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    3. In studies of humans, further quantify the relationships between exposures and outcomes, including:

    • Dose-response relationships across the full range of relevant exposures in the context of work.

    • Host factors, such as age, sex, previous injury, comorbidity, smoking, and physical condition.

    • Interaction of physical and psychosocial factors.


    1. Conduct tissue mechanobiology studies directed toward:

    • Characterizing ultrastructural and cellular responses to cyclical physical loading exposure for vertebrae/disc, upper extremity tendon and muscle, and peripheral nerve using in vivo (animal) models. This involves:

        — Determining time frame, capacity, and mechanisms of the repair and remodeling responses associated with cyclic loading and injury, including the effect of various patterns of rest and reuse after injury on the mechanisms and time course of recovery.

        — Developing quantitative dose-response models identifying dose-response relationships for injury for tendons, muscles, and nerves.

        — Determining the dose-response relationships between pattern of load (e.g., rate of loading, duty cycle) for repeated loading and functional and structural damage to discs, tendons, muscles, and nerves.

        — Developing an in vivo upper extremity loading model for neuromuscular disorders for the evaluation of mechanisms of injury associated with cyclical loading. Determining the missing steps of the injury pathways associated with repeated loading, especially for muscles, tendons, and nerves. Determining the role of conditioning and health on injury susceptibility.

        — Identifying injury thresholds for sustained and repeated loading (e.g., load duration or load repetition) for disc, tendon, and muscle.

        — Determining thresholds for critical pressure duration for chronic nerve injury.

        — Determining the earliest molecular changes that precede structural damage and inflammatory responses to muscles, tendons, ligaments, bones, and nerves during various types of repetitive loading.

        — Validating noninvasive measures of skeletal muscle functional changes and symptoms associated with repetitive use disorders by establishing their biological basis in controlled scientific studies, with

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