Okay it's 5 30 so I'll call to order the executive committee meeting for August 25 2020. Are we certified in compliance with the open meeting law? August 24th. Thank you. Okay next item of business is approval of minutes for the August 4 2020 executive committee meeting. Supervisor Abler. I'll move for approval Mr. Chair. Thank you Supervisor Abler. Is there a second? Support. Thank you Supervisor Procek. Under discussion any changes? Seeing none all in favor of the minutes for the August 4 2020 executive committee meeting say aye. Opposed? Motion carried. Next item is consideration of resolution number 11 the 2021 five-year capital plan. Supervisor Gehring. Is there a second? I'll support that. Thank you Supervisor Abler. Under discussion any questions on it changes? Okay seeing none all in favor of the resolution number 11 please say aye. Aye. Opposed? Motion carried. Consideration of resolution number 12 approving permanent easement for village of Kohler sewer interceptor at the Erie Avenue old plank road trailhead Supervisor Zigglebar. I'll make a motion to approve. Thank you Supervisor Zigglebar. Supervisor Abler. Supported. Thank you Supervisor Abler. Under discussion. All right the information okay very good all those in favor of resolution number 11 please say aye. Aye. Opposed? Motion carried. Okay consideration of ordinance number three creating section 1009 of disease control providing for enforcement of public health orders and legislative oversight. Administrator Payne. Thank you Mr. Chairman good evening. Good evening. Good evening. Nice to see such a nice turnout for our executive committee meeting. The Health and Human Services Committee recommended the proposed disease control ordinance providing for enforcement of public health orders and legislative oversight and there were four predominant objectives first to be transparent about our COVID-19 emergency planning to be better prepared if we experience a significant surge in COVID patients and if our local hospitals are on the brink of being overrun. The second objective was to be working more in collaboration that's been our secret to success not only on the county board but throughout Sheboygan County and the proposed ordinance adds the oversight of the county board executive and fine executive and Health and Human Services Committee providing more opportunity for input. Thirdly we changed the enforcement provision we expanded enforcement and penalty provisions provisions to have less onerous options that than what are currently in state law. In addition we don't want to tie the hands of our law enforcement officers or state district attorney with greater responsibilities. They are all stretched so thin as it is now and we certainly didn't want to give them even additional responsibility and then finally we specifically reference businesses and although most businesses I mean so many businesses are leading by example in Sheboygan County. They're one of the keys to why we kept COVID in check. If a business didn't comply with a countywide public health order, if we needed to intervene just as we do now if restaurants aren't preparing food and sanitary conditions we built that in. Our objective was to prepare for an emergency to be transparent and to work in collaboration and to provide our county with the tools we need to better serve this community. Those were the intentions. We hoped when we were preparing this ordinance that it would never be needed. If it was passed nothing would immediately changed and of course we hope it's never going to be needed. At the county board meeting it was introduced last week and sadly there has been so much misinformation on Facebook and being circulated about this proposed ordinance. I've never seen anything like it in my career yet amongst all this misinformation we heard some really helpful feedback. We got some really good input from the community and we appreciate that input and we made changes. So on the executive committee obviously received this as did the county board and I think the Sheboygan press actually built this into one of their online articles. The public could see it. The feedback we received was predominantly associated with three areas. Give us a little better sense of what the intentions are of this proposed ordinance. Why? Why are you coming forward with this? The hospitals aren't overrun. We're keeping COVID largely in check. What's the purpose of this? And again it's about emergency planning. It's about being transparent. So we built into the whereas statements kind of setting the stage for this that we were concerned about if things get worse that we're best prepared. We specifically referenced the hospitals that we've been collaborating with and getting information on what it would look like if their ICU beds or their COVID dedicated medical surgical beds became overrun. We sought their input. Hospitals were directly involved with this discussion. We specifically mentioned that if 50% or more are filled with COVID related patients, 50% or more that would be a trigger that we likely need to do more in our community to slow down the surge. So again seeking to be transparent. Communicate with the public what we're looking at, what the triggers are and what we'll do. We built in checks and balances that currently aren't in state law. Right now our public health officer could put out a countywide order. She hasn't done that to date. She has no interest or desire to do it going forward but she has that authority under current state law. I'll bet you about 50% of the emails and phone calls I received there was a comment or you know written comment or voice message or people I talked to that we don't want one on elected person to have this all this authority. That's kind of the irony of the proposed ordinance. We hear you and we had built in the oversight of the Health and Human Services Committee and the Executive Committee. Two very important committees of the overall nine that make up the county board. We changed that and built in county board because we have a few people say well these are just two committees and that's not the full board. So we built that in we made that change and then the third thing we did is we struck businesses entirely. We just pulled that out and I get that. I get that it was a lightning rod to some people and it was a little unclear just when that would be implemented or how that would work and with all the angst and everything that people are feeling. I can appreciate why that was a sensitivity. So we completely removed it. So those are the three changes we made that are before the Executive Committee this evening. Of course with all that said unfortunately this has become a very emotionally charged and political issue and as you know some people are using it to voice all sorts of frustrations. Regardless of their in the ordinance or not with all the uncertainty surrounding COVID-19 people are understandably hurting frustrated and fearful and this proposed ordinance was contributing to that angst. That certainly was not our intention but it is. Sheboygan county has the responsibility to protect the health and safety of our community. Public health is just one of a number of divisions in our health and human services department that do incredible work helping people in need. Our law enforcement officers do incredible work for this community. Our planning department protecting our water quality. Our job our responsibility is to protect the health and safety of this community. And though I know this proposed ordinance was prepared with the best of the intentions I can look in the mirror and I am proud of the collaboration and teamwork that went into it. I'm fine with it. I know we had good intentions. But I think at this time in our community our state our country we all need to be listening more striving to be more mindful kind and civil to one another. I raised my family in Sheboygan county. Parents grandparents great grandparents born and raised in Sheboygan county. My roots here run deep as I know they do with so many of you. And what's happening right now. I don't know if any of us are used to this. I know I'm not. There's a lot of pain and angst. And we are all feeling it. So right now I think these objectives are more important than the proposed ordinance. To this end after a lot of input thoughtful discussion with chairman Koch. We recommend that the executive committee move to file ordinance number 3. File it with the clerk with the amendments as shown. We've made some improvements based on input. So those amendments would be part of it. But the recommendation would be to file it. In other words filing with the clerk means the executive committee is recommending to the county board the ordinance not be approved. Not go forward. Next month the county board will get back together. It'll go to the full board just as any ordinance or resolution does. It's generally always a to county board process to committee process and the county board will vote on that. My bet is with the executive committee support for a motion such as this. My bet is the county board will file it and that will be the end of this. So I want to thank you but everyone for their input. But I would I want to again restate what I just said about all of us pulling together to fight covid and pulling together to be kind and patient and empathetic to one another our neighbors our friends. We are better than I think other communities who can't treat one another with respect or aren't civil. That isn't Sheboygan County. That's not the Sheboygan County. I know. So I hope everybody can support this decision tonight. I hope that it will be supported at the county board next month. And we do appreciate the input that we received and we've been listening. Thank you, Mr. Chairman. Thank you. Administrator Pan. So is Supervisor Abler. Is there a motion? Yes, Mr. Chair. Thank you. I'd like to make a motion to file ordinance number 3 with the extended changes that have been made to this document. Thank you Supervisor Abler. Supervisor Zigelbauer? I'll second that motion. Thank you Supervisor Zigelbauer. Under discussion. Is there any discussion? Any from the other supervisors? Okay. Seeing no discussion. All those in favor of filing ordinance number 3 signify by saying aye. Aye. Opposed? Motion carried. Consideration of resolution reaffirming membership in Bay Fort Wisconsin Bay Workforce Development Area Consortium and approval of amended consortium agreement. Supervisor Zigelbauer? I make a motion to approve. Thank you, Supervisor Zigelbauer. Is there a second? Thank you, Supervisor Geary. I will second the motion. Okay. Under discussion. Is there any discussion? Hearing no discussion. All those in favor of the resolution reaffirming our membership in the Wisconsin Bay Forest Development Area Consortium signify by saying aye. Aye. Opposed? Motion carried. County Administrators report. Thank you Supervisor Payne. Approval of attendance at other meetings or functions. Yes. Could we have a motion to approve the supervisors that attended this meeting please? I will second. Thank you. Thank you. All those in favor of that motion signify by saying aye. Aye. Opposed? Motion carried. Is there any other meetings attended? Okay. Review and approve vouchers. Supervisor Obler? We'll approve, Mr. Chairman. Thank you, Supervisor Obler. Is there a second? Thank you, Supervisor Zigelbauer. Any discussion? Okay. All those in favor of reviewing or the vouchers signify by saying aye. Aye. Opposed? Motion carried. Next meeting date. Is that Monday, Tuesday? It would September 21st work. I have one meeting, Mr. Chairman, that with the prey committee. Isn't that on Tuesday? It's on the Tuesday. Yeah, that's why I was thinking maybe the 21st, which is a Monday. And that's at 3.30 p.m. Which I know there's a few items on the agenda. It may be longer. So if we could do it five o'clock, that'd be just fine. Are we doing Tuesday or Monday? Or Monday. Why don't we? Let's do Monday. Okay. Supervisor Procek, is there a time that works best for you on that Monday? Just 3.30. Okay. Then that'll be at 21st at 3.30. All right. And then motion to adjourn. So moved. Thank you, Supervisor Obler. Is there a second? Thank you, Supervisor Gearing. All in favor of adjourn and say aye. Aye. We're adjourned. Executive Committee members, remember to sign the resolutions. Thank you.


Hey everybody, this is Brian and we're talking about the newest version of magic eight ball Which has not been released yet. It's going to be version 106 if you don't know what magic eight ball is it is a stock market prediction engine that I've been working on for about two years now I'll put the link down below, but you click the link sign up It will send you an activation code via your email and then you just come back click launch pass and send the code And it will let you in automatically All right some things that have changed I'm just gonna Scroll down here We have a whole bunch of new chat rooms I have an education section here where I've added a few folks like axe option zero DTE that's Ernie off his channel I think he's actually right over here and then option Sandy. She's over there. I've added yep Actually some mentors so people that want to volunteer to help other people out can and The chat rooms sometimes they are dead sometimes they are just I can't keep up with them because they get crazy Today's been kind of a calm day And I think the market's been kind of indicative of that it's been trading flat all day So let's go down here. This is the old system and I wanted to show you old and then the new one so today is gosh, what is today December 14th 2022 at 349 in the afternoon so the market's actually getting ready to close here very very soon Wow, I wonder if we're gonna see this in real time while I'm recording I tried to record these videos in one shot was zero editing just to kind of show that I'm not hiding anything Anyways point being this is the old version and it's split into two parts text wall and Chart and it's been criticized both good and bad The good is that it's been getting better in its accuracy so we're saying that the price is three nine nine two and There is a predicted closing of four thousand ten with a difference of eighteen dollars And then I've got a bunch of metrics and stuff and a forecast and some trades and these trades You can just copy and paste into thinkorswim I Love and hate this text while I'll just love with you I love all these metrics because it helps me as a developer But as somebody coming into this they don't understand any of this so it's been the harshest criticism is how do I use this? So I wanted to clean that up The other thing is this chart People coming in going this chart is bloody confusing How do I use this and I seem to be the only person on the planet that can figure this thing out and it's probably because I wrote it I have to admit looking at it if I didn't write it. I'd probably be very confused as well So I wanted to address those two things along with the accuracy. I've really been focusing on the code for the butterfly trades Iron condor I think is about as close to perfect as I'll get it Verticals is getting much better and in case you're curious about how accurate these are Bear in mind. This was not meant to be a trade generating system. It's meant to be an indicator, but in here. I do post I Tried to anyways every day the logs and I post in just a raw Brutally honest accuracy report of every single trade this thing generates Okay, so that's the old version New version here. We're gonna flip over into my development server boydromes, which don't get excited You won't see these channels. They're hidden But I have these up for test reasons, so I'm gonna go to SPX and let's just make sure we are in the newest one All right, so it's saying this updated at 1546 and It is currently 1551 so this may update while we're looking at it, but it's saying SPX I've kind of streamlined this SPX current price of three nine nine four and forty four cents is expected to move up Closing near 40011 but will range between four thousand three and four thousand twenty. So let's take a look at that So we're gonna flip here and sure enough. It's tracking up. We're at about four thousand and change We got about nine minutes left in the market. We're saying it's gonna end up about here So yeah, all signs pointing to about right there and we're also given this range now This is strictly for newbies that go. How do I use that thing? It's the very first line I've also added the version at the very top just in case you're ever confused what version is running and Then I've added this metrics block here for all the math nerds that wanted all these numbers including myself So we have the short term closing and long term. This is that three point prediction So short term is where we think it's gonna hit very very soon. You can see the difference here is minimal Closing is 40011. Yeah, it just updated. Let's go down to the newest one here guys All right, so four thousand one and near 4013 will range between four thousand five and forty twenty So yeah, we're expecting this to go up So short term will be very very soon. You can see that just happened closing This is where we think the market's gonna be in about the next eight minutes or so Long term forty ten. This is if the market had no end. It's just gonna keep going so in short Here's current Here's short term. Here's closing long term would be way up here meaning if it just ran till midnight That's about where it's gonna settle out.  Apologies Get rid of all this if you look at the options chain Well fail get out of there. There we go. If we look at an options chain Delta is the zero zero five Put in the zero zero five call. So if we look at the whole options chain It's basically the possible ranges of where this market will go. So something like Negative zero zero five so about right here down to and then just keep scrolling down Down in there somewhere So that's really all Delta is is it shows you the possible range, but then it shows you the center Which is 4,000 then Gex, which is more popular which is gamma exposure, which is also concurring that 4,000 So now you've got double concurrence here say that four times real fast where it thinks 4,000 is kind of the center And you notice how our short term is right around that gives you just kind of a confirmation right on the screen Volume winners calls meaning the calls are winning. It's currently pushing up and we can visually verify that on the screen The calls are currently winning With a strength of about half a percent which of course goes into our Expected move in volatility. I added this extra little Area in here called areas of interest no pun intended Which I may tone this down a little bit because you can see how volume one is wrapping So these are the volume nodes if you don't know what a volume node is it's an area of volume that has high traffic So you see the main node is 40 20 with a range between 40 20 and 40 30 What that means is we are actually if you look at this the price is currently below that nodes We're expecting the price to pull up. So it just kind of verifies everything. I've said so far The price is going to go up Node 2 which is 40 50 You notice this also has a volume and a rate of change. So what are we getting out of this? We have two nodes first and second. They're both pointing up so we can expect this by volume to point up and We get a nice range and we get the volume associated with it So you can see the relative strength between the two and the rate of change for each Open interest open interest is like a magnet for price. So I wanted to throw this in here This was actually a request from one of our members in magic eight ball Which basically shows the top two calls and the top two puts of open interest and shows you where the markets want to go Hot spots, these are relatively new. This is where I do a lot of math in the background and I try to crunch a bunch of numbers so this tells us where Within all of that nightmare the prices are wanting to go where are the real hot spots where everybody the volume interest all The math is really meeting You can see 40 50 3900 40 104,000 you see that number 4,000 repeated over and over and over and that's probably where the market's gonna go And then I have the trades I've been working on these especially the butterfly trying to get that more accurate and the chart has changed quite a bit So I'm gonna open this up This is what the chart looks like now So we have volume sideways so this blue line is the volume profile And we see the volume spiking right around 4,000 so all signs are pointing right to 4,000 We've got Delta Gex and a hot spot all right there Then we've got our main volume know which is also our long-term projection, which is 40 20 We've got our predicted close and our short term So you see the price is going to go up to the short term up to the close And if the market had no and it would just keep going to 40 20 But this also gives us the range that the price will go into so I've tried to make this chart way simpler And we have time across the top we have volume across the bottom and our strikes and this magenta line represents the price All right, let's flip over here and let's look at some more. Let's go to SPY for example Similar profile, but you'll notice something fundamentally different the text wall is virtually the same But the chart is actually different So what we're doing here is if the price is within the main volume note It actually zooms the chart in and adds in the hot spots So we can see this is that where we're expecting it to go and there's that three-point range between Long term short term and the predicted close and for SPY. It's right on that 400 mark But we've got some hot spots here So if the market had more time in the day and you see the price literally bounced off those that's kind of nuts We could actually put like a little butterfly here or here and make some money if it jumped up there Let's look at another. Let's go to QQQ go down to the newest one and Let's just kind of jump through it QQQ's current price of 286 is expected to move up closing near 289 But we'll range between 287 and 290 and then we have all the metrics that back that up We have our trades that we can copy and paste and our beautiful chart Which of course is telling us exactly what's going on here Now this one's a little interesting because you can see the price is within the hot spot Or I should say within the volume node and it's also within the hot spots So this magenta kind of area is that volume node and we can tell it because it's zoomed into this The price is in here and it's going to bounce around between these hot spots You can see it's actually gone down here to hit this hot spot. I think if you look down here is 297 I'm sorry 287. It's actually 285. Can you read my own chart jumped up to the short term and then bounces back down And it's been ranging right around hot spot one, which is actually our 285 So if we wanted to put a butterfly for end of day that'd be where we do it right around the 285 mark Again, we have made this dead simple So we've got our volume profile in blue so you can see it spiking out This is where the action is going to happen and you can kind of correlate that with our hot spots And that's also where the price is ranging around you can see it kind of doing this little dance around here So if this seems confusing bear in mind, this is still early version I've tried my best to clean it up special note. If something is not trading that day. I do put a basic forecast out there, so prediction for Apple on 1216 we're expecting this to go to about 145 and there's the volume to support it Tesla same deal. We got a forecast out there and then I added an ndx. I may remove this I'm just not a huge fan of ndx. It's so big and so unruly to try and chart The charts do get kind of looking like a modern art masterpiece because this thing does move around Oh, I heard the closing bell. So let's see how we did here. Oh, we are right at 3996 and change so magic eight ball was actually fairly close in terms of its prediction Let's flip back here and let's go to SPX All right, so it says Price of 399 83 expected to move up near 4,000 will range to 4,000 to 4,000 So there's our end of day You see how over time that range of possibility kind of narrows down and everything thinks that it is Going towards the 4,000 number So the main takeaway here is I've tried to make the text wall easier to read If you're new and you don't know what to do, just look at this top blurb If you're a metrics nerd like me, that's where you live. If you like doing volume and open interest I've made a special area just for you and if you just want the simplicity of copy and pasting your trades here We go. Of course, nothing is perfect and this does make mistakes. So please trade responsibly I've tried to make the chart dead simple to understand when in doubt look for that bright red line That's where the price is going to go to and you can see that happening right here Hope that helps and I will talk to y'all later


Hello everybody, my name is Johnny Blox and welcome back to Five Nights at Freddy's News. To be honest, it's not really much news because I'm only focusing on one very specific topic in today's video. Don't worry, tomorrow we got a lot of news on the Fanverse Initiative. The creative popgo's Evergreen Kane Carter said on Twitter that he has submitted a fan game to Scott to see if he can get into the initiative. And the creator of FNAF Plus Fizznom went crazy on Twitter with a Ask Me Anything which he revealed quite a bit of info on the game. But we're not here for that. We're here for everybody's favorite king of FNAF, Markiplier. With the other day he released a video titled Happy Birthday Chica. First off, the most important thing to take away from this video is Happy Birthday Chica, even if I am a couple days late. And in the video he says the following. So he reveals that quote in about a month he has to go film something that he is the main role in. Now a couple things stuck out to some people. Number one, the FNAF movie starts filming in spring and we are about to go into spring. And also if this was a Markiplier project like a heist with Markiplier 2, which I believe is still in the writing phase, I'm not sure though. Why would Markiplier need to specify that he is the lead role? Wouldn't we assume that if it's one of his projects he would be the lead role? So we got a few people thinking and there's been a lot of discussion recently about is Markiplier in the FNAF movie? Is he the main role? Is he Mike Schmidt? I'm just going to be straight up. We don't know. We have no clue what Mark is referring to in this video. He is a very busy guy. He says that so many times he's always working on projects for his community so this could just be another one of his projects. But again, why would he specify that he's the lead role? Personally, I don't think he's going to be in the FNAF movie. If anything, I hope he's a cameo. I think I speak for everyone in the FNAF community that Markiplier, Darko and MatPat are probably the three most deserving people who deserve a cameo in the film. Again, personally, I would not want him to be a lead role. I just want him to be a background cameo, a little Easter egg for fans of the community to find. Personally, I would find it very difficult to get serious and actually enjoy the film if the lead role is the guy that went purple guy and is that the bite of 87? He is a very memeable character, especially in the FNAF community where the whole is that the bite of 87 meme. So it is a very familiar face that would get a lot of people talking like, oh my gosh, the king of FNAF Markiplier is the main role in the FNAF film. But at the same time, I would not be able to take it seriously.  I think Mark's a great guy, great looks, great voice, great acting, he doesn't fit for me. I'm sorry. I'm a huge fan of movies casting big celebrities to play their lead roles. Also this movie is like what, five, six years into the making, they're only just starting the filming process? And I'll tell you right now, filming a film does not take just one month, especially if you are the lead role. Yeah, like I was saying, this movie has been years in the making and Scott wants to have it be perfect for not only the fans, but also the general horror audience. Yes, fans of FNAF very obviously are going to go see the film.  But also, casual horror fans are going to say, oh FNAF, that's that hit horror game. Yeah, sure, I'll go watch it. You can't expect everyone that is going to see the movie be a diehard FNAF fan. So while yes, Mark would be a very familiar face that would bring in a lot of brand new characters in, characters, fans into the fandom, I don't know, it's just, I don't know guys. Again, at the end of the day, we can only speculate. I came on here because I wanted to state my opinion, we'll also share a bit of the news. And in my opinion, it just feels like fanservice. You know, again, like it's been so many years and the making Scott wants to have it be perfect. And to have the main role just be the screaming King of FNAF guy. I'm not trying to diss on Mark, no way, no how.  You can make an argument for both sides, saying that he is in the movie and that he's not in the movie. Right now, all we know is that he's filming something next month, that he can't share a whole lot of that he is the main role in. But yeah, adding on to the whole is Markiplier in the FNAF movie thing. I just want to clear up a lot of confusion going on with the FNAF movie because it has been in the making for, again, so many years. There's, of course, a lot of misinformation out there. As far as the community is aware, the people working on the film are Scott, Jason Blum, the CEO and founder of Blumhouse Studios, who are producing the film. And I also believe 1492 films are also in the process of making the film along with Blumhouse. Chris Columbus is the writer for the film, and there are no cast members. I am telling you this because if you look up Five Nights at Freddy's movie into Google, the first thing that comes up is a article, or not an article, but a search result off to the right side that has a lot of misinformation. First up, you got two cast members who are definitely not in the movie. Search results like this can be edited by anyone and also IMDb. It's also much like Wikipedia, just a place where anybody can edit the information, which is why you see so many fake movie posters on IMDb for the FNAF film. I think the community has a very big issue when it comes to just taking every single thing at face value. Look deeper into things. Do your research and only trust official sources like Scott, Blumhouse and anybody else who is directly working on the film, Jason Blum, again, the CEO and founder of Blumhouse. He is on Twitter quite a lot and in the past has replied to quite a few people talking about the FNAF film. And this isn't only for the FNAF film. Again, security breach. That's a great example. There are so many leaks going around about the release date, the price tag, really just wait. We're going to get news. We're going to get the game. We're going to get the film eventually. It's a problem that I've had with the FNAF community for a long time. And it's unfortunate that we still have to deal with this to this very day. Again, I just wanted to hop on, share my thoughts, share some of the news. In conclusion, do we know that Markiplier is in the FNAF movie? No, we don't. I really don't like making videos like this, not only because I have to keep emphasizing the point of people to research, look into things. Don't take things at face value. That's the entire point of game theory. But also it just the subject matter is very clickbaity for me. And I feel like if I make videos like this, it just feels like I'm trying to mislead you guys. And some people will look at the title and the thumbnail and only think, Oh, Markiplier FNAF movie. Well, I guess he's in it. It also doesn't help that most people won't make it to the end of the video. And therefore don't see everything that I have to say. But if you did make it to the end, smash the like button. Subscribe if you're brand new. Again, tomorrow I'm back with FNAF news. I got a lot of stuff to talk about with the FNAF Fanverse Initiative. King Carter, Fiznam, and also a brand new event in FNAF AR is starting on the 1st of April. They better not fricking prank us with some absurd BS. And anyways, boys, it's been Real. Thanks for watching and I'll see you on the flip side. Goodbye.


Okay, so I don't have actionable in the title at least I'm gonna say it a lot So I'm gonna talk about the emerge consortium and in particular our experience with trying to determine what our Returnable variants so So the emerge network is a consortium of Institutions through a U01 mechanism funded by NHGRI where we took GWAS data 660k or million chips and phenotypes from electronic medical record and Through the consortium we all share genotypes and then we could get our phenotypes from the other sites So there are about 18,000 people in what we're now calling emerge one emerge was renewed this year to emerge two which added Geisinger and Mount Sinai to the existing sites and that the number of subjects is Increasing all the time and it's turned out to be a very very productive consortium Not just because of the data that we can access but also because of this interesting blend of people where we have You know the informatics people we have the statistical people we have the molecular people we have the ethicists We have the clinicians and we've all been able to really interact and learn from each other in this committee is a good example of that so the Consortium formed a consent and community consultation workgroup and that workgroup in turn Charged a return of results oversight committee to talk about what results were potentially Returnable so just to say that there's a lot of people in the original return of results workgroup And then the oversight committee actually added more people and what's interesting about the people who are here Is that there is a blend of clinical people and I have the clinical trains really hard to shoot it Anyway have the clinical training in the Right column But there's also the informatics people Molecular people statistical people And so it was an interesting blend though the one Disadvantage of that is that we all had to educate each other about our perspective Which took more time than I think if a bunch of docs had sat down But it but it did broaden out the discussion considerably and so I found it very valuable personally So these were a GWAS study. So it's a different kind of results So that we're looking mostly at common variants. So most of them aren't going to be high penetrance things that simplified our job There were however some incidental findings that we expected to find and have to deal with and then we expect future Issues when we're looking at copy number variation. We've actually already seen some deletions that are associated with bone marrow discrages and then We are now in emerge to employing a pharmacogenic array of many many many genes that will give us a lot more action ability So Okay, so these were the players in emerge one group health Marshfield Mayo and Northwestern and There there are about 18,000 people in emerge one. These are the new updated totals, which are going up But there's some variability among these groups. So group health for example that meet median age of the cohort is 74 For Marshfield, it's 48 There's a lot of variability every cohort had about 40% men which is typical except for Mayo, which had a peripheral vascular disease study and they had about 60% men most of the cohorts were very white with at least some representation of Non-caucasians at Northwestern and Vanderbilt. So not everybody was exactly the same We use the guidelines from the fabsitz paper on Reporting research results. Basically. It is an action ability standard of if there there is medical utility to the information It should go back to the patient I've highlighted in blue here that for the members of our committee were on that paper So it's no surprise that we were that we liked it And this paper I want to give credit to the original bookman paper Which set out the standards and and the fabsitz paper was really an update for newer kinds of data So now I'll give credit to Chris O'Donnell whose group nicely put together a beautiful paper on What are the variants on a GWAS chip that are used by clinical labs? And that saved us a ton of time and I highly recommend taking a look at that if you're interested in what's actionable on a GWAS chip This is anything that's used by a clinical lab So it's not necessarily a standard of what's medically relevant because some of these things here are autosomal recessive high penetrance early in life And so the person would know we decided to follow up on factor 5 Leiden and hemochromatosis We decided not to follow up on hereditary pancreatitis Where there is a variant on the chip that has an odds ratio around four or five for pancreatitis So The we were given a specific charge by the Ethics committee which was to look at what would change medical care We were asked to not look at something that impacts reproductive status i.e. we were told not to consider variant In the carrier state for a recessive disorder and then Very importantly, we're an oversight committee and all IRB decisions are local So we are advisory, but we are not telling people what to do And we tried to be very careful in our language to make say it's potential everything was potentially Returnable we didn't say anything what had to be returned everything's potentially returnable so we Struggled with a criteria for defining what is clinically actionable what actually gives direct benefit to the patient Medically not just information that the patient might like to have but actually would change medical care We are avoiding the clear issues for the purposes of this talk. None of these results were done in clear labs and Then we were charged with talking about how results might be returned and and probably most importantly Documenting what the results were that were found so it was interesting that ethics people didn't realize of course the GWAS people did that the first thing you find our chromosome Anomalies turn a syndrome a client-felter It's the very first thing you get because it jumps out on the QC when your genders don't match what they're supposed to match Or when you have extra X's in the presence of a Y So those were the first things that we dealt with Again, we're being very specific to the data we had and then the hemochromatosis and the factor 5 line Factor 5 line as it happens that variant is only present on the 1 million chip And that was run in a small minority of our samples because those were directed at non-crocation samples All right, so we went disease by disease And I can say one thing about how to shorten the process Which is that the more people that are at the table or on the call the longer the discussion is going to go and The more diverse the group the longer the discussion is going to go so Ultimately though, we decided that client-felter disease would be potentially returnable Because there are there is health screening that's done in client-felter's patients to avoid important diseases in particular testosterone is very useful in client-felters Notably in clinical care you come across incidental client-felters when you do bone marrow's and they're just Universally returned like nobody thinks twice about it if you come across a client-felter's you just give it back to them The patients are very favorable and their general response is well that explains a few things, you know So out of the 10 client-felters we found Four of them were known in the MR So it was really an advantage for us to be able to go back to the electronic medical record and say do these people know About this we don't have to return it if they already know about it And that's an advantage every study won't have and every IRB at every site allowed us to do that Happily for us the one mosaic client-felter's was among the known cases So we didn't have to deal with Separately, you know, if he's a mosaic does he need to know is that as actionable as and and I might add You can be a mosaic because you lost a Mua or mosaic because you lost a chromosome along the way the question is just where did you lose it? Did you lose it in your bone marrow and so you have a full client-felter's phenotype or did you lose it? You know in your whole body is not Is not xxy Of the six that were potentially returnable ie. They were client-felters, but we were Unable to find it in the electronic medical record because of course some of those people may have a diagnosis that just didn't find its way Into the medical record in effect one of the ones were calling known actually had turners in his medical record But we're we're sure they knew that it was client-felter's and that turners since it was a male but Of this we think and so it just says something about the medical records and also the doctors of those six One was already deceased and so that was you know not returnable one had documented genital urinary Abnormalities and was on testosterone and so even though they didn't have client-felter's They were doing an appropriate treatment The remaining four were all at Mayo and there was a local decision at Mayo to not return client-felter's Which we could talk about but I don't want to take a lot of time on because it's it was a long protracted discussion It never went to the IRB at Mayo though. It was Within the study group So when we turn to Turner's syndrome again There was a general feeling that most turners know their turners But that some turners could escape turnes is a little more complicated for a couple reasons But there are good reasons to know if you have Turner syndrome If you're young knowing about the infertility, of course is helpful if you're older. There are some complications Turners are treated with estrogen and they do have more medical screening interestingly the two patients that clearly had turners an XO and an X XQ minus so missing the long arm of one of the X's those were known in the EMR. We had eight other mosaic turners XO XX And and those can be acquired and many of these patients actually were quite older They four of them were from the group health study and they were in their 70s And so there is well documented loss of the X chromosome in the bone marrow So that can be just an acquired change that doesn't represent Turner syndrome at all Out of those eight three were deceased There are five of those eight had children documented in EMR only in one case though did actual births and pregnancies Appear in the EMR. So you don't know if children are adopted One of those eight patients though was documented to be infertile in the EMR And and none of these have been returned I'll come back to that I'm so factor five Leiden There was a sort of a sophisticated nuanced that homozygotes should be returned and heterozygotes not because the his the risk of a dbt or PE is so much higher in homozygotes and The interventions for heterozygotes are slight But there was some discussion and there was also a discussion of is there some age after which you would not tell the Homozygotes anymore because they would have presented by now Hemochromatosis Was the longest discussion so it's autosomal recessive It has a penetrance of 10% in males only 1% in females. It causes serious complications in death And the prevention is really actually quite simple of using phlebotomy to keep off the excess iron And screening by ferritin level very simple. There is not population Recommendation for population screening in hemochromatosis But the group felt very strongly that what we're doing isn't population screening if you know the genotype Is there a different level of burden to tell the person? So ultimately there was a mixed opinion on this one But the general sense was to return in males and not to return in females and of course that's what we had a Little debate about because we had some members of the group who are uncomfortable of with treating males and females differently But in this case the risks are truly different And I should say in hemochromatosis, of course if someone comes into clinic and says my brother has hemochromatosis We always test them. We don't you know, we don't go like well, maybe you don't need to know we just do it So coming back to what all the findings were I talked about The Turner's and the Klein filter for factor 5 Leiden three of the groups didn't have the one million chip at all and for the two groups that did have the one million chip They elected to not review the data. In fact, the the allele for factor 5 Leiden is quite rare in African-american populations and so the possibility to find in homozygote was quite low But nobody looked for For hemochromatosis group health is the only site that did not look and that's because the patients were so elderly that it Decided that it wouldn't be clinically relevant for them at that point for Marshfield they found 14 people who were homozygotes for the The major site six of those were male They found five of those had a diagnosis in the emr, which is an interesting proportion And in the rest there were no symptoms in the emr. They actually reviewed for heart disease other kinds of liver disease and Because they could not find symptoms. They decided not to return at Mayo They had about they had 14 5 also in the emr And they decided that they they have not decided about return yet They're still in the process at Northwestern They found six two in the emr. They felt that they could not return. This is the new gene cohort They don't they're not consented for return and they also don't really have contact with the subjects and finally for Vanderbilt They just have no ability to get back to the original subjects. It's a de-identified data set I skipped over for client filters the one returnable client filters that we had at group health We decided we would return it and the patient turned out to be deceased. So that saved that So the conclusions first of all Malia Fullerton Wrote up our experience and that paper was submitted to genetics and medicine. It came back for Very minor revision. So hopefully that will be in press in genetics and medicine and there's a lot more to the story That will be in that paper certainly we found that Incidental findings are going to remain an issue in research studies But I think that applies to a clinical genome when you're when you do an exome or a genome looking for a cancer gene And you find other things you really need to be prepared for how you're going to handle that information clinically actionable is a highly debatable term and and Importantly and I think we didn't really appreciate this going in it depends on the clinical context a lot So it depends if you're male it depends if you're female it depends on what age you are it will depend on what race you are and Many other factors. Do you do you still want to have children? If you don't want to have children then meaning to know if you're infertile is not a priority So I think that that's something that's going to be very hard to operationalize In emerged to we've divided this work into two committees. There's the CERC committee, which is community education and a couple other letters I should have looked up And the other is the actionable variant committee and so, you know, maybe you can get them to remain I didn't name it But I'm a co-chair with if the car cool-o and for the actionable variant committee We're going to be looking at risk source particularly for cardiovascular disease and then because we'll be getting this large amount of pharmacogenomic Data we'll be looking at those variants and those are our next steps. Thank you A couple of quick questions or comments Gail I may miss this at the beginning, but what was the consent status? and all the different sites about Actionability, yeah that you Barely missed it. It was on one of the slides But the fact was that most of the cohorts were not consented for return two of the cohorts were consented to return But for the other four sites each IRB indicated that if there was some Compelling reason that they would consider that and one of the things we had along they would consider actually returning results Despite what the consent form said We had a very long discussion about how you ask people if they want results without telling them They have results And so in in group health they actually went back and they just reconsented the whole cohort Well everyone who they were still able to get Went because that cohort started out as an Alzheimer's disease discovery cohort You know 15 years ago and nobody really thought that they'd find anything interesting like genetically in that cohort so I've reconsented several cohorts related to other studies because we didn't anticipate at the time of the original consent and and At UW that's our IRB's preferred process that you reconsent the whole cohort for return of potentially interesting Results with this giant disclaimer that you may not ever be giving them any but you just want to know And that way you're not stuck with well here are four people I'd like to tell how do I ask them if they want the information without tipping off that I have something useful for them So it's so we go with just try and reconsent everybody. It's not as efficient necessarily, but it it allows them to really make a choice Oh Yeah, so we're talking about hemochromatosis and and the fact that there is no recommendation for Population screening for hemochromatosis that the cost benefit is felt to not be worthwhile for screening What's not screening about this is we actually have the genetic data So that's the distinction I'm making and we're not spending any money to get the data We may spend money to do something with the data, but the data is sitting there The other comment that I'd like to add to that is that Bookman and fab sits both took the position and we took two that no one's even if you have the data You're not required to look at it You're not required to go digging through your data to find everything. That's potentially clinically relevant But if you if you are stumbling across it like the karyotypes that you can't ignore you find them Then then that's where your burden starts to to decide if you're going to return that information Does that answer your question? Okay One more question Terry Thanks, you made a very good point about Really that what's actionable and not depends on the clinical context, but then you said something about that it might depend on Resubdicity did I hear you correctly? And if so, could you explain well penetrance? Penetrance may be race specific. So as we move to variance that risk scores genetic risk scores, for example, those may become race specific and I you know, I'm particularly concerned about those Certainly the then the risk scores are primarily built around Caucasians because that's where our data is We don't have very much information. So so certainly there's no reason to believe that if You know most variants do translate across if they increase risk in this race They increase risk, but the amount that they increased risk by the time you're talking about odds ratio may not be the same at All and then the spectrum of variance is going to be different across Races so certainly for Turner syndrome. I'm not worried about race But for a risk score, it's I'm more concerned. Yeah I think we need to be real careful of that and I agree with you that the data may not be there But what what tends to happen that as people say well, we only have data in European ancestry people So we can't say anything about anyone else and I would disagree Right, I I totally agree with that statement. I and in fact, I've heard I was at a Seminole recently where someone said well, you know, none of this helps people who aren't white and I vehemently Disagreed with that statement. It's many of these things will translate But you you know, you have to decide what your cut-offs are if you're looking at a 10 or 15 percent increased risk That may be a five or even a 20 percent increased risk across a different background So we can't use it and even though it's rare if it's there, right for high penetrance alleles I don't think that that race is an issue. I think it's really for these low penetrance things. Yeah, I'll Put my stamp on that. Thanks for bringing that point up though. I didn't mean to muddle muddle that


Well, my dear students, the course is Labour Policy Pakistan and the topic is, rather the question is, what are the characteristics of legal right? Now, let us move on to discuss the characteristics of legal right. Isim and May Salmond summoned, a renowned jurist states that every legal right has the following characteristics. The first characteristic of legal right, according to Salmond, is that the legal right is vested in a person who may be distinguished as the owner of the right. This means that the legal right is vested in the person in which we call the owner of the right. The subject of it, which is holding a person's legal right, is also called the subject of right. The person entitled can also be called, or the person of inheritance can also be called. So, the technical words here are vested, which means given. Distinguished is also written, which means identified or notable or prominent. The definition of the owner's words is titled holder, subject means focus or subject matter, and titled means permitted or more importantly, the very important terminology is person of inheritance, which means person in whom legal right is vested. Thus, my dear students, this definition means that legal right is given in a person who may be notable as the title holder of the right, the focus of it, the person permitted or the person of substance, my dear students. The second characteristic of legal right is that legal right avails against a person. That legal right is availed against a person upon whom lies the correlative duty. He may be distinguished as the person bound or as the subject of the duty or as the person of in-see, dense, my dear students. So, these are the other characteristics. There are technical terminologies in this, come and discuss them as well. The word avail means aims, correlative means chorus, ponding or resultant. Duty means obligation. Distinguished means identified or notable or prominent, my dear students. The term bound means responsible or answerable. Subject means focus or subject matter or in-see, dense. This is a very important word. This means the ultimate bearer. My dear students, the second characteristic of legal right aims against a person upon whom lies the resultant obligation and that person may be identified as the person responsible or as the focus of the duty or as the ultimate bearer or the ultimate bearer. The third characteristics of legal right is that it obliges the person bound to an act or omission in favor of the person entitled. This may be determined as the content of the right, my dear students. To love oblige, you mean force or require. Act means to do something. The act of leaving something out and title means give the right. Content means substance or essence or heart or core of something, my dear students. Thus, my dear students, it requires the person bound to do something. That legal right requires the person bound to do something or leave something out in favor of the person given the right and this may be termed as the heart of the right, my dear students. The fourth characteristic is the act or omission relates to something which may be termed as object or subject matter of the right, my dear students. And number fifth characteristic is every legal right has a title. That is to say, certain facts or events by reasons of which the right has become vested in its owner. Now, question arises, where do labor rights stem from? Where is their origin from? To my dear students, we have certain labor laws in our country, in our provinces, which discuss some of them with you. Labor is a law related to employees' old age benefit act 1976. Laborers' rights are also present in this. Second is Provincial Employees' Social Security Ordinance 1965. Naturally, it is a law that creates rights and obligations. Third is Workers' Welfare Fund Ordinance 1971. Again, it is a law. It is not a policy. Therefore, the rights stem from this. West Pakistan Maternity Benefits Auditon 1972. It is a law relating to women's benefits, women's rights, my dear students. Apart from this, Workers' Children's Education Auditon 1972 is there. Companies, Profits, Worker Participation Act 1972 is there. Apart from this, Workers' Compositions Act 1923 is there. Apart from this, there are other laws. Laws create rights and duties. And the right of a person, the right of a person, is a work in its favour. It is an action that is bound to be done by other people. And it is bound to implement the law enforcing authorities and courts. Hope you have understood the topic. Thank you very much indeed.