of systems, and her review of systems otherwise was negative. Her past medical history is significant for migraine headache and PCOS. She has again the terioptic disc anomaly in both eyes, and she had a serous macular detachment in her right eye in 2007, which was repaired with a vitrectomy, endolaser, and SF6 gas at that time. And then her family history is obviously significant for optic disc abnormalities in both her mother and sister. And she also has a grandmother who had poor vision in one eye that died in her 30s. So, or excuse me, had vision problems in her 30s, but was never diagnosed as far as we know. So, this photo was taken the day that she presented this year. So, this is her current photo, and they didn't really have a good macular photo. So, this is the photo that we have. So, on her examination visual acuity in the right eye is 2800, 2125 in the left eye. And other than having had a vitrectomy and a central scatoma in the right eye, her anterior exam was otherwise unremarkable. So, here is her right eye. And you can see an abnormal optic disc with peripapillary RP drop out in hyperplasia, consistent with previous laser to that area. And then, it's tough to see here, but the central macula is just slightly out of focus here. Here's her left eye. Sorry, the previous picture was actually from 2007, which was the last time we had seen her. So, I apologize, this is her current picture. So, you can see elevation of the entire macula. You can see a pseudo hole of the macula, and you can see obvious abnormality of the optic disc with significant cupping. Here is her OCT of the left eye, or excuse me, of the right eye. And you can see a serous macular detachment with almost complete loss of the inner-outer segments there, which notes some chronicity to this detachment. And here's the OCT of her left eye. And you can see a large central area of subretinal fluid within significant amounts of inter-retinal fluid, both nasally and temporally, as well as superior and inferior. So, kind of a different configuration than her right eye, and that's pretty typical. We'll go into kind of the pathogenesis and what happens in these eyes. And here's some photos just through her nerve, superior right through the center of her nerve, and then inferiorly through the nerve and macula. And you can see, you can't even see the bottom of the optic cup in these. And you really need a swept-source OCT, where you get more thickness to be able to see the bottom of a lot of these optic nerves. And then you can see her left eye here, and you can see the same thing, the macular abnormality, and then as well just complete absence of any tissue posteriorly in the cup there that you can make out due to the amount of scan we're able to get. So, we'll switch there. So, that's her presentation. And now we'll go to her mother, who had three weeks of vision loss in her left eye. In 2014 she noticed some distortion and so she presented and you can see, again, she has an abnormal optic nerve and she has serous maculopathy that looks very similar to our first patient. So, she went under, she underwent part of the point of attractomy with endolaser to the edge of the nerve and SF6 gas tamponade. And you can see one month post up to six and twelve months. And so it took somewhere between six and twelve months for the fluid to resolve. But it slowly did over time. And this is her most recent photos and the most recent exam, she was 20, 30 in both eyes. And she does not have detachments in either eye. She's flat. So, we'll move on to our first patient's sister and here are photographs from 2005 when she first came in for her right eye and she was already status post laser, just some focal laser to the nerve for a serous macular detachment. She had not had surgery at that point. So, she was treated with attractomy, further endolaser and SF6 gas tamponade and she did well and flattened. And interestingly enough, this is one and we'll go into this a little more with familial optic disc abnormalities. But you can see the progression of her nerve from 2005 through 2014 in the left eye. And you can see that in 2005 I would, if I didn't know better I would call that a completely normal optic nerve. Even in 2010 I would say that's probably still normal. And then in 2014 there's an obvious optic pit with significant progressive cupping. So, and that's one of the interesting findings in these familial forms of optic disc abnormalities is they're not congenital in that sense. They're definitely genetic, but they're not they tend to be progressive or certainly can be progressive. So, she complained of she already had a history of having a part of this point of attractomy with gas and endolaser in 2003 and 2005 in a right eye. But she complained of sudden vision distortion in 2014 in May. In her left eye she had distortion and her visual acuity was down. And you can see she has a small cirrus, excuse me, she has a small amount of inter retinal fluid there. And the optic pit obviously which wasn't present in 2010. So, here are her post op results and so in a month you can see she kind of has a cirrus detachment. But then two months she's almost completely flat and three months she is completely flat. So, she did well until about a year post op. And then you can see the area of laser scar. Do we have a laser pointer here? Nope we don't. So she did well until about a year post op and this is not exactly through the fovea. But she's got superior fluid there. She's got the new laser obviously that you can see on both OCT and on the color photo there. And she's got some inter retinal fluid as well. So, she had a re-accumulation of fluid after being completely flat. And she had focal laser and C3F8 bubbles three times over the past year, most recently in March for this. So, try to help it go away. So, we'll move on to the portion here. Those are just again photos of the nerves of the left eye of the two sisters. So, cavatary disc anomalies will just go through the common ones and kind of what they are. So, optic pit is usually a focal cavitation that's isolated usually to the infrotemporal or temporal disc. They're typically small and they typically have a sporadic inheritance although there are some families that have autosomal dominant inheritance of optic pits but it's only been described a few times. It's mostly sporadic. Optic nerve colobomas are large excavations typically located in infrotemporal aspect of the disc and they can be anything from just involving a little bit of the disc to involving the juxtapapillary and peripapillary tissues. And they are no mutations include PAC-6, PAC-2. There's MAF, CSH-10. There are no genes that have been identified for the autosomal dominant form of colobomas. However, and these are typically sporadic as well but there are some families with autosomal dominant inheritance which may fall into kind of our category. And then morning glory disc would be the other cavatory abnormality and they have enlarged papilla with funnel shaped elevations of the optic disc and the peripapillary retina. They typically have a radial arrangement of the vessels and enlarged or multiple silior retinal arteries. They have a rim of elevated peripapillary tissue and then they tend to have a central glial proliferation in the base of that disc and that was described because it kind of looks like a morning glory flower. And again most of these are unilateral and sporadic. It's very rare but there has been a single case report of bilateral morning glory disc that included PAC-6 as the gene mutation. So familial cavatory disc anomalies have a little bit of a different thing. So there's been a large four generation family with 16 individuals that have been studied out of Iowa and they looked at the genetics of this disease and this was in 2007 they were able to locate this to the 12Q locus by a linkage analysis and they tested three genes, the GDF11 neuro D4 and WIF1 as they were all noted to be neuro development in that area and sequenced those and they did not find any abnormalities in those genes. So at this point the genetics are still kind of somewhat unknown although at least we have an area. So look for it. And so again this case study showed four of 16 individuals had progressive optic nerve abnormalities and ten of 16 had bilateral involvement. There was serous maculopathy and about half of them and five were bilateral and then the phenotype varied significantly from infected, excuse me, affected individual to affected individual. There were people who were just barely kind of because they were in the family you look a little harder and you could see something to those who had almost full morning glory disc type appearance. And again it's autosomal dominant as well. They determined. And some of the clinical features about 50% will develop a serous maculopathy. The onset is typically in early adulthood and we'll go into why that's important in terms of the possible pathogenesis of this disease. They're confined usually to the posterior pole and they tend to have relatively poor outcomes with 80% having 2200 vision or worse upon final treatment. So the clinical progression of this disease, the thought is that it normally develops in a two step process. You get intratenal fluid that's extending from the optic nerve into the macula and then if allowed to continue, then you tend to get a serous attachment through what they presume is an outer retinal break basically allowing the intratenal fluid to go to extend into the subretinal space. So it's not actually a subretinal space optic nerve communication. It's actually intratenal space where they tend to accumulate fluid and so that's important for the pathogenesis of this disease. And usually then just as I said the subretinal fluid doesn't communicate directly with the optic nerve, which is kind of important. So the pathogenesis is thought to be dysplastic retina and then they have some sort of a scleral or laminal kerbosa defect or enlarged openings that allow fluid and then you get this dysplastic retina that protrudes into the sub arachnoid space and communicates with it either through small openings in the sac or through small openings in the retina. And this has been confirmed by histopathology as well as swept-source OCT that you see this very dysplastic retina herniating into this deep area of abnormality and then back out again and you can actually find micro breaks on swept-source OCT in the outer retina. So the two models of evidence for them, although nobody's been able to confirm this, are it's either a result of vitreous traction or it's a result of pressure gradients or some would say some of both. The evidence for vitreous traction is that paris plaintive attractomy is the primary treatment that tends to work in these patients and just paris plaintive attractomy with PVD results at least in one small study of 11i is 10 of them redetached without any laser treatment to the optic nerve. Macular buckling has also been successful which would be more consistent with some sort of traction on the optic nerve or on the macula. Abnormal vitreous stranding is seen on swept-source OCT in the central optic cup and spontaneous PVD can resolve the maculopathy without any treatment at all and that's been shown in some patients. So there's also people who think that it's the differential pressure gradients between the CSF space, the intraocular space and the sub-retinal space that caused this. Some of the evidence for that is that they've shown vitreous substitute migration both intraocular gas as well as silicone oil has migrated into the sub-retinal space from the intraocular space after paris plaintive attractomy with the use of these. It's also been shown that they've gone into the CSF space into the sub-arachnoid space as well as gas. So there's obviously probably some overlap between these two scenarios. The big variable would be that ICP actually does vary and would allow for a possible large pressure gradient depending on the patient's positioning whether they're supine or upright. ICP can change significantly in the peripapillary area. And then it's also shown that vitreous can be incarcerated into these optic disc abnormalities thinking that it's actually kind of the pressure gradient sucking the vitreous into the retina when there's a pressure gradient. So the source of the fluid is also a question. So the source of the fluid being either liquid vitreous or CSF. So there's vitreous mucopolysaccharides in this fluid. India Inc. studies in Kali dogs which have a very classic optic pit abnormality have shown that India Inc. in the vitreous cavity goes into the sub-retinal space. And then you've seen the sub-retinal fluid, or vitreous substitute migration which also would say that this is possibly from the vitreous. But then this happens in infants who have a completely fully formed vitreous and should have really no vitreous liquefaction. So that doesn't really make sense for some liquefied vitreous getting in there. Again, intracranial vitreous substitute migration makes you think that there's something in the sub-arachnoid space communication that allows that to travel there. And then also nerve sheath fenestration reports have shown that if they do a nerve sheath fenestration to lower the CSF that can tend to resolve some of these detachments as well. So and the pressure gradient that's required to, even if you have a 200 micron opening in the optic nerve, to allow for vitreous substitute to go into another space due to surface tension is about 11 to 12 millimeters of mercury. So even with a really large hole it takes a relatively large pressure gradient to allow these things to migrate which is why we don't see it that often. So the management of this condition is a little bit up in the air because it's not that common. But pharmacologic treatments have been tried, mostly case reports, with variable success. Both acetylzolamide and corticosteroids have possibly had some effect. But it's difficult to discern because this sub-retinal fluid can wax and wane in an individual whether you treat them or not and even after treatment. And that also lends a little bit of credence to the pressure gradient differential depending on how much the pressure is changing. You can do laser photo-quagulation and you can treat right through the fluid and that actually can be helpful because it can be protective of the nerve fiber layer which we're always worried about damaging when we photo-quagulate in the maculopapular bundle. So you try to create a very light laser burn so that it's just uptake by the RPE and into the outer retinal layers and try to not injure the nerve fiber layer. And the typical 4-5 rows of light laser that are adjacent to the nerve about 180 degrees temporally. So that's kind of the typical. The surgical management which is the most common management would be vitrectomy typically with a creation of a PVD since that's thought to be possibly involved in pathogenesis. Usually with tamponade with a gas and then laser most typically but not always. And then with those you've noted up to 90% success in some studies with resolution of their fluid. And then macular buckling has also been performed which is shown to work in these cases. So we'll get back to our original case. So our patient underwent parspoint of atrectomy and laser nerve to the border and SF6 gas tamponade and she's a few weeks out from that now. So questions for me? Comments?