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Gradient vector flow (GVF), an elegant external force for parametric deformable models, can capture object boundaries from both sides. A new geometric deformable model is proposed that combines GVF and the geodesic active contour model. The level set method is used as the numerical method of this model. The model is applied for echocardiographic image segmentation.
Guyton developed a popular approach for understanding the factors responsible for cardiac output (CO) regulation in which 1) the heart-lung unit and systemic circulation are independently characterized via CO and venous return (VR) curves, and 2) average CO and right atrial pressure (RAP) of the intact circulation are predicted by graphically intersecting the curves. However, this approach is virtually impossible to verify experimentally. We theoretically evaluated the approach with respect to a nonlinear, computational model of the pulsatile heart and circulation. We developed two sets of open circulation models to generate CO and VR curves, differing by the manner in which average RAP was varied. One set applied constant RAPs, while the other set applied pulsatile RAPs. Accurate prediction of intact, average CO and RAP was achieved only by intersecting the CO and VR curves generated with pulsatile RAPs because of the pulsatility and nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR curves generated with pulsatile RAPs were also practically independent. This theoretical study therefore supports the validity of Guyton's graphical analysis.
Real-time three-dimensional echocardiography (RT3DE) is an innovative cardiac imaging modality. However, partly due to lack of user-friendly software, RT3DE has not been widely accepted as a clinical tool. The object of this study was to develop and implement a fast and interactive volume renderer of RT3DE datasets designed for a clinical environment where speed and simplicity are not secondary to accuracy. Thirty-six patients (20 regurgitation, 8 normal, 8 cardiomyopathy) were imaged using RT3DE. Using our newly developed software, all 3D data sets were rendered in real-time throughout the cardiac cycle and assessment of cardiac function and pathology was performed for each case. The real-time interactive volume visualization system is user friendly and instantly provides consistent and reliable 3D images without expensive workstations or dedicated hardware. We believe that this novel tool can be used clinically for dynamic visualization of cardiac anatomy.
Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.
Sympathetic outflow increases during head-up tilt (HUT) to stabilize blood pressure in the presence of decreases in venous return and stroke volume (SV). Otherwise, orthostatic hypotension would develop. Gender differences in orthostatic tolerance have been noted but the mechanisms are still uncertain. More recently, Waters et al. reported in a limited sample, greater susceptibility of women to demonstrate orthostatic intolerance following space flight. Therefore, it is important to understand gender differences in reflex blood pressure regulation. Recently, we reported smaller increments in muscle sympathetic nerve activity (MSNA) in healthy women during graded HUT and a non-baroreflex cold pressor test. The purpose of this report is to examine the hypothesis that gender differences in blood pressure control during HUT are related to important variations in MSNA discharge patterns.
We examined the distribution of the myosin heavy chain (MHC) isoforms (I, IIa, IIx) of the leg muscles of three groups of men and women (40 +/- 8y) that completed unilateral lower limb suspension only (ULLS), ULLS plus resistance exercise (ULLS+RE), or RE only (RE) for 5 weeks. Muscle biopsies were obtained pre and post from the vastus lateralis of all three groups and the soleus of the ULLS group. Distributions of all three MHC isoforms in the vastus lateralis were unchanged (p<0.05) from pre to post with ULLS. The soleus muscle, which contained no measurable IIx isoform, was also unchanged (p< 0.05) from pre to post ULLS. These results suggest that the percent distribution of the MHC isoforms per unit muscle protein in both the vastus lateralis and soleus does not change during the first five weeks of simulated microgravity. Further, resistance exercise during five weeks of ULLS or ambulation does not appear to alter the MHC distribution per unit muscle protein of the vastus lateralis.
In response to decreased usage skeletal muscle undergoes an adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. Accompanying a shift in fiber type is an increased reliance of carbohydrate metabolism and decreased reliance on fat for energy. These responses have been found with both space flight and ground based models of disuse atrophy including the chronically adapted rodent hind limb suspended (HLS) rat (1, 4-7, 10, 11). In addition, after space flight, the ability of soleus muscle homogenates to oxidize palmitate is decreased. We have previously shown that expression of the mRNA of enzymes involved in beta-oxidation is reduced in the soleus muscle of HLS rats. At the same time mRNA expression of enzymes involved in glycolysis was increased. This study extends these observations to address the question of whether the decrease in beta-oxidation is caused by a reduction in the capacity of the pathway to oxidize fat or the regulation is effected before fatty acids enter the mitochondria, i.e. the reduced capacity of the fatty acid oxidation pathway is because less fat is available for oxidation. The two key steps involved in fatty acid uptake into the cells are lipoprotein lipase and the transport of the free fatty acids produced by lipoprotein lipase into the cell via the carnitine acyltransferase system.
Immune function is altered in stressful situations, including space flight. This may result in increased risk of infection. Antiorthostatic suspension has been used to study the effects of space flight-like conditions on immunity. The mechanisms of promoting infection in stressful situations have not been defined, but catecholamines could play a role. In the present study gram negative bacteria grown with catecholamines showed enhanced bacterial growth compared to controls. Additionally, antiorthostatically suspended mice infected with Klebsiella pneumoniae showed decreased survival compared to restrained or normally caged controls. Therefore, stress-induced enhanced bacterial growth and immunosuppression could play a role in suspension-induced enhanced mortality due to infection.
Head-up tilt table experiments conducted in astronauts prior to and immediately after the NASA Neurolab Space Mission (STS-90) revealed that a reduction in stroke volume induced by moving from the supine to upright posture was associated with increased muscle sympathetic nerve activity (MSNA). Although this finding was not unexpected, lower average stroke volume and greater average MSNA measured after space flight in both supine and upright postures were positioned in a linear fashion on the same stroke volume-MSNA stimulus-response relationship as the average pre-flight stroke volume and MSNA responses. Since all astronauts who participated in the Neurolab orthostatic experiments completed the 10-min tilt table tests, these observations supported the notion that sympathetic reflex responses were not altered but functioned adequately after space flight in non-presyncopal subjects. In contrast to the Neurolab results, development of orthostatic hypotension and presyncopal events reported in astronauts during standing after space flight have been accompanied by attenuated peripheral vasoconstriction and less elevation in plasma concentrations of norepinephrine. The association between circulating norepinephrine (NE) and peripheral vascular resistance in presyncopal astronauts after space flight led to the conclusion that postflight presyncope can be attributed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic function. In the present investigation, we used graded levels of lower body negative pressure (LBNP) to produce linear reductions in stroke volume and performed direct measurements of MSNA to test the hypotheses that (1) elevations in MSNA during central hypovolemia are proportional (i.e., linear) with reductions in stroke volume and; (2) that the slope of the stroke volume-MSNA relationship will be reduced in presyncopal subjects.
BACKGROUND: The deconditioning syndrome from prolonged bed rest (BR) or spaceflight includes decreases in maximal oxygen uptake (VO2max), muscular strength and endurance, and orthostatic tolerance. In addition to exercise training as a countermeasure, +Gz (head-to-foot) acceleration training on 1.8-2.0 m centrifuges can ameliorate the orthostatic and acceleration intolerances induced by BR and immersion deconditioning. PURPOSE: Study A was designed to determine the magnitude and linearity of the heart rate (HR) response to human-powered centrifuge (HPC) acceleration with supine exercise vs. passive (no exercise) acceleration. Study B was designed to test the hypothesis that moderate +Gz acceleration during exercise will not affect the respective normal linear relationships between exercise load and VO2max, HR, and pulmonary ventilation (VEBTPS). Study C: To determine if these physiological responses from the HPC runs (exercise + on-platform acceleration) will be similar to those from the exercise + off-platform acceleration responses. METHODS: In Study A, four men and two women (31-62 yr) were tested supine during exercise + acceleration and only passive acceleration at 100% [maximal acceleration (rpm) = Amax] and at 25%, 50%, and 75% of Amax. In Studies B and C, seven men (33+/-SD 7 yr) exercised supine on the HPC that has two opposing on-platform exercise stations. A VO2max test and submaximal exercise runs occurred under three conditions: (EX) exercise (on-platform cycle at 42%, 61%, 89% and 100% VO2max) with no acceleration; (HPC) exercise + acceleration via the chain drive at 25%,50%, and 100% Gzmax (35%, 72% and 100% VO2max); and (EXA) exercise (on-platform cycle at 42%, 61%, 89%, and 100% VO2max) with acceleration performed via the off-platform cycle operator at +2.2+/-0.2 Gz [50% of max (rpm) G]. RESULTS: Study A: Mean (+/-SE) Amax was 43.7+/-1.3 rpm (mean = +3.9+/-0.2, range = 3.3 to 4.9 Gz). Amax run time for exercise +acceleration was 50-70 s, and 40-70 s for passive acceleration. Regression of X HR on Gz levels indicated explained variances (r2) of 0.88 (exercise) and 0.96 (passive). The mean exercise HR of 107+/-4 (25%), to 189+/-13 (100%) bpm were 43-50 bpm higher (p < 0.05) than comparable passive HR of 64+/-2 to 142+/-22 bpm, respectively. Study B: There were no significant differences in VO2, HR or VEBTPS at the submaximal or maximal levels between the EX and EXA runs. Mean (+/-SE) VO2max for EX was 2.86+/-0.12 L x min(-1)(35+/-2 ml x min(-1) x kg(-1)) and for EXA was 3.09+/-0.14 L x min(-1) (37+/-2 ml-min(-1) x kg(-1)). Study C: There were no significant differences in the essentially linear relationships between the HPC and EXA data for VO2 (p = 0.45), HR (p < 0.08), VEBTPS (p = 0.28), or the RE (p = 0.15) when the exercise load was % VO2max. CONCLUSION: Addition of + 2.2 Gz acceleration does not significantly influence levels of oxygen uptake, heart rate, or pulmonary ventilation during submaximal or maximal cycle ergometer leg exercise on a short-arm centrifuge.
Epstein-Barr virus (EBV) reactivation and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at 2 Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity (DTH) skin testing was used as an indicator of the CMI response, that was evaluated 2 times before winter isolation and 3 times during isolation. At all 5 evaluation times, 8 or more of the 16 subjects had a diminished CMI response. Diminished DTH was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal DTH responses for all 5 tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, during, and after the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least 1 occasion. The probability of EBV shedding increased (P = 0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (P < 0.0005) when DTH response was diminished than when DTH was normal. The findings indicate that the psychosocial, physical, and other stresses associated with working and living in physical isolation during the Antarctic winter result in diminished CMI and an accompanying increased reactivation and shedding of latent viruses.
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A new type of real-time radiation monitoring device, RRMD-III, consisting of three double-sided silicon strip detectors (DSSDs), has been developed and tested on-board the Space Shuttle mission STS-84. The test succeeded in measuring the linear energy transfer (LET) distribution over the range of 0.2 keV/micrometer to 600 keV/micrometer for 178 h. The Shuttle cruised at an altitude of 300 to 400 km and an inclination angle of 51.6 degrees for 221.3 h, which is equivalent to the International Space Station orbit. The LET distribution obtained for particles was investigated by separating it into galactic cosmic ray (GCR) particles and trapped particles in the South Atlantic Anomaly (SAA) region. The result shows that the contribution in dose-equivalent due to GCR particles is almost equal to that from trapped particles. The total absorbed dose rate during the mission was 0.611 mGy/day; the effective quality factor, 1.64; and the dose equivalent rate, 0.998 mSv/day. The average absorbed dose rates are 0.158 mGy/min for GCR particles and 3.67 mGy/min for trapped particles. The effective quality factors are 2.48 for GCR particles and 1.19 for trapped particles. The absorbed doses obtained by the RRMD-III and a conventional method using TLD (Mg(2)SiO(4)), which was placed around the RRMD-III were compared. It was found that the TLDs showed a lower efficiency, just 58% of absorbed dose registered by the RRMD-III.
Estimating uncertainty in lifetime cancer risk for human exposure to space radiation is a unique challenge. Conventional risk assessment with low-linear-energy-transfer (LET)-based risk from Japanese atomic bomb survivor studies may be inappropriate for relativistic protons and nuclei in space due to track structure effects. This paper develops a Monte Carlo mixture model (MCMM) for transferring additive, National Institutes of Health multiplicative, and multiplicative excess cancer incidence risks based on Japanese atomic bomb survivor data to determine excess incidence risk for various US astronaut exposure profiles. The MCMM serves as an anchor point for future risk projection methods involving biophysical models of DNA damage from space radiation. Lifetime incidence risks of radiation-induced cancer for the MCMM based on low-LET Japanese data for nonleukemia (all cancers except leukemia) were 2.77 (90% confidence limit, 0.75-11.34) for males exposed to 1 Sv at age 45 and 2.20 (90% confidence limit, 0.59-10.12) for males exposed at age 55. For females, mixture model risks for nonleukemia exposed separately to 1 Sv at ages of 45 and 55 were 2.98 (90% confidence limit, 0.90-11.70) and 2.44 (90% confidence limit, 0.70-10.30), respectively. Risks for high-LET 200 MeV protons (LET=0.45 keV/micrometer), 1 MeV alpha-particles (LET=100 keV/micrometer), and 600 MeV iron particles (LET=180 keV/micrometer) were scored on a per particle basis by determining the particle fluence required for an average of one particle per cell nucleus of area 100 micrometer(2). Lifetime risk per proton was 2.68x10(-2)% (90% confidence limit, 0.79x10(-3)%-0. 514x10(-2)%). For alpha-particles, lifetime risk was 14.2% (90% confidence limit, 2.5%-31.2%). Conversely, lifetime risk per iron particle was 23.7% (90% confidence limit, 4.5%-53.0%). Uncertainty in the DDREF for high-LET particles may be less than that for low-LET radiation because typically there is very little dose-rate dependence. Probability density functions for high-LET radiation quality and dose-rate may be preferable to conventional risk assessment approaches. Nuclear reactions and track structure effects in tissue may not be properly estimated by existing data using in vitro models for estimating RBEs. The method used here is being extended to estimate uncertainty in spacecraft shielding effectiveness in various space radiation environments.
Heavy ions are more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. We measured the induction of complex-type chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to accelerated H-, He-, C-, Ar-, Fe- and Au-ions in the LET range of approximately 0.4-1400 keV/micrometers. Chromosomes were analyzed either at the first post-irradiation mitosis, or in interphase, following premature condensation by phosphatase inhibitors. Selected chromosomes were then visualized after FISH-painting. The dose-response curve for the induction of complex-type exchanges by heavy ions was linear in the dose-range 0.2-1.5 Gy, while gamma-rays did not produce a significant increase in the yield of complex rearrangements in this dose range. The yield of complex aberrations after 1 Gy of heavy ions increased up to an LET around 100 keV/micrometers, and then declined at higher LET values. When mitotic cells were analyzed, the frequency of complex rearrangements after 1 Gy was about 10 times higher for Ar- or Fe- ions (the most effective ions, with LET around 100 keV/micrometers) than for 250 MeV protons, and values were about 35 times higher in prematurely condensed chromosomes. These results suggest that complex rearrangements may be detected in astronauts' blood lymphocytes after long-term space flight, because crews are exposed to HZE particles from galactic cosmic radiation. However, in a cytogenetic study of ten astronauts after long-term missions on the Mir or International Space Station, we found a very low frequency of complex rearrangements, and a significant post-flight increase was detected in only one out of the ten crewmembers. It appears that the use of complex-type exchanges as biomarker of radiation quality in vivo after low-dose chronic exposure in mixed radiation fields is hampered by statistical uncertainties.
The question of the appropriate extrapolation to low dose has long been a subject of controversy. A linear no-threshold model is favored by regulatory bodies as the basis of RBE assignments and estimates of radiation hazards to the general population. This model is largely supported by extensive application of the linear-quadratic survival formula "fitted" statistically to a wide variety of experimental data obtained at doses typically exceeding 1 Gy, and then extrapolated to mGy for practical applications, and even to the prediction of hazards from single electrons. Such extrapolations are questionable at best, and may even prove hazardous for risk evaluations. Fluence and geometry rather than dose based data are proposed as a basis for a limiting "threshold" for a "low dose" extrapolation. The proposed threshold is one where the fluence of particles is one per square micron, where on average only 2/3 of the 1 micrometers2 pixels covering an irradiated area are traversed by one or more particles. The corresponding dose threshold is determined by the LET of the bombarding radiation. For relativistic electrons this dose is about 0.032 Gy.
Confluent human fibroblast cells were exposed to 6 Gy gamma-rays or 200 MeV/nucleon Fe ions at 0.7 or 3 Gy. The cells were allowed to repair for 24 hours after exposure and chromosomes were collected using a premature chromosome condensation technique with calyculin-A. Chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results showed that both doses of the Fe ions produced higher ratios of complex to simple exchanges and lower ratio of complete to incomplete exchanges than the 6 Gy gamma-exposure. The ratios of aberration yields were similar for the two doses of Fe ions. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating this is the maximum number of chromosome domains traversed by a single Fe ion track.
The National Aeronautics and Space Administration (NASA) administrator has identified protection from radiation hazards as one of the two biggest problems of the agency with respect to human deep space missions. The intensity and strength of cosmic radiation in deep space makes this a 'must solve' problem for space missions. The Moon and two Earth-Moon Lagrange points near Moon are being proposed as hubs for deep space missions. The focus of this study is to identify approaches to protecting astronauts and habitats from adverse effects from space radiation both for single missions and multiple missions for career astronauts to these destinations. As the great cost of added radiation shielding is a potential limiting factor in deep space missions, reduction of mass, without compromising safety, is of paramount importance. The choice of material and selection of the crew profile play major roles in design and mission operations. Material trade studies in shield design over multi-segmented missions involving multiple work and living areas in the transport and duty phase of space mission's to two Earth-Moon co-linear Lagrange points (L1) between Earth and the Moon and (L2) on back side of the moon as seen from Earth, and to the Moon have been studied. It is found that, for single missions, current state-of-the-art knowledge of material provides adequate shielding. On the other hand, the choice of shield material is absolutely critical for career astronauts and revolutionary materials need to be developed for these missions. This study also provides a guide to the effectiveness of multifunctional materials in preparation for more detailed geometry studies in progress.