What's up guys and welcome to One Take. I'm Gil and today we're talking about Biohacker's Episode 1 titled Arrival. This video will of course have spoilers for Episode 1, but I haven't watched anything beyond that, so no spoilers for Episode 2 onward. Before we jump into the highlights of the episode, just overall thoughts, I thought it was a solid episode. I thought the opening sequence was a great visceral way to pull us into this intense situation, create some mystery. Why are all these people suddenly going into cardiac arrest? Why was Mia, or as we later learn Emma perhaps, the only survivor of that situation? And the cinematography in that scene really helped. If you noticed, a lot of it was done in a single take, and I thought that added to the immersion. And that wasn't the only strong choice with the cinematography this episode. I thought they made a lot of interesting choices. One that I'll call out is in our introduction to Dr. Lorenz. The first time we're in her class, most of that scene is shot from her perspective. The camera follows her as she walks around the room. When she's standing in front of all the students, we're looking up from her perspective. She's in the foreground and seems to be commanding this faceless mass of students as they raise their hand. I thought that visually looked interesting, and it created a sense of power and ego for this character. Speaking of which, I don't think we have a great sense for the characters yet. We know a little bit about Mia or Emma. We know a little bit about Dr. Lorenz. But the show has a mystery, and that mystery is drawing me in. However, it is a risky endeavor because part of the mystery is the characters themselves. We don't quite know exactly what Mia or Emma is after, and that's risky. Other shows have tried this. Westworld, for example, will often have a twist later in the season that sort of recontextualizes our understanding of that character. So actions they took earlier in the season don't fully make sense until you learn the truth later in the season. That's interesting. It creates that mystery, but it also creates some buffer between us and our emotional investment into these characters. If we don't fully know why they're doing what they're doing, we may not feel everything the show wants us to feel. That really hasn't been a problem for me so far in episode one, but it is a risk if they wait too long to shed some light on what Mia is up to. So overall, I was a fan of the first episode, loved the cinematography, I'm interested in the mystery. To some degree, I'm invested in the characters. I have a couple of worries about where it's going, but I enjoyed it enough to keep watching. Let's jump into the highlights of the episode, but first, just a quick reminder to hit the like button, hit the subscribe button and the bell icon so you get notified the next time we do a video and you can keep up with our coverage as we watch the rest of the season. I already mentioned the opening scene. I thought it worked really well as a brief introduction to the Mia character and it was just a great way to start because it was an intense situation. The cinematography helped to put us right in the middle of it and really feel it viscerally. So strong start. Then we meet Mia's roommates. So far these other characters seem to just be defined by their quirks and they don't really have any depth yet. You've got the biohacking guy, you've got the laid-back party girl, and then you have Chen Lu, the fast-talking smart girl, who did give a pretty good tip by the way. I did not know about the Netflix Chrome extension that allows you to watch on 1.5 or 2x speed. Very useful if you're doing a rewatch and just want to pick up on some additional details. Back in Mia's room, we see that she has some magazines and journals and publications about Dr. Lorenz. So clearly she's here, she's up to something. She came to the school because she's looking for Dr. Lorenz and is trying to get close to her. She is trying to keep that under wraps because she puts all those papers and materials, hides them inside of her speaker. We also see Mia look at a figurine that from a flashback we learned came from her brother. Her brother presumably died. We saw him at the hospital and later Mia tells Chen Lu that she has no siblings. Also we should note that at the hospital when her brother is being taken away, we hear somebody on the loudspeaker ask for Dr. Lorenz in the ER. So it seems like Dr. Lorenz had something to do with the death of Mia's brother. I'm also guessing that Dr. Lorenz had something to do with why Mia or Emma was the only survivor of the incident we saw earlier in the episode. Mia also tells Jasper that she's never been sick and I get the impression that she is telling the truth. Later in the episode Dr. Lorenz says that she's helped 8,000 people have children who otherwise couldn't. My question is did she perhaps perform genetic experiments of some kind on those children? Is Mia or Emma a product of those experiments and that explains why she's special, why she doesn't get sick, and why she survived that incident from the beginning of the episode? And perhaps her brother was also part of those experiments but in his case it didn't go so well and that's why he died. I also mentioned earlier that I loved that Dr. Lorenz's introduction the first time we see her in class gave that sense of ego and power with her in the foreground all the students in the background on top of that she says they are going to make God obsolete so they definitely sell the idea of ego here. Personally in this moment I got the sense of her as a villain also we know the main character is sort of investigating her so she's definitely painted as a sort of villainous character which is great setup for the twist we get later in the episode. Then we have the entire sequence of Mia seducing Jasper. I'm assuming she's only doing this so she can get closer to Dr. Lorenz so I'm not exactly invested in this budding relationship but I do hope we get more development of the Jasper character. What exactly are his motivations? In general I'd say I hope we get more development for some of the background characters overall like Mia's roommates for example. But I at least bought into the process of Mia and Jasper getting closer meeting at the party getting that drink him showing her his lab all of that felt organic to me and all of that worked. One comment on the party sequence though I've been praising the cinematography of this episode throughout visually the one part where the show has disappointed a little bit is when they show us some of the biohacking. For example at the party when they take eyedrops I had a feeling they were going to show us what do things look like from the characters perspective after they take those eyedrops. Now I was excited to see what they would show us but essentially it was just a red pink hue over everything we were looking at and I didn't find that especially interesting. Not a huge gripe with the show but because I was praising the visuals I expected more and it was a little disappointing. Another part of the episode where we get another biohacking example Chen Liu created some plants that can play music and overall that also just looked kind of cheesy and kind of hokey to me. So like I said not a major gripe with the show but I was hoping that the genetic engineering and the biohacking would look a little more interesting. So I mentioned we get a nice twist at the end of the episode and that happens when Dr. Lorenz meets with the journalist who she clearly has some history with. Earlier in the episode I got a villain vibe from Dr. Lorenz but here they try to build up some of her motivation and try to create some sympathy for her. The whole scene was a little bit on the nose the way they straight up ask her are you happy and that opens up the window for her to explain a little bit of her motivations but overall the scene did work for me and it did build some of that sympathy so we learn that she loves the sense of discovery. She loves discovering something that nobody else has and that's what gives her joy. She's also helped a lot of people she mentions all the couples who are able to have children thanks to her but I get the feeling that part of it the helping people part of what she does is a little bit of self-rationalization and she's primarily in it for that sense of discovery and for that personal sense of satisfaction she gets all this seems to have been at the expense of a personal life no partner no family etc so she felt like a villain now we get a little bit of emotional connection with her in fact I feel like we know even though we spent so little time with her we actually know a little bit more about Dr. Lorenz than we do at Mia because with the Mia character everything we're seeing is part of her ruse part of her pretending to be somebody she's not whereas I think Dr. Lorenz at least to some extent was being honest in this scene then interestingly enough we get a sort of role reversal Lorenz felt like a villain Mia's our protagonist in the next scene we see Mia spying on Dr. Lorenz and you see Mia's reflection in the darkness in Dr. Lorenz's window if this show were done from the Dr. Lorenz character's perspective then in this sequence Mia would come off as a serial killer or a stalker this is Jason from Friday the 13th stalking his prey so if the show can play with these alternating viewpoints where at times we see Mia as potentially someone who's up to no good and at times we see Dr. Lorenz as someone with ulterior motives it could be interesting to play with those perspectives so that's something which excites me about where this show could be going then in the final sequence of the episode we see Mia after the incident in the opener it looks like everybody else has died by that point and she's the sole survivor one of the health workers asks her what's your name and she says Emma my initial read on this is that she actually is Emma but she's taken on the fake identity of Mia perhaps so that when she gets closer to Dr. Lorenz Dr. Lorenz won't make the connection that Mia is the younger girl whose brother died so many years ago it's a little murky though because if Mia is the fake name she's going by why did she reveal her real name in this scene and how long has she been going by the fake Mia identity we see her wearing that necklace and clearly the guy she was with at the beginning of the episode thinks she's Mia because that necklace is prominently displayed there so it's intriguing I'm interested to see where they go with this mystery what is the Mia character up to I just hope that they don't let the mystery undercut good character development and in general I'm hoping that for the other characters like Jasper some of Mia's roommates we get some more development so it's not just the Mia and Dr. Lorenz show so overall I thought this was a solid start to the season I'm going to go check out episode two so if you enjoyed this video make sure to hit that like button hit the subscribe button and hit the bell icon so you get notified when we get the review for episode two uploaded probably later today and I'll say I'll keep going with these episode by episode reviews assuming the show keeps up with this solid quality if not and it's really just good enough to binge but not necessarily deep dive into every episode I might just watch the rest and then report back for a full season review either way make sure you're subscribed so you can keep up with our coverage and be a part of the conversation with that thanks for watching and see you on the next one take


Good morning, my name is Jose Ocasio-Christian and I am the Chairman of the Board of the Kailas Foundation. It is a privilege and an honor to be doing opening remarks on behalf of our foundation. And I look forward to sharing with you about our goals and about the expectations from all of us in this workshop. Our foundation's goals are to engage internationally, regionally, and locally. Advocate for those who are not aware of the importance that space domain has for them economically, socially, and diplomatically. And empower all those who make decisions, whether individually or collectively, to make those decisions that influence the development and the use of the space domain. Our participation today in this workshop as a part of this informal and unofficial diplomatic dialogue between the United States and China on Space Commercialization is a continuation of our relationship between the Chinese society of astronautics, the Secure World Foundation, and the Kailas Foundation for almost three and a half years. This workshop has been forged to address the most important aspects of diplomacy and international relations. Those things are communication, respect, and understanding. It goes without saying that the relationship between the United States and China has been tenuous at best throughout this period. There have been challenges between both nations economically, politically, and socially. This workshop and the efforts of communication between our foundations to develop these very workshops have been at times the only healthy communication or connection on space when it comes to U.S. and China. Throughout this entire time, the Secure World Foundation, the Chinese Society of Astronautics, and the Kailas Foundations have maintained a dialogue of respect and understanding of one another as we have facilitated understanding between our nations about the space domain in a time when many would have considered this practically impossible. We have carefully within the regulations and legal proceedings of both our nations been able to maintain this informal and unofficial diplomatic dialogue and have been able to share our findings with the government and leadership of both our respective nations. For this incredible achievement, I would like to thank both the Chinese Society of Astronautics and the Secure World Foundation for their patience, respect, and support for what they have done so far as well as what they have continued to do in this endeavor. To Mr. Wang, to Ms. Zhang, and the staff of the Chinese Society of Astronautics, I want to personally thank you for supporting this effort. I cannot say enough about what your efforts have done to educate audiences globally about space commercialization. And as you and I both know, we've talked about many times. We're just getting started. For everyone else attending today, the intent today is about interaction in order to dismiss perceptions and build respect. The United States panelists and speakers have chosen a different format for discussion to present a more candid approach about the discussion of space commercialization within the appropriate regulatory guidelines. On our end, we're looking for the audience to ask questions. If you're watching this video now or after the workshop, please do not hesitate to contact the Kailas Foundation on our website. Or for that matter, any of the foundations involved in this workshop today. If any of us cannot answer something, we will let you know either because of regulatory requirements or because simply we don't know what we don't know. But do know that we will do everything possible within the limits of what is possible to provide you the most transparent and honest answer to your question. We're eager to listen, respect and understand our Chinese counter-parkino speeches that we have many times previously, and seek to learn in order to best describe too many here in the United States about this very conversation. Again, it is an honor to participate in this workshop and I very much look forward to the future and the opportunity to continue this informal and unofficial diplomatic discussion. Thank you.


Matthew really nice what seemed like a convincing win in the first round here your thoughts on the game Yeah, it was interesting But actually I was quite lucky because you know I'm coach of the woman team and she played against Sophie Mia last year And we prepared this with Sophie to play finally The black change in the game, so I knew something about this hook G1 with the idea of G4 It was a game Zviddler manager off, but then it's very unclear, but I'm sure that it should be good for white But I couldn't find I want this hook G2 is very strange But then I realized that if she moved the night there was a trap No, it's like winning with G5 by force and it's what I did I think So this you were playing against Josephine who was in the German team and they were playing against the French women team Exactly, and then did it even get used at the Olympiad or it never got used there? Okay for Sophie and I we didn't play this line. So I was just lucky All right. Well, that's that's an interesting story talking about preparation We actually had Sebastian Mazer here before who also had a game today in which he used the preparation He had with you for five years ago. No more than five. We made this preparation in 2005 Maybe he doesn't remember, but it's 2005. I'm sure that's a long time back So were you having a look at his game while your game was going on? Yeah, of course Because I said, oh come on. I wanted to have the same position. I would like to have this is like winning on the spot So I was exciting for him, but we are both Struggling recently. So it's good for us to win the first round Right, and we were talking to him about this as well about how we always have a big French Contingent that comes to Gibraltar. Do you like it here? Yeah, but it's my first time actually So, yes, yes, I'm happy to join the other French here so far so good I really like the place of course is beautiful and I'm happy to come with my wife. So it's perfect so far Is she having she's having a good time? I hope so, but I don't know what she's doing because she's playing in the second room I need a good check. Also a good reason to finish quickly. Yeah, of course Now we've got a big calendar of social events, and I'm sure you've heard about it Anything you're looking forward to particularly? No, I just want to enjoy here my stay and For me, it's just a surprise. I didn't expect to come here because I never had the opportunity and this time I have so I just want to enjoy everything. Well, I'm sure you will we wish you all the best. Thank you. Thank you


I'll just yell and you guys can yell back at me and tell me if it's good or loud or what. Hi, yeah, thank you. OK, my name is Marissa Epstein, and I am a UX designer over at Lullabot, which I love. Maybe you've heard of us already, but Lullabot is a Drupal consultancy and we offer strategy, development, and of course design for some big brands like Sci-Fi and the Grammys. So today I want to talk to all of you about an approach for better understanding users using psychology so we can design for their brains. So by now I'm assuming that you're pretty oversaturated with the user experience doctrines, researching your audience to create personas and using big data for little details and having empathy for users. I'm teasing that, and I do not mean to knock UX. I obviously love it. But my point is to approach your design problems with a psychological perspective as well. Not meant to be a contradiction, but a supplement. Yes, we should not overgeneralize when talking about people, but it is essential to have a core understanding of the fundamentals of human perception, cognition, behavior, especially as this is relating to how humans function online. You guys can hear me? Is it good? OK, so to put this in context a little bit, I just want to look at the UX origin quickly. So user experience design is a term that was actually coined by a cognitive psychologist, Donald Norman, when he was over at Apple back in the 90s. If you aren't familiar with him, I love him, I would say he's a true UX teacher with tons of books and a very insightful perspective. So considering his background in cognitive psych, I think helps us see how we can utilize psychology as part of our own design practice. And it's a really great way to understand our users, their motivations, needs, tasks, and how they're really behaving and thinking. My favorite of all the books, by far, is design of everyday things. So in this book, he essentially writes that the principles of psychology will remain the same as will the design principles based on psychology. So I really love this idea of these timeless fundamentals because they're universal truths that are applying to everybody. So hopefully you can agree it's kind of important to think about. And I also think that approaching your design problems from this kind of psych background can add a lot of dimension to the UX team and as a result to the experiences you're creating. So hopefully you're convinced. And I encourage you to put on a psychologist hat as you solve your usability problems. And I'm excited to report that if you Google image search psychologist hat, you get a picture of a wizard. So thank God I checked. So my plan is to walk you through some of the fundamental errors, biases, and limits of your users. So we can hopefully be a little better equipped to design for them. And I'm gonna go through some of these fast, but I already put my slides online. So don't worry about scribbling. Now, I do hate to stand up here and dump on people, but we do need to be honest with ourselves. There are some things about our bodies, our minds, and our habits that really kind of suck. So I found this gift and I really just wanted to present this as my whole talk, but it's not long enough. But I think it makes my point perfectly. It's just titled users. So even smart people that we expect to know, better online just don't always get the water in the mouth. So I've gone ahead and totally old fashioned, you know how we used to make up personas with no research. I've made up two personas for you in the hopes of giving you a new perspective. So the first one is elderly Eleanor. This is my grandmother for being honest.  I mean, just imagine trying to do anything in DOS. I know that putting this up here, some of the developers are laughing at me and they're just like command line, but this is terrifying. So you have no search engines, no customer support, no Siri, so if you need help with a mistake that is really too bad for you. And some of the mistakes are irreversible. So it's no wonder that some of these older users are a little more reserved when using technology, right? I mean, younger users like us are fearless for the most part because we've grown up with helpful, well-designed OS and these responsive sites in our pockets that have all the answers. But back to elderly Eleanor here. So she has a PC, she has an iPad that she reluctantly accepted as a gift and uses them well enough to get the information that she needs. She looks up the snow predictions in Maine and has, you know, connects with family. But she also holds her iPad like this when she uses Skype and she doesn't exactly understand where the camera is despite many conversations. And so I mean, if you saw the quote, it was like just don't, please don't explain it to me. So another example that I love is I ordered a replacement part for her on eBay for something that she assumed would just continue to stay broken forever. And she didn't understand where it was coming from. Like she didn't go to the store, why are they? Where's it? So yeah, so I admit this is not your standard user. This is an extreme case. So I wanna move on to our second persona, which I also stole right out of my family. Good old Average Joe is my father. So, sorry. I figured that's better than the Google image searches of like stock photos and stuff. So Average Joe is way more familiar with technology than Eleanor, yes. And he even tries new things sometimes. He tried one of the very first floppy disk cameras, if you remember that. And devices play a pretty big part in his daily routine, and a lot of times he's using more than one at once. And I have to say Joe is very smart. He's an architect. He owns his own business. I would consider him to be quite intelligent, but then he gets online and he really struggles. So part of this is maybe he's using his phone in the car. He uses it while he's supposed to be listening to his wife tell stories. And it's really easy for him to forget what he's doing and just give up quickly, hit a snag, and just think that that's the end. And so it can really be difficult. You should have seen us trying to set his Fitbit up.  So anyway, this second persona, along with a lot of us, really hate anything that can be interpreted as distracting to our goals. So even onboarding that we think is so helpful and fantastic might look like a pop-up to Joe and he's just swatting it away. And the truth that I don't love is that many of us just don't care about the interfaces. We just don't wanna learn about them. It's not worth it to learn something new. A lot of people really do just wanna go online. Point A, point B, get off. So I mean, I think this group is a lot more inclusive than my first one, right? I think a lot of us are guilty as well. Which it makes sense. You can see here an aversion to technology is pretty mainstream. I think these last three sections are something like 84% of us. So the early adopters are pretty rare. So the rest of us and Joe are gonna wait until something is really commonplace. And even then when we learn to use it, it's gonna be super backwards. Now, I'm not saying all of this to suggest that we just human proof. I don't want this to be so negative as dumbing things down for a lowest common denominator. Rather, I want to have a little more positive spin. But enhanced usability and reduced mental effort required for everybody, not just our Eleanor's. We wanna make our websites so simple that we're streamlining the visits even for our power users. So to illustrate this point, I think a pretty good example of accessibility enhancement would be the curb cut. Hopefully you've seen these. They keep sidewalks wheelchair accessible. So they're helping people with disabilities, but also people with suitcases and children and dogs and heels and bicycles and on and on. So a lot of people are benefiting from this aid. And this principle applies to not just physical spaces. So think about big clickable touch areas, right? I mean, they're helpful for those with big chunky fingers or old slow hands and everyone. So let's embark on this goal together of enhancing usability. And I wanna start with just learning about our users' needs kind of quickly from a super high level. Have you guys seen this before? Thank you. Okay, Maslow's hierarchy of needs. So really quickly, man fundamentally seeks to satisfy the most basic desires first. So we have physiological desires like food and shelter. And then as these are met, we move up the pyramid to emotional needs like love and eventually to self-actualization. There is some debate here on how these stack if you can maybe jump up a little bit. But I do think there's some give. But my point is just, I think that we can see there's an order for the most part and that we should be matching our offerings to the right need. Also, I found this great design hierarchy of needs on Smashing Magazine. So I had to show this as well. So instead of physiological needs, we have functionality and we move all the way up to creativity. One point I wanted to make here is simply that creativity is at the top. So please make things work before you make them pretty. Also, it's a little sad really when we look at this and realize how much is being taken for granted because I'm sure many of you know the effort required to just make something like mostly work. And yet that's a very low value that we're getting here. And this brings me to the Kano model. This was created back in the 80s but I think it's still pretty relevant. So we have our basic needs at the bottom with the must haves, wants or performance needs. And then finally, latent needs or delayters. So you can see we have this left to right threshold of satisfaction and our must haves are completely below it. So functionality, reliability is just a bare minimum and no one's even appreciating it. But users will delight at thoughtful experiences that are meeting higher emotional and intellectual needs. So before I get into the nitty gritty too much, I just wanna add that there are thousands and thousands of tenants of psychology that we could discuss today, many of which have their own books or entire fields of study devoted to them. All of which I'm going to tell you about right now. Obviously that's not true. So this is a very high level starting point and I just sort of wanted to say that because I know that I have less than an hour now. So I've done my best to try to distill the bulk of human interaction into a pretty simple system. So as humans, first we discover something in the world and experience it. Next we think about it and try to understand. And finally we respond with actions, decisions and often mistakes. So each of these seemingly simple steps are actually pretty complex. So I'm gonna break each one down with a few examples, fundamentals and hopefully some good takeaways for you. I'm also going to take really awkward water breaks. Okay, so one of our hardest steps here is the very first, which is just getting users to even notice all of your hard work. Sadly, it's also really hard to keep their interest but I'll get there as well. So hopefully you've heard of Steve Krug, awesome information architect, real UX pro, but I really like his way of describing the situation. The user's reality is Billboard going by at 60 miles an hour. You probably don't need me to tell you this, bless you. But humans are overwhelmed with a fire hose of information. We're dividing our attention between so many distractions that as a result we really have a hard time focusing on any one thing. So there are a few issues to consider here, well there's a lot, but I'm breaking it down to vision limitations, attention spans, reading issues that are all getting in the way as we're trying to discover content in the world. So this problem starts right in our anatomy, literally with our eyeballs. So here you can see how we see, obviously very oversimplified, but the point I wanna make is sort of to show these receptor cells here. So in the center we have our cone receptor cells and these are creating what's known as our foveal area. This is a very small one to two centimeter area of focus right in the center of your vision and this is where you're reading and really putting your attention. So the rod cells around the outside are not as great and they're a little weaker at distinguishing color and shape, so this is what's creating our blurry peripheral vision. The point being that most of your site is being seen in this blurry peripheral. So it's getting pretty glossed over while users are hunting for one thing at a time with that little foveal area. So it's pretty common for users to overlook your small errors or updates. So please help site visitors scan pages by creating clear visual hierarchies. Be decisive in what you're drawing attention to because if you make everything really loud then they're not gonna really hear any of it. And if you can, keep your feedback either right in proximity to a recent action like clicking a submit button or if you have to put it in the periphery try to make it bright and flashy so that people will actually notice it. And obviously be careful when I say that I kind of thought, oh no, I want marquees. So if something is super important, be careful but do think about adding really strong visual cues like animation or sound because you know that you're gonna hesitate if you hear that horrible error chime. Now once we finally do notice something, our second hurdle here is to keep our attention. So fun fact, I had to keep changing the slide because the key's getting worse. That makes me really sad. So almost half of users will give up if a page takes three or more seconds to load we'll just bounce. Now whenever I hear this statistic I always laugh and think of a Louis CK joke about how spoiled the technology we all are just browsing on our phones and I did debate doing like a really bad impression of him but instead I would love it if you guys could just read it. So I wish this whole thing was a joke but it is real and sad. So our attention usually spans just a few minutes and again, how many exactly is debatable because it keeps going down. I think it was 12 and then 10 and now I think it's around eight but it depends who you ask. So just a few minutes and then even this is broken up by distractions. So you can really only expect like eight focused seconds of unbroken attention at a time and even that used to be 10 seconds that we lost to. So I just think it's really baffling how lame we can be, especially online. So I just wanna take a little tangent here and I'd love some hands. Just comparing the sort of brick and mortar experience to online shopping.  No, why? Okay, I think I got two hands which honestly I'm okay with that. Okay, compared to the 67% that we are suffering from online. So yes, we're busy and distracted but that's not actually the full focus issue that we're dealing with. So even when we're paying attention humans are still just focusing to a minimum and we're learning just as much as we need to to get by. Research shows we're actually relying on incomplete descriptions of things even if they're important and we need to remember them. So maybe you're familiar with this logo. I'm actually looking at quite a few of them. So the Apple logo is pretty easy to recognize, right? But not to recall. So in a study participants were asked to draw it from memory and they're not really, yeah, exactly, thank you. So they're not really that close. I mean, like most of them remembered that it's an Apple which was in the brief. Half of them have a bite but you can see my point which is that we're missing a lot of the remaining details. So this is how we rely on salient cues and then just generalize the rest of them. And it's just one example of how humans have learned to ration our attention and intentionally ignore things like parts of websites. So, just stop looking at these notifications. That's no good. Heat maps show us how humans skimmed on the left side of the page here in the red in a sort of an F shaped pattern. And you can see here that we suffer from banner blindness. So the green ads and all that stuff on the right over there because we've been exposed to so many ads in the past that we're just learning to ignore them. Now you've probably seen this but what I am so amazed by is that this has actually grown to the point of what's known as carousel blindness. I apologize for the quality but you get the point which is that even this site specific content which might be exactly what your users want is gonna be ignored because it looks just enough like an ad that it's generating the same blindness. So carousels end up wasting lots of space. Thank you. No, I honestly I just wanted to make that very clearly so that you all have another point for your next kill the carousel witch hunt. Please say it. Okay, so obviously as designers we have to embrace and accommodate these attention spans there's a few things we can do. Simplify your designs to reduce hunting and just reduce the cognitive load in general and I'm gonna keep saying that. Again, keep pages easy to scan if you can. White space is a great way to focus a user on something. Just like scrolling is really cheap. I hate arguing about that. But white space is great also because it can increase comprehension on the content it's in by as much as 20%. So break up your type into clearly labeled chunks. Use bulleted lists, infographics if you're feeling really sassy, title things but at least just make it really scannable again. Break up your tasks as well into smaller manageable chunks. Remembering that we have eight seconds of micro task. So really break the flow down. For a user flow where you get a lot of drop off like the online cart think about forcing focus even further by removing more and more options. So ads and even the navigation all together there's no shame in just until the transaction is complete. So there's one more level of complexity for discovery when it comes to website content. So usability consultant Jacob Nielsen pretty much sums up that we don't read. We're not readers, we're skimmers and as I've said already we're ignoring a lot of site content. Of all the statistics today this one blows my mind the most. Users have the most, at most the time to read 20% of the words on a page during an average visit. So put less please. Humans are wired for language but the problem is that evolution just hasn't kept up with us. Like how long ago was the printing press compared to all those other evolutionary milestones. So we're wired specifically for speaking language but not for reading it. And that's not even considering almost half of the country but is suffering from some form of low literacy. So when humans need to understand something instead we're hunting for visuals. Images, videos, icons and these are great because they give us a break from the reading or they can just simply reinforce the text. Which is also great because spoiler we also have terrible memories so a little repetition does not hurt at all. But obviously you're still gonna have some copy on your site and people will still have to read it. So the biggest thing you can do is just make sure that that type is legible enough for them to read really comfortably. Maybe you guys have heard of Jason Palmontal. He's from my neck of the woods in New England but he is an ambassador for legible type on the web. And this is just a tiny sample of his fantastic type scale which is essentially a good place to start when you want to figure out type sizes and spacing for your particular content in a particular context. So yeah, please go look it up. But my point also here is to find a balance between type sizes that are large enough to read comfortably but not so crazy big that there's so much scrolling that it's actually affecting scannability. Also please use some design basics. I'm not gonna get into that too much but don't set the type in some ugly hard to read display font. I would love that. And just be careful about your type setting. So even using all caps can actually really slow your readers down because we're using the tops of the letters to skim. And yes, I know. That was a nice moment this week. So lastly, you need to consider the words themselves. This is another area where you can simplify. Using short, clear words. Please do not get cheeky if you're gonna make your calls to action unclear. I know people wanna say let's go but where are we going? So also please make sure that you're phrasing and the nomenclature that you're using is correct for your audience and what their tasks are. So I'm gonna talk a little more about this in the next one but for now just consider that humans are scanning with that little foveal area for specific keywords. So either because it has to do with our task or something about us, we love our names. And also we really like the word free. So use these sorts of things to your advantage. Okay, so it's not all negative. I love people because we really, really do try to understand, we want to figure it out. We do have an innate desire to learn. So we try to create order and sort of navigate this complex world around us and we'll seek patterns but sometimes when there aren't any, so I hope it's no surprise to hear that as we go over thinking as well, there's a lot of shortcuts that we're taking and these can cause some misunderstandings. So I wanna run through a few basic concepts with this one to try to help us understand how humans understand. So mental models, also known as schemas are our greatest cheat sheet. So essentially they're conceptual models that individuals hold that are formed by how they believe that something works which may or may not be true. So for example, if you were taught as a child or saw in a book the stereotypical domination as the dog and learned that this is a dog, it's pretty easy to expand our model when we see this dog and quickly understand that it's part of that same system. So this is how we can kind of tap into existing comfortable mental models to teach something new. So to bring it a little closer to home, the floppy disk is great to symbolize saving or was great because it's a real world comparison and now people are like, what is that box? So the trash can is still great though. I love this example because it's so much easier to relate to people that were learning to use computers for the first time to just throw something out than having to explain the concepts of like clearing drive space and deleting files. So those are great to consider when teaching something new but if you can help it, please don't because nuisance systems of interaction require a lot more attention and effort. So users are gonna often struggle with them. Building off of the site patterns that people are expecting can really enhance communication. So really there's no shame in reusing them well, within moderation, right? For example, you can use the tried and true inverted pyramid approach. This is originally from newspapers but essentially you see that the most important information is at the top and it kind of goes down in hierarchy from there. Even though that is print and we're working in a digital space, humans have adapted our short form content pattern and we do expect to see prioritized content in the top third of the page. Please try to put information but especially the links where your users might actually go looking for them, where they expect them. So your cart probably goes in the top right. It doesn't have to be special. Like I don't wanna have to find it. We look for the, most of our links in the header obviously but some we might expect in the footer. Support jobs, et cetera. But if you do have navigation that's really unique, consider an activity like card sorting to better understand users' mental models. So you write the navigation items on flashcards and then you ask users to group them. So literally sort cards. And you just wanna make sure that everything ends up where they're actually gonna go looking for it. So another huge concept to understand when understanding this whole modeling idea is affordances. Can you guys show me if you know what I'm talking about? Okay, this one's not that hard even though it can sound it. This is another Donald Norman concept that he introduced many years ago and then has sort of continued to tweak because I think a few people misunderstood but essentially affordances define what actions are possible based on an object's properties. So for an example, this door affords several actions as possibilities, right? Knocking, opening, closing, slamming, turning the handle are all affordances here. So most of this is pretty straightforward because for the most part we know how doors work usually. But my point is that most of us know this because we've already created a mental model of doors and you didn't have to examine it to get in here. But sometimes we do need to learn something new and these affordances aren't always so well established with us. When we are lucky, we have perceived affordances that can be clearly understood. But during novel experiences, it's more often that they're hard to discover. So if affordances cannot be inferred, as designers we have a responsibility to provide what Norman calls a signifier. So this can be almost anything, it's usually a copy, a little messaging or a graphic or something. But good signifiers communicate what actions are possible and also maps out where they're taking place. So shower handles. Affordances of handles are pretty clear. You turn it and something happens. Hopefully it's water. But the colored signifier here is indicating hot or cold, right? And then of course there's a lot of them that can show you tub or shower and there's lots of extra special features since they're all unique. So this is how humans are using cues to better understand how to interact with objects and the world. And we need to make sure that these cues are clear online. Please make links look like clickable links. Remember when they were all blue and underlined and everything was in Times New Roman and there was no question. I know it was ugly, but it worked. Buttons need to look like buttons. I know this sounds really obvious, but I had to say it because I think as designers we've really taken the signifiers out of our interactions because we're sort of chasing this like sexy flat UI and everything. And now the banner and the title and the H1 and the call to action all look the same. And we're hurting a lot of usability and adding a lot of unnecessary confusion for our users. But not all of the confusion is our fault. I should say that. So as humans are mapping out the world around them it's really easy to draw our maps differently which isn't always wrong or an error. But what you think your site looks like might be way off from what visitors are seeing. So remember we're all coming from different backgrounds with different experiences and have formed different mental models. Especially if you're coming from a different culture or place it's common to interpret something differently. So that's actually right. Let's take red for example. This has some universal meanings, right? McDonald's. But a lot of the cultural meanings are contradicting each other actually. So red symbolizes luck in China. But mourning in South Africa. Masculinity in Greece. But the feminine childbirth in Japan. So this is another reason to do your research and make sure that what it means is what you think it means. Especially if you're branching out to a new market. And you also wanna make sure that your audience has the right amount of experience or the right background. Because you really wanna be careful if you have some experts coming to your site but we're not all experts. Because you can alienate people with kind of industry lingo. Now sometimes these mental models aren't in this sort of gray area. Sometimes they're totally black and white wrong. And the problem is often that we learn things wrong in the first place.  So if those were dogs, yeah, this is a dog. So these kind of errors are really tricky because they seem to be validated even when they're wrong, right? So they can be especially hard to pinpoint and correct. Another one that we really struggle with is cause and effect relationships. Part of this is because of the emphasis that humans put on timing. So if two things happen within 0.15 seconds or less, which is pretty fast, we're often gonna assume that the first one causes second. So in the same vein there, if the website doesn't react in some sort of way during that period, we're often gonna wrongly assume that our actions didn't have any consequences. I'm not saying the page has to load but like give us something. So that is why it's so easy to submit a form a second and a third time. So remember please to clarify your relationships as much as possible with informative, fast feedback. So remember that humans are seeking all the time to understand the impact of their actions. So progress bars, loading states, especially confirmation messages go a really long way. Okay, I feel so bleak up here. I know it's not super rosy so far with the struggles that humans have but we do have one more usability minefield left today. Simply put, humans act on misinformation and make irrational decisions. And I know that can be kind of hard to hear because we all think that we're rational but we're not. Humans do have really complex brains and we are equipped for great intelligence and creative problem solving but that's not the issue. The issue is that often we're just taking an easier way out instead of using our brains completely. So I'm gonna butcher this and do this really quickly but I just wanted to show you some of the sections of the brain and their functions. So at the base here we have kind of some of our most primitive areas of the brain. So the brain stem with the spinal cord going down and then on the right we have the cerebellum sort of known as our little brain. But these are controlling bodily functions like breathing, walking, but they're all tasks that we complete without any conscious effort. So our brains are really helping us phone it in. Next, the limbic system does a ton of regulation. Some of it unconscious, some conscious but specifically I just wanted to point out that little amygdala. So this is sometimes known as our primitive lizard brain because this is where our anxiety and fear live. So this is where we're still making those sort of caveman fight or flight decisions. And then finally, of course, we have our main evolved cortex which is divided into four lobes. So in the frontal lobe or tons of functions and one of them is making judgments. But it's not really as simple as saying that all of our decisions come from this little part of our brains because brain scans actually show us that decision making activates tons of the different sections that I've gone over today. So yes, sure, some of our thoughtful decisions are coming from a big evolved brain but a lot of them are being made below and more primitively. So in truth, our brain is processing most information completely outside of our awareness including some of those judgments. So really think about this one for a second because I think it's easy to deny we want to. It takes around 100 seconds to make a thoughtful, critical decision and that's in a pretty fast thinking situation. So just take a second for me and think about how long that is and then how fast most of your decisions actually are and if they're faster than that. I consider just like waiting for 100 seconds but I'm not gonna do that. So snap decisions we're making with emotion, unconscious decisions we're making with instincts but we're not really using logic in that little timeframe. And what's even worse is that there's a lot of evidence accumulating to show us that the greater purpose for logic is not for the decisions themselves but to justify them to ourselves later. So we're rationalizing any bad decisions away and reducing cognitive disness and feeling better about ourselves. So yes, we are rational, we're also judgmental. People really do judge books by covers and we judge sites in less than a second. So a study shows us that web users form first impressions of web pages in a 20th of a second and maybe you're wondering like I did what is shaping these first impressions. So according to a Stanford study the most cited factor used in evaluating a website as credible is the appeal of the visual design. So the right layout, typography, color is making a huge impact and it's making it immediately and I love sharing that if you're maybe in like a very dev heavy world or dealing with a difficult client because it kind of validates the significance of good design for the site's success. So hopefully this is clear. Humans love shortcuts and we continue to take them even after that first impression. So as I've said, we don't always care about doing things the right way. We're rushing around and as a result we're satisfacing making mistakes and slipping. So I wanna break each one of these concepts down a little more. Satisfacing is essentially a lot of the key points that I've made today but it's choosing the first reasonable option instead of the best. We would be much happier doing something we've learned to do even if it's a lot slower. As long as it's getting done we don't care. My favorite example of this is how people will go to Google and search for a URL and then click on it instead of just putting it into the browser. It's like, I know it's just an extra click but it's always an extra click. So when we talk about mistakes a lot of times we're actually grouping a lot of things together but specifically mistakes are made when we misunderstand rules or knowledge and so we don't know any better. So we're intentionally doing the wrong thing mistakenly if that makes any sense. So slips are unintentional, they're just accidents. These are based on memory or motor malfunctions like when you accidentally tap an ad on mobile. Nobody wants to do that and then decided it was a bad idea. But here's where this all gets really sad. Often we're making these errors because of poor user experiences that didn't consider every single situation and yet humans will almost always blame themselves. And so this can cause what's known as learned helplessness. Maybe you've heard of this from the behavioral psych studies but essentially users won't even try to complete a task if they've failed it in the past because they assume that they're the problem and they're not gonna succeed and that they shouldn't even bother. And it's kind of hard to catch these because people are embarrassed. They're not gonna complain about themselves so it's hard to correct these usability issues with user feedback. So my suggestion here dealing with this is twofold. We want to, well I can't move at all, we wanna combat these effects not only by trying to reduce the errors using a lot of the things I've talked about just making a simple, simple user experience. But we also have to acknowledge that the mistakes and the slips are going to happen and we just need to keep them as cheap as possible. So consider that the back button accounts for something like 30 to 40% of all web clicks. So allow for backtracking and if you have a really complicated system, maybe build in multiple undoes but please just don't make anyone start over. So this is something that I'm really fascinated with. I'm not sure exactly, I think this came out of researching plane crashes and they were trying to figure out what was like causing these horrible things to happen and how to obviously reduce them. So it's not that these huge losses are occurring because of a freak disaster. Usually it's a result of lots of little mistakes in succession. So James Reason gave us the Swiss Choose model to sort of illustrate that and you can see here how adding extra layers of defense can actually block these little mistakes from becoming a big loss. So keep your mistakes from going bad to worse with design redundancy and obviously lots of user testing. Okay, so we've seen today many of the problems that people have with interacting with the world, trying to figure it out and really doing anything about it. Now to be clear, I did not tell you all of this so that you could just feel bad about yourselves and go home and try to fix it. I'm telling you so you can accept it, expect it from users and adapt as a designer. And we should really appreciate all of these shortcuts because in reality, life is really hard. Life is so overwhelming that we need shortcuts even with their shortcomings. We're really lucky that our minds will gloss over the detail and keep us moving. So I actually do have one more persona for you today but this one's a little different. This one's a web savvy millennial that grew up with Google and is so in tune with website patterns that she once balked at the idea of somebody not knowing that you could click on a logo to get to the homepage. I asked my dad, I asked Average Joe actually how to get back to the homepage and he said you hit escape. So, but you see where I'm going here I'm sure except that this persona does not just represent me. I have a feeling that it represents a lot of you in this room and I just really don't want you to design for us anymore. I think it's really easy for us to misjudge these intricate interaction patterns that we might create as common sense just because we understand and you know I would encourage you to really stop and really think about if we're giving our users too much credit.  So for example plan for that moment when they're gonna swat away that useful onboarding information that they need and then plan again for the moment when they realize that they need it. If you only take one thing away it's just to simplify you know reduce complexity as much as possible. I love the way that Steve Krug put it he titled his user experience by Bible don't make me think and you should read it if you have not but that is not my point. My point is just to make things easy please. So reduce friction and excuse me cognitive load as much as possible and again we've talked a lot about this already create clear hierarchies and messaging maintain consistency across your site with familiar website patterns and you know common sense really helps. And also reduce choices if you can and I know that this one seems counterintuitive especially if you are doing user interviews because people really think that they want this but they don't and often users will suffer from what's known as analysis paralysis. So my favorite example of this is a psychological study with two sample tables of jam one with six kinds and one with 20. So consumers were trying more samples from the table of 20 but they were buying way more at the table of six because it was a lot easier for them to decide which one to actually pick up at the end. So the more choices that were given the more difficult the decision. Now I know this is a really tall order and it's easy for me to just stand up here and say this all but we do need to use our research as best we can to understand our users needs and really carefully prioritize them to the fundamental needs that we absolutely have to solve and the latent needs of delight and kind of work our way up from the basics. If you can just keep reminding yourself make a post-it to just return to their underlying goals and one way to break a problem down to find these underlying goals is to just keep asking why, why, why until their ultimate cause is clear and then make sure that these goals translate into the right tasks and micro tasks. I think it's easy to start like sketching the interface and here's where the button is but just make sure that like why is it even there and what do they wanna do. I really love the way that Theodore Levitt puts this. We need to remember that people don't want to buy a quarter inch drill, they want a quarter inch hole. So please streamline the flow wherever you can if you can and let your experience really get out of the way of the sort of A to B journey we've talked about. But again, if you can, if you have the time, the budget, et cetera, go beyond the task completion here and really aim to meet the higher needs of your users, aim to delight them. Think about like Freddie the Mailchimp, I love him and he's so funny and that was extra, that's just fantastic. So these enjoyable experiences can be caused by a range of things but pleasing aesthetics, incorporating humor, creating flow for your users are really solid places to start. I add novelty but we just have to be a little careful but defying convention can really arouse curiosity or satisfy a desire to learn so it can be a great one too. Another fantastic thing about creating enjoyment is that it can actually help with satisfying some of the basic needs. Enjoyable experiences are also perceived as easy to use and efficient even if they aren't and a fun, relaxed environment increases flexible thinking and problem solving. So one, this helps users to excuse any hiccups in the flow they might be having because they're having a great time or they might be so creative as to just work around them on their own. So I did my best to cram a lot in today but even so, I'm sure that you get that this is very high level and it's just a taste. So I challenge you all to dig a little deeper on your own and learn a little bit more about these psychological fundamentals. Please work to understand the fundamentals of human needs and behavior and combine them with your specific persona needs and knowledge to understand those problems more holistically. To truly solve a user's problem, we need to make ourselves familiar with the realities of this rocky usability terrain and adapt. Or put more eloquently by my favorite Donald Norman, we have to accept human behavior the way it is and not the way we would wish it to be. Thank you. So amazingly, we do have time for questions. If you guys wanna step up to the mic and ask any, otherwise you can get at me here or online. Yeah, thanks again. I thought you were just leaving really fast. I just wanted to add, is this on? You hear me? Yeah. That Donald Norman has an online course now at udacity.com and it's called the design of everyday things. Oh, fantastic. Actually grade your assignments and all that stuff. Thank you. How do you usually justify the addition of more scrolling when you could condense something more mostly to stakeholders? So how do I justify adding more scrolling when stakeholders think that no one goes below the fold? I think that that's tricky. But you know, I think the simplest thing is that we just say that scrolling is very cheap. The act of just the flick is very simple. And I know there's a statistic that I don't remember at the moment because I think in the past, people did used to struggle. They were used to the newspaper with the fold. But over time, we've gotten a lot smarter about it. And so I would encourage you always, when you can, to have a statistic and say actually, 2% of users can't figure it out. Whatever it actually is. How do you feel about hamburger icons? Can we stop recording? That's hard. I think that you really do need to think about your audience. So this is very funny to me because we're actually in the final throws of the process of redesigning lullabot.com, which uses a hamburger icon. And we kind of came to the conclusion that we can take a few liberties because we're dealing with, you know, we did our research and talked to our users and we are dealing with more technical clients that are, again, a little more in our space that are understanding. But otherwise, I don't recommend it. I think the greatest thing is, I think the first one I saw was maybe Squarespace. It says menu next to it. And that's so obvious. Like that's great because now you're touching all the people that get the hamburger thing and you're hitting everybody else with menu or nav or something. So I would suggest usually adding something else and just making it super obvious, you know, hover states and the like. One of the things I ran into in redesigning our website was we wanted to do that when you're talking about reducing choices. So you take this huge mess of a menu we had before and reduce to the small thing. But then the pushback was from people that they were expecting this individual thing in that menu and they don't see it there. And we come up with these, you know, canines for the different categories that we think they fill that, but then everyone has a different idea of what that thing is. That is very tricky. I think that, you know, I'm hesitant to say this, but if you have, you know, accordions or hover or something where you can actually expand them and it's easy for people to see all the options, I think that's great. Again, like I said, if you have the capacity to do more user testing and do card sorting and see what are the words that people use for them, what are the groups that they might put them in, you know, it might help with people finding them. But yeah, I mean, I think at the end of the day, sometimes you do need to have a gigantic menu, like Amazon or something that does show all the offerings, you know. I worked with an e-commerce site that had all these random products that don't match and you do have to have something to click on at pretty much every point that they're gonna sort of recognize is what they're looking for. I hope that's helpful. One other question. What are your thoughts on hover for desktop? Is it something we should keep doing or? Oh yeah. Is that like, did someone say not to or? Well, I know Bootstrap is switching over to like click menus and dropdowns, so what are your thoughts? I see, okay, I see what you're saying. So I think that hover states are for showing that things do things, but not always for doing the thing, if that makes sense. So I made this mistake, honestly. I created a website where you hovered over the navigation and it pushed everything down with this big menu, which means that if you get too close, you just like, you know, on the ocean and it's like really terrible, rocky thing. And so yeah, I think that if you can have a little teaser come out or a little something, maybe something fades in that's a little copy that's helpful, an animation color change, but yeah, I mean it depends, of course. So we could talk more about this for sure, like where, because if it's a little thing, you hover over a photo, you get a little information, I think that's great, but if it's real like navigation, I don't think that that should appear. I'm more referring to like a primary navigation. Yeah, I mean I do think that it makes sense to explore with like sub menus, you know, you can just click through. I see what you're saying now, yeah, absolutely, you don't wanna make people click and reload the page. And that is, that's horrible. Because then it should not take them more than 10 seconds, so just figure out all the things that are on the site by just hover, hover, hover. So I see your point, yeah. And so, you know, I've dealt with that before where there's so many things that you have to click to see all of the subnav for that individual page, and it's just creating so much extra loading. You think about how much does each one take to load and the manual effort of them to click every one, and it just, it seems like a pretty easy no-brainer to just make that a quick exploration task for them. Thanks. Yeah, I don't wanna talk about that one. Yeah, that's really, no, no, I'm just teasing. I mean, that is really hard. And so you, obviously, if you can translate it to tap, for everything, that's great, but I know that's really finicky because tap and clicker are pretty gray. Nobody else? All right, well, thank you so much. Thank you. Hang it up in cords here. Thank you. I was worried.


Okay, so thank you very much for inviting me to be here. David Dimmick sitting over here is really the clinical director of the whole Genome Sequencing Lab, so everything that's all the hard questions go to David. So the overview of what I want to talk about is our Diagnostic Odyssey Program. This is a whole Genome Clinical Program. Talk about just one slide on the initial case and really spend a little bit of time talking about laboratory certification for the Sequencing Lab and something that I think is equally important is certification of the analysis, not just the wet lab side. Selection of patients and why we have a clinical board, consent and ethics, whole Genome Sequencing Analysis, the limitations around this, opportunities for these collaborations and so forth, and then whole Genome Sequencing in my opinion is simply another laboratory method. In absence of clinical data, it doesn't have a lot of utility, but it's the context in the clinical environment where we believe you can use it today and we also can talk about getting paid for it as we go forward. So this was our mission statement back in 1999, so this isn't new to us, although we surprised a lot of people with the initial case, was to try to figure out how to use Genomic Sequence in the clinic. That has been something we've been working towards since 1999. In 2004, our goal was to get Genomic Sequence in the clinic by 2014. So this is the index case that most of you have heard about. This is Nick Volcker, showed up at 23 months of age. This is how he presented into the hospital. This is not after surgery. This is presentation at the time. Long story short, after almost three years, a diagnosis was made using exome sequencing that the child had X inactivation of apeptosis, XIAP deficiency, and a decision was made to do a core blood transplant, which has effectively cured Nick. So that captured a tremendous lot of media's attention, much more than we were really anticipating was going to happen, and even with Francis Collins and so forth running around talking about it, it's created some good news and bad news. There has been some whiplash towards us around this, that it's been taking advantage of the patient and the family. We can discuss that if you like. But one of the issues that we've felt very strongly about a clinical program is it has to be for clinical utility. And because of that, we've set up an approach that we use for our clinical delivery. It's nominated, the patient's nominated by two physicians inside the division. And it's to end the diagnostic odyssey. I believe that this is a realistic, practical approach that you can use today. It's actionable. What do we mean by actionable? It might not necessarily mean therapeutic actionable, and I'll come back to that a little bit more at the end. We have found from some of our families that being able to make a diagnosis, even if it's negative, is of a potential benefit to that family member. A case review is part of the committee. There's consent that gets involved, genome sequencing, data analysis, and then follow-up counseling. So the guiding principles behind this is that it need that all reasonable clinical testing has been performed. And so the notion is that this is a diagnostic of last resort, if you will. It's likely to have genetic etiology. It's very rare. We hope that it's monogenic etiology, and the notion of that is it simplifies the search space. So having it being extremely rare and expecting it to be genetic, you'd expect it to only be found in that patient. Or one other family member, if it's a compound heterozygote, or in the case of Nick, was an X-linked. These have distinct and unique phenotypes that are more likely to have a definable result. The ability for genome-wide sequencing to assist and enhance a medical decision-making. Again, I want to emphasize it's to enhance the medical decision-making. It has not been, Nick Volcker case wasn't either, simply in and of itself sequencing. I don't believe that that's the methodology we're talking about. We need the ability to conclude a genome-wide sequencing study. So it's very easy to get in one of these. It's quite hard to get out. Because where do you in fact define that you've finished the analysis? And that is a major issue as you start talking about cost and where you go forward on this. We insist that the parents both must be available, appropriate tissue and DNA must be confirmed, and monetary cost benefit considerations. And the other advantage of having this clinical board is that they are detached from the decisions. They don't gain anything, either fame, fortune, or tomatoes by being involved in this. It also we think is important for helping to make sure that when we're practicing this on the edge that we can back up and say we've had other people be involved in the decision-making process and make sure that it's to the benefit of the patient. That's really what the goal is. So the genetic consent is another issue that we deal with. And genetics assessment is involved very early on, obviously, with an MD geneticist. Typically it's David Dimick or David Bick. A pedigree analysis with a genetic counselor, I think these are self-evident issues. The consent process, then, is discussions of data return. I know David Valley hates the term personalized medicine. But I think in our case, we believe that data return is also personal. We think that the patient and their family need to have a decision around what type of data they get back and we consider that to be part of personalized medicine. There's multiple consent counseling sessions, largely involving how do we deal with this consent process and what types of data with the family like back. The family has time to consider the testing and data return, followed by written consent. The average is between six and eight hours. It's two to three sessions. We're working on trying to streamline this. I recognize that this is not amenable for long term practice across common disease. That's not where we are. I think we still have much to do before we can get to that level. But we do believe in this environment, you can go forward on this. One of the things we spend a tremendous amount of time on is building a software package that is CAPCLEA certified. This has driven a huge amount of costs and it's a major issue. And I'll just give you a couple of little things that you may not have thought about. We use data from all types of sources. Those data sources have to be frozen, validated, and confirmed that the algorithms are coming up with the appropriate results that we've had previously. Many of you have been involved in some of these data sets. When you all change those data sets, we have to revalidate. And on top of that, the evolution of this continues to go. We have a continual argument about when do we use the new tools. And the new tools can't be used in the clinical environment until they've gone through clinical validation before they come forward. And that puts a real pressure on the bioinformatics team and a chronic recurrent cost of how do you stay up with this as it goes forward. But I will tell you, many of your most popular databases that you're using when there have been changes, there have been errors. And we're thankful that working with these groups, they've helped us be able to define that. So I think if you're interested in getting in this game, it's not just the wet lab. In fact, I would argue the wet lab is the easy part, because the wet lab is somewhat stable. But the analysis, I'll give you a classic example. We use Casava 1.8. Most people don't use that. The reason we use that was because that's what Illumina uses in their CAPCLIA laboratory. So when we get the data back from them, that's where we have to start. We can't change that. That's where we start. Okay, so I can answer questions around that. The limitations are, what does actionable mean? I think we can have a lot of debates around that today and tomorrow and for the next three months. But I think this is critical to how we decide what's there. Alignment versus de novo assembly, I think this is also a major issue. And it may well be that some of our really rare cases here, that it's going to be unique, strange events that we can't capture that we're missing. And that could be a major issue for us. So what do we need? Well, we need more data. The availability of genomic sequence. There's lots and lots of sequence out there. Most of it is not available. We'd love to have 462 new genomes. We'd love to be able to share. I think this is a space where for these diagnostic odyssey, if we're arguing that it's unique, simply searching across somebody else's genome is an advantage. And I think that's one place that we as a group can work together. There's very little clinical data. And I think these are major issues around as we're starting to think about this, not only family history, but clinical data at all. Questions of clinical utility and value, these are major drivers and they're major obstacles. And I'll talk a little bit about that as we go on. So this is what everybody argues about. The cost curve, can we actually bend the curve? And there's arguments about can we use genomics? And this is back to what Howard McLeod was talking about. This is really boring economics. But this is really what drives a lot of this. But if you go out and you look, the Congressional Budget Office, this is after the latest round of debates in the last presidential election, was talking about preventative medical care. This report says we actually drive costs up by trying to do preventative care. And so if we're going to try to bend this and use that argument, we have to be able to show that it actually changes the health care cost. Well, we're all familiar with this and I hate to walk into this because there's been a lot of people talking about this that are much smarter than I am. But just as a simple, silly example and an example that we've used to some of our local businesses in Milwaukee, what if you use Plavix and you go in and you have 300 patients? What's the economics on that? So this is a true case of a major employer in Milwaukee. And they have approximately 300 patients on Plavix. You could argue that approximately 100 of these will have a genetic abnormality. And up to 50 of these patients may have a complication. So you can do some simple math on this. 50 people at $50,000 for an event. It's $2.5 million just to look at that cost. If you were to say you could do whole genome sequencing and analyze one gene, we can come back and talk about the economics, but I'm not worried about the cost. The cost is continuing to follow. It is not expensive to analyze one gene. It would cost about $300,000 to survey these three people. The argument is let's just switch to another compound. I just picked this one. It could be a different one. But there's other ways you can save money on this that we don't stop to think about on the academic side. Plavix is coming off patent. So if you get a drop in price on Plavix, you may actually want to do the genetic testing in order to keep people on Plavix. Because keeping the people on Plavix would reduce cost. And if you go through the calculations here, a simple $100 per month drop for this particular company is $240,000 per year in clinical costs. And so you can add this up. And you would find that over five years that looking at these 300 patients would save $3.9 million. Here's the problem. You're saving money. Who's going to put the money in in order to save the money? And this is the challenge. And so as we go back and forth, there's major issues around this. And I want to ask a question that if we can answer this, it would help. It's not what is the cost of a genome? It's what is the value of a genome? And I think that has to be the driver, not only to our studies, but to other studies. And so you can leverage it. Somebody has to pay for the upfront costs. How do you amortitize that across the other studies? So one gene test at a time, it's not cost effective. If you run a clinical laboratory, it's not cost effective to do this one gene at a time. It's expensive to keep that up to date. It is much cheaper to do one platform or two platforms chronically and across the whole thing. But what's the value of a patient's genome sequence? I would argue that a whole genome sequence is, in fact, family history with data. And I'll tell you what I mean by that. Back to the point of, did you have your family history discussion at Thanksgiving? Even if I have family history discussions at Thanksgiving, I have zero confidence in my family's knowledge of what diseases are in the family. So not only do we not talk about it, but when we do talk about it, it's inaccurate. Yet we put this out there. So I was quite surprised. I used to be on the FarmGKB advisory group, so I went in, look, how many drugs are there, or compounds, with genetic information? Well, the answer to that would be 370. It's a lot of information that we're probably not leveraging. How many diseases or clinical phenotypes are out there? Well, the genome-wide association studies, which I, of course, have criticized up one side and down the other side, but I got to say, there's 237 traits that have been attached to the genome. And we argue about, well, what's the predictive value of these? It's not very important. Well, we've gone on to do some genetic studies in animal models. I'm not going to go into all of this because it's way beyond this. But we are finding, actually, that these genome-wide association genes are having significant effects in both blood pressure and renal disease. And so I think it's going to play a role. And there are some groups that are now starting to say, how about if we do risk-position of complex disease from family history with known susceptibility loci? So this is a very interesting paper that goes through and models this. And I'm simply going to say, if you have a SNP that's been associated with a common disease and you report a family history of a disease, I would say there's some level of confirmation. The value of that confirmation is unclear. But I think one of the things that could be done by this group is ask those fundamental questions. If you have it, what does it mean as one example? Now, you're all familiar with this, salt and hypertension? How many of you believe salt causes hypertension? It depends. It depends, OK? All right, so from Scientific American in July 8, 2011, it's time to end the war on salt. And the reason for that is, is if you go in and look at the epidemiology, across the epidemiology levels, it causes a 1.1 millimeter increase in systolic blood pressure and a 0.6 millimeter increase in diastolic blood pressure on average. Salt on average is what your kidneys are for. But we very well know that there are patients out there who benefit from a low salt diet. I'm going to argue that the SNP data is very much the same thing. On a population level, it might not be very useful. But on an individual basis, is it salt or is it completely useless? I think these are fundamental questions we need to address. So whole genome sequencing, it'll be a long time before it's used clinically. I've been told this over and over and over again. We've had our clinical program for one year. We've had 50-plus nominations come through in-house. We don't advertise this outside. This is not something that you'll see us running a web page on. This is in-house physicians who want to use this technology to answer their questions. No one will pay for it. So here's a letter from insurance group from February 23rd to David Dimmick, and it basically says, as we have discussed, the situations where you determine that on average the cost of routine testing will exceed the current contract price of whole genome sequencing, we will authorize whole genome sequencing as a first-line clinical test. So we've put forward whole genome sequencing 10 times. Four have given pre-approval. So I think, again, as the cost come down and the utility comes up, it's not the cost, it's the value. What is the value of that genome sequence? So we've put together a team that's involved in dealing with our patients, the clinical care team. We haven't modified at all. We have a sequencing team. We have a clinical molecular testing team. We have a data assessment team. We have an LC team. Our ethicists are involved in the decisions and the clinical phenotypes and family history and the bioinformatics and electronic medical records pieces all swirl around. I won't tell you that I'm happy with where we are with integration. There's huge needs that we have to bring together these different data and make good quality tools for making informed decisions. This is where we'd like to go. There's a huge amount of data that can be drawn in and really try to pull this together in a clinical context along with a person's genome. And I think that's very valuable as well as that evolves. As people make gene discoveries, it adds value. I'm going to argue that maybe what we're talking about might be a little bit too slow. Because I think it's a rapidly changing landscape. Now that whole genome sequencing is being offered by many groups, I think we're going to see a massive rush towards this. And it's going to come down to the same way that consumers start demanding these issues. The cost is still a little bit high. But I think as it comes down, there's going to be more and more of a driver towards us. And the more data there are, the more we have to deal with. And I think this is going to be a very aggressive pace. And I think we need to think about that as we have these discussions. I have a large group of people that are involved in working in a variety of the projects here. This is the overall team that was involved in dealing with Nick. And I just want to summarize by saying, the cost for data generation will fall. Within the year, I'm going to guess it's going to be about 2,000 for a whole genome sequence. And we need to start asking, what's the value of these individual gene chips? Should we basically figure out how to take these costs and go forward with this quickly? Data management and clinical decisions is the challenge. I will argue over the wet lab. And I, again, want to emphasize, I think having a certified software is important. I think it is just another lab value whose context with respect to clinical presentation is critical to the utility. Genome sequence by itself is not a diagnostic. It will never be a diagnostic by itself. We need the other pieces around it. But it does have value now. And I think it can be a family history with data. For example, somebody who doesn't have a good family history, those SNPs, I would argue, have a potential window that could be leveraged. The question is, what's the value of that window? It's cheaper to develop a single platform rather than having to maintain proficiency testing for 30,000 genes. It's much cheaper for one platform. Data return, in our view, is part of personalized medicine. There's lots of education needed. I think this is the biggest challenge that there is. How often are these tools and tests available and the physicians aren't taking them up? Plavix is a classic example. I was just presenting to a vascular surgery group this last week. One out of eight physicians has ever ordered a test and they ordered it three times and it was rejected twice. So the issue is, well, why are we offering it if no one's gonna pay for it? And I think these are critical issues. So the needs, access to results from whole genome sequence, those of us that have it, we should share these. It really enables the aggressive use of that data. It's critical. My rate limiting step for helping the patients today is not enough genomes. Access to whole genome sequence with clinical information, how do we do that? Well, one may be some type of a banking type structure where you're able to go through and query across a phenotype and a specific gene. Can we use that as a way of sharing data back and forth without necessarily sharing all of the data? What types of tools can we use around that? What is the value of having the whole genome sequence? I think if we can answer that question, a lot of the things that we're fighting for and against will be clear. Demonstration projects to show the cost effectiveness and utility that comes back with value. Tools for integrating with family history, I think that's essential. Follow-up validation, how much? How much will you require for your clinical practice to decide once you have that variant, you're gonna believe it? And that's a major issue as well. Decision support tools and more powerful electronic health records. I think we're not in a good position to be able to leverage that with the current technologies and lots of education. I'm happy to take questions, thank you. Oh, I have one last thing, one last thing. So you all recognize this as part of medical care. In this day and age, you would have been burned at the stake. You all look at this as part of medical care. I'm simply saying that I think sequence is the same level. We just don't know how to use it the same way. And although maybe it has been overhyped, maybe it has been something that people think that we've taken advantage of, but is there really a special case for whole genome sequencing? We make misdiagnoses every single day. Not because we're trying to, but due to lack of knowledge about a disease. Nick was misdiagnosed, not by his fault, not by anybody's fault, but that's what we knew at the extent of that. It's not actionable, it stresses the patient. How about end stage renal disease? We give people that information. 25% of the people are still alive five years later. How about stage four cancer? We do this all the time. Evidence-based medicine? Absolutely. But exactly how do we do the population versus the individual? And we drive all of this data and the large numbers. It's a critical question that again, I think this group could tackle and how do you show clinical utility around that? And I think on average, we are making progress. At our institution, what has changed, how we do medicine today is simply because of Nick and the fact that we did it and no one thought it would work and our administration has bought into it. But for me personally, Nick celebrated his seventh birthday on October 23rd and he went Halloween trick-or-treating for the first time. That's why we're trying to do this. We're making mistakes, but I think collectively we can all do this better. So that's what I wanted to finish with. All right, questions? Do you have experience with your program of finding changes that were not what you were looking for but you still consider actionable and has other testing been required that weren't relevant to the initial diagnosis? Wait, say the first part again. So who do we have? So you're like Nick, you sequenced for this specific immune disorder. Are there cases that you've done where you found other things in the genome that were not relevant to the diagnosis of interest but that you felt needed to be followed up? Yeah, so in the case of Nick and with all, Nick was a whole exome sequence and everybody else has been whole genome. One of the big challenges we have is how do you match a phenotype with the genes you're looking for? So we have a case right now that is driving us crazy where it appears to be immunological by some of the clinical teams view and a strokes are happening on the other side. So half of the clinical team thinks the strokes are the problem and half the clinical team thinks it's an immunological problem and the drugs are causing the stroke. There's a great example of what we're trying to deal with so which one is it? So as we go through and look at the genes, if you find a gene that has been implicated in one of those others, it helps lead you in the right direction. We're pretty much done with those lists and it may well be now that we're now stuck with, we've ruled out both of those two categories. There's one right now that might be but that is a major issue.  So what do you do with that? So this is where having more genome sequence you could then say, okay, how many of those could we wash away that are rare or not rare? Does that answer your question? Yeah. Okay. But that was very interesting. Okay, how about if I get the question right? Yes. So do we have incidental findings? I mean, what are those? Right, we are not looking for incidental findings. However, however, we do have, and David can talk about this if you like, we do have as part of the data return, the families do have the right to ask for data, okay? So in those particular cases, we will go back in and look at those data and we will do validations and come back on that. Did I answer that right? Yeah. Okay. Discussion of the variant caller from Illumina. So as you know, there's been a thousand genome sequence by the thousand genomes project and I guess I would argue that we're still trying to perfect calling indels structural variants. If you call structural variants of five different programs, the intersections about 50% at best at this point. So, and indel is probably about 80% accurate. So by sticking with that manufacturer's caller, which is probably not one of the best ones out there. I mean, is that really necessary? Or as we move forward, do you imagine how we could implement things like GATK or other, I think it's a major challenge to decide what set of callers will be used because you're gonna be missing a lot of data. I mean, if you're not even calling indels or structural variants, then how can you go back to that patient and say they have no problems at all? Right, so it's a great question. So what do we deal with the fact of, first of all, there's no set analysis strategy that exists and there's variations in the different callers that come back, okay? So those are great questions. So the reason we started with the Cassava 1.8 is because that's part of their CAPCLEA certified delivery of data, okay? So that's where we needed to start with. So since we were using them to generate the data, that is part of their protocol, whether we agree with it or not agree with it. And one of the challenges of putting your clinical stuff out there and certifying it is you have to be able to certify that it's reproducible. So what you're using has to be reproducible, all right? So that doesn't mean there's not errors. That doesn't mean there's not things that are better, but it means that you can reproducibly go through this. So the challenge that we have right now as we go through with each iteration is bringing new software on. So if we now want to bring new software on, sure we can bring the new software on. We just simply go through now a whole certification process of making sure that GATK, when it makes a call, it calls it consistently. And then you make the decision around what do you do with that data that's consistent with it? It's not like in the research lab where you can pick and choose and take the best data. You have to settle on how you're gonna do it so you're at least consistent around that. And in no way says that there aren't better ways to do that, but those have to be continual iterations that you go through. Does that make sense? So that's just where we started. Now with the next iteration, we're rolling out more software and the next iteration will roll out more software and that's my point. Is that as we bring on our own wet lab group, this has been capically certified, we'll then have more control over what do we wanna do with the data analysis that comes out of that? It seems like a different call to anyone. Absolutely, I mean I don't wanna say for any stretch of the imagination that because we're doing it this way, that this has solved all the problems. We've simply put a stake in the ground and we're operating away from that stake. That's a moving stake and we have to continue to move on those. But I'm quite concerned, and I think that's probably the reality of where we're gonna be, that there's not ever gonna be one straight form analysis package that everybody's gonna agree on. I mean look at microwave analysis, this has been around for a long time, there's still big differences in how the analysis goes through. So I think another part that this group can do is make comparisons about what do these different tools mean and that of course is being done as part of the big genome groups as well. But those are also part of the decisions. If I can, since my name was taken in vain, I'll take 10 seconds to defend my point of view and then ask you a question. Yes. 10 seconds is just that medicine has always been personal. What it's not been is individual. So we ought to use the right clear term. The question is, the concern is how do you know you have the right answer when you think you have the right answer? There's lots of potentially harmful variants out there in the coding sequence, not to mention the potential regulatory sequence. So my concern, at least at the state of knowledge right now is how do we know we have the right answer without a lot of downstream biology? So in the case of NIC and in other projects that we have, we do the downstream biology. So that is one of the advantages of dealing with the immune system is that we have better ways to go in and do the downstream biology. So that was one of my points is, as you take on a case, one of the questions that we take in the case review is, if we think we find a variant, what are we gonna use to try to validate that piece? And so that is an essential piece and I think that's gonna be a major issue for a while and with some of them, it's gonna be even harder because if you don't have access to cell types, if you don't have access to tissues, what are you gonna use then for validation? So you can then start off and say, okay, we're gonna look at the known enterprise, okay? And then when we're done with that, we're done because we can't take it any farther. That might be one decision that would go into that process. You can't go off then if you can't validate it and do anything other than to say, okay, we're gonna look at all the 5,000 genes that are known for the cardiovascular system and stop there. That's one option that you could take. I'm not saying this is why, this is why I'm saying that we think that to end a diagnostic odyssey as a test of last resort, we've done everything we can possibly think of, we do run the risk of failing to find it but we've already failed to find it and so we're willing to say, hey, you know what? We can't do any worse. Let's not see, let's see if we can't make it any better but that's why I think this is not prime time for all common complex diseases for being part of making decision processes. I think we're a long way away from that. So Howard, I wanna come back to the question of the software which I think is huge and anybody could say whatever they want about how much a genome's gonna cost but the analysis of that genome is not gonna be included in the price and everybody talks about this but the analysis is key and de novo, we do everything on a reference which leaves out anything that's not in that reference and I think one of the things this group could do and put collective knowledge behind is what are best practices that we can do to begin to apply this and what are the validations that are best practice? What are, these are all really important questions regardless of what it can do. I mean, we as people who are practicing this should care about what people say about this, so. I agree, 100%. And best practices are gonna be one of the topics of the next meeting, standards and best practices. Question. Yeah, one question. Your description of the independent oversight and the consent, are these clinical oversight committees and clinical consent or is the IRB involved? It's clinical. Okay, great, thanks.