What you doing? I am texting really, really important people.  I'll call you back. How is she? She's... I don't have anything. And you follow us on Instagram and Twitter? It's awesome. Thank you. This is some Patreon follow. Oh no. She's squad. Oh no. BAM! Juicy content out of control. And follow someone personally. It's right down there. Oh man, this has never happened before. Anyways, we are reacting to a malalium trailer. Sweet. It's called Ima Yao. Watch your language. And... I dislocated my shoulder. Oh, it's hot and humid in here. Where's your top and powder? This is from Lidro. Jose. Oh. How do we say it? Yeah, you were right. Jose. We originally were doing it in the wrong... Because it looks like a Latin name. We were saying Lidro Jose. And it's not, it's Lidro Jose. Lidro... Lidro Jose. I think that's... If I'm correct, you guys taught me that. From what I remember... After we saw the tattoo... LJP is what he's referred to. Yeah, after we saw that film. The two films that we recommend the most was the Diaries one. Right. Something Diaries and then this one. Great. These are his two best films. Awesome. We also got something here that says, Do not read the synopsis. Okay. What's this called? I want to read the synopsis. So, we will not read the synopsis.  Stuff. Stuff that's... Right. As deeper meanings. And then also twists and stuff like that. One of the most exciting directors as far as my level. Yeah. In your level of excitement. Even before we start. Which one should we watch? Should it be this one? Should it be the Diaries one? Should it be something else? Let us know. Here we go. I'm going to read the synopsis. I don't know what it's about. Freaking love this man. Yeah, that's awesome. Freaking love this man. It does love this man. It did feel like a Francis Ford. Francis Ford Coppola. Yeah, it did. What's his name? Very stylized and just quirky and how he does most of his stuff. Did the hotel one? The hotel one. Oh, yes. Stanley Kubrick. No. No. Grand Hooded Best. Yes. He did The Islands of Dogs. Yes. Craven. Wes Anderson. That's it. I thought Wes Craven. Wrong Wes. Wes Anderson. Yeah. So yes, it felt quirky. Well, like he likes to do, obviously Wes Anderson is very quirky. This doesn't look like, this feels more Coppola to me. His obviously is more comedy, quirky style. Yeah. Coppola obviously I think is probably a good comparison for this one at least. And then maybe a little Alejandro and Yoritsu as well. Yeah. Right? I love the underlining score of the, I don't know if it was a trumpet or what it was. There was a couple of things in there. That was just going off. I skipped the entire time. I don't, I couldn't tell you what it's about. I'm going to look it up on IMDB. I'm not going to read this in the opposite. So don't look. Okay. Cool. I skipped this in the opposite. Apparently it translates to RIP though. Ah. All right. Which is rest in peace. Oh, no, no. Go away. Okay. I don't want to see the, I just wanted to see who's in it. If it's, I didn't recognize anybody, but yeah, I didn't. But I don't need to. No. And it feels like, if that's what we're seeing, it looks like what we've already experienced to know is that the primary figure, and this is the director, that the acting roles are all supportive to the vision of the director. I saw a lot of handheld in there. Yeah. A lot of handheld. It looks like it's again a group of people in the same village or the same area. It's a, it's an experiential thing with that group of people. Um, but I don't even want to try and predict because if there's anything about this director, I think he wants you to know, uh, you can't, you can't put me in a box. So yeah. So the other one would be Angamali Diaries. Angamali Diaries, which we saw the trailer and apparently it wasn't the official trailer, which is, um, I think why we were like, what is going on? Uh, in it. But those are the two. I honestly haven't been this excited for a new director. A new director? Nude. Yeah. He didn't saw Vishal. He directs in the nude. Oh, really? Yeah, you didn't know that. That's really free. It's, it's a little confusing when he says action. That's true. Uh, but anyway, I've not been this excited for a new director, not only new in our discovery, but really new in his career. Cause it feels like his best work is about, you know, to happen in the years to come. He also had that new trailer that we just saw that's coming out here soon. I believe. Yeah. Yes. We saw with the weird goggles thing. Yep. Uh, so that'll be exciting. But so what should be his next film we watch? Uh, I would love to talk to the man as well. Absolutely. I would like to see more of his stuff. Yeah. I want to see a lot more of his stuff before we talk. Yeah. Because sometimes it's, it's, it's hard sometimes because sometimes you get these opportunities to talk to the people. Right. And I've gotten because the people that help us out, they said, do you want to interview blah, blah, blah? Right. And I said, well, I want to, I just want to watch more of their stuff. Right. Absolutely. And then just the one thing or the whatever we saw them in. Yes. Uh, you want to be obviously more familiar with their work and especially somebody that we seem to admire a lot. Yeah. Uh, and the malolium industry as a whole we admire a lot. And I think it's Malayalam. Malayalam. I think some of, we've been saying malayalam and I think it's Malayalam. Am I? Malayalam. Is that right? Malayalam, did we finally get it right? Malayalam. Malayalam. Malayalam. Yeah, the accent on the yacht, I think. Malayalam. Malayalam. That's right. It's probably not. Um, but yes, it looks interesting, weird. It's only two hours long. Yeah. Original. Um, I have no idea what it's about, but that excites me. Yep. Uh, if it's weird and quirky, like, um, and it has a message. Do you see one of those directors that likes to have underlying messages? I'd be shocked if he isn't. Most great directors do. Yeah. I'd be shocked if he isn't. It did remind me a lot of White House though. Especially the trailer for White House. Yeah, a little bit. I think the trailer didn't have much talking. Except for... What? What? What? What? What? Such a good moment. What? I love that movie. Such a creepy, weird, frickin' awesome movie. Yeah, that was... You haven't seen the Lighthouse. Do yourself a favor. If you want a good artistic... Um, weird. Weird film. Weird. It's so good. Give that one a watch. Two-person film. It got... It got snubbed last year. Really did get snubbed at the Oscars. And we got the honor of seeing Willem Dafoe and listen to that brilliant man. Man, when you listen... If you ever get a chance to see a video of Willem Dafoe talking about acting, watch it. Just know what the interviewer we have. Yeah, not the... Yeah, no, get a good interviewer. But if you just let Willem talk about the craft, that man, you listen to him talk and you're just... Can I just do one scene with you, man? Can I just do one scene with you? Because everything you're saying is making me so excited. Well, what's his next film we should watch and also the next Malalallium film? I need to watch more for Hapthaseel. Malalallium. What? What did you say? Mal... Malalallium? I don't know how to say it. I know and I love it. Let us know. Let us know.


Zelensky. War won't end while Crimea is under Russian occupation. President of Ukraine Volodymyr Zelensky has said that the war will not end as long as Crimea remains under Russian occupation. We cannot imagine Ukraine without Crimea. And while Crimea is under the Russian occupation, it means only one thing. The war is not over yet. He said in an interview with CNN. When asked whether there was any scenario under which there could be peace without Crimea, Zelensky said it will not be victory then. Zelensky called Putin's reaction to Yevgeny Prigozhin's rebellion weak. We see Putin's reaction. It's weak. He said Crimea has been a part of Ukraine for a very very long time and solving the problem with the Russian occupation of this peninsula may become a decisive issue in ending the war. This was stated by German Chancellor Olaf Schultz in an interview with the German television company ARD. Speaking about the provision of military assistance to Ukraine, the Chancellor noted that Germany would continue to train the Ukrainian military and assist in strengthening Ukraine's air defense, in particular thanks to the iris T systems. We have transferred a lot of tanks and we will continue to do so. But at the same time, we do not want the weapons we are supplying to enter Russian territory. Schultz stressed. The German official also recalled that even in the Soviet era, Ukraine was quite an influential state, becoming in particular one of the founders of the UN.


Our last and final speaker today is Devin West. He's a fourth year medical student visiting us from St. Louis University School of Medicine. And he's gonna be talking about CPEO. Okay, good morning everyone. My name's Devin West, as he said, I'm from St. Louis University. And I spent the first two weeks here at the Moran. This is my third week. So I spent the first two weeks in neuro-othemology clinic. And so today I have a case to present to you. So I will first present the case, talk about the diagnosis, and then thirdly talk about just kind of the take-home points for us to have in practice. So the patient was a 57-year-old Caucasian female without a chief complaint. She was referred to us by her neurologist. And her story started in May of last year. She went to her optometrist for complaints of blurry vision. It was her routine checkup. And her optometrist noted some bilateral limitation of extracular movements and referred her to an ophthalmologist. The ophthalmologist confirmed that she had cataracts, visually significant in both eyes. And confirmed that she did indeed have some extracular limitations in all directions, both eyes, and also had some bilateral ptosis with the right eye being greater than the left eye. Which per her history was present for many, many years. And so this ophthalmologist then, prior to taking any action with the cataracts, referred her to a neurologist for a workup. Now speaking with her, her past medical history is significant for diabetes type two. Her last A1C was 9.7 in December of last year. Asbestosis and abnormal thyroid, which had been detected several years prior and she had had an ultrasound and it was determined to be normal and just kind of benign, multinodular type picture. Depression. And following the workup, she did have cataract extraction bilaterally in April and June of this year, which resolved the blurry vision. And her surgical histories there as well, some C-sections, cholecystectomy and tonsils and adenoids. So her family history, she has no family history of any muscle issues, no progressive weakness, no history of miastinia or any autoimmunity specifically, we asked about thyroid disease. She does have a fairly strong family history of Alzheimer's disease in both her parents and several aunts and uncles. Coronary artery disease and coincidentally, she has an aunt who is a non-blood relative that has a mirf. And her daughter, when she came to clinic to see us, her daughter was there with her and her daughter said that she from time to time has diplopia, has some double vision and has been told before that her movements are not completely normal. So I mentioned she was referred first to her neurologist and this was the workup that he had done. He did first some blood work. He obviously checked her thyroid, which was normal. She was negative for any anti-acetylcholinestrates or acetylcholine receptor antibodies, but she did interestingly have an elevated lactate and pyruvate. MRI was normal, bilateral carotid ultrasound was normal, swallow study was normal and he also did send her for some genetic tests. ANT1 opal 1, POLG, twinkle and milis, which were all negative. And then referred her to us for confirmation of the diagnosis, which of course is CPEO, Chronic Progressive External Ophthalmoplegia. So on exam, this is what we found, fairly normal except for stereo. We noted that she had limitation or poor stereo vision and facial, in terms of cranial nerves, she was normal except for a few noted weaknesses that are here. Bilateral, orbicular, succulite weakness and an incomplete blink in the right. And we'll look at the doll's eyes, movements in a second. Her thyroid was non-palpable and on slit lamp and fundus exam it was unremarkable, except for some peripapillary pigment changes. So I'm gonna play this video. This is Dr. DeGree doing her extracular movement exam and there's audio. Can you follow my finger with just your eyes? And you can see that she has limitation of gaze to the right and to the left.  I'm gonna check her saccades. Look at my thumb, finger, over here. Over here, can you look over that? There you go, thumb, finger, and there's slow, thumb, down here, finger, finger. And slow there as well. Now close your eyes as tightly as you can, tight, tight, tight, tight, tight. And I can easily overcome it. And as you can see, she has tighter. She has very little bells phenomena. Her eyes don't roll up when I have her. Close her eyes really, really tight. Yet she has really good facial musculature. Keep your mouth closed now as I try to open it. Very good strength of her mouth closure. Can you focus on your finger here?  Just try to keep focusing, focus, focus, focus, focus, focus, focus, focus, focus. And maybe she can overcome it a little bit.  She can get down further, keep looking down, but we're not able to really overcome that up gaze parruses. Okay. So very typical findings of CPEO, which we'll go over in a minute. So Chronic Progressive External Thalmoplegia first described in, as early as 1856, by Dr. Von Graf, who was instrumental in glaucoma and also pictured there designed the Von Graf knife, which I believe was used for cataract surgery for several years in the past. So the main symptoms for CPEO are progressive bilateral limitation of vision with progressive ptosis. And one study showed that the most common symptoms were difficulty with small print and difficulty with driving, so almost a convergence, divergence, insufficiency type of picture. But most patients are asymptomatic and often do not complain of dyplopia.  And actually, I didn't show up, but on exam she also had about 12 exophoria, which was similar in lateral gazes. But again, she did not have any dyplopia. So etiology for CPEO, it's not specific for any single disease. However, it is the most frequent manifestation of mitochondrial myopathies, hence the genetic workup that the neurologist performed initially. Now the history of etiology initially, it was just sort of thought to be a neurologic process. And then an early biopsy showed myopathy and so then people said, okay, well it's myopathic. But then brain biopsies from patients with CPEO showed some spongiform changes. So then it kind of swung back to the neuropathic side. And it wasn't until Olsen and others in 1972 did biopsies that showed the prominent ragged red fibers that we know from mitochondrial myopathies. And the consensus today is that it is a myopathic disorder. However, it is multi-system and may involve the nerves as well. And interestingly, there's no genotype or phenotype correlation. There may be, people may have CPEO with none of the non-genetic defects. And specific defects are not associated with any worse prognosis. So there's a list there at the bottom of some of the other differential diagnosis considerations when you find CPEO. But again, the number one or most frequent, it is the most frequent manifestation of mitochondrial disease. And so that's what we should think of first. Now, most important with CPEO are the associations which are listed there. Most we can observe on exam. A couple require that we take more action to get more objective data. That would be pigmentary retinopathy and the cardiac conduction abnormalities. So in terms of the evaluation, again, we've sort of already touched on all these blood work to rule out myosthenia and thyroid. Muscle biopsy which can show in the top right there the ragged red fibers on Gamori trichrome staining. And ECG, which is kind of the most important. And these patients are prone to heart block, syncope and sudden cardiac death. And so when CPEO is found on exam, that is one of the most important, if not the most important thing that we do. Fundus exam, ERG, MRI to rule out any mass or cerebellar involvement. Oculofaryngeal dystrophy is on the differential and so that would be the reason for a swallow study. And plus or minus Tensilon test for myosthenia. However, the Tensilon test, as you know, increases the acetylcholine which can slow the heart and in these patients that are susceptible to heart issues can be a dangerous thing. And then as always the genetic assays. Treatment, there's not too much treatment. We can divide it between mechanical and medical. You can use as pictured above the ptosis crutches added to glasses or tape to help the lids stay open. Strabismus surgery is sometimes performed but with a little bit of hesitancy because these patients obviously are myopathic and the muscles do not react to surgery or adapt from surgery as normal muscles do. And then some medical treatment. One study showed that coenzyme Q supplementation improved neurologic function and decreased the lab values of lactate and pyruvate but did not improve the CPE or the ptosis. So and others, other supplements are sort of anecdotal. So back to our patient. She, we did a full field ERG which was normal. We recommended that she have an annual EKG. We did a Humphrey visual field which was also normal and her daughter reported some of the similar symptoms that I mentioned in the family history so we counseled her daughter has never sought a work up for this and so we thought that she might be interested in that in the future. But these are the kind of the take home points. It's progressive extracular muscle restriction or limitation with weakness and ptosis. It's the most frequent manifestation of mitochondrial disease. No proven treatment exists. However, some anecdotal evidence is there for some supplements. And the serious complications include cardiac conduction, defects, retinopathy, endocrine abnormalities if you'll remember she was diabetic and dysphagia. So I wanna thank the neuro team that I worked with for the first two weeks for their teaching and help with this case and everyone else I've met I've had a great experience thus far, thank you. Any comments, questions? Okay, thank you.


I'm Phillip. I'm from Hamburg. I'm a software engineer. Works for a little online, online shop. I'm a GitLab hero. I got into GitLab and thought this is really cool. I don't have to set up a huge management tool or something for building pipelines. I started in a small company. I introduced them to use GitLab. Since then I'm focusing on using GitLab for everything, but only on the technical side. I influenced my colleagues to use issues as well. It's only one tool.  I think GitLab is the most powerful solution for us. For me, it's felt like home. It's feels like home. Every project is in GitLab and you can use a search. For example, a project and you see all the other information also there. There's only one way to find a documentation, for example. It's really cool to work with GitLab in the issue way. You have comments there and it looks good and it's really easy to use. I don't have to think about too much stuff. You can focus on getting things done.


U.S. pharma major Johnson & Johnson will not enforce its patent on the TB Doug by Dacqueline. How did the company come to make this announcement? And what does it mean for millions of TB patients around the world, but particularly in low and middle-income countries? The U.S. House of Representatives is looking for a new speaker after Kevin McCarthy was voted out. Why did this happen? And who might replace him? We find out why Guatemalans, particularly indigenous communities, are on an indefinite national strike demanding the removal of the country's attorney general. Salam, you're watching Daily Debrief coming to you from a different setting today, because the Delhi police's special cell raided the People's Dispatch and Newsclick offices and have sealed the office as well as the studio from which we normally operate, but we're using the internet to continue our coverage on Daily Debrief and on People'sDispatch.org. If you haven't already, this is a good time to like and subscribe to our YouTube channels and of course also share this video with your friends. Our first story is a big one. U.S.-based pharma major Johnson & Johnson, as I was saying a little while ago, has announced that it will not enforce its patents on Serturo, which is its brand name, for the salt bedakwiling, which is a path-breaking tuberculosis medicine, the first drug of its kind to be approved for wide usage in about four decades. It offers the opportunity to sort of increase access to TV medication for millions of patients around the world. And this will apply in 134 countries, low and middle-income countries. It's the result of sustained campaigns, sustained pressures from multiple groups and also comes soon after the Indian Patents Office rejected an application for a second patent on the drug by Johnson & Johnson. Joining us with all the details is Jyotsana Singh, health journalist Jyotsana Singh, who has been on the show frequently. Jyotsana, good to have you on Daily DB, as always. Tell us first how this came about, Jyotsana, before we talk about the massive impact that it's likely to have on the treatment of TB. So firstly, I think congratulations to you all for actually doing this Daily DB despite all the problems that have been imposed by the government and the Delhi Police as a special cell. So this is great and thanks for calling me. So yes, it is a really big development in the field of medicine and health sector. After decades, we have received something we have been able to break patent barriers which will give access to a lot of patients across the world. Before this, it happened in the early 2000s when the HIV medicines actually, there was a fight and the generic versions of those medicines came about. So it's a big deal. But this is no charity by the company. It is not that their hearts have changed. It has come, as you said, after a lot of struggle, a lot of struggle. I remember I started writing on this topic and started working in 2016. Since then, so many organizations and individuals have fought and the TB survivors and the TB patients have fought since 2016, at least or maybe before that, to really have this medicine cheap and accessible and available to everyone who needs it. So that is the thing. So just to ensure to tell you what the issue was, Johnson & Johnson is the company which has, which is the original company for this medicine Vidakulin, which is a very, very important medicine for drug-resistant TB. And before that, if you do not have this medicine in your treatment regimen, then you are dependent on certain other medications which have terrible side effects, something like an injectable called canamycin, which leads to permanent hearing loss. There are medicines which give you psychosis, make you suicidal. So we need it to replace those medicines and this particular medicine has a very good safety profile. But Johnson & Johnson held the patent over the medicine. So normally, something what is called primary patent, that is a basic patent on a medicine, it lasts for 20 years. So for 20 years, a company has complete monopoly over the medicine, they only manufacture it, they only sell it. After that, what kicks in is called secondary patent, where just by tweaking the medicine very less, like very little tweaks the company can do and extend this patent for many more years. In this case, it would have been for five years. So they wanted five more years after having after having had the monopoly for 20 years, they wanted more. And that is what the secondary patent which was, they applied for across the world despite the hue and cry by so many people, including patients affected by TP. So they did that. But then in the past few months, quite a few things happened. So as I said that people have been fighting since 2016, which has forced the governments also to take a stand finally on these issues. So the Indian Patent Office rejected the secondary patent application of this medicine. And that patent opposition was actually filed by two very courageous women who both survived extreme drug resistant TB somehow, but have faced terrible side effects. They went to the court saying that we supported others should not. So that was a big victory. Then after this, the Ukrainian and the Belarus governments, they actually asked Johnson and Johnson to drop this secondary patent in their countries. And after that, the South African governments competition commission that is their body, it has actually launched an investigation for NJNJ on JNJ on the pricing of the medicine and on asking for secondary patent. So there was a lot of pressure on JNJ finally that came up. And as in one of the shows, John Green, the famous American writer and YouTuber, he said that, you know, we have had these medicines for a long time. You just have to give it to the patients and they will be saved if they still die. It is because of the system. It is because of something else. And for the drug resistant TB patients, for a lot of them, it was this medicine which was one of the medicines, which was the reason. So yes, so it is good that the Johnson and Johnson has said it will not have secondary patents. Already, there are three companies from India who have the capacity to produce these medicines and it will happen. And just very shortly to give you a few numbers. So we have something around 1.6 million DRTB patients every year in the world. And if you look at the data, not more than 10 to 15% of them have actually got this medicine, though it should have been given to all of them. So that is where we are. More companies also mean more production, not only the price drop, which is very important, but also more competition. In terms of price, we talked about South Africa. So I am just giving an example. In South Africa, bit alkaline per patient costs something like 285. Let me try to interrupt you. I know it is my internet, but we are having a bit of trouble with your audio. Could you just take us through the last bit that you said once more, please? So if we talk about the pricing in that sense, how cost-effective bit alkaline is. So in South Africa, it costs something like US dollars 285 per patient. And it is only one of the medicines out of a cocktail of 4 to 6, which are to be given to the patient. So if we add the cost, it becomes a lot more than this. So now it will be cheaper. And Indian generics, when they start to produce, we will have more courses being produced. We will have cheaper courses for patients to grab. And so it will be good. And we should really thank the activists and the TB survivors who have continued to fight for this. Right. So by as much as two-thirds, perhaps the cost of the overall medication can be reduced, Josna, if I'm not wrong. Very quickly, because we're almost out of time. Very quickly, if you can tell us what happens next, this is by no means, of course, the end in the struggle to get TB medicines to patients. Yes. So we still have many more things where the prices should come down. One major thing is that the test for drug-resistant TB, that is by this company called Seafit, which is one of the subsidiaries of Dana, it costs a lot. They were charging 10 US dollars per test. They brought down the price a few weeks ago to eight dollars. But actually, even if they get reasonable profit, they should not be charging more than five US dollars for that. So that has to still come down. And the government and the company has to take a stand. Then there is another medicine called Delaminate, which is by a Japanese company called Otsuka. It is actually costlier than Bedakulin. And that is one medicine which is very safe for children. And when I said that you, what are the problems with older medicines? So there is this injection which you have to take daily if you do not have Delaminate or Bedakulin. And there are children who are given these injections for six months every day once a day. So to stop all that to happen, Delaminate is a very important medicine. But still there is no commitment from Otsuka to drop the price or to give up the patent. That has to happen. Pritomanid is a third drug, which is also, there are patent claims on it across the world. That, again, has to be fought and the companies should be asked to drop their patents and stop the IP barrier for all of this. I think if all of this happens, then we can actually think of eliminating TB and not before that. All right. Thanks very much, Joseph, for kicking off the show with that actually really important and historic in many ways story and hopefully it continues. And we'll have you back very soon, I'm sure. We're moving on now to the US where the Speaker of the House of Representatives has been voted out in what was a right-wing revolt within the Republican Party. Anish is with us and will tell us hopefully what this means because this is one of the most important political jobs in the United States. Anish, good to have you on debrief. Yes. Yeah. So just take us through the process. Anish, it seems to be the culmination of a thing within the Republican Party and McCarthy that's been ongoing for quite some time. Yes. I mean, we did the election itself, McCarthy's election and how it took about about 15 rounds of election for him to actually secure the seat. And it came pretty much with this one major concession, which was that a single member in the House can actually initiate removal process for the Speaker, a no-confidence process that we would call in our parliamentary system. And it clearly has come to bite him right now. And this is kind of historic in many ways because it's the first time that a Speaker has been removed while the legislature, the US Congress, was in session. And that pretty much brings the entire process of federal legislation into completely uncharted territory because they never had the system of having to deal with a temporary Speaker or, I mean, even the Constitution and the legal system is pretty much very vague on how this legal, sorry, this temporary Speaker is going to function. But obviously, the fight or the infighting that we see within the Republican camp is pretty much coming from a very interesting set of issues. First of all, we see that this was a very small minority that actually brought about this vote barely about eight people from the Republican Party who voted in favor of removing McCarthy. The rest of the votes were pretty much Democrats. So the small group of people belong to, as we all know, from the freedom caucus within the Republican Party, which is basically the very far right, usually known as the most pro-Trump section within the Republican Party. And they are the ones who have been calling for a set of cuts, major cuts in government funding and also spending on the Ukraine war. And it's quite interesting, the kind of issues that have come up because of this entire process. And it pretty much shows the kind of divide that even the most rapid right within the United States is going through, the kind of confusion it is going through within the elite, the ruling class and the US establishment itself. So Anish, given the importance of the job of the Speaker and the kind of level of seniority that the Speaker of the House occupies, what happens next? And who is likely to replace McCarthy? It's a very difficult thing to say who will be next because pretty much there's nobody right now who has a very clear support from across the section. What we're seeing is a very clear divide that is not very easily reconcilable within the Republican Party. And obviously the Democrats are having a field time of their own. But if things do not fall in place by say early November, even they might be in panic because that is pretty much the deadline for the temporary spending bill that McCarthy passed, which was the reason why he was kicked out of the office for gaining democratic support. And so if they do not have Speaker by then, they might not be able to pass a spending bill and which brings the government into a shutdown, a partial shutdown. But most importantly, first ever default in the over $31 trillion of US national debt. And so that is a major problem that like it's a ticking time bomb right now that the entire House has been brought into. And it pretty much is a situation where the Congress has been kept hostage by a small group of right-wingers who are not, let's remember, who are not that radically different from the other conservative counterparts within the Republican Party or even many of the establishment Democrats in the US Congress because considering many of their policies itself. But it's just that how averse to concessions that this small group are is what concerns the US ruling class. And this pretty much exposes a whole lot of laws within the US congressional, presidential system, the manner in which things function. But also it exposes fault lines that was always simmering within the ruling classes. And that pretty much is a situation. So you have obviously Jim Jordan coming in, who is the leader of the Freedom Caucus. But then there's also Skelly, who is the House Majority Leader. If you look at them, they're not that radically different. Both of them are very vehement Trump supporters and pretty much supported most of his policies while in presidency. So they're not that very different from each other. So we do not know what kind of change we can expect in the coming days or if there is going to be a timely change for the speaker's position. Alright, thanks very much Anish. And I'm sure you'll keep tracking that for us.  They're on an indefinite national strike that began on Monday. The strike was called last week and it's been called in protest to demand the resignation of Attorney General Consuelo Pojas for her attempts to intervene in the country's election results this year. Zoe Alexandra has been tracking that story and let's go over to her now to find out what's going on. Zoe, good to have you on debrief. Hope you're well. Tell us what's happening in Guatemala at the moment and since it's been on since Monday, what sort of progress has the strike made? Well, it's a super crucial story and as you said, we've been tracking it at People's Dispatch in essentially this repression against the semia party of the presidential elect Bernardo Arrivalo, which is essentially that these protests are against the actions that are being taken by the Attorney General against this president elect and his party and this all started in the first round of the presidential elections in the country where Bernardo Arrivalo, who is from a center left anti-corruption party, came in first in the first round and this was very shocking that he would be going to the second round of the elections. Many of the establishment politicians thought that they had it in the bag. They've been able to rule over Guatemala for years and all of the privileges that that comes with and so as soon as they saw that someone like Bernardo Arrivalo, who consistently speaks out against corruption, who has really allied himself with the movements in the country who has tried to take a stand against establishment politicians, when they saw his rise they said, okay, we need to use all of the instruments that are disposable at our disposal to act and so starting then the prosecutor, the attorney general began a campaign of criminalization against his party suspending the legal representative of the party attempting to make the party kind of inexistent and constitutional saying that it doesn't have legal status, even actions taken against Arrivalo himself going into the second round of the elections. I think the legal status of his parties, Moimento Semi, it didn't even exist, but again, he still went to the elections and won the second round of the elections against former First Lady Sandra Torres. And again, one of the first things he said is that he's going to defend his presidency and he's going to defend the votes of all of the people in Guatemala who voted for him and that he wouldn't tolerate attempts by the right wing to basically invalidate this election. And since then, since his victory, these attacks against him have increased and it's been interesting because as you said, the protesters now are demanding the respect of the electoral results and also the resignation of the prosecutor because it's essentially been sort of this conflict and this dispute between different, not different branches of power, but different institutions within kind of the legal system. So we see on one hand, the Supreme Electoral Court is validating their results and saying that yes, indeed, Moimento Semi can exist. It is a party. They won the elections. These are the results. And then we have another court saying that no, these charges have to be carried out against him and that, so it's been this kind of back and forth. This week, for example, a bunch of lawyers brought a letter to the constitutional court and asking them to reverse these moves that the courts have taken against the party Moimento Semiya. Currently, Arevalo is in the United States meeting with all sorts of different representatives to ask for their support, to say that he won the elections fair and square and that democracy has to be respected. What's interesting in this case is that there's sort of been unanimous international consensus in saying that Arevalo did indeed win these elections and that all of these attempts, for example, by Sandra Torres to not even respect these electoral results are undermining democracy. We've seen state department officials say this. We've seen officials from Europe say this. So there's kind of complete international consensus that what's happening now does constitute what the US would say is an attack on democracy, maybe undermining democracy, and what people in Guatemala are saying is a pending coup. And so that's why we've seen people on the streets saying these attacks continue. They've consistently protested and now they're actually going to this national strike to say no more.  We demand that these legal bodies do not be used in this kind of law fair scheme to invalidate their votes to attack the president-elect. Zoe, how are things likely to proceed over the next few days? Well, as I said, because there is this sort of international consensus saying that Arevalo did in fact win the elections, the Supreme Electoral Court, which I nicked out to mention, but has suffered several different raids actually. The authorities have raided the Electoral Court taking material, etc. And so I think that we are going to see that this situation will continue to escalate, especially as people march towards the capital city. Protests are expected to intensify. When Arevalo returns from the United States, I'm sure that he's having important meetings with legislators, with different think tanks, etc., to kind of get this support. But it seems unlikely and it seems difficult that the right wing will actually be able to sustain this attack on him and that in fact he will not be, it seems likely that the transition of power will continue, that he will be sworn in as president. But I think what's crucial is, and that we've, a lesson that has been learned, I think by progressive rulers in Latin America over the past several years, is that it is so crucial to maintain the pressure on the streets because the right wing will use all of the tools at their disposal. If they've been in power, they've definitely made maneuvers to occupy the courts, to occupy all possible spaces of power and that even if the executive is occupied by progressive, they have all these other tools at their disposal which they will use. And so I think that the streets which are historically of the people in progressive movements and those who want change and fight for change have to be, I think are recognized as an important tool in order to kind of maintain and consolidate power and show that the people are on the side of democracy and of having their votes respected and that if this doesn't happen, there will be a response by on the streets. On the streets. And I think that's a great note actually to wrap up this episode of Daily Reviews. Thanks very much Zoe as always for being on the show and of course for the work that you do. We'll be back with another episode hopefully same time, same place tomorrow. But again, take this opportunity to ask you once more to support us and the work that we do that people like reporters like Zoe do by subscribing to the channel of course. You can also head to our website peoplesdispatch.org for details on these stories and all of the other work we do. Thanks very much for watching. Stay safe.


Thanks Laura, am I supposed to keep time or is someone else keeping time? Wonderful. Oh fantastic so We had a phone conference about a week ago to discuss some of the potential topics for discussion in your materials There are some draft questions as well for session one and these are some that are a little bit Beyond that we've heard a few times this morning The question raised Whether genotyping should come before the phenotyping whether before patients are seen at a center It would be useful to get Whole exome or whole whole genome sequencing done first prior to their visit. I think that's a Major topic to discuss and may depend very much on what the goals are at the time We've heard that about half of the diagnoses are genetic and we've heard about half of the diagnoses are not based on genetics Even though they're probably all genetic disorders You could you know, that's half full or half empty I guess depending on your perspective I think an overarching question I had as I first got involved in in while learning about the network and And thinking about some of these things is who's the who's the network for is this for patients? Is it for scientists? I think the answer obviously is it's for both, but how do you balance the scientific goals? Which is often discovery almost always with the the needs of the the patients and the and often their local clinicians who are Looking for guidance And then a third one was is really, you know, what it what is the feasibility to having a standard approach to deep? really deep and comprehensive phenotyping across clinical sites across clinical specialties even and And back to this question of whether having certain sites in the network have specific areas of clinical expertise or whether It's best to to really be able to provide a comprehensive evaluation So let me open that up to the discussion, and I can't see everybody's name, so I'm going to point and nod So Sue Berry from Minneapolis So one of the things increasingly in clinical genetics that is emerging is a lot of us are taking the approach of starting out by Looking carefully as much as we're smart enough to do to figure out a handful of specific genes to look at And once we get past those people are saying go screw it Do an exome and so increasingly I think you're going to find that people are going to come to you with exomes completed and possibly negative How are you going to incorporate that data because you're going to need to it'll probably have to be reinterrogated because maybe it wasn't analyzed with the Act well, whatever we call now accuracy that will be required to ultimately define this and how do we how do we Because this what you're going to have is a combination of clinically accessed Standard clinical activity that's going to come to you Before you even see the patient because after we given after we get an exome and we got nothing then we're kind of stymied So what do you think about that guys? Yeah Rachel Ramoni from the coordinating Center So we have even in the early days had an experience of a previous exome Being brought in and those those are re-analyzed typically and in fact in one case They found what they believed to be a an entirely novel diagnosis on the basis of that of that reanalysis But you're gonna have to have a systematic way to do that because increasingly that's something you're gonna get from the beginning Yes, so those typically are being done at the clinical sites And so each site has its own means has its own pipeline So there there will be some variability in how they are analyzed But we hope also that the variability can be leveraged There's even talk in the network of sites taking you know taking an individual Exome or genome and analyzing it through their through their own pipelines if for instance at first it comes up negative at one site So I think You know Clinical utility and clinical exomes are going to focus on known genes and disease variants I think it's and at Baylor we've had the experience where when those exomes are moved to a research setting you increase the yield Not surprisingly, so I think the bottom line is that It's a continuity and a continuous process. There isn't it's not really, you know binary decision and Really at the end of the day my my sense is we should focus on what is most effective and efficient for the patient you know in the optimal world you would have an exome that's done clinically or and then Research interpretation and then you bring the patient in but I just think that you know at the end of the day of Integrating clinical practice into research you have to be practical and it's gonna be context-dependent so as I was sitting and listening to the Discussion and presentation earlier today. I kept thinking is there a difference between unknown diseases and undiagnosed diseases meaning These are entities that that we or certain individuals with specific expertise know Exist and it just takes putting the right information together like the diagnosis as opposed to as we as we well Know the monthly or weekly New disease relevant mutations or new disease relevant genes that are being Described and it seems to me that there might be a difference in how to approach those based on what the what the prior Suspicion is of different entities So Howard Jacob from Hudson alpha, so I want to come back to the question about The exomes and I think one of the challenges you're going to find is it's not so much on the technical side of Sequencing the genome whether it's exome or whole genome or the analysis But it's going to be the comfort level of the physician on being able to make the call So it's the classic end of one and so obviously if the variants been known to cause disease before It's much easier, but I see a huge range in in a physician's Boundaries if you will of well there will they'll make a call some will use model organism databases data some won't some want to have ACMG guidelines before they'll make a call others will go into the research And I think one of the big challenges is more on the clinical side than it is on the technical side of reading the genome and doing the analysis so I think one of the other things that is striking is just how much Pliotropy there is and that there are You know genes that many of us associated with a specific disease where we now know that well, maybe there are 10 or 15 major phenotypes that are different that can result from that and then on the other side of course the heterogeneity and so again it may depend very much on what the what the History is of this individual patient whether the first approach should be more careful phenotyping to guide Evaluation versus a broader brush No, I was going to say just along the same lines that we all we talk a lot about Best practices for this particular point of genotype first versus phenotype first There's certainly no best practices and that might be that could be a goal of the UDN within the UDN I know that there are Widely different approaches some sites do phenotype first We we at UCLA do the exact we do the exact opposite We don't the patients doesn't set foot at UCLA without a genotype with a whole genome or whole exome and That that has been Interpreted maybe on a what you mean Brenda I think by research level it was sort of like lower a little bit the the threshold of potential variants to be Explored to phenotype because we think that one of the practical issues is whether the deep phenotype if it's going to be The same for everyone then of course it doesn't need to be guided by a genotypic investigation But the question is is deep phenotyping for absolutely everything at every single You know organ is it is it practically feasible in in in sort of the real world of of managed care? I'm not sure about that This probably is a bit heretical, but if 75 percent haven't been found when DNA has been done We're all geneticists, so we know this genetic modification, but my question really is aimed at There must be other things like exposures to toxins the natural history Something happened in childhood that is actually what's going on Travel so that you were exposed to bugs and my question is really how much of that kind of data is part of the standard Workup so that if somebody had grown up in Africa you would know it and that would be Directing you to think about their genetic interaction when in the African either environment or Infectious disease So that's a good question, and I think You know certainly we've had some consideration that I think dr. Lee's case of earlier today My view of that as a non-geneticist was boy that was a situation where really the the phenotype in the history really led What what ultimately was a genetic probable answer? There are certainly things that can be sent through the mail. There are certainly things that can be shipped electronically One thing that can't be shipped electronically is the patient and there are some things so as a neurologist I know there are certain things that can be done as physiologic measures that may be Only one or two places in the country have the expertise to do it, but can be the essential diagnostic test To to make a diagnosis or to help interpret genetic testing So so that's the thing that you really can't do is the is the physiology So I'm suggesting though there will be pieces in the history the best source of history is grandma and My guess is grandma doesn't come very often But grandma remembers that something or other happened and I think as we move forward We're going to be really wishing we had more early childhood information or Exposures that that was a really dirty plant in the coming, you know, whatever There is a I was going to say there is a detailed exposure questionnaire as part of the the network Two questions now One is that as people will come with Genomes sometimes they have what looks like it could have be a causative variant But the clinician is really not in a position to explore that further. Is that the kind of case that might well be almost a shortcut to Directing information about About learning about that case And then the second question is how are we or how does how does the network propose to think about? epigenetic variants that will impact phenotype Anyone want to take a stab at addressing those? Well, I can talk about the first case we have seen cases where the diagnosis was already made But the referring physician didn't sort of accept that diagnosis because as you said, there's pleotropy. So specifically A really good gene variant was found and was reported as a variant of unknown significance because even though it was deleterious it was Didn't fit into the clinical phenotype and it turns out that all the clinical phenotypes associated with that gene were loss of function and This was a gain of function or at least, you know, we're pretty sure of that So that'll happen a lot of times and I think those are suitable candidates for us to pursue Because we really can't expect referring physicians around the country to know about those research aspects of it or the you know, the variability of the Potential pleotropy because it hasn't been defined yet As far as the epigenetic stuff someone else can take that Where do the where do the UDP patients come from are most of them? within a convenient drive to a tertiary Or research medical center, or do most of them come from more Rural areas or outlying areas they come from all over the world, but actually if they're in a rural area They're less likely to have had a tertiary care workup Which is required for us to accept the patient, you know having eliminated all the other stuff I would say about a third to Maybe even a half of our patients have been to one of the major medical centers Such as the Mayo Clinic or Hopkins or Cleveland Clinic or Harvard or Stanford, you know One of those Baylor places type places actually probably a half maybe even two-thirds Their comments or our discussion. Yes Good way of tapping in into that population for the future the population that hasn't been assessed at this point So there has to be another pathway Created to give patients the access Sure whose responsibility is that government well Okay, so I'm hired by the government Wendy If what she's sort of talking about is the justice issue in and and this this is There's two elements to this one of those the science which is incredible, but the other one is Access to care which is obviously Skewed in the setting if only half of the diagnoses are coming from genetics What are the other half coming from and do you have a way of knowing which ones are going to be which? So you know who to genotype first and then bring in versus, you know, do the whole work up I just have to say that a half of the diagnoses are not made from genetics It's much more than that What I said was that half of our diagnosis are made without using next-generation sequencing Okay, so a lot of these are like commercial stuff or get an enzyme assay or say things of that sort But I think that probably 90% of our cases are known to be genetic And as you said perhaps 100% of of all cases are genetic By suppose some trauma is not but nonetheless I mean it seems to me if it's 90% plus that are genetic Why wouldn't you get the genetics first and to lead lead your phenotype? And if I might answer the reason is that some of our patients who come to us at the NIH We don't get any genetics on because they don't They don't have objective findings. We sometimes make mistakes like that. Not very often anymore but or sometimes we can look at the patient and do a phenotype and Foon phenotypic analysis and make the diagnosis without any genetics at all and that means that we're wasting Exomes and genomes beforehand which subsequently have a responsibility associated with them, you know Incidental secondary findings getting back to the patient. Tell me what the results were etc. And And so it creates an additional burden. So I would I believe that really our phenotyping should dictate and guide our Genotype analysis rather than having our genotype analysis of basically guide a phenotype And why would you alter your phenotype? Incredibly much Because when you do an examination of a patient and have all your consultants around It's important to find out things and ask the same questions of one patient that you would of another You know not completely but to be thorough enough to look for things that you might not have thought of Based upon a genotype But just to push a bit more I mean if you figured out either the cost the time or the burden on the family to do this very wide Phenotyping and what the yield is have you done that type of analysis to know that versus taking a very targeted approach Which might be even deeper in a specific dimension if you were guided by the genes No, that type of analysis. We haven't spent the time on I Would just follow up on the last comment though. I think in terms of You know the long-term goals and the data generated by the UDN Identifying a gene before a patient scene is very satisfying from the standpoint of the family You don't have to travel etc. But in terms of generating deep phenotype data and linking that to genetic data linking that to other data and and Expanding the ongoing development of the Bioinformatic tools for future, you know, you lose that if you don't do the process And just back to the idea of plyotropy to or off-target effects that you know having the genotype alone may tell you very little about what is causing disability or what you know, what symptoms are Worth focusing on treating as opposed to you know, you have a ABC XYZ 3 2 Which means almost nothing to the patients and so it's in the that Conversation based on the phenotype. I think the very often is the most useful information for for the patients Yeah, I'm gonna take a stab at your question about epigenetics Okay, I definitely believe that I think whether there's data or not We all believe that epigenetics will explain a component of the missing heritability that we see and I think that the UDN is a perfect Venue to begin to explore this return of clinical application because you have deep phenotyping information We have deep genomic information and so I mean for example, I mentioned we're doing RNA seek part of the reason for that is You know to ask the question Globally in blood, do you see evidence of altered expression in the transcriptome which you could relate back to Not just a primary genomic defect if you had a gene candidate that was expressed But really also in fact an epigenetic alteration if you didn't have a structural or you know a mutation So I do think this is exactly a question that we need to be tackling in the future because that's the next stage of clinical diagnosis Time for one more. Yeah, I wanted to get back at the earlier question about diversity in UDN and so So one way to do that. I think and what the model we have trying to follow in Tennessee Is actually provide phone directed consultation. So because of The way we have advertised UDN services in Tennessee We will occasionally get physicians calling us from rural communities who Have a patient and they want to know Based on the presentation The patient may have or has whether that patient is suitable for UDN and we can Give them a good idea about our advice about hey, this is what you have to do You're close to Memphis go to and we have contacts you can go and talk to this physician And this is the pathway to starting a sort of baseline work up So I think that is probably one of the ways that we can Help a lot more patients and the follow-up to that is that we All sites or the one the sites that are going to be doing this They need to have a metric and record this because I think this is an important point that not only that UDN saw X number of patients in their site, but they actually helped guide Through a physician or a subspecialist in another medical center Care that actually helped that patient Okay, so our time is up. Let me just take a couple of minutes to to summarize I'll leave I'll leave this up. I think Certainly this issue of genotype first versus Phenotyping first probably there is no right answer And I think depending on who's doing it one approach may be more efficient the other But I think that is something for for discussion going forward. I think that the the main Importance I think of of having a network like this is is to make sure that all of that information is captured So that as was mentioned, you know, if you have a genotypic answer before you see the patient that may minimize the amount of Useful phenotypic information that is that is gotten but certainly Other ideas, you know for future and for areas of emphasis, I do think certainly ways of looking at Environmental early early life history elements and potential interactions Will be Important and then the last question on the slide I think is still one that that we didn't discuss very much But one going forward the question will be should there be a reasonably at least a kind of a minimum core Dataset that should be obtained for paces with certain types of complaints across the network so that if you are seen at a UDN site Should it be you know really expected you will get a completely different kind of evaluation depending what sites you go To perhaps based on what their expertise is or should this be something where there needs to be some At least minimum level of uniformity of what type of phenotypic data are collected and in what way they're collected But I think that's that's a very good. I think future question Thanks John So we now have a break scheduled for 15 minutes for those of you who are seeking caffeine There is a snack shop off the lobby that probably will be able to provide some for you And we are due back at 10 20 and then we will have questions 2 3 and 4 before we break for lunch. Thanks everyone


Good evening everyone. I have a couple of slides. Let's let it come on the screen there. Yeah, so always the post-land sessions are hard. So I will try to make it as interesting and interactive as possible. The first part I can try. The second part is only possible if you contribute to it. So I hope to get some questions and we will discuss more. So what I'm going to tell you today, of course, the session is about programming. So I will speak about programming. It's been new to me also because it's a new technology. But we started using it in our few campaigns. So I'm basically going to tell you about my experience to two case studies on how we used it so that you get some perspective on where you can use and what can be the use cases here. To start with, so we started a repranding or a repositioning for Upgrad three years ago. We repositioned it as an upskilling platform which is cool so that the new generation working professionals are excited about it. It's no longer a very academic focused organization on brand. It's more about talking to everyone who we feel is a customer who can upskill and get a better ROI from their career. So that's what we started with.  The first step or first stage of brand building is the awareness. So Upgrad did not have much awareness three years ago. So the first thing which we did for the first one and a half year was building awareness. So the first few campaigns were all about telling everyone that here is something like Upgrad and this is the place where you should come if you're thinking about upskilling. Upskilling was always a very small market because we Indians don't believe in investing in ourselves. We believe that we out of college, we got a job. Okay, that thing is done. Now I'm focused on my job. But a lot of things have changed, especially post Y2K when with the change in technology, people didn't realize that even if you want to survive in your job, you need to keep investing and knowing about your technologies. So that's where that's what we took in awareness saying that, you know, this is important for everyone of you and Upgrad is the place to do that. When you do awareness, largely it's a company bombing game. That is, you need to ensure that you reach as much of audience as possible. It's the highest frequency. So a lot of campaigns originated with TV as the center because we were just saying, let everyone see it. And we were trying to build virality in it. So this, and this is where we went on IPL, we went on Shark Tank, things like that. And then we clearly, beyond this rank, post and pre and post campaigns, what is the brand's strength like. So we saw it steadily go up. By mid of 2022, we saw that the increment in awareness which was getting created with every new campaign was shrinking, which kind of gave us an impression that, okay, now we have started going into the next phase where people largely, the TV we are talking about, know about Upgrad the brand, but they are not ready to buy it. So which is where the second stage comes in, which we call as the consideration stage. Now why is consideration stage important for Upgrad? Because Upgrad, although it's a brand for upskilling, it means different things for different cohorts of audience. For techies, it's about a platform which features their own newer technologies. For someone who is not in tech or someone who wants to go into managerial side of things, it's a platform where you can do online MBA. We have courses for HR professionals, we have courses for finance professionals. We have, I mean, you say we have a very large catalog of courses. So it was important for us that depending on the cohort we are talking to, they see Upgrad as something which is relevant to us. And that's where we move to consideration phase because if it's not, they will just say, okay, it's an upskilling platform, it's not for me because typically an upskilling platform in India is associated with tech. So that's where the second phase is. Now the problem with second phase or consideration phase is that you're telling different stories to different people. And that's where we consciously decided that even may not be the right medium because you can't target people there. It's, I mean, it's just pray and pray largely. So hence our focus has been in digital. Now the issue with digital is that digital, I mean, not now, probably pre-COVID has been a very restricted, I mean, what should I say, the inventory when compared to TV. TV can take you through the two billions of people, but digital still was restricted. Things have changed. And when COVID happened, what we saw was, yes, the digital inventory exploded, but at the same time it became more and more complex to control your targeting at every cohort level. And that's where we started thinking about our programmatic. And I'll tell you more about that. Of course, we have not, I don't think we have reached the phase three, which is conversion. I believe we'll reach there when the value proposition is very clearly established and it's more about just reminding the customer at the right point that upgrade exists. So that, in my view, will take another two and a half years to get there. What is programmatic? I'm sure after a full day of programmatic conference you're all aware of what programmatic is. From a brand side or from a buyer side, it's fundamentally about purchasing through bidding and targeted placements on web and app assets in an automated manner. And this is, I would say this is an evolutionary journey. Initially, buying ad spaces, and if you have been in digital since the 2000s, you put a bid and the next day is when you will know whether the add or not. A lot of things change with Google improving this technology. This is more, I see this more as an evolutionary way of doing these improvements where you can now get access to your inventory and change things very fast. So I would say that this is also an outcome of very large digital inventory available today. In the US, the digital inventory available is bigger than the TV inventory today. In India, we are closing that gap. So it means that you have very complex and large inventory and the best part about digital is this is indexed inventory. So for a digital marketer, you have a lot of parameters to play with, which humanly, manually is not possible, which is where technology comes in and that's what your programmatic is. It is great for the publishers because they are able to get better CPM now where it's no longer a homogeneous pricing. It is good for the brands, especially in running experiments. And this is where we fell in consideration phase. This is super important for us because when you target, you really don't know if this target can build consideration or not. And when you are talking about consideration, your frequency has to be high. So it's a lot of money. If you're going to put in money and then look at it a week later, seeing whether it's working or not. With programmatic, these experiments turn around time becomes really quick. In one day itself, you can make a decision, okay, this is not working. I leave that inventory and move to the next one. So I felt when we started on this tool or this technology was really useful at the stage we were in and that's where we have been using it in a big way. We are also seeing that programmatic inventory is getting, I mean, the digital inventory in India is getting converted to programmatic inventory really fast. Almost 40% of the digital inventory available in India is now programmatic. Last year, and this I would say was a monument event in the life of programmatic. Truecaller converted their entire inventory into programmatic. And this is very, I mean, this is very relevant because what Truecaller does is that Truecaller now allows you to target the people who are getting calls from your competitor and when the competitor calls, they'll put your ad there. Imagine, Upgrad ad is shown when somebody from SimplyLearn is calling a customer. Right? And these things are possible. So these are just a bit of statistics. We have been seeing the growth in it and we are expecting that this will only grow. From a 40% we are expecting by the start of the next year we will see a 45% age. And at a global level also it's growing at a high 26% age here. I'm talking about the conversion into the programmatic way of doing things. Let me come to how we used it and so that I can tell you a bit on our campaigns also. So what we did when we moved into consideration phase is that we stopped promoting in our brand campaigns Upgrad the brand. Instead we started promoting the sub-brands of Upgrad which is basically Upgrad data science, Upgrad NBA, Upgrad Doctorate, so on and so forth. Now when we are promoting something like this the problem is that I need to target the right audience which is relevant for it. And that's where this kind of technology really helped us. So the first one which you can see right, why Tiren is very very important. This was a tech ad which we did. Now tech is easier said than understood because it's not one program. It's around five-sixth program. There's full-stack development, there's cloud, there's cybersecurity, there's big data so on and so forth. And today we can actually cohortize the audience to some extent who are interested in each of these programs. So what we did was we shot this ad in five different versions. And we used each of this version to target a particular cohort. And we saw that some of the cases it's working, some of the cases it's not working. Then we realized what is the right place to put it. So this is where your media is moving today. It's been about more and more about granularity, more and more about targeting, and more and more about the right product show or right messaging show to the right cohort of the customer. This is, I'll talk about this campaign but then we'll take you through the case very first. So the first thing which we did or as the consideration way of doing things was we started doing ads at a business unit level which is basically now I'm talking about the sub-brands of a brand. Now if I'm talking about sub-brands also, as I explained, the cohort has to be very, very relevant. And this is one place we started using programmatic. Why? Because you can target a cohort but you'll never know what is the relevancy of that cohort for a particular ad. The cohort which is, which may work for tech, may work for MBA also. So what did we do with the programmatic? We tested out, we experimented and we saw what is the response coming on that. Once you do that, then you know that this works there. So that's one place we used. The second was a very interesting thing. So I told you about how we created multiple ads for the tech portfolio. When we tried to do the same thing for our AI ML portfolio, we realized that from a consumer perspective there are multiple types of consumer who comes and takes our product. There are people who are tech, I mean people who have a background in tech. There are people who don't have a background in tech. Multiple different transitions, someone who is in tech wants to move into tech, someone who is non-tech wants to move into tech, so on and so forth. So we said that if we can do five ads and do it successfully, why don't we do 120 ads now? So what we did is, and somebody was talking in the panel on this, we used fuzzparty data from certain fuzzparty companies to understand the covers, understand our audience better. Then we created an ad using, I mean with two data scientists, very famous data scientists, and the leading ones, in the top 10. But that one ad, basically the data scientist is talking about how by taking this course you can transition into a data scientist role. This is what they are talking about. Now the problem is the person who is seeing this ad may be a tech person, may be a non-tech person, may be a person who has some exposure encoding, may be a person who has no exposure encoding, so on and so forth. So what we did was, sorry, yeah, so what we did, I'll come back to that, what we did was we created 190 unique segments. And we created around 150 versions of the ad. Now how do you create 150 versions of the ad? That is where certain AIML tools can help you. When we got the idea, it was a Cadbury ad of Shahbukh Khan. So it's the same agency we used with. We used an agency to use the primary data. We used another agency to create the 150 versions of the ad and then we used programmatic buying to target those covers. So you can see that the reach was around 8 million. The frequency was nearly 2. We saw that when compared to YouTube, which is typically the campaign, the platform you use, we had a 20% improvement in the CPC. The returns were also good. So I'll show you the ad now. Yeah. So now because I've told you it's AI, you will find fault again, but for a person who sees for the first time they have a problem. Are you a working professional looking to shift to data science and multiply your annual CTC by 5x over the next three years?  Take the example of Kailash Narangi, no coding experience, but got a job with a CTC hike of over 100% after doing data science from Upgrad. So do you want to be the next Kailash Narangi? Are the first you? So this person he's talking about is our actual alumni. He took the profile of that guy and we created lookalike, around 190 lookalike, clusters of lookalike. And for each of them, we had a separate ad. Now what I'm trying to say is with so much of data available today and you have options to really do micro target. You have options to change things through experimentation. That's where all these technologies will help you. So these are the few things which we did. I'll just add one more speak about our last current the current campaign we are doing. So you can see the three photographs here. So this is, we have not started programmatic on this. But what we are doing this time is that I mean, at what each Upgrad has, when compared to anyone else in the market, is a large number of alumni who have successfully done transition after starting from us. And these are two stories. So we said that if we have 70,000 people who are willing to say that I am successful today because of Upgrad, why don't we start talking about that story? Now the issue is that testimonial is the least believed ad type in this world. Because people are just using testimonial to lie and lie and lie. So it's a complicated problem. So what we did is we said we told a few of our alumni that we want to make an ad but we want you to be natural. So we are not going to give you any script or anything. You come to our studio let's have a conversation. So three or four of them agree so they came to our studio and then our team started just talking to them. Each of these videos you see are two hour long and you can see the full version on YouTube. From that two hours we edited out 30 seconds and 40 seconds of it. And then we started using this on digital. The response has been quite good because these videos I am getting almost 75% completion of the video view. Typically people skip after 5 seconds. This I am seeing such great engagement. So this is another one which I am going to do on programmatic because again this is perfect because each of these person is a different profile. If I am able to create a micro cohort and start using programmatic to test out which ad works I will have a solution there once. So these are the two cases and third one I just told you in work in progress where we have used programmatic. So that's all I have. Thank you so much. Hopefully it was a good session. Thank you.


Hi everyone Sean with jaspyscasebrakes.com here doing 2020 Bowman draft sapphire five box break pick your team number 11 Where we're giving away the Detroit Tigers By two or more teams in this break get entered to win no max entries two teams one entry four teams two entries six teams Three entries etc. If you only buy one team you'll not be entered, but good luck with that team 32 cards per box all cards ship all cards are penny sleeved top names plus all colored numbered color is also top-loaded so Here is our list of customers and their respective teams So to figure out how many spots everybody has we're gonna copy the customer list over to a new sheet and Alphabetize So Ben young gets one spot David Sitco gets one Eric gets one Garrett gets one John a John B gets one John D Josh gets one Mark gets three Matthew gets one and Oliver gets one There you go. So we've got 13 names this time From Oliver back up to Ben dice roll randomizer name on top after five into two seven times Seventh and final time. Congratulations to David Sitco Seven times on the lit on the randomizer seven times on the dice. You got yourself the Tigers in this break Randomizer work your way now. Let's see if the boxes do to Here's our final list last spot mojo John Dean with the Orioles and the Cubs Good luck John last spot mojo 60% of time what works every time and our boxes we're gonna say yellow Hopefully it's gold most likely Marco Luciano for the Giants to co-aroby for the Rangers Matthew Libertura for the Cardinals Quinn cotton for the Reds Jordan Adams for the Angels Zach Deloach for the Mariners Adam Seminaris for the Angels Jimmy Glowanky for the Giants Dylan Dingler for the Tigers Luke Little for the Cubs and Spencer Torkelson For the Detroit Tigers and David Sitco Won the spot all for having at least two teams in the break Jeter Downs for the Red Sox Cade Cavalli for the Nationals Miguel Amaya for the Cubs Chris McMahon for the Rockies and AJ Vukovic for the Diamondbacks Jared Schuster for the Braves Shane McClanahan for the Rays Patrick Bailey for the Giants Jordan Groscians for the blue blue Jays Emerson Hancock for the Mariners Francisco Alvarez for the Mets Jordan Walker for the Cardinals Ian Seymour for the Rays Jeremiah Jackson for the Angels Alec Burleson for the Cardinals JJ Bleday for the Marlins Zach Daniels for the Astros Brennan Davis for the Cubs Bryce Monan for the Reds and it is a gold Logan Gilbert for the Mariners David Sitco And Levi Pratter yellow or sorry green to 50 for the Cardinals and Ben Young Uh, it's just the way they do it Greg They just don't do autos in bowman draft sapphire Uh bowman chrome sapphire they do they have autos another reason I think they do it too That's because bowman draft just came out I don't think they want to and there's so many bowman first in bowman draft Like so many players have bowman first in this compared to bowman chrome that I don't think they want to Take away from the autographs in bowman draft itself while bowman chrome doesn't have as many top line bowman first In it as bowman draft does So with bowman chrome sapphire You'll get remember you got a lot of rookies and stuff like that too in there So that's why they have autos in there because it's not taking away from the bowman first autos that are in bowman draft, I think Nick Gonzalez for the pirates Uh, that is Garrett Lespin O'Neal Cruz for the pirates nick Lofton for the royals Milan Tolentino for the Indians nick Swinney for the Giants Anthony Volpe for the Yankees Caden Polkovich for the Mariners Zach McCambley for the Marlins Aaron Ashby for the Brewers Liam Norris for the Diamondbacks Jason Dominguez for the Yankees John Bender Joe Ryan for the Rays Blake Rutherford for the White Sox and Jesse Franklin for the Braves Gerard Encarnacion for the Marlins David Calabrese for the Angels Nolan Gorman for the Cardinals Levi Prater for the Cardinals Andrew Vaughn for the White Sox Golden Spike winner in the past Maybe stock up on this dude Gage Workman Tigers Brady McConnell Royals Gerard Jones pirates Hayden Cantrell Brewers Alex Santos Astro Shaneling Lears for the Braves Nick Garcia for the Pirates Grayson Rodriguez for the Orioles Xavier Warren for the Brewers Bobby Whitjr Royals Mark Bassett Trevor Halver for the Yankees And our first color is Trevor Larnack 2.99 for the Minnesota Twins Matthew Shira And Mike Siani Orange to 25 For the Reds And Mark Bassett Does anybody know I think they're brothers, right? Mike Siani and Sammy Siani Is Sammy Siani supposed to be the better one? I thought Sammy Siani was the better of the two Is Mike Siani now? Has he surpassed him? Or are they not related at all? That just happens to be a coincidence But there's two guys in like a one year, two year period That both have a last name, Siani Maybe it's more common last name than I know Orange and yellow We're gonna go orange and yellow Corey Lee Astros Mark Vientos Metz Alika Williams Reyes Dane Acker Athletics Carmen Blobsensky Pirates Carson Ragsdale Phillies Nick Bitsko for the Reyes Jackson Kowar Royals Yeah Aaron Ashby Brewers Liam Norris Diamondbacks Jason Dominguez For the Yankees Josh Bender Or John Bender Joe Ryan for the Reyes Blake Rutherford White Sox Jesse Franklin Braves Travis Swaggerty Pirates And Landon Knack for the Dodgers Brady McConnell Royals Jared Jones Pirates Bailey Horne White Sox Burrell Careway Cubs Logan Hoppin Pirates Slade Sikoni For the Diamondbacks Jaren Duran Red Sox Xavier Warren Brewers Bobby Whit Jr Royals Mark Passette Trevor Halver Yankees Ethan Hankins Indians Reese Hines Reds Logan Gilbert Mariners Isaiah Green For the Mets And Yellow Matthew Dyer Bowman First To 99 For the Mets John Bender And Austin Wells To 25 For the Yankees And John Bender Two more boxes Aqua And Yellow Maybe Gold Probably Yellow Nic Lodolo Reds Austin Wells Yankees Warner Blakeley Angels Justin Fosquay For the Rangers Steven Surrey Tristan Casas Red Sox Max Meyer For the Marlins Mark Passette Alexander Canario For the Giants Tristan Lutz For the Brewers Carter Baumler For the Orioles Ben Hernandez For the Royals Thomas Suggis Rangers Zach McCandling Marlins Aaron Ashby Brewers And Liam Morris For the Diamondbacks Shane Vaz Rays Carson Tucker Indians Christian Chamberlain Royals Jordan Westburg Orioles Daniel Espino Indians Cole Henry Nationals Jake Ruhm Red Sox Casey Schmidt Giants Hunter Green Reds Holden Powell Nationals Adley Rushman Orioles John Denene Last Spot Mojo Tyler Brown Astros Ryan Rollison Rockies Justin Lange Padres Joe Boyle Reds Logan Allen Indians And our first color Elliot Maramos 299 For the San Francisco Giants Mark Passette And Bryce Jarvis Aqua to 20 For the Diamondbacks And John Alphs And last box Good luck Pat Perotcha Pat Perotcha Pat Perotcha Pat Perotcha Pat Perotcha No Pat Perotcha I think it's a green and a yellow Okay, so big names Nick Lofton Royals Nieland Tolentino Indians Nick Sweeney For the Giants Anthony Volpe For the Yankees Caden Folkovich For the Mariners CJ Abrams For the Padres Jordan and Wogu For the Cubs Hunter Bishop For the Giants Josh Jung For the Rangers Sammy Infante For the Nationals Kyle Isbell For the Royals Connor Phillips For the Mariners Mitchell Parker For the Nationals Hudson Haskin For the Orioles Ryan Murphy For the Giants And Casey Martin For the Phillies Brandon Fott Diamondbacks Trey Cruz Tigers Brett Batty Metz Addison Coffey White Sox Alec Thomas Diamondbacks Petey Halpin Indians Robert Fawson For the A's And Eric Ainge Ethan Hankins Indians Reese Hines Reds Logan Gilbert Mariners Isaiah Green For the Metz Riley Green For the Tigers Jeff Criswell For the Athletics Marco Raya For the Twins And our first color is Tanner Burns 250 For the Cleveland Indians And Garrett Lessman And Xavier Warren Yellow to 99 For the Milwaukee Brewers Finishes it off And that goes to Mark Bassett Nice team color matching on that one too There you go guys That was the break That was 2020 Bowman Draft Sapphire Five Box Break Pick your team number 11 From jaspyscasebreaks.com I'm Sean Jaspyscasebreaks.com Thank you very much for hanging out And I'll see you next time