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Clinical Trials of Lactoferrin in the Newborn: Effects on Infection and the Gut Microbiome
Nicholas Embleton
Wednesday, Sept. 25, 2019 · 11:25 a.m. · 01h 06m 39s
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thank you for the the microphones need to be a little bit lower
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from a great so am thanks very much to plough and
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and that's how yeah and and and i for inviting me
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so i'm gonna talk a little bit about a large study that
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we were involved in running looking back to foreign in preterm infants
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uh uh but if you just go you should is i've had funding from government sources but also charities
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and most importantly my my main disclaimers i'm
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a condition uh and i'm not a basic scientist
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uh and the tool today is gonna come to some aspects of preterm ripping nutrition in general
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as soon the challenges we face but to keep focusing on neck
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and sepsis some most of what i'm talking about is relevant preterm babies
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and and then talk a bit about lacked affair and um why we chose to start to get at
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the launch trial date and then touch on some of the mechanistic worked we still can working through the minutes
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and the more the quick question someone's poses how difficult
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can it be to the high quality nutritional a study
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and for us is conditioned the fear use amazing of the last few days
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uh what we want to know is how much of this is gonna change what we do
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when we go back to the naked and and this is the feeling depression anxiety robin feeding since i've been here i came critical
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constant uh that i knew what i was talking about but uh
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as i listen to several uh decades or centuries of research expertise
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i started to get increasingly worried um but was comforted by uh going stealing pick state in the other day
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that could be channel so just look ahead speak frankly and act boldly so
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that's what i'm gonna try and do for the next forty five minutes or so
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and his mike receive a of not won any awards
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i'm got any metals i'm got any on is in anything
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but i have looked after about two thousand papers less than a key like so that's my credential
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and so here we are this is set when you costly is in the north of england
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uh and we have three nick usenet big population air about three and a half million
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yeah with the largest unit uh we except all the babies in fall
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complex it real the people might some cases and i've mccain usable with us
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so reckon complex mix of baby is so beautiful city built
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on the banks of the river tying up the lovely pauper hell's
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and it would be impossible for me to come here and give
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a talk without uh discussing breaks it uh yeah we we do
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agree we would like to move from where we are but i'll propose is that we just move a little bit for the self
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uh what weather is considered back to uh than it is new console most the time
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a little bit about the colour we searched we were gonna collaborative group of technicians and scientists that
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if we we can i just people to connect yep the law sort of ten years or so
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a lot of our work has focused on the market by mum recently on the trampoline but we're also doing some parliament work
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uh chris due to start a lot of our work is the
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lot and enjoyed model in collaboration with china twos in the audience here
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where we retrieve a at some tissue at cities uh papers you go
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for next originally we get permission to take a little bit respected tissue
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and grow so uh do you know it's from stem cells in the lab and that hopefully
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will provide us with the probably appropriate model for testing some these interventions in the coming years
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so settle work is really focused on neck but we do have some long
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term follow up studies looking at the consequences of that a lot of growth
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on by the metabolic outcomes instant resistance and these things
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um and importantly we have a great north in a two by bank of which uh janet is the director
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um and in this we have an amazing number of samples from probably up the files and papers now
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at most of these cells to learn you in some polls we've already set up a system
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to retrieve salvaged lot so when you take a blood sample you send it all happens a little bit of
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each yeah you'll soon after they put the uh at the lab con
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you put it in the freezer for us so we can go back
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because of course looking of the five hundred gram papers it's simply not
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possible to go around taking blood from these papers one if you want
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and and in addition to all those uh samples we also have some
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samples of breast no contractual secretions and that's really what we're trying to do
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and we've also been involved in setting up some pretty big studies of the last few years
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uh the feeding trial this is two thousand eight hundred babies uh hopefully that'll
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be a available in the next few weeks it's coming at the new england journal
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the lack french while elfin that we'll talk about a mechanistic
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study mac high which was next to put in the elfin trial
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uh but we've also been involved in the trial of come exclusive you multiply from the point collector
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so just to kind of set the scene for those of you who
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are not and it's all just just to just kind of give you the
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perspective how difficult it is to feed these papers and just you know to
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show you what the new requirements on a anybody know who this guy is here
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any colombians in the audience at this is e. camp and i'll uh who won the tool
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fronts this year uh these guys cycle up
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and down mountains six or seven hours a day
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and then they do it the next day and the next thing they do this for three weeks at a time
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and doing this a period they consume somewhere in the
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order of seven files and could the calories a day
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yeah the still anyway about sixty or seventy kilos and just imagine how wonderful it would be
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consumes seven thousand calories a day of all this wonderful fruit uh but still be is
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then is that so that's what he needs in terms of energy expenditure to cycle down mountains
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compared to that up babies on that in a to unit probably require
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an energy intake of one about one twenty to one particular cry was today
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therefore our paper is required twenty to thirty percent more energy
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than the most energy consuming activity known to man quite incredible really
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and out of all of the energy expenditure new live about two thirds of that is consumed by the brains are
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quite easy to understand if we don't need mac region ten takes what babies may turn out with them some problems
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that's energy not just the shape proteins so twenty four
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twenty five we could probably require some read about four grams
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i keep about day to show you what that would mean you go
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is all from may require eating about fifteen beef but is it that way
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i mean can you imagine how upholding that would be but that just shows you how incredibly hind huge
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requirements on preterm babies and up the challenges that we face both in terms of giving birth branch nutrition
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but also mention attrition and how we deal out without them getting any scene actress inch white is all sepsis
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and and of course the most important outcome pass is long
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term come to power come the worst outcome for preterm baby
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is impaired your developmental function and humans is you know quite different from most other
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primates most primates have the wrap your brain
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growth prior to turn the ball relatively mature
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rest the humans we know that the rapid pure bring what happens in the
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third trimester and the first few months off the life of that term tight
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the between about twenty four weeks in to use of h.
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we acquire about ninety percent of our final addled brain volume
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and when we thinking about preterm babies
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say developmental a motor cocked approximately very important
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to say but also an interest in these aspects of a metabolism lights alive
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and lots of colour challenges we face but you the full of for the kind of freaky mobility is
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uh at the probably gonna be affected by nutritional intake since some level so but not the premature to
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lung disease to particular next tries into clients' isn't sepsis which is what we're focusing on and these two today
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again just to show you how far we've come this is data from our unit type the law sort of fifteen twenty years also
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and what you can see is that because there's a lot of colour popping
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around because we didn't have so many twenty three we babies twenty years ago
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all we see is that it every just station had just
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actually h. of the last uh fifteen years we've got better
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so so vibrant twenty three twenty four twenty five twenty six it's
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getting better and just taken out here today now unit twenty three weeks
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our survival on this means surviving to going hyman being alive at
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twelve months of age is now new would've sixty or seventy percent
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that's incredible compared to what we were uh maybe twenty years ago
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and we could spend a lotta time talking about why we've got data we actually haven't had any new medicines
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we've got the same surfactant same antibiotics the same still it's if we
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do better and more the key facts is an ability to work together
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both in a sing team but also the positions in the shared combined
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experience and knowledge is really what's make a difference here rob the single intervention
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when you think about these twenty or thirty percent of twenty three because you don't survive the twenty four we could is
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we now know that off the first few days of life the most common reason for prototype to die
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is due to lack consensus both of these key
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diseases a clearly closely related to any traditional feeding purchases
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so here is what you see in is that better nutrition on tacitly as like to improve survival
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and this is a problem of global weapons because you know i read about twenty million pay visible
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only the low birth weight will premature ever yes this is relevant to every country and every continent
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but as a vibe improves we face with the challenges of looking after increasingly
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complex papers papers you may have had neck and had surgery now have sure got
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so this is a certain relationship is we get better nutrition we need
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to do the the name wall to low cost the complexity that we face
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with a lot about breast milk i am and is is i'm not talking about that specifically today
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but clearly breast milk is the most cost effective intervention in the whole of inequality
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however much we think robotics or we don't think robotics work
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brass smoke from the market will always be better than prior baltics
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there's a lot of evidence that improves maturation of the brain improves maturation immune system
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but most importantly results and but according to from but probably count comes over the entire life of course
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so we're not a questioning the benefit of breast no clearly
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is as we've had lots of talks the question really focuses
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what can we learn from breast milk that man hours to improve nutrition and in these pages
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and this is my kind of simplified scheme of nutrition that i've been kind of trying
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to sort of think and and um and develop i guess of the last few years
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because to me nutritionist more than you change people get very bogged down in
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the in a two units about grams of protein or micrograms of this and that
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but really new agency just one part of what i consider the nutritional package
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so you just acadia mike can you change my can you can see section the pen as we could in
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some great talks today and yesterday the ball the functional
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components the h. m. o.'s the growth factors the enzymes
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but then also the interactions with microbe environment and
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the got micro prior to that with very interested in
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and then i would have the fourth components is the kind of technical say say papal aspects of feeding
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right breast feeding the impact of choose sensory experiences taste all these things are these
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the full components i think that we need to consider when we talk about nutrition interventions
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this is a picture of um how person who is say twenty three
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week so miking baby per exactly his brother died a few weeks of age
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uh i'm sitting content with his family his mom who's now a is all is an amazing little boy
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as you can see here members doing the right thing to do is any
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weighing about one half kilos and still he's actually trying to breastfeed before discharge
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so houses mom was completely committed to breastfeeding
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she hated expressing she said it made to feel like a cow haven't
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gotten that room eight times a day in express should enjoy any of it
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but you said she did it because she was convinced that it was best to
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have baby is very important message to us in terms of how we support encouragement
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but i'll be honest when i started doing nutrition research um maybe twenty
00:13:36
five years going now what i was doing studies of different amounts of protein
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i kinda just brought about a formula as being something that was effectively fluid nutrients
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you to put into this long tube uh which is
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got i see everywhere in the front row looking a disappointed
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have no idea of all the importance of because they know the g. but is what i thought they just to put in there
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and the and you produce displays product and effectively that's sort of nutrition isn't it
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just work at how much you gonna to pain and how much you're going to absorb
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and of course we've all learned a lot about twenty years is that it's much more complex than that
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they're all these relationships wouldn't have lights but also interactions with the immune system
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the and consistent and you microbes and so we've had to shift of thinking
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from thank you pressed knock the food to being a biochemical fluid that
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is allowing the mother in some way to perhaps signal to have baby
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but but this quick slide in here just remind all of us that are that we think about approaching a breast milk is being the
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kind of case in the weight fraction there are lots of different case
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in uh components propriety n. x. that is of no shire in that
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even breast milk has peptides that the some digestive of uh of protein intake got
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um so we have probably chases there but then of course you have to have anti pretty aces to stop break it all down
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and i think this just reminds us that one with talking about protein peptide fractions
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to understand complex your protein digestion and really how little we know him preterm infants
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and again this is like a simplified schema this is uh in a protein digestion one o. one for
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medical students or for a lot of us as nato just because we don't get to all this very well
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at the pretend babies very different they tend not to have the lower levels of the city that you haven't adults
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and so the do the rules approach chases expressed on the
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branch broader and lots of happy days is in the bacteria
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um and then when you finally get to the bottom and the right under ropes that are gonna from and the bacteria
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we we know that she nothing about they simply template is that
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when we come back to talking about protein and high up to select
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a fair and and how like to foreign maybe fleet interactive areas
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and we really don't know what's happening i'm in preterm babies very well
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and so that we start off with these complex protein structures bit by bit is you get on the tract
00:16:09
the protein is teenagers and switched into a party at the peptides amino
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acids to say we don't know in preterm babies very much about this
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so say we understand a different colour protein fractions case in some ways in the
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way component vertically compiler contains lots of a protein stuff like to when lex fair and
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we need to sort of stand back and uh be impressed by the complex if you don't know
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and how this whole protein wait dominated milk taking claw strum
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provides this ideal pilots amino acids that optimise bring the metabolic outcomes
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so it's hard drive proteins and peptides to occur and actually possess say these key steps
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we never talked about what we suspected got micro bites are gonna be very important
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and then it fell review here in the audience how complex
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the got micro white artifact we should really think about cells
00:17:08
as a c. put organism with all these back to being involved in lots of different metabolic an immune process yes
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but we need to understand human development would be impossible without these microbes
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so if we didn't have these microbes we would be able to digest foods in the way we do
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and is maybe no uh these when a when a half kilos if you happen more now
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so again which will take some comfort the old extra through be great note the last three days when
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you buy yourself and you get home tomorrow you can subtract one half kilos because it's not really you
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and we're here because we know that because the image of of life and that's uh say is the focus of our research
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it was a nice paper came back to be escape
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talking about human and evolution in the context of microbial world
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as if this is some sort of struggle i like a kind of talk of war when the
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one hand we have to learn to manage the
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beneficial microbes but then exclude the pathogens no harmful microbes
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and if you think about that that kind of challenge is very cute and pretend baby
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where the baby has to work out which bacteria and which other engines
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you should become tolerant to which ones you should elicit an inflammatory response
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and if you think about uh twenty four we baby who is supposed to be new trouble swallowing um your stick fluid
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how on earth does the preterm baby no that the befuddled is gonna be the good guys
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and the eco that's gonna be the bad guy says have no memory no teaching to do this
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so it's very easy to understand why can't micro
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prime development in britain base is gonna be so complex
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and you will know that the pattern of bacteria change a polite cool so what is kind
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of optimal for new pump a this is very different held a lot of the remote older
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um major impacts as we heard from sammy talking
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about when you would use breastfeeding and how that interacts
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with you mike why i'm so we've learned quite a lot about how this changes that that might cause
00:19:08
but we really don't know what should be helping pretend they've been if
00:19:12
you kind of extrapolated this croft backwards one of should these patterns look like
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because we have no mortal of healthy preterm baby by definition every
00:19:23
pretend babies unhealthy we simply shouldn't be nature didn't tables look after them
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so trying to work out what microbial community structure
00:19:33
is op when the pretend baby is incredibly difficult
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so if a lot about the interaction with that because usually mean system
00:19:44
between your bacteria to tend to take cells that we chant and some of these cells some prime
00:19:49
uh and and in part with the t. regulate two cells and how this impacts but the systemic means system
00:19:56
and when it comes talking about like to fair and we put start putting some extracts apparently got
00:20:01
just think about all the different ways in which that might act so it may
00:20:05
act as a few to certain bacteria some data showing maybe probe article certain different ways
00:20:12
it may uh prevent the growth of other uh uh back
00:20:16
to optically those around on as a source because it binds line
00:20:20
but there's also data shaded interacts with the fact that the d. n. interactivity regulate three
00:20:26
cell development so lots of different mechanisms by which like to for might be working their babies
00:20:33
and then like most talking about the clinical trials and thinking
00:20:36
about sepsis and you know all of our babies we suspect that
00:20:41
had the quite negative stuff infections that may
00:20:44
be associated with tractor to so on the skin
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um this slight difference somehow got to do something getting through all this system
00:20:54
if we really believe that like to for an is gonna stop a skin infection in our babies
00:21:02
so this is my simplified schema for clinicians uh just to
00:21:06
try and sort understand that we're talking about got micro pliable
00:21:10
communities sleazy commuters bacteria and this is continually interaction with new jeans
00:21:16
and they got an old when it happened like that that producing
00:21:21
no no lots and lots of steps before you then get to the stools so
00:21:26
whilst we do a lot of our work by sampling stool collected from a diaper
00:21:32
really all this interaction is happening way up high when they got
00:21:37
we simply don't have methods to us two weeks little what's happening to market by i'm open the temple i'm
00:21:44
taking the timeline them where most of the neck disease seems to occur
00:21:49
so by the time these bacterial metropolis of got down here they're likely to be very different
00:21:55
doesn't mean that we can't use this but we have to appreciate how restricted beyond studying
00:22:00
uh where we are so say welcome to far far away place this bit here is
00:22:07
in microbial terms a million miles from what's happening in the already
00:22:13
so we know that the lots of different at times three components the
00:22:18
likely to impact on caught my critique ecology septic you the h. m. o.
00:22:22
is but probably just every you shouldn't do you study will have some impact
00:22:27
on got microbial communities this is very different between brass benetton bottle fed babies
00:22:34
but then in turn all these microbes producing other key compounds we've heard
00:22:38
a lot about short chain fatty acids and have these may prime immune system
00:22:43
we know that some bacteria produce amino acids that we then may absorb lots of bile
00:22:48
acid synthesis is associates because microsoft production code
00:22:52
even some key bits means dependent on microbes
00:22:56
but also a massive for re event
00:22:58
simpler inflammatory uh mediate citizens sickening molecules
00:23:03
so this is unbelievably complex um i don't know why you humble clinician like me is going to
00:23:10
unravel what is happening athletically because we can't get the bits that we need to to get to
00:23:17
and we haven't talked a lot about it in the symposium this time around but
00:23:21
was trying to understand the importance the got
00:23:25
brain access this kind of bi directional biochemical
00:23:29
sickening partway lots of different sort of routes that connects to got to the brain
00:23:37
and as i say when we thinking about uh maybe like to friend also these compounds
00:23:41
thinking about the peptides that made them sell some activity in the bright
00:23:47
a little bit sceptical but how relevant this is in preterm babies
00:23:51
a bit pity there's been a lot of work in in adults linking
00:23:56
while patent bellhop it to certain diseases for example uh
00:24:00
people to develop parkinson's disease turn out to have a
00:24:04
history of constipation those present years before they developed the
00:24:08
symptoms of parkinson's so some really fascinating relationships to explore
00:24:13
and it's possibly to than the preterm babies some aspects of my tele t. may be part of
00:24:18
this part way um but the say we really don't have much work on this at the minute
00:24:24
so this is the normal colour process uh an in health ten babies
00:24:29
the c. g. microchips in jeans essential these components
00:24:34
use post come are covered in the turtle secretions
00:24:37
swear like this phrase the seats breast milk feats
00:24:41
that's what nature intended you're supposed to do these things
00:24:44
and they used to scare hyman gets my ex just seating from the environment around you
00:24:50
when you contrast that to pretend baby nothing about uh
00:24:53
pretend babies anything like what it is for to a baby
00:24:57
of mobile by c. section that put in clean plastic
00:25:01
incubators we wash and scrap and our whole joe hands
00:25:04
just imagine what bacteria can survive that whole process the column is the baby
00:25:11
then we stick needles through the skin we put bits of plastic they can
00:25:15
all be columnist we feed them with very abnormal regimes in the breast milk
00:25:21
isn't producer normal way comes into contact plastic and is tool before it hits the baby
00:25:26
then if you don't know what to you you give all these horrible uh h. two blockers and then they get lots of antibiotics
00:25:33
so it comes as no surprise that the preterm workable i'm is completely different to turn baby
00:25:40
so we've had this sort of dark comedy before that and there's this continue
00:25:45
interaction between these three components been the microbes the new jeans the immune system
00:25:49
um what's optimal the begin even live goals is different from also
00:25:53
but the end and we can think of neck in very simplistic
00:25:57
fashion as being a break down between these three components so some it may be more immune driven something
00:26:05
might be more microbial someone might be more you should but somehow there's a break them between these different elements
00:26:12
and we talked a lot about evolution and a lot of good great talk
00:26:17
um i mean it is absent fasting to think you know how breast milk people the level says
00:26:22
and this uh russian dubs and see nothing about you makes any sense except in the context evolution
00:26:28
what about preterm babies because preterm babies
00:26:31
have no pressure on evolutionary and effects
00:26:38
and we have joe do that you know two weeks see these changes before papers get next week
00:26:45
move into a more current this file to looking prattle double already quite sure how
00:26:50
to find the despotic pattern what we don't know is it the microbes causing the information
00:26:56
while the microbes just a consequence of the information is it
00:26:59
you should strike the information which should drive the changes in microbiology
00:27:04
so you really can't come pick this but we do know that the signal them in the microphone to to be had
00:27:10
next to save the most important thing that's because neck in channel to hails
00:27:16
a more children than all of channel to be keen yeah lymphoma put together
00:27:21
so if a lot of people this is just seeing all this is just a problem that
00:27:24
happens in preterm babies on and make you let's like we don't need to invest time in it
00:27:29
but you more like his channel to be the pretend baby dies neck but all of these uh
00:27:35
complex some cortical problems we think about the major
00:27:39
advances thing gotten the treatments and success these things
00:27:43
when you think back neck really our treatment hasn't changed in the last twenty years we
00:27:48
know better at predicting it we might be a little bit better prevented in some babies
00:27:53
we're looking up to more babies you survive precarious increase the portable paper is uh uh last year
00:28:00
we have our first surviving baby you wait any about three hundred and fifty grams
00:28:05
i'm not suggesting that's gonna be a common occurrence but somehow almost magically
00:28:11
we managed to feed that baby without him getting neck and he's now you're old and quite healthy
00:28:16
so this is increased mechanic complex for us we're looking up to lots of papers of the city
00:28:23
and i will be the third person to show noise spec uh in the talk today
00:28:28
uh which is thinking that neck is really just me the tip of the iceberg of got have a looking
00:28:35
below it all these other factors that relate to got
00:28:39
how often outcomes iteration of p. n. x. politics in cognition
00:28:44
so i like to think of the spectrum of got
00:28:47
health rather than a discrete yes no t. v. have neck
00:28:51
i think if we just go for yes no approach we could you do some of the
00:28:56
uh softball team what we're talking about because it's possible that lex brenda facts all these outcomes
00:29:02
so we use this horrible kind of his logical to neck tries in school it's it's really
00:29:06
for technical syndrome neck is not a single disease the end result of lots of different pathologies
00:29:12
lots of different chemicals to factors we never understand
00:29:15
the etiology and individual case treatment is specific concrete
00:29:19
see here this is the baby with practical to got to stephanie got neck
00:29:24
he is completely healthy baby what point along that line to be choose to say this baby now has neck
00:29:30
and if we can't be sure about where you want that i haven't uh to do studies tom pick it
00:29:37
so those of you who to nations the audience we can have great fun i've
00:29:40
a lounge arguing over which of these x. rays conclusively shows the baby has neck
00:29:46
which one doesn't uh if i told you that that you have
00:29:50
one point four males of this code aspirant would that change your opinion
00:29:54
all point five of battle really top point five but we love looking
00:29:58
at these things on the net two units no shade a few ballets
00:30:02
some of it to stand did some might have a little bit of amber like flat
00:30:07
people work together this is how we make anti racism in unit to
00:30:11
unit it's really pretty crude involves using a lot of the signal is
00:30:17
and things are very different between units so your approached how readily you will
00:30:22
stop feeds all start antibiotics request an x. ray would change impact on your instance
00:30:29
uh we know that there's variation in the rates of papers you get sent to
00:30:33
surgery so if your diagnosis usage connect the two fold difference between units in countries
00:30:40
how good is your histology g. really check this out you see shoulder that was a perforation
00:30:47
perhaps it was an isolated perforation we get a second repaired tonight's us and you miss it for twenty four hours
00:30:53
and then it looks like nick how do we work out with this was a perforation on like to start off with
00:30:58
and if you don't review we don't have high postmortem right see the independently reviewed these things how can
00:31:03
you be sure really what we're talking about this is a massive chimes face to set you need by markets
00:31:11
so read up to new castle uh as i say we've been working on this uh optically
00:31:16
uh chris stewart is little all the studies with with that janet myself for the last few years
00:31:22
uh i i could show you lots of pretty pictures as well so stop
00:31:26
it because we we found twelve twins or triplets we looked still might require
00:31:31
um what we were impressed by was how closely siblings cost of with each other
00:31:38
and maybe that's not surprising these babies in defining pages that being touched
00:31:42
by different this is some having antibiotics someone not that much you quite similar
00:31:48
so presumably the breast milk exposes maybe some genetic aspects really are
00:31:53
quite important of this somebody come back to twins a little bit
00:31:58
uh yeah we were also able to look at the micro prime and unsure how closely
00:32:02
the press now marked by maps this to my combined some display this again
00:32:07
as we said we know that breast no is a key driver of this
00:32:12
what will still be able to do is say with with janet sort of painstaking collection of stool samples
00:32:18
if you want a stool sample for preterm baby case speak to generate she's looks we got hundreds of thousands of them
00:32:24
but we can really look at the the button type the times he would twins were wanting gets neck and the other doesn't
00:32:30
the red one that doesn't get neck in the blue one doesn't this is shannon type testy
00:32:34
and you can see that maybe just a few days prides nectar
00:32:38
is low typist as you might expect in the bait with that
00:32:41
but if you go back a little bit the idea to really wasn't any
00:32:44
difference somehow in the to be predictive which of those was gonna get neck
00:32:49
we then also able to look at the differences in text and show how things changed
00:32:54
the baby pride to neck where you go all out you know increasing claps yeah that that's not surprising
00:33:00
but then one day he get he we has more you coronado
00:33:03
something else so it's just so difficult individuals predict what's going on
00:33:08
but also located these what we put the antibiotics and the
00:33:11
baby at energy and and then through talks marks gent these things
00:33:17
these antibiotics don't have the big impact my combined you might expect the they're
00:33:21
important but we're not able to really manipulate marked by as much as we think
00:33:27
oh so this was a great paper from where chris looking at forty babies with lots of
00:33:32
love it you know some people sums gonna show you how chaotic the mike my name is
00:33:37
so the bottom these dashed lines these the cool oh to use these
00:33:41
we the caps the others recur lies wrench caucuses in the top of the
00:33:44
stack like once the one three much lower density is things like the
00:33:48
food is so his one baby just an example just gonna get your and
00:33:54
uh i've days one two three four five six seven eight of wife so yes stuff or is it is it is then
00:34:01
it comes back again you can rely everything in the baby this
00:34:05
point times the curling goes way again if a dial up down
00:34:10
so completely random this baby every period of a few days
00:34:15
and then this is what it looks like in forty babies to just stand back and look at that
00:34:19
and just look how different and how chaotic it is one that we gained from raffle what's going on here
00:34:27
and uh maybe two three four is this one here how the percent
00:34:32
of everything that baby's got for five days per it was perhaps yellow
00:34:37
like i wouldn't like that to be my got but he was that to be fine
00:34:41
so yeah i think the key message small this is that this is completely chaotic
00:34:47
and and every babies unique and and working at the disease what is impossible
00:34:52
so his heat map where uh chris apply some clubs
00:34:56
assists statistics to break them down it different community types
00:35:00
and on the computer model a recommended that would have six different community types
00:35:06
uh one is dominated by pepsi uh that uh to backed epsilon scroll 'cause
00:35:10
except except for like six is the anyone with this substantial number of different eyes
00:35:17
and so each each of these i think but i am sample c. n. s. we have six
00:35:21
community types so if you hold the six committee types in your head this is what we did next
00:35:27
so we replace each those committee tights file that will talk to colour for
00:35:31
the next cross off and this is what it looks like these will control babies
00:35:36
these the net cases in these sepsis cases and you can see that each
00:35:39
day we have a sample we put them into one of those six different types
00:35:44
and what you see is that a the or maybe not surprisingly the less staff dominating the infant got
00:35:51
and that as time goes on you start seeing will be for the remote like
00:35:54
this appearance is what we're we were able to see was in the babysit got neck
00:36:00
they have many many more transitions that will move between the acme types
00:36:05
much more frequently than at the controls appear to be a bit more stable
00:36:10
so this was significant of calls holder statistics than this you can take the punches
00:36:15
so but we do believe this something about the chaos that's going on those babies got
00:36:20
that might be associated with that rather than just specific types of a texan
00:36:25
um i don't know if if that paying attention it that there's an animation here if you can click on it i haven't got a a clicker
00:36:33
and that shows a baby moving between the different media types
00:36:39
concern us like uh yeah the should be bought the bottom where you can actually move yeah so yeah so
00:36:43
this is a baby moving around before you get snack in red and then coming green is a baby who's healthy
00:36:49
and what you see in the baby with neck is that he's moving all over
00:36:53
the place before it gets neck where is the baby stays healthy kind of moose
00:36:59
to one kind of committee type and then just kind of
00:37:02
keeps around there so that's a bit stylised because we'll see chose
00:37:06
to examples that that make the point but i think there
00:37:09
is something here about the kind of chaos there's associated with nick
00:37:15
so say next a major challenge uh we've learned a lot but we still don't know how to prevent it
00:37:21
mechanistic understanding is really very limited the animal models is joe was point yesterday
00:37:27
i think a very very limited have a papers and of course we have lots of good practical challenges
00:37:33
the fear of neck dominates decision making the same should think of neck is being one end of the spectrum
00:37:39
so the question is does like to fair in would you said i'm or if you wanna about like
00:37:44
to fair in this important times microbial whey protein
00:37:48
presents in los trim breast milk tea is alive uh
00:37:51
in the presence of ass asked it is converted and select various in which again has
00:37:57
anti microbial antiviral activity does this happen in the present day the same way we don't know
00:38:04
uh we know the concentrations of vertically high in cross
00:38:07
trim we know that all mammals express like to foreign
00:38:11
and again uh reading what's the papers from a professor of the dial when his greed
00:38:17
understanding how these proteins existed before we we even mammals that that how you
00:38:23
find like to for any blooms is just amazing how this protein has persisted
00:38:28
and uh there are hundreds literally thousands of papers showing different
00:38:34
activities impacts of like to from which i'm not gonna go through
00:38:38
but you can just take it that studies of shared
00:38:41
impacts on microbes viruses phone go i didn't for development
00:38:47
lots of reasons this may be important in preterm babies los four
00:38:51
babies get point films on the cafeterias and liked friend may prevent this
00:38:56
events that he should disrupt spirits protein so lots lots of the we don't know wouldn't get poked and today
00:39:03
so say we agree that from from the you're a mother is probably the best source but these babies
00:39:08
get really write the amounts of looking the first few days a lot of moms they provide sufficient no
00:39:14
she will be complex friend is available the reason challenges with
00:39:18
the study is but it's like it to be very expensive
00:39:21
so what about using bovine like to for and widely available probably pretty cheap
00:39:27
similar in structure uh but is it similar enough so what the the cocker matter now
00:39:33
it's such a on uh what the lights from would be a good thing for preterm babies
00:39:39
so this uh it came out a couple years go to these all the troll
00:39:43
simply time babe is looking at the impact of lex for norm sepsis and they
00:39:48
and what you see is that in six trials uh you have
00:39:52
a significant reduction steps is in four trials a significant reduction in neck
00:39:58
uh so this look like a very promising uh uh intervention for us
00:40:03
to try uh just like also the this is the bomb place yeah
00:40:09
uh it's in the shape and study at was also significant parts of this
00:40:13
is sort of an ever printed all type or something we need to correct
00:40:18
anyhow a lot of data that suggesting this could be a grey intervention from papers
00:40:24
so what are the challenges will the trials on the power it's i think they're all issues about pointing masking
00:40:30
um and as will come onto this also quality of lights bram may differ between these trials
00:40:36
to be clearly felt to be justified in trying to put together a launch well how a trial
00:40:42
if like to fair in that was like it to be very save like the cheap really does
00:40:47
reduce neck of sepsis even if any would uses it by small amount what wonderful intervention we could have
00:40:55
uh this is a unit this is what an innate so you know
00:40:59
looks like is unbelievably complex a lot of technology a lot of equipment
00:41:06
very sick babies very stressed uh haven't
00:41:10
introduced clinical trials in setting is incredibly challenging
00:41:14
and um we still the ending we've been doing these trials for twenty years now
00:41:19
um but learning trials in this environment is uh is saying gonna be challenging
00:41:25
so how you could go to trial we need to make sure the oscar question that your
00:41:30
uses your parents topic things important gotta choose a great intervention could work at
00:41:36
how much the intervention to give them for how long and um which population
00:41:41
then you really short you choose a robust outcome that's really meaningful
00:41:46
uh we wouldn't get funding to do a big try like this without having it's ninety
00:41:50
percent confident they'd send the phones does would tell you to go away at that price
00:41:56
and and then when we get to get funding we can
00:41:58
pass if with the adults i'm doing huge trials of cardiovascular disease
00:42:04
uh so what about trial start well an about fifteen years ago
00:42:08
we put together motes is pretty group of nato just dietitian as we
00:42:13
forty two thousand three me two three times a year with online twenty organisational completely independent
00:42:20
and this is our meeting in two thousand night i say we
00:42:23
just technicians none of us have any academic time in our contracts and
00:42:29
and eh hey the six was he would've had the members from two thousand three and
00:42:35
then everybody else starts to come up come along with this it's like a good idea
00:42:39
and then they'll hissing uh back here at this great idea we should you try to something called like to for
00:42:46
i this amazing idea that we should you try the idea like feeding in the interface
00:42:50
i was so what it's about but i really just products imported a trial that was cool health and um
00:42:57
bill came along and decided that he would actually take the lectern on and
00:43:00
he stole the acronym from eight to being an intro back to fairly neon lights
00:43:06
uh so not only did he take my acronym he decided to
00:43:09
the trial john here decided to do this trial courts something different
00:43:14
uh i know is left to literally pick up the shit after that chose not they want to do
00:43:21
as the question was does supplemental by evan expanded preterm infants lesson thirty two weeks that
00:43:27
i was compared to placebo to secret is reduced sepsis some had a program glass case definition
00:43:34
this is the time line this is just to show you
00:43:37
scientists how hard it is to get one decent paper ow
00:43:42
two thousand line sounds like a good idea let's put an application in the save guys when yeah
00:43:47
this is a good idea as well paper application a bit later we were working both these together
00:43:54
then you're gonna get funding then the first supply racked friend pulled out then we have to
00:43:59
work at what to see but enhanced get approvals that we're already into two thousand twelve here
00:44:05
so tame the product design the trial was really complex uh
00:44:09
you see janet here sitting there laughing i'm at our ability
00:44:14
to try worker outlined it because some of these things here like to friends some of these things here we should go
00:44:20
so i thought we played over again now uh to see what you think we got the blinding right here you can see is playing around but lots of
00:44:27
stuff on a desk in a summary so uh at number one here who
00:44:33
thinks that's like to friend who thinks that's should go and stuff like to foreign
00:44:41
yeah that's cheating okay so this was like the fat
00:44:48
this one yeah like different or should or
00:44:53
the comment that suffered what'll uh this one yeah
00:44:59
it's gonna it's gonna be sure doesn't that this one yeah
00:45:04
this one yeah
00:45:09
a different this one yeah i know i know k. yeah i am i
00:45:19
am when people came in source of this table with all these different powders
00:45:23
uh i started taking photos we were worried that by the bill was gonna turn into
00:45:28
uh oh colombian friend here okay it was nice to die licensed for use in preterm babies
00:45:36
so we went with passing brown should win the angus at least it was different from um uh
00:45:42
from some sort of white should yeah like to friends nothing like multi text which is a powder
00:45:47
so we tried really hard we had a lot of quality control assurance ever
00:45:52
products a lot of complex is with your pinball we used a product from you
00:45:56
see then that we had to imported in the first time a big bag
00:45:59
of white powder arrived it was sent back because they weren't sure what it was
00:46:04
uh we always need to make sure it was like to fair and so we know it was definitely back to fair and and but
00:46:11
as as um uh uh we can discuss like we only know expect from we don't know about the
00:46:18
a fire activity we we knew a lot about i'm bindings of course very important that
00:46:22
we have a product that was not a two unsaturated uh a lot of code control about
00:46:29
an uh how long that would be stable full you know twelve months eighteen months
00:46:36
and we put news even because they've not had any these nasty viruses
00:46:40
we have to make sure it wasn't contaminated metals you commit mobile babies
00:46:46
then when we finally got the stuff and of course if you shape to
00:46:49
dissolve it you realise it faults because it's a protein where should it doesn't prof
00:46:55
so then we realised if we put a little bit of war to uh with
00:46:58
the lights parent plus one male of the mother's milk and then you shake it both
00:47:02
at the placebo and the lights parent a fraught thankless step for thirty minutes was double
00:47:08
does it is but i liked the premise that a little bit different coloured not surprisingly
00:47:15
and but we had these purpose ranges that provide a little bit of masking as well so this was alright short prayer
00:47:20
we print these parts with empress stock on the plot that nobody could look inside and try and work out what was what
00:47:27
and then you connect us range to this papa you make this up into
00:47:32
patches one each day of wife and you provide them to unit straight forward
00:47:37
problem solved until you realised that every hospital only had thirty seven
00:47:44
agree to hospitals as a different type of purples range the dental connect
00:47:48
to each other and we're still that it will connect the same angie
00:47:51
chips so then somehow we have to sort of work around that problem
00:47:55
i think it inspected by the director to make sure that we're doing everything properly
00:48:01
uh next problem was we were out stored at room temperature which is officially less than twenty
00:48:06
five cents a great but if any d. b. dominate to unit you'd like to get over
00:48:10
twenty five so we had to moderate the temperatures and make sure that we
00:48:14
could keep it in check it and and all the time the clocks ticking
00:48:19
see his we published it his will be started ten years of our life
00:48:26
and so can you imagine the complexity in providing this two
00:48:30
hundred thirty four different sites developing algorithms randomised nation programs we will
00:48:35
also setting up defeating try the same time so this was
00:48:39
all going all at the same time that's only just published now
00:48:43
and and then uh almost five thousand babies between those two trials
00:48:49
was a little bit of course i've about to the babies in both
00:48:52
and and then we try and set up the sample boxes to the new and um so i don't look anything
00:48:57
like this ten years go hand bribe on tap no wrinkles this is been a little bit wearing or the bus
00:49:04
so uh we recruited two thousand two hundred babies we have the
00:49:08
prime yeah ninety nine point five percent for instance or adverse effects but
00:49:13
late onset sepsis was no different in controls select a fan
00:49:19
and this is the chief investigator when he finds that was all i mean we were absolutely gutted
00:49:24
we set out because we feel would be something that uh of course we hiked up voices what we did the trial but we
00:49:30
didn't set out to prove this doesn't work while you do that
00:49:33
so we with disappointed and uh evan several short it made something better
00:49:39
um you know maybe some of these other made you know button up with the o. b. p. d.
00:49:45
not to make any that better people go oh yeah but two subgroups it
00:49:49
must work in the small babies or something like that so this was pretty specified
00:49:55
does it work in small babies or just uh some breast local just as a form no nope uh so
00:50:03
we will set around going wanna have to be do wrong and this was the principal baskets meeting
00:50:09
uh what's we'll have the results spell all the time crying working out what what did we do wrong
00:50:16
uh which also but maybe it's just through that it doesn't prevent sepsis
00:50:23
at least the lectern we use in the trial we did doesn't work on
00:50:26
the same coast like different works it just doesn't work to us this question
00:50:33
so when we do our minds only had a high quality trial for
00:50:36
the sun to babysit three on trial these always complex they would keep you
00:50:40
uh concerns about how uh basically that spirit that friendly and approachable to go see but
00:50:47
they showed really quite significant was all five point nine percent only four point six percent sepsis and
00:50:52
the lights for an l. g. g. compared to send him send him to see but some mass effect
00:50:58
a reduction steps is 'cause it's it's mortality and i pay
00:51:01
these data sepsis you got that right but four point eight percent
00:51:06
no need to decide on trial that a a is raised a few issues
00:51:11
uh and shame the trial which probably is by using telnet spread on twenty paper is
00:51:18
giving every twelve i was the c. last that says some team sent this is thirty three percent
00:51:23
they also did some still might quite probably filing of more going for
00:51:27
the top with the j. difference is low uh interacts in caps the others
00:51:31
sounds like a nice outcome but this is only in twenty three of
00:51:34
the hundred twenty papers are really just to be twenty number of babies
00:51:39
so why might we've seen things different uh obviously
00:51:43
to vincent methodology vector preparation the baby the different
00:51:47
uh we gave mall put those than in the men's any trial interestingly
00:51:52
five cents the infections immense anywhere fungal ones where as we fry
00:51:57
ready see fungal infections and u. k. now because people use performances
00:52:01
um a lot of on a consensus because in the first ten days as
00:52:04
a somebody how much will the light from will they proceed in that time
00:52:10
what about the babies put no but now this is an intention
00:52:12
streets analysis and and if you really just have five days financial protein
00:52:18
do you really think that that's going to it's a sin affected approval side like an i. b. stuff and maybe king sepsis
00:52:26
and so lots of the fact is maybe less very needs us chip
00:52:30
on t. n. or some other kind of factors were we to work
00:52:34
maybe the level of one binding was a bit too high a maybe the some problems to transport and storage
00:52:39
we were we were convinced the tight we have very good high quality quality control
00:52:45
uh we have to pass try set of one person say you should to pass tries to
00:52:50
but seriously would you risk giving a bovine protein that wasn't pasta rice that's not possible for babies
00:52:57
so of course or activity is gonna be key we simply don't have a method for knowing what the director from
00:53:02
we use really was the optimal product we could've used on all i we restricted by what we could get hold of
00:53:09
is isn't just rip robotics well of that about babies to proceed robotics their notes the synergy
00:53:15
uh so maybe it's the use even counts uh the responsible
00:53:21
for a file it's get it uh into about it you know
00:53:25
okay so i'm not going to talk about is indeed tell this is say we've used the often try on the civil trials
00:53:30
which is our my price study mechanisms affecting the gotta preterm infants where we collect
00:53:34
this tool in the year and we doing some work by multiplying work very similar
00:53:39
a tool only presented a very wrong and in our unit within self chimp lawton doings maybe work as well
00:53:46
so we have formulated baby is your randomised uh in the lectern trial
00:53:50
we comprehensive they've been out every day what these babes
00:53:53
are getting with getting pro baltics antibiotics what are we getting
00:53:57
uh we've got thirty thousand samples and these would cover the uh these
00:54:01
are all going to machines at the minute to date will be available soon
00:54:05
and of course we have to sort of understand what lex van was doing um why may not prevented neck
00:54:11
and we're gonna use this kind of twin a designer towards part is what we found was that at least a hundred bob paper is
00:54:18
in the trial with twins so if you have twins the both healthy that neither one of them get neck
00:54:24
uh what we did is we found of course that hoffa those twins would've
00:54:30
got the same intervention top both your like spread over both going to see but
00:54:34
and half will be discordant what we've got right from one would go to see but
00:54:40
and to some extent then we can additionally control all the
00:54:43
other things we've measured maybe we control person genetic factors here
00:54:47
all breast milk exposures in the papers you get disease
00:54:50
rossi looking how patterns change before they get to seize
00:54:54
and we use a match these just patient perspective later possible signed matched it them go twin
00:55:01
and the top away makes this is been a massive learning and him for all of us with
00:55:06
clinicians this is really hard to get your head around and understand the new techniques is they come in
00:55:12
we're doing a mixture of g. c. m. s. and l. c. mass i
00:55:16
would acute stools seaports micro what happens in but also looking you in plasma
00:55:21
lots of challenges but work with a great team who've got an extensive library of metropolis
00:55:26
and and just sort of say hey just in case it's true that this is my prediction i i honestly
00:55:31
think that there's gonna be some really important signals and you and and i can see how we could move
00:55:37
to using you as a sort of pattern recognition uh in in a preterm babies i didn't find the babies you
00:55:44
maybe have some ongoing informational high levels of protein breakdown or
00:55:47
something like this to use a great fluid stools by problematic
00:55:52
'cause the babies they could very much the first few days and if they get sick and haven't ideas to stop
00:55:57
eating complete was the un keeps coming so i think you could be really important fluid that we need to explore
00:56:04
uh yeah so these volatile organic compounds that you get on
00:56:07
g. c. m. s. we'll have orange unique smell print uh
00:56:11
if you got case you know which one is your couldn't
00:56:15
which was somebody else is this models being applied to neck
00:56:19
again this could be pets like technology so his uh help the twin he's
00:56:24
it with that can you see a loss of one of these organic compounds
00:56:28
uh a bunch of other events but yet but it's time to suggest you could maybe use this is bedside
00:56:33
technology and has already been used to detect
00:56:36
right boston seated still quite accurately in clinical settings
00:56:42
uh as i say the group uh the part was
00:56:45
doing lots of other work transcript layman's more histology using stored
00:56:51
a fixed half embedded tissue from the lapping get back to the porch archives
00:56:56
take out all the samples with neck and then do some work with these
00:57:01
uh we need better by mark 'cause i'm not gonna go through this but obviously we think that's how it is to compile the
00:57:07
urine compartment the blood compartment and think about all the different markets
00:57:12
that may be could use to allow us to better and predict
00:57:17
so these maybe rather than the different stages of the next season
00:57:20
terms of preventing predicting but also importantly allowing us the subtype classify
00:57:25
neck newspapers but also do more mechanistic studies of creepy that's it for the next few years
00:57:31
so that's why lessons to contrast intrusion incredibly complex and very very hard work what what's the lab
00:57:37
metalworking make you each instant function isolation maybe some special just pick one out of how it's gonna work
00:57:45
observation markers time studies oh was confounded sometimes very
00:57:49
happy confounded at least with an l. c. t.
00:57:53
but on that front isn't a human that frame of course we should focus
00:57:56
on fresh pressed no but uh as you said we need better essays by activity
00:58:01
if you really want to know the answer in clinical study you gotta clap right
00:58:04
to high quality i laos trials with function outcomes if we really want to move
00:58:10
all this amazing scientific knowledge actually improving the health of the places that we look after
00:58:15
so a massive thanks to everybody uh is part the team jen is in the audience increase you've done a lot of it
00:58:21
uh chris time than that great young group top one samples often does
00:58:26
frame portly old babies and the parents the parents you trusted
00:58:29
us uh with that babies lives to do these studies so
00:58:34
that is a good research is a massive team effort i'm just presenting on behalf of some
00:58:39
amazing actually operate as i'm gonna finish a bigger website for group you know research dot net
00:58:45
uh we put up happy we put all of slides if you wanna go read these slides with
00:58:50
the slides you can go and get it and i'm gonna finish that serve thank you very much
00:58:57
ah yes yeah don't understand you first and then not older huh first of all
00:59:04
a lot of twenty years ago i can proclaim ten percent molecule masses contributed
00:59:08
by and link carbohydrates classical also not a group or something because that's all
00:59:13
but until about two activity about offering strictly dependent on the presence of ah
00:59:20
it can bind tool up comes off i am but island um per molecule
00:59:25
and that's why you show the why versus brown other secular around and if it
00:59:30
if u. i. e. p. a. and remove iron it will be alive oh got it depends ah
00:59:37
my question is you obviously don't all of the us population
00:59:40
with ah because although i'm sure you get a lot of reading
00:59:44
it is uh i think i i love the yeah the data is that
00:59:48
the company you provided us with this provide us with the level of wine saturation
00:59:53
it's like a sensitive to stay on saturated any eight
00:59:57
percent saturated is my recollection of the whole batch i've
01:00:01
never have you discovered i have you uh detected an antibiotic that that a lot of people have to do that
01:00:07
yeah we i say we have all these still my crime samples but we haven't
01:00:12
we haven't got the data shows an outer science journal which nineteen i think yeah
01:00:16
gorgeous paper uh about degree of speculation and spectrum of
01:00:20
but yeah yeah with which is so i mean i i
01:00:23
i i we completely agree that that the actual type of
01:00:26
lex venue use is gonna be keyed it as a say
01:00:30
we could choose the product cafe wraps choose product that we would be
01:00:33
allowed to use that use something that was gonna be available in sufficient quantities
01:00:38
um the hostile the quality control regulations and that was not
01:00:43
happy on saturated but you could you could argue we could
01:00:47
argue all day about what would be the optimal formulation of
01:00:51
i was going to mix it with what the fraud which you have to look chopper or like if it is i am in it
01:00:57
you have circulated again and who's well we we any we we we make
01:01:01
with both uh and the repressed no commands pressed no 'cause for low levels are oh uh_huh yeah so we like
01:01:07
that's the best that we could do mean practically we have to find a way of getting into the baby so yeah
01:01:14
the older
01:01:18
oh would you look wonderful dog but you know she bought other question
01:01:23
and i hope you're not disappointed you don't get you know about so far
01:01:28
but i'm sure you'll get a number of atoms you're gonna but i
01:01:31
just wanna go back like different you know there are some very early studies
01:01:35
the lead to very much actually are here which i don't really might ask you
01:01:40
uh and and i just production nah internal causal tissues didn't
01:01:45
and uh have you looked at it and doctors productions backtrack
01:01:49
shopping doctor how an additional in a related research racial i don't
01:01:54
and that may be quite different maybe functioning as effectively maybe mall yeah i mean i am i mean of course
01:02:02
we didn't set out to explore the role of been talking mostly produce like to for entity that's very important
01:02:09
because of colour cost a lot of papers as well i spend
01:02:11
my time inch plating sticking trips in the morning clinical trials i mean
01:02:15
if if a whole research team was focused on like the friend of course this is where you would go
01:02:21
happens is set in the day i'm i'm a condition my interest is in whether some of these
01:02:27
ideas about h. m. o.'s like to friends totally m.
01:02:32
f. g. m. make a difference in the bay p. m.
01:02:34
as i say like that he was amazing but the and the day we have to take steps decide whether you provide
01:02:42
a baby at risk of whatever problem cognitive infected whatever you have to
01:02:46
tax that just to prove that some this theory makes say a difference
01:02:52
so that's why we chose to do this trial but i agree you could
01:02:56
that there's lots of other aspects of like to for you to explore these babies
01:03:03
yeah but that that's one thing i remember said sure
01:03:11
yeah oh yes because ah whole way information for you
01:03:22
and i think one of the chances in in a total g. is that hasn't been enough
01:03:27
a basic science in the in the preterm babies we still don't really understand the mechanisms lead into next
01:03:34
so to this the enjoyed system i don't know how many we've got growing but twenty
01:03:39
thirty something like this the growing uh it's uh parents are very happy to support us
01:03:46
the decision doesn't affect anymore to ship it just takes a piece of tissue to
01:03:50
it's not the cry used and then chris text of the laps we has essentially scrolling
01:03:56
and as you say that then provides the model because these cell lines come from
01:04:01
premature baby got and most often premature baby goats that are risk of
01:04:08
now because by definition they have next we have a few controls for
01:04:12
spontaneous intestine perforation script if you'd like to controls if the baby has
01:04:17
uh uh like us time clothes or something like that so yeah we hope
01:04:20
that in years to come this these really you know that that's correct that's
01:04:24
problem trials on the information absolutely yeah yeah absolutely we
01:04:31
don't something real trial because ten years ago men's any
01:04:35
wrote a paper that said this stops papers tying of mechanistic spaces
01:04:39
tire sepsis we wanted to crack on and see whether that was true
01:04:44
uh so if we could do well this in paolo we would uh set lay uh i don't know it's like the rest of
01:04:50
the world but getting funding in the u. k. for this is
01:04:53
almost impossible we basically full time technicians trying to do these trials so
01:04:59
a last question about that hostile most yeah maybe in all done huh factor
01:05:07
at all in on like like ah ah ah gentle face
01:05:12
i now know about functioning canary of an action
01:05:17
and location on and i'll be back off of ready
01:05:22
in this direction and ah yeah that's huh
01:05:27
a clinical up and they're all changed at all in peru but with an action
01:05:34
and yes if i question the doses nothing i mean that there is literally nothing on
01:05:40
the mechanisms by which like to foreign maybe work in these three template is
01:05:45
the the the half dozen small trials and and i know this will
01:05:49
work in in toddlers and infants and things like this but there's nothing in
01:05:54
in preterm babies in the physiology forgotten huge and
01:05:57
exposes the microphone and everything is so completely different in
01:06:01
pretend papers but i don't know that we can extrapolate
01:06:04
anything happens in a healthy toddler to to pretend baby
01:06:10
yeah how are really important information but often is not only if we brought pain in the
01:06:15
mail and whatever it is also within files it excels yeah probably more probable cause but macrophages
01:06:21
so if you have information in that issue you have went over the
01:06:25
phone but it's not because of milk but it's release by the south bay
01:06:30
with us i think we have to uh finish possession or like that might make you go
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