That's a very good question. Just as a very quick background, we published the payments aspects of financial inclusion report in April 2016, which was before the Fiji initiative started. It is a cooperation between the World Bank and the BIS through the commodity on markets and payments infrastructure. So once Fiji started, we started thinking that maybe we should use the Fiji information to update the report because the original report from 2016 contains seven guiding principles that helps and assist countries that seek to advance financial inclusion in their markets. So we think with the Fiji experience, maybe we can add on value. So what we did is that in October 2018, we reconvened our PAPI task force and we set ourselves three goals. The first one was to provide additional guidance on recent FinTech developments. The second was to produce tools to facilitate the application of the PAPI guidance. And the last one was to develop a measurement framework to assist countries in tracking progress. And both of these three work streams culminated in the publication of two reports in 2020. And I'll quickly present each of them since they contain a lot of useful information for Fiji as well. The first report was released in April of 2020. It was called Payment Aspects of Financial Inclusion in the FinTech era. And here we looked at all the new FinTech developments over the last few years because remember everything is very recent in 2016. There wasn't as much going on as there is today. So the first report is fairly limited on FinTech. It does mention it, but it's not so expensive as this report. So we put all the new developments and products in three groups, the products, technologies and access modes, and we sort of developed a big wheel in which we put all these things in place and we call it a PAPI FinTech wheel and it helps you to better understand the interactions between different technologies. The analysis of the report tells you that FinTech presents both opportunities and challenges in improving access to and use of transaction accounts. Opportunities. I'm thinking of improved design of transaction accounts. I'm thinking of better and easier access to your account and all kinds of other things that help people to get access. Of course there are risks and I'm thinking here of cyber risks, fraud risks and people not using the tools properly and then maybe getting into trouble. So these are what we did to do then. We looked at the seven PAPI guiding principles which we had released already in the original report and we came to the conclusion that the guiding principles as such are still very relevant. Nothing has fundamentally changed. We were very happy with that, but we decided that it would be useful to provide additional guidance and this we did by providing bullets or to be correct soup bullets. So the existing guidance is framed in bullets and where a certain bullet could use some explanation with respect to FinTech developments we added a sub bullet. So there will be six or seven or eight sub bullets which were added to the original report and I think this is in a nutshell what the report is trying to do. The second report which was released very recently in September 2020 and it's called Payments Aspect of Financial Inclusion Application Tools and this basically contains tools designed to assist countries in applying the PAPI guidance. I will not go into any details because it's very technical. It's supposed to give a hands-on help to people. There are six or seven annexes in the report. They provide questionnaires, they provide tables, statistics, tools, everything that a country can use. So countries who really want to get down to improving things can use it as a sort of a manual, a guidebook on how to implement the tools we set out in the 2016 report. One last thing of interest in my view is that we also added a tool we call the PAPI radar and it's kind of a visual gimmick where a country can visualize its status on each of the seven guiding principles by putting a bullet on a map and you get a radar and you can then put benchmarks in which like, for example, are the best countries or the G20 countries or any other benchmark you prefer. And this is a dynamic tool which will allow countries to see, you know, I make progress but I need more progress and two years later you do the same analysis and you see that you made progress. So this is really, I think, a visual tool that will be pleasant and interesting to use and also very good in indicating progress. So that's what we did in those, which is actually quite a lot for a few years. PAPI benefited in several ways from Fiji and of course Fiji benefited from PAPI. So I think we managed to establish a positive feedback loop whereby information from one goes into the other and the other way around. We benefited in particular from two specific ways. First, we used the information from the country programs run by Fiji, namely Mexico, Egypt and China. We also had other countries from members of the task force as well as World Bank studies. So we had quite a lot of experience with countries trying to apply our framework. And the second was the working groups and then in particular the EPA group or the Electronic Payments Acceptance Working Group. They did a lot of useful analytical work which we used as an input and as it happens it was a very useful way of cooperating in a sense because I think it was very complementary whereas in PAFI we look at the demand side. How can we get people to make more use of electronic payments by providing them help and things. The EPA working group was looking at the supply side and they were seeing how can we encourage shopkeepers and merchants to accept electronic payments. And I think that in itself was a useful tool. So this analysis also greatly stimulated our thinking and our fintech report. So I think was quite good that while the project was running we could interact in a mutually beneficial way and both improve our work. I think the future beyond Fiji looks very bright. I mean Fiji was very instrumental in putting a lot of wheels in motion. The participating institutions of course the Bill Gates Foundation as main sponsor but particularly the ITU, the World Bank and the CPI BIS have spent a lot more time focusing on financial inclusion. I think that is very good. We use this to make additional work and we started new studies but also I think just in deepening the existing tools. As I said before the PAFI framework is very helpful in putting people and helping people to seek to advance progress. Well these people can also use it in the future of course. It's not because Fiji is finished, everything is finished. We all are very much aware of the fact that financial inclusion is far from finished and needs to progress. And we simply need to keep on stimulating people to seek help and to look for tools and instruments where they can help. And Fiji provides these tools, the underlying documents like PAFI provide these tools and we just need to try to. And I hope in particular that the symposium which is running in May and June will put again a little bit more emphasis and spotlight on all the work Fiji's done. And I'm quite confident speaking for myself that Fiji will be instrumental in keeping the flame burning and help people in advancing financial inclusion.


Good evening church That was pretty poor. Good evening church Grace and peace to you in the name of our Lord and Savior Jesus Christ I am so grateful for the invitation from Bishop McKee and First Lady Smith to be with you this evening. I Don't know what that's all about, but maybe we'll find out at some point But it is a joy to be with you in North Texas I must say that this is such a beautiful venue But really the beauty is to see your faces and I hope that you acknowledge that too during your time here in this annual Conference every time I go through a memorial service. I I don't know a lot of the names But I gather that some of those names might indeed have been here last year that are not here now and One of the things I like to say all the time is that every day is a gift Every day is a precious gift and One of those precious gifts is being able to look at one another's faces when you gather in an annual conference setting And so I pray that during your time here in this session that you will Greet each other with a holy kiss and that you will gaze upon one another with gratitude and thanksgiving for the way In which Christ has it worked through each of you to be the body of Christ here in North Texas And I pray God's richest blessings upon you as you gather. I bring you greetings from the New York annual conference the The 430 churches and the 427 pastors and the nearly hundred thousand people that make up the New York annual conference There are a wonderful group of people very diverse group in their approach and style and culture And it's a privilege to serve them and I do bring you greetings from them Just about every Sunday in New York I have a chance to preach in one of my churches and when I'm there I normally say a standard line that I'll say with you tonight and that line is this I give God Thanks for and I fill in the blank Tonight I say I give God thanks For Mike and Joan McKee I give God thanks for a call to ministry that's resulted in faithful service all these years I give God thanks for the wonderful sacrificial way in which they give of themselves not only the places like you but all across the connection of the church I give God thanks for a new friendship that's emerged over these years that I absolutely cherish I give God thanks for a wonderful sense of humor and for a keen insight on how we are to live as the body of Christ And I think it would be all together appropriate tonight if you this annual conference would express your thanks To Mike and Joan McKee for their faithful service in your midst. Would you thank Would you join me in prayer Loving God, we do give you thanks for this day. What a beautiful day to be in the midst of your creation We thank you so very much for your claim and call in our lives, which we feel so significantly We know God that we are not alone, but that you stand with us in these days And we pray that as we continue our work as a church that you might continue to guide us on this pathway We pray God for your grace to be patient with us and we pray for the inspiration of your Holy Spirit to guide us with boldness and conviction We pray of God that we might be willing servants of yours in the way in which you call us to serve I ask your special blessings upon this annual conference session and Pray for each pastor who's serving a church For each person being commissioned and ordained For every lay person who faithfully serves in the ministry of the church to which they're affiliated Pray your blessings upon each pew in every church each community and Village and town and pray of God That your spirit might be felt in significant ways God we thank you for your word that speaks to us and we pray that as we talk about it for a while this evening And it might come alive for us And in these moments God I would pray a personal prayer that either through me or in spite of me You might speak to your church tonight. I Pray this in the name of Christ our Lord You know, it's always been interesting to me how we tend to glamorize history Looking back we tend to lessen the significance and the struggle that existed at certain points in our history a Couple months ago. I was talking to a couple pastors of mine in New York when one of them said I wish I had been a pastor in the 50s and 60s when it was easier to be a part of the church really Well, let's let's take a look at that one In the 50s, we were not at the point of ordaining women yet in the church And in the 60s we were in the heat of the civil rights movement that was attempting to gain Courage in the midst of violence discrimination and terrible acts of racism Politically in the 50s. We were in the middle of a thing called McCarthyism It was a campaign against a legend Communist in the United States government that bred skepticism fear and uncertainty in the most trusted and well-established governmental system in the world that sound familiar and I haven't said a thing about Vietnam an Undeclared war that left a trail of death and anti-political outburst that lasted for nearly 20 years Yeah, boy Those were the days my friends We thought they'd never end We'd sing and dance forever in a day We'd live the life we'd choose we fight never lose For we were young and sure to have our way. Yeah, the good old 50s and 60s Let's all go back and soak up all that peace and solitude and lack of controversy that made up those days We tend to glamorize history It's like a few years ago when I saw the movie Saving Private Ryan We came out of the theater and found ourselves walking down the street with an elderly couple who were very shaken by the movie and When I inquired as to what they were feeling this elderly man said I fought in a war That movie captured more of the reality of the gruesomeness of war than any film I've ever seen He said the only thing that it didn't reveal was the ugly smell of war It brought back so many memories of things. I wish I had never experienced and I never want to experience again Now I want to tell you that's a far cry from Lee Marvin and Ernest Borg nine running around neatly pressed uniforms in the dirty dozen or John Wayne giving some fancy speech in the longest day we tend to glamorize history Now that's what's so amazing about this first chapter of the book of Philippians Paul wrote this thing from prison And not just a prison. It was a first century prison This was not a glamorous place to spend your time most people around Paul were facing execution and Because of the convoluted governmental system prisoners could have been there for years awaiting for a final outcome There were not three meals a day and there was not a government issued Uniform for the prisoners to wear the conditions were dark because there was no natural light The the surroundings were neglected and there was this unbearable smell It was a place of humiliation and great pain Hygiene it was non-existent Chains they were heavy and burdensome food it was scant and unhealthy and Fear was a constant drain on everyone's mental attitude And it was in that environment that very Environment that the Apostle Paul wrote these words. I thank my God every time I think of you. I I always pray with joy because of your partnership from the first day until now This is my prayer he wrote That your love may abound more and more in knowledge and depth of insight So that you might be able to discern what is best and may be blameless for the day of Christ What has actually happened to me Has served to advance the gospel Talking about his imprisonment. He says what does it matter? The important thing is that in every way Christ is preached For to me to live is Christ and to die is gain Whatever happens Conduct yourselves in a manner worthy for the gospel of Christ. Come on Really From a from a first century prison cell I would be lucky to have a tin can rattled up against the bars singing woe is me woe is me Nobody knows the trouble I've seen what a testimony from a prison cell Take away the temptation of glamour and these words get a really powerful edge to them And it makes me wonder How can someone conjure up that kind of faith? That degree of courage and that level of inspiration when the circumstances seems so grim and discouraging It's absolutely amazing to me when I look seriously at those words and I erase the temptation for glamour These are serious words of faith that are spoken in serious conditions of deep concern I don't know about you But I've been struggling to find the right words to say these days And I can't help but shake my head in disbelief Every single week when I turn on the news and I hear of another Massacre in some public setting and I can't find the words when I turn on the television and I hear the constant Uncertainty that's emerging from our governmental leaders And I left the special session of the general conference in st. Louis a few months ago feeling pretty low I Witnessed what I considered the church at its worst And that had nothing to do with the decisions that were that were or were not made. It was just mean Painful and empty And I'd love to say that I serve a church That has a greater impact on the culture than the culture has on the church, but it's not the case It seems like we're taking our lead from the culture around us in the way that we've decided to treat one another and behave And as a result I found it pretty challenging to once again find my sea legs in my voice In the position that I hold it's tough But I know it's tough for you too I can't imagine what it's like to stand in a pulpit every Sunday in the same congregation and preach pastors And I can't imagine laity what it's like to try to Spread a Christian witness In a secular place I don't know about you But with a cloud of uncertainty hanging over my head. I don't find it easy To have a lot of joy And the right words They seem to be much more difficult to find I know I know I get it The situation facing the world and the situation facing our church in 2019 doesn't compare with being in a first century prison cell And it doesn't compare with being on a battlefield of war Or it's nothing compared to the violence and humiliation that many of you suffer from racism and gender bias and homophobia still It's okay to applaud. That's fine Still everything is contextual And every feeling is real And every time that we hurt While it may not compare with other situations The emptiness is still very real And as a result of what has and is happening to us, I'm struggling to find out Where it is that I stand Like many of you I grew up in this church Jim and Bart Marlene bickerton took their son tom the church when he was four days old and I have been in this church every day since The only job that I've ever held that was not in a united methodist church Was I stocked shells in a food land grocery store for two months between my freshman and sophomore year college Everything I've ever done has been related To the united methodist church And life for me for many years as a boy a youth a young adult a layperson and as a pastor I had days that were filled with eager joyful anticipation of what to expect when I went to church I have these memories of full pews and lots of children and churches that were focused on vision and building campaigns and All sorts of relevant programs Church was something to look forward to And even though I didn't always want to be there My church was a refuge from the storm But now in many places It is the storm Issues dominate the landscape And there's plenty of conversation about what will happen next will we survive and how in the world are we going to make it through I used to be able to stand on the solid ground that I could count on my church And it would be there But I can't stand there anymore I remember a day when the church was one of those places in the community where it was described as a place of security safety and respect It was a place where confession was made And a place where forgiveness was freely offered Pastors were held in high esteem Authority was respected Leadership was trusted and when you turned on the lights and opened the door someone Unexpected would come because of the reputation and the word on the street about this blessed thing called the church I remember when I in the last church that I served we had one whole wall was a stained glass window and there was a door And right in the middle of my sermon The door opened and this straggly transient came and sat on the front pew He listened dutifully to my sermon And when we shared joys and concerns afterwards he stood up and said I saw the lights on in this fine church I'm on the way from st. Louis to pittsburgh and I just thought I'd come in and see what was going on here And I'm looking to find my way I gave the benediction later in that service went to the back of the church to greet everyone and no one Come back to greet me because they were all greeting that guy And welcoming him into the church But I'll bet That if the door of that stained glass window opened today and the straggly fellow came in someone would think does he have a gun?  It didn't take a seminary education for me to learn Wesleyan theology I was raised on it And my parents were simple blue collar workers We learned from an early age what it meant to be filled with God's grace And we were taught about the value of personal holiness Where you actively found God through worship and bible study in small groups And we were expected somehow to convert that personal holiness into a social holiness A social gospel where you engaged with the world and you shared God's love and invited people on the journey And actually worked to accomplish the words that we use. We used to use more frequently words like invitation conversion And evangelism Church was a place of joy because of what Jesus had done for us And what we could do to make our lives a reflection of christ in all that we did But have you been on facebook or twitter lately? Or have you googled the united methodist church? Something happened to our theology Grace has been replaced with judgment Respect has been replaced with my way or the highway Honoring divergent opinions has been replaced with finger pointing and accusations And this wonderful Wesleyan theology of grace Hope joy loving kindness doing no harm and doing good seems to be harder and harder to embrace I used to stand on that ground with a lot of assurance That I would see it at work within the people who use the name christian But I just can't stand there anymore With that same assurance I beamed when I was elected to general conference for the first time in 1976 as a young person And you know the crazy nutty thing about it? I've been to every one of them since I was elected as a youth a young adult a layperson a pastor and as a district superintendent And now I'm a potted plant I am the product of a general conference I grew up there and I learned so much about church polity and structure in that setting I sat and listened in awe to the giants The ones who's got the floor and spoke And the manner in which they would not only craft a speech but create a proposal I saw and participated in these wonderful initiatives And I couldn't wait to get home to tell everyone about what happened and where we were going to put our emphasis for the next season love general conference But I can't stand there anymore. It's so mean So viral So divisive So backbiting I gave my heart and my soul that we could be a global church I gave so much of myself to it in some circles of the church. I was called Mr. Malaria I'd go to Africa and get off a van and they'd say oh here's Mr. Malaria That's not a term of endearment. I want to tell you But it was what I got I worked to raise millions of dollars to alleviate malaria And hunger and disease I deeply value the partnerships that were established and the ability to take teams to foreign lands to offer word for word of encouragement and hands of expertise, but now I truly wonder whether or not we can remain a global church Do you know that umcor giving is down 51% over this time last year? The cultural divide is huge And the line in the sand has very quickly turned into a canyon of differences Accentuated by colonialism and an unwillingness to appreciate cultural contexts I used to stand so confidently on that ground I used to stand so confidently on that ground, but I can't stand there anymore Oh the list could go on and on Don't you feel like we're in prison? Chained up and hampered by the conditions of the world and the climate of the church Don't you feel like you're in prison? It looks bad It feels bad And it smells even worse And it makes me appreciate the apostle paul even more In the midst of his own contextual grief And fear this man had this amazing gift of being able to proclaim in the midst of adversity and at an uncertainty this wonderful message A joyful belief if you will that god had claimed him and called him and would not let him go And was using him to make a to be a difference maker in the world I truly believe that no matter where the apostle paul went he was never very far from the Damascus road It was there that god called sol and converted him to paul It was there that his life was shaped and transformed from persecutor into proclamer And I think he never lost sight of what god had done for him And it seems to me that in the midst of our reliance upon human systems that are failing us at every turn of the switch We need a similar kind of spiritual revival in this church of ours. It's time for another Damascus road You know, my dad is kind of that way Four years ago this ageless wonder of a man called my father fell And broke three vertebrae in his neck He can barely use his hands now He was a mold maker in a glass factory and he used these hands to craft these beautiful molds That resulted in beautiful pieces of glass where and now he can't even use his hands And his body is fading in its ability But my dad at 83 says quote Every so often I throw myself a pity party, but then I catch myself And I thank god every day for the life I have And the wonderful life I've been given How does a man say that? When his body is falling apart How does a person confine confined to a prison cell proclaim Whether I come and see you or only hear about you in my absence I will know that you stand firm in the one spirit Striving together as one for the faith of the gospel without being frightened in any way by those who oppose you How do you do that? When you have invested all of your time and energy and relied On something that seems to be disappearing right in front of you How do you do it? We cannot stand on the solid ground of the history of this denomination anymore. It's too shaky And we cannot stand anymore on the assurance That our churches are safe and secure for people to come and feel as if they're welcome And we can't stand anymore with the assurance of standing on the ground That christian people are actually going to behave as christians when they engage one another And and we can't stand anymore On the solid ground of a structure and a polity that served us so well for all these years But now seems so shaky and uncertain We can't stand anymore when the things that we've relied on All these years the still of the night I cry out to my god. Where do I stand? Where do I stand? Where do I stand? Standing on the promises Of christ my king Through eternal ages let his praises ring Glory and the highest I will shout and sing Standing on the promises of god Standing on the promises I cannot fail When the howling storms of doubt and grief assail by the living word of god, I shall prevail Standing on the promises of god Standing on the promises I shall not fall Listening every moment to the spirits call resting in my savior as my all in all Standing on the promises of standing on the promises of god my savior Standing Sounds like an awesome may it be so By god's grace


So, this was the talk that I was assigned, and I'm going to try to do this and get us right back on schedule. So, pharmacogenetics is one of the things that I do, and there are two ways in which people think about pharmacogenetics. In general, one is this idea of rare, serious adverse drug reactions that everybody thinks they come out of the blue and therefore must have a genetic basis. And the other problem is that clinical response to virtually any drug that we ever use is characterized by striking variability and efficacy. These are data on from two sites in the Pharmacogenetics Research Network, looking at response to Simvastatin and response to an antihypertensive, and you can see that most people are at the average, at or around the average. And there's always a little bit of, there's always some people who are way away from average. So the question is why are some people up here and some people down here? Most people are in the middle, and I'll come back to that over and over again. So the notion of studying pharmacogenetics, understanding the genetic basis of variability in response to drugs, is what the Pharmacogenetics Research Network is all about. So the Pharmacogenetics Research Network has been in existence since 2000. This is the current makeup of the network. There are 14 clinical sites, and there are a couple of other sites that do network-wide kinds of things, and I'll tell you about that in the next slide. This is the structure.  You can read them if you want, or you can look on the web later. But they cover a range of disciplines, neuropsychiatry, implementation, cardiovascular oncology, endocrine and inflammation. The network is also a consistent working groups and has taken on for itself the idea of organizing national and international consortia to study specific drug responses. So this is the International Warfarin Pharmacogenetics Consortium, and C-PIC I'll talk about a little bit, and I'll say a word about PharmGKB in a second. In the last cycle of the network, one of the things that Mark Retain and Kathy Giacomini spearheaded was an alliance with the Genomic Medicine Working Group at Yokohama, led at the time by Yusuke Nakamura, who's now at University of Chicago with Mark, and the notion was that we would bring to the Japanese group proposals for genome-wide association studies for drug response phenotypes, and they would undertake for themselves at their own cost the genotyping that was involved. There are about, there are over 20 projects that have been done. It's a little slow to get the data out the other end because there's replication involved and that sort of thing. They're very much involved in scientific partners, and that's been a really great asset to the network. So in the current iteration of the network, the idea was to create network-wide resources that would be accessible to network investigators for a variety of uses, and that's what the network looks like now. There's a statistical core, there's a next-generation sequencing core, there's ontology cores, and there's an EMR core that we're involved with or that we direct. PharmGKB was originally a site for the network, but has since sort of spun off on its own. It's the Pharmacogenetics Knowledge Base, and their goal in life is to accrue data on the relationship between drugs and genes and variability and drug responses, and this is a screenshot from their front page, and they've been enablers for some of the international consortia work that we've undertaken. So I'm fond of this slide. It appeared in the New Yorker in 2000 when the famous press conference occurred in the White House announcing that the first human genome draft had been completed, and I'm fond of saying, when I show this, that we all look to this vision. Don't think it's going to be on paper, and it's interesting that she's handing her prescription not to a physician, but to a pharmacist. So it reinforces this idea of implementation science, at least, or delivery of genomic information as a team sport. So what I'm going to talk about is here. I'm going to talk about our Predict program, which is our toe in the water for implementation, and serves as a model for some of the other things that are going on in PGRN, and then this alliance between PGRN and the Emerge Network that you heard about yesterday, and I'll tell you a little bit more about in terms of a pharmacogenomics implementation project. So Predict was an idea that grew out of a mandate from our leadership to people like me and the leads in informatics to develop a system that would deliver pharmacogenomic variant data within the electronic medical record system at Vanderbilt. We started planning in the fall of 2009 and started implementing in the fall of 2010. This is the front of one of our brochures. So the notion is you select populations who are at risk for receiving a drug that has some actionable pharmacogenomic story. There are, and the way we define that is a drug that has something in its FDA label, basically. And I'll tell you how we've gone about identifying people at risk in a second. The genotype, not for the drug that you think they're going to get, but on a multiplex platform that assays many genotypes for many drug responses. And then you archive the data. You pull out the genotypes that you think are important, display them in the electronic medical record, develop decision support tools, track what happens when those decision support tools fire. I call that the easy stuff. Right, it is the easy stuff. So while we were planning, the FDA did us a favor. And that is that they changed the label for clopidogrel, one of the most widely used drugs in medicine at the time. And they changed the label to reflect the fact that clopidogrel is a pro-drug, requires bioactivation through multiple pathways, primarily CYP-2C-19. There is a common variant in CYP-2C-19 with a minor allele frequency of somewhere around 20%, about 2% of the population are homozygots. I'll show you data on that in a second. And the variant is a loss of function variant. It's a clear loss of function variant. So consider alternate treatments or treatment strategies in patients identified as CYP-2C-19 per metabolizes. That set the cardiology world sort of a flame. They hated this idea because their sense was that there hadn't been a randomized clinical trial showing that there should be alternate strategies. The FDA stands was, well, we know enough about the biology to say that this drug doesn't get bioactivated. So it's not going to work in treating people who are homozygote poor metabolizers with this drug. It's like treating them with placebo. And that's the tension that we all feel in pharmacogenetic implementation in a nutshell. So we have been implementing since September 2010. These are numbers that are about a month old now. And this is what happens when you look at 12,521 subjects. They're 2.7% that are homozygots, 18.9% that are heterozygots, 66% have no common variant, and 12% have something else that we don't know what to do with. And we don't deliver any advice. The only ones we deliver advice about are these two here. This is easy if you think it's only star two, but it gets a little complicated. And this is important because this is sort of where the sort of rubber meets the road, the blood and guts of these kinds of things. There are other variants that we have to take into account. And so we call people who are hypometabolizers. These are 334, mostly star two, star two. But there are other variants. This is star two, star two. So there are other variants that contribute to this, what we turn the homozygot per metabolizer. So we have decision support. This is what the decision support looks like. I'm fond of showing this and saying, if you see a typo on this, don't tell me about it because it's been through the pharmacy committee. It's been through the genetics committees. It's been through the informatics committees. It's been through the legal committee. And it's been through the pharmacy and therapeutics committee, which is the last gatekeeper to the way we use drugs at our place, just like everywhere else. And if there's a typo, I just don't want to know about it. This is we're not the only ones that are doing this, as I'll tell you about in a moment. The University of Maryland and other places are doing it. They have developed their own decision support. And this is what theirs looks like. So very, very similar. Ours is prettier, but it says the same thing. So this is the slide that I wasn't sure I wanted to show because it is a little bit early for this. But Josh Peterson, one of the people at our place, has been looking a lot at outcomes. And this is what happens when you take 7 and 1 half thousand, predict patients, and ask the question, what happens when they get clopidogrel? Now, only 1,600 of them got clopidogrel. And the reason for that will become clear in a moment. But bear with me for a second. So you 1,620 get a stent. And then we looked at what happens at 90 days. So if you're a normal metabolizer, the chances are that you end up on clopidogrel, a cheap, effective drug. If you're a poor metabolizer, that's the 2.7%, the chances are about 50-50. And we think this is a hard number to come up with because it's probably more like 70-30 that you're on an alternate therapy. The reasons that it's not 100% are there are lots of reasons why that is. If somebody wants to know what they are, I can tell you about them. It has to do with contraindications to drugs. And it has to do with physicians not listening to advice and those kinds of things. And what's very, very cool for me is that there's a gene dose effect. So if you're an intermediate metabolizer, doctors are smart enough to know that the evidence is a little mushier. And so some of them convert to something else and some of them don't. So there's a very nice gene dose effect. So that's our first look at outcomes. Dan, for the intermediate, do you have any signal related to the recommendations that some have made about Dublin clopidogrel dose? We're looking at that right now. I mean, that's a great question. Supposedly, it doesn't work. Supposedly. Well, quadrupling might work. That's the sort of, the 300 instead of 75. Yeah. You know, I don't want to go there. So this is the way that our electronic medical record looks right now. I'm fond of showing this slide because blacked out all the identifiers, except this one, just to make sure you know that I do see patients and this is one of mine. And I wouldn't say that it's the prettiest way of displaying it. But we display now five drug gene, what we call drug gene pairs, propitogel warfarin, simvastatin, thymopurines, and tecolimus. And this is the medicines that this person is on. Actually, the list goes down further. What's very cool is this particular patient has a variant in CYP-2C9, which would make you predict that they would need less warfarin. In fact, they take four milligrams on one day and three milligrams a day the other day. So that is an unusually low dose and that's probably why. So how did we get from one drug to five drugs? I'll tell you about that in a second. But this is what happens when you start to do multiplex testing. So you now, it's the same population of patients, but now we can look at the, remember we do the genotyping on this uniform platform and we pull out the genetic variants as the P&T committee says to us to pull them out. And only 11.8% of people have no variants. And I think, you know, this is pretty obvious. You know, the more you look at, the more likely it is that somebody's gonna have a variant. So at the end of the day, this is the argument for multiplexing the testing because if you did it one test at a time, you're always gonna have, the test won't benefit most people. If you do it 50 tests at a time, I tell people you're abnormal for something, you just don't know what it is. And so this is the way around that. So that's what we do. So another group that is at high risk came out of this study. So we used our informatics capabilities to find a cohort of about 50,000 people who make their medical home advantageable. They get all their care there as near as we can tell. So how many over the course of five years received one of 58 drugs that include pharmacogenomic information in there? The answer was a bit of a surprise. 65% got one medicine like that within five years. So we, and when I say we, I don't mean me, I mean the guys who do the work, Josh Denny mainly, developed a predictive algorithm that said, is this patient, does this patient have characteristics that make them likely to get clopidogrel, synvastatin or warfarin? Those are the three big ones for us in the cardiovascular space at least in the next five years. And so if you see a patient in your internal medicine cardiology, nephrology or diabetes clinic, the first thing you, if the first thing you see is this, then you click on that, you get this pop-up and the pop-up will tell you this person has a calculated risk score of 68%, which means that they're a good candidate for getting this testing preemptively before they get exposed to any of these drugs. So this is why we have 7,500 patients, not all of whom have been exposed to the drug. Cause some of them come into the program through this preemptive way. Others come into the program through an indication way. So patient, people who are gonna get a, who are going to the cath lab, they're tested. People who are scheduled for elective knee replacement who are gonna end up on warfarin, they get tested. People who come into the children's hospital with acute leukemia, they get tested because they all have indication specifics. Plus there's this preemptive thing. So this is the way it looks right now. I wouldn't swear to these numbers here, but around 6,000 of the patients come in through this prognostic testing and around 6,000 come in through this indication-based testing. This is where the number comes from. And what's interesting is that there are four drugs here. I haven't listed tackling this because that's just been added. And we would fire clinical decision support in 22% of the people on clopidogrel, 25% of the people on simvastatin, 100% on warfarin new starts. Because we always give advice on what the dose should be, but only for the new starts. And then around 3% for thiopurines right now. This is complicated, but it sort of gives you a sense of what the flow looks like. Start down here, if you're the provider, there are two ways in which you get the testing. One is that you order a drug and the system says, oh, this person has been genetically tested. Make sure that you adjust the dose appropriately. That's one way the provider hears about it. The other way is that the provider sees that predict little stickum and orders the testing prognostically. In either case, the genotyping is on this Illumina platform. Most of the variants are sequestered. Bad word, I know, but there it is. And the actionable variants are delivered to the electronic health records. So that's about six or eight actionable variants right now. The other reason to show this is that we do engage patients and there's a way that patients can actually see their own results. And the other part is up here, a lot of the work that has to go on before anything happens at all is an evidence review, review by P&T and other committees, and then development of the clinical decision support. St. Jude does it very much the same way. I'm fond of saying the two places that have the most advanced preemptive programs like this in the country are both in the great state of Tennessee. Or the state of Tennessee, anyway. Um. So what Mary Relling would tell you is that they looked at 4,000 patients admitted to St. Jude and about half of them will get exposed to at least one of a list that they have of 33 high risk medications, including a lot who get codeine or tramadol and those are patients who are expected to have high risk diplotypes and will need dose adjustment. And they have clinical decision support of the type that we have. The mechanisms are a little bit different, but the idea is the same. This is a TPMT genotype recommended before a drug is being given. Here is a person who has a CYP-2D6 ultra rapid metabolizer who's about to get codeine. So you have to be very careful with those. Those are the kinds of decision support that they've developed. So Mary has also driven the development of CPIC, the Clinical Pharmacogenomics Implementation Consortium in collaboration with the PGRN and PharmGKB. And it's now extended way beyond that. You heard from, has she gone? Mission Health? Where's she gone? Mission Health person has gone. She's not on the, she's confabbing. She's confabbing. So you heard that she's part of this as well. So lots of institutions, lots of countries, and we have observers as well. So that's CPIC. I'll come back to what CPIC does, but Mary, Teri mentioned it yesterday as well and showed some of the publications. So one of the things that distinguishes the Pharmacogenetics Research Networks is that there are 14 sites, and each of them is funded to do their own pharmacogenetics stuff. And to creating networks, creating intersite synergies has been a challenge. And one of the ways in which we decided a couple of years ago when the last cycle started was to create something called the Translational Pharmacogenomics Project that would bring together sites that were interested in implementation. And the overarching goal is to implement the CPIC guidelines into diverse real-world settings. So that's what the implementation part is. I'm gonna talk a lot about implementation, but I just wanna make sure that you remember that pharmacogenetics needs a lot of discovery as well. It's not just about implementation. How am I doing for time? So there are four aims, which I'll go through in a second. There are six sites in the original incarnation, and then there are two other sites that are about to be added, including Mark's site at the University of Chicago. And they interface with CPIC and with PharmGKB to develop educational tools, a toolbox of implementation solutions, and some annotation that it turns out to be important for implementation. So CPIC, you heard about yesterday, lots and lots of guidelines. I stole these slides from Alan Schildinger who directs the TPP, so they're all mine. So these are the guidelines that have been published, and there are many others that are in progress, including a bunch of updates to these guidelines, which are scheduled every two to three years. These are the ones that are coming and updates are coming. The aim, too, is implementation. So most sites are looking at CYP2C19 and Clopidigral. It says all sites, but I'll say most sites because we've added these two new sites. There are other implementations that are going on at various sites, and these are listed here. And the two models, one is the targeted, you sort of see a patient who's going to the cath lab, so you do CYP2C19 genotyping on them. That's at the University of Maryland, and Mayo has projects in both spaces. And then we're doing this preemptive genotyping along with St. Jude, Ohio State, University of Florida, and Mayo's doing some of that as well, and Mark's program is sort of a hybrid, but mostly like this, mostly the preemptive program. These are some of the counts. You've already seen some of this.  St. Jude has some data on TPMT, just to show you that many places are doing this. And then we have a very, very long list of implementation metrics that we're looking at. So the lessons that we're being learned, I think I will read you this slide, just to say that it's a whole lot more complicated than we would have thought, although anybody who thinks about it for a while would have realized how complicated it's gonna be. You have to have institutional support. You have to have the leadership of the institution say this is what we wanna do. Like at Mission Health, like at Vanderbilt, like at St. Jude, the people at the top of the pyramid say this is what we're going to be known for and this is where we're gonna invest. The decision support is obviously important. The problem of education that sort of goes in a recurrent loop, you have to do it over and over and over again. And then as you're implementing, you have to watch what you're doing to see what's working and what's not. Aim three is to develop formats to report results to prescribers. As this business of star two, what does that really mean and how do you translate a star two genetic result to something that is actionable or not? That's what this is all about. And then aim four is dissemination. So we've written a lot of papers, including this paper that sort of summarizes what we have done, we think. So that leads me to the Emerge-PGRN partnership. You heard something about Emerge yesterday. Emerge has great strengths in electronic phenotyping, in capturing large populations in privacy science and in other things that I've probably forgotten about. The Pharmacogenetics Research Network has this capability in developing drug gene guidelines in the CPIC and developing a platform which I'm gonna tell you about in a second. I'm thinking about CLIA, although we all think about CLIA. So there's this interaction between the two networks. The interaction starts with this platform. So, and this platform was not designed to be an implementation platform, but it's not a bad way of doing this, I think. So when we developed this, we have this next generation sequencing capability within PGRA, and Debbie Nickerson and others said, well, we should develop an abbreviated list of important pharmacogenes that everybody's gonna be interested in. Her vision was that everybody's gonna genotype all their patients on this platform. So there'll be thousands and tens of thousands of people. I don't think that's gonna happen, but it is being implemented in Emerge. So each of the genes was nominated by one of the PGRN sites. We had lots of balloting. The rules were every site got to have at least two of their favorite genes on the list, but we all had to agree that these were important pharmacogenes. So CYP2D6, for example, probably was nominated 14 times because it's an important pharmacogenes. And these are mainly what they are, metabolism transporters and targets. Targets are things that individual sites study. There's a, and this is on a nimble gene capture in the next generation. Sequencing platform is currently high-seq being transformed, transported to my-seq and perhaps ion torrent. This is what happens when you interrogate individual subjects and look at how many single nucleotide variants they have. They have around 1,300, around a couple of dozen that are novel and around, again, a couple of dozen that are unique. And the problems are that everything works. I'm on top of it. Everything works except the two genes that we think are the most important ones. And that's CYP2D6, and we're spending a lot of time trying to get CYP2D6 right. Mark knows all about that stuff, Mark. Mark and Mark know all about this stuff. It's problematic because there's dozens of variants and the phenotype that you're interested in or the genotype you're interested in are people who have loss of function variants on both alleles. And then there's a second problem that you're interested in, people who have gene duplications. There's a pseudo gene right next door and there's fusions between the pseudo gene and the real gene, so it becomes pretty problematic to ask. And we think there are solutions to that, but it won't be just a plain old next generation run. It'll probably be PCR-based selection of targets and then next generation sequence and the way it looks. We haven't attacked HLA much, but there's some real HLA variants that are of interest and then I won't talk about this. So the EmergePGX project grew out of a conversation with Terry and I had about trying to figure out how to use this platform in an implementation space within the electronic medical record. So the notion is develop a list of actionable variants and you can do that through Emerge, through CPIC, through whatever you want at an institutional level. Identify the target patients in a nutshell. Most people are using some kind of variation on the Josh Denney algorithm. Come back to that in a second. Re-sequence on the platform. Identify the actionable variants. They're gonna be six or eight or 10 of them right now. And those, you stick in the electronic medical record, you deploy the decision support, just like we've done within Predictor. Then you track outcomes of some sort and Mark Williams has been working with Josh, Peter Sutter on the outcome side of it, but the sorts of outcomes that I've shown you are the kinds of outcomes we're gonna focus on. And then aim three is to take all the rest of them and put them in a repository for somebody to do something with. So this idea I keep on coming back to of a genotype, phenotype repository. This is gonna be about 9,000 subjects, so not enough to do very much with, but a start to thinking about how this should be done. We're planning to recruit, this is the important part of this slide, around 8,000 subjects, but if the Air Force wants to contribute another 5,000, we're happy to take them as well, since they're... 8,000, 9,000. Okay, right. So the initial target drugs are no surprise to most people. These are the nine sites within Emerge, the top seven are adult sites mostly, and the top, the bottom three are children's sites mostly. So the children's sites are focused a little bit on different drugs and a little bit different algorithms, but basically the adult sites are mostly focused on clopidogal, warfarin, simbostatin, some of the five hearings, the things that you've heard about already. Subject selection, I've just outlined the ones that are using some kind of preemptive selection strategy. Gail Jarvik has also come up with this other strategy where she's gonna start to look at patients who have unusual drug responses or unusual genotypes and then try to figure out whether she can get them incorporated into this dataset to look at some rare things, and this is the last slide. Okay, so where we are right this instant is we've collected about 3,000 of the total 9,500, so 9,500 is close to 7,800. The first 300 samples are in process right now. We want to be able to deliver by the end of the year at least 100 samples from each site. Some sites are able to just go back into the biobank and grab 1,000 samples because they're consented. So other sites have to go and consent people prospectively to do them. So the accruals are gonna be different at different sites. We're working on the second part, which is pretty standard and involves the EMR staff at each place. And then the third thing is to think about what this repository would look like and we're starting to think about that. We're having an Emerge meeting next week and one of the things that we've decided to do is to create use cases for what, you'll hear about this next week Rex, we'll create use cases for what this repository might look like. So one use case is we're really interested in knowing how many instants from OSES there are among people with cupidical. So we're gonna collect specific information that will enable those use cases. And another thing to point out is that among the 84 genes are five that are on the ACMG list. They're actually eight, sorry, six, they're actually eight. Two of them are drug metabolism genes. So we sort of, I didn't count those because we're gonna be counting those as part of the implementation of the pharmacogenetics part. But these are gonna be the ones where there may be incidental findings that we're particularly interested in tracking down and we'll have the electronic record so we'll be able to sort of see what the frequency is and what the phenotypes look like along the lines of what was told you about before. So that's a brief overview of where we are with implementation within eMERGE and within PGRA. Great, thank you, Dan. Questions for Dan? Oh, yes, please. In general, how are you viewing and handling informed consent for this being, I noticed on your order sheet it did make it very clear this is genetic testing and you had some little boxes for opting out and those sort of things. So how are you thinking about consent in this context? So the, well, let me talk about what we've been, I think that's sort of the extreme case and that's that the predict project itself which looks at a very restricted number of pharmacogenes is viewed as a quality improvement initiative and so we actually tell the patients about it and we hand them a brochure but there's not an IRB consent form that goes with it. They can say, oh, we don't want to do it and you, of course, wouldn't do it. This, of course, is quite different. Dan, could you step by the mic so that you could? This, of course, is quite different because we're doing sequencing and we're going to find other steps. So there's a formal consent process that we have gone through and it's IRB approved and we have a consent form that says this is what's going to happen. Yeah, I just, I'm asked because I'm interested in trying to sort of, if you will, crank things down a little bit and my view is I've often felt that the routine pharmacogenetic testing, that is the interrogation for the known variants, is the most opposite thing to Huntington's disease testing that there is in genetics and that this is just trivial and I really think we can waste a lot of time with a lot of angst about risks and benefits and informed consents and risk to relatives. So who cares? Just do it. We agree with you and we're doing it, we're doing it exactly the way you would want us to do it. So we don't get informed consent to get creatinine to adjust a dose of a renal excreted drug. And we sort of look at the pharmacogenomic variants the same way but obviously what we're doing within this particular project includes next generation sequencing of genes that are on your list. So there there's a consent. That's different. But I think it's great that you guys have this more graded response and thinking about it instead of having the deep tendon reflex of oh my God this is genetic testing. Well the problem then becomes if you want to report what you're going to do then you have to go to the IRB and say now it's not quality improvement only, it's we're looking at a data set. Other comments? Yes, Adam. Just curious, I'm noticing the data you're going through from the predict study that you had clinical data decision support fire 24 or 24,000 patients and then you had 6,000 progressed to actually ordering. Have you done any assessments as to why why some of those aren't going through? Or is it music? One of the things we're struggling with right now is that EMR thing that says predict test up in the corner. Not you know every time people see it they look at it and they say you know it doesn't really require consent but it still requires a discussion with the patient about what's going to happen and so in a very very busy clinical environment we think in a very busy clinical environment we think that that's probably the major reason that people don't want to do it. I know that there are patients for example that I see because I'm in a referral environment where the algorithm will say fire and yet I will see that, I see that patient once a year and they get all their care at some other hospital and so it's not useful for us because we really want to follow what happens to these patients so I don't do it in those kinds of environments all kinds of reasons and we're looking into it but basically the capture rate is small. Great, any other comments? If to come. Just to mention in response to the earlier question that there's a site specific variation on the return of incidental findings in the context of this project and some sites are returning the incidental findings and others are not. That's part of the informed consent which varies by site. Great, thank you. So our next presenter will be Terry Minoglio who's gonna talk about James.


Welcome to the third week of the Educals Massive Open Online course. I'm Shelly Sanchez, and I will help you complete this part of the course successfully. In this unit, you will gain a foundation in digital learning and teaching pedagogy. You will also learn about your students' digital footprints and evaluate how students currently use technology, the internet, and social media to learn, share, and communicate. All teachers have studied different learning theories that guide their instructional practice. How many of the learning theories you read about during your education and training specifically relate to learning with technology and digital devices and the internet? We are educators who teach students who are growing up in a digital world where they connect and learn with others online. Therefore, we must add to our knowledge digital learning theories and approaches which highlight how students learn with technology, mobile devices, the internet, and social media. In this unit, we will evaluate various digital learning approaches such as blooms, digital taxonomy, connectivism, SAMR, TPAC, and design thinking. These digital learning theories and approaches help us understand what skills our students need to navigate the digital world successfully, safely, and responsibly. Some of our students' digital footprints began before they were born. When my daughter was in my womb, I shared images of her in my womb and news about her development with friends and family online. Friends all over the world know my daughter's name and about some of her first moments. My daughter's birth is much different than my birth. I can't immediately locate my baby pictures. My mother knows where they are in the scrapbook in a box somewhere in the house. We need to realize that our students are growing up in a connected world in which they will share personal information, images, passions, ideas, opinions, and more. In this unit, you will survey students to discover what they have already shared and share regularly online. Then you will identify specific digital skills you believe students need to gain based on these findings. The information and data we collect from the surveys will show us how different our students' journey with technology is from our own. Many of our students began using mobile devices, tablets, gaming devices, and computing devices as toddlers. They connect with people around the world to learn and exchange ideas. Our students share information freely and trust the information they gain from people they have never met in person. Students need their teachers to provide them guidance in navigating the internet safely and protecting their digital footprints. Thank you for going on this digital learning journey with us. Your completed tasks will help you to better guide your students in this vast digital world. We look forward to seeing what insights you have gained this week when it comes to determining what skills your students need to navigate their digital journeys. We also look forward to reading your reflections about this unit in your portfolios.


In this video, I want to discuss the importance of outlining your presentation in advance and how to go about doing so. So first of all, let's talk about why outlining is important when preparing to give a presentation. First of all, outlining allows you to test the scope of your presentation to make sure that you have an appropriate level of depth and breadth of information that you're sharing and that you have the right amount to fit within the prescribed time for your presentation as well. Outlining also allows you to examine the relationships between the different ideas that are part of your presentation and see it all kind of together. Outlining allows you to align the supporting material effectively and make sure that your supporting materials are where they should be, that they are under the appropriate main points and that they're doing their job by supporting those main points. It allows you to look for balance. In other words, it's one main point extensively more involved than the others. And if so, how can we balance out those main ideas to a certain extent or degree? Finally, outlining helps you stay on track. It keeps you from veering off on the different rabbit trails as you're preparing your speech and as you're putting your materials together and allows you to look at things and say, okay, does this all fit within the main idea and under that main ideas umbrella? So now that we know that why outlining is important, let's take a look at the different types of outlines that we have that we can use. First of all, we have what we call preparation outline. As the name would indicate, this preparation outline is used in advance of your presentation. It's what you would use when you're putting this information together. And it's going to be pretty thorough, as we'll discuss. It should be fairly thorough, but it's what you would use when you're putting all this information together so that you can kind of look at things like the scope and the relationship between these things and the alignment of those supporting ideas. All of those things would happen as you're preparing your preparation outline. Then you're also going to have a delivery outline, which may be a little less formal, maybe less detailed. It's going to be just your speaking notes, essentially, the notes that you need to remind you of what it is you wanted to talk about and point you in the right direction to help keep you on track for giving an effective presentation. So when you think about the preparation outline, there are a few things we want to keep in mind that we want to make sure that we're doing. First of all, preparation outline should use full sentences. As you can see in the introduction area, the body area, these are all full sentences. It's almost like a manuscript. It's not a full manuscript, but it's built essentially like a manuscript using full sentences. We want to use the principle of coordination, which is the idea that main ideas ought to be together, subordinate ideas ought to be together and coordinated in the same way, indented at the same level, so that we can identify, quick, okay, this is a supporting idea for main point one or main point two or whatever it is. So coordination means everything ought to be lined up in that way. Subordination means that things ought to be grouped underneath those areas to which they are subordinate. So the supporting material for main point one should be located underneath in an indented in an indented way, but underneath main point one and the same for the supporting points for main point two and so forth. That information that relates to a higher level topic ought to be located beneath that topic within the outline. That's how to label the constituent parts. So you can see here I've labeled my introduction, I've labeled the body so that I can clearly delineate between those two things, differentiate between those two things and keep the flow of my speech in clear order. We also finally should look for balance. We should look at this to make sure that all the ideas are balanced in a way. It doesn't have to be exactly balanced in the same exact same amount of time, but if one main point has a ton of information and another has very little, then we either need to balance that out by shifting some of that information or cutting back on one and adding to the other or cutting the smaller one all together and just expanding the other points if they're that important. As far as the delivery outline goes, delivery outline should be made up of keywords and phrases. It should not be full sentences. It should not be as detailed or as large in a full sheet of paper as your preparation outline. These should be smaller. Your delivery outline should be on note cards and only use keywords and phrases. We're still going to use the principles coordination and subordination. So coordination, making sure all those bullet points match up out there and then we're using the same kind of indentation and same kind of markation for the subordinate points. There, as you can see, instead of bullet points, we're using hyphens to differentiate and they are indented that as well. Finally, we can include some different delivery cues. If we know we're having trouble in one section and we need to remind ourselves of things, we can add things like eye contact or remind ourselves of visual aids by writing in show chart here. Now, you want to be sure you remember not to say those things out loud, obviously, if they're on your delivery cues, but they can be very helpful in keeping you on track, reminding you to do things. We can add delivery cues for sure to our delivery outline and have them available as part of that outline. Hopefully, this gives you a better idea of why outlining is important and some of the things we can do to create effective outlines. If you have questions about how to create effective outlines, please feel free to email me. I'd love to hear from you there. In the meantime, I hope that you have a renewed understanding of why outlining is important and a way to outline a speech for the most effective delivery of a presentation.


Emerging SARS-CoV-2 amicron sublineages B.A.4 and B.A.5 rays concerns about potential immunovasion. Show that both B.A.4 and B.A.5 are able to escape immune response induced by prior B.A.1 infection, but that this effect is less pronounced in vaccinated individuals. This article was authored by Khadija Khan, Farina Karim, Yoshika Gonga, and others.


So we're here in the neo-node booth here and who are you? I'm Stefan, the founder of the Föhr company. Based from where? It's based in Stockholm, Sweden. Sweden. So you're doing new products? Yeah exactly. It's a cover for smartphones and here are some new demos I can show you. So what does it do? It enables and takes advantage of the surface outside the hand of the device. So you can't let you see it. You can't control the content outside. There's one I can show you, a map demo. So you pan on the left side and on the right side you can add zooming action. I have also a very easy paint program. I can show you that you can use both sides at the same time. Also tap and button? Yeah, you can do that. All the way around? Yeah. So how far does it go with the sensing area? So this is just, what is there? It's a cover and we have sensors all around. Nice. Can we take it off? Yeah, sure. So is this a prototype? Yeah. What's the production? Close to production but still we have something to work on. But it looks like that. It's on a battery cell. So it's like... How long? I think now it's about three to four hours. It's a little bit depending on how much data you can get to the device. So how do you charge it? I have a non-charger, heuristic charger. You can call the same but there it is. Alright. You see it's very thin. Light? The PCB itself I think it's 0.5. It's very thin. PCB. That's awesome. And so you don't need to have it on, right? It's Bluetooth or? Yeah. Exactly. So you can have it do it again here. So how soon is it on the market and how much it's going to cost? We're not there yet, but it will be a good price that the consumer thinks is decent. Is it possible to have a way to add this support for all the famous apps like Google Maps? Can you somehow teach the phone to do this functionality on existing apps? Yeah. Like keyboard shortcuts or something? To this cover I have an API in the library that you can put on top of everything. But you of course then need to re-change, rewrite the original application. So you have to change the app? You cannot do it without changing the app somehow? We had my touch event on top of it. So you can have a combination. Alright. Cool. And what do you do before the company? Only this? This is the first product. First product? Yeah. So where have you come from before? I have different background, but mostly with user interfaces. So is this already in articles written about this? Media? No, we have not done that yet. We are very slow to introduce us to the market right now. After this video is going to be many million people going to talk about it. Yeah, I'm happy to do that. Would you like to do some kind of kickstarter or something like that? I'm not sure. I'm sure. We are thinking of different options. So you're talking right now right here with potential distributors? Yeah. But they are happy to come visit our website and have contact with me. It's Fuffer.com and they found everything on that site. Right. It's right here. Yeah. Fuffer.com


With the current federal budget challenges, sequestration is set to take effect March 1st unless Congress agrees on a spending bill. The Navy's chief of information, Rear Admiral John Kirby, explains exactly what this means to the force. Sequestration should it be enacted requires all the services to take about a 9 percent cut across the board in their operating accounts. For the Navy, this would be another $4 billion in fiscal year 13 alone that we would have to try to recoup. So, somewhere to the tune of almost $9 billion over the course of the rest of this year, but we're already well into the fiscal year. Currently operating on a continuing resolution, the Navy is taking several belt tightening measures to preserve its operation and maintenance funds. Sequestration will cause further cuts that will drastically affect training and ship and aircraft maintenance. These cuts could also jeopardize future operations and readiness. Navy leadership is working to reduce the effects of cutbacks while still planning for the best and worst case scenarios, noting ships and aircraft already deployed will have everything they need to complete the mission. So I can tell you, Navy leadership, the Secretary and the CNO have been focused on this like a laser for many, many months now. And these decisions that they're making, though difficult, they believe are prudent and the right thing to do. More importantly, many of them are reversible. So that should we get a spending bill, we'll be able to turn those decisions around, put the travel back on, put the conferences back on perhaps, and more importantly get our training and maintenance into a healthier position. Admiral Kirby also said that service members do not have to worry about their paying benefits. The best thing sailors and their families can do is to stay informed. For the latest news and information on sequestration, go to navy.mil. From the Defense Media Activity, I'm Petty Officer Amara Timberlake.


In our last video, we explore the astonishing discovery recently made upon the Giza Plateau. Hidden in plain sight, another great sphinx. However, this doppelganger of the better known, long-claimed Soul Guardian of the Great Pyramids seemingly possesses a greater level of undiluted erosion, indicative of both sculpture's tremendous age. The questions are, however, just how great is their age? How long have the sphinx, or indeed the Great Pyramids, been here on our planet? Furthermore, the tremendous levels of erosion seen on the Pyramids themselves not only do the Pyramids display a level of erosion indicative of a prehistoric timeline, but they have seen many additional efforts by a number of now lost civilizations, each far more capable in regards to stonework than the modern man, created a number of layers of far less eroded casing stones, each displaying a varying age, this evidence indicative of several attempts at conservation. These factors all but support the following posit, made by a number of researchers, all claiming that the sphinx, and indeed we feel the Pyramids themselves, are in actuality as much as 800,000 years old. The most recent studies were surprisingly presented at the International Conference of Geoarcheology and Archaeo-Mineralogy held in Sofia, titled Geological Aspect of the Problem of Dating the Great Egyptian Sphinx Construction. The authors of this paper, mainstream scientist Manitchev Vacheslav from the Institute of Environmental Geochemistry of the National Academy of Sciences of Ukraine, and Alexander G. Parkomenko, Institute of Geography of the National Academy of Sciences of Ukraine, have blown the whistle regarding what we have supported for a number of years. The starting point of these two experts is the paradigm shift, which has been initiated within the quote debate, which has been intended to overcome the orthodoxy within Egyptology, referring to the possible remote origins of the Egyptian civilization, and, on the other, physical evidence of water erosion present at the monuments of the Giza Plateau. Which although suspiciously mainstream researchers, such as West and Scouge, have made over the years, specifically titles the water erosion controversy, which deliberately overlooked that the Sphinx, having once been recorded as having been surrounded by a body of water, namely Anibis Lake, meaning that the enclosure was once designed with the intent of holding water, itself in turn concealing the Sphinx's possible true identity. Instead, focuses on the erosion clearly made by rainfall and ancient water levels, features we indeed claim were later additions. According to Manichev and Parkomenko, quote, The problem of dating the Great Pyramid Sphinx construction is still valid, despite the long term history of its research. Geological approaches and other scientific methods permits us to answer the question about the relative age of the Sphinx. The conducted visual investigation of the Sphinx allowed the conclusion regarding the important role of water from large bodies, which partially flooded the monument, with the formation of wave-cut hollows on its vertical walls. The morphology of these formations has an analogy with similar such hollows, formed by the sea in the coastal zones. Genetic resemblance of the compared erosion forms and the geological structure and petrographic composition of sedimentary rock complexes leads to the conclusion of the existence of long-lived freshwater lakes within various periods of the lower Pleistocene era. These lakes were distributed in the territories adjacent to the Nile. The absolute mark of the upper, large erosion hollow of the Sphinx corresponds to the level of water surface which took place in this early Pleistocene age, end quote. A link to the research can be found in the script. It is a vindicating exposure of ours and others' work, one which we find highly compelling. Kent Weeks is an Egyptologist, a Connecticut-based archaeologist who studies the culture and artifacts of ancient Egyptian civilization. He's a man who owns a comfortable home in a wooded part of old lime, yet one senses this is but a stopping place to hang his hat. Since long ago, Kent Weeks hung his heart in Egypt. Early from Seattle, a lifelong love affair with the mysteries of Egypt was ignited within Weeks from an early age. He recalls that he never cared about anything else. Reading about Egypt and archaeology was all Weeks was interested in doing from the age of seven. My parents didn't think it was dumb and my teachers encouraged it. I never outgrew it, says Weeks in one of his books regarding his incredible discovery within the Valley of Kings. After pursuing qualifications in the field, Dr. Weeks became aware of the need for a dependable and comprehensive mapping of the tombs and other numerous monuments in the Theban region. Weeks decided to create a project to survey and map the Theban West Bank and thus the Theban mapping project was created. In 1987, while following up clues from ancient texts, the reports of earlier explorers and the results of remote sensing surveys, the project examined an area to the northeast of the entrance to the Tomb of Ramses, the 9th, where he felt a long neglected tomb might be located. Located a mere 70 meters from King Tut's initial resting place and totaling an incredible 121 chambers with connecting passageways, it is the largest and quite possibly oldest tomb ever discovered in Egypt. An immense underground system which lay forgotten for thousands of years. It has also been an incredibly expensive tomb to excavate. Incredible architectural supports have been required because of damage to the tombs, although we suspect this is due to the tunnels immense age, maybe far older than we are led to believe. Additionally, several tons of very ancient flood debris from past Flash Flood events from Earth's very distant history has also required removal. Just how old are the tunnels Kent Weeks found in the Valley of Kings? The Great Sphinx displays similar scars from past submersion from seawater. Some conclude these ancient monuments may even predate the last Ice Age. Unfortunately, it had been looted on several occasions, leaving little in the way of precious artifacts strewn amongst the debris from the past alluge. The remains of numerous mummies which have been discovered during archaeological works are just a drop in the ocean regarding the treasures once buried in the chambers thousands of years ago. Finding such items within millennia of junk can be a painstaking and time-consuming task, something which continues to this day. In the spring of 1995, a team of Egyptologists entered a T-shaped extension of the tomb which goes to the east. The researchers were overwhelmed with the magnificence of the tomb. Although it was badly damaged, it remains a beautiful example of what we believe is original Egyptian art, the true constructors of the pyramid. The rock-cut image of the goddess Osiris still located in the tomb, protecting the burial chamber's occupants. Although mainstream archaeology, including weeks, states the preservation of the human remains was very poor. We proposed these mummies to be several thousands of years older than claimed. We believe this discovery to be an incredibly important and incredibly ancient one, proving that there was once indeed a great flood, a premise now held by countless individuals who have studied the facts of our history. As always, thanks for watching guys, take care. Rising nearly 400 feet above the desert floor in a remote section of New Mexico within ancient Anasazi territory is a place named Chaco Canyon and within stands an imposing natural structure called Fajada Butte. Hidden from the world for over 700 years along a precarious narrow ledge there lay a secret ancient astronomical observatory. Subsequently given the name Sundagger, and the reason why is nothing less than remarkable, it has been revealed that for more than a thousand years, the Sundagger has been revealing to all aware of its creation the subtle changing of the seasons. In 1977 it was thankfully rediscovered when rock art and petroglyphs were spotted nearby. Anna Sofaire, who was cataloguing the rock art, was one morning greeted by the Sundagger, slowly traveling across the wall, traversing the strange spiral patterns which were etched upon them. The intelligent Anna realized that the Sundagger could have been connected to the petroglyphs, so along with her colleagues she came back at various dates throughout the year, eventually establishing the following information. On the summer solstice, the Sundagger appears near the top of the largest spiral, and over a period of 18 minutes it slices through the very center, cutting the spiral in half before leaving it in shadow for another year. On the winter solstice, two daggers of light appear, lasting for 49 minutes, during which they frame the large spiral. Finally, an equally fascinating and more complex light show occurs on the spring and autumn equinoxes. The large spiral is carved in such a way that counting from the center outward to the right, there are nine grooves. On each equinox, a dagger of light appears that cuts through the spiral on different angles. Meanwhile, a second dagger slices through the center of the smaller spiral. These light shows, which had been going on for centuries, continued for several years after their rediscovery. However, in 1989 it was found that the granite slabs had shifted. The alignments that had been arranged so carefully were no more. It also seems impossible for us modern people to realign them as all attempts have failed. Was this Sundagger really made by the Anasasi Indians? Or was it a far older surviving relic? One that they were merely aware of. A relic, which has unfortunately eroded away. Similar ancient light displays marking the solstices and equinoxes can be found at other locations as well, such as in the southwestern United States and Mexico. In a ruin in Hovenweep National Monument, near the borders of Utah and Colorado, light beams also illuminate spiral petroglyphs on the summer solstice. At Burl Flats in Southern California, a winter solstice sun points a finger of light to the center of five concentric rings in an early Chumash rock art display. Were these monuments once used by a lost, ancient advanced group of marauders as calendar sites while traveling America? Perhaps one day we will know for sure. Thanks for watching guys, and until next time, take care. New Caledonia, a French territory in the South Pacific, comprising dozens of violence. It is best known for its palm-lined beaches, and life-rich lagoon, which at 24,000 square kilometers, is among the world's largest. Yet what many who investigate and visit the islands are unaware of is the enigmatic mystery of the tumulis, found particularly upon the Isle of Pines, with over 400 of the structures found upon this one small island. It's argued as merely natural formations via volcanic activity. This hypothesis, however, has since been disproven, and their artificial origins have been confirmed. Yet this is not the most peculiar fact a surface surrounding these mountains. Intriguingly, it is a very little, if at all, photograph set of artifacts. A series of small, man-made cement cylinders, each measuring around 40 to 100 inches in height, and between 40 and 75 inches in diameter, they are the oldest cement artifacts officially discovered anywhere on Earth. Made from a very hard, homogenous lime mortar containing bits of seashell which garnered carbon dates of around 10,000 BC, putting their earliest official creation at around 3,000 years, before man was even supposed to have reached the Pacific from Indonesia. It is no surprise then that many now try to claim that the cylinders never existed, and instead a mistake was made in regard to the actual basis of the tumule, which have since been also revealed to have once been created using ancient concrete. However, this claim of convolution does not explain how we have many independent references to the cylinders found in a number of books and other articles of media dating to and just after their initial discovery. Also the measurement of scale, which is clearly far too small to be attributed to the measuring of the mound's inner chambers. Furthermore, due to the controversy and impossibility to explain them using the already established chronology, in regard to the migration of man, we have motive for many individuals to simply disappear the artifacts and in their place create a conspiracy to attempt to discredit their existence in the first place. Were these concrete cylinders buried in the tumule for some reason? We still do not truly understand the function of these mounds, yet could they have protected these artifacts for untold millennia? It's also, from a great flood, we find such possibilities highly compelling. There are countless ancient ruins found throughout Sri Lanka, which are all indicative of a lost technology, and thus a lost civilization having once been responsible for their creation. One of the most striking of these, being the Sagiria Mountain, an ancient stronghold made atop natural plateau, a sanctuary far away from the troubles that would have presumably been occurring below. Yet one of the most astonishing relics found within this ancient land is a rather well-hidden one. Although the water reservoir built into the Sagiria site could offer one a subtle initial clue as to their existence, one would have to investigate the surrounding environment very carefully, or be given local knowledge to ever find our next ancient anomaly in question. Hidden close by to the ancient mountainous stronghold, and now almost completely submerged into the surrounding landscape, gargantuan ancient water reservoirs, first documented by a Mr. Tennant from the UK and noted upon by William R. Corliss within one of his many volumes regarding lost civilization. The remaining enormous water tanks found with the aid of the locals all completely aligned with equally cut square blocks. One of the tanks, which the locals knew by the name Petheriacorn, has since been measured to be around 7 miles in length, 300 feet broad, with 60-foot-high earthworks along its biggest embankments. They are largely believed to have been constructed to gain complete control and subsequent mastery of irrigation throughout an impressive span of land. We approached an expert engineer to find out just what sort of feet these giant tanks would be. We received back an estimated price of around $4 million to merely construct the largest sections of the earthworks. They were undoubtedly an unimaginably large undertaking, one which we believe was beyond the capabilities of any ancient group known to modern history. Perhaps the sheer enormity of the undertaking, along with the fact that they would have been far easier to conceal than that of the Great Pyramids, for example, is a possible motive as to why there isn't more known about these marvelous groundworks, or why there is very little documented study and why any that has been done was by independent historians. Regardless, we find these incredible, gigantic, hidden ruins highly compelling.


Happy Holidays, just try them out. They're so cute. Look at JB. I want to give them. They're cute pajamas. Oh my God. They're so cute. Oh God. Are you guys, it is our Christmas Eve. Well, it is Christmas Eve and I'm going to be cooking and doing everything today because my husband is off. So for our dessert we're having chocolate cake. I like to add things to my chocolate cake and I typically use an icing, homemade icing to make the cake taste authentic. So I have one and a half of this triple chocolate fudge. In my opinion this is one of the best box cakes. It's very, very moist. It comes with a pudding in the mix but I also add additional pudding. So I'm going to add half of this box of chocolate pudding by Jo-Oh and then I'm going to of course add my eggs, Crisco oil and then I'm going to add coffee to this. Not a lot. My husband doesn't drink coffee but this is probably like one fourth of a cup. It's not going to make a big difference, okay? What is that? Is it good? Is that player your Walkman? The presents are open. You want to hold that up for mommy so I can take a picture of it? I've been asking for those for a long time. Like this Walkman. It's so cold. He's listening to Stevie Wonder. Oh my goodness. So what's your favorite toy so far, baby? Oh my God. This is what my homemade chocolate icing looks like. See how it's thickened up from the previous vlog and these are my three. I didn't think I would have three. I'm going to move this laptop out of the way. I'm editing videos. So three fairly large nine inch cakes. That's how much batter that turned out. I hope I have enough icing. I don't think I will. So we'll try to be... I like the icing in between the layers to be pretty thick and I don't mind the icing outside to be a thin coating.  I didn't have enough icing but look how that icing just spills out. And this on top is crumbled up cake that I had left over from. Yeah. So, shout out to the heiress for giving me a different idea for doing my homemade cranberry sauce. That's in her message last night. She forwarded me a recipe that she had been using as a girl. She was posting all types of things. She was going to go for cranberry sauce. I'm like, what kind of sauce is this? Yeah. I used what I had on hand so I was able to find cranberries at my local Walmart because yeah, some of the other grocery stores didn't have them. So what I did, I added two tablespoons of maple syrup. The recipe actually called for I believe one cup of raw honey. I don't really care for raw honey that much. I know. I used the juice of one orange and I also had some fresh orange juice in there. I also used a little bit of cranberry juice. I used one teaspoon of ground cinnamon and a cap full of apple cider vinegar. The recipe called for a lot more but I want to see how this tastes. So right now I'm just waiting for the cranberries to pop and then it will basically solidify. It will turn into a gel consistency. You can make this in advance but my neighbors stopped by. Let me get this out the way. We're ruining the presentation girl.  When I tell you these are some of the best desserts I have ever had besides my own. This is a local. If you're here in Arizona it's called sweets but it's up here near me, sweets and treats in their local. When I tell you this brownie, I almost killed this brownie. After two bites I was like, oh no, I'm not going to be able to do this. Sugar cookie with that icing on top was bomb. This was a snickerdoodle that JV killed. Fresh crispy treats and don't really care for too much but when I tell you these desserts were so good. My Bible book, my Bible book, show me your Bible book. It's Alec and who this is and we also have Pac-Man and my mom. It's going to be a snowman. The first thing you need to do, oh that's right Santa, sorry. So the first thing you need to do is everything up here you need to color red. Even up here color it red, okay. And I got another one just in case. This one doesn't? No. Okay, now you're going to hold it right here at the tip for five seconds. Right there, that's good and hold it now, five seconds. Press it down. I don't know how to tell the snow. Okay, alright. Now how about you do a nose. Needs a nose, right? Oh yes, Santa. Got a big red nose. Why does Santa have a big red nose? We don't know, child. Maybe he has to flu. He has to have a huge beard, right? Yeah, a huge beard with a cold nose. Oh my goodness. You don't want to cover his entire nose, baby. It's going to cover half of his nose. What perfect? Like that. It's okay, it's okay, this looks perfect. He did really good, sweetheart. Little. This chicken is, uh-oh, look at that, look at that, fall off the bone. Fall off the bone, yes. Extra from my neighbors. Look at this chicken though. I already tested it and it's falling off the bone. These greens, look, you don't have to add pork to have good greens. More over here. Perfect. Done. Bon appetit.