Welcome to MOOC course on Introduction to Proteogenomics, today we have last lecture of this whole course. In this MOOC course you have been introduced to the concepts of genomics, proteomics and proteogenomics. An effort has been made to help you understand various steps of data generation, analysis and interpretation. Though the field of proteogenomics is still evolving, its contribution to the development of science, particularly in precision medicine cannot be undermined, there are many tools which are currently being used for proteogenomics. I hope you got a good understanding of these tools and publicly available resources which you can also start using for your own research. The National Cancer Institute, USA has constantly made an effort to bring research communities together for fighting the common evil of dreadful disease like cancer. In this last lecture, you will be introduced to the various initiatives of NCI toward development of a cancer free world. This lecture is essentially a brainstorming meet of cancer clinicians, researchers and industry experts which we conducted to mark cancer moonshot India program at IIT Bombay. So let us have this interactive session about cancer moonshot India and a perspective shared by Dr. Henry Rojugus. It is a great honor to be here. I mean, I know about the year and a half ago when I read to Sanjeev and Sanjeev and talked about the program that he was developing here in India, but one of the things I ended up doing was contacting a lot of my colleagues that knew his work and the one thing that they did indicate is that the work that is being produced in his laboratory is exceptionally well. So it is just an honor to now be here knowing that India has joined this international effort that is one of the outshoots of the United States government. So what I thought that I would do is to sort of give simplistic overview of how we ended up doing what we do now within the National Cancer Institute. More specifically, two years ago, how the cancer moonshot actually got established. So let me give my little history here from a simplistic level. People don't know why the National Cancer Institute enjoys these large scale programs. So I actually don't know from a proteomics background. You can know me. You can look it up. I actually come from a proteomics background. And I've classically trained in California and drug development. So one of the things that did attract me to the National Cancer Institute when they recruited me was their history. And the history, you need to understand where genomics fits with proteomics. Though if people talk about genomics, large scale, and you mentioned the word National Cancer Institute, the one everybody's going to recognize is the cancer genome atlas. And that program actually got created in 2006 when it went public. That's the key when the program went public. And the program at a 10-year window has done an incredible job from a cataloging-based perspective to develop these great resources that the public needed to use. In the span of 10 years, they went to about 35 different cancer types looking at a catalog of over 14,000 individuals. But the part that a lot of people might not be familiar with is that when they launched the cancer genome atlas, but when they were trying to develop it, they did not simply want to go after the genes. The National Cancer Institute, where they were formulated this program, they wanted to go after proteins. And at the very same time that we launched the TCGA program, based on the genomics landscape, we went after proteins. And that program is one that affectionately is referred to as the CPTAP. Now, the reason they wanted to go after proteins at the same time as genomics was for two basic reasons, which were talked in the various sessions that people now have been holding. One of them is you absolutely want to figure out the biology of cancer. One of those individuals that I think our market discovery is very great, but unless you understand, even though my biology of the disease, it's very difficult to make a novel discovery that you find, which is an anecdotal observation and making that discovery clinically actionable on a wide scale. That's very difficult and very rarely quite honest. So understanding the biology is extremely important. The other reason that it's very important to understand that proteins exactly what your therapeutics is going after is the key word therapy. While immunology is very promising, the vast majority of drugs that we still get toward patients, they're typically chemical based. And the chemicals, there's very few that target DNA, such as interbinding strands. The main variety of drugs will target a protein. So you really need to understand from those perspectives what's the quality of these proteins and exactly the efficiency and the binding constant of the target you're trying to go after, not in inference, which is typically commonly done. But here's not what happened. Before the cancer genome apparatus got launched, we were starting to think about it in the early 2000s. And that's when the first drop of the immunogenome got created. That really led to this great interest of looking at the molecular biology of cancer. But at the same time, there was a publication that got released looking at ovarian cancer early stage using an emerging technology at the time, which was mass spectrometry. They made a claim that they're able to use omyx without even recognizing the protein and simply recognizing a pattern of an instrument and using that as a predictor for early stage ovarian cancer. Very promising to raise a lot of interest with a lot of cancer directors back in the U.S. But fortunately, it was found that the study, the way that it was designed, the way that things were interpreted were not correct. So the reason what we ended up doing at the end said it was quite interesting. When it came to CPTAC, we did not go after biology in 2000s sense. Unlike the genomics landscape, they felt at the time that technology was premature and you could trust the data. So CPTAC first had to show that you could take these emerging technologies and do your best to try to understand the analytics. Standardize it where you can, if you can't standardize it, try to harmonize the measurements in the analytical workflows. Once you're able to show that you can actually come back with measurements that can be representative of biology, not the measurement that's representative of an artifact, that the way you take a sample, the way you process a sample, the way you do your instruments, then the board would give us permission to work with the biology. So this is what we ended up doing, which is quite interesting because it's very rare to mention the Health Adultery Standards Initiative. But we ended up doing that to bring pretty old mix to the state of genomics. So for the very first five years, CPTAC basically tried to go after the analytics of mass spectrometry and we looked at two folds, which was actually discussed in the past two days. One, we looked at the discovery states. Here we basically showed, if you take a lot of people refer to a shotgun, I quite frankly am not a fan of the terminology shotgun, but I tend to basically refer to a genomics. This is a deep-dive comprehensive measurement of trying to look at everything we can at this level, exactly doing genomics. And in that space, we basically showed if you had standard operating procedures, we did elaborate ground-bound studies, we actually had eight laboratories throughout the U.S. and we did an international run, and we showed you a very good concordance of your measurements across your laboratories. But the one that we really wanted to put our mark on is the one that exactly we do in genomics. Once you do a deep-dive, they need to develop gene panels. These gene panels are actually the drives that are going with trials today. So we wanted to develop that same space when it came to proteomics. Now it turns out this measurement technology that a lot of people refer to as today as multiple reaction monitoring, you have different ways of praising it, but this is not something that CPTAC never developed like any such imagination. It's been used in clinical lab for over 30 years. We're simply using it for the measurement of small molecules. What we wanted to show is what other laboratories were already using is could the measurement of target and aspect be applied to the measurement amount of a peptide. Informatically sticks the information back up to the measurement of a protein. So what we ended up doing there, we basically looked at MRM, which was already being used in laboratories, but it's really due diligence on the accuracy and precision across multiple labs was yet not demonstrated. It's very important to have that proof before you go back to a tumor point. So we basically, again, we developed a Rob Robin study. We had laboratories that distributed around the West. Then we did an international Rob Robin study and we showed that this is a very good, quantitative, reproducible measurement tool. The other thing that we wanted to do at the time was explore the clinical space if you find an interesting biology and if the biology is best measured using these technologies, what would it take to get the technology approved by the regulatory agency? So what we ended up doing is one of the things that we did was quite nice that in the US to get a diagnostic device approved such as an IDMIA, you need to get regulatory clearance. And those, and there's two types. The first we need to go after is what's referred to as the 510 today. So we actually worked with the regulatory agency in the United States. We worked with the clinical chemistry community. What we ended up doing was quite novel. Typically, manufacturers will submit 510K to the regulatory agency. And then the FDA will mark up the document putting all their comments and concerns on what they just submitted. But typically, when that goes back to a company, they'll never read it to the public. We decided we wanted to make that very transparent. So we worked with them. We put out a workshop and we actually submitted an official filing to the regulatory agency using this type of measurement technique. But because we made up all the data but we did not make up our other ones for workflows, it allowed the FDA to mark up the document. And then once we got the documents back, because we worked with the clinical chemistry community, we published all their markings on it. So it's a great way of making very transparent exactly the kind of questions you would give if you were just to make your instrument these measurement techniques to get them approved by the FDA. The other stuff we recognized is that a lot of the reagents were being commercially sold. We felt that the quality was not the level of standards that we wanted to see these within the research and ultimately within the clinical grade world. So we worked with various manufacturers to kind of elevate the standards when they sell these reagents to the public domain. The other one was we started going to meetings and people were always saying, I have an asset, I have an asset. In fact, one meeting that I went to and said quite openly is that one person stood up and they said, I already got an asset that every human protein that's out there. I was quite surprised when I heard that. After the meeting, I had basically approached this individual and said, explain to me how to develop an asset to every human protein. What turns out, what they were talking about was a theoretical-based asset where an asset is basically running a buffer. In a clinic, that's not considered an asset in using that terminology. So what we decided to do within CDTAC we basically then started developing fit-for-purpose-based criteria that begins to define exactly what an asset is. What's nice now is that that has not been accepted by the international community or specifically one of the prominent journals of MCP. Now they've adopted those criteria within the journal itself. And this was also done in pharmaceutical industry with the Clinic of Northwest Laboratories and the regulatory agency and the clinical labs in the United States to develop these animal sort of criteria. So this actually now represents five years' worth of history for the CDTAC-based effort. Again, we had to go back and we had to show that the measurement you're able to obtain is basically trustworthy. You can actually believe in the measurement of being a representative of biology. Once we did that, we went back to our board and then we got the issue. And what we decided to do was quite interesting because obviously at the NCI, we had the cancer genome appels. That now has five years' worth of history of our CDTAC. And they're generating a lot of interesting information and what our proposal to them was we want to take the exact tour that just got genomically sequenced within the cancer genome appels program. And at the same time then, we would actually now go after the proteins within that sample. And we would believe that a year to layer a comprehensive protein measurement above a comprehensive genomics measurement, you're able to obtain additional biology that is either difficult to obtain or simply not feasible through genomics and soft. Now think about that. Because at the end of the day, and I saw it today, a lot of people said, well, in proteomics, that's always much better than genomics. The reality is, when I couldn't move into a clinic, two things is just going to drive your decision. And that is, is the test clinically relevant for the disease you're trying to go after. And the other thing they're going to ask is, well, how much is the test and what's your throughput? Because the reality is, if transcriptomics is able to predict the same thing as proteomics can, somebody at the hospital is going to say, well, why do I need to measure my proteins? Because it's lower throughput and it's a higher cost. So that was the cable that we took. Could we find additional biology? So in the next five years, we decided to go after three cancer types after the cancer genomics.  I'm not going to go through all the details, but suffice to say, in each one of these cancer types, we were able to identify additional biology that was missed simply because we can't obtain it from genomics itself, or it's just a better way of integrating the data set between you, at least within the genomics and within the proteomics landscape. Furthermore, what we learned from this lesson was that if you simply go after one type of an omen, whether it be genomics or transcriptomics or proteomics, most likely you're going to be missing key biology that could be inferred from one of those other omen. So integrating those worlds would become very important for our program. So, with that in mind, I heard that question today, so I quickly then put this next slide in. One of the things that I started to be and that people were asking me, in fact before I ended up going back to my board to come up with the next version of CTTAC was the exact question that somebody just asked at today's conference. And that is, well, you ended up doing proteomics and you threw it above genomics, and you guys found all this additional biology, why don't you do proteomics then? Because it's much better. Well, my philosophy has been should you do genomics and proteomics and which one's better? Well, one of you, no one really knows the answer yet. And here's why. I'll break it down into two components for you. One, let's look at biology itself because that's the part that I tend to love the most. If you look at the cancer genome atlas because the TCGA would be there for 10 years, it really was a clinically actually deployable yet. You're basically trying to figure out biology because those samples were not collected with a clinical question yet in mind. It was basically cataloging samples. TCGA, as I said, in a 10-year window they went after 34 cancer types and they basically genomically characterized over 14,000 individuals. In the process they basically identified all these actionable mutations where now we have small molecules and all these small molecules are driving a lot of our precision oncology trials. So that's the good news. Now you can look at the other side of the story which is what we're learning about three to four years now into this sort of science and driving our clinical trial. More and more we're learning that a lot of these individuals that we identified all these actionable mutations a lot of them really are not responding that well to the treatment that they're being administered within our treatment arms of whatever clinical trial that they're being deployed on. Furthermore, if they do respond we're finding out that those responses are actually short-term. This includes toxicity that could occur that once you get there you have to put them on another arm when you're in that trial itself. So the question becomes what? We don't know. But what we do know with absolute certainty is that there's still a tremendous amount of biology that's missing from that picture. Now this is the biological version. Let's flip it to a clinical way of thinking. A great little paper came out about three years ago by Tito Bulbor who used to be at the cancer institute and I moved to New York City. So Tito, when he ended up doing it, was quite interesting. He basically said, let me actually go through the regulatory agency back in the United States and ask the question about a 12-year window when people start using the term precision medicine, precision oncology. The reality is you're talking targeted therapy and if you look at all the targeted therapy drugs that have now been approved by the FDA there's just about over seven. And your window spans about 12 to 15 years and what he ended up doing was he took two common criteria that's used all the time in our trials and that is when you look at the individuals you ask, well, what's going to be their overall survival? And at the same time, what's the progression of free survival of these individuals? He excluded the exceptional responders which is what a lot of people love to go after and again to be very fair this is solid and typically mid-stage and what he found out was for all those drugs that have been approved from a targeted perspective on average those two criteria it's less than three months so that's really not that good again, it's very promising on oncology but it's still we could do a lot better so using these two criteria the argument of missing biology and then the argument of can you begin to play in the sandbox of clinical trials that influence directly the next iteration of the CX program so this is actually CPTAC so this is actually CPTAC today again, these are five-year programs and the next iteration we know that that will be contingent on the science that comes out of these programs so we still have a biological law that's exactly what we did within the next component we're being held responsible to go after at least five more cancer types hopefully more but at the minimum we have to go after five samples that we get from our patients these are all treatment IH samples every sample goes and we partner directly with the cancer genome athletes they will do comprehensive genomic characterization then the sample of these are also goals to our characterization centers along with our data analysis centers at the same time that we run a biological arm we have now an official translation arm for the very first time the Cancer Institute is now partnering with the ongoing proteomic laboratory with an NCI-sponsored clinical product we have three types of cancer types that we're going after for that component that involves a series of drug trials but again the part that I think that's quite nice about CPTAC is that the data we got born about 12 years ago now everything that we produce we put it in the public domain which is listed on the bottom of the slide everything from genomic information to proteomic information and the agent that we develop which are typically antibodies any of the assays, all the SOPs that we produce our assays against all that is placed in the public domain the argument is is that we know it's suddenly being used by the community and we believe by giving it back to the people it drives the science and hopefully patient care you're able to accelerate it not just within your country but across the globe because that's our goal ultimately and so once this program got launched here's something now here's Melvin Star that happened in the Cancer Institute so CPTAC while it was one of the first ones that started to mix these two worlds together from a programmatic official level it's not the only one that's starting to do that now there's two other ones that recently got launched just over two years ago because of the cancer moonshot one of them is referred to as the Apollo program and the other one is referred to as ICPC to the International Cancer Reporting General Consortium so very simplistically the Apollo program is one so these programs actually got started as follows I think a lot of us and especially myself I was extremely moved in the early 2000s by the inspiration of Paul of the former vice president of our country Joe Biden when he actually launched the cancer moonshot now you can go through all the details of what the cancer moonshot is what I enjoyed the most was I tried to simplify it into three simple objectives that we want to achieve from that one of them happens to be we want to accelerate the progress in cancer research there's many ways that you can do that you can do technology development and other components but the other two were the ones that I've always had my parts in which is what CPTAC has been doing for the past 10 years one is you wanted to see greater cooperation but here the way that this was phrased it was not within your own university it was not within your own country they were hoping to try to explore international collaboration and the third one is the one that I was very happy with they wanted to see a lot more sharing of your data the reality you can look at the genomics landscape a lot of the information that you're developing is pretty much pre-competitive because they're basically observations and a lot of those observations it's not yet a clinical relevance behind them so releasing the data is not detrimental in fact it's actually beneficial because the other individuals are able to take your data sets you can recognize more but again you're able to drive science a lot further so using that as a backdrop the very first one that we wanted the pilot taking the CPTAC model and trying to bring other organizations into it became one that involved the US federal government specifically three of our agencies and that program now is referred to as Apollo so Apollo is one right across my hospital has to be one of the largest hospitals for the Department of Defense which is the birth of the cancer center in fact that's the one that you see a lot of the presidential helicopters and congress and other representatives get treated at but that said though we basically walked across our street we met the cancer center director there was an opportunity to begin the pair up the National Cancer Institute the Department of Defense and the Veterans Administration and the deal was very simple they would begin to adopt a lot of the metrics a lot of the standards developed by CPTAC and they would also begin to implement this sort of proteogenomic based approach to look at the science of their veterans and of their family members and the part that's quite nice again is that we signed this partnership predominantly one main criteria is that all the data that they would produce would be placed in the public domain so that's what that involves the US federal government then the next thing I find out what I'm called by the White House by representatives of the cancer room shop program they said so we kind of like we ended up doing from this federal government perspective it's your opportunity to basically make this on an international level I started to think about it and the deal was quite appealing I have to admit it so this is what we ended up doing so we started to ask myself the following what if you can actually take this proteogenomic model and begin to scale it on an international level if you were to do that then you would have each country which is the best in making these decisions along with their various representative government they would be in the best position would be of most significance to their own nation furthermore they would adopt a lot of the metrics and standards if applicable developed by the US city type program but again a part that becomes very critical for me happens is that of any data that you produce from any of these official partnerships regardless of where you're from what country we want to see the data be placed in the public domain we can hope that in your country or at the same time the United States we would post those data sets for you that becomes a key criteria we'll decide on partnerships so that said here's now what transpires so in early 2016 in mid-summer so in January the cancer moonshine was launched then we quickly launched in polo and then I get this call we would like to see the scale on an international level the very first country that signs on in July is one so at that point we're in Australia so we have four institutions now within Australia that hold this partnership I thought my job was done I could give myself 20 nice hats on the back I got one I'm down at the White House I basically go home and tell my daughter oh look what great stuff I'm doing next thing I get another phone call a week later we loved what you did is you're an opportunity to expand this and by the way we want to see it expanded in 8 weeks no idea why 8 weeks was important it turned out the reason it was I found out later on because something was happening in New York City at the United Nations but they weren't telling me at the time but I felt it now would be something very interesting to go after after all it's very rare that you ever get to work for leaders within your own country so I thought it would be interesting so we did so in the span of 8 weeks we went from one country to four institutions at this point now we're spanning 8 countries and now it's involving 16 institutions pretty impressive but it's amazing when you send an email and it says on behalf of the Vice President of our country there's something we would love to see happen it's amazing because my name doesn't carry much weight other people names do now this is September of 2016 keep that in mind right now we're pretty much at the end of 2018 so the question is whatever happened to this program so this program actually has taken a beautiful life on its own today now this program has an official name it's not referred to as ICPC this program now involves 12 countries that spans 31 institutions collectively they're going after 13 cancer types they're not all different cancer types some do overlap but that's fine because the dream the vision that I've always had for this is ultimately when the US produced their database to me ultimately to understand cancer you really want to make it representative of the diversity of individuals and of the diversity of their cancer themselves it's that culmination I think that you're able to better understand the disease on a global scale so what has the program done in the past 12 months so here you go so in the last 12 months alone these are some of the activities that the program achieved the very first dataset that we released to the public actually comes out of Taiwan it was a cool little study that we did on global cancer because of the people that they happened to choose back that put into public domain we also welcomed at that point two other or three institutions spanning two countries early in the Canada year we brought in Korea University and of course as Sanjeeva mentioned the other country that we brought in born was Indiana in May of 2018 we also held a series of local cancer round table sessions basically raising awareness within each country and within their governments that helped them raise money to do the research which is one of the good things that we're doing here today I don't think we should be having a lot more of these to raise more awareness than the funding the other thing we ended up doing is we actually launched a training program of students we piloted that at this point Australia Korea University and the other thing that we're starting to do which is quite nice is that we're starting to take some of our laboratories and we're starting to convert them to become clear certified so they can take the actual test when they develop a targeted based acidity and take it directly back to their two networks and potentially begin to further fuse together the genomic panels along with proteomic panels in influencing how best to actually treat the individual itself the last time we all got together it was in the United States in Orlando Florida just took place a couple of months ago and as you can see it's a great family event I have to say a big tradition now that we started each represented from each country we all hold flags as a sense of pride but again it basically shows one thing that I've learned from this is that two and a half years ago when we thought about this idea and then two years ago when we actually launched it everyone would say you'll never get the data in place in the public domain it's happening we're starting to release it and there's other cancer data that says that we're released within the next six months once those manuscripts get accepted there's really no barrier which is what I'm learning if you simply ask and you actually are very cautious and you're very clear on what you expect things can happen so let me leave you with this final thought so I think a lot of farmers have been made when it comes to genealogy and I'm the first one to admit that because I see how it definitely benefits patients however here's the reality of the statistics today within the United States on average on a yearly basis just shy of two million individuals will hear the words you never want to hear and I tell everyone that's in a research lab go spend or train in a cancer hospital because you really understand the impact of what patients go through when they're retreating and the ones that cannot survive from the disease itself they will hear the words that you've been diagnosed with cancer furthermore on average within the United States just over half million individuals pass away from one of its many diseases and it's not just one disease it's a series of diseases that defines cancer but this is not an issue for the United States this is why we develop ICPC and I think it's great that we have India on board this is a global issue on a global basis itself on average on a yearly basis 14 million individuals are diagnosed with cancer and these are the ones that we're able to report furthermore just shy of 8.5 million individuals will die again from its many diseases so while I think a lot of progress has been made I think there's a tremendous amount of work where we still need to go forward with and quite frankly I think the work that people are doing here and the idea of combining what we've learned from genomics and fusing it now with the measurement of proteomics and in the future I think fusing it even with metabolomics I think that's the key where technology has become very mature and there's an opportunity to combine them that's the opportunity to take because you're able to get more biology out of the disease itself so with that I want to say thank you very much in today's overview session you are provided the knowledge of the various programs run by National Cancer Institute in the United States it was clear from Dr. Henry Rodriguez lecture and discussion that genomics and proteomics are complementary and they're of course indispensable for the understanding of disease pathobiology you are also introduced to the importance of generating high quality data and the various efforts the CPTAC undertook to make proteomics more reliable among the research community the cancer moonshot program aims at collaborating with international labs to gather comprehensive proteogenomic information of various cancers India has recently joined this initiative and now we have become the 12th country to participate in ICPC International Cancer Proteogenome Consortium to specifically look for breast, cervical and oral cancer we are sure that you'll be able to appreciate the importance of international collaborations data sharing and proper quality controls if we are to understand the disease biology and find drug targets against cancer in the future the field of proteogenomics is still emerging and every day new software and new tools are being used it is not possible to cover all of them in this course however we hope that with this course we are able to lay a foundation and instill in you the enthusiasm needed to take proteogenomics research forward thank you and all the best


Hey everybody, Dr. O here.  So like I said, there are 12 pairs of cranial nerves. They're usually going to be named using Roman numerals, so I think it's very important that you know the Roman numerals, 1 through 12. That'll be very helpful for you. Cranial nerves can be one of three types. They can be purely sensory, whether it's just somatic sensors or special sensors doesn't matter. They can be purely sensory, they can be motor, or they can be what's called a mixed nerve, which is going to have both a sensory and a motor component. Before we go through the cranial nerves, let me give you the mnemonic device that I used growing up. I was 16 years old when I first learned this and I still remember it, so it seems to work. The mnemonic device that I used, it was on old Olympus towering tops, a freeloading vagrant German view to hop. Please no offense to Germans, it's just how we fit it together. So on old Olympus towering tops, a freeloading vagrant German view to hop. So each of those words is the first letter of the 12 pairs of cranial nerves. You may see some slight variation, like I'll put up on the screen here, on old Olympus towering tops, a fin and German viewed sum hops. So the difference is there is that the vestibulococlear nerve, V, can also be called the auditory nerve, but you don't see that very often. And then also the accessory nerve can be called the spinal accessory nerve. So just keep in mind, you're going to see different mnemonic devices based on the terminology used. Okay, let's go ahead and jump in. So here we see cranial nerve one, the olfactory nerve. This is a sensory nerve involved in your sense of smell, like the name implies. So it starts here with about 20 bundles of nerves and their receptors there in the olfactory epithelium, those nerve, so when a signal gets sent to them, they're going to send that signal up through the olfactory foramina or tiny holes in the crib reform plate of the ethmoid bone, and that's going to travel up to the olfactory bulb and then it's going to work its way back to the temporal lobe, where your olfactory centers are. Anything else about that?  That's why water has to be driven into your nose to get infected with the brain eating amoeba. Trust me, you don't want to do that.  I would have them smell coffee and other things that had pretty strong smells, and if they could smell them and recognize them, then cranial nerve one was working. Okay, excuse me. Cranial nerve two, the optic nerve. So this is going to be the sensory nerve involved in vision. So the origin of this nerve is the retina. The retina is where the photoreceptors are that allow you to see. And information from the optic nerve, so the optic nerve itself, each optic nerve is going to be a bundle of about a million sensory nerves, so you have these two bundles of one million sensory neurons traveling from the eye as the optic nerve. And at the optic chiasm, you see that some of them cross, and now it's called the optic tract. It travels to the thalamus, specifically the lateral geniculate nucleus of the thalamus, and then back to the occipital lobe. If you want to test the function of the optic nerve, then you have someone look at something, right? Like a, like a snail and eye chart or have them read the paper, these types of things that tells you that they can see. So the optic nerve is functional. Cranial nerve three is the ocular motor nerve. So like the name implies, motor to the eye. So this is going to be a motor neuron, and it's going to control, let's jump ahead here, it's going to control four of the six extrinsic eye muscles as well as your intrinsic eye muscles. So it controls the superior rectus, inferior rectus, medial rectus, and inferior oblique muscle. So it controls four of the six extrinsic eye muscles that control the movement of the eye. And then when I say, so what kind of muscles are inside the eye, the intrinsic muscles are going to be the ones that control the shape of the lens. So you can see both near and far. And then also the muscles that control the iris or control the diameter of the pupil. So if you want to assess the function of this cranial nerve, you have a patient go through the cardinal fields of view. If they can follow your pen or follow your eye and you have them move the aisle over the place, then the, then those four extrinsic eye muscles are working. And then if you want to test the intrinsic eye muscles, you could, you could make sure their pupils are constricting and dilating or you could have them focus on accommodation, have them look at something far away and then something near. So that would be how you would assess the function of this nerve, cranial nerve three. Next, we have cranial nerve four or the trochlear nerve. Trochlea means pulley. This is the smallest cranial nerve of the 12 pairs. And this is a motor nerve. This controls one of the six extrinsic eye muscles. It's called the lateral rect, sorry, it's called the superior oblique, lateral rectus is an abducent. It's called the superior oblique. And the reason this is called the trochlear nerve is that trochlea or pulley-like structure the tendon goes through. So the trochlea nerve controls the superior oblique muscle that turns your eye down and to the side. So if you want to assess the function of the trochlea nerve, have have someone move their eyes or look at something in a way that causes the eyes to go down and to the side. So that's the trochlea nerve, cranial nerve four. Let's forget about the eyes for a moment. The trigeminal nerve, cranial nerve five is called trigeminal because it has three branches that I'll show you in just a second. This is a mixed nerve, meaning it has both a sensory and motor function. So big picture, it's just sensation to the face. The sensation to the entire face is controlled by the trigeminal nerve and motor to the muscles of mastication, the muscles of chewing. So let me show you the next image here. So sensation, just remember there are three branches. So if you want to assess the function of the trigeminal nerve, you need to make sure that people can feel the ophthalmic branches up here above the eyes, maxillary branch. Your maxilla is your upper jaw and the mandibular branch.  If they can feel on both sides of the face, all three of those areas, then the sensory portion of the trigeminal nerve is working. And then you ask them about chewing. I guess you could have them clench their teeth, but or you can talk to them about, are they having any difficulty chewing, these type of things. So the primary muscles of mastication, as you can see on the screen here, are the temporalis and masseter muscles. And then we have the pteragois, but we covered that back with the muscles. So that's going to be the trigeminal nerve, cranial nerve five, so sensation to the face, motor to the muscles of mastication. And we talked about how to assess that. Then the last cranial nerve for this video is the abducens or cranial nerve six. This is going to be a motor and it controls one of the eye muscles that I actually said earlier. So cranial nerve six, the abducens controls the lateral rectus muscle, which allows you to abduct your eye. So it turns your eye to the side. So if you want to assess the function of cranial nerve six, as long as you did your cardinal fields of view correctly earlier, then you've already assessed the function of cranial nerve three, four and six. All right, that's your first six pairs of cranial nerves. I'll come back with the second six in the next video. I hope this helps. Have a wonderful day. Be blessed.


Okay, Lydia, Lydia. I'm not sure how to pronounce that now that I think about it. Lydia, forgive me if I have it wrong. This is your sheet three, and I'm just gonna rename that model. So I'll have to remember it. And sheet one, I'm pretty sure is is B or, whoops, label these so I can remember, brand A, and sheet two, B. Okay, so here is brand A, and this is the intercept. I think I erased that by accident. This is the results of your regression when you, and it looks like you regressed it properly. You've got an intercept of 250, price of brand A coefficient of minus 0.56, and a price of brand B coefficient of plus 0.34. And I think those are right just from memory. What I'm gonna do, I am going to copy those, control C, go over here to your model, and I'm just gonna pick a place down at the bottom, control V, and I'm gonna label that B or A in the A. That's brand A data. Let's go over here to brand B. I'm gonna copy that same information, model, and I'm gonna go right there, and this is B or A in B. So now I got the information I need to construct the model up here. What we need to do in this cell that you've got 257 right now, just a raw number, we need to construct an equation that tells us how many units of sales we have based on the price of A and the price of B. And I'm gonna do that just click equal, and this is model A, so brand A, the intercept plus this coefficient times the price of A plus that coefficient times price of B. And you see now that we've got that equation in there, B27, which is that intercept, plus B28 times B8, B8 is the price of A, and you can think about that. As the price of A goes up, the sales of A go down. As the price of B goes up, the sales of A increases. So now let's do the other equation, equal that intercept plus that coefficient. Times price of brand A plus that coefficient times, it is driving me nuts here. You put this on pause because they get it to, okay, let me do that again. I'm gonna click in that cell, equal the intercept plus coefficient times price of A plus coefficient times price of B. So now we've got an equation for both of these. The equation for the sales of B, model B, says that it's 320 plus the B sales go up as the price of A goes up, and then the price of B goes up, the sales of B go down. So those are your equations. Now we just need to connect these things. The revenue equal price times unit soul. And once we get that, remember we can just copy that down and you already have that sum, so that's correct. The cost, so you've got entered in there hard coded and really that needs to be an equation again, equal the unit soul times the cost. And the same thing's true here, equal unit soul times the cost. And that should be summed down, that's okay. Now we need this to be also an equation again, and profit is nothing more than equal revenue minus cost. And that one we can copy down, and you've got that summed up correct, okay. So now we've got this 15,930 is our total profit based on this model. If the price of A is 200, then we get 59,30. If I change that to 250, you can see that everything updates. And the key thing that I did that you didn't have, when I first got here, this sale just had a hard number. And all I did was to link it, equal that total profit. Okay, that is the basis of the model that you'll use throughout the rest of this problem. And the next thing you wanna do is use the data table. Okay, now we're ready for the data table. The tricky thing about the data table is remembering what is the row cell and the column cell. What I like to do is to take those cells, go to home here, and I'm gonna say that is my row cell, and then my column cells, or remember, I'm gonna make that yellow, and that, those cells. So that helps me remember what are my row cells. I mean, my row cell is cell B8, and my column cell is B9. So to do the data table, we select that key corner cell and then highlight everything that we want from 200 to 600 vertically and 200 to 600 vertically. Horizontally. Then we go to data, what if, data table. And here is why you need to, well, I color-code those things. My row input cell is the green cell. Just gonna click on that. And I click here in the column input cell, get that blinking cursor, then I click there. And that is the data I need. And I just click that. I'm gonna go ahead and format that a bit, make this dollars. And there you go, there is your data table. So I hope this helps. I just wanna mention one thing. I'm gonna email this spreadsheet back to you so you can reverse engineer it. And remember, you can just click on a cell to look at the formula and follow that all the way through. If you double click on a cell, you can see not only the formula that's written there, but also the sales that it's dependent on. The other thing you can do is to go to, I think it is formulas, and I wanna trace dependence. I'm gonna go there, let's see if it'll, here. See there, I just clicked on it and it shows that I connected this cell to that cell. This cell is a dependent of that cell. If I go here, trace dependence, it doesn't have a formula to show that, but let's go here. I'm gonna go to that one, trace dependence. And that's a good one because you can see that the sales of A and B are both dependent upon the price of A. And if I click on the price of B, same thing is true, that the sales of A and the sales of B are dependent upon those prices and they affect the revenues which go downstream. So I'm gonna just remind you that you can see that.


I promise you, you're going to want to see how I made this big zitty. Two chicken breasts. Cut each breast in four big chunks. Now we're going to boil this chicken, but we're definitely going to add some danos. And some green onion. Get you another pot of water boiling. Add just some salt. We're using one pound of panay pasta. Now get your boiled chicken and just simply shred it apart. Now we got all our chicken pulled. Get your danos. Sprinkle it on the chicken.  Pour it right over the top. Mix it all in. Now get you a 13 by 9. We're going to add about half the noodles.  Put about half the jar in. Mozzarella cheese. Now we add our chicken. Add the rest of our noodles and the rest of our marinara sauce. Use the rest of your mozzarella cheese. Get your danos cheesening. I'm not showing you the label yet, but wait for it. It'll be available soon. In our 400 degree oven, we go 25 minutes later. I just showed you how to do it. Go make it. Yum yum, get you some.


Abstract pre-organization is a fundamental design principle used by nature which enables multiple functionalities to be expressed in a synergistic manner. This results in improved performance when compared to random or isolated arrangements as demonstrated by the use of uranium sequestration as a model application. The resulting material has chelating groups populated adjacently in a spatially locked manner, displaying up to two orders of magnitude improvement over a random and isolated manner. Furthermore, this material can reduce uranium concentration from 5 ppm to less than 1 ppb within 10 minutes, even while being exposed to high levels of competing ions. It also has a capacity of 5.01 mg per g for seawater uranium extraction, making it one of the most efficient materials reported to date. This article was authored by Chi Sun, Yen Pei Song, Brianna Aguila, and others.


Welcome to Sheboygan County government working for you. My name is Adam Payne County Administrator and co-host of this program with Chairman Tom Wagner and today is a little bit of a bitter sweet taping for us because today will be the final TV8 program with our good friend and Director of the Health and Human Services Department Tom Eggebrecht. Tom welcome. Thanks Adam We were just talking a little bit off the air about the next chapter and I know Tom's looking forward to that But before he leaves us we're gonna learn a little bit about the Health and Human Services Department today It's our largest department one of 19 just under a 34 million dollar budget a lot going on so much important work in that department and Tom please start by Remindersing a little bit.  Sure I've got you know for four decades of Service now in terms of human services ten first ten years was spent in the private agencies in Milwaukee And I've been involved in county government now for 30 years So Sheboygan County for nine years Brown County 11 years before that and Manitowoc County Ten years prior to that and I know Adam that during the time I worked in county government When I had the chance to meet people from Sheboygan They were always down to earth. They were always gracious. They were always friendly So I always had a high regard for the work being done in Sheboygan County Even before I landed here So once the position opened up and I had a chance to apply it piqued my interest I would say through that process having a chance to meet you and Now mayor Mike van der steen who was county board chair at that time Roger Otten who's served on the county board for a long period and serves on our health and human service committee Each of you were on that interview panel and I remember it being I would say More of a conversation than an interview. I left that interview Hoping I'd have the chance to work for Sheboygan County. I remember my wife Reporting to me that she received a phone call from you As as you were preparing to make an offer and she talked about how uplifting that was that has left a very very positive You know impression with her about Sheboygan County about you and about this place and I would say that Having had that opportunity. I've never looked back everyone. I've met everyone. I've worked with has been extremely Gracious friendly. I've enjoyed it. I would say it has been the pinnacle of my career and on many levels My life as well, so I really appreciate being here. Wow. Well, thank you for sharing that and We are so grateful you've been here for the last nine years There's a lot of your peers and staff as you know that are happy for you and Pam But at the same time and the dearly miss you so thank you for sharing that and I'm glad you ended with the county that you felt So good about absolutely wonderful well Focusing on the department in those roles and responsibilities What is the mission of the health and human services department and I know you have a number of staff Working in core program areas give us a little snapshot. Sure. So all counties are responsible by statute for providing safety net services for people experiencing economic hardship health issues Safety issues they might be, you know vulnerable and at risk of abuse and neglect So all counties in the state are responsible for providing health and human service Programs and some counties do that in the form of several separate departments We here in Sheboygan and this is one of the things that has been a blessing for me We have an integrated health and human services department So some counties might have a separate department of public health separate department of community programs Here we're combined and we work under a mission of improving quality of life and self-sufficiency And we do that through several programs as you mentioned and we do that through four separate locations So our main building downtown across from Fountain Park in Sheboygan Offers child protection juvenile justice behavioral health services and our public health operations At the job center on Wilgus Avenue. We offer economic support Programming we have an aging and disability resource center in Sheboygan Falls also known as the ADRC So that Operation provides information and assistance to persons who are aging or have disabilities who might be facing the need for long-term care And we also offer our senior dining program and adult protective services through that location And then lastly child support operations are located in the courthouse annex and child support is directed toward assuring that non-custodial parents Participate in the financial well-being of their children. So there's a lot of work with the courts. So that location is very convenient for them Tom and I we we both now have been around the block for a little while and Chairman Wagner was a school principal teacher. So he worked with a lot of good people good co-workers I've been here now 20 years and I take such pride and Pleasure and work we can with so many good people good-hearted passionate people and Though health and human services may be one of 19 departments when I think about your staff. I Think it's just incredible the work they do that the very challenging and important work that they do and they are very skilled And working in a number of areas please touch on that a little bit talk about your staff and the different skill sets that you Need to have a good team. Absolutely. Yeah, currently we employ a hundred and eighty nine individuals next year We're looking to add a couple more But the number is currently 189 and that staff comes to us from a variety of walks of life So we have people that gravitate to working with us who come from the banking industry from healthcare industry from educational institutions In some cases many cases our staff are fresh out of school And in some cases It's people that have worked for other counties and know a little bit about Sheboygan much like myself who gravitate to work here So we employ as I think about it again pretty diverse group of individuals We've got secretaries account clerks accountants Software professionals business analysts social workers social service aides doctors nurses behavioral health therapists and more So again, it takes all of those people working together to deliver the services that we do I'd like to put in a plug also I Love the fact that we are an employment source for many members of the community And I would encourage anyone who would like to know more about health and human services to make a general inquiry if we can offer information guidance or employment, I would love for us to do so and Folks can make contact with our department by phoning our general number at four five nine three two oh seven We're sending email and care of human dot services at Sheboygan County comm And I'm confident that whoever receives that message would be happy to speak with anyone about employment opportunity well nice overview and as you said just Wonderful caring hard-working people passionate about what they do passionate about making Sheboygan County even a better place and I've just really enjoyed getting to know your staff better over the years wonderful people and and as we talk about a lot in County government on not only good people, but it's about Collaboration it's about partnerships and your department perhaps more so than any has a tremendous number of Partnerships both internally with other departments, but externally with other organizations nonprofit organizations Please touch up on that a little bit and why that's so important to be sure that we're providing good service Yeah, you're right Adam We do employ a number of individuals But the work that we do would not be possible without those partnerships and that exists in two different forms In one a formal contracted relationship So we actually enter into contracts with over 90 separate organizations in the current year And there's about 15 million dollars invested in Those relationships so when you think about our department, we provide some services directly most specifically in the form of behavioral health counseling and in some cases public health nursing But beyond that at our core. We're a case management agency So we assess needs we make arrangement for services We enter into contract for services and those services can include group homes job placement services inpatient Hospitalization crisis response services, etc Then the other type of relationship that we have is with community partners in general outside of contracts But certainly no less important and I would say that the relationships We've had with law enforcement locally have been exceptional I can't say enough about our sheriff's department or local police departments and the collaboration and assistance we receive from them Schools who made mention to Tom and his background in education Schools are such critical partners for us hospitals as I mentioned We work closely with the United Way on a number of initiatives Unbalanced again, we would not be able to accomplish what we have been able to accomplish without those relationships What example I could offer of that collaboration and again viewers might be interested Do an online search for healthy Sheboygan County 2020 and you'll see some information there about the community Agencies that have partnered with us and each other in the interest of assessing community health needs in the interest of developing Health improvement plans, so we work with hospitals agencies school districts United Way in Developing those plans every three years and setting a course that we collaboratively work toward so I think that's an excellent Example of the collaboration that you're describing. No one's paid to do that No, one has to do that, but this community comes together in the interest of doing that. I think it's pretty special I'd also like to make a brief plug when we put our budget together Annually we have a public hearing that's held every June It's important to me and I think it's important to our staff that the work that we do Be responsive to and reflect the interest and the needs of the community. So in June, there's a public hearing opportunity I'd love for us to receive feedback from the public about how we're doing what we should be doing So in the interest of that collaboration not only is it important that we partner with agencies But I think it's also about partnering with the people we're here to serve and so far It's been pretty successful and you've been and your staff have been an outstanding listener You do listen to the community. I think back to the community conversation years ago And hearing about all these programs and services But we didn't have key people to coordinate it and make sure that they were putting people in need and touch with the right Organization you responded to that United Way with path welcome, baby more recent initiatives and the one that really comes to mind to me Tom is the Lakeshore clinic the community clinic that Kristen Blanchard Stearns is the executive director of Wow, I mean, that's just an incredible success story for Sheboyin County And it was our health and human services department even Predating you with and wonder Jim and Dale Hemp and steel who wrote the grant to get that federal Those federal dollars started and now look at the needs that's addressing with dental care and other needs in the community And our department was a part of that so You certainly can take pride in that your staff can take pride in it And I know the county board does because if it wasn't for the county board providing some of those seed dollars some of those resources support Those types of partnerships wouldn't have happened so well done and thank you. Thank Tom. Thank you Adam Welcome Tom. Thanks Tom Sheboyin County's budget. I think your health and human services makes up about 23% of it But not all that is a tax levy and that I think your budget is around 34 million dollars So what percentage or what a dollar amount if you if you know that is is levy from the local property tax Fairs and then what are your other sources and ensure? Yeah, you're right. We get exceptional support again working here. It's been a gracious Giving supportive community. We do receive about 14 million dollars annually in levy support Which is just about 40% of our budget The vast majority of it then comes from State and federal funding sources, so there's different grants. There's different appropriations that we receive and about four million then comes from user fees, so If you need to reside in an assisted living facility through department sponsorship Those individuals would contribute a portion to that cost of care. So again, that's about four million dollars annually So those state and federal sources we actually have 50 different funding sources that come in through our department and they each have different qualification standards different documentation standards different reporting standards and that's where those Secretaries and accountants and business analysts that I referred to earlier Help us keep all of that organized and it's no small challenge. Trust me It's it's a little bit daunting, but it's also a blessing and that we're diversified, you know We have many sources of funds. So as things shift and change in any one front. We have the capacity To think about and pursue correction in other avenues. So it all works together Right as a county board supervisor for the last ten years and then being the chair for less two and a half It always strikes me as Relative especially to the state and federal funding that those are constantly changing all the time that your people have to be you know, whatever was Well, might not be the next year or changes and you're you have to be extremely nimble from what I can tell Yeah, you do have to be nimble which is which is sometimes a challenge You know working within a government process and it's good But it involves vetting it involves decision-making it involves sharing of information at the same time The world is kind of changing very rapidly in the background. And you know as you as you mentioned that Reflect on new staff that have joined us and my advisement to them was it's going to take you two years To feel comfortable with what you're doing and that two years you're going to realize that you will never be comfortable But you just kind of you know acclimate to that kind of Mindset because it's very very real and if we can't change we don't survive Yeah, we think so and that note just to follow up I know we just received a notice from the federal government of a three hundred and set about three and seventy five thousand dollars on a For our treatment courts over I think the next four years. So yes that that would be one of those examples We're very very gratified to receive that Jackie McGlowski our behavioral health manager wrote the application for those funds So I'm very indebted to Jackie and that's one of several that we receive in the course of what we're doing Well, a lot of things change obviously all the time and as we talked about yet to be nimble What do you see for 2019 as far as some of the challenges that are out there for health and human services? Yeah, the challenges for 2019 are not a lot different than what they've been for the last couple of years So we talk about the opioid epidemic. We talk about drug treatment court We've touched on children's mental health those continue to be kind of preeminent concerns if you will Thanks for mentioning the grant. We just received that is going to help us bolster our treatment court efforts One of the things we have planned for the new year is adding an AODA Counselor who we expect to be working more closely with addicted individuals and partnering with our sheriff in the interest of diverting people from incarceration when treatment might be indicated or helping inmates with community re-entry Following incarceration. So it's not enough to simply be released from those correctional settings I think we have to pay attention to treatment needs housing needs employment needs if people are truly going to be successful So we're adding resources on that front. We're also going to add a couple of Therapists to our staff One to work more closely with the schools in the interest of kids who are experiencing crisis who have deep end needs I know it's a challenge for for educational facilities to try to figure out what's going on with kids and Sometimes the answer rests with those kids sometimes with families sometimes with schools sometimes with communities And so we want to get a better handle on that. So we're adding a therapist to help on that front We've pursued a path of becoming better informed about the impact of trauma in people's lives So we're adding a therapist to help kids who've experienced Horrific circumstances early in life heal from those experiences and hopefully get on a better path moving forward We're going to bolster child welfare Services again that area has seen the brunt of the impact from the opioid epidemic So we're adding a supervisor not in the interest of more closely monitoring staff, but hopefully being a More ready resource for staff and guiding them through some of the complexities of cases that we're seeing We're going to be contracting for in-home safety services in our child welfare arena So we've seen an explosion in terms of out-of-home care in recent years We need to do a little bit more to figure out if we can keep kids safe at home in Lou of out-of-home placement and then lastly I know that this has been a couple of years coming But we're going to be able to expand some transportation services to rural areas of our County We applied for grant dollars this year. We received notice Hopefully we're going to get a couple of vans yet at the end of this year that will prepare us for 2019 to offer I guess trips to folks living in rural settings. We've done a pretty good job in terms of medical transports This will bolster that and offer transports if someone needs assistance going to the grocery store or getting to other service facilities We're looking forward to doing that. You talked about our child welfare. I know in our child protect Protective services. There's been just a I think you use the word explosion and then I hear from other counties, too So you want to just talk about that a little more or why that is occurring. Do you sure well as I touched on a Good amount of that relates to the opioid epidemic over the course of the past seven or eight years our Numbers of children and out-of-home care has expanded by over 300 percent so 2010 I think we had 64 children in placement for the year last year 219 in placement for the year and Many of those Circumstances relate to addicted parents or the presence of drugs in homes. I think through the first half of this year Out of the four to five hundred calls that we've received for child protection involvement, we've had 113 children who've been exposed to drugs whose parents are addicted or who themselves Might be addicted at birth It's not uncommon for infants to be born to addicted mothers and to be addicted themselves So 113 out of that group Are facing those issues So the way our child welfare system works calls our screened in terms of is an investigation Warranted and then when investigations are done. There's either Substantiation or closure of case those cases that are substantiated move to ongoing services and out of a hundred and fifty five open cases 100 of those cases are Indexed to drug issues within our system. So when we've got those circumstances in homes Out of home placement for those children becomes kind of an important response That's what's fueled the increase in that out of home care So we've done a couple of things to try to address that number one We have an opioid detox program that we're prioritizing access to For any parents who are willing to change willing to go through treatment willing to go through detoxification But then we've also partnered with the district attorney over the last couple of years To fund a special prosecutor in his office that will help us move toward termination of parental rights When parents aren't able aren't willing aren't prepared to go down that path. So we prefer not to do that I prefer to keep families together. It's traumatic for kids to be separated from families But at the end of the day kids also need Permanency they have a right to a safe home and if natural parents aren't able and willing to go there the district attorney helps us pursue petitions in court for consideration of Terminating those rights which then allows those children to be placed in adoptive homes Okay, and pretty hard to be a parent. It's hard challenging to be a parent anyways, but to be a parent when you're addicted Yeah, it's a pretty tough tough for your children. So it's not just the Addicted person. It's obviously the children who are suffering absolutely. Yeah, it does. We do have a treatment facility And do you want to talk about that a little bit? Sure. So in terms of opioid detox We actually have a protocol within our department of administering a drug called Vivitrol, which helps reduce The cravings if you will Through addiction. So we're helping people through detoxification And we do that through injection of Vivitrol as I mentioned We have a community based residential facility that houses persons during their period of detox And we provide comfort medications to them and then it's typical for individuals to go into a Probably three month or so residential treatment program and we've got contracts with a number of Entities much as I was talking about earlier for provision of that service Following discharge from those facilities those individuals would be enrolled in intensive outpatient programs Through our guidance and we're hoping to bolster that in the new year One of the things we found is that not everyone is ready and prepared to step into treatment So one of the additions we're looking at for the new year also is employing recovery coaches people who themselves have gone through the battle have headed on a path of recovery and might be able to assist us without reach and and support to the Individuals who are considering getting enrolled in the program. Well, thank you Tom. Thank you Tom and thank you Tom Thank you Viewers are following the toms here What a nice overview so much going on at Health and Human Services So many programs and services that your staff administer Many of the challenges are ongoing. Many of them are new and It's just remarkable how many people you help and and what's all in front of us And as you reflect on the last nine years if we just focus on Sheboygan County and some of the key challenges that have come your way and Some of the changes you've made What stands out to you of some areas that you know fill you with pride or gratitude on what you and your team have been able to do Probably first and foremost and this is not one that's particularly Apparent to the community It's nothing that you can look at on a spreadsheet and say oh, yeah I see what that's all about But the one that stands out for me that I think will provide the best return on investment over the long term is our embrace of becoming better trauma informed as an agency so The health care system. I think it's just beginning to understand and grapple with The the health impacts associated with adverse childhood experiences. So when kids have been through trauma Neurologically, they're compromised emotionally They're compromised and we for the past three years have embarked upon an initiative whereby all of our staff are being immersed Immersed in better understanding about trauma and its impacts So I think that'll carry the department and the county well into the future As part of that We we have to be more welcoming as an agency. I love the new addition We've been able to put on our building It is far more welcoming and inviting than it used to be you mentioned the community conversation on mental health 2014 one of the comments was it's difficult to access services. So we established information and assistance staff in our department to help people Accessing service whether it's through our department or elsewhere in the community. I think that's a valuable resource our drug treatment court The partnerships we've had with United Way you touched on it In terms of welcome, baby community partnership for children the PATH initiative We've partnered in the region with other counties to expand mental health services And to develop a child advocacy center and that is specifically Ozaki in Washington counties the last few years We've partnered with to do that. I Think we've improved our business practices over my time here. We've been able to achieve nine consecutive positive budget Outcomes and I'm very proud of that Proud of the work that our staff are doing and overall I think that we just have an excellent team I'm not here to take credit for anything but to give credit To the work that those guys are doing and I think that the county is in great shape and will be for a long time to come I'm so pleased to have been a part of it We're so pleased to we're here as well. It is bittersweet in the last few seconds. We have remaining I just want to again say how much we've appreciated Tom's leadership and the tremendous value Vision work ethic that he brought to Sheboygan County. You have built a stronger team. You have a wonderful team and None of us are irreplaceable, but Tom is going to be tough to replace. We're going to miss you my friend. Thanks Adam So thank you. Pleasure working here. Best wishes Tom on behalf of the county board. Thanks. Thank you for all your work You as well. If you see Tom before he heads out. I think his last day is October 19th That's correct So I'm not quite sure when this will be aired But if you get a chance to reach out to Tom and wish him well, please do Hopefully we'll see him from time to time, but I know he's headed to warmer climate and Please join us next month when we have our finance director Wendy Sharnon here to talk a little bit about our budget process Which is just about wrapped up and looking pretty good a lot of teamwork a lot of hard Work has gone into the budget, but once again We're poised to have a very modest property tax levy increase under 2% and frankly That's pretty remarkable when we get into the programs and services and demands we have so thank you for joining us Thank you. Tom mega-brecht best wishes. See you next month