Elimination sequence optimization for SPAR

SPAR is a large-scale computer program for finite element structural analysis. The program allows user specification of the order in which the joints of a structure are to be eliminated since this order can have significant influence over solution performance, in terms of both storage requirements and computer time. An efficient elimination sequence can improve performance by over 50% for some problems. Obtaining such sequences, however, requires the expertise of an experienced user and can take hours of tedious effort to affect. Thus, an automatic elimination sequence optimizer would enhance productivity by reducing the analysts' problem definition time and by lowering computer costs. Two possible methods for automating the elimination sequence specifications were examined. Several algorithms based on the graph theory representations of sparse matrices were studied with mixed results. Significant improvement in the program performance was achieved, but sequencing by an experienced user still yields substantially better results. The initial results provide encouraging evidence that the potential benefits of such an automatic sequencer would be well worth the effort

Estimating Trabecular Bone Mechanical Properties From Non-Invasive Imaging

An important component in developing countermeasures for maintaining musculoskeletal integrity during long-term space flight is an effective and meaningful method of monitoring skeletal condition. Magnetic resonance imaging (MRI) is an attractive non-invasive approach because it avoids the exposure to radiation associated with X-ray based imaging and also provides measures related to bone microstructure rather than just density. The purpose of the research for the 1996 Summer Faculty Fellowship period was to extend the usefulness of the MRI data to estimate the mechanical properties of trabecular bone. The main mechanical properties of interest are the elastic modulus and ultimate strength. Correlations are being investigated between these and fractal analysis parameters, MRI relaxation times, apparent densities, and bone mineral densities. Bone specimens from both human and equine donors have been studied initially to ensure high-quality MR images. Specimens were prepared and scanned from human proximal tibia bones as well as the equine distal radius. The quality of the images from the human bone appeared compromised due to freezing artifact, so only equine bone was included in subsequent procedures since these specimens could be acquired and imaged fresh before being frozen. MRI scans were made spanning a 3.6 cm length on each of 5 equine distal radius specimens. The images were then sent to Dr. Raj Acharya of the State University of New York at Buffalo for fractal analysis. Each piece was cut into 3 slabs approximately 1.2 cm thick and high-resolution contact radiographs were made to provide images for comparing fractal analysis with MR images. Dual energy X-ray absorptiometry (DEXA) scans were also made of each slab for subsequent bone mineral density determination. Slabs were cut into cubes for mechanical using a slow-speed diamond blade wafering saw (Buehler Isomet). The dimensions and wet weights of each cube specimen were measured and recorded. Wet weights were also recorded. Each specimen was labeled and marked to denote anatomic orientations, i.e. superior/inferior (S/I), media/lateral (M/L), and anterior/posterior (A/P). The actual locations of each cube cut were documented and images distributed to define ROI locations for other analyses (to Raj Acharya for fractal analysis, to Jon Richardson at Baylor College of Medicine for DEXA, and to Chen Lin at Baylor College of Medicine for T2* MRI analysis). Quasistatic mechanical testing consisted of compressive loading in all three mutually perpendicular anatomic directions. Cyclic loading was applied for 10 cycles to precondition the specimen and results calculated for the eleventh. For one of three directions tested on each specimen, the 10 cycles were followed with loading to failure. Testing is currently proceeding and once completed the results will be correlated with data from the other analyses. One of the main points of interest is the relationship between fractal dimension and mechanical properties. Throughout preparation and testing all specimens were maintained hydrated with physiological saline and stored frozen when not being used

Impact of Non Steroidal Anti-Inflammatory Drug Administration Pre- or Post-Resistance Training on Bone

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load. The effects of giving NSAIDs pre- and post-resistance training over multiple training sessions are not yet well defined. Therefore, the aim of this study was to elucidate the effects of NSAIDs when administered pre and post simulated resistance training (SRT) in a small animal model. We hypothesize that gains in bone mass and increased bone size will be diminished in adult rats given ibuprofen before each training session, but will be enhanced if ibuprofen is given after each exercise bout. Methods: Fifteen 5-month-old virgin female Sprague-Dawley rats completed 9 SRT sessions at 75% peak isometric strength for 4 sets of 5 repetitions; each contraction included 1 sec isometric + 1 sec eccentric contraction. Animals were blocked assigned by body weight to one of three groups: (1) ibuprofen (30mg/kg) before exercise, placebo after (I:P)(n=4), (2) placebo before exercise, ibuprofen after (P:I)(n=5) and (3) placebo before exercise, placebo after (P:P)(n=6). In vivo pQCT scans measured changes in total volumetric bone mineral density (vBMD), cancellous vBMD, and total area at the proximal tibia, and cortical vBMD, cortical bone mineral content (BMC) and total area at midshaft tibia from days -7 and 21. Body weights were measured at days 4, 14 and 21. Results: There were no significant changes in body weight over the course of the study (P:P -2.6%, I:P -2.3% & P:I -3.8%, day 21 vs day 4). Furthermore, there was no significant difference across time in midshaft cortical vBMD, but the P:I group did exhibit a significantly different response in cortical vBMD when normalized to body weight (+5.1%) (p\u3c .05) compared to I:P (-1.4%) and P:P (-0.3%). There were no differences among groups for change in cancellous vBMD, total vBMD and total area at the proximal region, as well as cortical BMC and total area at midshaft tibia. Conclusion: These data are preliminary but suggest that ibuprofen given after exercise may produce additional gains in cortical bone following resistance training; we have no evidence thus far that ibuprofen taken before exercise has any effect. Supported by Huffines Institute of Sports Medicine and Human Performance, Texas A&M University

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65-78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values

Effects of Multiple Bouts of Long-duration Hindlimb Unloading and Recovery on Rat Plantaris Muscle

Exposure to microgravity results in a rapid reduction of muscle mass. However, few studies exist designed to examine the effects of multiple long-term exposures to microgravity with alternating recovery periods on skeletal muscle. To determine what happens to the recovery of skeletal muscle when faced with subsequent unloading and recovery periods. Male Sprague-Dawley (6 mo) were assigned to the following groups as shown in figure 1 below: 28d hindlimb unloading (1HU), 28d HU session followed by a 56d recovery bout of normal cage ambulation at 1g (1HU+REC), 2 cycles of 28d HU with a 56d recovery period between unloadings (2HU), 2 cycles of 28d HU as in the 2HU group, but followed by an additional 56d recovery at 1g (2HU+REC), and an age- and housing-matched control group (CON). On the final day of the experimental period, plantaris muscles were excised and weighed. The 1HU+REC (0.548 ± 0.012), 2HU+REC (0.562 ± 0.015), and CON (0.550 ± 0.013) showed no statistical difference (p\u3e0.05) between each other. The 1 HU (0.442 ± 0.020) and 2 HU (0.431 ± 0.011) groups were significantly less (p\u3c0.001) than recovery and aged control animals but were not significantly different from each other. The results show that the plantaris muscle presented reduction of muscle mass with initial and subsequent exposures to microgravity. However, with the recovery period, animals were able to regain lost muscle mass, similar to age-matched controls. These findings would be relevant for astronauts participating in multiple long-duration missions throughout their career

Effects of Voluntary Resistance Exercise Training During Recovery From Hindlimb Unloading on Rat Gastrocnemius Muscle

As research continues to examine the deleterious impact of long-duration spaceflight on human muscle mass and function, there remain gaps in our knowledge of muscle physiology, especially in examining how muscle’s ability to recover or rehabilitate from unloading may alter the results of multiple exposures to microgravity followed by 1g recovery. The purpose of this study was to analyze the effects of resistance exercise training of gastrocnemius muscle mass and anabolism during the initial recovery period immediately following a bout of unloading, as well as to examine the role that exercise may have on a subsequent period of weightlessness. This was achieved in rodent models of simulated spaceflight (0g), recovery (1g), and resistance training (\u3e1g) using male Sprague-Dawley (6 mo) rats randomly assigned to the following groups: 28d hindlimb unloading (HU), 28d HU followed by a 56d recovery period of normal cage ambulation at 1g (1HU+REC), 2 cycles of 28d HU with a 56d recovery period between unloading (2HU), 2HU followed by an additional 56d recovery at 1g (2HU+REC), or an age- and housing-matched control group (CON). In addition, following the initial 28d HU period, two groups of animals were given 7d recovery at 1g followed by a 7wk (3 sessions/wk) moderate-intensity, moderate-volume voluntary resistance exercise program (EX) in which the animals were trained to perform a squat-like motion with full extension of the lower limb and resistance was applied incrementally by weighted pouches over the scapula to ~65% bodyweight. At the conclusion of the experiments, gastrocnemius muscles were carefully excised, weighed, and evaluated for cumulative (24h) rates of protein synthesis (FSR). Values of both muscle mass and FSR were lower than control during periods of unloading (p\u3c0.05), but with recovery, control values were reached for mass and surpassed for FSR. Interestingly, there was no significant difference between the mass of 2HU and 2HU+EX (p\u3e0.05), and both were diminished in comparison to control animals, suggesting that benefits of exercise during periods of ambulatory reloading after disuse/microgravity may not be additive. In conclusion, our data suggest that given adequate recovery, microgravity-induced losses of muscle mass can be fully restored to control values, and this adaptational response persists even with multiple exposures. These findings may have important implications not only for career astronauts, but also for individuals who have been subjected to casting of a limb or a period of bed rest following severe injury or illness

Impact of Anti-Resorptive Treatment on Recovery of Bone After Disuse

Bisphosphonates (BP), drugs that inhibit bone resorption, are used to minimize bone loss in long-duration spaceflight, extended bed rest, and acute spinal cord injury; however, the long term impact of BP use on recovery of bone after disuse is not well understood. This experiment tests the hypothesis that the BP zoledronic acid (ZOL) administered 7 days before hindlimb unloading (HU) will protect against loss of bone mass during 28 days of HU by suppressing bone resorption activity while also diminishing the ability of cancellous bone formation rate (BFR) to recover following HU. Male Sprague Dawley rats (6 mo) were assigned to aging control (AC), HU, and HU+ZOL groups and subjected to 28 days of HU, then to 56 days of weight-bearing recovery (REC). One group of rats was given 2 fluorescent labels 7 days apart to measure BFR in the final week of HU and the other group was given the same labels in the final week of REC. Histomorphometric analyses of the proximal tibia and distal femur showed lower osteoclast surface, a measure of bone resorption, 35 days after injection and 119 days after injection (-50% and -75%, respectively, compared to HU). This verified that ZOL successfully suppressed bone resorption. Dynamic histomorphometry revealed that cancellous BFR was lower in ZOL+HU versus AC both immediately after HU (-96.6%) and after the recovery period (-99.9%) (

Raloxifene Enhances Material-Level Mechanical Properties of Femoral Cortical and Trabecular Bone

We have previously documented that raloxifene enhances the mechanical properties of dog vertebrae independent of changes in bone mass, suggesting a positive effect of raloxifene on material-level mechanical properties. The goal of this study was to determine the separate effects of raloxifene on the material-level mechanical properties of trabecular and cortical bone from the femur of beagle dogs. Skeletally mature female beagles (n = 12 per group) were treated daily for 1 yr with oral doses of vehicle or raloxifene (0.50 mg/kg d). Trabecular bone mechanical properties were measured at the femoral neck using reduced platen compression, a method that allows the trabecular bone to be tested without coring specimens. Cortical bone properties were assessed on prismatic beam specimens machined from the femoral diaphysis using both monotonic and dynamic (cyclic relaxation) four-point bending tests. Trabecular bone from raloxifene-treated animals had significantly higher ultimate stress (+130%), modulus (+89%), and toughness (+152%) compared with vehicle-treated animals. Cortical bone from raloxifene-treated animals had significantly greater toughness (+62%) compared with vehicle, primarily as a function of increased postyield displacement (+100%). There was no significant difference between groups in the percentage of stiffness loss during cortical bone cyclic relaxation tests. These results are consistent with previous data from the vertebrae of these same animals, showing raloxifene has positive effects on biomechanical properties independent of changes in bone volume/density. This may help explain how raloxifene reduces osteoporotic fractures despite modest changes in bone mass.This work was supported by National Institutes of Health Grants AR047838 and AR007581 and a research grant from Lilly Research Laboratories. This investigation used an animal facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR10601-01 from the National Center for Research Resources, National Institutes of Health. Disclosure Summary: M.R.A. has research contracts from Eli Lilly and the Alliance for Better Bone Health. D.B.B. has research contracts from Eli Lilly, the Alliance for Better Bone Health, and Amgen; owns stock in Amgen, Eli Lilly, Pfizer, and Glaxo SmithKline; and is a speaker/consultant for Merck, Eli Lilly, the Alliance for Better Bone Health, and Amgen. A.S.K. and M.C.K. have a family member employed by Eli Lilly. H.A.H. and W.A.H. have nothing to declare

Relating gravitational wave constraints from primordial nucleosynthesis, pulsar timing, laser interferometers, and the CMB: implications for the early universe

We derive a general master equation relating the gravitational-wave observables r and Omega_gw(f). Here r is the tensor-to-scalar ratio, constrained by cosmic-microwave-background (CMB) experiments; and Omega_gw(f) is the energy spectrum of primordial gravitational-waves, constrained e.g. by pulsar-timing measurements, laser-interferometer experiments, and Big Bang Nucleosynthesis (BBN). Differentiating the master equation yields a new expression for the tilt d(ln Omega_gw(f))/d(ln f). The relationship between r and Omega_gw(f) depends sensitively on the uncertain physics of the early universe, and we show that this uncertainty may be encapsulated (in a model-independent way) by two quantities: w_hat(f) and nt_hat(f), where nt_hat(f) is a certain logarithmic average over nt(k) (the primordial tensor spectral index); and w_hat(f) is a certain logarithmic average over w_tilde(a) (the effective equation-of-state in the early universe, after horizon re-entry). Here the effective equation-of-state parameter w_tilde(a) is a combination of the ordinary equation-of-state parameter w(a) and the bulk viscosity zeta(a). Thus, by comparing constraints on r and Omega_gw(f), one can obtain (remarkably tight) constraints in the [w_hat(f), nt_hat(f)] plane. In particular, this is the best way to constrain (or detect) the presence of a ``stiff'' energy component (with w > 1/3) in the early universe, prior to BBN. Finally, although most of our analysis does not assume inflation, we point out that if CMB experiments detect a non-zero value for r, then we will immediately obtain (as a free by-product) a new upper bound w_hat < 0.55 on the logarithmically averaged effective equation-of-state parameter during the ``primordial dark age'' between the end of inflation and the start of BBN.Comment: v1: 12 + 6 pages (main text + appendices), 7 figures; v2: fonts fixed in figure

Treadmill Running and Tower Climbing Resistance Exercise Mitigate Disuse Bone Loss in Mice Equally Well

Ground-Based Model for Lunar Disuse Bone Loss During spaceflight, astronauts are susceptible to decrements in bone mineral density. This suscetibility leaves astronauts at an increased risk of fracture and compromises their likelihood of repeat missions. Our ground-based Lunar model simulates disuse bone loss. Through our novel exercise regimens, we were able to mitigate losses seen by group members not exercised