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The Bone Talk: Resilience and resilience engineering explained - Dr. Richard Cook, DevOpsDays Chicago 2020

The Bone Talk: Resilience and resilience engineering explained - Dr. Richard Cook, DevOpsDays Chicago 2020

What is resilience? What is resilience engineering? This talk will ground your understanding of those terms using the compelling example of bone. Bone is the archetype of resilience and medicine the archetype of resilience engineering. The features of bone development, maintenance, and repair are graceful extensibility and sustained adaptability. They give the skeleton its capacity to grow, to retain strength, to remodel in the face of stress, and to repair damage. These are costly, effortful, energy requiring activities that are strike a fine balance between competing demands. We have learned – with great effort and much experimentation – how to anticipate and channel these features to benefit individuals. More recently, discoveries about how bone resilience remodeling is guided have provided opportunities to modulate some resilience signals directly. Everything about bone commends it to this community as the primary example of resilience and resilience engineering.

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DevOpsDays Chicago

September 01, 2020
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  1. © 2019 & 2020 by Richard I. Cook, MD, all

    rights reserved www.croixlorraine.org 1 Cook, RI (2020). DevOps Days Chicago 2020 1
  2. © 2019 & 2020 by Richard I. Cook, MD, all

    rights reserved Richard I. Cook, MD Principal Adaptive Capacity Labs Brooklyn, NY Emeritus Professor of Healthcare System Safety Royal Institute of Technology Stockholm, SWEDEN A few observations on the marvelous resilience of bone and resilience engineering Conflict of interest statement and disclaimer: The speaker has no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies; expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the biological subject matter or materials discussed in this presentation. The presentation is not an endorsement of or recommendation for any therapy, method, medication, or form of treatment. Nothing in this presentation should be construed as medical advice. 2 Cook, RI (2020). DevOps Days Chicago 2020 2
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    rights reserved A simple talk about complex systems 3 Cook, RI (2020). DevOps Days Chicago 2020 3
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    rights reserved The marvelous resilience of bone Bone is not a model of or a metaphor for resilience. Bone is the archetype of resilience. Assertion: Question: What is resilience engineering? 4 Cook, RI (2020). DevOps Days Chicago 2020 4
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    rights reserved The marvelous resilience of bone Bone’s resilience is… ✦ ‘Woodsian’: • graceful extensibility • sustained adaptability ✦ expensive: requires continual energy and resource inputs ✦ delicate: • can be disrupted by loss of feedback • susceptible to disease ✦ limited: has a peak and then diminishes over time Woods,DD. Four concepts for resilience and the implications for the future of resilience engineering. Reliability Engineering and System Safety 141: 5-9, 2015. Woods,DD. The theory of graceful extensibility: basic rules that govern adaptive systems. Environment Systems and Decisions 38:433–457, 2018. 5 Cook, RI (2020). DevOps Days Chicago 2020 5
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    rights reserved ✦ Bone is continuously remodeled: • adult skeleton is replaced every 10 yrs • making new bone is in dynamic balance with destroying old bone • demolition and construction is directed by mechanical strain ✦ Bone repair is an extension of remodeling that engages additional mechanisms. ✦ Bone is the primary store for essential elements calcium and phosphorus. ✦ It’s all about signaling: • there is no master controller • a messy, layered network with lots of crosstalk between the organism, anatomical regions, cellular, and intracellular (organelle) levels [You want complexity? Here's some real complexity!] The marvelous resilience of bone 6 Cook, RI (2020). DevOps Days Chicago 2020 6
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    rights reserved The marvelous resilience of bone X10 X100 Bone has complex macro and micro architecture. Figure credit: basicbiomedicalkey.com https:// basicmedicalkey.com/bone-3/#ch08fig7 & #ch08fig8 7 Cook, RI (2020). DevOps Days Chicago 2020 7
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    rights reserved ✦ Use of bone mass is energetically efficient. ✦ New bone is laid down along strain lines. ✦ Regular strain leads to a regular pattern. • The pattern is tuned (the organism is prepared for similar future stress). • Much of the pattern emerges (i.e. it is not programmed). ✦ There may be an optimal strain experience. The marvelous resilience of bone continuous remodeling 8 Cook, RI (2020). DevOps Days Chicago 2020 8
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    rights reserved Duncan-Bassett JH, Williams GR (2016), Role of Thyroid Hormones in Skeletal Development and Bone Maintenance. Endocrine Reviews 37(2):135–187. Bellido T (2014). Osteocyte-Driven Bone Remodeling. Calcif Tissue Int 94(1): 25–34. doi:10.1007/s00223-013-9774-y. Remodeling ✦ lay down new & absorb old in balance osteoblasts & osteoclasts ✦ realign structural strength to fit the need ✦ local direction with global modulation ✦ repair microfractures ✦ recycle Ca and P The marvelous resilience of bone 9 Cook, RI (2020). DevOps Days Chicago 2020 9
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    rights reserved The marvelous resilience of bone macro and micro scales interact Figure credit: Lavríková, http://fblt.cz/en/skripta/xi-regulacni-mechanismy-1- endokrinni-regulace/5-hormony-stitne-zlazy-a-pristitnych-telisek/ 1 kg Ca2+ signals 10 Cook, RI (2020). DevOps Days Chicago 2020 10
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    rights reserved • balanced • continuous • energy consuming • fiendishly complex! OSM PTHrP sclerostin TGFb IGF-1 CT-1 Sema4D S1P ephrinB2 EphB4 Sema3a OSM RANKL Sema3B Wnt5a OPG OSM interleukins RANKL signals (partial list) The marvelous resilience of bone Remodeling is ParaThyroid Hormone related Protein 11 Cook, RI (2020). DevOps Days Chicago 2020 11
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    rights reserved The marvelous resilience of bone 25 y♂ Patient reports that he "kicked a lamp post in a fit of anger" and later noticed he had "difficulty walking" ... Figure credit: https://radiopaedia.org/cases/tibial-midshaft-fracture 12 Cook, RI (2020). DevOps Days Chicago 2020 12
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    rights reserved Betts DC, Müller R (2014). Mechanical regulation of bone regeneration: theories, models, and experiments. Frontiers in Endocrinology 5 (211): 1-14. doi: 10.3389/fendo.2014.00211 Hematoma Injured periosteum callus woven bone cartilage “reactive” “reparative” “remodeling” hrs - days days - wks wks - months yrs - lifetime time The marvelous resilience of bone Repair 13 Cook, RI (2020). DevOps Days Chicago 2020 13
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    rights reserved The marvelous resilience of bone Rosado MA, Vernacchio-Wilson J (2006). Paleopathology and osteobiography of the people of Peñuelas, Chile’s semiarid north. Mem Inst Oswaldo Cruz, Rio de Janeiro 101(Suppl. II): 85-95. (fig. 24 - 26). ~1400 AD 50+ yr old ♀ Chilean 14 Cook, RI (2020). DevOps Days Chicago 2020 14
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    rights reserved Queen’s University School of Medicine https://meds.queensu.ca/central/assets/modules/cast- application/thumb_spica_cast.html • Bone repair mechanisms will knit broken pieces together. • Reduction restores alignment. • Keeping the ends stationary is essential. • Mechanical stabilization is key. The marvelous resilience of bone 15 Cook, RI (2020). DevOps Days Chicago 2020 15
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    rights reserved External fixation (closed reduction) Internal fixation (open reduction) Betts DC, Müller R (2014). Mechanical regulation of bone regeneration: theories, models, and experiments. Frontiers in Endocrinology 5 (211): 1-14. doi: 10.3389/fendo.2014.00211 “The Bone Room”: http://52.62.202.235/lower-limb/hip/femur- fractures/femoral-shaft-fractures The marvelous resilience of bone 16 Cook, RI (2020). DevOps Days Chicago 2020 16
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    rights reserved Smith GE (1908). The most ancient splints. British Medical Journal March 28, 1908: 732-4. Edwin Smith papyrus, ~1600 BCE. The marvelous resilience of bone 17 Cook, RI (2020). DevOps Days Chicago 2020 17
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    rights reserved Isn’t this resilience engineering? The marvelous resilience of bone 18 Cook, RI (2020). DevOps Days Chicago 2020 18
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    rights reserved • is engineering applied to a resilient system; • depends on resilience already present; • requires understanding how resilience plays out; • can be successful even without understanding the mechanisms of resilience; • benefits from knowing what modulates resilience. Resilience engineering… 19 Cook, RI (2020). DevOps Days Chicago 2020 19
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    rights reserved ✦ Bone is the storehouse for calcium. ✦ The skeleton is continuously replaced. ✦ Old bone is dissolved & calcium recycled. ✦ New bone is laid down along strain lines. ✦ Repair & replacement use similar mechanisms. ✦ The balance between destruction and construction has local and global regulation. The marvelous resilience of bone 20 Cook, RI (2020). DevOps Days Chicago 2020 20
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    rights reserved The marvelous resilience of bone "Life isn't all beer and skittles." Hughes (1857) Tom Brown's Schooldays 21 Cook, RI (2020). DevOps Days Chicago 2020 21
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    rights reserved •Osteogensis imperfecta •Paget’s disease •Osteoporosis •Osteosarcoma •Ricketts, malnutrition •Hyperparathyroidism Fassier FR (2016). Osteogenesis imperfecta. In Sabharwal S, ed., Pediatric Lower Limb Deformities: Principles and Techniques of Management. Springer- Verlag. (fig 16.1) The marvelous resilience of bone 22 Cook, RI (2020). DevOps Days Chicago 2020 22
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    rights reserved •Osteogensis imperfecta •Paget’s disease •Osteoporosis •Osteosarcoma •Ricketts, malnutrition •Hyperparathyroidism Charles JF (2017). Paget Disease of Bone; Paget's Disease of Bone; Osteitis Deformans. In The Merck Manual. https:// www.merckmanuals.com/en-pr/professional/musculoskeletal- and-connective-tissue-disorders/paget-disease-of-bone/paget- disease-of-bone The marvelous resilience of bone 23 Cook, RI (2020). DevOps Days Chicago 2020 23
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    rights reserved •Osteogensis imperfecta •Paget’s disease •Osteoporosis •Osteosarcoma •Ricketts, malnutrition •Hyperparathyroidism UPI (2016). Most hip fracture patients not told they have osteoporosis, survey suggests. UPI Health News. https://www.upi.com/Health_News/2016/05/19/ Most-hip-fracture-patients-not-told-they-have-osteoporosis-survey-suggests/ 8351463670870/ The marvelous resilience of bone 24 Cook, RI (2020). DevOps Days Chicago 2020 24
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    rights reserved •Osteogensis imperfecta •Paget’s disease •Osteoporosis •Osteosarcoma •Ricketts, malnutrition •Hyperparathyroidism Welcome Collection Gallery. M0018166. http:// catalogue.wellcomelibrary.org/record=b1080628 The marvelous resilience of bone 25 Cook, RI (2020). DevOps Days Chicago 2020 25
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    rights reserved •Osteogensis imperfecta •Paget’s disease •Osteoporosis •Osteosarcoma •Ricketts, malnutrition •Hyperparathyroidism Wellcome Collection. Ricketts. https://wellcomecollection.org/works/kpftgz5u The marvelous resilience of bone 26 Cook, RI (2020). DevOps Days Chicago 2020 26
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    rights reserved •Osteogensis imperfecta •Paget’s disease •Osteoporosis •Osteosarcoma •Ricketts, malnutrition •Hyperparathyroidism Myhre A (2004). University of Washington, UWMC Roosevelt Clinic, Musculoskeletal R. http://uwmsk.org/residentprojects/ hpth.htmladiology The marvelous resilience of bone 27 Cook, RI (2020). DevOps Days Chicago 2020 27
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    rights reserved Alexander C (2001) Idiopathic osteoporosis: an evolutionary dys-adaptation? Ann Rheum Dis 60:554–558. Young adult (normal) Elderly adult (osteporotic) Looker AC et al. (2012). Osteoporosis or Low Bone Mass at the Femur Neck or Lumbar Spine in Older Adults: United States, 2005–2008. National Center for Health Statistics Data Brief No. 93. Osteoporosis The marvelous resilience of bone 28 Cook, RI (2020). DevOps Days Chicago 2020 28
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    rights reserved The marvelous resilience of bone …blocking bone resorption is one way to decrease bone loss and prevent fractures… Stimulation of bone formation can also reverse skeletal fragility; new therapies based on this approach have recently been developed. Bone health and osteoporosis : a report of the Surgeon General. Rockville, Md. : U.S. Dept. of Health and Human Services, Public Health Service, Office of the Surgeon General; Washington, D.C. 2004, p. 32. 29 Cook, RI (2020). DevOps Days Chicago 2020 29
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    rights reserved The marvelous resilience of bone Increase osteoblast activity ↑ Reduce osteoclast activity ↑ treating osteoporosis by tipping the balance bone remodeling PTHrP 30 Cook, RI (2020). DevOps Days Chicago 2020 30
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    rights reserved teriparatide OSM PTHrP sclerostin TGFb IGF-1 CT-1 Sema4D S1P ephrinB2 EphB4 Sema3a OSM RANKL Sema3B Wnt5a OPG OSM interleukins RANKL signals (partial list) abaloparatide The marvelous resilience of bone ParaThyroid Hormone related Proteins 31 Cook, RI (2020). DevOps Days Chicago 2020 31
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    rights reserved The marvelous resilience of bone Regulatory Toxicology and Pharmacology 86: 356-365, 2017. It’s still not all skittles and beer. “abaloparatide significantly reduced incident vertebral fractures compared with placebo (relative risk reduction =  91%; 0.5% versus 5.6%; p < 0.001) … McCloskey, E.V., Fitzpatrick, L.A., Hu, MY. et al. Arch Osteoporos (2019) 14: 15. https://doi.org/10.1007/s11657-019-0564-7 32 Cook, RI (2020). DevOps Days Chicago 2020 32
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    rights reserved The marvelous resilience of bone • acts on resilience mechanisms; • depends on deeper understanding resilience; • sustains adaptive capacity; • generates new types of hazard. This type of resilience engineering… 33 Cook, RI (2020). DevOps Days Chicago 2020 33
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    rights reserved The marvelous resilience of bone Two different types of resilience engineering: • acts directly on resilience mechanisms; • depends on deeper understanding resilience; • sustains adaptive capacity; • generates new types of hazard. • engineering applied to a resilient system; • depends on resilience already present; • requires understanding how resilience plays out; • can be successful even without understanding the mechanisms of resilience; • benefits from knowing what modulates resilience. OSM PTHrP sclerosti n TGFb IGF-1 CT-1 Sema4 EphB4 Sema3a OSM RANKL Sema3B Wnt5a OPG OSM interleuki signals (partial ~3500 yrs old ~5 yrs old 34 Cook, RI (2020). DevOps Days Chicago 2020 34
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    rights reserved The marvelous resilience of bone What relevance to devops? Lots of claims about resilience in IT! Diverse uses without agreed on meaning. [on purpose?] Implies that resilience is reliability++. $sed 's/reliability/resilience/' marke3ng.txt 35 Cook, RI (2020). DevOps Days Chicago 2020 35
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    rights reserved The marvelous resilience of bone What relevance to devops? There is a lot of resilience & resilience engineering in IT! It's above the line. 36 Cook, RI (2020). DevOps Days Chicago 2020 36
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    rights reserved The marvelous resilience of bone acmqueue | november-december 2019 41 software design People working above the line of representation continuously build and refresh their models of what lies below the line. That activity is critical to the resilience of Internet-facing systems and the principal source of adaptive capacity. Imagine that all the people involved in keeping your web-based enterprise up and running suddenly stopped working. How long would that system continue to function as intended? Almost everyone recognizes that the “care and feeding” of enterprise software systems requires more or less constant attention. Problems that require intervention crop up regularly—several times a week for many enterprises; for others, several times a day. Publicly, companies usually describe these events as sporadic and minor—systemically equivalent to a cold or flu that is easily treated at home or with a doctor’s office visit. Even a cursory look inside, however, shows a situation more like an intensive care unit: continuous monitoring, elaborate struggles to manage related resources, and many interventions by teams of around-the-clock experts working in shifts. Far from being hale and hearty, these The resilience of Internet-facing systems relies on what is above the line of representation. RICHARD I. COOK, M.D. 1 OF 11 TEXT ONLY Above the Line, Below the Line ACM Queue 2019 App Ergo 2020 RI Cook and BA Long, in press. Building and revising adaptive capacity sharing for incident response: a case of resilience engineering 37 Cook, RI (2020). DevOps Days Chicago 2020 37
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    rights reserved The marvelous resilience of bone Thank you! 38 Cook, RI (2020). DevOps Days Chicago 2020 38