Good afternoon everyone, first of all apologies for all the technical technology based inconvenience that you had to face the entire day today. There were some technical issues at our end in terms of internet disruptions that happened in our lease line due to which many of you were not able to connect to a view after 12.30. We believe that the scenario has been restored, so just to get a feedback of what has happened over the past two days, we have created a small survey and the survey link if you actually look at your whiteboard right now, we have given you a survey link over here. What I would request all remote center or coordinators or the course coordinators who are present at the remote center is to click the survey and fill it in the next, fill it before today evening. So, that we can understand what has happened, what went wrong in today's session and also if there were groups who are not able to do breakout session properly, what we are thinking of is giving them an alternate slot sometime this week during this week where they can interact with the other group members from Monday to Friday this week for three hours and they can present their work and get feedback. So, all course coordinators please note kindly use this link to get feedback to provide as a feedback for the activity that was done today. So, I will just write it over here. So, this survey is intended to give us feedback about what happened about the lab and breakout session. We had visited few of the groups where the sessions were going on and we had given them guidance on how to do certain activities, but one thing we realized is that many of the centers had not completely understood the teacher or presenter view of a view which needs to be properly exploited to make better use of what do you say the a view conference software and do the breakout session. So, what we are going to have is over the next half an hour we will have our studio team explained to you the teacher or presenter view of a view and our studio team will be Sushant from our studio team will be explaining to you about various functionalities of a view when you use it as a teacher or as a presenter. The importance of this session is in the fact that many of you will be interacting to your mentors for the OER creation. So, we will have a group of mentors who will be helping you out in OER creation with whom you can ask doubts etcetera. So, these mentors will be joining on board this week in IIT Bombay excourse page and next week they will be interact they will start interacting with you in a view. So, this knowledge about a view both as a teacher. So, now what you do is you view a view as a student the functionalities are very limited when you do a view as a student. So, but when you interact with your mentor sometimes the mentor will provide you with additional control as a presenter in which case you can do a lot more with a view like give upload documents do a desktop sharing in chat on use private chat functionality create folds etcetera which can then be effectively be utilized for a meaningful interaction. So, I will invite Mr. Sushant for the session. So, over the next half an hour or till around 3.30 you will view a view how to use a view as a presenter over to Mr. Sushant. Good afternoon to everybody this session should have been given to you earlier, but we also realized that we need to we have to give this session to everybody. So, that people know everything about how to handle a view as a teacher you have been using it as a student, but you have never used it as a teacher. So, I will be you know going through all the features of a view that can be used as a teacher I will share my desktop and I will show you how a view interface is used I have just shared my desktop it will be up in a minute at your end I hope everybody is able to see my desktop right now there is a view screen on my desktop can you please reply on chat if you are able to see my desktop please just send a reply yes or no on the chat window I see a lot of yes if in case if somebody is not able to see the desktop do not worry we are also recording this session and this will be available offline also and this session is also live on YouTube. So, if you are not able to view it on a view just go to YouTube studio IITB channel and it is also the video is also available live right now on YouTube also if you are not able to see it on a view. So, I hope everybody is able to see my desktop right now. So, I will start with the a view interface so, first what you do is you just you start a view by clicking on this icon that is a view. So, when you click on this you get a interface to type in your username and password. So, once you type in your username and password you enter the classroom and there are list of classrooms that are available which you can join in. So, you have to enter the classroom which you are supposed to join at that time because all the classrooms are available at all the time, but the timing of the classroom is very specific. So, now so, like your group classrooms were available in the morning, but they will not be available in the afternoon right now. So, if you try to join them join the groups now there will not be any person logged in right now there. So, right now you are logged in into FDV classroom so, this is the FDV classroom right now that you are available. So, after you log in first the thing you have to do is you have to click on this video button. This is the start and stop button of your video though it says video over there this is the start and stop button of your video. Once you click on this you will get a screen I will just go from desktop sharing to a document I have a document where I can show you I think the document is not available here. So, I hope you have tried you know the start button and video button. So, once you click on that button you see an interface where you are able to see the camera options you will be able to see select the camera then select microphone and there is a bandwidth option also there to select. So, what most of the people are doing is they think that their bandwidth is ok. So, they are selecting 512 and above. So, what we suggest is whatever your bandwidth is please select 256 as your bandwidth when you start the video. Because whatever your bandwidth is if you select 256 it will stream seamlessly across all the remote centers. But if your bandwidth goes down if you select more than 512 bandwidth in the bandwidth option then if your bandwidth goes down by some reasons or some of course some reasons then there might be some problems in the connections or the transmissions of the problem. So, we suggest that every time you start the video you select with to you start with 256 and VPS bandwidth KVPS bandwidth sorry. So, after you have selected your camera then after you have selected your microphone proper microphone then there is a start button. Once you click the start button I hope you are able to see my desktop right. So, once you click your start button a video of your own your own live video appears on the right hand side top corner. So, here right now you are seeing that my video is available here. If your video is not available if the video does not start it will show you a blank screen that means there is some problem with your capture card or there is some problem with your connection of your camera. So, once you start your video you should be able to see your own live video on the right hand side top corner. So, this assures you that your video is been streamed live. After this I will just go through this user list these four tabs this user list chat viewer and the questions tab. So, what this user list is where you can see all the users which are connected right now or whenever you will be logged in in the user list you will see all the users that are connected right now and who are live there is an AV status check box here. So, once you click this AV check box you will also be able to see who have started their video and who have not started their video. So, see if this video icon is showing in all those against all these remote centers that means their video audio is on. If it shows a cross here that means their video and audio is not on they have not started their video. So, this AV status check box if you click on that it will show you whose video is available and whose video is not available. So, this is not necessary to keep this on all the time because it will also consume your bandwidth. So, you can just check just to check if video is available you can just click on this check box and you can deselect this. After this so this user list is where from where you can select the center to interact. So, right now what I am doing is I am giving a lecture and this is been streamed live to all the centers. So, everybody is able to listen to me, but nobody will be able to you know interact with me unless I allow it. So, for that a teacher has to you know select a center whichever center he has to interact and then he has to you know right click on that center and click on start interaction. So, once you do that you have to just right click click on start interaction once you do that you have to go to the video wall button this is the video wall button. I cannot show you right now because I am sharing the desktop if I go to a video wall then this desktop sharing will be closed. So, once you select the center and you go to this video wall button you will be able to see both yourself video and in the remote centers video. And once you select them you will be able to interact and the interaction will be two way. So, the other center also will be able to interact and his audio will be available to all other remote centers. So, this is the way to select a remote center see in the viewer option in the viewer tab you will be able to see their video. So, now I have selected Goa college and their video is available here. So, like this you can select a center and their video will be available. So, lot of people where you know having confusion between after selecting they were not able to see their video. So, this is because if you are in a document tab or in the whiteboard tab you select a person you select a center and you are not able to see the video here. So, right now there is no video select there is no video of a center here. So, what happens is once you the remote center is selected the video is available, but the video is available in the video world tab or the viewer tab. So, you will have to go to these tabs to see the video. So, now we have done with the interaction session. So, then there is a chat module here this chat is a public chat. In this chat everybody can post their chat messages. So, whenever there is a you know audio problem or whenever there is a confusion that if you are not audible or if you are audible or not you can always post your chat message here and ask everybody if you are audible or not. So, this is a you know better way to ask if you are audible or not. So, do not you know keep asking if you are audible or not through your audio itself you can just post it on your chat you just post it on the chat if you are audible or not and the people will you know reply. So, please also make sure you look after the chat window also. Then there is a questions tab here the questions tab is separately given here because this chat is a public chat people post a lot of you know unwanted messages also and there are a lot of messages that come and go here. So, that is why if you post a question here it might you know get lost in the all the chats. So, that is why there is a questions tab here where you can post specific questions that you have. So, if you post a any questions that you have that it will appear here. So, this is a questions tab. So, now I will you know this after this I will show you how to make us make a student a presenter. So, this thing will be you know useful for you after this workshop when you yourself will be having a mentor-mentor interactions at your end. So, IIT Bombay will not be you know involved in this you alone with your participants will be interacting through a view at your end. So, at that time this will be very useful for you. So, right now assume that you are the teacher like right now I am the teacher assume that you are the teacher and you have selected some center. So, now you have selected Goa college and you are able to interact with them, but they will not be able to use any of these features of a view unless you give them the presenter control. So, what you have to do is you will have to deselect them first if this if any if any of the center is selected you have to deselect them first after deselecting you have to select the remote center you want to make the presenter. So, whichever center you want to make the presenter click on that center go down there is a make presenter option here I will repeat again just left click on that center and then there is a make presenter button. Once you click that make presenter button what happens is the presenter control goes from your side to the excuse me to the student whichever you have selected and what happens is that person becomes the presenter and you are deselected after that center becomes the presenter the center what the center should do is he or she should start the presentation immediately by just asking yes or no if they are audible on the chat and if they want to interact with the teacher or any of other student they have to do the same thing at the as the teacher does to start an interaction. Once that you get the presenter control you become the presenter and you are being now the teacher and you have all the controls. So, now you can go to any center you can right click and you can click on start interaction. So, what I suggest is once you have been given the presenter control you go you just select the teacher and click on start interaction so that you and teacher will be able to interact otherwise you would not be able to interact. So, once you have selected click on your teacher right click on your teacher and click start interaction so that you will be able to interact and the audio video will be on after that. So, if you so now if you want to present something so let us say you have a PPT or a PDF file. So, we recommend that you if you have a PPT you convert into PDF and then upload it on the documents tab this I am sorry I have just stop the document ok. So, there is a documents tab here. So, once you go to this documents tab I cannot go to it right now because I have shared my desktop if you go on this documents tab you will see a small library option here on this corner. So, once you click on that library option you will get a pop up window to upload your document. So, whatever PPT or presentation files you have just convert them into PDF because PDF uploads very quickly at in a view but PPT sometimes have a problem. So, convert them into PDF go to this documents tab we will get a library option in this corner click on that you will get a pop up window where it will ask you to upload your document. So, just browse your document wherever your document is select your document and click the upload button there will be a upload button there if you click on that upload button it will take 45 seconds to 1 minute to upload the document depends depending on the size maximum it will take 1 minute. So, at that time it will show you some it will show you an option here at this on this tab that the document is uploading. So, once you upload the document it will take you know under 1 minute to process the document in its own format and then it will get uploaded and once the documents get uploaded it will be visible here and there will be 2 arrows on the top to you know go forward and backward in the document. So, this is how you can upload a document here then there is a whiteboard tab on this whiteboard tab what you can do is since we use an eyeball take note tablet. So, we can you know write anything on the tablet and it appears on the whiteboard, but what you can do is you can also use it as you know you know you can just type it there is an if you click on this whiteboard you will get a tool box on this right hand side bottom corner or left hand side top corner you will get a tool box in that tool box there are many options to select pencil or use you can select you know the thickness of the pencil or you can select a text option. If you select a text option you will be able to type on the whiteboard. So, there is no need for a you know take note or a white you know writing pad if you click on just click on that text option you will be just able to write it on the whiteboard then I will skip this video sharing part because this is not working properly right now then there is this desktop sharing option. So, right now how I have you know shared the desktop the same way you can click on this desktop then there will be a two options here this is a screen area then there is an application. So, what screen area does is if you click on screen area and start desktop sharing it will give you whole screen of your desktop the whole screen will be visible right now your a view is visible right now. So, now my desktop is visible if I open a ppda it will be visible whatever happens on my desktop is visible this is the option when you select this screen area then there is another option does the application this what this option does is if you click on this application button and then start application button a pop up box will appear which will show you all the applications that are open on your desktop. So, right now there are there is a chrome then there is a control panel open here then there is a ppt open here. So, if I click on the application it will show me a box and it will show me what all applications are open in my desktop. So, it will show me chrome then it will show me ppt. So, if you have a ppt if you want to share something from the chrome does chrome browser you double click on that chrome or you double click on the ppt what it will do is it will only share that application I will show you how it does. So, right now what I am doing is I have clicked on the application and I have you know I have got a pop up box I have got a pop up box where I can see all the applications that are open here. So, what I want to do is I want to you know show something on my browser. So, I have you know on that pop up box I have a chrome written over there. So, I what I do is I double click on chrome what happens is when I double click on chrome whenever I open my chrome browser at that time only it will be visible in the desktop sharing option. If I minimize my chrome I guess it shows a blank screen right Sajan ji Sajan ji it is showing a blank screen right now. So, I guess it shows a blank screen or it shows a black screen. So, whenever I open the chrome browser that time only you will be able to see the chrome browser. So, that is the you know point of this application sharing and screen sharing. So, I am just sharing my desktop the whole screen again. So, this is how what the desktop screen area and application sharing is for all about. Now, this video the I will skip this 3D and 2D viewer there is then there is a video wall button. Video wall button is when you are not presenting anything you just want to interact face to face. So, if you have selected a person if you have selected any remote center and you want to interact face to face that time you have to click on this video wall button. Once you click on the video wall button you will be able to see your own video on this right hand side corner in a small window and you will be able to see a very big video of the center in this middle corner in this middle screen of the A view. So, that is how you can you know interact face to face. Then there is a polling option here this is this polling option is like you know KBC or something where you ask a question and you know ask you ask people to just you know press you will you have been given 4 options and you ask people to select any anyone option. So, this polling is like that only what this polling option has is if you click on this polling option there will be a option there will be a button to enter your question. So, whatever if you have a question and you have 4 options you can just enter that question and then there will be options to enter your the 4 options also. So, you just type your question first after that there will be 4 or 5 options whatever 5 or 4 options that you have it will ask you to enter all those options there and it will ask you to save it. Once you save that question it will appear at the very bottom list of the questions that are available in the polling option then there is a check box against that question. So, whichever question you want just click on that check box against that option and start polling there will be a button here called start polling. Once you click on that start polling a pop-up box will appear on every for 2 minutes for on everybody's computer on everybody's desktop whoever is connected and they will be you know they will have a option to select any answer and submit. So, once they submitted you will be able to there will be a button to view statistics. So, once you check box once you check box your question and click on view statistics it will show you how many people have answered 1 have many people have answered 2 how many people have answered 3. So, this is a very quick you know quick way to get response to questions, but you will but of course, you will have to have those questions ready at your end first with the options. This was all about all these tabs and features that are available which can be used as a teacher, but remember once you give the presenter control to someone the presenter that presenter control goes to that person and you are disconnected as your audio video is disconnected and he becomes a teacher.  So, remember that this is the presenter control button ok there one more important setting once you go to the video wall button once you go to this video wall button actually the default setting is it shows a very small box of video both the presenter and the teacher here, but you can you know change that option there is a settings button on the right hand side corner once you go to the video wall button, there is a settings button on the right hand side corner, if you click on click on that there is a video layout button at the at the last, if you click on that video layout button and if you select the middle option then you will be able to see a very big video of the presenter. I will repeat there is a right the right-hand side top corner once you click on the video all button on the right-hand side top corner there will be a settings button. Once you click on that settings button a pop-up will appear. You have to click on the video layout button and select the middle option which will give you a very bigger picture of the center rather than being a small small you know boxes of pictures there. And so what these features whatever I features that I showed you documents desktop video wall these features will only be available to you once you have the presenter control unless you have the presenter control you will not be able to use these features. So, when you will have to have a presenter control to use all these options. So, you will have to ask the presenter to give you the presenter control so that you can use these options. So, this was this you know this was the thing which happened in this group discussions a lot that they were not able to you know the teacher said you start presenting and the student was not able to use all these options because they did not they also did not know that how this presenter control works. So, these were all the features that can be done and that can be used as a presenter and that can be used when you you will be interacting with your present with your students after this workshop jk. So, that is all from my side I will hand over the control to jk again if you have should I take questions. If you have any questions relating to this session if you there you can hand raise now I will just release all the hand raises if you have any questions regarding this session or how to use a view just press the hand raise button will there is there are no 10 minutes 10 15 minutes we can there is RC Patel yes RC Patel my question is regarding white board. Yes sir please. As a mathematics teacher as a mathematics teacher I have to write lot of expressions on board. So, for writing a mathematical expressions is there any as you suggested that iPad what that you are using. So, what we are using is what we are using is this eyeball take note. This connects as a USB ok. Yeah you have that right, but I want some more suggestion that advance version of it. No we actually suggest this eyeball take note only because this is a cheaper option and the white board is not that you know smooth. You will it is better you know it is better to use a you know any other you know software on your desktop and you share the desktop ok. Whiteboard is can be used, but you have to you know be careful while writing and you know why because if you write very fast it is not that smooth. So, you will have to you know be careful with that your audio is gone check your mic cannot hear you not audible sir just check the mic headphone So, whiteboard can be used to you know type any you know broadcast messages or anything like that that can that can also be used or else if you have the take note you are still not audible. If you have the take note there is a software called XOX just a minute I will type the name of the software on the chat XOURNAL. So, this I have type the software name in the chat XOURNAL this software you just open this software and you can use that take note in this software also and it gives you a gives you a very smooth writing also. So, you can use this software and you just desktop share your desktop. Thank you am I audible now. Yeah yeah you are audible yeah. Thank you thank you very much I will follow you. Yes MPST me. Hello good afternoon Sushant sir actually in the morning when we were conducting the session as a teacher group. So, my participant was presenting a video sharing the desktop. So, while the video was going on we were not been able to see if the viewers can see that because by the time the connection got lost if you remember. Okay okay. In the morning rather in the afternoon 12 after 12 30. So, we did not come to know when exactly the connection got off because our video was going on, but we did not knew that whether the viewers were able to see that or not. Okay. So, this connection problem was because of you know there was there was a problem at IIT Bombay server only. So, this can happen at your end. No that is not the issue sir. I wanted to know actually our video was going on now. So, we did not come to know that the connection is lost. So, how can we come to know as a group or see. Okay. So, what you can see there are you know default is like what is the in the users list. Okay. You see the users list always right at that left hand side. So, if you see users connected there that is one option that is one. Sir actually we shared the desktop and from sharing the desktop we opened the desktop and we had played the video. So, we could only see a video in the full screen. So, I was not been able to see that a view screen there at all. Okay. Okay. Okay. Yeah. Good afternoon ma'am. Good afternoon sir. Yeah. So, I got your problem. The problem is that when you sharing the video then you minimize a view. So, you cannot you do not know that when it was disconnected. Yeah. So, we do not recommend to use the desktop sharing for the video. The problem is sharing the desktop is that it uses only one frame per second and video uses mostly 24 to 30 frames. So, that would not be effective. So, if you have a video you should upload the video on YouTube and share that or you should upload the video on the interface of a view and then share. And for the problem if you recorded the video then you can just play that video in the library and you can say that at what time it was available to you or to the viewer and we will be giving another slot in the next week to do the activity of this group and later you can do the if it is it was not successful. No. Second time when we got connected we again showed it. So, we started from the first thing. I mean the very first thing because we didn't knew when it got disconnected. So, we did it. So, it was all fluently, smoothly done. Okay. Thank you. Thank you, sir. Thank you. M.E.S. Pillai 1100. Do you have any question regarding the interface? Save you. Yes, ma'am. Hello. Good afternoon, sir. Good afternoon. Actually during that activity breakout activity because of some network problem the interaction was interrupted and we couldn't complete that activity actually. Okay. So, right now we logged in in our group, but members were. Okay. No problem. That is okay, ma'am. That is a problem with all the centers because that was a problem with the ITB server. Okay. So, we know that a lot of people were not able to present and a lot of people were not able to interact with each other in the groups. We are going to give them time in the coming week. We are going to give them slots to interact and give the presentations. Okay. So, do not worry about it. We will give you time to present all the material. So, do not worry. We will be giving you slots to interact. Okay, sir. Yeah, G.H. Raishwani. Hello. Yeah, good morning. Hello, good afternoon, sir. Good afternoon. Sir, we have made the session of video trading. Can you just elaborate once again for us? I will, you know, you can go to YouTube and you can watch the video there because right now J.K. will be taking over the session. You can, after the session you can just go to YouTube, type in studio IIT Bombay and that session is already been recorded. So, you can watch it on YouTube. Okay. Okay. So, I will hand over to J.K. to continue the session. Hello, everyone. Few administrative inputs before moving on. The link that has been shared, the bid.ly, the shortened link that has been shared on chat. Only course coordinators or workshop, the remote center coordinator who is present in the center right now, only they need to fill it. Individual participant need not fill the survey. It is only for the course coordinator for us to understand whether you were able to do the lab activity yesterday locally and breakout session today. So, there are several RCs who are not able to present their work to other RCs today. So, for those RCs convenience, we have asked for alternate date on which we could set up a convenient group interaction. Now, there are also other RCs in Karnataka, for example, who are not able to join today, yesterday than today's session. Now, we will be arranging an ABU session to all of them in this week where we will be grouping that all those RCs. So, if your RC was not able to participate in the breakout session, please give a feedback in our survey so that we can include you in that group and you can present to the RCs who were not able to present. You can all come together and take a session, present each other's work and get feedback from others also. So, do not worry even if you are not able to do anything this week. We will ensure that you get a slot sometime across this week for 3 hours where you can present your work to others and get feedback. So, what we will do right now is we will do a floor transfer. So, we will break for T at 3.30. So, we will start a floor transfer session at 3.45. So, I will be visiting all RCs and I will be taking feedback from each of the RCs about the activities that was done yesterday and today and generally about FDP2 because see FDP2 we are focusing on the pedagogy. So, there could be lot of doubts especially regarding flip classroom implementation, video creation. So, yesterday you have done lot of activities at your end. You have all created Moodle activities for specific Moodle elements. Now what we are going to do is in the IIT Bombay X all the RCs Moodle courses with test user credentials will be provided in the IIT Bombay X page where you can log in and explore what all they have created. Now that is an important learning for all of you because each of the RCs, each of your colleagues have actually worked on different aspects of the Moodle and have understood how to use that Moodle. So, this information they have understood and they have presented it in a user friendly manner. So, we will put these up in the IIT Bombay X page and we will also put up new discussion forums so that you can find people from your own domains and if you have not formed a group yet you can use this discussion forum to find colleagues from other RCs who have not formed a OER team. So, I have seen for people who want to leave early you can leave at around as soon as your question is asked you are free to leave, but if you want to listen to what others are asking and others you want to learn more from their questions you can go ahead please continue with us we will be available till 5.30 today here and we will be giving you a feedback. So, let me now give you a broad overview of what was intended of yesterday and today's activity. Yesterday in the first FDP all of you have explored Moodle as a basic user and a basic teacher you have just explored elements like a label or web page along with quiz and discussion forum. Yesterday's activity was meant for you to go deep into the various different activities that are available in a basic Moodle installation so that you can use these while you create your OER. You can think of using these while creating your OER. Now an important thing is each activities use will depend on the context will depend upon the subject that you teach the learners that you have. So, you will have to choose which activity will be most useful which activity will be most convenient. I am now going to show you a website where lot of details about Moodle is provided. This is a website created by the UNSW University in Australia. They are showing you examples of what you can do with Moodle. It has been developed extensively for their faculty because they use Moodle as an institutional learning management system. So, you will learn a lot more about Moodle, what all functionalities Moodle has. What I am going to do now is I am just going to share that particular page with you. So, this is the web page of UNSW Sydney University. This is the page where they talk of what you can do with Moodle. And there are two important sections that you should go through. The first one is the tools, functions and strategies table. So, you can see for each Moodle tool or the activity as we say it tells us what its function is and the type of learning and teaching strategy that it is aimed for. So, what is useful for information transfer? What is useful for co-creation of content? What is useful for communication and interaction? What is useful for assessment? All these has been provided over here. Now, these light box gallery, media collection, etc. are very specific plugins that they have installed. But many of the others like workshop, forum, chat, messaging, etc. are available in a standard Moodle installation. There are few specific plugins which are available for their Moodle, which you may not be able to get for free. But others you can actually look at over here. And this summary table is a very important table that you need to understand. So, as to decide for what activity you will use a particular Moodle resource or Moodle activity. Then there is a section where they are talking of various strategies, various active learning strategies for which you can use Moodle. When you want to introduce a topic or a concept, what kind of Moodle tools are ideal? When you want to explore lot more about it, what kind of functionalities would be ideal? These are the learning activities. So, remember the learning activities or the learning purposes that you did in digital bloom taxonomy. So, this is similar to the learning activities that is there in Moodle. And these are some, again these are some guidelines. You can use a particular tool for multiple different stuff. And it really depends on your context in which you can use it and how useful it is. So, use these as best practices or guidelines to better explore Moodle. And you can use, you can also discuss with your colleagues. Now, you have seen many of you would have explored Moodle more as a instructor. So, please do have look out for resources like these so that you can get the best out of the tool called Moodle. And you will be able to do a lot more things rather than just information transfer with the Moodle. As I said, I will do the flow transfer at 345. People who are who want to take a tea in between can go now at your RC. I will be available here throughout. I will do a flow transfer at 345 sharp. So, what I will do right now is in the A-view. I will stop the A-view sharing. So, I will stop the A-view sharing and I will just have a look at all the questions that has been posted. So, I hope the shared desktop has been explained by Sushant both as a teacher, as a student. Again, for teachers who are unable to find a group member from the same domain, what we will do is we will put up a discussion forum on 15th of May where the discussion forum will be divided based on the domains from which you are. And you can find people who are unable to. So, you can do discussions based on the domain topics, etc. Find new members using that particular discussion forum. So, these main questions have been addressed. So, at this point, if there are RCs who want to interact with us, please do a hand raise so that we can interact with you starting from 345. Again, for general information of all participants, all the A-view sessions that we are having right now is also streamed through our YouTube channel. To locate our YouTube channel, please go to YouTube and search for Studio IIT Bombay. You will see our channel. Subscribe to this channel so that you will be alerted of all the A-view interactions that are happening at IIT Bombay. So, you will get an alert. You can also use your smartphones, etc. to subscribe to our channel. Go to YouTube, search for Studio IIT Bombay. So, 1005 has a question. While Mr. Sushant was explaining about A-view features, why is desktop was not shared whereas someone else was at your studio? He said everything was shared. So, for most of the A-view interaction time, these functionalities were shared. The problem was that when you move to explain, let's say video wall and other things, we will have to move away from desktop sharing. We will have to move away from the desktop sharing mode due to which you will not be able to see that at your center. But what we are going to do is all the explanations are available in YouTube. You can go to our Studio IIT Bombay channel where this explanation is more clear. What additionally we are also trying to do is create small tutorials for each aspect so that larger amount of people will get benefited out of it. We will create a playlist with all the major tools and functionalities. That plan is anyway on. It will take us some time because there are a lot of video creation activities also parallely going on. So, it is just because of our own bandwidth that we are not able to find enough time to give a thought and create good videos. But rest assured, we will be creating a lot more videos as the number of RCs have also increased. So, it is even more important for us to create these small videos and put it up in the public repository. It will also be available in our YouTube channel. So, RC1406, doing an interaction tomorrow may be slightly difficult. Please ensure that you give at least two to three options for interaction data. Because we will also have to see who all others, which all other people are willing on the same date and then only we can give a lot a slot. That is why we have asked for at least three possible dates when you give for feedback in our feedback. General information to all RCs. The next week, we will try to do a lot more, what do you say, at least provide you with video information much well in advance about what the activity would be. The activity is that now that you have created a modal course about a particular module, what you have to do is suppose you had to ask for trained teachers in creating your own glossary activity. The lab activity will be used that particular module in your own domain and create an in-class activity where you inside the during the lab session, you will have to execute an active learning strategy through which all the people will be taken through step by step in creation of a particular glossary activity and you collect the feedback about what happened. And this entire activity has to be presented to other RCs, what you conducted in the lab session, what all were the different websites that you created, the modal sites that you created and the activities that generated out of this so that we will have a repository of different sets of modal activities which I mean maybe a mechanical person will take one topic, they will create a database, another electrical person will use another module or activity and they will create let us say a glossary out of it. Somebody else may create a lesson activity, somebody else from let us say management domain will create a wikis. So, we will as an RC you will have a different types of resources getting created across different domains which becomes a rich repository that you can showcase to other RCs or other teachers as well. So, the next week's lab activity is that inside the lab you will have to take one module from all the six that people have created right now. As a group you would have done just one activity. Now, we will publish all the modal courses that was created in the yesterday's lab session and you will have to use those modal courses to create an activity for your own course, your own topic. This is the in lab activity which should happen on Saturday afternoon from 2 o'clock to 5.30. At the end of that day the course coordinator need to consolidate what all resources were created and the next day during the breakout session as an RC you should present what all work were done within the RC, what all topics, what all resources were created and how the interaction happened. So, this is what needs to be done in the breakout session for the next Sunday. Do not worry even if you have not heard the entire section clearly. We will be updating the IIT Bombay X course in the upcoming week with the necessary instructions well in advance so that you can prepare it at your end. RC 1331 you have an issue of heavy rain and power cut due to which you missed the second half of the presentation about on Avio from 3 p.m. to 3.43 p.m. Please note all the interaction sessions are available in YouTube. Please go to studio IIT Bombay channel in YouTube. So, go to youtube.com in the search bar type studio IIT Bombay. You will be able to see all the videos that has been created specially and at the top the live streaming interaction would be seen. So, you can look at the segments which you are absent for and get the necessary information. So, it is 3.45 now. So, for people who are asking for instructions for the next breakout session please do not worry it will be uploaded in IIT Bombay X course on Thursday. That means with the next release we will be uploading the instructions for the next breakout session. The lab activity and breakout session. So, there is RC 1063 you wanted topics for flip classroom. You can select your own topic if you are asking about OER. You can select the topic yourself and use activities for design activities for flip classroom based on the topic of your interest. There is 1103 question about how to take feedback. You can use polling functionality which is available in Avio. You should create a poll and you can take feedback. Let me now start the interaction with remote centers. Please use a hand raise button to please use. So, in case if people want to go out for tea and come back please feel free to go and come back no issues. We will start the interaction there are few remote centers who have already raised their hand. I am going to do a floor transfer to each of them. So, this is RC 1229 Sardar Patel Institute, Andheri. Hi, good evening sir. Good evening. During the breakout session we had a problem with the presentation that I believe is going to be taking care of in some other day during the week. Yes. The problem is this week we have the university exam and all that because of which we are going to be unable to attend the breakout session. So, how will that be taken care of for us? Now we can directly come on 26th and I mean the next breakout session that is 25th and 26th or 26th and 27th if I am not wrong. So, let me check with the team over here. So, it is a logistical there are other activities that are going on the studio in the next week due to which we will be unable to open up the studio for I mean the A-view classrooms. But let me speak with the team over here and see how it could be best managed. If it is possible as far as possible try to see if there could be at least two alternative days in which all of you can assemble at one place and interact with the other groups. The possibility is very less but then too we will still check. Yeah. Because as I said we have the exam. So, I understand that many places there are holidays people are on holiday and they specially come for these two days of interaction. See if nothing works out at least we will try to set up a slot in the next Saturday where you can do a breakout. But as far as possible try to do the breakout sessions in this week itself because many of your colleagues have already indicated preference for this week itself through which you could do the presentations with each other. And so if it is not possible at all then what do we do? Do not worry we will try to accommodate. Do not worry. The user ID and password has already been uploaded in that form that was given. Yes. So I think actually we were just waiting for the presentation rights to come to us or we were waiting for the presenter rights or the teacher rights on the AVI the link got disconnected. Okay yeah I mean there was a technical issue at 12.30 today due to which that happened. We will try to figure that some modality for the time being. Okay. Thank you sir. Okay let me now go to RC1039 IPS Academy indoor. Check your mic. Ma'am you are not audible. Unable to hear you ma'am. Unable to hear you ma'am. What you can do is check the mic settings. I will come back to you. This is RC1065 Phinolex Academy. Am I audible sir? Yes. Please go ahead. To just ask we had a session we had a good session interactive and we were able to explain our moodle work. Yeah. But we were supposed to get the feedback from the other RCs that was not done or there was some problem regarding the connections. Yeah. And the feedback from other RCs was not able to we are not able to collect the feedback. Okay so what we are going to do is I mean while we are uploading the courses so what you should do is in the moodle course that you have created what we will be doing is we will be giving this all the moodle courses to in IIT Bombay so that all participants can also login and give their feedback. So please make sure that you create a feedback which a feedback module which can get multiple feedbacks from the participants. Okay sir okay. And we will also. One question sir. Yeah. It was regarding the mentor-mentor interaction. It is going to happen in this coming week and each RC will have a mentor. So it is so the mentor-mentor interaction is after you have formed the OER groups. So it will happen only from 27th. Okay. So the your mentors will be available for interaction from 27th because they would have done an open educational resource. They have experience of open educational resource creation and report writing. So you should utilize your mentors expertise in creating your own open educational resource and you could do you could get an evaluation from them about how your activity is is it targeting appropriate levels etc. And that is the purpose of this mentor-mentor interaction. Okay. And look sir my last question. Yeah. See there are seven now seven participants RC right now. Okay. Three of them are from one domain that is electrical engineering. Okay. Three are from another domain EXTC that is electronics and telecommunication. Yeah. And only one person is there which is from computer applications domain. Okay. So that single person can do OER or not. No so single person group is completely not allowed in for OER creation. We are going to create a discussion forum in IIT Bombay EX where we will be posting dividing it based on the domains. So you can go to the respective domains so you will be related to computers computer science and related domain. Okay. The person in computer application will be in the domain computer science and allied. Okay. So you could you could go to that particular discussion forum and look for people who are look for people who are alone or try to see if there are groups who could accommodate one more person in their team OER team. Okay. From other RCs. Yes from other RCs. Okay. If nothing works out. And if you are not able to get anyone till 20th please inform us so that we could also talk to other course coordinators and try to put you in a particular team. Okay. Okay. Okay. Will it be okay that if there are four participants. So in exceptional in exceptional circumstances we would allow four participants. Okay. Okay. Thank you. Okay. Yeah. Let me now go to RC 1146 knowledge institute of technology. Yeah. RC 1146. Am I audible? Yes. Go ahead. Sir actually I have raised my hand to give the feedback of the last two days. Yeah. Tell me please. No problem. But the thing is that yesterday we have done what we can we could do we have done it. But the thing is that time sufficiency was somewhat less actually. This is what we feel from our side. Okay. What was that? What was that? Activity. What was the topic? Which model activity you had? Database. Database. Database. Okay. Database. You were in which group? Creating a database activity. You have done it. Group 4. Group 4. Were you able to participate in the breakout sessions? Yeah. Yeah. We have participated in breakout session in the morning. Okay. Actually we have done it and we have presented it. Okay. But I hope that we haven't done completely. What are the things the entire details we haven't given I suppose. Yeah. See that was never the see complete mastery of a database activity was never the intention of this particular exercise. The exercise was that you will be able to. So the rationale of this exercise was that you will be able to search for the information you will be able to find out necessary information, collate it, synthesize it and then create something new. See this is what any new teacher would do. So suppose you are given a new topic and asked to create a lecture tomorrow, you will be doing the same thing. Right. So this exercise was a simulation of that particular thing. So you will know what to look for and today's activity when you get, when you see what others have done, what others have done for the same particular activity, you will also get to know what they have also seen. Okay. So this was only a exercise to let you experience in terms of us as a student what active learning is and what active learning actually means. So you as a learner, as a learner, you try to get information, try to make sense of it and synthesize it and this is what you should do and now you have given me an excellent feedback saying that you yourself are not satisfied with whatever you have done in terms of the synthesis. I mean there is no better learning than what you have just said right now. So the exercise is meant to elicit that only. So do not worry even if you haven't learnt fully but at least now you can be assured that you have the sufficient skill set to explore and make more out of it and this is what any facilitator should do, any learner should do, any teacher should do. Here sir. Thank you. Thank you. Okay. Let me now go to RC1225, RC1235, sorry RC1235, Dr. Mahalingam College of Engineering. It is slightly amusing when you actually realize that you are suddenly on screen. Yeah. Please go ahead sir. Good morning sir. Yeah. Good morning. We have done the breakout session. Okay. And in our group only I think four other RCs they are connected. Okay. Yeah. And everything went well sir. Okay. Great. Do you have any queries or any questions to ask me regarding the activity that you have done? So as we have completed in the morning session, so whether you have to participate in the next week, this breakout session sir? I mean these, are you talking of the alternate ABU sessions? Yeah. Yeah. No. So I mean if you have participated in the ABU today, so the alternate sessions are for those people who are unable to present their work or get connected to the ABU system. Okay. So this is RC1400. I am not able to see your video but please go ahead and ask the question. Women's Polytechnic Puducherry. Good evening sir. Good evening. Yes sir. Sir here in our RC there are 26 pupils are attending the course. Okay. So all are having different domains. Okay. Is it compulsory to form your batches in the domain or we can combine the pupils? Okay. See so this question is a general question that many RCs would also face. So I would request all RCs to closely listen to these answer. So there is a scenario where people are from different domains and it is very difficult to group people for the OER in a single domain from the RC. Now there are two ways of solving this. The first one is that you select between yourself, you decide on a topic in a particular domain and work on it where all three can provide some input. There are 14 common domains that we are putting up. 13 of them are subject specific and one common domain on educational technology. So you could select a common domain of educational technology and create resources for that or you could select any one of the common subject domains that people are comfortable with and form a team. So this is the first way in which you can solve it. The second way is that we will be opening up specific discussion forums on May 15th where we will be putting up discussion forums for each of the domains. So there are 14 including like electrical analyte, computer analyte, mathematics, science. So there are 14 different domains that we have identified. So we will be putting up discussion forums for each of this. As each participant please go through these forums and try to find out people in these forums by posting messages and trying interacting with your friends or other ITBX participants. So you will be able to find out people from other RCs and together once you decide inform your course coordinator that you will be forming a team with a person from another RC and you will be forming a team. If till 20th you are unable to form a team please inform your course coordinator and course coordinator you are requested to consolidate all the people in your RC who are not able to form a team by 20th and inform e-outreach so that we could match the people's domain and try to find out suitable people from other RCs. Thank you sir. Thank you Hermit. Is that fine sir? Hello. Thank you sir. Thanks for your kind information. Yeah. So let me now go to RC1411, Kalasalingam University. Hello. Sir, are you audible sir? Yes, yes you are audible. Yes sir. Yeah sir. Actually the same question that you answered earlier no sir with me also and thing is that I have an option right I am going to join with the people belonging to the world of mathematics and engineering. Okay. And I am going to account the topic of operation research in which all the three people can put their own inputs into it actually. Okay. So may I join like that sir? Yeah absolutely that is fine. That is fine, that is fine. Thank you sir. So one more thing sir, one more question sir. Yeah. So today morning sir, today morning we are making a presentation and we belong to 90th group actually and we were not able to see our video. That means we are not able to share our desktop on the screen. Can you repeat? Sir, today morning sir we are making a presentation. Okay. And we belong to a group line. Yeah sir and we were not able to share our desktop. Okay. And actually they were able to see I think so but it was not actually confirmed but we have made a presentation fully and they told at the end it is okay your presentation is seen. Okay. But we are not satisfied with their presentation. We are not able to see the particular screen in which our desktop actually shared. Okay. Okay. So it may so have happened that your group teacher may not have given you presenter control due to which you are not able to share your desktop with them. Desktop with them. We are not confirmed. Yeah. Yeah. So do not worry during the next breakout session that is why explicitly we had Sushant explain all the different aspects of A-view. So during your next presentation make sure that you get your presenter control and you are able to show them what you want to show from your desktop. Thank you sir. Okay. Thank you. Yeah. Thank you. This is RC1427 PA College of Engineering. Your video is not being published. So I will come back to you. Check your video and audio. We are unable to get anything from you. Please raise the hand once you have completed. Now this is going to be RC1308 Roland Institute of Technology Orisa. Hello. Hello. Good afternoon sir. Good afternoon. Sir I have three queries sir. Okay. Sir a day before yesterday in our place Cyclone because because of that we could not able to like get the A-view session completely 1pm to 5pm yesterday. Okay. Then today we somehow we try to communicate and also like involved in the breakout session with our group ID 8. Okay. But we could not able to present because yesterday what happened we do not know that is why we could not able to present our activity. Okay. So see will you be ready to do an alternative presentation? Suppose we scheduled sometime this week with other groups. All the members are coming from different colleges so I could not give the assurance like when we are going to otherwise 26 possible sir 26 27. See 26 27 we already have activities. So let me see how best we can look at arranging the interaction. See one important thing is how you do this model activity yourself doing see yesterday's activity was a in lab activity. So you need not have any interaction with others. Sir. Okay. And to understand what was what has to be done yesterday you can refer to the videos that have been uploaded in our YouTube channel also. So were you participating in the interaction from yesterday morning? Yes sir. Morning to. Morning we have. Yeah. Morning to. We have. Yes sir. Okay. So I mean the instructions for yesterday's activities remain same. So have you created a model course for your RC with the allotted activity? Yes sir. Today morning after getting like during breakout session what information I got according to that we have done sir some model account we have done and all the activity we have done but not completed. Okay. So what I would recommend is over the coming days you work offline and try to consolidate that work try to complete the work over the coming few days for that you need to interact with your other colleagues either through emails or through chat or WhatsApp you can use those mechanisms to communicate with your colleagues and complete the work that was allotted yesterday afternoon and also try to see which so we will be publishing the slots that would be tomorrow we will be emailing all the people who have asked for an alternate session or who are absent will be putting up slots you can join any one of those slots and if that is also not possible let me try to see what other mechanisms we can work out in terms of logistics because it also requires a lot of logistics planning at our end also. Okay. Okay sir. Yeah. Sir next question. Yeah. Seven members. Okay. So for OER like we are one geology like biology staff is there and four computer science people is there and two electrical people is there. Okay. So shall we go for educational system so that we will make three groups. Absolutely that is also fine so your computer science staff can also look for maybe one group of computer science staff can also look for topics within computer science otherwise you are free to use educational technology and create a small course in Moodle as an open educational resource. Okay sir. Okay. Okay this one. Yeah. Thank you sir. Okay. So let me all RCs please wait for five minutes we are just making a small hardware change at our end so I will restart the interaction with all RCs right now. My video you will be able to see my video but it requires five minutes for us to do the recording at our end. YouTube streaming will be cut off right now and we will restart YouTube streaming in five minutes. Meanwhile these are some generic instructions for. So please hold on to your questions right now our studio team are making some minor changes in the hardware so that the video is more proper and it is visible for the YouTube audience.


Okay. Does that sound okay? Does that work? Okay. Terrific. Mark, congratulations on your exceptional leadership of NHGRI. And I want to acknowledge Colleen McBride, who has built this amazing program over the last ten years, which is really a cornerstone program that people across the country look to in terms of integrating behavioral science and genomics research. I also want to thank Barbiesekker and Colleen for inviting us to be part of this exciting event. It's a true honor, and it's a delight to see so many friends here, not only from NHGRI, but also NCI and NIDA and NIAAA. So it really shows that it's one NIH and highlights the importance of integration. I'd like to share with you our work today on nicotine dependence pharmacogenetics and personalizing treatment. And I want to start for those who are not nicotine addiction researchers with just two background slides just to try to bring everybody up to speed. So a very quick, simplified view of nicotine and the brain, so to give some context for some of the genetics research. So nicotine binds to nicotinic acetylcholine receptors, which are found on a variety of neuronal subtypes in the brain, and then this cartoon is a dopamine cell body. They bind with high affinity to a subtype referred to as the alpha-4-beta-2 subtype, but also to many other subtypes. In binding and affecting the signaling in the passage of different ions through this channel, this pore that opens up, it alters the signaling of the dopaminergic neurons, and it changes the firing of the neurons to a rapid burst firing state. In doing so, it increases dopamine release. Now the ventral, this is actually a rat brain, but the ventral tegmental area is an area rich in dopaminergic neurons, as well as nicotinic receptors. All of the cross-hatch areas are rich in nicotinic receptors, so you can see they're widely distributed throughout the brain. But importantly, these types of events occurring in the VTA, where there are important projections to the accumbens, nucleus accumbens, which is known to be an important part of the brain, part of the basal ganglia that plays a role in the anticipation and experience of reward from drugs of abuse, such as nicotine, as well as other natural rewards. And also important to some data that I'll present is projections to prefrontal cortex, which is actually bigger in us humans, but the role that dopamine plays in terms of top-down cognitive control, which is very important for behavior change. Now DSM-4 and soon DSM-5 illustrates criteria for nicotine dependence. A majority of smokers would meet the criteria for nicotine dependence, but not all smokers. And some key hallmarks of an actual diagnosis include tolerance to the effects of nicotine, meaning it may take higher doses to achieve the same level of comfort or reward from nicotine used in larger amounts than originally intended, and importantly, interfering with social recreational-occupational activities, meaning having to run outside and smoke in the middle of an important meeting because you're going through raging nicotine withdrawal. Unsuccessful quit attempts continued use despite knowledge of the health consequences, and I don't need to educate everyone today about what those health consequences are. We all know that smoking remains the greatest preventable cause of morbidity and mortality. And a hallmark that we focused on in our research are nicotine withdrawal symptoms that occur, even and particularly within the first few days following a quit attempt, including depressed mood, insomnia, anxiety, irritability, and something that we've had an increased focus on, which are cognitive deficits, and specifically, subjectively reported by smokers as difficulty concentrating or having a fuzzy brain. And we're focusing a little bit on that in terms of looking at that as a target for therapeutic efforts. Now, it's surprising, though, that despite a great deal of support going into the development through pharma and also NIH for the development of therapeutics, there are really only three classes of medications that are FDA approved for this, despite this being a significant public health problem, despite the fact that still, other than maybe in California, it's nationally about one in five individuals continue to smoke, but we have only three approved approaches. And as you can see, they help people quit smoking, but they're imperfect. So compared to placebo, and these are data that are reviewed and crossed across a number of studies and meta analyses, NRTs like nicotine patch, nicotine nasal spray, nicotine lozenge basically can double the quit rates. And you get 20% of smokers who are successful in quitting and remaining quit for six months after the target quit date. Bupropion, the next FDA approved medication, also known as Wellbutrin, which is an antidepressant treatment, works by increasing levels of dopamine and norepinephrine, has been shown to be somewhat superior to NRT, but still you're getting maybe 25%, one in four patients able to successfully quit. Varenicline or chantix, the newest kid on the block, in the news quite a bit lately for some rare neuropsychiatric events, both varenicline and bupropion have black box warnings associated with them. But even with what's considered the best in class, at least in terms of efficacy, only about 30% able to quit. So it really underscores the point that there's an urgent need to develop new therapies and improve the outcomes of existing therapies for nicotine dependence. So what I want to talk to you about today in the 45 minutes that I have, is to give you, tell you a couple of stories that illustrate how genetics research can help us get to the point of identifying new therapeutics through genetics, but also improving the outcomes of existing treatment. And I'm proud to say that we've patented a smoking mouse that, no, I'm just kidding, I wish we patented a smoking mouse. But I just really like that picture. You notice he's having his cup of coffee, which highlights the importance of triggers to smoke. But these are the two areas that I'll be covering today. So starting with how do we translate from genetic findings to new medications for nicotine dependence? So we've done a lot of genetic analysis, mainly both pathway and systems based genetic analysis. We've also done GWAS. But I wanted to highlight the results of this study in particular because it gave us some clues that is now leading to a medication development program. And what we did is we looked across 11 different genes that are important in the nicotinic receptor and nicotine system more broadly. And unlike some previous studies that focus mainly on genes that code for different nicotinic receptor subunits, because these nicotinic receptors are made up of multiple subunits. In addition, we wanted to include proteins that are important in either the biosynthesis of the endogenous ligand for the receptors acetylcholine. The receptors aren't there for nicotine, they're there for acetylcholine. And also enzymes that play a role in the metabolism of acetylcholine or the vesicular transport. So a broader kind of nicotinic and endogenous system pathway, 170 SNPs plus 329 ancestry informative markers. And this is just to show you there when you think about a system there are many different chemicals involved both in the biosynthesis of acetylcholine, the breakdown of acetylcholine, you know transporters that affect how long acetylcholine stays in the synapse and then of course the receptors that bind both acetylcholine and nicotine. And what the results of this SNP analysis pointed to was a signal on a gene called choline acetyltransferase or chat. So we looked doing both individual SNP and haplotype analysis and we found signals across this choline acetyltransferase chain. I'm going to call it the chat gene, easier to say. And it's involved in catalyzing the synthesis of this endogenous ligand acetylcholine. And we found associations of a number of different chat SNPs and haplotypes in a clinical trial with 472 European smokers associating not only with nicotine dependence but with ability to quit smoking. And I would argue that ability to quit smoking is really the ultimate clinical phenotype that we care about because this is the behavior that we want to change. Now of course these were nominally significant. I mean there were a number of different SNPs that we looked at. So we weren't really satisfied until we were able to identify, obtain independent validation of these findings. So we talked to our colleague Meng Li at UVA who had samples of European and African American smokers over 2,000 samples from a number of different families. And he was able to find also that the same SNPs showed associations with multiple measures of nicotine dependence. And some of his data is published in the first data and then a second study published as an independent replication. Now the function of these SNPs were unknown but it suggested to us the idea that in fact maybe we should be thinking about not just medications that target the receptors like varenicline but those that target levels of endogenous acetylcholine as potential effective therapeutic strategies. So how do we do that? Well there's no available chat enzyme modulator. I mean that was the gene that we focused on. But in fact there's cholinesterase inhibitor medications that are FDA approved and these serve to increase the duration of acetylcholine in the synapse allowing more binding with these nicotinic receptors that are expressed on these various neuronal subtypes. And the other feature of this that sounded interesting to us is that these cholinesterase inhibitors are FDA approved to treat Alzheimer's disease. Now I have a line of research that I don't have time to show but we have proven across multiple studies that working memory and an individual's level of top down cognitive control is an important factor in their ability to quit smoking, to ability to risk cravings to smoke and so forth. And this has been shown as being important for a variety of drugs of abuse. So we were particularly interested to find in the literature that these cholinesterase inhibitors not only improve working memory and Alzheimer's disease but also in studies of healthy volunteers.  So we looked at a drug called galantamine. It inhibits acetylcholine and it also we were interested to us because it acts as a PAM or a positive allosteric modulator at the nicotinic receptors, particularly those that have alpha five binding sites. And these are particularly sensitive to nicotine. So converging evidence sort of imperfect in terms of direct relationships but the converging evidence said, let's take a shot at it. So we don't go right into humans with this because those are big costly studies hard to fund without some good data. So we as part of having a P 50 Center of Excellence funded by the National Cancer Institute, we're able to take some money and give it through our developmental funds to a new research investigator new faculty member named Heath Schmidt at the University of Pennsylvania. And that allowed him to develop a nicotine self administration paradigm in rodents. And so you can see there's a rat with an indel dwelling catheter through which they can receive saline or nicotine. And to acquire nicotine self administration. They first do this on a fixed ratio schedule. And the animal learns to press one bar to get a nicotine infusion and another bar, they don't get anything. It's an inactive bar. And so he establishes so the rats, I guess they like nicotine, they learn to administer nicotine by pressing the bar. And what he tested is whether an IP dose of galantamine right before putting them in the operant chamber chamber versus saline would somehow alter the likelihood that they would want nicotine or anthropomorphizing but I think you get the idea. So his results he first looked at acute administration. So this is the total number of lever preface. The more they lever press for the active bar, the more they want the nicotine. So a five meg per kid dose of galantamine reduces the amount of nicotine self administration. So they're reducing their nicotine intake with no effect on the inactive lever bar. And Donapasil is also a colon esterase inhibitor. And at these two doses and somewhat of a dose response fashion, you also see the rodent self administering less nicotine in the presence of these colon esterase inhibitors. However, smoking is not a single acute event. People smell chronically. So what he did is he used a chronic administration paradigm, comparing saline versus the five or the the point five or the five milligram dose that's this dose. So this dose here actually delivered chronically showed a significant reduction over time of the extent to which the animal self administered nicotine. So this is very promising to us. He also showed in a model of nicotine reinstatement where you extinguish the behavior, and then you give them a single nicotine prime that the mice given the saline before the nicotine prime reinstated and were lever pressing like crazy after they got that nicotine dose. But if they were given galantamine, they didn't reinstate and that's considered a model of relapse also. So with that compelling evidence, our postdoc who is now a an assistant professor at Penn was able to receive a K 23 grant to study the effects of galantamine on cognition and smoking cessation in a short term study in human smokers. So she and Heath are working closely together to try to advance this. I'm hopeful that this will work. Who knows? But it's certainly a good pathway in illustrating how genetics led us to this point. Now what I want to focus on now is really the crux of the talk, which is how we use genetics research to identify biomarkers to be able to improve the outcomes of the existing therapies we have. Can we get smarter about who we give particular medications to the choice of therapies, the duration of therapies based on genetically related information. Our work in this area is based on an extremely simple premise. That is, as people nicotine a clear nicotine more quickly to and it's an active metabolites, they tend to smoke more. This is because smokers like to keep their nicotine in a very comfortable range. Too much nicotine makes people feel nauseated and not enough nicotine in a chronic smoker makes them experience withdrawal. So people titrate their smoking. And we also know that there's individual variability in the rate of nicotine clearance. And so the hypothesis is that this alters smoking behavior and smoking cessation. Now of course, it's if you want to get a complete genetic picture, you want to look at all of the nicotine metabolites. But the real action is in this red circle. Nicotine is converted to codeine and it codeine is converted to trans three hydroxy codeine. And 80% of the conversions of this metabolism of nicotine occurs right here. So we focused initially on here and subsequent research has actually shown that these other metabolites don't have significant effects. But both of these conversions, nicotine to codeine, codeine to three hydroxy are mediated by the cytochrome P 52a6. So nicotine metabolism is genetically influenced. This is work by Gary Swan and his colleagues. These are heritability studies comparing MZ and DC twins, where they were able to estimate that in terms of nicotine clearance and codeine clearance, roughly 60% of that influence is due to heritable genetic factors. Now identifying those particular genetic variants is challenging. This has worked on in Rachel Tyndale's laboratory, it's showing the frequency of the Cyp 2a6 genetic variants in European ancestry populations. These variants here, which are infrequent in the European ancestry populations, more frequent in Asian populations, are rare, but they're null variants. So if somebody has two copies of these alleles, they're not actually creating any Cyp 2a6 enzyme and will not be able to metabolize nicotine. And these more common ones are reduced activity variants. To this state, Rachel's lab has identified more than 30 different alleles. The genotyping for Cyp 2a6 is very complex, so we had the idea that there's more to it than just the genetics, and we had the idea that maybe a phenotypic biomarker would be better. In addition to the complex genetics, the reason for going to a genetically informed phenotypic biomarker is because of the importance of environmental factors that also influence nicotine metabolism rate that would affect smoking behavior. And this has worked by Neil Benowitz showing that females metabolized clear nicotine faster than males, and females on all our contraceptives metabolize nicotine even faster. So what we wanted to do is have a phenotypic marker Cyp 2a6 activity in nicotine metabolism rate, and we thought this would have greater utility in predicting quitting success and as a biomarker for targeted therapy and treatment response. So over the last 15 years through funding for the Pharmacogenomics Research Network with my colleagues Neil Benowitz and Rachel Tindale, we've set out on an odyssey to develop and validate this marker. The first five years of the PGRN grant were about some of the research that I just showed you, characterizing the Cyp 2a6 variants, assessing the analytic reliability of this marker, and in the second phase, and I'm going to show you all of this data, we did a retrospective analysis into various different clinical trials to look whether there is association between nicotine metabolism rate assessed at baseline and treatment outcome. And now I'll share with you, we're moving into the proof-of-efficacy cost-utility phase, which is sort of the third and perhaps final phase of validating a biomarker for use in clinical practice, and I'll go through this briefly. So again, the biomarker, the nicotine metabolite ratio, is based on the ratio of 3-hydroxy-containing over-containing. And it's highly correlated with genotype. These are genotype-based categories of normal intermediate and slow metabolizers by genotype, so it's correlated with genotype, but as I mentioned, it's not just about the genotype, or even this genotype, there's more going on. We wanted something easy to measure in clinical practice, and this shows that plasma measures, which were the gold standard, are highly correlated with saliva measures, so potentially you could actually have a spit test in a doctor's office to characterize someone's nicotine metabolite ratio. It's stable over time in regular smokers and independent since time last cigarette, a physician would not need to have the smoke or go smoke outside before testing it. It's a stable measure as long as they've had a cigarette in the past seven days, and importantly, it reflects both genetic and environmental effects on CYP2A6 activity. All of these features would make this biomarker easy to perform in clinical practice. So we have three clinical trial populations performed at the University of Pennsylvania. They're comparable, roughly half of participants were female, varying racial distributions with the highest proportion of non-whites in the first NRT study. On average, folks smoke about a pack of cigarettes a day and they're moderately dependent. The first question was, can we just predict with a simple patch who is gonna benefit from the patch and who will not? It was a standard clinical trial as an open label trial comparing nicotine patch for eight weeks to nicotine nasal spray plus seven sessions of behavioral group counseling, very high retention rates in this clinical trial, and here's the upshot. So for all these slides, you'll see on the Y axis is the percent of people quit. This is always biochemically confirmed. Smokers don't always tell you the truth about whether they're smoking, so that's an important point. Here, along these axes, you can see that we're separating it for illustration into groups. These are the slowest metabolizers by the NMR. A less slow, faster and faster. And this is end of treatment data and this is the six months later. So you can see here at the end of treatment with each increasing quartile of group they fall into as the NMR gets faster, as they become higher and they become faster metabolizers, the odds of quitting is reduced by about 30%, okay? And that is maintained at six month follow up even four months after they're off the patch. With the nasal spray group, we really don't see any effect because A, people can self-titrate with the nicotine nasal spray and we did find slow metabolizers gave them less, gave themselves less, fast metabolizers gave themselves more and generally it's just not as an effective treatment because it has some adverse of qualities and people don't like using it. Proof of mechanism or at least one mechanism, faster metabolizers have lower levels of plasma nicotine from the patch because they're clearing it more quickly. However, we don't think it's all about the nicotine because the nicotine levels somebody has on the patch are just not that highly predictive of their quitting success and I'll get to that. We think there's more to it than just the fact that the fast metabolizers are clearing the patch nicotine faster. Validation is important. A second study now of 568 participants and you can see the quit rates here. The slow metabolizers are kind of moving away from the pack 42% quit at the end of treatment and with these groups about half is likely to quit the second to the third quartile. Well, if you slow metabolizers do so well with just a patch treatment that they can buy over the counter what about if we extend it for six months? Why does anybody think that addiction can be treated like an acute illness when things like hypertension or diabetes require long-term therapy? So we did a trial, standard treatment for eight weeks followed by placebo patch for 16 weeks versus active patch for 16 weeks and here's what we found. In the normal metabolizers it didn't matter extended treatment didn't do anything partly because the patch is just not that effective for faster metabolizers. Slower metabolizers during the period when they're still on the extended patch which is six months, 50% of slow metabolizers if you extend their patch will be quit at six months. One and two smokers quit. That's an exceptional quit rate for people who know about getting smokers to quit. So we then wanted to say, okay, well what are we gonna be able to do for the fast metabolizers? And we also wanted to know because we had a hunch that it's not just about the nicotine is there some general liability to relapse the fast metabolizers have beyond just clearing nicotine faster? So we tested this into a bupropion placebo controlled trial, bupropion delivered for 10 weeks versus placebo and group counseling. And here's the results of that trial. We did have a significant NMR by treatment interaction. And what you can see is that this is the placebo group now. Slow versus fast nicotine metabolism is highly predictive of quitting success even on placebo. And I can say more about this in the question answer period but there's something different about the brains of slow and fast metabolizers. It could be how quickly nicotine is cleared from the brain, the rate of return to about variability of nicotinic receptors after nicotine is cleared but even on placebo with counseling only only 10% of the fastest metabolizers are quit compared to 32%. But the other thing that's remarkable about these findings, if you're a slow metabolizer why take bupropion? You get no additional benefit from this medication. You do well with counseling only or as I showed previously, counseling plus patch. If you're a fast metabolizer, don't bother with a pill that may have additional cost and side effects. In fact, in this group, the odds of success with bupropion for placebo are 5.6 times greater the odds of quitting with bupropion. So it really started to suggest to us a strategy. So to summarize, we've shown that the slow metabolizers in these groups here have a significantly higher benefit from nicotine patch than the faster metabolizers. We verified this in a completely independent study showing slow metabolizers do better with the patch. We've also shown though that these fast metabolizers you can restore their deficits, you can revive their quitting ability with a non-nicotine medication like bupropion. We also have preliminary data showing that Chantix also a non-nicotine medication has similar effects. So it leads us to the idea that a slow metabolizer would do well with patch over the counter and some counseling, but fast metabolizers really need a non-nicotine medication like bupropion or verenicline. Another point for those interested in lung cancer and the toxic effects is that it's not bad enough, not only do the fast metabolizers smoke more and have a harder time quitting, they also suck more toxins in from their cigarette. So the faster metabolizers in the fourth quartile and the smoking topography where we measure puff inhalation, inner puff intervals, they are sucking in more toxins and that's also showed here because this is NNAL, a tobacco specific carcinogen. And so they're double screwed. They smoke more, they can't quit and they smoke in a way that actually exposes them to more of the toxins that will increase their risk for tobacco related disease. Now I wanted to say a word about a cluster of SNPs on chromosome 15, the alpha-5, alpha-3, beta-4 gene cluster which has received a great deal of tension in relation to a very robust reproducible association with heaviness of smoking, accounting for about 3% of the variance in heaviness of smoking, but a clear signal that's very reproducible. So looking at that now through PNAT in a study within our team led by Andrew Bergen, he took over 2,600 treatment seeking smokers from across eight different clinical trials and combined the data for smokers receiving different treatments into single treatment arms and did this type of mega-analysis and what he found is that the risk alleles for heaviness of smoking from these two SNPs and alpha-5 and alpha-3 were associated with reduced quitting rate at six months if they were on placebo, but those same SNPs were associated with an increased quitting rate if they were on NRT and that would be any type of NRT. So in fact, it suggests that these SNPs may have some predictive validity for smoking cessation, although the data suggests that part of this is mediated through heaviness of smoking. The issue is though, there are limitations that for one thing that the grouping, it's not as clean to do this across multiple studies and pool them and also I think because of that, the amount of variance accounted for in predicting quitting is low. However, we hope to be able to address that in this study that's nearly completed. So this is our second generation pharmacogenomics research network. It's a UL1 grant. I'm pleased to say it's not as the primary funder but NHGRI is a funder of this grant as is NCI and as is NIGMS. So it's a major effort. It's an international trial for sites, I can say international because one of them's Canada. So that still counts. But it sounds more impressive than national trial. And this is the first prospective stratified pharmacogenomic trial in smoking cessation treatment, 1200 smokers where we're oversampling the slows. So 600 will be in the slow group, 600 in the normal group and then based on their slow and normals will then be randomized to placebo, nicotine patch or veranicline which is now more widely used than bupropion. So not only will this be sort of the next study to actually be on the retrospective studies to provide the evidence base for using the NMR for targeted therapy but because we'll be genotyping for all of the chromosome 15 SNPs as well as other candidate SNPs we're considering using a chip that NIH has developed to really do a comprehensive analysis. We'll be able to develop an algorithm that combines both phenotypic and genomic markers and then to test the utility of this, not only in terms of efficacy but working with our health economists to look at the cost utility of this targeted therapy and personalized medicine. I'm happy to say that we're over the 1050 subject point and we will have all subjects accrued in September with our readout of the end of treatment effects analysis by the end of the calendar year, if not sooner. So we're very excited about this. In anticipation of this, there are two companies that are funded through SBIRs that are developing point of care tests that can be done in doctors' offices quickly to be able to assign people based on the NMR. I don't have any financial interest in those companies unfortunately but we're really hopeful and we're trying to work with them and share our data so we would like to see this translated to practice. So in summary, our genetics research suggests that modulation of endogenous levels of acetylcholine may be an effective therapeutic strategy for nicotine dependence treatment and we've shown that a genetically informed biomarker of nicotine metabolism rate, the NMR, shows promise for tailoring smoking cessation treatment choices and it raises the question of then how do we translate this to practice and I've had the privilege of working with my colleague and friend, Alexandra Shields and who will be speaking next and addressing those issues. I want to make some acknowledgments. It takes a village to do these studies. First, this is the PGRN group. So here we have the little Canadian flag. I am, the best thing that, well, one of the best things that NIH ever did was create this multiple PI model so that we can share leadership and work together in that way. Our institutions like it, so Rachel Tyndale is my colleague and co-PI on the bench side and I'm on the clinical research trial side but we have a large number of collaborators. I won't take time to mention all of them. It's a really terrific team with health economists, psychologists, pharmacologists, geneticists, behavioral scientists and more. I want to acknowledge also Penn faculty who've been involved specifically in the data that I presented as well as trainees and staff who worked on the data that I shared and importantly, we could not do it without funding from friends at NIH and this is the funders of our U01 and also want to acknowledge the P50 that's been funded through NCI which has helped us get to this co-inesterase inhibitor and other medication development studies. So I thank you very much for your attention. Thank you.