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.

Transcript

1. © 2019 & 2020 by Richard I. Cook, MD, all rights reserved
   www.croixlorraine.org
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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.
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3. © 2019 & 2020 by Richard I. Cook, MD, all rights reserved
   A simple talk about complex systems
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4. © 2019 & 2020 by Richard I. Cook, MD, all 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?
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5. © 2019 & 2020 by Richard I. Cook, MD, all 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.
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6. © 2019 & 2020 by Richard I. Cook, MD, all 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
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7. © 2019 & 2020 by Richard I. Cook, MD, all 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
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8. © 2019 & 2020 by Richard I. Cook, MD, all 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
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9. © 2019 & 2020 by Richard I. Cook, MD, all 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
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10. © 2019 & 2020 by Richard I. Cook, MD, all 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
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11. © 2019 & 2020 by Richard I. Cook, MD, all 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
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12. © 2019 & 2020 by Richard I. Cook, MD, all 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
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13. © 2019 & 2020 by Richard I. Cook, MD, all 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
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14. © 2019 & 2020 by Richard I. Cook, MD, all 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
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15. © 2019 & 2020 by Richard I. Cook, MD, all 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
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16. © 2019 & 2020 by Richard I. Cook, MD, all 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
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17. © 2019 & 2020 by Richard I. Cook, MD, all 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
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18. © 2019 & 2020 by Richard I. Cook, MD, all rights reserved
    Isn’t this resilience engineering?
    The marvelous resilience of bone
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19. © 2019 & 2020 by Richard I. Cook, MD, all 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…
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20. © 2019 & 2020 by Richard I. Cook, MD, all 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
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21. © 2019 & 2020 by Richard I. Cook, MD, all rights reserved
    The marvelous resilience of bone
    "Life isn't all beer and skittles."
    Hughes (1857) Tom Brown's Schooldays
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22. © 2019 & 2020 by Richard I. Cook, MD, all 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
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23. © 2019 & 2020 by Richard I. Cook, MD, all 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
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24. © 2019 & 2020 by Richard I. Cook, MD, all 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
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25. © 2019 & 2020 by Richard I. Cook, MD, all 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
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26. © 2019 & 2020 by Richard I. Cook, MD, all 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
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27. © 2019 & 2020 by Richard I. Cook, MD, all 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
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28. © 2019 & 2020 by Richard I. Cook, MD, all 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
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29. © 2019 & 2020 by Richard I. Cook, MD, all 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.
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30. © 2019 & 2020 by Richard I. Cook, MD, all rights reserved
    The marvelous resilience of bone
    Increase
    osteoblast
    activity
    ↑
    Reduce
    osteoclast
    activity
    ↑
    treating osteoporosis by tipping the balance
    bone
    remodeling
    PTHrP
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31. © 2019 & 2020 by Richard I. Cook, MD, all 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
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32. © 2019 & 2020 by Richard I. Cook, MD, all 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
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33. © 2019 & 2020 by Richard I. Cook, MD, all 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…
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34. © 2019 & 2020 by Richard I. Cook, MD, all 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
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35. © 2019 & 2020 by Richard I. Cook, MD, all 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
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36. © 2019 & 2020 by Richard I. Cook, MD, all 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.
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37. © 2019 & 2020 by Richard I. Cook, MD, all 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
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38. © 2019 & 2020 by Richard I. Cook, MD, all rights reserved
    The marvelous resilience of bone
    Thank you!
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