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Biomedical subjects

S V Dawson

Publications and source records attributed to S V Dawson.

At least 19 recordsLinked to original sources

Multi-stage model estimates of lung cancer risk from exposure to diesel exhaust, based on a U.S. railroad worker cohort.

A California Environmental Protection Agency (Cal/EPA) report concluded that a reasonable and likely explanation for the increased lung cancer rates in numerous epidemiological studies is a causal association between diesel exhaust exposure and lung cancer. A version of the present analysis, based on a retrospective study of a U.S. railroad worker cohort, provided the Cal/EPA report with some of its estimates of lung cancer risk associated with diesel exhaust. The individual data for that cohort study furnish information on age, employment, and mortality for 56,000 workers over 22 years. Related studies provide information on exposure concentrations. Other analyses of the original cohort data reported finding no relation between measures of diesel exhaust and lung cancer mortality, while a Health Effects Institute report found the data unsuitable for quantitative risk assessment. None of those three works used multistage models, which this article uses in finding a likely quantitative, positive relations between lung cancer and diesel exhaust. A seven-stage model that has the last or next-to-last stage sensitive to diesel exhaust provides best estimates of increase in annual mortality rate due to each unit of concentration, for bracketing assumptions on exposure. Using relative increases of risk and multiplying by the background lung cancer mortality rates for California, the 95% upper confidence limit of the 70-year unit risks for lung cancer is estimated to be in the range 2.1 x 10(-4) (microg/m3)(-1) to 5.5 x 10(-4) (microg/m3)(-1). These risks constitute the low end of those in the Cal/EPA report and are below those reported by previous investigators whose estimates were positive using human data.

Adult↗

Risk assessment for benzo[a]pyrene.

Benzo[a]pyrene is the most studied carcinogenic polycyclic aromatic hydrocarbon and one of the most potent, and it is often used as a toxicological prototype or surrogate for all carcinogenic polycyclic aromatic hydrocarbons. Quantitative risk assessment of benzo[a]pyrene has been hampered by the quality of the data sets available for quantitation. The EPA has calculated both potency slopes and unit risks using the linearized multistage model. We have confirmed and refined that analysis. Risks based on feeding, inhalation, and intratracheal administration of benzo[a]pyrene show fairly good concordance. Others have applied the Moolgavkar two-stage model to the data and estimated a lower potency for benzo[a]pyrene. We think that such conclusion is premature. Longer term exposures of animals to benzo[a]pyrene are necessary to provide the data needed for more refined carcinogenic risk estimations.

Animals↗

A California air standard to protect vegetation from ozone.

Evidence shows that the current national primary ambient air quality standard, if attained, would still permit substantial injury to vegetation. Thus, in March 1987, the California Air Resources Board (CARB) began consideration of the evidence for the effects of ozone (O3) on vegetation, and of several possible state ambient air quality standards designed to protect vegetation, especially crops, from O3 injury. In its review, the CARB addressed a number of issues relevant to such a standard. One issue considered by the CARB is the relationship of an ambient air quality standard to natural background levels of O3, which would greatly influence the practicality of attainment. Attainment of a standard close to natural background could entail excessive costs. Another issue considered is the occurrence of oxidants other than O3 that can damage vegetation. Throughout much of California, O3 accounts for over 90% of the oxidant air pollutants, and the CARB considered whether, in keeping with current practice, O3 should be used as a surrogate for total oxidant air pollutants. A major new piece of information presented to the CARB was an assessment of the economic effects of several potential standards. This assessment, produced by University of California scientists at Riverside and Davis, calculated the benefits of the potential standards in comparison to current O3 levels and estimated natural O3 background. This assessment was developed using field chamber response data, local crop data, and local O3 concentration data as inputs to the California Agricultural Resources Model, which accounts for both supply and demand effects. Because of California's varied climate, agricultural production occurs on a year-round basis, with overlapping growing seasons for many crops. Over long periods of time, O3 levels may vary markedly because of the influence of various factors, and a 1-h standard may not be an accurate indicator of growing season O3 exposure. A moving three-month averaging time has been proposed as a way to approximate the growing seasons of California's 200 crops. However, a sufficiently stringent 1-h standard would serve as a surrogate for a growing season standard. The CARB reviewed evidence supporting both long-term and short-term standards. Agriculture dominates the economies of some regions within California but is a minor components of other regional economies. Because the San Joaquin Valley is California's most important agricultural area, the CARB reviewed evidence for a regional standard for this area that would be more stringent than standards for other parts of the state.

Journal Article↗

Analysis of air pollution effects: uncertainties in proceeding to standards.

Uncertainties in the collection and assessment of scientific information make ambient air quality standard setting difficult. Uncertainties occur in the estimation of the medical parameters under test due to the inherent random variability encountered in sampling the parameters. The most common method of dealing with random variability is statistical significance testing. The main caution offered in regard to that analysis is to avoid calling a nonsignificant result negative, unless the circumstances are such that the smallest effect which indicates likely harm to health could have been detected with sufficiently high probability. Uncertainties also play a crucial role in evaluating the implications that even statistically significant test results have for human health. A signal-detection model, developed to explain expert performance in evaluating the results of such diagnostic tests as X-rays, is presented as an analogy for the situation facing experts who are evaluating the implications of health data that is being considered for use in setting a standard. If criteria are too strict for accepting data as evidence of harm to health, then it is argued that, as a consequence, the decision process will not have sufficient ability to discriminate against false-negative results. False-negative results are those that incorrectly conclude there is no threat when, in fact, a particular level of pollutant is actually a threat to health.

Air Pollutants↗

Interaction of oscillatory and unidirectional flows in straight tubes and an airway cast.

Because oscillatory resistance of the respiratory system is often measured during tidal breathing, we studied the interaction between simultaneous oscillatory and unidirectional flows in three straight tubes (radius ranging from 0.3025 to 0.679 cm and length either 30.7 or 173 cm) and a central airway cast (tracheal radius 0.685 cm). Oscillatory flow was generated by a loudspeaker, airway pressure was measured with a transducer, and flow was calculated from pressure changes in an airtight enclosure mounted behind the flow source (loudspeaker plethysmograph). Oscillatory resistance, i.e., the real part of impedance, was determined from 2 to 64 Hz. In the absence of unidirectional flow, frequency dependence of resistance was observed for the two 30.7-cm-long tubes to match previously published theory. Frequency dependence of resistance for the airway cast was similar to that of the tube of comparable inlet radius. In the presence of unidirectional flow, oscillatory resistance at low frequency was independent of frequency and determined by the magnitude of the unidirectional flow. Oscillatory resistance at high frequency was frequency dependent but still influenced by the magnitude of the unidirectional flow. Our results indicate that the presence of unidirectional flow alters the oscillatory resistance of tubes and the cast at any given frequency, presumably by changing the shape of the boundary layer.

Airway Resistance↗

Use of the choke point in the prediction of flow limitation in elastic tubes.

Work on flow limitation in elastic tubes of the body first relied on simple descriptions and intuitive modeling. Mathematical modeling led to the identification of a wave speed mechanism analogous to that of hydraulic flow in sluices and in supersonic nozzles. The basic pulse wave governs in the fluid-filled elastic tube. How this wave speed depends on the pressure-area characteristic of the tube is reviewed, and the determination of maximum flow rates for a given head, as in frictionless flow, is cited. The analysis of flow limitation for significant friction is briefly sketched, and the apparent paradox for viscous dominated flow still involving wave speed is resolved. Example applications include an analysis of density dependence of flow limitations, an exploration of implications concerning area and elastic modules at choke point for expiratory flow data is outlined, and predictions of flow from pressure-area characteristics are made. A summary of how airway system properties affect flow rates is given. Some of the difficulties of using flow data to infer airway properties are cited.

Animals↗

Indirect estimation of physiological distribution functions.

Multicompartment models, such as sums of exponential decays and sums of effects of different ventilation-perfusion ratios, are cast in the form of integrals. Difficulties in obtaining the density function in such an integral from measured values of the integral are attributed to amplification of error in the inversion solution and to the limited number of measurement points. The present approach to control the effect of the error is regularization with the use of a non-negativity constraint on the density function. The answers are sums of the influence or kernel functions of the integral wherever the sum is positive, and zero elsewhere. Such non-negative answers not only ensure that true density functions are obtained but also permit the answer to fall abruptly to zero. For example, a delta function can be much more closely approximated with the non-negativity constraint than without. A rule is developed to choose the value of smoothing parameter so as to minimize an approximate upper bound on the integral of the squared error of the answer. This typically tends to result in some oversmoothing. Functions tested without error and with 2% relative error are as follows: one of the kernel functions (best results); rectangular boxes and delta functions (fair results); and wide boxes (poor results).

Models, Biological↗

Wave-speed limitation on expiratory flow-a unifying concept.

The mechanism limiting forced expiratory flow is explained on the basis that a local flow velocity reaches the local speed of wave propagation at a point, called the choke point, in intrathoracic airways. This theoretical approach to the "waterfall effect" leads to selection of the analogy of constricted open-channel flow to apply to the elastic network of airway tubes. Quantitative results are derived for the case of negligible friction by use of the Bernoulli principle. Shapes predicted for the maximum-flow static recoil curves depend only upon the nature of the pressure-area curve at the choke point in the case of negligible friction; and the magnitude of the critical rate of flow depends on reference values of cross-sectional area and elastic modulus at the choke point, on gas density, and on the static recoil pressure. The present theoretical results are used to interpret previous experiments, but quantitative applicability is limited because of frictional effects and lack of knowledge of choke point conditions.

Animals↗

Airway geometry by analysis of acoustic pulse response measurements.

Serial distribution of airway properties determines in part the response of the lung to high frequency oscillations. We measured the response of excised dog lungs and lobes between 156 and 10,000 Hz and determined the area-distance function of the acoustically equivalent structure having rigid walls, regular branching, and negligible internal losses. The utility of this techique was tested by determining the effects of air trapping, removal of pleura from a dried lung, central airway smooth muscle tone. A strong correlation was found between relative changes in equivalent acoustic area and relative area changes measured radiographically in individual airways at corresponding distances. We conclude that despite departures of the properties of the real lung from the characteristics of the acoustically equivalent structure, changes in the area-distance function computed by this technique provide reasonable estimates of the magnitude and serial distribution of actual changes in airway cross-sectional area.

Acoustic Impedance Tests↗

Resistance of intrathoracic airways of healthy subjects during periodic flow.

The resistance and reactance of lower airways were measured as functions of the frequency and amplitude of periodic flow in three healthy subjects by relating flow, produced with a piston pump, to the difference between lateral tracheal and alveolar pressure, estimated plethysmorgraphically. Resistance consistently increased with frequency; reactance was small never exceeding resistance. This result cannot be explained by distortion of velocity profiles by inertia because, in long pipes, resistance increases only when inertial forces are large and reactance exceeds resistance. Theoretical analyses of airway resistance suggested that the results reflected inhomogeneity. In lung models which considered airway wall distensibility and inertial reactance of airways, resistance increased with frequency and inertial reactance was small. These results imply that in health, as in lung disease, resistance is determined by the distribution of resistance and reactance within the lung and is not simply the total resistance of the individual airways. As flow amplitude increased at constant frequency, flow-pressure relationships became distorted and resistance increased, due probably to motion of airway walls and further distortion of velocity profiles

Adult↗

Properties of lung parenchyma in distortion.

This study offers a basis for evaluating and developing models of stress-strain behavior of the lung in distortion. Tensile forces were applied along three axes to cubes of dog lung parenchyma. With axially symmetrical force-loading, expansion was reasonably symmetrical and pressure-volume relationships were reasonably conventional in range, hysteresis, and time-dependent behavior. When the force load was changed on one axis only, that axis appeared more compliant than it did during symmetrical loading and the other axes changed length in the opposite sign. Similar distortion was apparent at the alveolar level. Data for five specimens over a range of applied loads are filed with the National Auxiliary Publications Service; graphical examples are presented herein. Relationship among the compliances for symmetrical and asymmetrical loadings were consistent with elastic theory. We derived the elastic coefficients, bulk and Young's moduli, and Poisson's ratio from the data. Poison's ratio was about 0.30 in air-filled specimens, but was lower (0.16-0.24) and increases with stress in saline-filled specimens.

Animals↗

Malathion and malaoxon environmental levels used for exposure assessment and risk characterization of aerial applications to residential areas of southern California, 1989-1990.

Between August 1989 and July 1990, California conducted a Mediterranean fruit fly eradication project in southern California which included repeated aerial applications of malathion bait to urban areas where approximately 1.6 million people resided. Concern about the safety of these applications prompted the California Department of Health Services to prepare a risk assessment. The current work presents the estimates of environmental levels of malathion and malaoxon, derived from mass deposition rates during application and monitoring of air. We estimated short and long-term malathion and malaoxon levels on outdoor surfaces, plants, and soils (0.1 and 1.0 cm mixing depth), using a simple first-order exponential decay model and literature half-life values ranging from three to nine days. Direct monitoring data were used to characterize short-term air levels. Average and upper-bound malathion levels immediately following an application were 0.091 microgram/m3 and 0.207 microgram/m3 in air; 22 and 52 mg/m2 on outdoor surfaces; 3.8 and 9.6 micrograms/g in plants; and 1.5 and 3.5 micrograms/g in soil (1 cm mixing depth). Malaoxon levels were 0.039 microgram/m3 and 0.110 microgram/m3 in air; 0.15 and 0.46 mg/m2, 0.03 and 0.09 microgram/g, and 0.01 and 0.03 microgram/g, respectively. Estimates of average and upper-bound levels over the duration of the eradication program were roughly one-third the immediate levels in all media. No field measurements were available for co-products other than malaoxon, for environmental persistence, or for concentrations on surfaces, soil, or plants after repeated applications. Because of limited monitoring data, and the likelihood that similar pest-eradication programs will be conducted, additional studies are warranted to more accurately characterize the environmental fate of malathion and human exposures after aerial application to residential communities.

Animals↗