We believe that the compact characteristics of the CCD which are optimal for the spaceflight environment will also fulfill the needs for an in-house exercise device or for a nursing home. It is well known that impaired balance is associated with aging and with an increased risk of falling. Balance training exercise in the elderly has been shown to reduce risk of falls. In particular, resistive exercise has been shown to increase muscle strength in the elderly, and increases in muscle strength and balance are associated with improvements in performance and mobility, which are important determinants of quality of life in the elderly. Finally, by focusing on resistive exercise in the abductor and adductor muscle groups, this device is expected both to improve lateral balance and reduce the rate of age-related bone loss by stressing those muscle groups that attach at the hip and thus provide significant mechanical loads on the proximal femur.

The current year of the study, ending 8/31/09, was devoted to starting a training study to demonstrate that cardiovascular and resistive exercise could improve measures of muscle strength and endurance. The study components included training on the CCD at our facility and pre- intermediate and post training testing at the Exercise Laboratory at the Clinical Research Center (CRC) of the UCSF Clinical and Translational Science Institute. We have made considerable progress:

1) The CCD was installed in 12/2008. We also brought new personnel onto the project so that the training study could be carried out at UCSF. Mr Tim Streeper, an Exercise Physiologist, was brought in to lead the training study. Dr Lynda Frassetto, Medical Director of the CRC, joined as our Study Physician. Dr Kathleen Mulligan, director of the CRC Exercise Lab, became a co-investigator. Drs Frassetto and Mulligan have been instrumental in use of the CRC for the pre and post training strength and V02max testing.

2) We carried out pilot studies to reveal issues with the study logistics and operation of the CCD. These pilot studies revealed multiple technical issues with the operation of the device in strength training and stepping mode. These problems were identified and fixed in the first part of 2009, which delayed the projected start of the training study from March to May 2009.

3) We started the training study in May 2009. As of time of this report, three subjects have finished the full twelve week study, with four more subjects in initial and intermediate phases of the study. By the end of the project period, four subjects will have completed training.

4) Initial results are positive. On average, with three subjects complete, VO2max increases by an average of 7%, and leg press strength by 60%. Hip abductor and adductor strength increase by 20 and 68% respectively. Given that the technical problems associated with the early part of the study have been addressed, we expect to make considerable progress towards completing the study in the coming year.

We believe that the compact characteristics of the CCD which are optimal for the spaceflight environment will also fulfill the needs for an in-house exercise device or for a nursing home. It is well known that impaired balance is associated with aging and with an increased risk of falling. Balance training exercise in the elderly has been shown to reduce risk of falls. In particular, resistive exercise has been shown to increase muscle strength in the elderly, and increases in muscle strength and balance are associated with improvements in performance and mobility, which are important determinants of quality of life in the elderly. Finally, by focusing on resistive exercise in the abductor and adductor muscle groups, this device is expected both to improve lateral balance and reduce the rate of age-related bone loss by stressing those muscle groups that attach at the hip and thus provide significant mechanical loads on the proximal femur.

For cardiovascular exercise, the stepper is bolted to the platform. The stepper allows for 8" maximum displacement between petals at high stepping rates. Balance training is carried out during the stepping motion, as the subject moves the passive Stewart platform in concert with the displayed visual cues.

For resistive lower body exercise, the subject is loaded onto the platform with four pneumatic subject load devices attached to the subject through a shoulder harness.

Together, the SLDs provide a maximum resistive load up to 435 lbs in 5 lb increments. The device is designed to support the following resistive exercises:

• Squats: 20" maximum vertical displacement with a maximum load up to 435 lbs. This exercise is carried out on an empty platform with the stepper removed.

• Abductor/Adductor exercises: the stepper is removed and replaced with a horizontal rail system allowing 15" horizontal leg motion in each direction against a maximum load up to 435 lbs.

• Heel raises are performed with the device configured for squats, against a maximum load of 435 lbs.

• Leg extensions are carried out with the device configured for squats. A bungee configuration is employed to produce high levels of resistance.

The device in its current form will be transferred to UCSF where it will be employed in a training study with the goal of qualifying the CCD for eventual inclusion in the Flight Analog Project bedrest study. For eventual flight status, the device will be redesigned to obviate the need to replace the stepper and horizontal rail adjustment in transition between exercise modalities.

We aim to devise a time-efficient integrated battery of countermeasures that can be conducted in the confines of the lunar habitat to minimize the risk of musculoskeletal injury. These countermeasures will be validated using a 10-degree head-up bed-rest simulation of a lunar mission. The specific objectives of the countermeasure battery will be to preserve muscle strength and cardiovascular fitness; to minimize decrements in postural stability, dynamic balance and the ability to make corrective actions prior to a fall; to preserve functional performance on mission-relevant tasks; and to minimize bone loss in the proximal femur.

This will be accomplished through a combination of novel resistance exercises on a device designed by our commercial partner that will load specific muscle groups at the hip and in the lower extremity. It will also allow balance and coordination training. We hypothesize that the combined effect of this multifaceted intervention will be to significantly reduce the risk of a work-related falls and subsequent injuries. We will test our hypothesis by randomizing half of our subjects to a group which will undergo the integrated countermeasure and the other half to a control group. Pre- and post-bed rest, we will compare indices of balance, muscle strength, and skeletal density and function using a combination of functional and strength tests, serum and urine bone markers, and CT and DXA imaging of the hip, spine and tibia.