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Hi, everyone. Um, we are, we are pleased to reintroduce doctor Wellington. Um, he was an academic foundation doctor and aspiring neurosurgeon. So we are fortunate enough that he'll be speaking about artificial intelligence in healthcare and research. Um, so I'm just going to pass over to doctor Wellington. Fabulous. Can you hear and see my screen? Yes, we can. Fabulous. Ok. Thank you so much for the, um, for the introduction and the a of um presenting here today. So, yeah, the presentations were amazing by the way, so well done to all of you and the posts are great as well. So I have been invited today to talk a bit about artificial intelligence and research and my background pretty much is, um, I went to Cardiff University. I created within a top 10% of, uh with honors and basically I've held quite a lot different um, national International leadership. Um And within that, I've been able to tain quite a prolific research profile. Now, I wanna do neurosurgery. So A I and healthcare and surgical innovation are really important to me paramount towards the future of surgical and within there's been a lot of innovation for example, the development of medical medical robotics, tele how we can use A I for global neurosurgical applications. And really all of this is for the betterment of patient care, want to implement machine learning, deep learning A I robotics, even though expensive and within current climate may not be achievable. Um But at this moment in time, we're seeing the future applications to really benefit the the uh the future generations. E what we want to do is employ all different applications such as medical robotics and A I. To really think clinical research um which I'll get onto in a bit my publications and presentations. I have um I have had a bit of experience which is related to um machine learning A I within neurosurgery. But within this, I see a lot of papers um especially as a review editor for you see a lot of papers, you know, using an implementing A I in a various um plethora of ways I have to talk about it and to delve a bit deeper and give you a bit of a crash course on what clinical applications, the benefits, the drawbacks, et cetera, we can get from it. So you are um these, these six things. So you know, the application drawback and advantages of machine learning, natural language processing A I medical robotics, personalized medicine and VR and these are the moments in medicine and so are big hot topics um about looking in these and becoming adept in using A I use and statistics programming, et cetera because it's more valuable uh well invaluable to um researchers and doctors, especially the older generations. So first of all, I'm just gonna talk a bit about the basics of machine learning. So machine learning really means one thing and that's using a machine to learn from preexisting data or qualitative or quantitative data to then help to really different outcomes and different functionalities. So for example, what, so this model here, which I've taken um taken from Christopher S pen is really looking at how we can, how machine learning works and how its life cycle is. So for example, in business, let's talk about business and economics in business. Business, let's say there's a big company, we get that later, but we want to, you know, quality improve, we want to service evaluate. So what they do, they have certain data requirements, say we wanna look at a population um of um I don't know uh finances between a particular population, what we can do or um having them interviewed or et cetera. And using quality of data data, we can use the data and explore through the software, it'll analyze and the data against a set model that model then which is fine tuned, will then allow the analyze it in a specific way. So then we can use the I to propagate certain functionalities. So for example, um it sounds really complicated but it actually isn't the software behind it and how they um how they compute these things is complicated and there's a lot of complex mathematics. But what, but what we wanna do as doctors and researchers is use this application. So a couple of things we can do with it. So machine lo and predictive analytics. So for example, we can have a look at data from um I've written patient records, but nowadays, we can actually use software to image it and then convert it into um ere and then that can be analyzed. And what we can do records is with the machine learning A I we can predict, for example, we can compute in the probability of first health outcomes. For example, say um the um A I or machine learning for um let's say looking at a risk factor for pe and then we can then according to that you look at hospital readmissions. So say the um yeah and demographic and risk factor we can compute. For example, when that will come on my Neil, we can all be in really, we can use it as an artificial meaning that the if we have the software, we can up um have a look at the CD or the chest X ray, for example, and then it will less diagnostic or management plan. OK? Not always, it's not always right. And this is where it learns from analyzing many, many different populations, many different who then get a better prediction stability. So what clue maybe it's something we can't and then we can have a look and delve into it. So we're still human operated. It's not sole function yet personalized medicine. This is where it's quite interesting. What we can do is we can use machine learning to predict strategy implementations on an individual basis for the best patient care. For example, if say you have a complex cancer patient who on XYZ chemotherapy, it's not working et cetera. We could use machine learning to go analyze through the data. All for the patient records do then pick on and they will pinpoint it for us. Um Clinical decision support. Um We can ample triaging um in we can have a where it analyzes eres or you know, presenting complaints, et cetera, compute that and then give sort of categories. So say the um the A I think is not as high priority as say an M I. It will put them into a different category um uh category also with decision making. So say we're on an MDT and we have a pathologist looking at a slide, we can use A I um to look at an analog a slide um to for his pathological reasons. And that will give them say, you know, prognosis of say um a glioblast or a multiform or something identified on a brain section. And then population health management. So we can analyze data in large populations to identify trends and patterns to inform the development of public health initiatives. This is really important for, you know, over the recent years with COVID-19 uh communic. So we could use this ti we can use this for infection. We can even use it for no's disease and how we can implement public health measures in. So all in all the take your message earned from data to learn from our experiences to then combat our patient outcomes. Now this is a sort of, you know the diagram. So we have you know, network so we can take measurements some parameters from say uh their pulse, their new score, their observations, um you know their circulatory, their rest. We can use any bit body parameter and we can compute that into data, then that data will be uploaded and it'll go usually into a secure cloud server such as the NHS um system. And then we can do different things with it. We can data mine, we can classify, we can learn from it. We can predict we can make an algorithm like well scores, you know, compute hi and we can also uh um and it can be then made into a we can do as clinicians as while this is happening, we can remotely monitor the patient. But but a consideration a rec you should be considering what are the ethical considerations with using data from a patient calling and analyzing it and then blah blah blah blah, what are the ethical considerations, you know, especially with if you go to practice within the NHS patients is number one, there are hackers are people, there are governments who will actively want to acquire this data. Is it truly is your is your health, is your data truly printed? Keep that in mind. So the whole the rest of this talk because that is one of the biggest fact when it comes to implementing A I, we need to always protect patient data regardless of um you know, regardless of the propagation of patient. So this was a paper which myself and um published med student um and outcomes and challenges of A I within neurosurgery collectively and ex exponential useful neurosurgery. But you know, there are considerable factors we need to concern such as ethical considerations. Um This is not just for neurosurgery, this is for surgery, medicine, psych, and update a quantitative qualitative data, whatever you can compute, make it into something which we can learn from and which software can learn from. What we did find is that it improves patient outcomes and training by augmenting neurosurgical capacity. Meaning that these the these applications helped with training, it helped with education, it helped with patient outcomes, it helped with um it helped with augmenting surgical theater. It's just helped in a long enhanced diagnostic prosnostic outcome, perioperative decisions. So there's certain technologies such as in vivo and in vivo is used in um um for example, in brain tumor surgery where on neuro oncology, where you can take a piece of, um, a suspected tumor from a, um, from a margin and I, and computed then interpreted by a pathologist. And it will give you that whilst the patient is under a general anesthesia. So, you know, these applications are, you know, it's all very futuristic and if you're a futurist and this is really up your alley and we can then have A I to surgical plan. Neuro brain lab is um something we use in um in neurosurgery, we can look and plan, plan our surgery where exactly we are gonna go the depth, the parameters, we can decision natural language, another subject and in turn, handles, text each input and converts it into complex synthetic and funnel. We could have a software which interprets that and puts it into data that is pretty much got you. So this a lot of times for your chatbot. So there's such applications to Mandi and Pharma bot. Um Mandi being the more complex um NLP applications. Um and it's used in pediatric, I think, I believe. Um and Pharma bot for example, which will give you on et cetera and this is done any, you know, pharmaceutical or um or medical opinion. This is done through A I. The issues being is that we don't, there is uh fluctuant it, it, it's not something you can would feel comfortable and sign it off straight away. Um We can triage in critical care situations. So you know, example, say you have patients who's come in very from um and have a I to basically predict the prognosis, predict, you know, survivability, for example, and how we should manage. Um We can you guys medicine again, it's we can use natural language processing qualitative data to then put it into a more personalized plan between patient and doctor, which will inform the MDT clinical support. We can augment many medical services triaging being a good one and the improvement of clinical outcomes within emergency settings. Um Clinical trials to uh holistically and statistically, they can be a nightmare and this is why it takes many years to um you know, publish and go on to approve. Um but we can use natural language processing to device data and streamline drug discovery such as predicting targets and identifiers. Um II can't see that but if anybody knows who this chap is, I'll be, I'll be very impressed, but artificial in intelligence really incorporates three things. Mm deep learning and all that. Your natural language processing and the use of robotics. So your computers, your um your for example and A I really is, it represents a plethora of advanced machine technology derived meaning understand from extensive data inputs in ways that make human capabilities like us, we can adapt and it's II imagine it as the human version or well the machine version of adaptability we adapt, we learn. Yeah. And this chap is called Alan Duran in the 19 fifties. He did a quite a bit of work on A I. So you might know him from like the um from World War Two, et cetera. But this chap um pioneering artificial intelligence. So in so are all looking about, let's put it all together into A I OK. Now can be used for ma mass of different things, disease. So for example, we can have um use A I to see what it thinks in life from, from something we can't see from the naked eye um diagnosis, medical imaging, we can plan and it's useful in MDT S and personal we you can use for discovery. Um We is diagnostic, they can prog off within clinical systems. Again, clinical trial assistance and this curate dot A I, this is act as medicine. We actual well, this A I was used to appropriate dosing strategies over a certain time based on small acted exclusively from the treated individual. So say a person's been on an an hypertensive for a while it that we can you decrease more than two of their responses. It's very interesting. And again, I me robotics this a da Vinci system. So I'm just gonna let this play the Da Vinci surgical system is the most advanced platform for minimal invasive surgery available in the world. Today. The integration of high resolution 3D vision W risked instruments and intuitive motion control enable the da Vinci surgeon to transcend. Three network components comprised the Da Vinci surgical system, an ergonomic surgeons console, a patient side cart with four interactive robotic arms patients seated at the console. Chief surgeon views a remarkably clear 3d images filters and translates the movement of the surgeon's hands on the controllers to four interactive robot. The precisely control a movements of the Da Vinci events are enabled by the computer processors of the system. The dedicated processor, millions of safety checks over the of a procedure for enhanced surgical precision of wrist instruments are designed with a unique wrist architecture that provides seven degrees of freedom for a range of motion greater than even the human wrist. This proprietary design enables surgical maneuvers impossible with conventional laparoscopic tools. The system requires that every surgical maneuver is under the control of the surgeon. Redundant safety checks, prevent autonomous movement system moves surgery forward with a new level of technical capability that enables minimum invasive surgery in complex procedures as never before, she provides a streamlined surgical experience that benefits the hospital, the surgeon, the or team, and most importantly, the patient. So as you can see the da Vinci and this here is the versus they are you're in for a while. But the issue within the NHS, for example, being a public socialized system is that it's incredibly expensive and such companies such as CM E robotics um or Medtronic, these, you know, it is very expensive to be implemented being said you can only see these uh these robots in very tertiary centers with a lot of funding. So say you're working in the middle of nowhere, you're gonna be using su basic surgical technique. OK. So medical robotics, why is important and why is it advantageous? He the big thing, the surgeon doesn't need to be in the um and certain procedures with glob for for example, in global surgery, this can be elsewhere. You could be on the other side of the world operating one of these machines and and literally treating the patient at the same time. Now, the issue being is that you're not there. So if a combination happens and you're the surgeon operator be there. But other than that, for places where you cannot get, you know, you cannot get to the use of surgical robot is ever increasing. Ok? As the video was showing it's decreasing, it's decreased in inaccuracy of all. And it's um so that can be very useful and very articulary medical assistant. So um robotics can actually be rehabilitation. Um loads of different, you know, for spinal, there's different braces you can use now. Um quite a few hospitals actually, especially the London ones, Pharmacy Dispensaries are now robotic and if automated. So it reduces the risk of narrow again and medical transportation. Um believe it or not, and going back to the Victorian era, probably a robot would have been a car. So the future surgery um um from the FOS Task Commission from uh from Asset Surgeons of Edinburgh um of England. They published this um back in 2022 which I had you on there of writing here. But what basically um what I wanna allude to is that technology such as A I machine learning robotics implemented within different parts on surgical care, for example, perioperative and electrical emergency, surgical care, patient pa um where all these arrows are, it can actually determine where you can actually implement these things. For example, in the consent procedure, which um we talked about here a bit. Um You can actually use A I technology to optimize the consent. Um And this means like communication can be spread over time. Um and it can improve the patient's understanding. The doctor just doesn't overhaul them with um jargon. Um It makes it more di um digestible for the um for the patient undergoing surgery and you can use it in the per se set such as, you know, anesthesia surgery as I was talking in vivo, those sorts of different things. And this report I would read it um and have a have a little look at it because that is the future of where we are heading. Hindering it are the ethical money and people who can operate robotics. It is very different training and it's very different skills you need so many. Thanks for listening. Um Those are my um so that's my email. That's my Instagram. That's my ex, more than welcome to take any questions and more than welcome to message me on any of those platforms on linkedin. So thank you very much for the opportunity. Great. Thank you so much for that informative talk. Um We have a few minutes for any questions. If anyone wants to pop them in the chat, I mean, I can start us off. Um I'm also very interested in A II was wondering how you were involved with, um, like that interest in A I and getting involved in A I research breakthrough really was I knew academic neurosurgical career and at the moment, regardless of neurosurgery or anything, it's massive within, um, healthcare, um, and research. So I wanted to really scope the literature for example, and I got involved with the, the FOS test report, which was really my big introduction. Um And when that happened, I had a better comprehension, better understanding and I could then use it and see where we can innovate. Um, and med tech at the moment, even though some people don't like going into it because it's another alternative career to being a doctor. It's actually an important aspect of where we are heading, um with, um, with the future of medicine, the future of surgery. But the problem being is that it's quite inaccessible, especially, you know, it's not really covered in medical school curriculum. It's not really, um, it's talked about, but it's one of those you know, one of those objectives of the, NH I, you know, we, there's so many issues that we can't really, I, and the fundings on there. So, just to keep, just keep it in mind and it's really useful if you're gonna indicate or do a post graduate, you know, fellowship or something like that because a lot of the time the research is gonna be involved in that, like my A FP project will be that. So, um, so, yeah, that's how I got involved. Very much. Great. Yeah, it's, it's important, especially really topical now. Um, you know, med tech and A I. So, yeah, thank you very much. That's been great. Um Are there any other questions? Thank you. It's, it's great to hear that talk. Um, what's, what's your opinions on ho how do you think patients might feel with the introduction of A I to clinical practice? Mm. Good question. Again, it comes under the ethical umbrella like that. It's very mixed. I think if, for example, the patient is going for surgery and the surgeon's not there and the robot's doing it. I mean, there's a lot of sci-fi films which basically to condemn robotics and it goes all wrong dystopia and all that. It's probably precise than a surgeon doing it cos they all human error. Um, well, to an extent. Um, and I think it should be more, I think it should be more, er, or more awareness for the implementation of innovation. Definitely. But I can see it's gonna take many generations for, um, patients to get accustomed to it because they wanna see people even COVID telemedicine and not seeing patients that again, um, human factor is still a massive maintenance of medicine. Yeah, absolutely. You're right. I suppose that might be a, a limiting element as well. Anyways, thanks for that. There's a question in the chart. I don't know if you've seen it. Yeah. So opportunities to train on Da Vinci. Um Again, it depends on what center you're in. Depends if they have access, depends if they have funding for it. The other big thing is there are courses out there which you in surgical robotics, but their a surgery definitely has robot and urology. There are courses out there by the Royal Colleges but regarding other different um depends if they're adopting it and it depends if the centers have it. So you're gonna have to be in a major trauma, a major s um surgical setting for it to have that any other questions at all? Yeah. Can't see any in the chat. But thank you very much for also giving out your socials and your emails. So hopefully if people want to reach out, they can. Um So yeah, thank you very much. Once again. No problem. And we have our next speaker here, um who I'd just like to re to introduce. So we are pleased to introduce Professor wjz Dillo, the Dean of the N I NIH R. So the National Institute of Healthcare Research Academy and he'll be speaking about NIH R careers. So, thank you very much for attending. Um And I'm just going to pass it over to you, professor. Great, thanks. And hopefully I'll be able to share my screen. Yeah, that's fine. It's not sharing the pa, is it II think it's coming up now. Is it coming? Yeah, we can't see the presentation yet, but we can see you on the screen. How do I get the presentation to come? Oh, there we go. Oh, did you see it? Yes, it's just not in presenter mode at the moment. I know it's come now. Um Yeah, there we go. And then if you click on a mode, let's see. Um There we go. It works now. Brilliant. OK. Sorry for that technical hitch. Uh So afternoon everyone. I'm w di di uh dean of the Academy and it's a great pleasure to be here this afternoon. It's an amazing sunny day outside. So you're all very dedicated by uh by being here today. OK. So I'm gonna give you a whistle stop tour of, of, of why as a medical student, you might consider doing any research during your clinical training once you qualify um and roots if you uh like kind of research of, of clinical academic careers. And so there is no reason I've got in my first slide, why you can't go from being a medical student to a professor in any of your specialties or in general practice? Ok. So why do you want to do research as part of any clinical career? Well, research as part of the HS constitution that you're probably aware of. We did uh evidence based medicines for new therapies. What's really important. And I think is now there's hard data for that for this is that research active hospitals have better patient outs than those hospitals that are not research active. Uh And and there may be many reasons for that, but that's, that's really interesting to note. Uh patients value the opportunity to take part in research, particularly if there's not many treatments for their condition and the quality care, the care quality commission C QC audits also have a research in terms of you. Uh I think it makes you a better clinician uh helps you appraise evidence. So you're taught lots of things as a medical student. And actually you find what you're taught as a medical student, student. A bit more complex. When you start uh talking about patients with multiple conditions, really look at the evidence very carefully and be able to appraise it. So that um when new treatments come up, you can decide for yourself whether a patient's gonna benefit from it or not. It's good for your career. So um this one's not mentioned very much, but it the the reality is is that you will come out with a medical degree and actually if you're gonna go into, er, an area or an area of the country where you want to work, if you're the best person for the job, then you're likely to get it. So, jobs are, the best jobs are competitive and, uh, people who have got more on their CV will, will be more competitive. That's just, uh, reality, the, er, potential for a clinical academic career. The the I think the, the beauty for me is what you can do. So you can do clinical work, but you can also do research and teaching alongside. So it ends up being a portfolio career which I think is really exciting. Um And the bit at the bottom is not mentioned very often either. It's, it's actually very fun and interesting cos no days, no, two days are the same. OK. So this is where your you guys are at. Some of you may have done an intubated BSC. Some of you may have done an in phd. Some people have already done a BSC or a phd before they enter medicine. So graduate entry me, me, me medical students. And so there's a vast array of people who will have done some research um either prior to medical school or at medical school. And then obviously there's the specialist foundation program which is used to be the academic foundation program. So in your year one and two, in your second year, you can do four months out, uh doing research, teaching or management. So that's another thing worth thinking about. And then as you move forward through your career, if you're going down a medical route, this is more for, for that route. But it could be really kind of any career with, with whatever names come up for a general practice, for example. So here your pre phd uh and, and the opportunities here, er, er, or a number of opportunities here. And we'll talk briefly about those as the PG cert, the associate P I scheme uh one year research fellowships. You could do uh a master's in research or an academic clinical fellowship at the ACF which N HR Fund. So these are all pre phd. Give you some time out for it to, to do research while you're doing your clinical training to get you competitive for A phd and then during your kind of specialty years, um uh I II think anybody in an academic type of specialty, it's a good idea to do A P HDI. Think it gives you very good training. Uh And, and your thought processes as a clinician, I think are much better because you don't just follow guidelines and you follow the evidence uh and can think about things very differently. Uh And we'll talk briefly about MRC and RR Doctoral fellowships uh and Wellcome Trust phd programs which, which fund clinicians to uh their phd. And at that point, you might CCT and become a consultant for the next 35 years, maybe 40 years for you guys by the time as retirement age increases. Um So, so that would be uh a standard NHS consultant job with most consultant jobs having zero research time in there. So if you want some research uh time in your uh job, you can go down a clinical academic career route. Uh And what the first way to start. That is kind of down here, the N hr clinical lectureships uh uh or the Wellcome Trust Early Career Award which again fund uh up to 50% of your time for research. And then if you uh are interested in having more time devoted post ct to uh uh to research, you can then get personal funding from these schemes. The MRC clinician scientist and RR on the Well Trust Care Development Award didn't really worry too much about the names. They're basically giving you funding for your salary at consultant level plus usually a person and research time. There's also other opportunities that you can get involved in research if you're not um if you want to do more clinical. So you can do, you can become a principal investigator for clinical trials, which some people do. Or there's the c scheme that will briefly mention the clinical academic research partnership. There's 5050 50% clinical and 50% research. And then here at chair level. Uh so this is a clinical called senior lecturer on the academic side, reader or adjunct professor and then professor at the top here. Uh and even at professor level, you can apply for your own funding for your salary to protect your research time. So the N HR Fund, research professors and the MRC Fund Senior Clinical Fellowships. So they, they, you've got basically a pathway here of funding from medical school on the left all the way through to a chair on the right. And, and these are all open and available to, to everyone. Ok. So let's start pre phd, which is probably the most relevant er for, for, for many of you er II think the special foundation program we've mentioned um with the uh applications are probably about now um or coming up for the next year and, and as you said, four months out in year two. So as we move forward, then further things that you can get involved with is the uh MH RPG Cert. So this has just been launched a couple of years ago and it gives you a general overview of clinical research delivery. Um It will give you some training, it's, it's online um and, and it can be done as part of your uh clinical work. Um So this is something worth thinking about as a, as a, as a taster to get you going. The Associate P I Scheme you can also do alongside your clinical works. A principal investigator that's somebody who's, who's uh usually clinical, uh usually a consultant level is, is the person responsible for conducting a research study at a site. And essentially you would join the principal investigator and support them. So it's, it's, I guess it's a bit a bit like being a AAA junior doctor in, in a team. Um The consultant is leading the trial and then you're helping them as associate P I uh for a six month period. And it gives you an opportunity to see how it all works uh and get mentorship uh from that uh local P I and then you get a formal certificate for uh for this as well. So, so this is again an early taster of uh of research and then one year fellowships are useful. So this uh buys out your salary for a year to carry out some clinical research. You can do a masters in research during that, obviously, that's associated with fees. But um there are places where you can get er funding for that. Um And a lot of different hospitals and a lot of different mechanisms for these one year fellowships. Um There's local charities that fund them, there's biomedical research centers that fund them. Um So bottom line is, this is quite a good way to build up your CV before A phd. Uh And there are a lot of s out there if you look for them and then the, an academic clinical Fellowship, which you're probably familiar with now, has been running for uh 16 years or so. Er, this is, er, in local centers and, and here as part of uh kind of ST one onwards you get nine months of protected time, over three years, er, during clinical training. So you might, might be in three month blocks, might be a day a week, might be in a nine month block. And the advantage here is that you get delegated time in the lab or in the clinical setting that you're in, you can uh get pilot data for a phd. That's what these are aimed for, er, and for relationship with your supervisors and start preparing a phd application. And then next level up is obviously the phd. Um this is a three year commitment. Uh And the biggest factor here is, is obviously getting funding. Uh by this stage, your, your salary has gone up from the 14 lb an hour which it is at the moment or when you start. Um And so each of these comes in at about 303 150,000 lbs. So somebody, so you're asking the funders really to fund you for, for, for that amount of money for three years, for a phd when, when you, when your track record is, is, is perhaps not so strong. So, so this is why these are competitive, uh because it's a lot of money but it is very valuable. Um So one of the things that you need to learn about is is is who to go to for the, for the funding. So, learn about the funders remit and they are very different. So the Wellcome trust um is, is very much at the Discovery Science end, at the Basic science end, uh what the MRC is kind of more in the middle if you like uh they're uh they're um all the way from fundamental science to early clinical trials and preventative medicine. And then at the right end, er more applied research is is where N RR comes in the National Institute of Health Research. Um So the aim of NR HR is to improve the health and wealth of the nation. Um and this only funds clinical and translational research. It doesn't fund any basic or animal science research. And the aim here is that within five years at the end of research there there'd be health benefits. So this is more at the applied end. So the good news now is that actually there's funders at each of the stages very early on the way through to applied research. So what is an uh MRC or an NRL doctoral fellowship give you, it's a personal award, it funds you with your clinical salary for three years. It pays your phd fees, it pays the money you need to deliver the research, the consumer boards and it also pays for travel to conferences. So this is this is a pretty, um the, the fellowships are, are, are, are pretty amazing in terms of an opportunity to, to really develop your career and, and get paid and, and have protected time. So this is obviously competitive and that's why ideally you would have done some research beforehand, either A BSE or one of the pre phd type uh uh programs that we've discussed. Uh and generally for fellowships, it's about project uh about the person, how good you are about your project that it's going to be cutting edge and have impact and the place where you're doing it, the center is important. Uh It doesn't matter where the center is, but it needs to be a center that the funders can feel that is going to be able to deliver the research. Um And uh it's important that uh that you think about the training needs that you do and patient and public involvement particularly for an hr applications. So the standing on the candidate, the track record, the importance of the research, questions, strength and weakness of application uh and the candidates uh choice of appropriate sponsor and what the location offers. So those are a really important part of the assessment criteria. The Wellcome Trust have moved their model. So, whereas MRC and N hr you applied directly, the Wellcome Trust have given out centers who applied after a competition. Um And uh so what happens here is they block funding to a, a particular university, they would advertise uh a clinical phd and then the people who have got the best track record and CVS will get funded. Uh So the, the mechanism of funding is slightly different here and usually the project is decided after the person is awarded. So again, I won't go through any of the details here, but these are available around the country as well. So why do a phd, what what happens to you during your phd? Well, I think this is really useful and ideally, it would be great for all clinicians to do um who are in an academic type specialty. Um I mean, the first thing is that you learn to become a scientist and think and analyze evidence. Um So that's really important. So when you then see a patient and you think of all of the New England Journal medicine papers or something else you might be reading at the time and relevant, you can actually use that knowledge uh and assemble it in a much, much more balanced way than somebody who's, who's not done a phd. Uh It's important to find a mentor who's gonna support you through your career independently. You develop your research skills, uh You need to keep abreast of the clinical developments in your specialty. Um And then later on, you'll be attending meetings and presenting your own data, which becomes a very exciting part of it. Uh And obviously, it is important to publish your work as well. So hopefully you've got your phd, you've done pre phd opportunities. You've got now more competent, you've done your clinical training. You're, you're, you're getting your CCT. So I guess this is the, the, the critical point for most people is, is where do I go next? Do I go into a full time NHS type job or do I want a more portfolio career? And this is, this is where probably for most people, it's the, the, the big decision. So here you could, as I say, um get an NHS consultant job, lots of them around at the moment, 34 years to 40 years, pretty much doing the same thing. I think it, it, it's obviously in most people will obviously go down this route. And I think it's very important that we have very good consultants, but I think it is also very difficult to, to do the same job for the, for 3540 years. So you might start off as an NHS consultant, but then I actually want a bit more of a portfolio career with either teaching research or management. So that's worth thinking about whether you go down a research career or any other career. Um If you want to go down a clinical academic career, then really there's um so if, if you're mainly wanting to do an NHS job um in a specialty, for example, one of the options for research is that you don't have to get your own grants. You can participate as a principal investigator of P I for clinical trials. So this will be new drugs in your, in your specialty that are coming up. Pharma need to trial them in patients. And so they will go to hospitals and, and ask for uh principal investigators to lead a part part of that big multicentre trial in, in that hospital. Um, Pharma wants the centers to deliver to time and target. Uh they will fully fund the costs for the study. Uh um and the treatment, er and they'll fund, they'll pay the P I some time. Um And the important thing is obviously we won't get new therapies into the clinic for our patients unless we've got uh P is doing clinical trials in hospitals. So this is one way that you might be able to maintain some research in your post CCT clinical consult career. And for example example, there's some are listed there underlined, these are people who have, people have probably heard about uh Wegovy and, and the, the weight loss drugs. These are people who are NHS consultants who have led this um this trial for example of semi blue. Uh and this will be, you know, a um a trial that's been done in maybe 20 hospitals. But these are people in the UK that have been involved in this trial. So these are NHS consults that are contributing to um really important impacts for, for, for our patients. If you want a bit more research time in your clinical uh consultant career, then there's the Mr Cnr R car, the clinical academic research partnership. So here the idea is that you get your consultant job and then you decide that you would like to do some research and you can actually get the, the slides out of date. Now, you can actually get 55 pa so half your time as a uh consultant for five years now, as well as consumer consumables up to five years. Um and the, the NHS trust guarantee that they will return those five PS at the end of your three years. So you have security but it gives you five years out um of doing further research um as a consultant. And here you need to be working with a successful team with a good track record uh for to, to be successful because obviously this is a challenge to otherwise do if you want to go do down more of a research route and, and have a go at a, at a, a more er research heavy uh clinical career, then um the, the first stages really are the N hr clinical electors or the Well, well trust early career award. So the N hr Clinical Elector C LS that people will have heard of here. You, you get a four year award. Um You can do 50% clinical to finish your training that you need to do to CCT and then 50% for research, you are supernumerary. So they actually pay for your 100% of your salary. So this means that actually for most um registrar type jobs, people are doing service delivery rather than clinical training. Here, you are uh fully funded for four years. And so you only need to do the clinical to complete your CCT and the rest of the time you can concentrate and research. And the the the aim here is really to see um is to give you the time to further develop your um research skills after your phd and apply for the next level of funding, which would fund you for five years, consultant level at 100% to, to, to do research and clinical. So the Wellcome Trust early career award is is similar, it, it's basically AAA post phd um opportunity. So that by the end of this, that you'll be ready to uh develop your own research program. And then really the uh the door to most clinical academic careers in terms of permanent um posts and universities are are the uh kind of clinic and scientists or advanced fellowships of the career development award from welcome Trust. These are five year awards, they fund um 100% a consultant salary and they also fund your research. So these are the phone individuals who have really done um outstanding research to date. Um So they're pretty competitive uh but um this will allow you to continue your research and post doctoral research as a consultant. Uh it will fund you at consultant level and it will, er, fund usually a person and, and your, er, consumables to deliver the research and, er, travel to meetings. You obviously need to have done a phd or an MD and, and have shown that you can publish well. Uh and here, um after, after, after you've completed five years of this, you, you will um be usually running your own group and, and most people who get one of these go into a professorial job within five years of completion. Um So the, the, the, the names are there, they, they're all essentially offering a similar thing. A post doctor will offer 100% for five years for MRC up to eight years and two goes from well trust in a RR. So this is, these are, if you want to, to, to become a full academic, these are the things that you want to be thinking about. And then right at the top, if you, if you've done well and you've got your permanent post and you want to continue with protected research time, you can apply for the research professorships and the uh senior Clinical Fellowships. They're essentially an extension of that er earlier clinician scientist. But um AAA higher level and funded uh these are usually about 2 million each. So very important if you're gonna go down an academic pathway or, or any pathway really is, is to find an important mentor. These are the two people that mentored me throughout my research career and they can, they'll be able to give you advice on what schemes are available, but also impartial advice on your research career. Er cos they'll have been through it and know what, what, what the current um potential career pathways are. So I would actually say it's never been a better time for, for doctors to consider uh research as part of their clinical career. Um, so I think it's important to build your CVI. Think that's important whether you want to continue long term in a clinical academic career or whether you want a job of your choice and a specialty of your choice. So there's been a lot of um noise about BSE S not counting for, for uh foundation program, it's gone to pi A, there's noise about B ES not counting for specialist training programs, but I can tell you if you want a fellowship or you want a job in a uh in a um, in a highly competitive area, everybody will be looking at what your CV looks like. So, so don't be disheartened by that. It's really important that you find an important area that you're interested in and that you're passionate about. So, the, the, it's uh it needs to be something that other people recognize is clinically important in, in, in health care, but also that you're interested in cos you'll be doing it for a long time if you're uh in, in a clinical academic career. And then the next thing to do is go and find somebody who's working in the area and email them and find them at a meeting. So you need to look for people who you, you might want to work with. Um uh and most people are very happy to talk to people uh about potential projects uh and funding and they need to apply for funding. And bottom line is apart from some hours, there's nothing to lose. So um you uh uh you, you, you make your own opportunities, I think. So nothing's gonna fall in, in, into your inbox. But if you uh go out and seek opportunities, um there's plenty of opportunities available and, and after this meeting, you can start today once you've had a um uh uh hopefully been um invigorated by the day. OK. So just to finish up, I thought I'd tell you my story. Um So this is my uh my shiny slide as I call it. So this is, this is uh this is one of the things that uh my, my, myself and my team have done is over the last decade or so is um come up with a new treatment uh er for ovulation in IVF uh which would be safer. This is baby heath who was born and this is a picture on the BBC website from a couple of years ago when we came up with this treatment, we've also come up with a new treatment for menopausal flushing based on, um, studies in animals. Um, and that's now been M hr approved, the FDA approves out this year. Um, lots of publications. There's a bit out of date that there's probably about 300 now grant income is about 26 million. And you can see, I kind of went through the specialist registrar training and then all the way up to um uh I was uh had we trust phd funding. Uh Then I had three subsequent um N hr um fellowships, I had a clinician scientist for five years, then a career event fellowship for five years and then a research professorship for another five years. So I II stopped my fellowship funding. So I've been funded for 18 years th fully funded externally. Uh And that allowed me to develop my research career. And I think I was around 50 when II was then taken on by the university rather than external fellowships. So that all that's my shiny slide. Um And that's great, but let's tell you how it really starts. So this is the real story cos that's the shiny slide and we only show the bits that, that the, the, the, the shiny bits. But actually II started medical school in 1988 with nobody in the family who was a medic Um And so I knew nothing about a clinical academic career. Uh So that's the first point to make. Um And then the second big opportunity for me was the, uh and that was my aim at that point was with the inner city GP cos I didn't know anything different. I didn't know. Uh the only thing, the only per people I'd interacted with in healthcare was general practitioners and I thought it would be pretty cool to be an inner city GP and do some good. Ok. So then what happens? I do well in year one and two and the Medical Research Council at the time used to fund fully fund um if you were from a low income background, uh your BSE. So I thought, well, I'm not gonna do it if II don't get the funding because I couldn't afford it. But if I got the funding, I would do it and I did well in that. And that was probably the 1st 1st real important thing for me in terms of first taste of research and thinking that that might be a good thing to do. Ok. So at this point, I'm still gonna be an inner city GP. Um And then as I kind of went through house officer and sh training II trained at Barts, which is a very good er, endocrine unit, still has a very good endocrine unit. And I was in, I was inspired by that and I thought actually, maybe I want to become a clinical endocrinologist, not an academic endocrinologist, but a clinical endocrinologist. Uh and then I did my specialist uh registrar training. I got my Well Trust phd uh really enjoyed that. And then by the end of training as I was coming up to CCT, um I then thought, well, actually this has been quite fun. Maybe I should do some research uh as post CCT as a, as a consultant. Um So that, so that was kind of it moved, we've moved very much from uh one area to a completely different area with the opportunities that, that, that, that came up. And then here's the dilemma that I kind of mentioned at post doctoral level is do you continue on a permanent NHS consultant, post, lots of them available. You, you turn up, you do your work, you go home or actually do you go for a, a five year clinical senior lecturer appointment at uh imperil, which is where I applied for an nr scientist and then what happens at the end? So there is some uncertainty and, and, and I kind of had a dilemma here, but I got the NH a scientist and so I decided I'd go for it, didn't think there was um didn't know what happened at the end. But actually, as I say, most people who get one of these have all gone to, to, to chairs because there's actually a shortage of people in in clinical academic careers who, who go down this pathway. Um So next thing I did was apply for an N HR senior fellowship er er towards the end of this, this post. Er, and actually it was rejected, they said I didn't have enough complications. Uh they didn't like the project, er, and that was obviously quite disheartening, so you have to go back. Um and then I applied again but this time for a lower award, a N hr uh career development award and this was funded, but only if I got another million out of the MRC to to fund the grant. So uh that was uh a bit annoying. So then I had to apply to the MRC and luckily that was successful. And so both of those got awarded and that, that was where the IVF study was funded from. Um So um that kind of just gives you an idea that it's, it's not plain sailing, but there are opportunities and you have to, you have to keep going if you want to, to, to succeed. But actually, you've always got a clinical career that you can fall back on. So actually, as clinicians, we, we're really quite lucky. So, what do I do now? Um So now I'm a consultant endocrinologist in general medicine and, and mainly endocrinology at Channel Cross Hospital. I was on the wards last week. Uh I'm a professor in Endocrinology and Metabolism at Imperial and lead a research team uh as well as doing teaching. Uh about four years ago, I was appointed as head of division er of diabetes endocrinology and metabolism imperil. So here um II oversee the strategic direction of the division and support new people coming through. And then uh about three years ago, I became, uh I'd been involved in training. I've also been funded by the N hr for a long time. And so to give something back, I was involved in training for about a decade. Uh And then um took over his N Hr Academy Dean. Uh uh And here we've got a budget like I oversee of about 100 and 50 million lbs a year. So that's the amount of money that's available just from the N HR for, for, for doctors and, and uh other healthcare professionals for capacity development. So the A CFC LS Fellowships have all come from that budget. And then um middle of last year, I was appointed scientific director to the N RR board. And so a procedure can put to the 1.4 billion lbs per year in HR and you spend on clinical research. So, so I'm really showing you this to say that you can have a portfolio. If you go, go down a clinical academic career, it's a very exciting, you can still do clinical work, you still do teaching, but actually, you can do things um in terms of uh uh supporting other people and bringing other people through. Uh and it becomes incredibly exciting because no two days are the same and actually you can, you can start having an input into um moving the dial and, and, and improving things for the next generation, which hopefully we're doing. So, if you want more information, the catch website, if you've not come across, it is very useful. Um And that's got a lot of information on as well. I will make my slides available as a PDF to the organizing committee afterwards and it'll be sent around if that's helpful. I'm very happy to take questions. Perfect. Thank you so much, Professor Dlo. That was super useful. I think this career pathway is just unspoken within medical school and being someone who's also interested in academia, it is really, really useful and eye opening to see what I could go into in the future. So, thank you very much. Um And if anyone has any questions, please pop them in the chat and I can read them out. It's just a question. I mean, II might have missed this, but as of now, currently like within a week, how much um how much clinical exposure do you get? So, so what I do is I do weeks on and off. So I think it's quite difficult to, I think it works better to do. You're either on completely. So I was on the ward covering the inpatients and then doing clinics and then we do um, a block of that and then you're off and then when you're off you want to start on other things and then it doesn't blur in, I think when you're doing a day, a day, a week or something like that, that becomes a bit more tricky unless you're just doing outpatients. Um, you know, there's kind of hangovers from the previous week, et cetera. So that works well for me. But, you know, any model, uh, is, is, is good. Great. Thank you. We have a question in the chat. Um, so someone's asking, how do I know if my research idea is important and viable? So that's a really good question. Um, so one of the things I talked about was patient, public involvement and, and has got this at his heart, MRC are moving to that and I guess for me it would be go and talk to a colleague who's really not interested in what you're doing, um, er, or, you know, or, or, or mums, dads, uncles, aunts, actually, I don't talk to your mum and dad cos, I hope they're gonna be supportive. But as you go and talk to people who really haven't got a vested interest in you. And just see. So if I said to you, this project will look at XY and Z but could cure cancer. That sounds quite important, right? If I said to you, I know, look at toenails and you know, whether, you know, uh 11 kind of toenail clipper is better than another. That doesn't really seem as impactful. So it really is pulling in. So when you're sitting on, um, grand panels as, as, as I do and many people do, um, what you're, what you're trying to do is my specialist is end diabetes Enterology. So I know the important things in that area. But for example, a dermatology, I won't know anything about that. But if you tell me that eczema affects, you know, 25% of the population and it causes 100 million lbs worth of NHS spend. And you've got a new treatment or a new pathway that you're looking at that suddenly becomes important. So it, it's, it's, it's really talking to other people as well as and then to know if it's viable, that's really working with your supervisor to make sure that methodology and statistics, et cetera is all is all uh thought about. Um we have another question. So for a surgical trainee, how does one maintain surgical skills whilst doing a phd slash doing research on the side? Yeah, that's, that's a good question. So we thought about that very carefully. So for N RR Fellowships, you can do up to 40% clinical for, particularly for surgeons. So it is very important that you, that you maintain your skills. Um and, and for, and for the advanced fellowships, for example, the research professorships again, you can have up to 40% clinical time doing your cutting. I think one of the other things is that, that's advantageous with the fellowships is, I mean, we all know that, you know, you're supposed to be in training until you get your CCT. But actually, for example, diabetology, you'll probably do about 5000 diabetic clinics. You only need to do 100 for your training, but that's what the service needs. So actually, if you're on, if you're on a clinical lectureship, for example, that pays 100% of your salary or a fellowship, um you can then just do your cutting if you like rather than do all the other stuff that you probably don't actually need to do. It's, it's your cutting that you need to maintain and, and the number of procedures and that's the same for cardiology and other specialties. So there is a recognition by funders that certain specialties, you know, certainly need more research time, um more clinical time as part of their research. Great. Thank you. And I don't think we have any other questions. Um Thank you very much for your talk. No problem. Great. And I'll send the flies around. Yes, we'll distribute those around. Thank you. Great. Thanks. So, moving swiftly on. So we have our final talk now. So we are pleased to introduce our keynote speaker, Doctor R. Sandra Se Bles Apologies for the pronunciation and she is an assistant professor at of Neurology at Harvard Medical School and the principal investigator of the laboratory at the vaccine and immunotherapy Center at the Massachusetts General Hospital. So, thank you so much for being here today. Um And I'll just hand over to you. Thank you so much and thank you for uh the kind introduction and it's, it's, it's really a pleasure to be here. Um And it's, it's truly an honor to, to follow the, follow the, the, the previous speakers as well. Uh I think it, it just flows really, really nicely um because they um the story I want to tell you is a much more of a uh basic science story and the arc of, of going really from, from bench to bedside with, with a lot of uh concentration on, on the bench on the preclinical work. Uh As, as, as you mentioned, I'm um I'm a researcher, I'm a scientist, I'm trained in as a, as a neurobiologist and I'm a phd, not an MD um however, working. Um and, and I am in, in the Department of Neurology but also have the my group is in the vaccine and immunotherapy Center um crossing and spanning multiple departments from the Massachusetts General Hospital and Harvard Medical School. So it truly is one of these unique locations where you, you have access to basic science development from, from the very, very uh incipient stages of a, of a concept of a scientific concept and the reach and, and the pull in a way to to the need that, that patients have the direct access and contact with, with uh with patients and with clinical medical problems that need solving that, that uh demand solutions from, from us, from the basic scientists. And we're working very much hand in hand with clinicians uh all along through the process from concept and all the way to implementation. So I will, I will tell you a story about uh uh uh a cell therapy in this case, a more unconventional cell therapy because it's, it's based on B lymphocytes, which most of us don't really think of uh when, when you mention cell therapies. Um and I'll, and I'll try to convey, you know, a little bit of um the basic science um around this and I'll just share my um slight in a second. Um Hopefully, you all can see this um with, with um um OK, let's see if it's progressing properly. Yes, with a little bit of background in um B cells as a little bit more than antibody uh generators. Uh Then we'll go a little bit into the background of um how we could use these cells as a therapeutic agent in uh for regenerative medicine and more than one pathology. Um And we'll go a little bit into the, into the cell biology and, and the mechanistic work that we are doing. And finally, I'll, I'll conclude with uh a clinical application uh one towards which we're heading and, and some which we're already implementing in, in our center and across departments as I was mentioning. So most of you might know B cells as uh obviously this the source of antibodies. Um but they are interacting with multiple components of the immune system and they have many other roles uh including very importantly, modulatory roles uh in in, in terms of dampening the inflammatory response as well as activating it. Um And this whole story started with, with research that, that we were performing actually in wound healing. Uh And with, with an I, an idea towards diabetic wound healing. And this is an an image that I captured a number of years ago uh at a confocal microscope. And I, we were looking, I was looking at whether or not nerve regeneration was different between uh wounds that were treated with B cells versus were controls. And we saw this exuberant growth of cutaneous nerves uh into the injury site into granulation tissue that um used to be uh uh essentially an an open wound. All of these are preclinical studies and these are animal studies uh at this point. But when I saw something like this and and this is really one of these moments where you know, your your thinking starts to change and we were working in one model. But um at the moment when you, when you see a result like this, uh with my, my neurobiology background, uh II thought we need to, we need to translate this as soon as possible to uh a central nervous system injury. Um And in, in the, in the traumatic brain injury in the, in the CNS injury, there are a lot, the, the, the inflammatory response to an injury is extremely well orchestrated and it resembles a lot of uh peripheral injuries such as such as a wound, of course, with, with different cell types. However, the uh inflammatory infiltration into, into an injury site in the brain um resembles a lot uh uh what you see might see in the cutaneous wound. Uh and, and there's initial damage and it's, it's really cer certain cell populations that come in sequence. Uh And, and uh either do damage or help with, with repair, of course, in the, in the context of a neurological injury, any damage is irreversible um uh for, for the neuron. So it's a very different problem. In this case, we need to be able to um uh uh prevent as much of the damage as possible. So, the application that we're really thinking about here is is traumatic brain injury, which I don't need to uh explain uh you know, the, the, the importance of and the, the importance of finding um um therapeutic uh uh interventions which currently don't really exist. Um There is a, there is a very complex cascade uh and, and serial uh uh intervention points that we were considering because if we can reduce inflammation early on and potentially promote neurogen generation or at least uh uh neuroprotection, we might be able to prevent the long term neurodegenerative consequences of, of uh traumatic brain injury, which are also well documented. Um So we did that, we applied this the, the B cells as a direct therapeutic strategy um crossing from wound healing and all the way to uh traumatic brain injury and in traumatic brain injury, which is the the the focus of today. Um we really observed marked benefits of uh just simple application of the cells at the, at the lesion site um around the time of injury at the time of injury. This is again, this is a mouse model. It's an animal model. And what you're seeing here are cross sections through the brain of these animals. And we were measuring the lesion size. Uh and what we observed was that the, the overall lesion volume was reduced by about 40% when we treated with B cells as compared to other controls such as T cells or, or just saline. Um And the benefits were also that certain regions were protected and, and when you have, for example, hippocampal uh protection, uh it also can observe all the functional benefits that come with that neuroprotection. The advantage here with a unilateral injury to uh one side of the brain is that the animals recover very well. And you can administer a variety of behavioral uh assays and studies to really see whether whether um behavior and and function was, was uh also impacted and, and benefits from this treatment. Um And, and indeed what we saw in the animals that were treated with B cells that, that started at the same level with all the other injured animals. And these are sham lesions. These are not uh not, not really injured. Um The animals that were treated with B cells recovered extremely well recovered almost to an indistinguishable level from the shams. This is AAA test of um uh kind of sensory motor function where where the animals need to kind of hold their balance and walk on a on a rotating beam. Um Again, functional assays that uh test the, the um uh the, the, the functional uh the the function of areas that would be disrupted by the injury. So uh a series of other tests that you can administer. This is for example, a learning and memory test where we saw the exact same benefit with the B cell application, bringing the animals almost to um to sham levels to to noninjury. So it really uh functionally and structurally benefited um uh the the recovery after traumatic brain injury in this model. And this is just a summary of the various systems in which we our group, but also other groups have used uh mess so far, this is relatively a new concept. However, um there are several groups who used it in um in in pathology such as ischemic stroke. We have done the syp traumatic brain injury. We've done it also in, in skin uh lesions and, and also uh other groups in myocardial infarction. So really recovery after injury to uh the heart muscle and in every case, this is what gives us confidence. We there were benefits associated with just introducing these cells uh at the, at the, at the lesion site. So, of course, um we're asking, you know, we're having an effect, we're having, we're having the feno uh But um we're not knowing what the mechanisms are and we can have a discussion of how much we need to know before we apply it into clinic. Uh But of course, we as, as basic scientists, uh it's, it's the focus of our, of, of my lab, of my group, particularly to, to work out some of the mechanisms in in this. Um So, what we're able to do is to put these cells into the brains of animals directly into an injured or noninjured uh brain, retrieve them after some period of time and investigate in this case, using uh flow cytometry. So which, which uh characterizes each cell individually in terms of uh protein expression or surface markers. Um And, and ask what happens after, after a period of time in, in situ. Um And what we did observe was that there was a, there was a very interesting time dependent response of the exogenous B cells. So the donor B cells that were placed at the site of uh CC uh which is a type of traumatic brain injury that involves a uh direct cortical impact, a direct cortical uh contusion. So we're talking about moderate to severe traumatic brain injury, quite, quite uh serious uh lesion. And what we observed was that there was a time dependent um generation of a lot of cytokines and chemokines in these cells that started with um a variety of, of inflammatory and antiinflammatory cytokines. There was, there was a very, a very generalized activation of the cells which over time over about 10 days resolved into a more regenerative anti-inflammatory response where regulatory cells. So the, the concept of regulatory B cells or B RS um uh uh become the, these populations become dominant after some time. And this, this is a Disney plot of um multiple cytokine expression where, where you can see an overlay of all the uh subpopulations of B cells in this case, uh found at the injury site. And what you see in, in gray are cells that don't really respond. And the colored um uh areas indicate various cytokines. Each color being a, a marker or a cytokine. And what you see is that over time, there is almost like uh an initiation of activation until the entire population is really activated with a variety of cytokines being present while after 96 hours uh to, to um um basically 4 to 6 days. Um we have a resolution into populations that become much more regulatory. So the, the uh uh antiinflammatory cytokines such as IL 35 TGF beta, il 10 now dominate, which means there is a response and it's a regulatory response of these cells uh under the in injured environment conditions. And we've done a variety of investigations. I will show you ki kind of busy slides but I will, I will focus on certain aspects of them because we investigated uh no one by one asking questions as to what are the changes? What are the effects of B cell introduction into this environment? Do they change dynamics of infiltration? Do they change? What immune cells can infiltrate into the, into the area? And it turns out uh the answer is no, the the the uh injury or non injury is what dictates how much inflammation and how much inflammatory infiltrate we have in the in, in the brain. And the addition of B cells doesn't really change the numbers of cells that come in. However, if we think about the behavior, so the the phenotype, the functional phenotype of the cells that infiltrate, that is a different story. So although the same number of infiltrating cells come in when the B cells are present. And in this case, in all these grafts, um red indicates the control, which is the default uh the default injury response where just saline was administered as a control and the blue uh bars indicate the B cell treatments and in a variety of um inflammatory cytokines such as TNP, particularly TNF alpha and IL six. we're seeing a decrease in inflammatory cytokines when B cells were present. Uh but now not in, we're not talking about the B cells. We're talking about the infiltrating immune cells such as monocytes that turn into macrophages or neutrophils that infiltrate into the injury site. And the, the interestingly, it's not a unidirectional effect. It's, it's both that the inflammatory cytokines are reduced. And the anti-inflammatory pro regenerative or protective cytokines such as TGF beta or IL 10 are increased at the same time. So it's a very complex dynamic regulatory response and just to go in a bit more. Oh and, and there is of course, the microglia population that is the, the resident uh myeloid cell population of the brain uh is also reducing its activation when um when B cells are present. And this is of course, at at longer time points. And importantly, this effect of of reducing activation, immune activation, essentially neuroinflammation in the brain extended to what would be called chronic time points, which is two months post injury, which is very, very important. Uh uh for what we were talking initially about the development down the line of neurodegenerative uh uh conditions. So we're seeing a general modulation of myeloid populations by the presence of B cells. And I don't have the time to show you all the data that that went into this. But we really broke down those myeloid populations to understand which ones were the regular, the, the ones that responded to the B cell uh presence. Uh And we found that it's primarily the, the classical monocytes. Uh in this case, they're identified by the presence of a factor called B6 C. Um Those were the most responsive in, in the sense that they reflected this both reduction in proinflammatory and increase in anti-inflammatory factors only in response to the presence of these cells in, in the injury. So to summarize all that information, what we're seeing is that first of all the treatment with B cells. So addition of B cells at the injury site at the time of injury modulates the cellular microenvironment and doesn't change the numbers and the infiltration of immune cells. But it changes very much the cytokine response, the activation patterns and, and the responses of those cells as they infiltrate into the injury. And the main mediator of this immunomodulation appears to be a myeloid component, which is primarily the monocytes, mac macrophages, uh uh infiltrating at the acute stage of injury and microglia during the chronic stages. So our current model for how the B cells might be responding to the microenvironment. Again, all of these factors are in development. We are, we are going to keep on working and identifying more and more receptors and more and more effector pathways. I'm sure uh as, as we're looking deeper into this with the current mechanism. Um As a working model is that the B cells really undergo a phenomenon which we've coined uh praxis which is a response to injury. Um It by detecting uh uh molecules in the injured microenvironment, uh uh damage associated molecular patterns that are detected by TLR or toll like receptors uh on the surface of the cells. Um We've identified that these uh the my eight mediated toll like receptor pathways are essential to um result in the proper activation of the B cells and triggers the response from these cells. Uh um of production of, of both pro and antiinflammatory cytokines which then modulate other adjacent classes of immune uh uh cells and what we are, um we're, we're expecting and we're, we're um hypothesizing is that this really is a, an cascade. It's a tweak at the beginning of the sym then becomes self-sustaining. So the B cells don't need to um to persist in the microenvironment. And indeed, they, they disappear, they die in, in about two weeks after application. But the uh inflammatory regulatory cycle is, is self-sustaining with uh the immune cells at the, at the injury site. And uh another aspect of this is that we've looked at whether or not the monocytes and and and macrophages are necessary for this response. And we've depleted uh systemically circulating monocytes and macrophages using uh clodronate in this case. And when you do that, um you do the the clodronate depletion in animals before the injury and then you treat uh with B cells. What we observed is that in those animals that didn't have that many circulating and therefore infiltrating monocytes and macrophages, the protective uh effect of B cells was reduced greatly or abolished. Which means um uh in uh be cells would protect almost to the levels of sham uh the the injured animals. While if the um in in the clodronate disruption, where monocytes circulating monocytes are depleted, um be cells would not protect, provide this benefit. Uh And we've seen this in, in other paradigms as well. Um And which indicates that these, the, the presence of these apparently inflammatory cells is required in order to uh um in the B cell activation and regulatory phenotype switch that we are seeing. So, for example, 10, which is the classical cytokine um that, that is associated with regu regulation in immune cells. Um The, the when, when um when uh inflammatory macrophages were depleted, um the B cells that were locally present in the brain did not produce quite as much. And so, what we've really seen is this bidirectional um effect of an an inflammatory um milieu that that's triggered. Um and then subsequently triggers regulatory uh counter effect of the vessels that we're applying in situ. Um And this is really to summarize what I've just mentioned um that we have a time dependent and it's very, very important to the time dependent uh uh dynamics that you see in a lot of different systems. If you, if you look at, at a snapshot, you might not get the full picture. Um And what we're seeing is that B cell treatment really modulates the cellular microenvironment in a, in a very complex way. Um It's uh uh it, it's, it's primarily depending on the infiltrating myeloid uh uh monocyte macrophage cells. And it's a um it's, it's um interactive uh uh requirement that the inflammatory cells are coming in. The inflammatory microenvironment is generated in order to uh uh trigger the uh regulatory phenotype and consequent uh uh regulatory switch in the whole microenvironment. So, this is really um our updated model uh that, that the inflammation at the site of injury. Um yeah, uh uh attracts monocytes and macrophages into, into the injury site. Um And normally you'd have a lot of activation and an inflammatory phenotype initially in these cells that would produce a lot of inflammatory cytokines that would um enhance microglial activation. So you have a peripheral, as well as a central inflammatory response that facil uh that, that just promotes neurodegeneration over time. Whilst when exogenous B cells are present, they are able to modulate this initial step uh switch these regu these inflammatory monocytes into a much more regulatory phenotype and therefore create a more neuroprotective microenvironment. Again, this is only a, a partial, obviously not a complete uh protection. So, in the next next slide I just wanted to show you, you know, some, some of the next steps, these are, these are recently published uh studies. So you can look uh deeper into, that's why I didn't go too, too much into, into a lot of detail. Um But some of the next steps that we're uh looking at is really understanding what is going on at the molecular level. Now in the cells that we're introducing as well as in the cells of the microenvironment. And one of the methods that I just wanted to um to highlight is a spatial transcriptomics that's very much uh um kind of late. Uh the the latest in in the area that we are able to uh look at gene expression. Uh Now at a subcellular level uh with a with subcellular resolution and really see with, with up to in this case, depend depending on the method with various uh numbers of genes. But in this case, we were looking at over 300 uh gene expressions in in various cells. And you can identify clusters of cells. For example, here, we're seeing infiltrating cells that are present at the injury site in a whole section of the brain. Um And we're analyzing each one of these e each one of these dots that you're seeing here is uh a transcript. Uh And we're able to uh currently in, in practice, we're, we're uh going to do differential analysis in, in all of these um cells and uh seeing gene distribution, gene expression across the entire brain is extremely helpful because it really highlights uh uh genes and, and, and that are not affected too much by the injury and some that are affected. And, and really allows us to look at subsets of neurons of astrocytes of microglia, as well as the the infiltrating immune cells and seeing the the changes in gene expression there. Uh this is really just uh uh uh these are currently because we are in the active process of, of uh analyzing and, and generating data for this. So really to, to summarize um what we've seen is that B cell application as it's a, is a, is a viable therapy. It truly is a cell therapy. In this case, we're adding cells in numbers that are not physiological and in, in uh timelines that are not physiological, we're really manipulating the system to apply uh uh these cells at the injury sites. And we're seeing that it accelerates and improves healing both in, in wounds and also in the brain. Um And we're seeing complex regulation of the microenvironment of the injury by, by uh immunoregulatory pro regenerative cytokines. Um And, and we're hoping for these cascading uh neuroprotective effects down the line. But an important point I wanted to end with or uh kind of transition into sorry uh is that they are effective, they're safe because of they have a very limited lifespan as I was mentioning of about two weeks in situ. And they are quite accessible if you're thinking of how do you translate this into the clinic? This is a, this is a great investigation in a preclinical animal model. But does it have any hope of moving into clinic? Uh and it's in a, in a way it's very accessible because B cells can be isolated from peripheral blood. And in terms of what we're thinking uh uh for, for uh brain injury, but also for other applications uh is that we've, we've already uh implemented this whole system with a donor apheresis uh that gives you a concentrated um apheresis product from where you can isolate um in a clinical um uh GMP GLP facility, uh isolate pure B cells uh that then can be administered uh intravenously. Um And we have, in fact uh done in this, in the context of neurodegenerative disease in, in a s uh amyotrophic lateral sclerosis. Uh We've already uh uh done this in, in 22 patients to two people with a s uh with, with very good response and no, no detrimental effects that, that we've observed. Um And I just wanted to highlight the, the, the speed with which this could be done in, in one case where we've designed this, we've, we've conceptualized this, this based on all of these results in a variety of systems. We, we develop B cells as a concept for neurodegenerative disease. Uh We went to the FDA, which is a regulatory agency here for, for all new drugs uh in, in, in the US. And uh they required us to, to give some proof of, of safety and efficacy uh in animal models. We had, we, we, we designed the study, we got the approval for the animal mo uh model and, and study, we ran that over the summer of one year. And by the fall, late fall of the same year, we were able to administer uh uh f the first, the first infusion into a, to a patient. And I just wanted to, to mention this because this is really a tremendous kind of team effort and requires these kind of centers where you have, you have uh uh uh access to both the academic uh you know, all the, all the P hds and all the M DS basically working together in various departments. So we were here in the vaccine and immunotherapy working on preclinical data. I'm also in the Department of Neurology we were working with, with neurologists from our end interfacing with the FDA, with the I RP of the institution uh to, to get approval for all of this. Uh We were building capacities to, to do the GMP cell preparation with another institute in the area uh which is the, the Dana Cancer Institute um that, that prepares a lot of cell therapies including card um and going all the way to therapeutic administration So it's cross department, uh and obviously all of this feeds into data analysis and hopefully this, this will be a published soon. It's currently under under review and, and uh it should be, should be hopefully published soon. So with this, I think this was a, this was a large but it really uh highlights the fact that you can go from bench to bedside. In this particular case, it was under one year, but it was based on all of the preclinical scientific work that you've seen and, and some others that I haven't seen uh haven't shown. Um So with this, we're, we're up to time. So I would like to thank, first of all, my, my team of uh of extraordinary uh researchers and a lot of them are actually medical students from the UK. Uh And it's a, it's a great pleasure to, to be here also for that reason. Uh It's, it's really uh uh an, an extraordinary group that, that we have and extremely productive and, and extremely enthusiastic and I want you to thank them all, but really to highlight it's not just, it's uh our whole center, it's a Neuroscience Center is the Cancer, the, the Dana Harbor. And it's, it's really um uh uh a collab collaborative environment that allows this type of studies and research to happen. Uh And of course, uh uh the, the NIH for, for funding some of these, but there is also a quick component of philanthropic uh funding that goes into it. So, with this, I will and uh thank you all. Uh and I'll take any questions. Thank you. Perfect. Thank you so much, Doctor Soles. Um Does anyone have any questions? Questions? I don't see any questions in the chat. Um But thank you very much for such an informative talk um about the immunotherapies. Um And yes, thank you so much for coming. It's been great. Ok. Now I'm just going to hand it over to the rest of the team for um sharing the prizes. Uh Hi again. Um Thanks for that uh council and thanks to all the brilliant speakers, uh Doctor Sho and uh professor, uh it, it was a greatly amazing talks and uh we really hope everyone enjoyed it as much as we did on the other side. Uh Just as I say, the presentations were excellent, really high standard as well. Uh But unfortunately, we do have to um um pick um uh a winner. Um And so what I'll do is I will initially announce the raffle winners. Um So for those who joined um the five raffle winners are, I'm sorry for pronunciation guys. Um II, do apologize in advance. Um We've got Albert um Ria Krishni, Nalua and Jen uh Congress guys. Congrats for that. Um We'll be in touch um uh about these prizes. OK, via email. So do expect an email from us. Now again, for the oral presentations, it was really difficult. The scores were um quite close. And so I'd like to say that for first place. Um We've got Zenia. Um So, and second place oral presentation, we've got Gagan. Um So congrats to you both. And again, many thanks for those who uh did present the stand. And um otherwise guys, if, if there's any outstanding questions, feel free to uh post them in the chat. Otherwise, uh thanks everyone for attending. We really hope you enjoy uh enjoy today. There is a feedback form. Mih, do, do we have that? Uh Yes. So for those of you who are attending uh and who have stayed throughout, I will just send the feedback form to the chart and as soon as you leave this meeting as well, it will be sent to your email. Uh And as long as you fill out this feedback form, you will receive a certificate of attendance for this conference as well, which you can add to your portfolios. And thank you very much to everyone for coming. We really appreciate it. Thanks. Uh Thanks guys and thanks me, uh cancer has just posted the ques membership code. So feel free to copy that as well. Um And yeah, uh thanks all for attending. Thanks to the committee for such a great uh conference. Um Thanks all we'll hang about if there's any questions, but otherwise feel free to, to leave. Ok. We'll be in touch to those with prizes by you know, and so.