What's up everybody Jason here from jazby's case fix calm We just sold out a jazby's nine box off-season basketball mixer random teams where we're giving away a LeBron James rookie PSA Giveaway, so the way this works guys is first. We'll do the break you get a random team From all of these boxes here. We'll pop them open Distribute the hits out then at the end of the break. Let's take all 30 customer names that bought in paste them on this list here and Custodial number one wins the LeBron James bowman rookies and stars 2003 which is a PSA nine and I'll show you guys right here in person Put a nice little PSA holder Very nice again. These are always gonna rise guys. I think these are valued between See what highest sells highs like a thousand, but I think they're within the 750 to $900 range But again always increasing in value. So that's a nice LeBron rookie right there That we are giving away in the break Just for buying in or winning a spot So let's do the randomizer to see what team you're gonna get in the break and again customers from Catherine all the way down to Christopher Got spots in the break itself straight up and then Andrew All the way down to Andrew Got spots in hangar number 12 and 13. So five customers here in 12 and five customers here in 13 So congratulations guys. Good luck and here are the teams everybody gets a random team So let's roll the dice and we got ourselves a five and a two for seven times. So good luck seven times One two three four five six seven Gary down to Anthony All right Six and it's you seven times here one two three four five six seven Since the summer Houston Rockets down to the Cleveland Cavaliers All right, so Gary from Donner's hangar 12 you have the Rockets right here with the Warriors Andrew Dunder Matt with the Wizards Cory with the Nuggets Hilaryos, that's how you say it. Sorry man. Oh with the Jazz Kim with the Magic Christopher with the Lakers Cory with the Bucks Christopher you have the Pelicans and the Hawks Nancy of the Spurs Catherine with the Blazers Matt Michael sorry with the Grizzlies Matt L with the Heat Ryan You have the Knicks Michael with the 76ers Amber with the Clippers. They go here with the T. Will's man Christopher with the Nugget Kinks John with the Celtics We have Stuart with the Mavericks Chen with the Bulls David Tran with the Raptors Catherine with the Pistons Chen with the Suns John with the Hornets Andrew with the Nets and Matt with the Pacers and Anthony Venturino with the Cavaliers All right guys if anybody wondering for the football mixer looks like someone did grab the last spot in the football mixer So we are just 19 Spots away 19 spots away and this fills the mixer guys for football So get this rolling. Sorry 18 spots now. I would you guys like to trade with each other Anthony or? You're gonna keep your team I David is you want to trade for the Raptors for Cavs or if not, let me know close it You Gary yes that filler is for a 2020 mosaic hanger football box That's Anthony cat. So he's gonna hold on to the calves. It looks like all right then Let's just close the trade window So Again after this guys, I'm gonna do the contenders break and then after that I mean, I think we can squeeze in the football mix and then we can call it a night So this is what we're out now. I should be done by 945 so we can get The contenders four box break in and then the football mixer. I think it's gonna happen tonight guys All right, so there's some of the heavy-based stuff to get it over with early on And then the rest of it guys, I think once we get done with the two chronicles boxes and illusions with the revolution I think from there on out to be pretty quick. So this might take This might only take under 30 minutes. Who knows I Guys good look Darren Fox LeBron James backstage pass that's Cavaliers edition John than Isaac we got a little Lonzo ball little Gerald Green Kobe Isaiah Thomas You're now You Chris Middleton Jordan Bell bones a worse Rondi Hollis Jefferson another LeBron James insert Cavs edition I Robert Covington Our last stack right here, so I think we already got both autographs What other rookies we could potentially get dang The way Howard little Covey and Sir Markel's folds There you go. All right. Coolie. Oh, let's move on to the next one.  Sorry, then we have a chronicles hobby box coming up after this All right guys. Good luck. A lot of rookies are gonna build up here guys Here's a Zion first of many Anthony Davis Jackson Hayes Kendrick Nun couple Yanis Cam Reddish Brandon Clark Tyler hero Peter Washington, Jr Jordan pool really hot you more What are you talking about Gary? LeBron James hometown heroes Jordan pool Kendrick nun John Morant You're watching the break now Gary we already randomized the customer names for the break This this is the actual break kill Alexander Walker Jericho over John Morant I'd like to do it Andrew. We just got to fill up those two fillers Which would be the RMBs for those I think it was like the last seven or eight teams remaining Carson Edwards Cam Reddish Zion Williamson, but if it doesn't I'm sure it'll go tomorrow though So I think we have a randomizer R&B for like the bangles and a few of the teams and then there's a second one for the Dolphins I think Eagles and some other teams in there Deondre Hunter LeBron James score Luca Rui Saiku Update Kendrick Nun. Yannis Kobe White Montice Daivo Yannis Keldon Johnson the LeBron Deondre Hunter Brown and Clark RJ John Morant and a Kyrie Irving update. You got a John Morant Marquis And a bronze PJ Washington, Jr. So yeah guys these rookies are really do add up in this chronicle. So there's a lot of value I'm gonna penny sleep to topple these at the end of the break so that way we could just continue on But that's that right there will be top-loaded penny sleep does well Let's move on guys Kam Reddish another John Morant Jared Kovar Yannis Yeah, Kam Reddish Tyler here with crusade Brandon Clark Tyler hero Cameron Johnson Cameron Johnson Kam Reddish Kobe White Yannis Langford LeBron a Zion hometown heroes Tyler hero Rui-Ajimura Keldon Johnson Zion Kendrick Nun RJ Brennan Clark R.J. Barrett not so little Let's use Daivo Luca Cameron Johnson KPJ Kobe White score Keldon Johnson inserts All right KPJ Cameron Johnson again Jordan pool Kendrick Nun Jordan pool RJ Saiku KPJ Kendrick Nun a Zion Penini threads Deandre Hunter Deandre Hunter Eric Cacheau RJ Cameron Johnson McKellivan Walker Brennan Clark RJ Barrett PJ Washington jr. Yannis under the combo back-to-back Deandre Hunter Kobe White and a Zion bronze very nice So again a lot of rookies here guys It definitely will add up I guess that will penny sleep and topple these at the end of the break So we'll leave that stack there And let's get done with the lost chronicles. So this one's not going to have as many rookie cards It still will but This is the hobby version. So you're looking for more numbered cards and of course at least two autographs So let's pull some fire in here guys I can't do that Gary because that would mean that the first half of the people already paid the full price So we have to just get that filler done I canceled the other one earlier because we hadn't done am but I can't cancel this filler now And like charge people half for the next one because that means the first half would have paid the full price No prism updates are all over the all over the print run of chronicles I think you're more likely to get color prisms and hobby though I think I've only seen like base and like silvers and like chronicles like hangers and fat packs and stuff like that I think hobby you get the prism color updates probably Carson Edwards Yannis Kobe whites and that is actually numbered to 10. Wow. I almost skipped that right there four to ten Kobe white Very nice Kamran is a Rui Silver Jared Colver Zion a bull bull number 39 out of 49 Goga Vita say there is Garland Zion We got a Zion crusade And our first auto is Alvin Hayes for the Washington Bullets that are we going to the Washington Wizards? and Matt Arnold Or nine out of 25 Jackson Hayes PJ Washington jr. Tyler hero of ron Kendrick nun and a luca majestic 33 out of 49 for the Dallas Mavericks It's going to stew it Kendrick nun Rui Hachimura R.J. Barrett a goga Vita to the 149 luca Carmelo Anthony prism update And Daniel gafford hometown hero autographs to 99 Chicago bulls going to turn Brandon Clark cameras Cameron Johnson burning Clark there a Rui black box to 249 Kendrick nun and a Zion red 67 out of 149 very nice out of phoenix That is going to go to Christopher Gerard. Look at that Very very nice John Moran and little Trey young our revolution box This is 2018-19.  All right Let's go to illusions. All right. Good luck everybody Ben Simmons to 99 Lucas sharing stars insert Kamratas rookie Got a goga Vita to bronze Kobe white You got a bronze davante Graham and a autograph Daniel house jr. For the Rockets went to Gary Kendrick nun rookie Kevin porter jr. Steve Nash insert Rui Hachimura A Cameron Johnson 7 out of 99 Tyler hero insert Goga Vita to rookie PJ Washington jr. To 25 Romeo Langford rookie Eric pass y'all Lebron James We got a terry on Prince to 99 for the Brooklyn nets trey young cowl guy a John wall number 17 out of 25 Yanis inserts Jerry Colver rookie Damian little to bronze Anthony Davis Matisse Tybal We got Jalen a wall rookie Ty Jerome Danny green Living legends oscar robinson 3 out of 5 oscar robinson. How about that? Milwaukee bucks that's going to Corey. That's pretty cool 3 out of 5 Luca Donchich rj Barrett's Master your little insert Terrence Davis You have a James Harden third. Wow. How about that man? Jersey number 13 out of 99 James Harden for the Houston Rockets and Eric has y'all nine out of 10 gold for Warriors That's a nice one. This is a nice box and jenna Let me quickly just penny sleep all this So we have four boxes left guys Two crown royal boxes<PHONE_NUMBER> We have a 1617 spectra box and a 1920 obsidian basketball box So I should be done with this by 945. Like I said, I'll quickly do the contenders break Should take me about 20 minutes by 1010 We do that filler for the football mixer and then we break open the football mixer guys And then probably going to call it a night after that unless something else feels while I'm breaking Let's go with 1718 crown royal first There's a Donvin Mitchell die cut rookie TJ Warren Milo's John Wall Jamon Green Denzel Valentine Josh Jackson and Dennis Smith jr for Dallas number 299 We got a Paul George die cut 299 for the thunder Then we got Jawan Evans little patch Otto 8 out of 25 Clippers going to amber and a Markel's vaults for the Philadelphia 76ers going to Michael All right, next one Orzingis Lucas Amonich and Russell Westbrook How about this jam around 71 out of 75 die cut or sorry, that's not jam around Wait, it is jam around. Wow Jam around on the front But De'Aaron Fox on the back. How crazy is that? Insert You know, I'm gonna have to take it I'll probably have to randomize this honestly Here, I don't want to damage this All right. Well, I know in the past We've had stuff like this and for the most part I think we've always randomized them. So Just to be safe just so customers don't say hey We're just gonna randomize it Jam around on the front. I don't know if this was intended to be De'Aaron Fox It was one or the other obviously So we'll randomize it and that's a little error Jordan full relic and Colin Sexton Little patch auto for the Cavaliers Anthony with that one I think we've had that a couple times with obsidian, but the autograph actually matched The player so we gave it to the player in the front But since this is an autograph them, we can't prove which card it was supposed to be I think we even had an autograph of the wrong player in the back on the front too I don't know quality control guys All right, let's go to spectra. All right, we got a Julius Randall We got for the piss pistons Contavious Caldwell Pope Little Dica 21 out of 25 Pistons going to Catherine We have a spectacular swatches marquette Morris Also in the checklist it shows both teams regardless Eddie So they're comparing Darian Fox and John Morant I'm at I don't see how that one makes sense because they're two different teams But I get what you're saying Darian Fox. I just honestly think that one's a typo Malik Beasley nice patch Next era gold eight out of 10 Okay, well, we could go by the checklist, but I mean I'm still gonna have to randomize it regardless Has two teams on there. So Bryce Johnson rookie jersey autographs neon green So this is expired by member Panini. They have it. They'll give it to you. If not, they'll give you some points Clippers Excuse me guys, sorry Just depends rich if it's an older product Um, and some of the autographs you've already seen live them I would assume it's quick. It just depends on if they're live or not I think if they have it ready, I think they ship it out pretty fast, but it's whenever That's never really the case the red thing. It's It's the players that are not ready to sign yet. So it takes a while All right. So Bryce Johnson card number 28 is l.a.c. So l.a. Clippers That's going to amber We have Justin Anderson in the zone Autograph for the 76ers What a Michael number 299 Deontia Davis Or Deontia Davis are That's Memphis Grizzlies to 149 And look at this guys. We got a nice one here. How about a rookie patch auto of brandon ingram? Very nice player now for the pelicans got her first start over there all star already Very solid player, but this is going to go lakers, of course christopher with that one Very nice and the last one here is Mark price 399 cleven cavaliers spectacular swatches On card as well. All right, cool Let's go with the last box here guys obsidian basketball Graham Williams and Dennis Schroeder Kind of sad. Maybe it's going to get traded to the leakers Buddy Hill Eric Pashall purple and Damien Lillard gold 8 out of 10 for the Portland Trailblazers going to Catherine. How about that? 8 out of 10 Pashall number to 75 Luke Canard Detroit Pistons another one for Catherine That's 27 out of 50 And the last one here is new colo melly To 75 for the New Orleans pelicans Go ahead Christopher. You're gonna get a top loader for this. So show that a little bit later Yeah, guys, let me quickly look this up And yes, both teams are on there regardless So Grizzlies and kings So here's this randomizer Oh So here's the dice holder guys This is for the Lebron James giveaway and this is for the heir to the throne grizzlies and kings And uh, just wanted to give you a little quick recap too. So besides that randomizer there Nicola melly Luke Canard kind of seen the last few hits here Very nice stuff here And then we got Colin Sexton some nice stuff here numbered from illusions autograph there out of 10 Eric Pashall Zion from phoenix Out of 149 gafford elvin haze out of 10 Kobe whites And then there's a huge stack right over here that's all going to be top loaded and penny sleeves that i'm pointing at Above right here And then that'll be penny sleeve and top loaded as well So just this randomizer here So dice rollers gonna work for both. Let's roll the dice and we got a four and a three for seven times Uh, so let's go with the randomizer here first doesn't make a difference. Let's do that first. So seven times four and a three. Good luck one two three four five six seven Goes to the sacramental kings And that was seven times Sacramental kings that is christopher Tag it really quick All right, and seven times here now. Number one's gonna win this LeBron James right here guys Very very nice one ps89 So good luck seven times one two three four five six seven boom seven times number one Wow matt l Button straight up and I believe you one spot mojoed this I think this was your only spot in the break. There it is guys. All it takes is one Yep, one spot in the break. I got the Miami Heat as well So there you go. Congratulations matt. You just got this LeBron James coming your way soon So appreciate it guys. This was the uh jaspys nine box off season basketball mixer on jaspyscasebricks.com


So, thank you very much. I think I'm going to retitle our talk as the nightmare of the virtuous cycle. Because really what we're talking about is we're going to keep changing everything. So it's dynamic. And so our panel, Katrina, Robert, Sharon, and myself, really have tried to capture this framework in our discussion points for panel three. And this is a work that was done by everybody through a string of emails over the last several days. So thank you, everybody. The challenges are the dynamic nature of the genomic medicine data. Looks like I have this out of order here. So next generation data is going to continue to evolve. With major changes expected in the near term, these include increased read length, decreased cost, and increasing the use of whole genomes for clinical purposes. And so I think you can just start to imagine what is that going to mean as we go forward on this. Dynamic analytics and laboratory reporting is nascent and will change rapidly as the knowledge base increases. So correction of errors in the literature and early reports, I think we're seeing some activity around ClinGen. But there's a whole host of things we have to be thinking about including the basic research where we're basing a lot of this. We don't have the same level of clinical ecumen, if you will, around that. The conversion of variants of uncertain significance and genes of uncertain significance to knowledge, Heidi and the previous group covered that well. Genomic data's impact on treatment will remain dynamic as the knowledge base increases in all aspects of reporting. So there's the primary results, there's secondary, and there's all incidental, and those are going to be some fluidity between these as we go forward. So there's, of course, sources of errors inside clinical reporting. There's the limited genotype-phenotype correlations. This was also discussed previously. Both correct and incorrect correlations exist in the literature, and this will also continue to change. And the range of phenotypic expression is uncertain or unknown in many cases. And sometimes the rare disease may give us an outlier, if you will, of what that gene really, really does. So we need to be thinking about that as we go down the road. An over- and under-reporting of the results based on varying clinical platforms and guidelines. By this I mean, or we mean, that looking at some of the different sub-specialties may look at this slightly differently as we go down the road in terms of guidelines. Ares and sequence data, these include incomplete sequence information, error rates depending on the type of variant, and errors in the sequencing analysis pipelines, errors in sample tracking, other standard clinical laboratory errors, and then errors in combined sequence data with other clinical data at the level of the treating physician. So remember, the report that's coming out is one piece of the data that the physician is using to make the diagnosis. It is not, in and of itself, the diagnostic. So the changes in treatment and care are also going to be impacted by this. Clinical implementation is going to change dramatically with the emerging definitions of what is actionable. We've had a little bit of discussion around this, and what's clinical utility. So the different medical specialties could have different definitions on what is actionable. So I know our clinical geneticists view this a little bit differently than our cardiologists. Clinical utility is going to have a different meaning to the patient, to the physician and the payer. This comes back to looking at the personal utility that Jeff mentioned in the first panel, and how will these different definitions be managed in the context of the dynamic nature of the genomic data. So keep in mind that this virtuous cycle that we're talking about has an impact to trickles down through each one of these different decision lines and the different areas that we're talking about today. Increasing numbers of drugs with companion molecular diagnostics or theragnostics are tested and approved. Indications for the existing drugs may be paired with molecular tests as knowledge is gained. As an example of one of the drugs, there's others that are coming out on the market. For the companion diagnostics, there's something important to think about this. So you'd think that it would be just really easy, okay, genome's been sequenced, hey, let's just look at that DNA and use that as information around that. But the companion diagnostics are tests that are submitted along with the new drug applications and the FDA targets the precision medicine, and what's important about this is it relies on a specific methodology. It is not just go look at a random sequence. So that's a big issue around this. It generally focuses on the limited numbers of mutations, so it's not in the same realm of what we're talking about for genomic sequencing, and it can have the strongest indication for efficacy. So alternative analysis of a specific gene may be approved, BRAC is an example of that. But once the genome exists, the data can be used for companion diagnostics. Is there a means to link it to the drug? Now let's keep in mind that with that notion, is the FDA going to agree with your genomic sequence as being part of that, and that's one of the issues that will be mentioned in a moment. So the changes to treatment, pharmacogenomics, obviously is likely to become more common across the clinical continuum. Current next generation tests often have minimal pharmacogenetics testing involved in it. So will the data be regulated differently? So are we talking about the DNA diagnostics having one level of regulation and the pharmacogenomics having another level of regulation? I mean, there's some significant issues that need to be sorted out around this. And how will this data be related to the patient's genome be stored in the EMR for future use and when new medications are prescribed? And what does this mean for existing medications that a patient's on? So the reanalysis of the genomic data, this is the virtualist cycle that I'm thinking about. Where are the variants data going to be stored long term? So there's one thing about having the knowledge base, but what about for that individual patient? Who's going to do the reanalysis? How will the rate of reanalysis be set? How will the reanalysis be paid for? Will variants be reanalysed in the context of either the primary, the secondary or the incidental context? And those issues are going to have a significant role about each of those events above. In what category will the variant be for pharmacogenetics? It could be primary for new drugs in the future. It could be secondary for a drug that a patient's currently taking when the patient is sequenced for different diagnosis. We need to be prepared for reanalysis to not only uncover new and actionable findings, but to also result in some prior findings becoming irrelevant or incorrect. And that's the downside of this as part of this virtualist cycle. We will for sure, we are already finding that there are changes that need to be made in this dynamic data set. Then we have the issue of duty to inform. So what do we do with this information? So are changes needed in the laws and the regulations required to what constitutes duty to inform? What changes to the dynamic knowledge of the patient's genomes are mandate, re-contact and re-reporting. So if there was, and I'm not saying there is, but if there was a patient portal, is it sufficient to simply deposit that data in the patient portal? Should there be a separate clinical visit? Who will and how will this be paid for? And should all data types be updated or only the primary? In other words, if you find a new secondary, new incidental, what are the decisions that are going to be made around that? How can the physician and the patients be updated without alert fatigue? They're all aware of this as a challenge. If there's, you know, Heidi's team and ClinGen is finding more and more data, I mean I can imagine in the not so distant future that every day there's multiple things that are being updated. How do we do this in a way that it helps us improve the practice of medicine? Will there be different rules applied to different specialties? And I think everything we're talking about is falling into some of these categories. Are there different rules for the different variant type? I'm going to say there probably are going to be.  So the guidelines for reporting results from the different types of testing are still evolving. ACMG has recently announced new recommendations for germline testing, but it doesn't include pharmacogenomics or common alleles. Efforts are underway to define somatic mutations, but things like methylation status, how are these going to be managed inside these guidelines? There's no agreed guidelines on other areas that are being pushed out there. RNA expression, circulating DNA, and single cell analysis, all things that are right on the horizon of appearing inside clinical laboratories. How and who should these guidelines be defined and evolved? And how will the changes in these data types be updated? It is likely that the different tests will be performed by different laboratories. How will these data be integrated, interpreted, and conveyed to the patient and the physician? Again, it's an amalgamation of data that's accumulating in multiple sites. So solutions for these challenges, I'm going to use this word loosely, solutions, because I think it's more that I've been talking about if you have no idea how we're going to do this, is you have to bring geneticists, pathology, specialty groups with the payers. I think that we need to have those discussions with them together to set guidelines. I think it also needs to require us having patient advocates involved in this as well. We need to fund and develop clinical trials. I use that in quote type studies to look at data return, duty to inform within these three areas of rare disease, cancer, and healthy patients. And I'm just wondering if some of the programs that are already underway in this portfolio, there couldn't be some other pieces tied on top of this. Is this a separate study? I think you could do this for really a limited amount of dollars to look at as we're reporting early on what's the outcome towards the end of these studies. I think these are going to be some important issues to look at. What should be done to define the clinical utility and what is actionable? Obviously, this has been mentioned before. The double blind clinical trials are not the correct study design, but how should this be done? That's been mentioned by the other two groups as well. So the main points, I'm going to summarize this here. We're doing a little bit of a hybrid of the other two panels. So I'm a talking head, and then we're going to have Robert come up here and talk about the way Caesar's taking a look at some of these activities. But I'm just going to finish the main points here, why Robert comes up, just because I couldn't get Robert's slides in without screwing up the formatting. So this is a technical error on my part, why we're doing it this way. So the dynamic nature of genomic medicine, data creates a series of problems in returning results to patients and physicians. Physicians outside genetics have little understanding of this dynamic nature and limitations of the different methods. Returning genomic data to different ethnic groups, age groups, and levels of education and wealth make it more complicated. But tests can be rapidly integrated like the NPT and disrupt current technologies. And can the FDA diagnostic process keep up with the rapidly evolving genomics data? Genomic data reanalysis and retesting will increase as utility increases. Genomic sequence is only the first of the omics types in this dynamic data that will be incorporated into healthcare. And the challenges across multiple disciplines, governance, and legal requirements make finding solutions problematic. Okay, Robert? We need to switch the slides. Can we switch to the, can we move to Robert's slides? I think she's trying to put the money. Thanks. So under the theme of changes in evidence we thought we might expand the discussion a little bit into looking ahead to some of the challenging areas and thinking about those. So, you know, to some degree, let's see, is it this one? I'm now the presenter, okay? Spacebar, okay, thanks. So to some degree, Howard has touched really focusing on diagnostic exome and genome sequencing. And so what I'm going to talk a little bit about are some of the ideas we've already touched on with regard to secondary findings, medical action ability, penetrance, intermediate and scalable phenotypes, and population screening. And part of the reason is because we are, I mean, there are two analogies that come to mind, the elephant where we're each touching a part of it, and also the plane that we're, what is it, we're assembling as we're flying it. I love that one. And part of it is that we have to somehow put scalability and structure into place for the medical care system, which is a blunt instrument. While at the same time being nimble and being able to iteratively and experimentally do creative clinical research that helps us see the path in front of us. I'm only going to use a few examples from CSER, not nearly encyclopedic, just because it's what I know best. Remember, there's nine different sites. And in terms of the scalability that people like to talk about, you know, hundreds of thousands, millions of participants and subjects, this is pretty small as potatoes. Here's some of the sample sizes there of the people who are enrolled in CSER. So take this with a grain of salt, but it also allows us to really drill down and explore different kinds of clinical trial models. Pretty much the focus in CSER as it is in some of these other groups as well is what are the medical behavioral and economic outcomes that we are focusing on? And what can we find out? Thus inform some of the group and scalable initiatives that we're talking about. Now, CSER's been great at moving beyond the ACMG 56, looking at larger numbers of actionable findings and also finding them in the various sites. So you can see that there's a huge range of sites. If you look at the third column on the right, there's a huge range in which different sites are returning different groups of supposedly actionable findings. This is one of the strengths, I think, that allows it to look at things in a granular fashion within a small-scale clinical research exercise. And looking at it a different way, if you take the nine CSER sites and a couple of other sites across the spectrum from NHGRI, you can see that some experimental studies are really returning a single gene or a small number of genes. Some experimental studies are returning a very large number of genes, up to almost 5,000 as we are in MedSeq. And so we're gonna be able to look across these studies and I think say something about them without having had to make an a prior decision about how to proceed. I will also say that several of the sites in CSER, and I know in some of the other consortia as well, are looking really rigorously at health economics. David Veenstra's work suggests that with some of these panels, there is an acceptable cost per quality gained. And that's really exciting for secondary findings. Whether this can be transferred into the greater population realm is, of course, a very salient question. I think it's on everybody's mind and that you may already have internalized this. But it's really important to make a very clear distinction, at least in my mind, between opportunistic screening that we've all been talking about with the secondary or incidental findings and true population based screening. Opportunistic meaning that there's an infrastructure in place. It's sort of ordered by people who ostensibly know what they're doing. It's relatively cost neutral because you've already ordered the sequencing. There's some recommendations that are in place we've been discussing. And it's all fitting within the medical model where there's a certain amount of secondary findings that are allowed to be cycled back into the clinical encounter. Population based screening, as such as we do with newborn screening, current newborn screening. We have nothing like the infrastructure in place would obviously add cost. There's no recommendations yet. It's very much this public health model with all its attendant, unforeseen downstream clinical consequences. So you might be surprised to hear me say this, but I think we really ought to be gathering very rigorous evidence before we endorse this. Now the problem is that outside this room, there is an extraordinary momentum moving sequencing in this direction. And so we've got to somehow accommodate that enthusiasm and that energy while at the same time collecting the data that's important. I do think randomized clinical trials have their place in this, such as our MEG-C project where we're doing with healthy people. I do think there's a lot to find there. If you look at 4,600 well-established genes, we're finding that 21% of people are carrying a risk variant of some sort or other and 92, that's for a dominant or semi-dominant disease. And this is 92% for recessive carrier traits. And we're looking as all the other CSER sites are at exactly what doctors are doing in this information. What is their real life downstream use of such information? Others such as Jonathan are looking at clever ways to try to make actionability less of an abstract term and more of a rigorous term. Jonathan's created, for example, a semi-quantitative metric to define actionability. Katrina's group, for example, is not only talking about medically actionable conditions, but unpredictable, mild, adult onset, short, and lifespan. These are things that really speak to what systems want and what people want beyond what we assign as medically actionable. And finally, I just show you some exciting results when you try to take this into a large-scale project where people are followed for many years. We've looked at the pathogenic variants in 462 people who are exome sequenced in the Framingham Heart Study, and were followed for at least two decades so that their phenotypes had a chance to emerge. And we're finding that suggestive clinical features are present in a high percentage of them, whereas if you model this and those without the pathogenic variants, the percentage is not nearly so high. And this is a remarkably significant difference, despite the small sample size, we're seeking to replicate this now. So the last slide, I would just say, I think this idea that we've been hearing about scalable phenotyping and intermediate phenotyping is really exciting. One can imagine it sort of segwaying and aligning with the new wearables phenomenon, where people are getting biochemical or chemical evidence along with other types of phenotype evidence, where people are enrolled en masse to be part of our research infrastructure. And we think the physicians think it's going to be the norm. I think the physicians will adopt to it when they get information that's useful to them just as they did with NIPT. And I would encourage us that in many situations before we scale it up, where we could be throwing a lot of arrows, but not very accurately, we try these things out on small scale clinical research studies. We are nimble in that regard, and we find our true aim in that way. Thank you. So Howard, do you want to moderate from there or from back here? I'll do it from right here. But I want to just see if Katrina or Sharon want to add any additional points quickly. Yeah, thanks, Howard. I just wanted to speak to a few of the things that both you and Robert mentioned based on the experience from our CSER study. So one point I wanted to make is that the value and meaning of the information may be context specific for the participants. So for instance, in our CSER study, we're focusing on returning carrier status. And this is in couples who are interested in becoming pregnant soon. And so they have a real near term interest in learning this information. But in some of the other CSER studies, they are also returning carrier findings. But I think it's not as meaningful in the context of the reason why the sequencing was ordered. And so there may be a very different reaction to people, to that same information, depending on their life stage. And so even though the information may not change over time, it just may be they're simply not ready yet to learn that information. I also wanted to give an example from our study where we've kind of changed our minds in the direction from a pathogenic variant to more of a benign variant. And that was the example that Gail talked about earlier. Where the first time we saw that variant, we were more likely to call it likely pathogenic. But then by the third time we saw it in 50 people, we were thinking maybe this is not a pathogenic variant. But we had already reported it out to the first person. And so what do we do? We go back and tell that person that we've changed our minds in a different direction than I think most of us are thinking about when we're talking about how the results may change. In our study, we also ask people what they're interested in learning about. People come to their genome information with a preconceived notion of what might be found. And even though we may not think something is particularly actionable to that person, it may be. So for instance, if they have a strong worry about Alzheimer's disease risk, it may be very relieving to their minds to get that information back, even though it's not something that we would normally think about testing for. And so I think we do need to take that patient perspective into account. And finally, I just wanted to mention the work that we're doing in ClinGen in terms of defining actionability. And we have started off in a very specific context where we're looking at clinical actionability in the context of returning secondary findings in adults. But I think that we realize this definition is going to change when we're talking about children or talking about somatic variants or other kinds of context. And so I think this work is just beginning to define what actionability means. Sharon? Yeah, I just wanted to make two points. One, to feed off of what Katrina just said, so we're in like the opposite. We're returning a very similar number of recessive carrier status in our project, but it's children newly diagnosed with cancer. And my favorite quote from the interview with the mothers when she was asked about things like carrier status, she goes, yeah, that's fine. I'll worry about it when I'm a soccer mom again. So that like in the context of another illness, they're happy to have the information, but it is a very little import, which is very different than adults considering having children. I just wanted to kind of highlight again, which we already did a bit, is the limitation of companion diagnostics, because sometimes I hear that, well, the way we should do this is through that process. And the current companion diagnostic process very much freezes the technology. Whatever technology was used for that test is what's approved. And so laboratories often have to import different assays to do that specific mutation, which they also have a perfectly good other assay for. But more importantly, I really think that genomics very much outpaces the regulation. Once a drug is approved for one mutation, there's little incentive. Even if you find three additional mutations that predict response, there's very little motivation to increase, to change the companion diagnostic, and particularly for drugs that have already expired, like they're not patentable. There's really no financial incentive for that type of research, and I think it really needs to be supported by NHGRI and NCI and the Disease Specific Institute. And conversely, there is actually a counter incentive to do research on mutations that might confer resistance to treatment. And there's really no regulatory process very well designed for that right now. So for example, the EGFR T790M mutation is very well described in the literature to actually confer resistance, particular inhibitors. And that really doesn't fall within any of our regulatory framework right now. So I think we do really have to think about how to support research on mutations that will convey response as well as resistance to both new drugs and existing medications.


Camden Town is an area of London where you can find everything, markets, music, food, handcrafts and more. In the diverse atmosphere, every person becomes special. Camden Town is a crazy place and let's have a look at this entertaining place where the story of big names were written. As Charles Dickens, Amy Winehouse and Elle Mother, Red Cat, who was famous for her bad temper and black magic. You got a lot of things, you got a lot of crazy people and it's really interesting for me and I'm from Chile. We are not so crazy than here. Quite busy. It's like, you know, you get to know. Okay, so how was it? You always get a thought. But that's because she doesn't know me. If she ever stepped into the darkness of one night with me, she would. Of the reaches of the kn-


Hey guys, it's Monica. Thank you so much for joining me. In this video, I'm going to talk a little bit about some of my things I've been enjoying in the last, what, two months, maybe, and probably a little bit of a rant, but not much. And yeah, I don't know. Maybe, maybe a little bit of this, a little bit of that. So if you're interested, stay tuned. Tomorrow, well, maybe today by the time you see this, because, well, Sunday, I'm going to a sprinkle, and I'm like a sprinkle. I had never heard of a sprinkle, but apparently it's quite a popular thing. My niece is having a baby, and it is her second child, and she's having a girl.  So even though she had a shower, like about, I think maybe two and a half years ago, she's going to have a sprinkle for her little girl. So yeah, we're going to go for a sprinkle. We're going to meet my mom, my, one of my daughter-in-law's, down at my mom's house, and my sister, and we're all going to go together, and enjoy a little bit of a sprinkle. I just think that's so cute. And last week, Mother's Day, last weekend on Mother's Day, I had everyone here, and we did a little bit of a barbecue. We sat outside, and we had a fire pit going, and we just kind of chit-chatted, and it was very, very casual, very low-key, but it was, it was so nice to have everyone, not everyone. You know, obviously, we all thought of my dad, and you know, and we thought about my nieces that went here with us, but just to have a good amount of the family members together, and you know, not really have to wear masks, and just, just relax. So I had a wonderful, wonderful Mother's Day with family, with my kids, my grandkids, and my mom and my sister were here, and my brother-in-law, so it was just really, it was really a nice day. So I was super blessed to have had my family members with me on Mother's Day. I know it. So I hope that you guys all had a great one. However, you spent the day. So a couple of things. It's May, and here in New England, the weather is finally starting to warm up, and of course that means you have to be all the more diligent right on sunblock and sun care. So I've never ever stopped being diligent about sunblock and sun care. I just amp it up a little bit more in the summertime. You know, I wear more hats. I wear, I always wear sunglasses. I think because I wear sunglasses, even on a cloudy day, that helps prevent me from squinting, you know, into the sun as much. So sunglasses, I have several different styles of sunglasses. I love them all. I wear them all. Many of you see them. I have a couple.  And I think the more sunglasses you wear help, it really helps you, especially if they're darker sunglasses, and kind of helps you not squint so badly into the sun. So that said, a couple of things that I have really been using and enjoying a lot of is obviously the color science. This is their Sun Forgettable Total Protection Face Shield. This is 50 SPF. I think that whatever you do, whenever you're done your skincare, whatever sunblock you put on your face, that first step of sun protection, I think it needs to be something super, super strong, at least for my skin. And I think you can use Retin-A. You can use all the anti-aging or whatever you want to call it, products. If you are not using something good to block the sun, the harmful rays, it's all for naught. It is really all for naught. So whether or not you use a makeup, a foundation with sunblock in it, I don't think that's enough at all.  I really like it. And they also have the Regular Broad Spectum. This is SPF 45. This is the white one. The Tinted one, I'm all out of. I've got to get some more, but I want to go through some of the products I have before I buy that. But the Dermatology, this is a white, it leaves a little bit of a cast, but it does absorb into your skin pretty quickly. The Sun Forgettable, this one from Color Science, their face shield. I've used Color Science products for a long time. I bought some. I've been gifted some over the course of time from Color Science. I really like this a lot. This is the 50 SPF. This plays super nice with my makeup, the Dermatology. This one plays nice with my makeup. And also probably the one that is the most affordable is going to be your Australian Gold. And this is their Botanical. This is 50 SPF. This is their Tinted Face. This is what I use a lot. I've used this for a couple of years. This is a non-greasy. So when I put this on, non-greasy, right? I put this on, I have to have a little bit of an oil mixture with it. I should use a little bit of Squalene Oil or something that I mix into this because my skin is dry. So Color Science and the good old dependable Australian Gold Tinted. And they've got a couple of different tints now. Sunblock. This works super, super good. And then I also have, of course, the Powder. This is the Color Science Powder one. You know, when you use this Powder one, you're going to make sure you shake it really, really good. I tap it, shake it around. Then I open it up.  And then I put it on. Then you can see, you know, the coverage. And sometimes I do my face. Sometimes I always do my hands. I have this in the car. I would never depend on just this solely for sun protection. I don't feel it would give me enough. So I do my skincare in the morning. I put everything on that I'm going to put on. And then I put whatever sun block I'm going to be using as my base, whether it's going to be the Color Science or the Dermatology brand, or if I'm going to go right into the Australian Manual Gold that absolutely is used. I put that on. I let it dry, whichever one it is, before I go into the next phase. And the next phase would be my foundation. You know, whatever you use for sunblock is going to be important. What you cannot do is depend solely on your foundation. Most foundations are going to have an SPF of 15, some might have 13, some might have 20. But in the summertime, whatever, at least me, I don't wear enough foundation on my face to get enough coverage that I need for my sunblock. So I've been using the number seven. This is the Protect In Perfect. And this is all in one foundation. This is the 50 SPF. This does really good on my skin, but never alone. You know what I mean? I only couple this with another sunblock underneath so that I make sure that I'm covered. I would never depend on sunblock in my foundation because, like I said, I don't wear enough of it to really adequately cover. And then I also have the other number seven. This is the one, the Hydro Luminous. I really like this, but this is not yet sold in the States. You can only get, I think, in the UK. But this is really, really nice. I like this a lot. When I use my Estee Lauder, I use a bunch of other foundations, and they all have a little bit of sun protection in them, but never enough. So just make sure that, you know, you're doing all this treatment for your skin, anti-aging and all of that stuff. If you're not using good sunblock, it's all for not. Truly, it's all for not. So I really love my number seven, but one of the things that I've noticed lately, and I don't know why, but I think it's been oxidizing on my skin. I've been getting more of a little bit of an orange tint. So the thing that I've been using all the more, and I've talked about this before, I bought this at CVS. And this is the Flower Beauty, and this is what they call their Light Illusion Perfecting Powder. I think this is awesome. I don't usually wear a lot of powders at all. In fact, very minimum. But what I do is, I will brush this powder on, and it will even out my foundation. Like, if I feel that I'm looking too orangey on my face because of my foundation, this lightens and brightens it right up. I really like it. It doesn't make my skin look cakey. I use it as a combo setting and finishing powder, I guess, you know what I mean? Because it's just a beautiful, beautiful light veil of coverage. And you can, of course, put as much on as you want, but I use it very, very lightly. And it just kind of gives me a better, more brighter, brighter skin, which is something that I really like. And I have been super enjoying the, I got this in Octoly. I talked about this in one of my previous videos. I still don't know how to pronounce this. Palladio. This is their cream, their, their blush. I have several of them. I've been using this one. Oh my gosh, I really like it. What it does, I don't know if you can even pick up color, but it just gives you a little tinge of sun-kissed look, you know what I mean? Just a little bit of a, you know, brightening look and pink kissing, pink sun-kissed look. I love it. So I do enjoy my ColourPop. I've been using this awful lot. This is the ColourPop blush that I got, Vogue Press Powder Blush. This was given to me, Marlene Fab and Glam, had given this to me along with the Stone Cold Fox palette. I don't know if I've talked about this before, but you know, it's a really color. So she had sent this to me and I absolutely love this blush. So what I've been doing is I've been putting this blush on and then on top of it, I've been doing a little bit of that look and I just think it gives me that little sun-kissed look on my face. I absolutely love it. So I've been enjoying, enjoying the heck out of those blushes that I received. I got like six of them, all different colors. I really, really like them a lot. They're so super awesome. I bought, and again, this is Marlene Fab and Glam talked about this Daily Dose of Love from Essence, right? Essence. And I bought this because she talked about it and she said what how pretty these shades were. And I'm going to hunt for pink. I'm going to hunt for something with a lot of pretty pinks in it. And I thought, hmm, I'll try it, right? So I bought it. I really like it. It does give me a little fallout, but you know what? Just about every, every shadow I wear gives me fallout. And I just take a big fan brush like this and I just brush it off my cheeks. But this, I really like. I think this is really cool. Now, if this had a more pinkier pink, it would be perfect. It's got pink. It's got mauve. It's got a peachier color. It's got some glimmers and all that stuff. And then a really light, light pale poisellantly pink color. It's got a lot of pretty colors. I can do an awful lot with that. I've worn that palette a lot, but I also bought, and this is the hottest palette to get. This is the Morphe Vintage Rose palette. I went into a couple of different altars. They were sold out in the store every single time I went in. So finally ordered it online. And this is what it looks like. I don't know if you can see it. I thought these colors, I thought these colors were really pretty. So it has, it has sort of a beige. It has a couple of mauves. It has some pinks. It really has some really nice shades on here. So I have been enjoying this and it's really affordable. It's Morphe, right? It's not, not going to break the bank, but I've been wearing a lot of these little pink pops in the middle and then all around the lid shades and all that. I've been really playing around with my, my eyes. So this I've been enjoying this month and it took me forever to get it, right?  I don't mind ordering it, but I want to see it in real life first. You know, I want to see the colors. And in altar, all I could do is look at pictures. I want to be able to see it. So I finally ordered it. I really like it. This is the vintage rose. I like the color combo.  And the other one that I got, I think I mentioned this too and I've been using the heck out of this. This is the Lorac Pro Matte and I like this. This, for a smoky eye, for me, for a smoky eye has almost every color. It's got a pinky, mauve color. It's got sort of a corduroy color. That's a little bit warm for me. A latte color, a chocolate, a jet black, a burgundy, all mattes. I think I got this in Coles. I think I got this in Coles. So I just, yeah, I just have been enjoying the heck out of all that really a lot. My, my color pop stuff has been awesome. And this palette, the Stone Cold Fox, I mean, I've used this a whole lot, a whole lot. So really like it. The other thing that I have been liking an awful lot is the, and I kind of missed the date on this because this actually was available to the General Park public on May 9th. They, they had a big promotion on it. This is the City Beauty Ultrafirming Dry Oil. They sent me this for review. I think I got this about two months ago and I was able to try it pre-launch and then I was supposed to talk about it at the launch. And I just, the last two weeks in my life have been like totally nuts. I mean, totally, totally nuts. Anyways, I've been, I've been using this. I took this with me when I went away on vacation, when I went to a wedding. And this is ultrafirming oil. You put it on your neck, your decolletage, your decolletage, right?  I love how this makes my neck skin feel. Instead of feeling thin and creepy, I, my skin feels more supple.  I have a ton of wrinkles, but I feel that this gives me, like, I will use this on, especially on a special occasion. And I feel it plumps up my neck skin. Is it going to be something that over time will continue to plump up? I don't know. Maybe, maybe not. But I do like this and there is a coupon. I know it's a pricey number, but to me, this is sort of like that.  So yeah, I really like this. I'll make sure I link all the information below. I'll tell you guys, you know, I've been, I have been a real estate agent for 36 years. I've seen markets, good markets, bad markets. I, you know, I know when the market crashes and I've seen what happens to home values when they plummet and when they sky rise. I have never seen a market like this in 36 years. So this market is totally, totally insane. And I, you know, it is really difficult to be a buyer in this market and buyers say the seller's not sympathetic and the seller's not giving them a break. And it's really difficult to be a seller in this market because the seller gets like, you know, 60 offers, right? And these offers are all over asking and they're waving contingencies. People are buying without a home inspection and they're saying they'll make up any shortfalls on an appraisal. Some people are waving appraisals and I don't know. It's like, it's, it's very, very scary. It's a scary real estate market out there and everyone, everyone in the industry, we're all holding that breath. We're trying to, you know, go along with the flow and show the properties and advise our clients as best as we can. And if we're dealing with a seller client, advise them to really look at all the offers, you know, make a decision. But I tell my buyers, you have to be prepared for banking, maybe seven or eight, nine or 10 offers before yours might get accepted. So it's almost like learning to love rejection. Oh, no, we didn't accept your offer. Better offer. Oh, thank you. But no, thank you. The more you hear that, the closer you're going to get to that. Yes. That's what I tell them. So, you know, hang in there. But what, what a market it's like, totally insane, totally insane. So that's not anything I've been enjoying this past month. It's just what has tied me up being so super busy between that and training and, you know, doing the pre licensing classes and all that stuff. It's like, it's just an unbelievable market. So I would say, thank goodness for my podcast. I listen to a lot of podcasts. I listen to when I'm driving, when I'm trying to exercise, when I'm trying to walk around.  And I think it gives me a whole awareness of what's around me and not that I'm paranoid and not that I think something's going to happen, but I am way more aware of what can happen in situations than I ever was before because some of these podcasts are just unbelievably in true crime. You know, they're all true stories, especially riveting is the one that's happening in Indiana right now from the, the Delphi, Indiana where the two girls a couple of years ago were murdered on a hiking trail and the Abby and Libby, you know, Abby and Libby, and one of the girls actually filmed the guy on her iPhone and he actually had his voice on the bridge telling them to get down. They probably have a lot more than that, but they've recently arrested a guy that is like maybe 15 or 20 miles away from them from where this happened and they arrested this guy because he had abducted, raped and beat and was probably going to murder a neighbor girl, a nine-year-old neighbor girl, I mean really, you know, unbelievable and they caught him in the nick of time. So now they're looking at him to see if there's any connection to the Delphi case, you know, and I don't know if there is or there isn't, but thank God, you know, as morbid as it sounds, thank God they arrested this guy before he could do anything worse and what a creep, you know, who knows what he's done, but I sure hope they find the guy that really, if it isn't him, who the person that really is responsible for the murder of those two sweet little girls, you know, they were just 12 years old, 12, 13 years old, little girls. So anyways, yeah, podcasts, that's been another favorite of mine, I really like that and the probably the very last and I didn't bring it in is my apple cider gummies, my apple cider vinegar gummies. My weight has been at a standstill, I haven't lost a pound these last two weeks, very, very frustrated, but I feel great and, you know, I just, I feel more energetic and I'm doing that with intermittent fasting, so I think that's helping somewhat and I just have to bust through this standstill so I can ditch the COVID weight.  Anyways, that's about it for me, I know this is a little bit all over the place, but just wanted to say hello to everyone and tell you about some of the things I've really been liking and yeah, I'll let you know how the sprinkle goes in my next video. Thanks so much for watching guys, bye bye.


Hi everyone, Joe for Jaspy's casebreaks.com doing a random number block randomizer for the following teams right here Cowboys Colts Raiders Bucks Redskins Steelers Vikings and Saints Right there works just like our number blocks if you're not familiar with it Please read that item description there big. Thanks these folks for getting into the action. There are the numbers right here Let's roll it. Let's randomize it six and a five eleven times each one two Three and 11th and final time after 11 we've got a fan sanity down to a couple Roberts Paste their names in here and then 11 times for the numbers one two Three and 11th and final time after 11. We've got five down to four Now remember zero will get any and all redemptions including one-of-one redemptions But it's a mood point because Robert has both zero and one been ten He has five Dylan with six David with two Robert with nine and seven Jack B with three Robert with eight and four Let's order these numerically. Let's print this out and we'll get to the break which will be in a separate video Jaspy's casebreaks.com


Hi, I'm Stu Miniman, and welcome to a special Cube interview here at the Schneider Electric offices in Boston, Massachusetts. Happy to welcome to the program a first-time guest, Irvay Coray, who is the Chief Digital Officer at Schneider Electric. Thank you so much for having us. It's a little rainy, but that's what we can expect in Boston, but a lovely view. Thanks so much. Thank you. Great. So first of all, give us a little bit about your background. The Chief Digital Officer today, we love talking to the CDOs. You've been a CIO, you've been a CFO, and we'll definitely get into some of the organizational dynamics as to who reports to whom and who owns what and the like. Sure. So indeed, I started in finance. Actually, I did a lot of work in M&A. After a while, we acquired a pretty large company called AAPC, and I became the CFO and really working essentially on post-merger integration. So how do we put all those pieces together? And when you do that, you quickly realize that actually technology is on the critical path all the time. So I developed quite a keen interest at that time for technology, and that's where Schneider decided really to change its setup, to evolve its organization. We had a program called One Schneider. We created the CFO position, and that's where basically I took the helm as the CIO for Schneider Electric. And over the time, then, digital became a thing. It was not just about how you digitize the company. It was also how you create the digital business. So that's how we created Schneider Digital, and I became the CFO. So all of these sounds like super logical right now. Of course, it was far more chaotic than that, but that's the overall arc of the story. Lots of politics we understand, organizations, large M&As, we understand that there's challenges, things to work through. If you could for our audience, just frame Schneider Electric. I actually, disclaimer, I worked for American Power Conversion way back longer than I'd like to even admit. But uninterrupted power supplies, they really helped create a market, had some excellent technology, strong engineering background, which is what led me to that company. But Schneider Electric today, of course, much bigger than just APC. Give us a little bit of a frame. So Schneider Electric is a pretty large global corporation. I think we employ something like 140,000 people, so pretty large, multi-billion company. We basically are in the business of energy management and industrial automation. We're specialists of that. Our core value proposition is really bringing efficiency on sustainability to our customer. We do that in a number of areas, whether it's buildings, whether it's large infrastructures, data centers, factory floors, on industrial processors. But sort of a core common thread, if you will, is how you bring efficiency, sustainability to our customers. Great. You talked a little bit about your background as a CFO was to help with the merger. Bring us up to what is your role as a chief data officer? What is the mandate you have? We're going to spend some time unpacking digital transformation. We always say that the difference between a company before and after that digital transformation is that data is so important. You must be data-driven. You must understand it. And therefore, often there is a CDO involved. So what led to this role and what is that specific mandate that you have? Sure. So I did mention just before that we had the concept of efficiency, which really we have a value prop about safety, reliability that over time evolves towards efficiency and sustainability. And in order to provide efficiency, whether it's in a building, whether it's an industrial building or process, what needs to happen is not just with hardware. You need to be able to extract data from products, from systems. You need to be able to make sense of that data to analyze it and then to act on it. So sort of close the loop from data to insight, insights to action. So that's where for us, the digital transformation was not just about digitizing ourselves, but it was also about augmenting the value proposition that we have for our customers, augmenting what we can offer our customer base with those services that could push the boundaries of efficiency and sustainability. And they were all about adding an information component, a data component on top of the best hardware on software. So that's sort of the evolution. And you were speaking about the mandate. So the mandate is really around four things. First is really the digital business, so how we create digital offers that are going to augment to complement our existing offers, making, you know, taking advantage of cloud, taking advantage of analytics, AIs on providing, predictive maintenance, providing optimization services that can augment our value prop. It's also about bringing the ecosystem of partners that can really reinforce those value props, those digital offers. So it's really first about that digital business. Then it's about digitizing ourselves on its three things. It's first how we engage customers, so customers and partners, so thinking about what's our digital footprint, how we create basically a digital experience for our customers and partners that is even better than the one we're having on the physical world. Then it's about operation through our backend systems, making sure that we have a backend system that scales on the last mandate is security. Okay. It's a pretty broad mandate. A lot of things going on, 140,000 people working for Schneider, not to mention you talked about your customers, your partners, all these things. Absolutely. What's the scope of this? How many years ago did this start? Is there a phased rollout that you're looking? Is there just a budget assigned to it? Bring us a little bit as to how this all rolls out. Sure. A couple of things. I would say we started three years ago, really the digital mandate, only that started well before. Because actually, if you're in the business of industrial automation, you haven't waited the advent of IoT to connect machines to a supervisory layer, to controls, et cetera. Now what happened is, of course, the power of the cloud, the power of analytics, and you could take things even further. So really three years ago was when we started thinking about Schneider Digital. On the way we thought about it is we didn't want it to be something totally on the side of the business. So it's not a separate PNL. It's not a separate organization. We're serving the businesses. We're augmenting the businesses. We're providing them with transversal capabilities. We're providing our businesses with digital services, platform level components that they can reuse, et cetera, so they can go faster in addressing their customers. And it was critical for us to find that appropriate distance, if you will, because you need to incubate a digital business. But at the same time, if it just happens on the side, you never augment the core. So you lose the main benefit out of it. Yeah, it's nice that you have the background of also being a CIO. Everything that I'm hearing you talk about is what we hear from many leading companies out there that it's not just doing what the business asks. It's helping to often create new products, or in many cases even it's innovation, helping to drive the business. You mentioned at the end of one of your last pieces, talked about security. It's something critical when you're talking about data and in your CDO role. Tell us a little bit about the security of how that's involved on this total solution. Sure. So for us, it's of course became more and more important over time. And we really had to rethink how we're approaching security, right? Going away from this idea of defending the perimeter, moving to concepts much more like a zero trust approach. Because the world has changed, we have employees that like to work from, their taxis and planes. And we had really to rethink the posture of Schneider Electric and also how we work with customers and how we can help our own customers improving the cyber security of their building or industrial operations. So we see it as a pretty broad mandate actually quite end to end. It's not just about building thick walls. I think the times of perimeter defense are long gone, but it's really about thinking about it as a full cycle from identification to recovery and putting a risk-based approach and some continuous improvement approach into it. A lot of discipline, basically. All right. Intervie, are there some partners that were important in this digital transformation? So overall or specific in security? Both. So yes, I mean, we have big partners and you could guess, right? I mean, of course, we're working a lot with Amazon, we're working a lot with Microsoft, we're working a lot with Salesforce, on the system integration side, we've worked with Capgemini, with Accenture.  I mean, we try to be more and more very considerate about what we want to do ourselves and when we basically delegate some functional points to partners. And then we also created an ecosystem of partners around security. And Schneider is a very partner-centric company because we actually work with full partners most of the time. So working as an ecosystem is actually something that's pretty natural to us. We just had to learn how to do it in the digital age. Yeah, that's great. A company of your side, right? It's not only the suppliers there, but building that ecosystem. Yeah. Anything more on the security side that you want to call out regarding that journey? So, you know, we've been working, we've developed a lot. I mean, we felt that security was, it takes a village, right? And the ecosystem approach was even more important. So we've been working with Zscaler on a network level security. We've been working with IBM on Deloitte on other areas. We've been working with Silence as well. I mean, I wouldn't, that's a long list, right? But we've tried to build an ecosystem both at a service level and at a solution level. Because the problem often with security is that, you know, you can have a lot of point solutions that would solve very narrow problem. But it's really, you know, what really makes a difference is your ability to integrate, is your ability to have a pane of glass where you can figure out correlations and then pretty quickly take actions. So we're striking that balance between adding solution that would add you a new source of information, new understanding of your context with the ability to act on this information. Yeah. And, Irving, what lessons have you learned going through this? You talked about the balance between what you do in-house versus what you look to outside. That's a general trend we've seen in cloud for the last 10 years or more. So, you know, looking back as to what you've done so far in three years and any advice that you'd give to your peers? Probably three things. So the first thing you mentioned is the ecosystem, right? Is that it's not us versus them. It's how you embark an ecosystem of partner and how you bring some logic in that ecosystem. So that's really key. The second thing is really scale. I think I always say that in digital it's always super easy, you know, to come with the latest shiny object to do a proof of concept, etc. But usually that doesn't matter. The key source, the secret source is how you scale. And often and in particular in today's world, people tend to have a misconception of scale that this is just size. Actually, very often in digital scale is about replicability is how easy can you replicate, which is a slightly different concept when you think about it.  On the third point would be performance management. Actually, we've spent a lot of time defining and maybe that's my roots as a finance person long time ago. But it's, you know, what does success mean, right? What are the metrics of success? We call them the true north, what true norths are we pursuing? And how do we allocate resource? Because at the end of the day, you only scale if you're able to allocate resource. So if you want to have a sophisticated digital organization, you need to start by having a sophisticated resource allocation process. Yeah, how about the outcomes? You know, what if ultimately your end user customers, what do they see out of this digital transformation? And also would love if there's any commentary on the employees, we understand, you know, getting them involved training and the like can be challenging. But, you know, ultimately, you know, how does digital impact both your external and internal customers? Sure. So let me unpack that right in terms of true north outcomes. The key thing we look at first is how we create the digital business on how much are we creating adoption, right, with our customers. So we really track, you know, how many new things we on our ecosystem, how much more value are we creating to our customers are those customers adopting those new value points, those new solutions, those new, those new ideas. So so and of course, you know, how much are we growing behind that, etc. But it's really this idea of value and adoption to start with. When we look at the, the engagement, the customer side, we look at the customer satisfaction in the physical world, and we compare it with the customer satisfaction in the digital world. And we want to be at par. When it comes to the back end, we look at how much we're simplifying that back end for, for, so we're tracking technical depth and so forth. And then on security, we look at external scoring, so that we always, you know, keep ourselves honest with external assessment on how we're doing. So that's basically, you know, how we look at the four dimensions that I was beginning that I was mentioning at the beginning to answer the second part of your question, which was more around employees. And it's a huge effort, of course, you know, creating the organization, a lot of recruitment, a lot of training, we've been working a lot, you know, providing you with a digital citizenship course and up to very technical course, we refold completely our approach to learning. And there are many, many aspects of the employee experience that we've been working on, I mean, providing mobility, providing, you know, on finding that balance, right, between security and enabling the new world of work where people are going to work on the go and offering them a much better level of access, basically, to the corporate resources, mobile and so forth. This has been a massive transformation over the years.  The role of the CIO has changed an awful lot, you know, over the length of our careers. So, you know, what are you seeing in those dynamics you've worn both of those hats? And, you know, where do you see things going and anything you feedback you'd give to the industry to make the lives easier of the CDOs and CIOs out there? Well, I think it's, you know, I would say I've seen the roles held very differently from an industry to another. So, you know, it's probably hard to replicate from, you know, the energy management and industrial automation industry to others. But in an industry like ours, where the products are becoming digital, because basically, you know, you want to create data in the real world, you want to be able to process that data, create insights from that data, and then you want to be able to act on the real world based on those data. You really need to look at those two aspects. And there was a great, actually, paper from MIT, a while ago about digitized on digital. So, really, I like to say digital is really about creating this digital business, you know, real world data, transforming this real world data in insight and action and then acting in the real world, while CIO has mostly been about how you are digitizing the company, right? So, the employee experience, the customer experience, the partner experience, having transforming your backend into a machine that scales, on both equally share that last mandate, that's even a broader mandate at the level of the enterprise that goes with security. So, that's how I would roughly, if you will, you know, define the space. Irving Karey, thank you so much for sharing your experiences. It's been a pleasure talking with you. Thanks for having me. All right. I'm Stu Minin. We're here at Schneider Electric's office in Boston, Massachusetts. And as always, thanks for watching theCUBE.