I thought that chapter 9 of book 2 was really interesting when it talks about you need to keep in mind the nature of the whole and how you are a part in it, and then you have to act in accordance with the whole and your nature as a part. That really reminded me of Epictetus, always commenting on how you have to keep track of where your place is in the logical whole, and I see Marcus really is doing that a lot with the passages that Sarah was pointing out too. There are other part whole arguments. As your research has shown, it's not always very easy to figure out what my part is in the cosmos. So if I sit down and think, what is my role in this cosmos? Of course I haven't been through all the lessons about physics and logic that one needs to do. Of course Epictetus doesn't think I need to do those necessarily, to figure out my role and my part. To some extent all of this stuff about making sure you are doing your part, to me is more mysterious. For all of you embarking on your life and figuring out what you are going to do with your life and where you are going from here, and so forth, and some of you are even graduating and so forth, and so this is really, I won't be one of those guys that asks you what's next, don't worry, but this is on your mind. It's not very helpful to say sit down and reflect about your position in the cosmos, I think. Now Marcus Aurelius is Emperor of the Roman Empire, so he has a fairly clearly defined role, and it's important for him to recognize what are the responsibilities of this role, and not be a Nero or a Caligula, and failing to do your role, because lives and empires and so forth hang on it. I think here Epicureanism is more intuitive, it's easier to follow. It's not that I've got some part in this grand cosmic structure, it's that I've got these rather obvious things, they're called pains, and one needs to get rid of them in order to be happy, whereas one needs to figure out one's cosmic role. I actually find it to be an anxiety-producing idea, not an anxiety-relieving idea. Maybe I should be Emperor of something like Rome.  Or maybe my role really is philosophy professor, and so I need to concentrate everything on doing that, but how do I know? I have these doubts about it. And as students, definitely I have doubts about it. Yeah, in terms of reflecting on my cosmic role, control is the opposite of the fact that I'm not having any anxiety, because I'm so small in this gigantic universe and my role is so insignificant. And then also in mind that they're like in capitalism, I think there would be the, oh yeah everyone has this role from maybe some kind of preset destination that you're born into, but you can kind of decide how do you go about that role and manifest that role, but that role is kind of already set in some way. And I feel like in a more contemporary sense, you could look at it as like everyone kind of has these set gifts or set natural talents that we have, and reflecting on that in relation to the culture, how can you best fit that nature into this system? Both of those points are very good. The second one, don't worry about figuring out whether you should be a philosophy professor or emperor, because what you're going to be is determined from the beginning of time and even earlier than that, because it's from a set of cosmic cycles that's eternally repeating itself. So in a sense my role is exactly what I'm doing and where I'm sitting right now, and by the way I'll see you in the next cosmic cycle right here, everybody sitting in exactly these positions, and that's not only going to happen again, but that's going to happen an infinite number of times. Now whether you're happy about that or that's a terrifying idea, most people are, I'm going to be sitting in a room with, you think you're never going to sit in a room with Monty Johnson again once this term ends. I got news for you. Ever heard of infinity? So in a sense your role is exactly where you're at. So concentrate like Laura was saying on what you're doing right now and how you're reacting to those things. So I think that's a really good point, is that they're fatalism, and you put it in a good technical philosophical way, they're compatibilism. Compatibilism means they believe that human freedom is compatible with fate and determinism. And so don't worry about it, don't do too much about that if the universe and Zeus wants you to be a Roman emperor, you will be. And that's exactly what will happen. And then your other point, the first point that you made, is also very good I think. And that's that reflect on how small and minute and puny you are. And there's all these great times in other fragments here and Marcus Aurelius, who is the most powerful man in the world at the point and time that he's writing, is saying basically I'm nothing, this is a speck in the overall scope of this cosmos. And one way to relieve depression and anxiety that is very effective actually, is to do things like reflect on the immensity of the cosmos and the smallness of this. So if you find yourself sort of bummed out look at some of these NASA pictures that show you vast nebulas and things like this and concentrate on the cosmic scale of things and it makes your own problems shrink to a vanishing point to some extent when you put them into relation to the infinities of time in both directions that are surrounding you and the vastness of the spatial cosmos and so forth. I think both of those are really solid and stoic points, stoic ways of dealing with this. Now did somebody else have a hand? Yeah, please. I know stoics are deterministic. So I had a question about what he means on the fifth paragraph which is you'll give yourself this if you carry out each act. Is it where you're last, free from all randomness? This is book two, section five. What is the name of randomness in my context? Okay. At every hour give your full concentration as a Roman and a man and I believe that I might have to check the Greek there but it probably says human on purpose as opposed to on air but it would be relevant to Dylan's research if it had a gender term there. Can't tell from the translation. To carrying out the task in hand with a scrupulous and unaffected dignity and affectionate concern for others and freedom and justice and give yourself a space from all other concerns. You will give yourself this space if you carry out each act as if it were the last of your life. Free from all randomness and passionate deviation from the rule of reason and from pretence and self-love and dissatisfaction with what's been awarded to you. Okay. So in part randomness is glossed by the phrases that follow from that from the what we call the exegetical and there. So randomness i.e. passionate deviation from the rule of reason and from pretence and self-love and dissatisfaction with what's been awarded to you. So dissatisfaction on I was born poor. I am a mere UCSD student. I didn't get into Harvard. I'm not the valedictorian who's going to be giving the graduation speech. All of that is this emotional stuff that's random and inhibits you from playing the best part you can in the immediate circumstances. Of course there's not randomness in the physical sense of like an Epicurean swerve of atoms or something. That isn't possible because everything is faded. So it doesn't mean some non-deterministic thing. It means basically incidental things concentrating on and thinking about incidental things like those of you sitting here checking Facebook messages and so forth on your computers. Instead of trying to figure out what this wisdom this ancient wisdom has to tell you about your life you are deviating into random things based on passionate desire for a dopamine hit when you see that somebody liked you posting a photo of your cattle or whatever. That is not giving your full concentration as a human being, as a student, as a mind and so forth on the task that is set before you. So that's I think how to interpret randomness there. Not attention to what's essential but attention to something that's incidental and accidental. And that's within your control. You could concentrate on what's essential and the possibility of this wisdom and learning something from it right now or you could be playing Tetris or whatever. I'm not totally up to you. So this piece of advice is meant to focus us on that. Okay, other comments? Anything else people just liked or disliked? Okay, Noah? I really liked in book 2, chapter 16, first line when it says even mind and violence to itself most of all whenever it becomes as far as it can in our approach and a tumor, kind of tumor of the universe. But that was really nice. Yeah, that's kind of weird imagery, but what does this mean? I want to become a tumor on the universe, right? No, that's when the mind does violence to itself. I see having resentment and so forth turns you into this hideous tumor on the universe instead of being a functional healthy part of the universe. So we're all part of the universe and we know that the universe is alive because if part of something is alive then the whole of the thing is alive, right? And we know part of it's alive because we're part of it and we're alive so we know the whole thing must be alive. And the question is are we healthy parts that are making it function and flow in a continuous way or are we something more like a tumorist? Outgrowth on the universe.  It's like really insulting thing to say, right? But if you think that the universe is an organism then there is some kind of logic to that idea. But what is it that you liked about this? Does that turn of phrase or...? I thought the phrase was really interesting and just again referencing your own place in terms of the whole and not trying to justify yourself just on your own basis but just by how you live and reference to everything as an unity. Okay.  Which one do you like? Section 3 in Book 3. Where it talks about all these deaths and so it's about T's cure and Susan and Phillip don't die themselves. I don't know, I just thought that was kind of big. So all these great people, much greater than you, have died. Pretty terribly, too, suddenly. A democratist was killed by lice. That was invented by somebody in the Hellenistic age to make fun of him. And then he says, and socrates by lice of another kind meaning the accusers in Democratic Athens who had him put to death. So that's just a kind of clever insult. So why are you reminding me that all these great people have died? Well, one thing, it is good to remember that because it actually alleviates fear of death to some extent. So why am I so worried about the fact that I'm going to die? People a lot greater than me have died. And also it's universal. But then he says, what does it amount to? You came on board, you set sail, you've now reached land, step ashore. I think came on board, stepping on board the ship is like being born. Sailing is living through life and then you're reaching the end of it. It's like reaching land. And then what do you do when you reach land? You don't stay on the boat and say, oh no, you step ashore. And then there's a couple of options. If you come to another life, so if you are reincarnated as something else, nothing is empty of gods even there. So that will still be a good fate to have. You'll still have this portion of the divine, even in that case. If you come to unconsciousness, so if death is like some people think some sort of deep sleep or not even aware of it, there's no perception that's just kind of oblivion, then you won't be subject to pains and pleasures. Of course pains and pleasures are just as bad on this sort of thing. You might think, well it's a relief to think I won't have pains, but it's a bummer to think I won't have pleasures, but remember pleasures are bad emotional states too. You'll no longer be the servant of a vessel as inferior in value as that which serves its superior. One is mind in the guardian spirit, the other earth and blood. And he, not in these books, but in other sections goes in for this kind of language a lot, that we're just flesh and phlegm and some bones if you take away mind. Mind is the only, you've got to concentrate on mind and identify everything with mind because the rest of this stuff is just this horrible sort of grotesque bodily functions that inevitably break down over time. Now I really like the first one of the book too, and I was reading this on the bus yesterday before I got off the bus and went into a meeting with someone who I would exactly describe as being meddling ungrateful, violent, treacherous, envious and unsociable. And so this actually worked as a, effectively worked as a consolation for me. And the entire meeting I was thinking we have to find a way to cooperate because I should not become angry and what I want to do is just consult this person and put them in their place. I want to figure out a way that this will be like mutually beneficial and manage to turn around the meeting and the outcome and actually improve and I felt better about it afterwards. But it was just random that I happened to be meeting this preparing for today and then went into a meeting with an upper administrator that this fit. And so this is one of these things, these pre-meditations what is supposed to reflect on in the morning.  Think before you go into it.  But I've got to find a way to work with that. I mean, first of all, I've got to find a way to not make it affect me and I'm not undermining myself by feeling emotion but also by not being able to carry out my plans because I can't cooperate with this person because of these attitudes I have about them. And so if one thinks that then it might be that you don't come across someone like this. You might somehow be lucky enough not to come across an envious person during the day. Good luck in Southern California, you know. But you might, and then that would just be a happy thing. Be like, you prepared yourself for this outcome and then it wasn't actually a problem but the thing is that it always is a problem and there always are people like this. There's people that don't give up their seat on the bus to a crippled elderly person that they should have done and it's going to make you angry and you've got to find a way. You've got to realize not only are we all in the same boat but we're all like parts of the same universe here. And the existence of that vice and so forth is a problem for me too and I have my own vices that are setting other people off my own kind of envy and jealousy and so forth that when other people encounter me is exactly what they're thinking. But this is one of these remember that none of this has been published. This has also been burned if these underlings to carry out the instructions they were given. But this man is a personal journal. He's just writing these reflections to help himself get through really troublesome times on a big campaign in foreign lands and so forth. And I just think what a wise thing to think and that it can actually help you get through the day to meditate on this ahead of time. I related that part to this cognitive behavioral therapy technique called like imagery based exposure where you pretty much like it's used for PTSD you imagine yourself in a situation and let yourself feel all the feelings that you would feel when it actually does come and you are way less affected by it. This is a sort of example of one. I kind of want to loosely connect what you said to section 4 of 3, the first line did not waste the remaining part of your life thinking about other people unless you were doing so with reference to the common benefit. I mean thinking about what such and such a person is doing and why what he is saying and what you are doing to your own center. Essentially I feel like I do to myself a lot too where I spend a lot of time thinking about what others believe and think mainly about me rather than focusing on myself and centering myself and trying to see what effect I have on the world rather than trying to make myself out to be what I feel others want me to be. And I kind of resonated what she said with other people they do things in their life and I kind of like anchors me but rather just like making sure that doesn't have an effect on me and knowing what's like true to me and what gets me. Well said and it turns out that other people you can count on other people being so self-absorbed that they aren't actually people close to you are too worried about their own lives and in a healthy way if they really concentrate on it but one can certainly waste a lot of time being concerned with how


University Health Board has always been committed to energy management and decarbonisation. To meet Welsh Government's net zero target, we needed to take significant action. But through Welsh Government Energy Services Refit Programme, we've been able to meet this challenge and deliver the scale of the projects that was required. We actually worked as part of the project team in the Health Board. We previously supported the tendering for the Refit contract up front, providing strategic guidance, in particular to access funding and manage what is a multi-million pound project. We'll continue to support the team to identify and develop new phases of work and access funding. Working closely with the Health Board, we've implemented a whole range of energy conservation measures to reduce both carbon emissions and energy costs. LED lighting, solar PV, building management systems, fan replacements, even pipework installation. Working in live healthcare environments presents challenges, but early engagement with all stakeholders is key to gaining access to required areas while minimising the disruption caused to medical staff, patients and visitors. Having these energy improvements installed has made a significant difference to the Children's Hospital for Wales. It means we can care for our patients in an improved environment that offers them both comfort and wellbeing. Through sustainable action like this, we can improve equity for children and their families and therefore for future generations.


I'm out here at La Puente skate park meeting up with Dan and Heli again We're going to skate and it's going to be a good day. It's sunny. There's no wind and I'm in California. Oh so close It's the rail here and it's orange so we're going to talk about rail safety today I have the ultimate railcoach here Dan. I'm going to revisit my back 50s and my front 50s and try to get this blonde slide But uh try to get the blonde slide that you've already done. Yeah Like a real one though. Yeah, you want to slide like I say from the like from the middle from the middle bar Yeah, maybe I'll give that a crack a few goes and we'll do the 50s Somehow I feel like a blunt is scarier. Oh less scarier because you're on the other side of the rail You're to the safety side. Yes my second trail on a rail it literally went well third tricks I learned backboards from board to fakie from pump fakie in that order I learned those before 50 50s feebles any of that bold slide guy. Yeah from plon to fakie was my third trick on the rail Yeah, Hailey Yeah, you got that I gotta stand it up more. Yeah There's a lock I'm going to stand here to keep you from popping over to this side too much. I'll push you back. All right Here's the your cheek. Yeah My front foot or back foot your front foot needs to be like uh, no no wherever I try to keep my front foot probably like Where the second bolts are just below them because yeah, yeah Is that weird? I'm like trying to be down here Well, if me if down there works is whatever works for you Whatever keeps your body weight on the side you came from is what you need to do But in reality your front foot can be anywhere. Yeah, you got that myself.  It's like a handbrake Got it.   It started off oney. Yeah, they felt good. Next try That was the right idea though. I want a real one. I want you to do a real one too.  How do you do that? The same thing but to fakie Or you just push it. Yeah, you just like lean You just kind of go with the lean and you just kind of fall out to fakie Yeah, oh wow Yeah, you got that Yeah, it's actually almost easier to slide far to fakie. Yeah, because you're kind of going that way. Yeah, it's like a front tail I was ready.   How are you shaking it?  She is not smart. Let me do the try these 50s. Okay.  Okay, right off the gate the whole rail I'll probably get out now. Now now getting out early Because I don't really I'm gonna be so mad. I would get out. What are you laughing at? Superstructure. You need the whole round now Get out early. I don't know if we're trying to like cross lock it or heel lock it or whatever. Whatever works To a lock Yeah, you're a heel side guy.  Just go with heel then go off the end If it's that's what you're doing. That's what you're doing. I have to keep that Do you see that triple X the first movie and Vin Diesel slides that king curve rail on a lunge tray? I don't remember if he's heel or toe That was the most heel-y heel side I've ever seen. Yeah, I feel like it was it because I think front smith in my head, but just Yeah, that's what you do.  Yeah, it's just scary.  Okay middle rail and then Yeah, yeah back 50s are safe. Yeah first try Still did it though. What's back 50s are easier to hold longer.  Yeah, you got it.  No way try one Try one Try one try one try one my goal of today was to do some 5os on this whole thing if he does the first try I'll be very upset I hear right let him do it for me That was so good That was so sick dude Sean You just that was my goal for today. It was to get into a front 5o at the beginning of the rail I didn't even care if I went off the end of it. I think like it's a ledge Why and I generally when I fly go I'm kind of crooked like this Yeah, so I feel like I can have my weight in the back pocket and still be away from danger That's incredible. Do you want to do another one? All right, well now what? I don't know nose grind on the rail. Yeah, he's probably over the crooked right It's just a crooked grind. I could probably cook it. Okay Like lean straight over it once you're in yeah You like stand straight over top of it once you're on it and you can just grind forever standing tall stand tall, baby His first nose grind Baby's first nose grind a backside table Yeah, why would you do this all the time? I don't know why you make it a thing I can't do you do it literally all the time I feel like you know when you have tricks that are just in your pocket and so I'm not so much Yeah, that's like my back tails like I can do them, but I can't do them. Yeah confused. I always get into a board side I think that's a common problem. You've got it right here Table first track table. That's fine It was fine grinded the whole rail Yeah, that's most of it almost all of it. Y'all don't at the beginning. Let me try to do a better one Yeah, do a better one. Yeah, lean to the side you came from There it is. How's that? Yeah, try it back 5.0 try to No way you're trying them on the live like back salad try back salad the rail Just grind like the last foot of it. How even what do you mean? Just do it just like a rail or ledge but on a rail back uh Heel side I think whatever side works for you Well salad Yeah, yeah, so just just try to back 5.0 salad either way. I'll just like Yeah, like that just do that Yeah, yeah, it's a feeble lock in but lift it up and tapper Yeah, you got that. Yeah, next track Wow.   You just did it. That was sick. Well, I'm coaching session. Okay back side lift slides Do a back 50 50 but then don't I have to think when I backflip or else I have to aim it like I'm gonna do back 50 50 and then I over rotate my scoops I like Ollie and then 90 because if I try to 90 on the way up, I'll hit the rail Yeah, my friend Leon is sure. Yeah, that's how he does him He's like just ollie and then turn he goes try to ollie into a front board. Yeah from the other side of the rail Give it a go Maybe stall one on the curb.    Yeah brand new 65 dollar shoes. We're not good 65 us That's about a hundred dollars Back up the rail. You already did one on the left. You gotta do the rail now My prediction is he's gonna at least get into it first try. I like that prediction You just not bored No, uh-uh go do it Get on at the beginning. Okay.  Yeah, one raised curbs. Okay. You've never done it on a rail though Well, okay. Well do one that doesn't suck. Yeah, all right. Yeah, he said first try I said you're at you're gonna at least get into it. Hey, I said you're gonna break your board That was so good I feel like it's not as bad like yeah In my head, it's like You know what I feel like hitting the rail on the way. Yeah, that's why you do the late Okay, so then here's what we got to do since you're just kind of rifling through all these tricks Let's do a trick that I think you might actually be genuinely scared of what back Smith How do you even it's it it's a it's a you can do this. It's a toe side lock. Do you think of like a ledge? No, no, I think of it as you want to rotate it back up just pinch toe side Dig in this pocket like your toe side pocket when you get in and you just sit on it Parallel with it and then you just that's how you have to turn like that much Yeah, but I feel like if I got parallel with it I'm just gonna like no no because you just pop Think of it as a back 50, but then you just turn it a little bit And don't I'll like you hide like I'll do a baby alley into back Smith's on rails I'll try one on. Yeah, you got it Okay predictions First oh definitely slip in the back flip first You got it. Just just try it.  I just I just want it to be different Yeah, just push it just like that and it's gonna go Okay, this one's gonna slip in the back flip No, this one's looking in the back flip Oh, yeah, you got that next try. Yeah. Yeah, go faster and just push it Like here's the make Third tries to charm third tries to charm. Hey, what do you think is it gonna break a truck?  You're stoked. Was that your first one on a real? Yeah ever. Wow.  No, because I feel like front people. You're like Okay, next he can front people really well front salad Yeah, you can I seen you do it I seen you walk the whole rail and have a city. No, you're drunk.   Nope. Nope. Nope. That was front feebly. That's to our side.  You pinch exactly like a front 5-0, but you tweak salad Yeah, that wouldn't flip over Yeah, you don't want that. No. Yep. No. Yep. Now. Yeah No, no wrong pinch Yeah, that's how There it is. No, it's not You always end up in that position. I don't know why.  Yeah, it's coming Yeah, don't you don't really tap this trick. You really got to sit on this one for a second There we go Well, you didn't tweak it super far, but it was definitely it Good I don't know what else All right, here we go. We need to do this No, I can't even back side bixby What? Yeah, it's just a shot at front board. What were we gonna say Sean?  You know what happened to Bama Jiro What trick is it? Oh, yeah Yeah, dude, go ahead do that You're not familiar with having to bam. You're not familiar with what happened to bam He tried an ally lift just like 13 railing Body disfaced Yeah, it was it was like the end of his hand wrap for you First try What's up Bama Jiro chin still intact. Oh, he's yeah, he was like he smashed it like chin. It was it was bad Yeah, it was probably the best thing that ever happened He was my favorite skater. Yeah as a young man. Yeah


Good afternoon, everyone, and welcome to this webinar on COVID-19 vaccines for myeloma patients. My name is Ana Vallejo. I'm the myeloma patient group communications manager, and I will model this webinar today. First of all, I would like to thank you all for joining us today. As you know, COVID vaccination has raised a lot of questions, and especially around patients, about what is the best vaccine for patients or how COVID vaccines might affect myeloma and elamines treatment. MP has developed a Q&A on COVID vaccination that you can read on our website, and we hope that we can solve some of your questions during this webinar. Before we start, just for your information, just mention that this webinar will be fully recorded and will be uploaded to the MP, to the myeloma patient group website, which is www.npu.org, and it will be also available in our YouTube channel. Before we start, I would like to make a small summary on the webinar's agenda. The webinar is scheduled, as you know, from five to six, so the presentation will last about 40 or 45 minutes, and then I will open the session for questions. There are two ways in which you can ask questions to the doctor. One of them is using the microphone in your computer, as I'm doing now. Just press the right hand button that you will see on your screen. I will unmute you, so you can ask the question directly to the doctor, and the other possibility is to do that in writing, in the question and answer window. I will receive those questions, and I will read them to the doctor, so she can answer them. As you know, the talk will be given by Dr. Ana Sureda, head of the Mathology Department at Instituto Catalon de Oncología in Spain, and on behalf of MP, Dr. Sureda, I would like to thank you for your collaboration, for your time preparing and giving this webinar, and for summarizing for the patient community the most important updates on the approved COVID vaccines in Europe. Thank you very much for helping us always with these kind of activities, and the floor is yours. Thank you very much, Ana, for this kind introduction. First of all, I would like to thank MP, and especially you, for inviting me to participate in this webinar, which I think it's not so easy, because unfortunately, when we talk about COVID-19 vaccines in multiple myeloma, and of course in other hematological malignancies, probably we have more questions than answers, even nowadays. So I'll try to give an overview on COVID-19 infection, and basically I want to highlight some aspects that at the end will lead us to discuss COVID-19 vaccines in patients with multiple myeloma. So let me see if I can share the screen. Sure. Okay, is that okay? Yeah, it's fine now. Perfect. Thanks so much. So that's the title of my presentation, and of course, as Ana has said, we will be able to have some minutes for Q&As after the presentation, and here you have my disclosures. So here you have the agenda for the presentation. I'm going to introduce you a little bit to the respiratory viruses in hematology and what they represent for us. Of course, I will be discussing then the introduction of SARS-CoV-2 COVID-19 infection, the clinical impact of this viral infection in hematological malignancies in general, and of course in patients with multiple myeloma. And then I will be going into seroconversion to SARS-CoV-2 infection, and then, of course, the vaccination plan in oncohematological patients with a specific mention to multiple myeloma. So let's start with respiratory viruses. And here in this slide, I have tried to put hopefully quite a comprehensive list of the different viruses that we can eventually find in our patients. So the first group is basically a DNA virus, and here I'm sure that you can recognize some of them. Herpes simplex virus belong to this group, varicella sorters, CMB, EBB, and other herpes virus 6, 7, and 8. And we have to recognize that basically the first infection when we talk about these viruses, it's happening during childhood and in young adults, and usually disease comes because of an endogenous reactivation, and it's very infrequent to have exogenous re-infection. This is completely different from the situation that we see when we talk about community respiratory viruses, and here you have flu, metanomavirus, rhinovirus, enterovirus, coronavirus, and we will be discussing quite a lot about it. And here we never have an endogenous reactivation, and it's usually an exogenous infection. So that's another way of looking at these different type of viruses. And so when we think about community respiratory viruses and we think about the different type of hosts that we can have, so if we look at adult people that are not immunosuppressed, we have to say that the period of viral excretion is really quite low, that the viral load per drop is also quite low, and this is quite different from what we can see here in immunosuppressed adults. So basically patients with hematological malignancies and multiple myeloma. Here the patient can be eventually excreting the virus for many days, eventually for several weeks, and the viral load in each drop is quite high. Basically the infection in many cases, here in the non-immunodepressed adults, is being produced through the hands, although also it's related to the inhalation of respiratory drops. And if we look at children, so children, non-immunosuppressed children are basically characterized to have multiple and very close contacts, and they also present with a high viral load in each one of the drops. So basically immunodeficient patients and children's are the most effective ones. And in this slide, basically you can see the number of patients that have positive samples with respect to SARS-CoV-2 since the time of diagnosis, and probably this is being better seen here in this graph that basically represents that when we talk about immunocompromised cost, so basically looking at patients with hematological malignancies, the viral load is higher, and basically the peak is a little bit later than the development or the peak of the symptoms. And then this area under the curve, which is basically this area that I am showing here with the pointer, is really very high if we compare it with the immunocompetent adults. And that's one thing that we have to take into consideration. Another important thing to take into consideration, and these graphs have been taken from a paper that was published several years ago by José Luis Pena, who is a hematologist working in one of the hospitals in Valencia, and he was basically looking at the community-acquired respiratory virus. So the hospital admission rate, which was directly related to respiratory virus, was 22%, and the overall mortality was 18% in the population of hematological patients that he was looking at. So that's another important thing to take into consideration. And I'm not going to go through all the different risk factors that immunocompromised hosts have to develop this community respiratory virus infection. But as you can see, I mean, there are quite a lot of them that also have an impact in the disease progression to lower respiratory tract infection, basically lymphopenia, all the rage, smoking, for transplant patients have those TBI, the type of donor allogeneic stem cell transplantation. And of course, there are other factors that are associated to mortality related by these viral infections. And finally, I mean, to end up with this part of the presentation, and as I have basically been mentioning a little bit before, we have to take into consideration that there is a mortality which is related to the development of all these viral infections. As you can see here for coronavirus, for rhinovirus and metanomovirus. So that's a kind of a very quick summary of what we were working with in terms of respiratory virus when talking about patients with hematological malignancies immunosuppressed patients, but not very far away ago. We had what I have called here the tsunami COVID-19. So what's SARS-CoV-2? So basically it belongs to the coronavirus family. And coronavirus family, it's a very large family of viruses that can cause illness that has really quite range in terms of signs and symptoms. And it can go from really a common cold which does not have any clinical significance to producing severe disease. It's a better coronavirus and the natural reservoir are bats and the final hosts are humans and eventually horses. If we look at some biological characteristics of SARS-CoV-2, I want to highlight that this RO index that basically represents the average number of people that can be infected by each sick person is around three between 2.5 and 3.5. And if we compare it with the seasonal influenza, it's really significantly higher. The transmission is basically through big drops. And so this is why we have, let's say, to keep this security distance. There has no fatal transmission being described. And it has also been described some fecal oral transmission, but basically it's a respiratory transmission. From a clinical point of view, we can separate the infection into three different stages. The first one basically is characterized by some clinical symptoms of signs which are related to the viral response rate. But then we continue with the stage two and the stage three, that it's basically the pulmonary phase and the hyper inflammation phase that it's associated to the different clinical characteristics of this type of infection, which is quite different from what we knew from prior respiratory viruses. As you know, COVID-19 pandemic basically emerged in Wuhan, which is in the province of Hubei in China, and that was the late December in 2019. And here I have highlighted some numbers that it's very clear and this slide, it's a little bit old, which are completely outdated nowadays. The most important thing is that really very quickly and as in a different way than other viruses that basically appeared here in China, but they remain here in China, COVID-19, SARS-CoV-2 basically spread out throughout the world in this kind of picture that I am presenting here. And unfortunately, this picture probably has bigger red dots than the ones that I am presenting here. If we look just bringing as a matter of example, a kind of numbers of patients being diagnosed per day in Spain since, let's say, mid-March, that was basically the official lockdown for the first wave. And unfortunately, although we were quite good in stopping the virus transmission after the first wave with really very strong lockdown measures from July last year, basically one wave has been mounting on top of the other one and we are around what we consider the fourth wave. And of course, these waves have been associated with a significant number of people dying from this viral infection, something that probably none of us would have thought that this was going to happen to us, I mean, before December 2019, at least myself. So what's the clinical impact of SARS-CoV-2 in hematological malignancies? So the epidemiology of this respiratory virus infection in oncohematological patients is somewhat in parallel to that of the general population. And I'm just going to show you an example of that. But we have to take into consideration that the clinical behavior is completely different in immunosuppressed patients. So the clinical picture is more severe. We have already seen that the viral expression is much more prolonged in immunosuppressed patients. There is a more frequent transition and I have already shown you maybe quite too quickly some prognostic factors to move from an upper respiratory tract infection to a lower respiratory tract infection. And we have a higher mortality rate in this situation. This is what I was telling you before about this quite similar epidemiology between what has happened in the general population and what has happened in our hematological patients. And this figure here on the right-hand side has been taken from one of these official information coming from the Ministry of Health in Spain. So starting here on the first in March in 2020, that basically represents the new cases diagnosed by PCR during the first wave. And here you can see which was the number of newly diagnosed COVID-19 infected patients in a retrospective analysis that we did basically looking at the infection of hematological patients during the first wave. So from the beginning of March to basically the end of May. And that's let's say the title of this paper. And here we try to analyze the risk factors and the outcome of COVID-19 infection in patients with hematological malignancies. And we put in a special emphasis in looking at those patients that had been transplanted either autologous or allogeneic stem cell transplantation. And we identified, first of all, some risk factors for these patients to develop severe pneumonia. The first one was hypertension. That's very important to remember because sometimes the risk factors for morbidity and for mortality related to SARS-CoV-2 infection is not exactly related to the underlying disease but it's related to the comorbidities that the patient in this case has in addition to the underlying disease. So hypertension was able to increase in this analysis twice the incidence of severe pneumonia. Also we have to take into consideration infopenia. And also we have to take into consideration inflammation parameters like CRP. Another important thing is that we were able to identify some risk factors that were associated to mortality related to COVID-19 infection. And I want to highlight age, which maybe it's not a surprise for anybody. Those patients that had active disease at the time of infection also had a higher mortality rate. Notropenia was also an adverse prognostic factor, as I have mentioned, for the development of pneumonia inflammation. And basically we are using CRP as a marker for inflammation. And last but not least, the performance status of the patient that had also a significant impact in mortality. So another example, because I have to say that initially we didn't have any information about it, but I mean the scientific community and all the allied partners were so quick in producing information regarding the impact of this infection. In this case, hematological malignancies that the literature was completely overloaded with different manuscripts. And here you have another analysis that was published by the Italian group also looking at the clinical characteristics and risk factors associated to COVID-19 severity in patients with hematological malignancies. And what they found is something quite similar to what we found in our retrospective analysis. So age was an important prognostic factor. And there were some specific hematological malignancies, acute leukemias, lymphoproliferative disorders, and I would include here class muscle myoplasm as a lymphoid malignancy that were adverse prognostic factors in terms of mortality due to this infection. And finally, at the end of last year, December 2020, we had the information coming from a systematic review and meta-analysis in more than 3,000 patients that had been included in prior retrospective analysis. And here you have the take home messages. So the mortality appears to be high in patients with hematological malignancies and COVID-19 infection. There were some prognostic factors that were quite constant in the different manuscripts, in the different analyses that were published. So basically age, all the patients older than 60 years had a higher mortality related to the infections, also non-white patients. Having received recent systemic anti-cancer therapy was also in some cases associated to an impact in the mortality, but of course there was also a higher proportion of patients that were able to survive. And in this slide, you can see what I have already said in a kind of a graphical way. So adult patients, as usually happened, do less well than children. Here you can see the impact of age, also the not so clear impact of recent anti-cancer treatment, although there are some manuscripts or some analysis that indicate that recent treatment has a negative impact in terms of morbidity and mortality, and also the impact of race non-white patients doing worse than white patients. So we have had a look, let's say, an overall look at the clinical impact of SARS-CoV-2 in patients with hematological malignancies. What about the clinical impact in patients with multiple myeloma? And here, as a matter of example, I'm bringing a paper that the Spanish multiple myeloma group, the Gempe Temma group, and this paper was co-authored by Joaquín Martínez López and Mary B. Mateos. So we were looking at the clinical characteristics and prognostic factors for those patients with multiple myeloma that were admitted in a big number of Spanish hospitals in hospital because of COVID-19 infection. And we also wanted to compare the outcome of these patients with the outcome of a population, of a general population of patients, so patients with non-hematological malignancies that had been admitted at the same time in the same hospitals where these multiple myeloma patients were admitted. And to make this story short, we basically included almost 200 patients reported from 73 hospitals and just to show you that this analysis came from the patients that were admitted during the first wave, so March and April in Spain 2020. And this analysis is ongoing. So the, I mean, one piece of information which is important is that the inpatient mortality was higher in patients with multiple myeloma than in patients with non-cancer, 34 percent and 23 percent. Among multiple myeloma patients, the inpatient mortality was 41 percent in male. It was higher in the elderly population of patients, older than 65. It was also higher in patients with active and progressive disease at the time of being admitted. And also renal disease was a negative prognostic factor in terms of mortality and morbidity. And all these factors were independent prognostic factors when we did these multivariate analyses. And here you can see, I mean, the same information I have given you in a graph, in a more graphical way. So age older than 65 was an adverse prognostic factor, the presence of renal, renal disease, also patient with active disease or progressive disease at the time of being infected, some specific multiple myeloma features at the time of diagnosis and treatment. And prior stem cell transplantation did not have an adverse prognostic impact in the series. So of course, I mean, just focalizing our attention in patients with multiple myeloma, it's clear that these patients with multiple myeloma represent a vulnerable population of patients that was clearly recognized. And here, as an example of the multiple efforts that have been done over the last few months to establish an adequate management of patients with multiple myeloma during this COVID-19 pandemic, I'm putting here this consensus paper coming from the European multiple myeloma network with many very famous names that probably you will be able to recognize. And to finish this part of this, of the presentation, just a summary of some mortality rates looking from different, let's say, countries or eventually areas, looking at different types of hematological malignancies. And we have to recognize that, let's say, mortality rates in some cases are above 30%, or eventually 40%, and this has to be taken into consideration. So when we try to think, because I mean, we have already seen that for those patients being infected, and basically for those patients that had to be admitted in the hospital, because this is one thing that we are probably analyzing now, and we have not analyzed so much, or we did not analyze so much at the very beginning, because all these studies were basically focused on those patients that had to be admitted because of COVID-19 infection. But of course, we were missing, and this is one thing that it's being analyzed nowadays. We were missing those patients that had COVID-19 infection and did not have to be admitted in the hospital. But for those patients that had to be admitted in the hospital, we have seen that the infection is really severe. We have been able to identify some prognostic factors. We know some figures in terms of mortality. But then what happens when patients are being infected with COVID-19? And that's the other thing that we need to take into consideration, because these considerations about seroconversion will take me to discuss with you some question marks that we still have nowadays regarding the vaccination plan. So what we know about seroconversion, so which is the capacity and that's very important for patients that are immunosuppressed to mount an immunological response, either a humoral response or a cellular response when patients go through a severe COVID-19. So what you can see here in this paper that was really very recently published only a few weeks or months ago, or very in 2021, is that in general the capacity of patients with the underlying diagnosis of cancer, the prevalence of IgG after having gone through COVID-19 infection is significantly lower than in those patients that went through COVID-19 infection, but did not have the underlying diagnosis of cancer. And this is one thing that we have to take into consideration. And I'm bringing here some examples that are basically looking at hematological patients, indicating the somewhat low capacity of hematological patients to mount a humoral and eventual cellular response to COVID-19 infection. So in this study that included a small number of patients that were infected by SARS-CoV-2, only two out of 12 patients were able to generate IgG antibodies. So that's an example of the capacity of patients with hematological malignancies to develop IgG antibodies against the infection. And this is one thing that we will have to take into consideration when talking about vaccinations and vaccines in this specific population of patients. And here I have brought some really very quick examples that have been taken from very recent publications that have appeared in the literature. So in these analyses from CLL patients, the percentage of patients that were able to develop IgG antibodies in front of SARS-CoV-2 were 67% in this study looking at the small numbers of transplant patients and patients being treated with CAR-T cells. The percentage was 60% and in AML, in this really very small group of patients, 88%. And in this study, which was a prospective study that was published in January this year in the Annals of Oncology, the authors were basically looking at the seroconversion capacity of patients with cancer, basically solid tumors in relation to healthcare workers in an oncology unit. So in this specific case, the data showed that there was no clear difference between the capacity to detect IgG antibodies against SARS-CoV-2 between cancer patients and healthy subjects. But this is one thing that we have to take into consideration when let's say looking at the capacity to respond from an immunological point of view to the infection first and potentially to the vaccination later on. So let's go back a little bit, not talk about COVID-19 and just think about vaccination in hematology, which is our prior experience. I mean, I'm sure that all of you are aware that many hematological patients have a vaccination calendar and this is one thing that we are doing every single year and that for transplant patients we have a very clear vaccination program to try to give the patients all the immunity that has been lost because of the transplantation procedure. And here I'm bringing this example that it's being discussed almost by everybody right now about the role of RETOXIMAP to allow an immune response to vaccination in lymphoma. And the summary of this slide is that the use of monoclonal antibodies and the CD20 in this specific case and here data basically come from the information we have from flu vaccination is that it's quite difficult to mount an immune response for those patients that are under RETOXIMAP treatment or have just finished RETOXIMAP therapy. So that's one thing that we need to take into consideration. If we look at patients with chronic lymphocytic leukemia, so it's also quite clear and this information comes from the flu vaccination is that the response of these patients to this specific vaccine was not so good enough with quite a lot of responses coming from different studies that have already been published and even this is not only the case with RENTOLYChemotherapy but also there is a low response rate to flu vaccination in patients that are being treated with ebrutinib that you may know it's really a quite extended and almost universally used, let's put it this way, bitcaying inhibitors in patients with CLM. And we have identified and this is not the setting still for SARS-CoV-2 but there are some prognostic factors that can eventually impact the immune response of the patient to vaccination. If we talk for instance about transplant the shorter time interval between transplantation and vaccination, low lymphocyte counts, low immunoglobulin levels, the presence of active graft versus host disease, the active immunosuppressor therapy and eventually RETOXIMAP therapy over the last 12 months. So that's one thing to be taken into consideration but of course it's very clear that what we want to achieve with vaccination in general not only immunosuppress patients but also in immunocompetent people is this what we call the group of immunity to try to stop the infectious capacity of the virus as much as possible as it's more or less depicted in this graph that I am showing here in this slide. So taking all these things into consideration which has been the vaccination planning in Hong Kong hematological patients and I'm going of course to give a special mention to multiple myeloma patients. So first of all I think that everybody's aware that the development of vaccines against SARS-CoV-2 has gone through a quite not different but a more speedy process than the traditional development of vaccines in a situation outside the one that we are living and here you can see that the normal process which is presented here in the upper side of this slide with preclinical studies, development of preclinical and toxicity studies and then clinical trials starting with phase 1, phase 2 and phase 3 and then submitting all this information to the regulatory agencies FDA, EMA and then start with the large scale production which can take quite a long time several years. It has been really speed up when we talk about SARS-CoV-2 vaccine development basically because many of these phases have been mounting one on top of each other to try to accelerate as much as possible this process and try to reach this kind of group immunity that we were discussing before. So these are the vaccines that we have nowadays. So basically I want to mention these messenger RNA vaccines so the Pfizer BioNTech which was the one the first one that we had in the market and then the Moderna vaccine you know that we have two different shots here and basically separated by three weeks then we have the non-replicating vector vaccines that are basically using adenoviruses and here I want to mention the AstraZeneca vaccine and then the Johnson vaccine that basically is the last one that has been approved and it's being distributed by different European countries and here the responses to the vaccines against SARS-CoV-2. So with higher rates with Pfizer and Moderna and with somewhat lower rates but of course we need to understand that the development of the different vaccines is not exactly the same so maybe with the other types of vaccines. So I mean I'm just bringing and I have to apologize because these slides are in Spanish just I want to give you as a matter of example how the process of vaccination has happened in Spain and I imagine that it has been quite similar in different European countries of course always taking into consideration the specific aspects that apply to the different countries. So here you have let's say a kind of advertising that was published in the official web page of the Spanish Society for Hematology and Hemotherapy basically indicating the pressure that the scientific societies have put in the healthcare system and the Ministry of Health to try taking into consideration the high morbidity and mortality that COVID-19 infection has in hematological patients to try to put a pressure to try to include this specific group of patients in the vaccination programs that are in Spain and I guess that this has been quite similar in other countries was basically related to the age of the patient. There were and there was a manuscript that was basically collecting all the recommendations coming from the Spanish Society of Hematology of Vaccination COVID-19 vaccination in a hematological patient and that was really a big document that was under the umbrella of the Spanish Society but had the input and the participation of the different working groups and then we ended up with let's say a press note that was published on the 11th of March this year indicating that transplant patients, solid organ transplants and oncohematological patients were candidates to be to receive vaccination or to be vaccinated in a priority way. When talking about vaccination we have to take into consideration several aspects and probably some of the questions that we'll be coming later on will be touching these different aspects. First of all we have to take into consideration that hematological malignancies are diverse and are not exactly the same. We have to take into consideration the absence of scientific evidence regarding the efficacy of vaccine in patients with hematological malignancies because as you know these patients were actively excluded from the pivotal perspective clinical trial as usually happens and we have some available scientific evidence regarding all the vaccines that we have been using for many many years in this population of patients. So when do we have to vaccinate against COVID-19 and which are the general recommendations this slide is quite busy and for the sake of time because we want to focus our attention in multiple myeloma patients I'm just going to go to this slide that tries to give some recommendations on what to do with patients with multiple myeloma and other plasma cell disorders and taking into consideration I hope you can see while this slide that the mortality of COVID-19 infection was higher in these patients in multiple myeloma patients that we have seen than in the general population of patients and the other thing that we have to take into consideration is the poor response that we have seen in several analyses when talking about influenza vaccines. So we have to take into consideration those patients that are severely neutropinic. The recommendation is to vaccinate every single patient even patients with smothering multiple myeloma and other less aggressive let's put it this way monoclonal gamopathy. So if the patient has active disease we try to our recommendation is to vaccinate the patient without stopping the active treatment but basically between cycles some days before the beginning of the next cycle if the patient has the multiple myeloma and the control we can eventually consider to hold the treatment between seven days before and seven days after vaccination there are some indications to eventually stop glucocorticoids during vaccination and to avoid high dose immunoglobulins at least one month prior to vaccination but nevertheless I think that it's very important to take into consideration that we don't have clear evidence in the literature that what we are doing is the 100 correct thing so we are basically extrapolating some of the recommendations from other settings and I basically want to finish my presentation with let's say some information regarding the efficacy of COVID-19 vaccine in our patients so this is one thing that we really don't know when we talk about vaccination and all the discussions on which are the patients that we need to vaccinate when these patients need to be vaccinated the most important thing are not the adverse events that we can assume that are associated with vaccination but basically what we really don't know is the efficacy of COVID-19 vaccine in patients with hematological malignancies and I have brought here two very quick examples that have with two papers that have just been published I mean one of them it's almost still not impressed I mean it's impressed but they are really really very new this paper analyzes the efficacy of Pfizer vaccine in patients with CLL and I have just highlighted here things that I wanted to mention you and basically I mean these 52 patients were compared with 52 sex and age much healthy controls so we have to take into consideration something that we might eventually guess with information that we already had that the response rate was significantly reduced in CLL patients with respect to healthy control that the response rate was highest in those patients that achieved the clinical remission after treatment followed by treatment naive and it was quite low in those patients that were under treatment at the time of vaccination that also those patients that were treated with btk inhibitors or penetraplugs plus minus anti-city 20 antibodies the response rate were quite low so that's one thing to be taken into consideration and a similar information can be taken from this very recently published paper that was published online only in April 19 that was looking at the response to first vaccination in patients with multiple myeloma so these are things that we need to take into consideration and unfortunately we don't have answers to these questions so we still need to learn which is the best way to vaccinate patients with oncochematological malignancies because we can eventually assume that the umumeral response and the cellular response is not going to be as good as in the healthy population of people and that we eventually will need to change the schedule of vaccination just according to the response rate that we get and here I wanted just to highlight some limitations to vaccination that are related maybe to daily problems how is the vaccine being distributed centralized versus decentralized administration of vaccines in some areas we lack a comprehensive list of patients with hematological malignancies and this does not make our task really very easy so these are the future challenges that I have already expressed just a little bit before the access to vaccine the security and efficacy of vaccination but basically I think that security is an issue but probably the most important question marks are on efficacy the probability to circumvert after vaccination the cellular response to vaccination and I think that this is my last slide which basically summarizes what I wanted to share with you something which is very clear nowadays but maybe six months ago or nine months ago was not so clear so the vulnerability of patients with hematological malignancies to SARS-CoV-2 infection that we have been able to identify some prognostic factors which are quite constant in the different analysis and that have already been presented hematological malignancies are quite very heterogeneous and because of what I have seen patients with hematological malignancies have been prioritized in the vaccination programs and we really need to learn more about it because maybe responses are going to be lower than in the general population of patients and maybe and we should be we should work in the future in select a better vaccine and the best time point for vaccination so thank you very much for your attention and now I'm happy to take some questions and comments so I'm going to stop sharing the presentation. Thank you very much doctor for this wonderful presentation we already have some questions but before going and respond them I would like to remind people in the webinar that they have two ways to ask questions one of them is in writing in the question and answer window and the other one is just clicking the right hand button so I will I will mute you and you can ask the question directly to the doctor. One of the questions that we received in fact so many times is about those articles in the Lancet and blood I know you mentioned that in your in your presentation as well but they show that the vaccine might be less effective in myeloma patients what are your thoughts about that and and also even if the vaccine is less effective I guess there is very important to get vaccinated anyway for patients. Yeah so let's say I think that I would like to make some remarks on that I think it's very important to get vaccinated no doubt about it and I think that this is being demonstrated on how I would say that at least in the European map all the governments have tried to prioritize as much as possible vaccination in multiple myeloma patients and in oncohematological patients in general after having said that I think it's true and probably either although we don't have a lot of information already published in the literature because as you have seen these two papers that I have briefly presented are really very new probably and this is also my guess although I don't have a personal experience on that the capacity of multiple myeloma patients in this specific case to respond to vaccines is not going to be the same than the healthy population of people and maybe the response rate is going to differ between different subgroups of multiple myeloma patients. We need to know more about it and I think and this is what we are doing in Spain so there is a proposal in which many hospitals will try to participate to analyze in depth the response to vaccination both the humoral response in terms of antibody, IgG antibody producing and the diesel response of hematological patients to vaccines in the way that we are vaccinating now our patients so we are following the label so two doses for Pfizer for Moderna which are the basically the vaccines that are being used at least in Spain and I think that in other countries basically for patients with hematological malignancies so we need to study that we need to understand which is the response and which patients within a specific disease group are going to respond better or worse and when we know that and I think that this is going to be done in parallel because the science is moving so fast in this field then probably all these studies are going to be moving in parallel we will need to understand if the way that vaccines are being used nowadays is the best way for our patients. This seems to be at least for the time being the best way for healthy people and these are the population of people that have been studied but we don't know about these specific populations so but independently on that I think that the message is that everybody or all of you need to get vaccinated. Thank you doctor and relation with what you just said about the vaccines and the different vaccines that we have there are some questions about what is the difference between them between all the vaccines and what vaccines is more recommended to patients one of the questions says that for example in in the Netherlands they are using Moderna for patients but that person asked if it's the same in all countries and then what is the difference between. Okay so basically basically the recommendation is to use this messenger RNA vaccines because when talking about immunosuppressed patients we can always think that vaccination can eventually produce the disease itself and of course this is one thing that we don't want so in principle I would say that Pfizer and Moderna are the ones that are being used there are differences between them but from a practical point of view that does not seem the case and I have to say that we are using Moderna in our institution to to vaccinate all our hematological patients and I think that probably there are some issues related to the supplies that may change that or eventually policies but I would say that probably there is no difference between Pfizer and Moderna at least that I know of but we are still starting with the whole process. Thank you doctor and one of the questions that we are receiving now is can myeloma patient be vaccinated with Pfizer with a 42-day interval between those one and those two? Well this is one thing that has been let's say publicized a lot and in principle that was not I mean that was not the time interval that was in the label but there are some studies indicating that the rate of immunity does not change after having said that I go back to the information that we have and the information that we have basically relates to healthy people so it's always a question mark on which will be the impact even using 21 days for patients with multiple myeloma in this case. I'm sure Sorriana I'm sure that that many countries or all the most of the European countries are conducting nowadays and I'm sure and I know that many studies trying to follow really very closely the response rate of patients to vaccination and probably and this is what always happens in science unfortunately that at this specific time point we really don't know exactly 100% the truth and if we are going to discuss the same issue maybe in one year some of the questions that all of us have will have completely been solved by all the investigation that it's being done nowadays. Thank you doctor the next question I am a myeloma patient on third light of treatment of with chemotherapy based on linalidomide, exasamide and dexamethasone how does this chemotherapy that affect my immunity to COVID? Well let's say we have already seen that at least in some studies active disease and active treatment it's let's say a risk factor let's put it this way for developing COVID-19 infection so probably even within multiple myeloma patients it's not the same thing to have the disease information and not being under any specific treatment that being with active disease I assume and that's the reason why I mean you are in a specific under active therapy so that's one thing to be taken into consideration we always have to think that and the let's say the infectious risk it's not only because of the line of treatment that you are receiving right now but eventually also because of the prior history of prior treatments of a longer standing disease so that's another thing that has to be taken into consideration so at the end of the day the prior treatment history of the patient has an impact if in many aspects and probably will have also an impact in the risk of getting the infection so I would say that in this specific situation it's clearly indicating indicated the vaccination with all the question marks that we have discussed before thank you doctor and I just also some clarification of one of your previous responses you mentioned that for patients usually it's recommended Pfizer and Moderna and and some people have some questions about if you only can access to the AstraZeneca vaccines or Janssen and you should get vaccinated anyway so do you have to wait until you have any other available no I think that it's as always in this life is a question of balancing risk and benefits cons and pros I think that the message is that vaccination will be the only way to stop COVID-19 pandemic with what it represents and that all the vaccines have demonstrated efficacy so if Pfizer or Moderna is not available AstraZeneca or Janssen have been approved by all the regulatory agencies FDA and EMA and they can do the job thank you doctor and one of the questions related to this topic as well I have been vaccinated once with AstraZeneca can I ask for the second vaccination with Pfizer or Moderna I'm not so sure how how to how to answer this specific question I would say and that I would probably continue with AstraZeneca I don't have clear ideas if let's say switching to a different one makes a lot of sense yeah and I guess that will depend also on the guidelines of each country and how they decide absolutely this is one thing that I mean I have tried to mention during my presentation and of course because I am Spanish I have focused my attention basically in what we are doing in Spain unfortunately it's a moving field so probably if you review different guidelines the guidelines are not going to say 100% the same and probably the guidelines are going to change over time and of course I'm sure that there are different regulations in different countries that will make things a little bit different thank you doctor next question I'm a 70 for chemotherapy and a little might dexamethasone as a third line of treatment I have had to vaccination and have antibodies how is my risk level well you are not 100% free but having antibodies if they last long enough let's say I think that you are in less risk than many of other people so let's say we are being vaccinated and we are being told we still have to take care and to continue with the same let's say distancing measures that we have been taken for the last one year and a half so but of course at least for the time being you have antibodies which does not prevent 100% to be infected but it prevents a lot and that the same person asked my vaccine was AstraZeneca good third vaccination help we don't know thank you doctor one of that well the next question what is the efficacy on the vaccines on different strains do the vaccines cover all of them or only some of them so I think that the level of information that we have is not exactly the same with the different vaccines so it's and probably I mean for the vaccines that have been more news in the market more or newer in the market so for instance AstraZeneca and Janssen there is I mean there is quite a lot of scientific work to try to overcome these issues so for instance AstraZeneca seems to be less effective with the South African variant for those mild and moderate let's say uh infect infective cases and it it's a it seems to be efficacious or efficacious for the britannic variant but they are doing quite a lot of studies uh first Pfizer seems to be effective for the UK and for the South African variant and it seems that for Moderna although the at the end the level of antibodies does not seem to make a difference but it's the effectiveness seems to be somewhat reduced with the South African variant but I would say that this is quite the preliminary information depending on the let's say the the the sources that you read maybe the information is different but um and probably we will be having additional information but that's basically the information I have and of course probably the ones that appeared first and with and with what we have more experience probably have let's say a more solid data regarding specific variants thank you doctor I know we are over time and I would like to ask you as the last question and probably the rest of the question that we have maybe they can send them by by email we have the questions here so maybe we can send them to you by email so I would be happy to answer all the questions that we have not been able to answer now so the last question uh do you have any recommendation for smoldering myeloma patients even though we are not in treatment with chemo I would like to know if there is any special attention when receiving the vaccination I mean I would say and this is one thing that we are doing we are we are vaccinating patients with a smoldering myeloma it's true that maybe I mean the risk of COVID-19 infection is not going to be exactly the same because the disease in inverted commas is not active you have not received prior therapy just because of the disease but but the recommendations is that uh that you and let's say the rest of the people in this situation get vaccinated thank you doctor and and the last question and now for real is I am a myeloma patient and I'm doing I'm going to be treated tomorrow with the ratumumaf prevision and dexamethasond and I start at year of 21 uh day with Lena Lidomite I had my first dose on Pfizer on uh 26 on April what should I ask so to get I mean if the first dose is already in then you have this you have to have I mean you have to get the second dose um in patients with active treatment let's say the recommendation but let's say the level of evidence is what we have right now is to try to vaccinate uh in the week before let's say in this case because Lena Lidomite it's Lena Lidomite Dara and Lena Lidomite or Dara and dexamethasond Dara and Lena Lidomite and yeah I think Dara and Lena Lidomite okay so Lena Lidomite will be most of it continuous but with Dara tumumaf so probably I would give uh let's say the second shot uh one week or between the last week before receiving the next dose of Dara well thank you very much doctor and uh well thank you for responding all the questions if uh we keep uh receiving questions I will send down uh by email to you so you can answer them and just remind everybody in this in this webinar that this webinar uh has been recorded and will be uploaded to the myeloma patient Europe website uh which is www.wmpyoutube.org and it will be available also in our youtube channel so thank you very much for your time doctor and uh thank you all for for joining us today and have a nice evening thank you thank you very much for the invitation thank you Anna thank you


The police in Liga says the command is investigating threats by the indigenous people of Biafra Aipop and Yoruba's separatist groups. Commissioner of Police Hakim Udumosu has vowed that no breakdown of law and order or attacks on soft targets would be tolerated. He spoke at the stakeholders forum on security, which Governor Babaji Desangolo presided over. The CP said the command was aware of agitation for the Odra Republic by some Yoruba secessionists, and the threats to disrupt law and order in the state. The police chief disclosed that 24 persons belonging to the groups have been identified and have been closely monitored.


Hello and welcome to CBA 15 my name is Jesper Hornberg and I'm the lead on innovation and scaling at the Global Resilience Partnership. Do you think that you have an idea that could change the way stuff happens in your community and do you want to work with peers and experts in the field to develop the idea and hone the pitching skills so that you are ready when you're meeting potential partners and funders? Well then I suggest you join us in the Dragon's Den. Please submit an idea and I look forward to seeing you there. Thank you.


This is Witchface news for Friday the 22nd of September 2023. I'm CMDR Buur. In Elite Dangerous News this week, we take a look at what might be hidden inside the update 17 teaser trailer. After Fdev released their annual results we consider what they might mean for the future of Frontier Developments and Elite Dangerous. As always if you enjoy our videos please do hit the like button and if you haven't already be sure to subscribe and ding the bell so you don't miss any of our Elite Dangerous content and if you'd like to help directly support the Buur Pit you can also join our Patreon links to that and everything else are below. At last week's pitcon event in Nottingham in the UK Frontier chose to release a teaser trailer for the next update to Elite Dangerous update 17. Included on the end of that teaser was the expected release date for the update, that release date is October the 16th, just 24 days as I speak these words. Frontier hosted the latest episode of their frameshift live live stream last night and some significant portions of that live stream did concern themselves with the teaser trailer and what commanders thought they'd seen in it. Arthur told me when speaking to guest developer Max did say however that there was at least one detail that as far as he was aware no one had yet spotted. We've been over the teaser trailer with a fine tooth comb and having thrown the tooth comb away because it's coated in caustic goop we can now talk about what we think we're seeing in there. The teaser which is presented in a glitching found footage style shows around a minute and a half of what is very clearly some sort of Thargoid surface installation but it's not something that we have in the game right now or at the very least it's at a different stage of something that we have in the game right now. I'm going to make some assumptions here but there are too many indicators and familiar objects to ignore what we believe we're looking at is likely the next stage of one of the Matrix surface sites that appeared in the game recently. I say the next stage because the Matrix sites whose purpose and nature isn't even slightly understood make creaking and rumbling noises and have sand and material falling off of them the indication at least appears to be that they are in fact growing or pushing out of the ground somehow. I'm going to talk right out the gate about the opening shot because what it shows whilst very vague is we think significant. The video starts high above a planetary body so high that you can see the curvature of the surface quite plainly. As our viewpoint moves quickly forward a very large gaseous cloud can be seen coming over the horizon and whilst it's difficult to be sure at its centre we think we're seeing a large solid spire like structure. We're at some significant distance still so whatever we are seeing must be very large. The next scene shows further inside the cloud and we see two large organic spires protruding from the ground one with a beam of bright green light emitting from its centre. As the scene continues a bright point of light launches from what looks to be a patrolling revenant more on that in a moment and it rises quickly into the sky. Rather than continue rising however the object reaches altitude and then seems to travel horizontally almost like a patrolling aircraft or perhaps aerial drone. On the extreme right of the scene is a further organic structure that we think reappears throughout the video off to one side and whilst it's difficult to be sure it looks to be extremely large. We think this may be the base of the central spire that we're seeing over the horizon at the start of the video. As the video continues we're shown various Thargoid matrix like structures and protrusions at ground level until we see what looks to be one of the objects from the current version of the sites that when scanned is identified as itself a matrix. The I'm going to call them petals of the matrix are rather ominously slowly opening. Also the base of the matrix looks to be much wider and deeper than what we've seen so far. It looks like it may have pushed further out of the ground and more of it is now showing above the surface with root light structures underneath that you can clearly see through in the opening scenes of the video. Next we see a couple of scenes of Thargoid revenant drones moving around but it becomes rapidly apparent that some of the revenants we're looking at are not the same as the ones we've become used to. They are larger and have at least two search lights on the front whereas the current crop of revenants sport just one such light. If I had to guess I'd say these drones are the Thargoid equivalent of the Goliath drones that are often found in human military installations. I also think it was likely one of these Thargoid Goliath drones that launched the bright light aerial drone that I spoke of at the start. Again all the while there is the presence of the very large Thargoid structure off to the side of the screen. We currently have no idea what purpose all these structures serve is it a Thargoid citadel maybe or perhaps an actual hive. Your guess is as good as mine. We can clearly see there is another form of the revenant drone on the way. My personal feeling is that perhaps we're seeing it launch an eye in the sky style drone of its own or a loitering weapon system perhaps. I do think we're looking at a very very large central structure surrounded by spires and that the barnacle matrix structures themselves are opening up. The whole scene is very Geiger-esque and frankly the stuff of nightmares. As I mentioned at the top of this piece update 17 arrives on the 16th of October. Frontier developments released their annual report last week which always makes for interesting reading in one way or another. I will preface this by saying that we are not by any stretch of the imagination proficient financial analysts but we do have some very basic understanding of these types of reports. This can obviously all be quite dry material to chew through so we're going to focus on two important key performance indicators both of which have gone down this year. The first is a thing called a beta which is the worst acronym in the universe but it basically stands for earnings before interest taxes depreciation and amortization. Pretty thrilling stuff right? The second is the company's cash flow. This is perhaps a bit more obvious in that it's a measurement of the amount of cash that comes into and out of the business in a given period. In any company a decrease in the worst acronym in the universe may be an indication of low profitability. It generally means the company has had rising costs but they have been unable to pass those costs along to the customer by raising their prices as one example and so this number goes down. The cash flow represents the amount of cash the company is generating from its activities before paying off any debts and stuff like interest. Frontier did note in the report that the decrease in their cash flow of around 10 million pounds was due to the acquisition of complex games the developers of warhammer 40k chaos gate and also a purchase of shares to slot into their employee benefit trust this year and were it not for these two contributing factors the cash flow would have in fact gone up. Overall their pot of cash actually looks pretty healthy still. The two indicators we've isolated here aren't by any means the whole report but they are a simple way of understanding what's generally going on with any business. If they are rising that's a good sign if they are falling it's not so good and Frontier probably have got a bit of a bumpy road ahead to get through as a result. Looking at this situation with a calm head I don't think the sky is falling by any means but it may mean we'll see a tightening of the corporate belt buckles and possibly a reduction in more casual spending across their stable of existing titles including a leak. I'm going to guess that licenses like warhammer age of sigma and formula one are expensive for Frontier to get and as a result the board are going to want to see a significant return on those two investments which is why we've seen them become such a big focus for fdev in recent months. It is interesting to note that games released before the start of this financial year delivered 72 percent of the total revenue in that period with Jurassic World Evolution 2 being the biggest hitter. Fdev have also stated that Elite Dangerous is still making money as part of that portfolio of games. Frontier note that their post launch nurturing strategy delivered solid numbers this year i.e looking after the games they already have released has paid off well for fdev now and in the past and it continues to be a staple of their overall corporate strategy. As a company they have also declared a refocusing of their strategy and this made for some very interesting reading indeed. Johnny Watts the new CEO who took over from David Braben just over one year ago now notes that in January 2024 the company will be celebrating 30 years since Frontier was founded in 1994 and that benchmark has provided quote the perfect context in which to look back at our games and reevaluate what makes a Frontier game when it comes to our project selection decisions end quote. In analyzing their successes fdev have now defined four project selection pillars these being strategic experience gameplay and longevity. In the report they go on to state that their biggest past successes to date all align under those four project selection pillars. They then go on to list their favored game genres that they see as staples of fdev's identity. Those listed genres are CMS games or creative management sims so titles like Jurassic and Coaster etc and they have two more CMS games currently in development one for financial year 25 and one for financial year 26. This genre far and away is what Frontier considers to be its strongest suit. Sports management with the F1 manager series being the current focus real-time strategy this way lies Age of Sigma turn-based strategy here be Warhammer 40k chaos gate and finally open world space simulation with the genre defining elite series of games. Just to underline that again fdev have this week said that they have five genres that they see underpinning the company and those genres are creative management sims sport management sims real-time strategy games turn-based strategy games and open world space simulations. Odyssey now two and a half years ago was a significant bump in the road absolutely. Odyssey did however arrive off the back of seven years of significant success with elite dangerous performing extremely well for fdev and that can't be ignored or trivialized. My personal assessment is that they very much need f1 to start earning its keep and they clearly have a lot riding on Warhammer Age of Sigma. I was personally excited to see fdev were making a Warhammer RTS game I was less excited when I learned that it isn't in the 40k universe and had a smaller more console centric scale and approach to real-time strategy but I'm of the total annihilation and supreme commander generation which were very different games to what Sigma appears to be reaching for. Frontier is undoubtedly facing some challenging times there's no two ways about it and I do think the company is likely about to go through somewhat of a fire storm you can't escape the fact however that fdev have listed both elite dangerous and the space simulator genre as part of their strategy going forward. I think the next year could be a galvanizing process for them they're already looking at what they do best and are refocusing the company toward that and having been through the fire they'll likely emerge stronger and wiser. Were you reassured to hear Frontier refer to space simulators as one of their pillar genres? Have you seen the update 17 trailer and what details can you see that we might have missed? Let us know in the comments below that's it for now thanks very much for watching we'll be back later this week with more videos until then 07 commanders follow the greens on the way out and do keep clear of the toast rack we very much look forward to seeing you next time


This is stock number 10426. We are here at Summit Automotive in Fond du Lac, Wisconsin. You're new and used Jeep and Jeep Wrangler headquarters. Today we are checking out this super clean 2017 Jeep Wrangler Unlimited Rubicon hard rock. This vehicle has a 3.6 liter Pentastar V6 motor and has been fully safety and inspected by our service shop has a fresh oil and filter change. All the fluids have been checked and topped off and this Jeep is 100% ready to go. Black clear coat is the color we shoot all of our videos in 1080p 60 frames per second. So if you have HD capabilities on your computer tablet or smartphone device turn them on right now because it is like you're right here looking at the vehicle with me and definitely your best way to check out the vehicle quality and condition wise before seeing it in person. If you want to check out more photos in the upper right hand part of your screen is a link right to our website so check us out there. Moto metal painted in chrome chrome doughate alloy rims. General grabber tires on here LT 275 65 R 18s and they have right around half to 60% of the tread left maybe even 70 60 70 I'd say has a Fox shock Jeep suspension little bit of a lift kit on there has the LED lighting group so you get the LED fog lamps the LED headlamps the LED running lights it comes with a worn 9.5 CTI metal winch front metal bumper and you do get the cull induction sport hood fender flare is a nice shape and the passenger side rim no scuffs or scrapes on that as you go down this side of the Jeep you can see just how clean the body is how reflective and mirror like that paint is we take these HD videos so if you are far away or even if you're close behind just cannot make the trip down you can still see the vehicle hear the vehicle and have confidence in what you're looking at before even get here so that when you do get here there's absolutely no surprises and once more down this side very clean no dents or dings in fact we offer a summit auto fast-pass option on our website in the upper right hand part your screen where you can apply for financing get pre-approved see a payment quote even appraise a trade if you have one all from the comfort of your own home lower rockers and underbody looks really good and the back rim is an excellent condition as well and that's some of all fast passes in the upper right hand part your screen back tires have just a little bit less than half the tread left frame under body looks good there see it has the factory metal bumper it has a insert where you can put a heavy-duty tire carrier on there you get the receiver hitch and four pin wiring and that is a metal bumper you get the red-toe hooks you get a matching spare tire and wheel that's a full tread on there that was a brand new tire so you can compare that to the ones that are on it comes with the alpine factory subwoofer you get your off-road kit and you also have your case for your front hard top pieces you get your door hinge and roof bolt holders down there and the hard tops and nice condition on the inside you get your three bolts on each side two on the top for a total of four and two quick disconnects to take that hard top piece off gate shuts nice and solidly and as you go down this side the Jeep just as clean as that passenger side that hard top color matched very nice condition and down the rest of this side very very clean door hinges I didn't see any corrosion on them they look really good you do get heated mirrors inside this Rubicon hard rock package gives you the black leather interior there are no rips or tears on these seats Rubicon stitch backrest you get all-weather floor mats the red sway bar disconnect and the axle lock buttons right there and as we hop inside the vehicle here you can see that this one has 57,780 miles the digital outside temperature and compass display get the custom Rubicon instrument cluster there comes with the leather wrapped steering wheel cruise controls on the right Bluetooth and information center controls on the left if you ever wonder if it has the alpine or not just look at that speaker right there and it'll tell you and this one also has auto headlamps comes with the Uconnect 430N radio with the factory navigation AM FM and Sirius XM radio capabilities as well and it does have a hard drive on here that you can store pictures and music on and it's 28 gigs worth of storage you got your window buttons your climate controls your heated seats stability control downhill sis control your five-speed automatic transmission and four by four shifter passenger side all-weather floor mat and seat are an excellent condition no rips or tears on that this Jeep smells very clean doesn't smell like it's ever been smoked in and the head the front roof pieces are in nice condition too we'll take a quick look at the back seats and then we will check out under the hood also has a hundred fifteen volt 150 watt plug-in right there the back seats are just as clean as the front seats no rips or tears back here it does have the latch child safety system we have a factory all-weather floor mat back here as well those latch systems are for your child car seats those seats do fold down for extra storage and you can see they go almost completely flat which is nice if you got a haul a bunch of extra stuff you do get child safety locks on the back doors and we'll take a quick look under the hood I would personally like to thank you for checking out the video today and hopefully from this HD video you will have been able to tell just how clean this Jeep is all the way around inside and out under the hood we have the 3.6 liter pentastar v6 motor engine base very clean runs very smooth this Jeep has been fully safety and inspected by our service shop has a fresh oil and filter change all the fluids have been checked and topped off the vehicle has been gone through mechanically 100% and is 100% ready to go we're gonna do one more quick walk around here and to see more pictures of this Jeep or one of our other 450 new and used cars trucks SUVs minivans Wranglers you name it we got it go to our website www.summitauto.com full pictures and descriptions of every single vehicle from two locations all at summitauto.com and if you'd like to check out more HD videos like this one you can go to youtube.com slash summit auto remember to like subscribe and share on this video and all the videos that you see there in fact in a second you will see a link to subscribe to our YouTube channel on your left a linked more Jeep Wrangler videos like this one on your right and if you have not been to our website on the bottom link to this vehicle on our website click those check us out and we really look forward to helping with this super clean 2017 Jeep Wrangler unlimited Rubicon hard rock thanks again