 The title is a little bit of a play on words in a sense, so I'll talk a little bit about some of the things that we've been doing at the Australian synchrotron around the areas of the gestion of food and milk and infant formula in particular. And to those that were at the top, or who were listening from Lund Fizkem two days ago when I gave a presentation, there's some at the start that's similar but the rest is different so they don't fear too much if it looks familiar. So I wanted to thank Tommy and Selma in particular, not only for the invitation but also congratulations on bringing this initiative together. I think it's excellent timing and it's great timing also because I'm moving to Copenhagen in July, so only about six weeks now until I move over. So I'll literally be bringing Aurora Australis to Northern Lights and hopefully I'll look forward to meeting many of you and working with you on some of the problems around food and other things that we can tackle. So I'm currently based at Monash University which is in Melbourne, down the bottom of Australia there and it's almost literally on the other side of the world from Copenhagen. It's amazing what this zoom thing's done for forgetting people together. And so I'll be 20% still Monash and 80% Copenhagen from July so if you're coming to Copenhagen, please look me up or give me a call and I'll come over the bridge and say hello for sure. So I'm going to talk to you a bit about what we've been doing in the area of lipid digestion and structures that form during the digestion of lipids and with a bit of a focus on milk and infant formula, as I alluded to. So I'm sure many of you are at least somewhat familiar with this idea that the lipids that we ingest in the form of food or there's pharmaceutical ingredients, some instances contain mostly triglycerides or at least glyceride based lipid molecules and our bodies really well designed for breaking down those triglycerides into monoglycerides and fatty acids to facilitate digestion. So our body doesn't absorb triglycerides and glycerides intact. So our digestive process is geared around breaking those down and triglycerides are by far the most prevalent lipid in the lipids that we consume in our diet. And so in the physical chemistry area, we know that when we bring monoglycerides and fatty acids together in an aggressive environment, but they're likely to self assemble and form some interesting structures. And so some of you will be familiar with my cells and lipid zones and perhaps you've come across some of the other self assembled structures shown here through through your sort of interactions with people in the in the liquid self assembly area. I'm conscious that not everybody's a liquid person. And like two days ago Tommy where everyone else knew about this. But the, I guess the big question markets in the middle there is because, although, you know, we're probably the last groups coming to this area and people have been interested in this problem for quite some time of understanding the structures that are formed during that absorption process. And so what's formed when under what conditions, and then how does that then impact on absorption, not only at the lipids themselves but also other components that might be there so poly soluble vitamins or drugs in a pharmaceutical context. So we've been interested in this problem for a while of what happens when they when triglycerides are breaking down by the body. We know that they'll self assemble and forms different sorts of structures with the questions of what what really happens in a physiological environment and how can we get close to to really understanding that using some of the techniques. You know at a disposal and in particular small angle scattering is a good one for tackling this type of problem because of the length scales that are involved. So, so we, so we'll talk a bit about milk and so when, you know, when you when you come across milk usually in a, in a conference context or, you know, in the scientific literature the focus is almost always on either the the player at the surface of a fat droplet and the proteins that are associated with that, or perhaps the casein micelles or other components that are not part of the core sort of triglyceride droplet. But what we know is that the triglycerides comprise more than 98% of the liquid that's in milk, but only 2% or less and much less than 2% in a lot of cases is due to the other the fossil liquids that are present in that trial layer so it makes sense that if we're sort of interested in lipids and what lipids are doing during the process of digestion that we need to worry about the triglycerides but they're largely not addressed. You know, in the literature really at all, that's probably more in the physical chemistry literature than anything, and they're so they're sort of a poor cousin if you like of the fossil lipids and other components but I think really important in driving some of the structural transformations as we'll see. So some people are going about looking at these types of systems using in vitro lepolysis models, so you can simulate the sort of gastrointestinal environment, so chemically and enzymatically in a temperature controlled pH controlled environment and track the process of that breaking down of the triglycerides and monoglycerides and fatty acids. And so it was only fairly recently that we've taken this model and the key thing was to sort of couple that up to a synchrotron scattering facility. So the facility in Australia is a really nice small angle x-ray beam line. Down here it's in Melbourne, right next to our main campus in Monash, so very handy for us. And that's really been a critical factor in our sort of access to the facility to develop this capability. And so in simple terms, we take a synchrotron x-ray source, so high flux, high intensity, really nice setup, and we couple that to a flow through a system. So we have our lipid system in here digesting, so in the context of this talk let's say milk in here digesting, we flow that through a capillary, and if there's ordered structures forming in the system then we'll get diffraction from those structures that are formed. So I'm assuming to a degree that most people are familiar with small angle x-ray scattering or you may not be on this call if you've never heard of it, but I'm not entirely sure of the background of everybody on the call. So the important thing is if there's order in the system then we'll see diffraction and we can correlate that diffraction to the structures that are formed. I won't go into that for today's talk, but what we'll see is some interesting behaviour in a second of what happens. The important thing then is that that then allows us to get time resolved and real time structural information without disturbing the system. So we don't have to take samples and then analyse them offline to extract that structural information about the system during digestion. We can do it in real time and by using the synchrotron source we can acquire that information, that structural information on the seconds to minute timescale which is the relevant timescale for digestion. So if we take milk and we pinch x-rays on the milk as it's digesting, so our milk's flowing through our flow through loop if you like, so it starts off life as an emulsion, so relatively unstructured system. We can see that during digestion, so we're now forming those monoglycerides and fatty acids during the digestion process that we see different structures forming and then disappearing and replaced by other structures and so this will be on repeating a second. So we'll talk the way through it. So we start off with our emulsion. We start to form the malophase here that's due to calcium formation, so there's calcium in the digestion buffer as there have been in intestine. We see a small micellic cubic phase forms and then disappears. We have hexagonal phase forms and disappears. We have a biocontinuous cubic phase here that's actually left at the end of digestion. So we know from our filtration profile that we reach essentially 100% digestion of the milk in this format and so this is the structure of those digested fat droplets at the end of the digestion process. So that's how cow milk behaves. This is just biobind milk straight off the out of the fridge and so a number of questions that arise from that, so this is sorry I should just elaborate. So this is the video where we've turned it now into a contour profile. So it might be a bit easier to see some of those changes during digestion. So this is that the malophase, the malo sapes that form. You can see our hexagonal phase in here. There's some indicative peaks of micellic cubic phase and we end up with the biocontinuous cubic phase at the end. So that transition or transformation essentially from an unstructured liquid fat droplet at physiological temperature to this highly ordered biocontinuous cubic phase structure during digestion. And we can we can see that structures that formed the self-assembled structures inside the remnants of those fat droplets if we do some cryo TEM on those digested systems. And that all makes sense for us from a physical chemistry perspective. So we're going to generate more polar lipids. So we expect to see a certain order of appearance of different self assembled structures as we go from the less polar to more polar lipids. So this critical packing parameters that is the sort of conceptual framework for understanding that in a physical chemistry sense and that actually does make sense. So nature does actually follow some of our kind of artificially not artificially assembled laws but geometry rules in these in these systems. So back to food. So what do we have to do to milk then to upset its behaviour from a structural perspective. So this was the commercial homogenised milk straight off the shelf. And if we have free drive milk powder, then you can see that there's almost no difference in the structures that are formed during the digestion process and the kinetics is pretty much similar. So if we take raw milk, so Holstein cow, so I think they're Danish I think originally. So we can see that the we do fall into by continuous cubic phase and hexagonal phase but the digestion rate is much slower. So this milk hasn't been homogenised. So we're seeing a direct effect there of the reduced sort of interfacial area that's available with the larger fat droplets. So it takes longer to get to the point of forming these these particular structures. And if we let it run for long enough, then we'll get to the bicontinuous cubic phase. Likewise, if we freeze milk or freeze dry milk and reconstitute it, then again we get back to the bicontinuous cubic phase at the end of digestion. So there's not a lot of difference there. It's actually quite hard to to upset the behaviour of milk during digestion from a self assembly perspective. So is it just a divine milk thing? So is it just cow milk that does this? The answer is no. So goat milk also forms bicontinuous cubic phase forms hexagonal phase transiently during the digestion. It actually seems to form two different bicontinuous cubic phases here in succession. And interestingly at the end of digestion, the bicontinuous cubic phase in this case has disappeared. And so, so we know that goat's milk contains a much higher proportion of medium chain fatty acid liquids. So perhaps that's part of the reason for that, that we're running up in a slightly different overall compositional space than you would see with cow milk, but it does go through these self assembled structures on the way there. So, cows and goat milk form these self assembled structures. So is it a mammal thing? And if it is, then we'd expect that human milk might behave the same way. And so if we then look at human milk and so we're at a slightly higher pH in this instance, then the others are typically run at 6.5. So we can see again we form a bicontinuous cubic phase, hexagonal phase is a bit more prominent for human milk. So we've got different lipid composition to what we have in the cow milk. We can see that if we just stir milk without adding our lipase that we generate the lamella phase and that's because of the bile salt stimulated lipase that's present in human milk that's not present in cow milk. So in cow milk we just see a flat line essentially, or no feature from the lamella phase until we add in the lipase whereas in human milk we don't need the lipase to start the digestion process because it has its own lipase already present. But essentially we see similar structural transitions to bovine milk. If we actually look at pH 6.5, so we know fatty acids are there and they're important in this behaviour and it's really critically dependent on where we may be with respect to the PKA of the fatty acids. And so if we drop the pH slightly and run human milk at pH 6.5 instead of pH 7.5, then we actually see that we form an inverse micella cubic phase. So we're going to form the bicarbonate cubic phase that we see in the case of the cow milk and the goat milk. And this is important also to come back to this behaviour but we've seen that this is actually quite signature for human breast milk at that pH. So to kind of jump ahead if we're trying to simulate at least the structural behaviour of human breast milk then that kind of gives us a bit of a roadmap to aim for under those same conditions as we saw. A slightly different behaviour for bovine milk. So you might ask well what then happens with the vegetable extracts that are part of a lot of people's diet and intended to substitute for milk? So if some of this structural behaviour is for some reason important then we're not there yet in understanding why then perhaps it'll make for an interest in contrast. Or perhaps they all behave very similarly, all you need is a light liquid in that form by continuous cubic phase because it seems to be the case so far in the data that I've presented so far too. So if we have a look at some vegetable extracts or milk if you like to call it that. So if we take soy milk then and digest soy milk under identical conditions to the bovine milk and human breast milk that we saw earlier, then this is digesting, digesting, digesting. So we're actually on our titration profile we're consuming sodium hydroxide so we're producing fatty acids. There's nothing wrong with the digestion we're producing the monoglycerides and fatty acids, and we get to the end point of digestion so we get to the end of digesting the soy extract, where it's quantitatively digested to monoglyceride and fatty acid, and all we see is some of the calcium So soy, the lipids that are in soy extract, don't support that self assembly behavior in the same way that we've seen for those for those different mammal milk. So we've looked at a range of different mammal milks and they all form some degree or other higher order sort of self assembled structures whether they be in this micella cubic phases or really highly ordered by continuous cubic phases. And then if we take the vegetable sources, then we don't see under the same conditions those systems supporting that same, I guess, sort of broad pattern of self assembly where they don't form those higher ordered structures they tend to, to just form calcium types that don't self assemble in the same way that the mammal milks do. So very interesting discrimination in the behavior there. So probably knows what's coming next, infant formula. So question then is well where does infant formula fit into these things because it's, you know, it's meant to be a substitute for human breast milk. But we know that, you know, to, you know, to a greater or lesser degree, they may or may not contain different milk components and so, so where exactly do they fit and can we use some of this scattering to kind of interrogate whether this I guess there's similarity to, to some of the mammal milks and to human milk in particular. So if we take different infant formula then so we've got four different infant formulas here. And I'm not going to give you the brands obvious reasons. I'm not saying whether some are better than others, but they're certainly all different for these two are very similar. They're quite different to these two. So the top two systems both form self assembled structures. So this one forms a micellar cubic phase and has almost identical phase behavior to human breast milk that we saw earlier. This one forms an inverse hexagonal phase it doesn't fall micellar cubic phase during digestion. These are all suggested under identical conditions to the baby milk I showed earlier in human breast milk at 6.5 these two don't support that self assembly at all. And we know from the liquid analysis that they're that they're different as well and these two more than likely have a high much higher vegetable content let me put it that way than the than the other two. We don't have the access to the composition directly so we've looked at the liquid composition separately and so I can see one of the important things is that they're they're all different and that so they all have different starting triglycerides and at the end of the process and that yields, you know, different, you know, some similar to others but broadly different, you know, monoglyceride and and fatty acid compositions at the end of digestion so we can try to sort of try and I guess pulls some of that information together and see if there's anything in the way of trends and so if we take some principle component analysis and and look at what are the major drivers in terms of composition and and where does that sort of fall in terms of dictating the self assembly behavior. And so we can see that we're in when we're in the sort of positive space of the PC one so we're with where we tend to have sort of higher unsaturated fatty acids and tend to have lower parmitic acids then that tends to drive this. This formation of the inverse micella cubic phases is what this I to signifies. And the others the others is so the opposite I guess so the opposite trend and then if we look at what happens with the monoglycerides, then my parmitin which we know is a critical component at the end of the digestion for human breast milk and it shows up as our sort of PC one driver but it's sort of less less clear really that it's driving so PC ones not really just helping us to discriminate between the self assembled structures so we can sort of see that there's self assembled structures on either side of this this sort of crossover line with PC to we tend to see when we when we have a sort of a positive profile in PZ to tends to sort of indicate that we might see an inverse micella cubic phase in that case. The opposite being true when we have a lot of monoholian prison. So, and that that again is broadly consistent with the idea that the human breast milk tends to form inverse micella cubic phase, rather than than the other structures at the end point of digestion. So, this is this is only a few moments coming. But we've been thinking about how can we sort of use that and try and design some systems that where we might deliberately want to go on and mimic. mimic these some of these milk systems from a structural perspective so you know the design of infant formula has really been driven by compositional matching not by trying to match behavior or match structure. So, so looked at it a little bit differently and said, well, what we need to do with bringing together certain liquid compositions and whether we can start to mimic the behavior of some of these systems separately and so well deliberately and so actually just gone left my group and gone over to the Australian synchrotron to start working on the new biosex beam line that's being built there at the moment. So he spent the last couple of years looking at this problem and other problems for those that know and he's, he's been a prolific scientist over the last four or five years, which has been fantastic for my group and he's become a real feature of the Australian community. He's, he's taken what would normally be a very complex mixture of triglycerides that constitute milk so many thousands of different potential combinations of different fatty acid, different fatty acids in different positions on the triglyceride and said, well, can we take homo triglycerides and generate the same sort of structural behavior if we kind of bring them together in a bit of an educated way but with increasing complexity and so if you're really interested in this work, you know this we've put out a couple of papers on this now and I'm only going to show one slide of the actual results, but he's, he's done this for both line milk and for the human breast milk as we'll see in bringing these homo triglycerides together to develop systems that structurally mimic the behavior of human breast milk during digestion. And so the upshot of a lot of his work, if we take this as our kind of target performance for the indicator if you like, where we're forming an inverse micellic cubic phase to the endpoint of the gestion, then he's found that if you take one through to six triglycerides in the right proportions that you can't mimic the behavior you can't get it to form the same self assembled structures, but if you bring in the magical seventh triglyceride, then from a structural perspective you can see that that we can pretty much mimic the self assembly behavior of human breast milk by bringing those homo triglycerides together in the right composition, forming an emulsion. So it's just emulsified in case in and digesting in the same way that we've digested the human breast milk. So, so that's really like human milk by design, but from a structural perspective, not from a compositional perspective. So there's some interesting discussion I think to be adding that's that's sort of an evolving story around what that might mean from a nutritional perspective. So, so some take home points. So self assembly occurs inside these milk droplets during digestion and it was shown that in in real time in a physiologically relevant format if you like. And we've also obviously shown that the structure formations really critically dependent on lipid composition and that we can self assemble we can assemble these systems and with sufficient patients and been time determine what what we need to do in terms of bringing compositions together in order to get them to form specific specific structures that can mimic the behavior of over on milk or human milk or potentially other systems if we would like to do that. So I guess in a nutshell, where does that all fit into the biggest picture. So there's people in my group. So the talk in London two days ago was largely around the drug delivery aspects of some of this and always happy to talk about that but not today. We're also looking at can we use this to generate you've seen some of the very quick snapshot on the mimics front but also fortifies fellow things like infant premature infant nutrition where the digestion behavior of that is really important and understanding the digestion of that under sort of premature infant gastrointestinal conditions is really the sort of next frontier in some of that work. And then the sort of third aspect to this is why so why do these, why do we see this clustering where the mammal milk for these rich self assembled structures and the vegetable sources don't when it may be just kind of coincidence that the mammals, the lipids obviously that are in mammals was going to be different to the lipids that are in vegetables. Overall, but you know it does. I don't believe in coincidences in nature we don't yet know the reason why there's a difference there and I've probably headed off the main question that I often get asked during when I give this talk but you know perhaps there's some other other play that's got nothing to do with necessarily with lipid self assembly but is perhaps an immunological, you know, an immunological reason for that self assembled behavior and perhaps those structured particles interact differently with the biology in the gut and that's one of the areas that I'll be interested in working a lot more in when I can sort of clear my head and come over to Copenhagen and look at some of these questions. So, lastly some acknowledgments so Australian syncretron's been great for this work in the staff at Australian syncretron particularly Adrian Olly, who I didn't squeeze his photo in here is he's been an integral part of our group really for a few years now. And so he deserves special thanks. But yeah, Andy, Melinda Salim, Chazella Rana and Chazer have really done the work that's contributed specifically to this talk so thanks again for the opportunity Tommy and Selma for presenting some of this work and look forward to any questions. Okay, thank you. Thank you very much for excellent representation. I think it's good to see that you point out the importance of lipids even for going into more plant based food because there's so much focus on the protein part that you tend to forget the lipid part of it. So you have got a lot of some questions here so I will, to speed up things, I will read. So from Alessandro Marangoni, fascinating work, did you do for a couple of samples wax? Are these pure liquid crystal or is there crystal in material, particularly for the lamellar face with the calcium? So yeah, so the calcium soaps tend to precipitate out and we've never actually gone looking to be quite honest, but I suspect that there probably is. So, and the sort of clue of the additional aspect of this is we're often looking in the wax for what's happening with drugs in these systems so we're really interested in when we incorporate drug molecules and so we're often looking in that space but we're not specifically looking for crystallization of the lipids. Andy has looked at that a lot obviously with the homo triglyceride systems you're much more likely to run into that situation when he's got high saturated lipid content in some of his mixed emulsions so there's certainly some evidence of crystallization in those systems. Okay, so that's interesting. Something to do when you come to Copenhagen to look at this and you can do it in Max. We've already got the data, we've just never gone looking. Okay, okay. So there's a question from Lars Nilsson. Very interesting president and I didn't quite get to why the behavior between raw and homoenized bovine meal course different. It's related to the opposite side and differences in the composition of the interfacial lay you know when you homoenize it you break the membrane and so on. Yes. So, the, the phase behavior is the same. It's just a lot slower because of the difference in droplet size so you're right there. Because the membrane constitutes such a low fraction of the total amount of lipid in the system, using this approach is not really the way to try to understand that because we're obviously seeing the dominating behavior of the triglyceride core. So we would need to use a different technique or, you know, maybe use a contrast matching neutron experiment to try to elucidate that behavior but we haven't haven't gone there yet. And then there is another question from Alexander Maragoni. And he says on the point of plant based milk, the versus mammalian milk and self assembly, could it be the position and distribution of the fatty acid. And the role they play in mammalian milk saturated fatty acids are in position as and to while in bed, they go to position as and one as as and to that could that is. Yeah, that does the amdys work, I think. I think that that is true. And I think that the PC that perhaps I didn't spend enough time on the on the PC a analysis that supports that that is that that is the case. So, you know, the differences in the lipid distributions are driving that some of those differences in the value but I want to know why. So why, why do mammal systems have those specific lipids. So, is it isn't that we just have those lipids in our body and it's a coincidence that they form that they happen to support the formation of those structures, or is there an evolutionary or otherwise reason why those lipids are there, because the self assembly provides some other process that we don't yet know what that is. So perhaps the formation of cubic phases in the gut as immunological consequences, because we know that cubic phase particles can act as really good vaccine adjuvants, for example. So, questions that I'm sort of interested in getting it to the heart of I think Chris has got his hand up to me for a question. Yeah, I was just going to say, we have a raise hand to me. I don't know the rules so do I have to raise hand to put the question in there. You can have your questions now so just go ahead. Thank you it's really fascinating research Ben thank you very much. You got me thinking about the fact that the million milk that the gestion leads to complex structures would you speculate that the energy intake of these lipids. So they are designed to deliver energy more in a more sustained way, rather than being rapidly absorbed in the body like with the other type of lipids. Is that needs to think. I think that's, that's an interesting hypothesis, for sure. And so Anna, who's at the front there, one of her tasks in her, she didn't quite get there was to compare the rates of absorption of lipids with different structures that are fall. She kind of got obsessed with what was happening with drug is a lot of what people do because most of them come from a pharmaceutical background, not from a physical background so I try and push them to towards other questions but. So yeah that's that's still still an open question. My original hypothesis was that actually it was the other way around that the formation of the cubic phase for example maybe gives you better access and higher surface area to the particles. Further life is to to drive digestion in people for example if you had like compromise digestion capabilities and evolutionary thing maybe that's kind of a compensatory mechanism but I don't I don't think I believe that now. But yes, again, still an open question. Thank you. So there is a question from so she's fine. And it's as interesting research does the difference structure and fake or face baby during that yes they mainly lead to taste or nutritional differences or other premises a little bit what we have talked about now but what about taste them. Does it taste. Yeah, yeah, we're interested in what we've been looking mainly at intestinal digestion so you don't taste obviously what's already in your intestine. Now in your mouth. The lingual lipase can perhaps suggest a very, very small fraction of of liquid that's present. And it's quite interesting I've got a separate. experiment or thought that I've wanted to explore for a little while there. Because we know that some specific fatty acids. Act on bitter taste receptors so actors in his antagonists or inhibitors of bitterness in our taste. And so what I want to know is whether those fatty acids are produced. Bivalent bilingual life is in an infant as a way of avoiding the baby rejecting the taste of the mother's milk. Purely hypothesis. But I would be really interesting to take some gets get a baby to spit out some lingual lipase and you know see what fatty acids are generated generated in the early stages of suggestion of breast milk. Yeah. Okay, so the nutrition question is an interesting one because we have got data showing that you do get differences in rates of absorption of sort of co incorporated hydrophobic compounds, depending on what the phase sort of trajectory is. So, you know, that's a question that's, that's definitely ongoing as well but there's certainly enough evidence now that different systems are for facilitating that to a greater or lesser degree. So, so there is a final question from Alexander Marangoni, maybe you want to post it, post it yourself so we are still a couple of minutes left so please Alexander. Thank you very much for the amazing presentation I just wanted to mention. Have you tried or seen any work on the LC structures that would get formed by SN2 let's say two monopalmitin versus one monopalmitin. I mean, in these non lamellar faces they probably have very different behavior and what I was just commenting is that you know if they're a position to the saturates they get assimilated as monoglycerides in the body right if they're position one and three, they get split into fatty acids then react can react with calcium and then they become insoluble calcium salt so a natural selection would have like push the saturates at position two, just for energy right otherwise you waste a lot of that energy but but I think that you're onto something here about the self assembly of the of the two versus the one species of the saturated monos right. Yeah definitely so we haven't taken the two and the one separately and deliberately digested those it's partly because it's hard to to get the OPO in isolation. There's always other things in there that's going to confound the data anyway unless you unless you can point us in a source of pure OPO. And that you know we can take the more complex system by these and try to try to pinpoint what's happening compositionally and relate that to the structures that are formed. You have the PC one in this case. And for us I called it because we've got you know we're in the PC one same panel be on this the slide at the moment. And so I'm pointing the finger at it instead of the pointer. Give me one second. And so the monopalmaton that's more prevalent in the bovine. More for it we know definitely more prevalent in human milk. But in the manual books generally compared to the vegetable sources is is really discriminating factor between the two so that makes sense compositionally. Then if we look at the differences in phase behavior we don't actually so we can see that you know this is a self fulfilling prophecy that the bovine human and goat. Milk's are on the positive PC side but that's because that's because what we've seen over here that we already knew we suspected that would happen but it's not allowing us to really discriminate between modes of self assembly when we look at the you know the minor glycerides driving that are primarily driving differences in behavior but you know the more subtle differences on this side who seem to indicate for that inverse micella cubic phase formation so we need to probably do a bit more to interrogate this. Yeah this this this link but there certainly does seem to be some even in these much more complex systems where it's hard to make those really definitive calls. There does seem to be some links there that we'll be able to exploit if we can do some more pure, you know more pure positionally defined systems so. Thanks for your interest because it's it is really the next the next thing I think in this area, so it is probably taken too far of a link in going to the homo triglycerides and sort of skip that that part.