Biomedical subjects

J W Wilson

Publications and source records attributed to J W Wilson.

At least 19 recordsLinked to original sources

PubMed2006

Does expiratory flow limitation predict chronic dyspnoea in adults with cystic fibrosis?

Tidal expiratory flow limitation (EFL) may promote dynamic hyperinflation and contribute to chronic dyspnoea. The purpose of this study was to assess the contribution of EFL to chronic dyspnoea in adults with cystic fibrosis (CF). The presence of EFL was determined in 102 adults with stable CF (forced expiratory volume in one second (FEV1) 17.3-91.5% predicted) and 20 age-matched control subjects using the negative expiratory pressure technique. Measurements of inspiratory capacity (IC) and spirometry were performed, and chronic dyspnoea was evaluated using the modified Medical Research Council scale. EFL was present in 34 subjects (33%), with 18 subjects flow limited in the sitting position and 16 subjects flow limited only in the supine position. Flow limitation in the sitting position was associated with older age and lower FEV1 compared with flow-limited supine position and non-flow-limited subjects. A significant reduction in IC accompanied EFL in both the sitting and supine positions. Flow limitation in the sitting position was associated with significantly higher levels of chronic dyspnoea. Ordinal regression analysis indicated that EFL was the best predictor of chronic dyspnoea in a model that included FEV1 % pred. Expiratory flow limitation in cystic fibrosis is associated with reduced forced expiratory volume in one second, older age and dynamic hyperinflation. Expiratory flow limitation significantly contributes to chronic dyspnoea in cystic fibrosis.

Adult↗

PubMed2005

Validation of the HZETRN code for laboratory exposures with 1A GeV iron ions in several targets.

A new version of the HZETRN code capable of validation with HZE ions in either the laboratory or the space environment is under development. The computational model consists of the lowest order asymptotic approximation followed by a Neumann series expansion with non-perturbative corrections. The physical description includes energy loss with straggling, nuclear attenuation, nuclear fragmentation with energy dispersion and downshift. Measurements to test the model were performed at the Alternating Gradient Synchrotron and the NASA Space Radiation Laboratory at Brookhaven National Laboratory with iron ions. Surviving beam particles and produced fragments were measured with solid-state detectors. Beam analysis software has been written to relate the computational results to the measured energy loss spectra of the incident ions for rapid validation of modeled target transmission functions.

Aluminum↗

PubMed2005

Computational methods for the HZETRN code.

Asymptotic expansion has been used to simplify the transport of high charge and energy ions for broad beam applications in the laboratory and space. The solution of the lowest order asymptotic term is then related to a Green's function for energy loss and straggling coupled to nuclear attenuation providing the lowest order term in a rapidly converging Neumann series for which higher order collisions terms are related to the fragmentation events including energy dispersion and downshift. The first and second Neumann corrections were evaluated numerically as a standard for further analytic approximation. The first Neumann correction is accurately evaluated over the saddle point whose width is determined by the energy dispersion and located at the downshifted ion collision energy. Introduction of the first Neumann correction leads to significant simplification of the second correction term allowing application of the mean value theorem and a second saddle point approximation. The regular dependence of the second correction spectral dependence lends hope to simple approximation to higher corrections. At sufficiently high energy nuclear cross-section variations are small allowing non-perturbative methods to all orders and renormalization of the second corrections allow accurate evaluation of the full Neumann series.

Algorithms↗

PubMed2005

The prevalence of benign breast disease in women with polycystic ovary syndrome: a review of a 12-year follow-up.

A cross-sectional study of benign breast disease (BBD) was conducted to determine the actual prevalence and follow-up importance of BBD among women with polycystic ovary syndrome (PCOS) in conjunction with an ongoing prospective cohort study. The present study involved a subset of the original group of 244 women with a diagnosis of PCOS and 244 control women matched by age and race. A total of 240 women (116 cases and 124 controls) were included in the present analysis. The majority of women in each group were Caucasians (93 and 96%, respectively). The median age was 46 years in the cases and 47 years in the controls. Screening mammography begins at the age of 40 and has been carried out in 69% of cases and 66% of controls since the study began. Family history of breast disease was observed in 27 cases of both the groups (p > 0.05). Neither fibrocystic breast disease, lump thickening, calcification, fibroadenoma, pain, redness, discharge nor hyperplasia showed a significantly higher prevalence rate in cases than in controls. Eleven (9%) women with PCOS and 21 (17%) controls underwent diagnostic or curative surgery (relative risk: 0.56). These results, in contrast to the previously published literature, do not allow us to conclude that there is a higher risk for BBD among women with PCOS, and the proportion of women with a positive family history of breast cancer was significantly greater in women with PCOS compared with controls. Our observation is that having PCOS does not appear to affect surgeons' decisions to remove BBD.

Adult↗

PubMed2005

Reduced bone density in cystic fibrosis: DeltaF508 mutation is an independent risk factor.

The aim of this cross-sectional study was to determine the prevalence and identify determinants of reduced bone mineral density (BMD) in adults with cystic fibrosis (CF). Adults (88) with CF (mean+/-SD age 29.9+/-7.7 yrs; forced expiratory volume in one second (FEV1) 58.2+/-21.5% of the predicted value) were studied. BMD at the lumbar spine (LS) and femoral neck (FN) and body composition were measured using dual-energy X-ray absorptiometry. Blood and urine were analysed for hormones, bone turnover markers, and the cytokines tumour necrosis factor-alpha, and interleukin-6 and -1beta. FEV1 (% pred); CF genotype; malnutrition; history of growth, development or weight gain delays; and corticosteroid use were analysed. BMD Z-scores were -0.58+/-1.30 (mean+/-SD) at the LS and -0.24+/-1.19 at the FN. Z-scores of <-2.0 were found in 17% of subjects. Subjects who were homozygous or heterozygous for the DeltaF508 mutation exhibited significantly lower Z-scores than those with no DeltaF508 allele. Multiple linear regression showed that the DeltaF508 genotype and male sex were independently associated with lower BMD at both sites. Other factors also independently associated with lower BMD included malnutrition, lower 25-hydroxyvitamin D level, lower fat-free mass and lower FEV1 (% pred). In conclusion, reduced bone mineral density in cystic fibrosis is associated with a number of factors, including DeltaF508 genotype, male sex, greater lung disease severity and malnutrition.

Adult↗

PubMed2004

Optimal testing parameters for blood cultures.

The effects of volume of blood, number of consecutive cultures, and incubation time on pathogen recovery were evaluated for 37,568 blood cultures tested with the automated BACTEC 9240 instrument (Becton Dickinson Diagnostic Instrument Systems) at a tertiary care center over the period of 12 June 1996 through 12 October 1997. When the results for this study were compared with previous data published for manual broth-based blood culture systems and patient samples obtained in the 1970s and 1980s, the following were found: (1) the percentage increase in pathogen recovery per milliliter of blood is less, (2) more consecutive blood culture sets over a 24-h period are required to detect bloodstream pathogens, and (3) a shorter duration of incubation is required to diagnose bloodstream infections. Guidelines developed in the 1970s and 1980s for processing and culturing blood may require revision.

Adult↗

PubMed2004

Measurement of basal, substrate induced and total P-glycoprotein activity in bronchoalveolar lavage T-cell subsets.

BACKGROUND: P-glycoprotein (P-gp) is a member of the ABC transporter superfamily. P-gp activity can be detected by measuring efflux of fluorescent substrates such as rhodamine 123 (R123). Our objectives were to evaluate P-gp activity in T cells freshly isolated from bronchoalveolar lavage (BAL) and to develop a strategy to distinguish between basal, in vitro substrate-induced, and total P-gp activities. METHODS: Cells were obtained from blood (n = 44) and BAL (n = 34), stained for expression of CD3, CD4, CD8, and CD14, and incubated with R123 (0.13 microM) +/- cyclosporine (5 microM), a specific P-gp inhibitor. P-gp activity was detected as median fluorescence intensity (MFI) and percentage of cells falling below a pre-established cutoff. RESULTS: BAL T cells displayed significant basal P-gp activity, which was most apparent when measured as percentage below the cutoff. Induced activity (difference between P-gp activity measured after load and efflux) was determined equally well when using the MFI or the percentage below cutoff parameter. Total activity was represented by the efflux parameters (MFI or percentage below cutoff) or by the activity-time area under the curve (AUC) method. The two efflux parameters correlated well but were insensitive to the time-dependent nature of dye efflux. In the AUC method, two samples with identical R123 brightness or percentage below cutoff after dye efflux can have very different total activities, depending on their basal activity. The AUC method was also most sensitive in distinguishing between P-gp activity in peripheral blood and resident lung T cells. Application of this methodology to the comparison of P-gp activity in BAL and peripheral CD8+ T cells best revealed the elevated total P-gp activity in BAL T cells. CONCLUSIONS: We have systematically evaluated several methodologies for analysis of P-gp activity and arrived at a novel and robust strategy amenable to standardization and evaluation of the effects of P-gp modulators in vivo and in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

A new Mars radiation environment model with visualization.

A new model for the radiation environment to be found on the planet Mars due to Galactic Cosmic Rays (OCR) has been developed at the NASA Langley Research Center. Solar modulated primary particles rescaled for Mars conditions are transported through the Martian atmosphere, with temporal properties modeled with variable timescales, down to the surface, with altitude and backscattering patterns taken into account. The Martian atmosphere has been modeled by using the Mars Global Reference Atmospheric Model--version 2001 (Mars-GRAM 2001). The altitude to compute the atmospheric thickness profile has been determined by using a model for the topography based on the data provided by the Mars Orbiter Laser Altimeter (MOLA) instrument on board the Mars Global Surveyor (MGS) spacecraft. The Mars surface composition has been modeled based on averages over the measurements obtained from orbiting spacecraft and at various landing sites, taking into account the possible volatile inventory (e.g., CO2 ice, H2O ice) along with its time variation throughout the Martian year. Particle transport has been performed with the HZETRN heavy ion code. The Mars Radiation Environment Model has been made available worldwide through the Space Ionizing Radiation Effects and Shielding Tools (SIREST) website, a project of NASA Langley Research Center.

Cosmic Radiation↗

PubMed2004

Radiation analysis for manned missions to the Jupiter system.

An analysis for manned missions targeted to the Jovian system has been performed in the framework of the NASA RASC (Revolutionary Aerospace Systems Concepts) program on Human Exploration beyond Mars. The missions were targeted to the Jupiter satellite Callisto. The mission analysis has been divided into three main phases, namely the interplanetary cruise, the Jupiter orbital insertion, and the surface landing and exploration phases. The interplanetary phase is based on departure from the Earth-Moon L1 point. Interplanetary trajectories based on the use of different propulsion systems have been considered, with resulting overall cruise phase duration varying between two and five years. The Jupiter-approach and the orbital insertion trajectories are considered in detail, with the spacecraft crossing the Jupiter radiation belts and staying around the landing target. In the surface exploration phase the stay on the Callisto surface is considered. The satellite surface composition has been modeled based on the most recent results from the GALILEO spacecraft. In the transport computations the surface backscattering has been duly taken into account. Particle transport has been performed with the HZETRN heavy ion code for hadrons and with an in-house developed transport code for electrons and bremsstrahlung photons. The obtained doses have been compared to dose exposure limits.

Cosmic Radiation↗

PubMed2004

A space radiation transport method development.

Improved spacecraft shield design requires early entry of radiation constraints into the design process to maximize performance and minimize costs. As a result, we have been investigating high-speed computational procedures to allow shield analysis from the preliminary design concepts to the final design. In particular, we will discuss the progress towards a full three-dimensional and computationally efficient deterministic code for which the current HZETRN evaluates the lowest-order asymptotic term. HZETRN is the first deterministic solution to the Boltzmann equation allowing field mapping within the International Space Station (ISS) in tens of minutes using standard finite element method (FEM) geometry common to engineering design practice enabling development of integrated multidisciplinary design optimization methods. A single ray trace in ISS FEM geometry requires 14 ms and severely limits application of Monte Carlo methods to such engineering models. A potential means of improving the Monte Carlo efficiency in coupling to spacecraft geometry is given in terms of re-configurable computing and could be utilized in the final design as verification of the deterministic method optimized design.

Cosmids↗

PubMed2004

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module Crew Quarters.

With 5-7 month long duration missions at 51.6 degrees inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through a dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (CnHn) is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in equivalent dose to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry.

Astronauts↗

PubMed2004

Deep space environments for human exploration.

Mission scenarios outside the Earth's protective magnetic shield are being studied. Included are high usage assets in the near-Earth environment for casual trips, for research, and for commercial/operational platforms, in which career exposures will be multi-mission determined over the astronaut's lifetime. The operational platforms will serve as launching points for deep space exploration missions, characterized by a single long-duration mission during the astronaut's career. The exploration beyond these operational platforms will include missions to planets, asteroids, and planetary satellites. The interplanetary environment is evaluated using convective diffusion theory. Local environments for each celestial body are modeled by using results from the most recent targeted spacecraft, and integrated into the design environments. Design scenarios are then evaluated for these missions. The underlying assumptions in arriving at the model environments and their impact on mission exposures within various shield materials will be discussed.

Aerospace Medicine↗

PubMed2004

Uncertainties in estimates of the risks of late effects from space radiation.

Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits.

Aluminum↗

PubMed2004

An improved Green's function for ion beam transport.

Ion beam transport theory allows testing of material transmission properties in the laboratory environment generated by particle accelerators. This is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are the main emphasis of the present work. In consequence, an analytic solution of the linear Boltzmann equation is pursued in the form of a Green's function allowing flexibility in application to a broad range of boundary value problems. It has been established that simple solutions can be found for high charge and energy (HZE) ions by ignoring nuclear energy downshifts and dispersion. Such solutions were found to be supported by experimental evidence with HZE ion beams when multiple scattering was added. Lacking from the prior solutions were range and energy straggling and energy downshift with dispersion associated with nuclear events. Recently, we have found global solutions including these effects providing a broader class of HZE ion solutions.

Aluminum↗

PubMed2004

New calculations of the atmospheric cosmic radiation field--results for neutron spectra.

The propagation of primary cosmic rays through the Earth's atmosphere and the energy spectra of the resulting secondary particles have been calculated using the Monte Carlo transport code FLUKA with several novel auxiliary methods. Solar-modulated primary cosmic ray spectra were determined through an analysis of simultaneous proton and helium measurements made on spacecraft or high-altitude balloon flights. Primary protons and helium ions are generated within the rigidity range of 0.5 GV-20 TV, uniform in cos2theta. For a given location, primaries above the effective angle-dependent geomagnetic cut-off rigidity, and re-entrant albedo protons, are transported through the atmosphere. Helium ions are initially transported using a separate transport code called HEAVY to simulate fragmentation. HEAVY interfaces with FLUKA to provide interaction starting points for each nucleon originating from a helium nucleus. Calculated cosmic ray neutron spectra and consequent dosimetric quantities for locations with a wide range of altitude (atmospheric depth) and geomagnetic cut-off are presented and compared with measurements made on a high-altitude aeroplane. Helium ion propagation using HEAVY and inclusion of re-entrant albedo protons with the incident primary spectra significantly improved the agreement of the calculated cosmic ray neutron spectra with measured spectra. These cosmic ray propagation calculations provide the basis for a new atmospheric ionising radiation (AIR) model for air-crew dosimetry, calculation of effects on microelectronics, production of cosmogenic radionuclides and other uses.

Algorithms↗

PubMed2004

The energy spectrum of cosmic-ray induced neutrons measured on an airplane over a wide range of altitude and latitude.

Crews of high-altitude aircraft are exposed to radiation from galactic cosmic rays (GCRs). To help determine such exposures, the Atmospheric Ionizing Radiation Project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on a NASA ER-2 high-altitude airplane. The primary instrument was a sensitive extended-energy multisphere neutron spectrometer. Its detector responses were calculated for energies up to 100 GeV using the radiation transport code MCNPX 2.5.d with improved nuclear models and including the effects of the airplane structure. New calculations of GCR-induced particle spectra in the atmosphere were used to correct for spectrometer counts produced by protons, pions and light nuclear ions. Neutron spectra were unfolded from the corrected measured count rates using the deconvolution code MAXED 3.1. The results for the measured cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and neutron dose equivalent and effective dose rates, and their dependence on altitude and geomagnetic cut-off agree well with results from recent calculations of GCR-induced neutron spectra.

Aircraft↗

PubMed2004

The impact of pharmacogenomic factors on steroid dependency in pediatric heart transplant patients using logistic regression analysis.

Many pharmacogenomic predictors of drug response are now available, and include both drug metabolism-disposition factors and drug targets. Information on statistical approaches to analyzing large clinical data sets in relation to genetic polymorphisms is limited. The objective of this study was to evaluate whether logistic regression could identify pharmacogenomic predictors of outcome in a large data set in a complex transplant patient population. Seventy pediatric heart transplant patients were studied. Patients were followed for at least 1 yr post-transplantation as outpatients, and weaned from corticosteroids if clinically appropriate. Logistic regression analysis was used to identify the predictors of steroid dependency. The dependent variable was the presence or absence of steroid therapy at 1 yr post-transplantation. The independent variables were the patients' transplant age, gender, MDR1 C3435T and G2677T, CYP3A53B and cytokine polymorphisms. By chi-square test for the MDR1 C3435T polymorphism, 12 of 18 (67%) patients in the CC group were still on prednisone, whereas only 18 of 47 (38%) of the CT/TT group were still receiving prednisone (p = 0.04). For the IL-10 groups, two of 15 patients with the high producer genotype (13.3%) remained on prednisone, in comparison with 16 of 28 patients with the intermediate producer genotype (57.1%) and 15 of 26 patients with the low producer genotype (57.7%, p = 0.01). Logistic regression analysis confirmed MDR1 C3435T (p = 0.021), and IL-10 polymorphisms (intermediate producer genotype p = 0.015; low producer genotype p = 0.013) as independent risk factors for steroid dependency at 1 yr after transplantation. This approach identifies pharmacogenomic factors, which can be studied more extensively in larger data sets, and used in prospective studies to individualize immunosuppressive therapy following solid organ transplantation.

Adolescent↗

PubMed2003

Radiation risk and human space exploration.

Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented.

Aerospace Medicine↗