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  • 1
    ISSN: 1573-0646
    Keywords: bisantrene ; hypersensitivity ; histamine release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine of ninety-three patients receiving Bisantrene on an every three week schedule developed an anaphylactoid reaction with a variety of symptoms. Most reactions occurred in patients who had multiple exposures to Bisantrene. Investigatiors utilizing Bisantrene in ongoing clinical trials should be aware of this life threatening toxicity.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2017-06-26
    Description: Nodal regression of orbit effect on gravity precession of gyroscopic satellite
    Keywords: SPACE SCIENCES
    Type: NASA-CR-78875 , R-309
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  • 3
    Publication Date: 2017-06-27
    Description: Effect of nodal regression of orbit on gravity gradient precession of gyroscopic satellite in testing general theory of relativity
    Keywords: SPACE SCIENCES
    Type: NASA-CR-82592 , R-309
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  • 4
    ISSN: 1573-0646
    Keywords: bisantrene ; CL216,942 ; pharmacokinetics in humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bisantrene, 9,10-anthracenedicarboxaldehyde bis ((4,5-dihydro-1 H-imidazol-2-yl) hydrazone) dihydrochloride were evaluated during a Phase I clinical investigation. Bisantrene at doses of 20 to 280 mg/m2 was administered by variable infusion rates to nine patients with advanced metastatic cancer. Bisantrene's plasma clearance followed a triexponential pattern with a harmonic mean terminal half-life (t1/2 γ) of 26 h. The steady state volume of distribution (Vd ss ) was large, averaging 627 l/m2. Plasma clearance averaged 42.6±6.7 l/h/m2. The cumulative urinary excretion of bisantrene was 3.6±1.6% at 48 h.
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  • 5
    Publication Date: 2011-08-16
    Description: Orbiting-gyro relativity satellite and atmospheric composition experiments with models
    Keywords: SPACE SCIENCES
    Type: COORDINATED SCI. LAB. 1 AUG. 1969; P 123-147
    Format: text
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  • 6
    Publication Date: 2019-07-12
    Description: The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.
    Keywords: Aerospace Medicine
    Type: E-17763
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  • 7
    Publication Date: 2019-07-13
    Description: To validate and further improve the Integrated Medical Model (IMM), medical event data were obtained from 32 ISS and 122 STS person-missions. Using the crew characteristics from these observed missions, IMM v4.0 was used to forecast medical events and medical resource utilization. The IMM medical condition incidence values were compared to the actual observed medical event incidence values, and the IMM forecasted medical resource utilization was compared to actual observed medical resource utilization. Qualitative comparisons of these parameters were conducted for both the ISS and STS programs. The results of these analyses will provide validation of IMM v4.0 and reveal areas of the model requiring adjustments to improve the overall accuracy of IMM outputs. This validation effort should result in enhanced credibility of the IMM and improved confidence in the use of IMM as a decision support tool for human space flight.
    Keywords: Aerospace Medicine
    Type: GRC-E-DAA-TN29847 , 2016 NASA Human Research Program Investigators'' Workshop (HRP IWS 2016); 8-11 Feb. 2016; Galveston, TX; United States
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  • 8
    Publication Date: 2019-07-13
    Description: Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model with terrestrial data. Results and Conclusions: With the implementation of auto-regulation and hydrostatic modeling capabilities, the model performs as expected in the maintaining the CA (Central Artery) compartment pressure when simulating orientations ranging from supine to standing. The model appears to generally overpredict heart rate and thus cardiac output, possibly indicating sensitivity to the nominal heart rate, which is used as an initial set point of the regulation mechanisms. Despite this sensitivity, the model performs consistently for many hours of simulation time, indicating the success of our quasi-static implementation approach.
    Keywords: Aerospace Medicine
    Type: GRC-E-DAA-TN38845 , NASA Human Research Program Investigators Workshop (HRP IWS 2017); 23-26 Jan. 2017; Galveston, TX; United States
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  • 9
    Publication Date: 2019-07-13
    Description: The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.
    Keywords: Aerospace Medicine
    Type: GRC-E-DAA-TN36570 , Annual Meeting of the American Society for Gravitational and Space Research; 26-29 Oct. 2016; Cleveland, OH; United States
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  • 10
    Publication Date: 2019-07-13
    Description: Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.
    Keywords: Aerospace Medicine
    Type: GRC-E-DAA-TN29818 , 2016 NASA Human Research Program Investigators'' Workshop (HRP IWS 2016); 8-11 Feb. 2016; Galveston, TX; United States
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