Last year at the Re-Deploy conference, my colleague Dr. Rictough Chef offered among the a lot of cogent and clear talks on descriptions of resilience and also resilience design that I’ve yet to come throughout. I’m embedding the video below, however I’m also consisting of an interenergetic tranmanuscript for those who choose reading rather than watching and also listening.

If you’ve at all been interested in resilience and also Resilience Engineering, I really carry out recommend spending the time to check out this.

You are watching: The resilience of bone is thought to come from which of the following


I"d favor to start by thanking Paul and also Adrian, Mary, James of the AV folks right here the theater for the occupational that they"ve done, putting together a conference and also likewise trying to set the stage for us. I"m not going to talk around myself at all because it"s not incredibly interesting, but I will put on this display screen my, my only political statement for the day. And if you have an interemainder in my national politics, you have the right to go look up and you"ll understand everything. The title of this talk is a couple of monitorings on the marvelous resilience of bone and also resilience design. There"s an extremely lengthy, little print disclaimer below about all the points that I"m not going to execute and the points that I execute do and also the things that I shouldn"t perform and that I"m disclosing right here. And a bunch of points around my previous aget and also stuff. Very amazing. This is a simple talk around complicated systems and also many of you are taking care of intricacy in some create or other and also trying to battle with, through the consequences of that. And I"m going to talk around a space that exhibits all of these properties, but that is not your residence base. I"m going to talk about bone and I think in the finish that you will certainly, my hope is that you will certainly concerned think that bone is not a model of resilience or an allegory for resilience, yet the archekind of what resilience is that when we attempt to understand also resilience, the first point that must come to mind would certainly be bone. And if I succeed this particular day for you later on when someone claims, what is resilience, the instance that you will provide to them as bone. I"m also going to need to talk a small little about resilience design bereason the design part of resilience engineering is, is a pretty complex sort of concept and a lot more challenging to pin dvery own than simply resilience itself. Okay. We"ll just execute those 2 points. That"s it. Nopoint big. And bereason my kids are all in proclaiming and they"re constantly telling me to cut to the chase in conclusion, let me say this the, the, the bottom line right here is pretty straight forward at leastern around bone and also resilience and exactly how it functions. bonus repetitively remodeled. Many of you probably are not mindful of this, but your skeleton is reinserted about eextremely 10 years. And that"s pretty impressive because from your perspective, the skeleton is a kind of static point. It"s always tbelow. You have it. And as long as you do not execute also many bad points to it, it doesn"t adjust exceptionally a lot. But in fact, your skeleton is constantly being replaced. The making of new bone is in a dynamic balance via the ruining of old bone. And this is a procedure that"s power requiring and takes place all the moment. And bereason it"s happening at this bit level, you do not notice it. But if I were going to pick one thing to remember from this talk, it is the concept of this dynamic balance between production and destruction, which then offers the platcreate for all the resilience that we watch. Resilience is constantly existing, it"s constantly enacted, it"s constantly requiring power and we are unconscious of that because the majority of of the time it"s happening in the background and also at a fairly little bit level so that we don"t check out it playing out. The various other point is that the demolition and also construction of bone is directed by mechanical strain. And this is really vital because resilience is focused on specific kinds of things in using via miscellaneous sorts of mechanisms to achieve a certain ends. We"ll talk a tiny bit around repair of some added mechanisms. I don"t desire to talk about that in detail. Um, bone. But the various other thing is that the system of bone is not simply a skeletal system in the sense that it holds us up. It additionally offers other features. It"s the main save in our body for calcium and also phosphorous, which are both very important minerals and also extremely, incredibly hard to gain from the environment. And crucial to have. And it turns out that calcium is the most vital ion in the body. ultimately, this idea about resilience is that it"s all about signaling. Tbelow is no grasp controller and resilience. There"s no high God of resilience, which directs everything and also organizes it. In fact, it"s a messy layered netoccupational that is actually performing these functions and we"ll present you a small bit of the netjob-related even though it"s not yet well taken and also there"s lots and also many crosstalk in this netjob-related and the majority of cell level integration of the tasks that are going on. Cells respond in a means that makes this all possible. bones resilience is what I would contact Woodsian. And this is after Dave Woods. Dave Woods has, if you haven"t looked at it, you absolutely need to. The four ideas for resilience and the implications for the future of resilience design and also relicapacity engineering and device safety. But basically he"s gained 4 different principles around what resilience is and also the last two are the most important. One is this principle of graceful extensibility, that the mechanism has, not a sharp boundary, however a rather soft boundary that that permits expansion of its attribute. And the various other is continual adaptcapability. The principle that we are constantly adapting all the time, it"s a never stopping, never before avoiding procedure. And that, that"s what makes the totality point go. The various other thing around resilience is it"s expensive. It needs consistent and also power and resource inputs. It"s breakable and deserve to be disrupted by loss of feedearlier. It"s at risk to condition and it"s restricted. It does not last forever before. I do not recognize if you recognize this, but you"re all going to die sooner or later. And so re"s a limitation tright here. There"s a type of a, a sell by day for this in, in this resilient system as tbelow are in many kind of. Okay. So that"s, that"s so the first thing I"ll point out is that bone has actually both a facility macro and micro architecture. On the left you check out a photo of a area through a bone and you see the hard external edge referred to as compact bone. And then the inner bone, which is dubbed cancellous bone, which is simply sort of woven point through all these spicules. If you expand also that a bit, you"ll look inside. You"ll watch that in truth there"s a micro architecture here which has actually acquired these main points which are canals. You watch them prominently displayed here via the circular cells, aligning them and also developing this bony material. Bone itself is not living material. It is the bony, the stamina part of bone stuff is hydroxyapatite crystals. They"re not natural material, however they"re laid dvery own by organic processes. But there is this framework and also architecture below, which is, it has actually a D is various at different scales yet all integrates together. brand-new bonus lassist down alengthy stream lines. So it turns out that bone has sensors that permit the detection of mechanical strain and redirect the process of chewing up bone that is ruining old bone and laying dvery own new bone so that the new bone is aligned alengthy the lines of stream. This is a really vital principle. Bone is expensive to make, difficult to preserve, incredibly demanding of sources and also energy and also you don"t desire it. It provides teleological sense not to usage as well a lot to execute this. So we"re extremely sparing in the means that we make bone and also the continual strain that organisms experience leads to a consistent pattern in the method that bonus lhelp dvery own. If you look at the photo on the top left, which is a slice with a femur, the head of the femur there you deserve to see what looks favor a small boxfavor thing appropriate at the guideline of the head of the femur. And that box prefer structure, which looks favor a little line going sort of that, that kind of marks the diameter of the spright here there, that line and also that box that"s inside tright here are current bereason of the fads of strain that are brought about by locoactivity, by being upappropriate. And it"s prevalent across all of us to have actually that pattern tright here. Even though it"s not programmed almost everywhere in molecular biology, there"s no, no gene that states make bone and also lay it dvery own in this specific pattern inside. It"s the constant experience of strain that reasons the bone to be restructured in that method so that it becomes powerful and supports those lots. by the means, there may be an optimal strain suffer. This goes possibly a metaphorically to the concerns of burnout and also things choose that. You deserve to have as well much strain. You can accumulate fractures for instance, faster than you deserve to heal them. And so we view damages that come from high loading over time. The remodeling of bone, this continuous procedure is going on in the background is actually fairly complicated. But the essential point is that it"s locally directed yet internationally modulated and also it produces the repair of microfractures that we"re accumulating all the time. So the reason our signal skeleloads are strong is not because bonus, so impervious to damage, however because small damages are constantly being repaired. This process of remodeling that"s going on is identifying and resolving these small fractures all the time. And as a repercussion, our experiences that bonus, solid and long lasting that procedure fits right into the recycling of calcium and phosphorus also bereason it turns out that the chewing up of bone that happens in the little cells you see below mostly at the left of the slide, which are called osteoclast, is done by secretion of hydrochloric acid, which dissolves the bone and then returns its mineral ions back right into the circulation where it deserve to be supplied for various other purposes. Calcium is really vital bereason every one of our contractual activities, your heart, your muscles, and also in truth the inside cell tasks all depend upon calcium feature. Calcium is by much the many tightly regulated ion in the body. And so having actually a huge supply of calcium, which is in short a short supply human being is actually incredibly handy. You have actually around a kilogram of calcium in your body and also it"s a lot of 99% of it is stored in bone. The method calcium homeostasis has kept is using of facility thing that involves the kidney and also the gut and absorption, vitamin D, parathyroid hormone and also a variety of various other things. But basically there"s this very big complex regulate network-related that is basically regulating the level of calcium your body by taking calcium when it"s in low, when it"s low in the, in the body, low in circulation and also, and also taking it from bone by increasing the amount of osteoclastic task and also the rerotate of calcium and depositing calcium as soon as you have a surfeit of it right into bone, creating it at that time. And this happens in small areas. It has, and it additionally has very large impacts. The number on the appropriate is sort of a schematic of some of the signaling that goes on. And I"ll simply display you a list of some of the signals that are right here. And this is simply a partial list of some of the signals that are affiliated. And they have actually funny names because of the way the research study is going on and not all entirely meaningful or, or simple to follow. But there"s one below in specific I"d favor you to pay attention to which is P T H R P, parathyroid, hormone associated protein, which is among the signals that is involved in this procedure of directing the the usage and also remodeling of bone. Okay. Deep science. Let"s go to something a little little bit even more straight forward. Here is a radiograph. This is an X Ray taken of a 25 year old male that pertained to the emergency reporting that he had kicked a limp short article in a fit of anger and also later noticed he had quote, challenge walking unquote. you, you could be able to, even those of you who are not medically trained might be able to check out in this image some evidence of the obstacle that was connected in. And although the report does not encompass anypoint explicit about this one suspects that alcohol was involved below at some point. But what happens of course, is that you can sustain a fracture choose this. And then the fracture gets repaired. How many kind of of you have fractured a bone, extensive percent of the audience, at leastern fifty percent. And you will have noticed that when you fractured the bone, that tbelow was a duration of time as soon as it was unsecure. And then progressively it came to be that you felt a lump tright here underneath the surface. If you touched it, you might feel that it was swollen and lumpy and also that over the next year or so, that lump went amethod. And that process is related to the resilience of bone and the techniques of repair. And you watch here on the left when you first break a bone, you have a - you injure the periostin, which is the cellular lining that covers the bone. And then you have a hematoma, which isessentiallya bruise in the bone. And this activity causes the influx of a entirety bunch of different kinds of cells, notably cartridge cartilage cells, which then fill up the area and carry out a type of short termsort of connection between points. And then there"s this intrusion of the cartilage by these energetic facets that lay dvery own bone and what of course they carry out over time as they lay dvery own fairly thick amount of bone of what"s called a callus and that"s what you were feeling in the year after you broke that bone. That lump tright here is referred to as the callus and also it"s bone. It"s continuous bone in the in the normal feeling, however the procedure of remodeling which takes years thereafter or months to years after that. That process of sin, anxiety and also strain progressively sculpts that callus dvery own till it is ago to extremely much favor what the bone was before that is detecting where the strain is, causes excess bone to be chewed up, new bonus lhelp down, however just in the areas wbelow the strain is high and this remodeling process slowly restores the form of the bone and also you"ll have actually noticed that your very own callus progressively became less and much less until you finally didn"t notification it. That"s the remodeling process that"s going on all the moment and also it does take a long time, yet it"s a very vital one bereason aacquire, it restores these attributes. Now this is something that"s been going on for an extremely lengthy time. It doesn"t turn out exceptionally well. Here"s a picture series of images from aa, an Indian excavation from about 1400 a D these are the bones from a interment site of, an elderly at the moment, 50 year old Indian womale who had actually broken her femur. And you have the right to see the break here. It"s pretty clear that there"s one that"s been badly damaged in the various other that"s not there show up. And fairly noticeably there"s the area wbelow the break has occurred is an extremely big, thick clumpy thing. And you"ll additionally alert that the new bone is the repaired bone is much shorter than the various other one. This woguy would have actually walked if she walked at all after that through a destructive limp because one leg was around an inch and a fifty percent shorter than the various other. And the reason this happens is because the muscles that organize together across the length of the bone, when it"s broken, pull the bones, the bone ends across each other so they"re no much longer aligned and shorten it up. And then of course the very same healing process goes on and it heals in that awkward position. Why is this not a trouble for us now? Well, in fact, now we understand this and we protect against that. We understand that bone repair mechanisms will knit broken pieces together, right? If you know that, if you"re going to have actually a fracture, that the normal response to that will be to knit those pieces together. And the totality point of this is to then produce a, an alignment prior to that happens by what"s referred to as reduction. That indicates reducing the fracture so that it simply a currently aligned and then maintaining those, the place of those bones reasonably stationary relative to each various other so that the healing process will finish up restoring that original fictional create. And as those of you that have broken somepoint and had actually a actors, no mechanical stabilization is the crucial. You have to save the mechanical alignment of bone in place for a long sufficient period of time that that will certainly heal and also be relatively solid and also then you have the right to take that cast or whatever"s holding it together off. Yeah. Uh, a relatively considerable amount of effort has been put into this and trying to uncover methods to, to provide this stabilization and reduction. There"s a point referred to as outside fixation. A few of you may have watched someone with an external fixator on. This is not uncommonly offered if the bone if the injury has broken the skin. But you have the right to also perform what"s called interior fixation or an open reduction and internal fixation that w where you perform a surgical procedure, you watch this in the middle wbelow you reduced with the skin, you go dvery own to the bone and then you execute something to organize that bone together. You might put a plate and also some screws in, or as you check out in the image on the much ideal you could perform what"s called an intramedullary nail. This is a lengthy spike. It"s about this long depending on how huge the perboy and it"s a huge lengthy, it looks choose a nail. And then what happens is you gain the person in the appropriate place, you minimize the fracture by putting traction on the leg, pull it acomponent like this. So that the ends of the bone are now in line and also then you take a hammer and also you"d drive the nail dvery own with the hip from the height as you view all the means dvery own and also cross that and bridge that broken area and also then you put a tiny pin in the optimal to host it there so it does not slide out. You can view why I"m an anesthesiologist, but in all these situations, the totality allude of this is to to enable the herbal healing processes to make the bone and reclaim the bone place of feature that it was in before. It"s the worry is what is that place and what is the function? We don"t heal these things. We are not. The orthopedic surgeons execute not heal bone. What they do is they rearvariety bone and also host it in area for a long sufficient duration of time that the natural procedures that are durable in bone will certainly lead to a desirable outcome. Okay. This is a pretty vital idea. In truth, physicians in general are not healers, although they"re frequently explained that way. The body is the healer the physician creates, if they"re lucky, a situation where the alignments and also the attributes are such that the healing have the right to take area. But we depend upon that healing. And in truth, we understand for circumstances, if you have deficiencies of nutrition or various other conditions that the healing is, deserve to be quite hard. This concept around fixation is actually...and also healing is actually fairly old. Here"s a photo on the left of some splints that were taken out of aa tomb in Egypt and reported by George Smith in 1908. And the British clinical journal, these are the most ancient splints that anyone has actually discovered. You watch some of the broken bones tbelow and also the splints were wrapped roughly this. And there"s a point referred to as the Edwin Smith papyrus Iris from around 1600 BC, which you watch below on the right. And this is a, the first clinical text that we recognize about and also a part of this is devoted to taking treatment of broken bones. here, here"s it. Here"s the hieroglyphs composed on the left. And and also bereason I"m sure you"re a little rusty and also you"re very hieroglyphics. I"ve added the translation on the appropriate. but here"s what it claims. This is for a damaged bone of the arm and also it states that it must just area him prostrate on his ago via somepoint folded between his 2 shoulder chisels. Though it need to have spcheck out out with his 2 shoulders in order to stretch his top arm till the break drops right into location. That"s the reduction we"re talking about though must us make for him two splints of linen and that should us use for him. One of them both on the inside of his arm and also the various other of them both on the underside of his arm though have to us bind it via your move. This is the word for plaster of Paris, but Paris hadn"t been designed yet and treat it thereafter with honey every day till he recovers. It"s pretty great medical advice. And in reality there were a groups of human being in primitive Egypt and ever since who are bone setters whose attribute it is to create reduction and fixation and allow or bone to heal. So I would argue that this is a sort of resilience design that is, we understand also the resilience of the mechanism that we are handling and also we are doing design. So that that resilience plays out the lengthy methods which are desirable, that that develop a preferred result. The resilience isn"t ours. We didn"t develop it. We"re not the owners of it. We"re not the generators of it, however we understand that it"s tright here. And interestingly enough and also enough research you, you, you are able to get this type of building that, that will enable you to manipulate that and also heal in excellent attribute. So simply to review, you recognize, the entirety idea below is that that we are getting multiple attributes for bone. It"s a storehouse of calcium and also other points. It plays a actually a number of different functions. it"s a constantly undergoing replacement and also there"s this balance that exists, this dynamic balance in between the devastation and construction and also resilience engineering in this case is using design to a durable device that counts for its success on the existence of resilience. it needs of expertise just how the resilience plays out. It deserve to be effective also without understanding much around the mechanisms of resilience and also it benefits from better expertise of the resources and also modulators of resilience. It was recognized reasonably beforehand, for circumstances, that nutrition is pretty essential to bone healing. Well, pretty good, huh? Now the famed Thomas Hughes created in his book, Tom Brown college holidays, college days. Life isn"t all beer and also Skittles. bone is not perfect. There are a number of diseases of bone. One"s called osteogenesis imperfecta. This is a trouble, a inherited difficulty where bone does not make the right calcium and also lay points dvery own. There"s a disease dubbed Paget"s disease wright here bonus actually absorbed too a lot. There"s osteoporosis. Several of you may recognize this bereason you may have actually elderly parents or you may be approaching old age yourself and you might note that that osteoporosis is a major cause of morbidity. In the USA tright here are cancers of bone. There"s an osteosarcoma, which some of you have actually heard about. Tbelow are problems connected through malnutrition. For circumstances, rickets, you see this in bowed-leg youngsters offered to be exceptionally widespread in the USA, not watched extremely much anymore. And then you have the right to have actually disorders of the signaling, hyperparathyroidism have the right to, which transforms on the osteoclast and reasons them to chew up bone can actually, you can have a tumor of the parathyroid that seats secretes also a lot of this stuff. And out of manage via the calcium regulation mechanism causes the chewing up the bone and the damage of bone leads to fractures and also kidney stones. And so I want to take one example of this, which is osteoporosis. It"s a very important medical problem. I don"t desire to speak to it a condition bereason it"s most likely a, a, a, a organic consequence of aging, however it"s, it"s even more noticeable in older civilization and also it"s especially got a choice for women. you view below a set of radiographs actually that are from CTS of a item of a vertebra and also a normal perboy. And then with osteoporosis. And the procedure below is, is one that wright here the absorption of bone has actually end up being higher than the production of bone. And so you shed bone mass over time and it"s, it"s actually quite difficult to, to counter that. The goal would be to block the, absorb the resorption of bone and, and also type of revolve dvery own, modulate dvery own the osteoclastic activity or to boost the production of bone, revolve up the osteoblastic activity in order to build this sort of stuff. many of you will certainly identify that the consequences of osteoporosis, typically hip or vertebral fractures in elderly women, women that are older, the typical perkid is a womale that age 60 or 70, currently 70 or 80, who has actually a hip fracture or a vertebral fracture. These are really not so a lot a problem through the fracture per seas the fact that the bone has actually shed its strength because of this imbalance between creation and devastation. And there are two means you deserve to solve this. One is you can attempt and also revolve dvery own that, that process that"s chewing. And the other method is you have the right to attempt and also rise the osteoblastic activity that lays down bone. You"ll remember that I talked to you previously around the signaling service that goes on right here and also that I asked you to pay attention to one specific signal, which is parathyroid hormone associated protein. P, T, H, R, P. And over the previous 5 years, actually the study goes ago about 15 or more years or possibly also much much longer. There"s been many interest in understanding the signaling, signaling procedures and also trying to usage them. And tbelow are now drugs notably abaloparatide and teriparatide, which are molecular signalers, which mimic PTHRP. Tright here are molecularly occurred points that are choose parathyroid hormone reput the protein and the presence of these at intervals, you need to carry out it, you need to develop the stimulus at intervals, generates a signal, which claims basically turn up the osteoblastic activity that provides bone and you offer this stuff, it"s an injection you give it when a week or twice a week to people that are at threat for it. And interestingly enough, abaloparatide considerably reduces the incidence of vertebral fractures compared with placebo, via a danger reduction of around 91%, which I will tell you in the medical world is the huge deal, right? We don"t obtain that kind of threat reduction extremely frequently. And so many world, particularly those at risk for osteoporosis notably, interestingly enough uh, white womales, older of a European extraction and smokers specifically we"ll acquire this drug from their medical professionals. I want to allude out that it"s still not all Skittles and beer. There are, there are problems through these drugs in tbelow and at leastern in rats, at extremely high doses, a consistent expocertain to abaloparatide can create some cancers. That is, you deserve to revolve on these mechanisms in methods that cause disastrous outcomes. But this is a type of resilience engineering. I would certainly, I would certainly offer you this as a form of resilience engineering. It transforms the underlying resilience mechanisms that are existing in the device. It relies for its success on a really deep knowledge of resilience. That is you have to actually understand also and also have the ability to manipulate the signaling by the method that drug has actually offered in microgram amounts, right? So we"re talking, you know, things were only a couple of molecules of this are actually getting to the cells. it, it tends to retard the loss of the adaptive capacity of bone. And it likewise, by the method, generates brand-new types of risk, which is somepoint those of us interested in resilience design should probably think around because work-related on resilience design may not all be Skittles and beer. There might be some downside to this, which is concerned our manipulation straight of these effective mechanisms that involve signaling bone reminds us that resilience requires consistent energy and also sources. The background of bone shows up in its structure. You deserve to tell what has happened to a perboy by looking at the structure of bone, which I think is an extremely interesting kind of point. If you think at the organizational level of your own area, you deserve to check out the history of the organization and the design of its software application. it has its own pathologies. It"s delicate to a variety of disruptions, and also it turns out that bone is a lot easier to you. Bony resilience is a lot much easier to use than it is to create this resilience design that I talked around. The first type of resilience engineering, you can speak to it resilience engineering kind one, if you favor, yet this initially kind of resilience design is engineering used to a durable device. It relies for its success on the visibility of resilience in that mechanism. It deserve to be successful even without expertise incredibly a lot around the mechanisms of resilience. It does benefit from higher knowledge of the sources and also modulators of resilience, and also that"s at leastern 3,500 years old. We"ve been doing resilience design for 3,500 years. There"s other kinds of resilience engineering, the one where human being are making use of the modulation of the signaling in microgram amounts to alter the balance. That dynamic balance in between damage and development. That leads to a more or much less static looking image of your skeleton is only about 5 years old. It is a straight, it is an effort to straight alter the resilience of the living device. It"s therefore gained some hazards attached to it, but likewise some excellent possibilities, particularly the truth that micrograms have the right to be provided to affect. This tells you just how effective it is. It relies critically on the success of for its success on deep expertise of resilience. You wouldn"t 3,500 years earlier, 2000 years back, a thousand also years earlier, also even 60 or 70 years back, this would certainly have actually been inconceivable. No one can maybe have imagined doing this. This is the result of many kind of, many type of hundreds of years of intense initiative to try and understand these mechanisms and also many kind of, many kind of brand-new approaches that have been brought to bear only in the past couple of years. It does geneprice new kinds of hazard, but it"s specifically exciting to me bereason it"s, it is a various, it"s qualitatively a different kind of resilience engineering that is, I"m trying to engineer the resilience fairly than you execute engineering that exploits the resilience. And I think we often confuse these two or talk about these two as though they were one. And I think interestingly enough, many type of in world who are interested in resilience initially are interested in trying to enhance resilience or construct up resilience or make resilience more powerful or find new ways to generate resilience. And a whole bunch of various other sorts of descriptive terms, which is that resilience engineering that"s on the ideal hand also side, right? It"s the modulation directly of resilience. But if we look at it a bit even more carefully, we would certainly watch in the background of your own domain and many others, the presence of resilience design over a much longer duration of time. That is human being understanding resilience is present in your mechanism and also finding means to make use of that resilience to engineer the means in which that resilience is brought to bear. And so I would give you PagerDuty and also Rundeck and all the other sponsors of this conference as examples of resilience engineering, their attempts to carry the resilience, which is situated in the human being that are actually maintaining your units to bear in means that permit it to flow more efficiently to regain that feature. And I think we provide that to perhaps some brief shrift in, we"re so fascinated by the idea of resilience and producing resilience that we immediately want to carry out this thing over right here. Not recognizing that to perform that calls for rather a deep knowledge of the resources and operational characteristics of resilience. And that"s quite a huge undertaking. But I would indicate to you that you are doing resilience design in your work on a day-to-day basis. It may not gain that label or a title, however just what you are doing eexceptionally day and also, and also prefer the orthopedics surgeons, you understand sufficient around the resilience in the device to have the ability to engineer it such that the resilience will play out in means that are fertile and useful. You understand also that you need to modulate that by providing the various sorts of nutrition and raw resources and other points. You understand that those are, are essential for that resilience to play out and also enumerating and understanding those things, which has actually been the heritage in orthopedic and orthopedics for at least a 3,500 years is essential to making progress. Tbelow is the possibility of doing this type of resilience design the type two or, or the other kind, the direct manipulation of resilience. But I think it"s going to prove to be a lot more tough for us bereason we will have to have actually a really intimate knowledge of what resilience is and also exactly how it functions in these systems in order to be able to carry out this incredibly successfully. Well, as my psychiatrist friends check out, I see we"re coming close to the end of our time together. So why is this important? I think you are the world that are the majority of likely to be in a place to acknowledge and also possibly to not manage, yet let"s say modulate the way resilience is supplied and engineered the design about resilience to attain particular ends. I think you"re also quite sensitive to the means in which resilience is fragile, the kinds of illness, the repertoire, just like Paget"s condition and also osteosarcoma and also all those that we experienced on bone tbelow. Tbelow are pathologies in your institutions too that will certainly tend to Rob your skeleton of the resilience. And tright here are additionally uh, procedures in the background, which are, which are involve continuous renewal such that we do not really check out them, we check out them as static. The brand-new people coming to your company to learn about units, the old ones leaving, the restructuring of architectures, the contact, rotors, all of those points are a type of background process of, of destruction and also rebirth that creates a type of dynamic balance that preserves resilience and also provides it easily accessible for dealing with the kinds of troubles that you"re going to enrespond to. It"s thus that I commend to you the principle of bone as a design for not as a version, as an archeform for resilience. And I hope that once people say to you later on, what, what is this resilience thing? What, tell me what resilience is. What does resilience mean? Or have the right to you provide me an instance of resilience or resilience engineering that the initially instance that will come to mind for you is bone. So I think it"s really beautiful. I think it"s, it"s gained a quality to it that is, practically, dare I say spiritual. that, that has actually so many of the elements of resilience constructed right into this one nice instance, that exploring it and understanding it is likely to prove to be extremely useful for you later on.

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Thank you extremely much for your type attention.