GIS approaches for the estimation of residential-level ambient PM concentrations.

Spatial estimations are increasingly used to estimate geocoded ambient particulate matter (PM) concentrations in epidemiologic studies because measures of daily PM concentrations are unavailable in most U.S. locations. This study was conducted to a) assess the feasibility of large-scale kriging estimations of daily residential-level ambient PM concentrations, b) perform and compare cross-validations of different kriging models, c) contrast three popular kriging approaches, and d) calculate SE of the kriging estimations. We used PM data for PM with aerodynamic diameter [less than or equal to] 10 [micro]m (P[M.sub.10]) and aerodynamic diameter [less than or equal to] 2.5 [micro]m (P[M.sub.2.5]) from the U.S. Environmental Protection Agency for the year 2000. Kriging estimations were performed at 94,135 geocoded addresses of Women's Health Initiative study participants using the ArcView geographic information system. We developed a semiautomated program to enable large-scale daily kriging estimation and assessed validity of semivariogram models using prediction error (PE), standardized prediction error (SPE), root mean square standardized (RMSS), and SE of the estimated PM. National- and regional-scale kriging performed satisfactorily, with the former slightly better. The average PE, SPE, and RMSS of daily P[M.sub.10] semivariograms using regular ordinary kriging with a spherical model were 0.0629, -0.0011, and 1.255 [micro]g/[m.sup.3], respectively; the average SE of the estimated residential-level P[M.sub.10] was 27.36 [micro]g/[m.sup.3]. The values for P[M.sub.2.5] were 0.049, 0.0085, 1.389, and 4.13 [micro]g/[m.sup.3], respectively. Lognormal ordinary kriging yielded a smaller average SE and effectively eliminated out-of-range predicted values compared to regular ordinary kriging. Semiautomated daily kriging estimations and semivariogram cross-validations are feasible on a national scale. Lognormal ordinary kriging with a spherical model is valid for estimating daily ambient PM at geocoded residential addresses. Key words: cross-validation, geographic information systems, kriging, particulate air pollution, population-based studies. Environ Health Perspect 114:1374-1380 (2006). doi:10.1289/ehp.9169 available via http://dx.doi.org/ [Online 8 June 2006]

**********

Large-scale, population-based epidemiologic investigations of the health effects of ambient air pollution often rely on measurements from a network of air quality monitors maintained by the U.S. Environmental Protection Agency (U.S. EPA 1995a, 1995b, 2005). The Air Quality System (AQS) is the only national ambient air pollution database currently available for public use in the United States. The availability of individual-level health outcome and covariable data from national-scale studies that often characterize participants over the course of several years enables researchers to study the acute effects of ambient air pollution using individual-level data (Liao et al. 2004, 2005a; Sullivan et al. 2005; Wellenius et al. 2005; Whitsel et al. 2004). This approach requires measures of daily particulate matter (PM) exposures, ideally assessed as close to the individual level as possible, such as at participant residences or in immediate proximity to participants themselves. Because daily measures of ambient PM concentrations from the AQS are unavailable in the large majority of locations, spatial estimation methods using geographic information systems (GIS) are increasingly being considered to estimate geocoded location-specific ambient PM concentrations, such as kriging methods. Important methodologic and practical issues still need to be resolved, however. This study was designed to a) assess the feasibility of large-scale kriging estimation of daily residential-level ambient PM concentrations, b) perform and compare cross-validations of different kriging models, c) determine and contrast the most appropriate kriging approaches, and d) calculate the SEs of the kriging estimations.

Materials and Methods

We obtained from AQS the P[M.sub.10] and P[M.sub.2.5] (PM with aerodynamic diameter [less than or equal to] 10 and 2.5 [micro]m, respectively) data from 1993-2004 (U.S. EPA 2005). The data from 2000 were used for this study after eliminating duplicate records and converting all measures to the same units and denominator. We calculated "monitor-specific" daily averages based on [greater than or equal to] 18 hourly measures. Monitor-specific daily averages were set to missing for monitors reporting < 18 hourly measures on any given day. If more than one monitor was operating at the same location on a given day, we then computed "site-specific" daily P[M.sub.10] and P[M.sub.2.5] averages by taking the mean of the monitors' measures. We also obtained the longitude and latitude for each site from the AQS database. These data served as pollutant- and site-specific daily source data for our study (Liao et al. 2005b).

We geocoded 94,135 addresses of Women's Health Initiative (WHI) Clinical Trial (CT) participant residences and examination sites in the contiguous 48 United States and District of Columbia, after assessing geocoding vendor error (Whitsel et al. 2004, 2005). Daily P[M.sub.10] and P[M.sub.2.5] concentrations and the associated estimation errors (SEs) are estimated at these geographic locations by the Environmental Epidemiology of Arrhythmogenesis in WHI study (Whitsel 2006).

We used ArcView GIS (version 8.3) and its Geostatistical Analyst Extension (ESRI Inc., Redlands, CA) for semivariogram determination and cross-validation and for subsequent spatial estimation of daily location-specific PM concentrations. Three frequently referenced spatial models (spherical, exponential, Gaussian) (Cressie 1993a; Davis 2002) were considered using the weighted least-squares method (Gribov et al. 2004; Jian et al. 1996) to obtain the "optimal" daily semivariogram parameters (range, partial sill, and nugget). Based on the daily semivariograms, we performed ordinary kriging to estimate the daily mean PM concentration and its SE at each of the 94,135 geocoded addresses. Next, we performed the standard cross-validation--an iterative procedure that omits site-specific PM data points one at a time and refits the model using the remaining data to estimate the PM concentration at the site of the omitted observation. We assessed the validity (also termed "goodness of fit") of each semivariogram using three cross-validation parameters readily available from the ArcView software package: a) the average of prediction error (PE), where PE is the average of the difference between the predicted and measured daily PM values at each monitoring site; b) the average of standardized prediction error (SPE), where SPE is the PE divided by the SE of estimation across all sites; and c) root mean square standardized (RMSS), the standard deviation (SD) of all SPEs across all sites. Additionally, we assessed the goodness of fit of each semivariogram by the average of the SEs of the estimations, generated by the kriging procedure, across all 94,135 geocoded addresses. The expectations for a good-fitting semivariogram and kriging model are an average PE and SPE near 0, an RMSS near 1, and a small SE. If RMSS < 1, there is a tendency toward overestimation of the variance; if > 1, there is a tendency toward underestimation (ESRI Inc. 2001). These criteria were consistently used to guide our model selection processes throughout this study (Liao et al. 2005c).

As an alternative to using the automatically calculated semivariogram (calculated using the weighted least-squares method (Gribov et al. 2004; Jian et al. 1996), one can also manually specify the semivariogram parameters to improve the cross-validation parameters in ArcView. We selected six least satisfactory daily semivariograms throughout year 2000 and manually adjusted the semivariogram parameters to obtain the best achievable average RMSS and SPE (RMSS as close to 1 and average SPE as close to 0 as possible). The cross-validation parameters from the weighted least-squares method-calculated semivariograms were then compared to those of the manually adjusted semivariograms.

We performed daily ordinary krigings on both the original scale (regular ordinary kriging) and the lognormal scale (lognormal ordinary kriging) (Cressie 1993b; Johnston 2001) for all WHI CT addresses for the year 2000 and compared the cross-validation parameters between the two kriging procedures. Lognormal ordinary kriging was used because it has the ability to eliminate the negative predicted values, which is a problem in ordinary kriging, especially when the source data contain extreme values.

Results

Characteristics of the site-specific daily average P[M.sub.10] and P[M.sub.2.5] concentrations. During 1994-2003, the number of monitoring sites that provided GIS-usable daily P[M.sub.10] data varied widely (range, 120-1,340). On 17% of days, GIS-usable data were provided by [greater than or equal to] 400 monitoring sites; on 39% of days, by 200-400 sites; and on 44% of days, by 120-200 sites. The corresponding values for P[M.sub.2.5] during 1999-2003 were 33% of days by [greater than or equal to] 400 sites and 67% of days by 148-400 sites. Specific to the year 2000, there were averages of 325 P[M.sub.10] and 456 P[M.sub.2.5] monitoring sites operating per day across the contiguous United States, with minima and maxima of 148 and 1,061 sites for P[M.sub.10] and 178 and 1,019 sites for P[M.sub.2.5]. As a result, there were 118,791 site-days during 2000 for which we can retrieve measured P[M.sub.10] data and 166,796 site-days for P[M.sub.2.5] data. The mean ([+ or -] SD) of P[M.sub.10] and P[M.sub.2.5] from these retrievable site-days were 26.29 [+ or -] 58.13 and 13.14 [+ or -] 8.59 [micro]g/[m.sup.3], respectively, with medians of 21.33 and 11.20 [micro]g/[m.sup.3], respectively. A right-skewed distribution of both P[M.sub.10] and P[M.sub.2.5] are evident, especially for P[M.sub.10]. Figure 1 illustrates the spatial relationships between the geocoded addresses and the PM monitoring sites on an optimal day and a typical day. The mean distance between each address and its nearest PM monitor was 12.35 km, with an SD of 13.98 km, a median of 7.81 km, an interquartile range of 10.53 km, and 99th percentile of 68.36 km.

Comparisons of three widely used spatial models. Tables 1 and 2 present summary statistics of the cross-validation parameters (PE, SPE, and RMSS) comparing three widely used spatial models (spherical, exponential, Gaussian) for P[M.sub.10] and P[M.sub.2.5], respectively. In general, both average PE and average SPE are very close to 0, with a very narrow range of variation from the 366 daily cross-validations. More specifically, > 95% of average PEs were within [+ or -] 2 [micro]g/[m.sup.3] of measured P[M.sub.10], and [+ or -] 0.5 [micro]g/[m.sup.3] of measured P[M.sub.2.5], an average measurement error that we considered acceptable. In terms of RMSS, we considered > 95% of cross-validations as acceptable, but there were days when RMSS indicated a slight over- or underestimation of the prediction variability. These data support the overall validity of using kriging-based estimation approaches to estimate location-specific PM concentrations across the contiguous United States.

Comparisons of default and manually adjusted semivariograms. Table 3 presents the cross-validations and actual kriging estimations from the weighted least-squares mean method calculated semivariogram and manually adjusted semivariogram. For the 6 days when the PE, SPE, or RMSS indicated a less satisfactory default-calculated semivariogram, these three cross-validation parameters could be improved satisfactorily through adjustment of the semivariogram parameters by an operator. However, the application of such "improved" semivariograms to the estimation of P[M.sub.10] concentrations at geocoded locations across the United States did not necessarily provide better estimation of location-specific PM (i.e., smaller SEs). To the contrary, the average SEs from the default semivariograms were smaller than those from manually adjusted semivariograms. Because each average SPE of the default-calculated daily semivariograms was close to 0, and each default-calculated daily semivariogram produced a smaller estimation error, we recommend using the default-calculated semivariogram, even though the RMSS from the default-calculated semivariogram was not fully satisfactory.

Comparisons of regular versus lognormal ordinary krigings. We applied regular ordinary kriging (spherical model, default-calculated daily semivariograms) to estimate daily P[M.sub.10] concentrations at geocoded addresses (n = 94,135) of WHI CT participants and examination sites in the contiguous United States. We examined the estimated P[M.sub.10] concentrations and identified 22 days during 2000 when estimated values exceeded the range of observed values. In some cases, the estimated values were negative. The number of addresses affected by this problem ranged from a few on most days to 3.5% of all addresses. This problem was related to skewed P[M.sub.10] distributions and to small numbers of extreme outlying values or operating sites on some days. We therefore compared regular ordinary kriging and lognormal ordinary kriging anticipating that lognormal kriging would attenuate this problem.

Table 4 lists the 22 days on which regular ordinary kriging yielded estimated P[M.sub.10] values that were outside the range of measured values. For comparison, the minima and maxima of the measured and estimated P[M.sub.10] concentrations from both regular and lognormal ordinary krigings are also listed in Table 4. In summary, during 2000, lognormal ordinary kriging effectively reduced the number of problematic days from 22 to 1. Even on this one day, lognormal ordinary kriging yielded a minimum value that was closer to the range of measured data than that from regular ordinary kriging.

Table 5 shows the mean values of cross-validation parameters of daily P[M.sub.10] semivariograms for both regular ordinary kriging and lognormal ordinary kriging. Cross-validation parameters were within the acceptable range from both regular and lognormal ordinary krigings, except for the 22 "out-of-range" days as defined above. On these out-of-range days, the SPE was well within the acceptable range for both regular and lognormal krigings, but the RMSS was > 1 from both approaches. Even so, for these out-of-range days RMSS from lognormal ordinary kriging was closer to 1 than that from regular ordinary kriging.

We then performed regular and lognormal ordinary kriging to estimate P[M.sub.10] concentrations at geocoded addresses of WHI CT participants and examination sites, based on year 2000 P[M.sub.10] data (94,135 locations and 366 days). The mean, SD, median, and maximum of the daily mean SE of the estimated P[M.sub.10] from the regular ordinary kriging were 27.36, 83.35, 13.93, and 1160.20 [micro]g/[m.sup.3], respectively. In contrast, those from the lognormal ordinary kriging were 16.29, 6.65, 15.05, and 67.46 [micro]g/[m.sup.3]. Clearly, the distribution of the estimation errors from lognormal ordinary kriging was considerably less skewed and had fewer outlying values than that from regular ordinary kriging. Alternative methods (winsorizing extreme P[M.sub.10] values; using ArcView's "no-sector" option to search for measured data points from a circle centered around a location that needs of an estimation--i.e., disabling the default "sector" search for measured data points in the four sectors of a circle, reducing the range or nugget) were less effective in estimating predicted values within the range of measured values (data not shown).

Similar to the situation observed in P[M.sub.10] estimations, lognormal ordinary kriging also effectively eliminated the negative or out-of-range problem that occurred in about 5% of P[M.sub.2.5] data when using regular ordinary kriging. Other cross-validation parameters were comparable between the lognormal and regular ordinary krigings (data not shown).

Comparisons between national and regional krigings. From the 61 days when 900 or more monitoring sites were operating in the year 2000 in the 48 contiguous states, the first of such days from each month was selected for comparisons between ordinary kriging models on a national versus regional scale. National krigings and cross-validations were performed on these 12 selected days using daily site-specific P[M.sub.10] data. Regional krigings and cross-validations were performed on the same data using the regional map (Figure 1) that divides the U.S. continent into five regions (northwest, southwest, middle north, southeast, and northeast). These five regions were created based on the assumption that different semivariogram parameters would be needed for different geographic areas. In general, for both regional and national krigings, the average SPE and RMSS from cross-validations of semivariograms calculated for the 12 selected days were very close to 0 and 1, respectively (Table 6)

Discussion

Classical methods often assume that measures are uniformly or randomly distributed. The assumptions are often inappropriate for analysis of environmental measures because values at neighboring locations are rarely independent, particularly over short distances. This form of dependence (spatial autocorrelation) nonetheless makes it possible to interpolate values at unmonitored locations from known values at monitored locations. Kriging is one such interpolation method originally developed by mining engineers (Krige 1966). It is especially attractive in this setting because it takes the spatial autocorrelation structure function (variogram) into account by considering known values from monitored locations, weighting them with values read from the variogram at corresponding distances, and splitting weights among adjacent locations. The method thereby ensures that interpolations do not depend on monitor density (Legendre and Fortin 1989). By doing so, kriging yields best linear unbiased estimates, in this setting, of location-specific daily mean ambient PM concentrations and their SEs.

Large-scale population-based epidemiologic investigations of the health effects of ambient air pollution often rely on data collected from a network of air quality monitors maintained by the U.S. EPA--the AQS data (U.S. EPA 1995a, 1995b, 2005). It is revealing to compare kriging with interpolation methods used in the well-known time-series and cohort studies of PM effects on mortality and cardiovascular disease (Abbey et al. 1991, 1999; Dockery et al. 1993; Katsouyanni et al. 1996, 2001; Miller et al. 2004, 2005; Pope et al. 2004; Samet et al. 2000a, 2000b). These studies uniformly estimated PM exposures using area-based arithmetic averaging or nearest-neighbor imputation--alternative methods that have important limitations (Moore and Carpenter 1999). Such limitations include the assumption of homogeneous exposures within study areas and the inability (or failure) to estimate exposures or associated PEs. For example, when daily exposure was of interest and there were no operating PM monitors with a study area, data pairs (daily PM concentrations, death counts) were unavailable in these studies. In addition, when longer-term (monthly to yearly) exposure was of interest, area aggregated exposures were based on available measurements within a given time frame. If there were five 24-hr measures in a month, for example, the monthly average exposure was calculated as the mean of the five readings. In contrast, our kriging-based approach estimated daily mean exposures and SEs at geocoded addresses of participants and their examination sites across the contiguous United States that can be readily integrated over time with little influence of missing data. Studies in the geosciences have also found that kriging provides consistently improved interpolation accuracy over traditional inverse-distance weighting and other, simpler spatial interpolation methods (Zimmerman 1999). Another important advantage of GIS-based estimation over the traditional area-average approach is the availability of both the location-specific estimated pollutant concentrations and their SEs.

Our goal in this study was to contribute methodologic and practical insights toward standardized, semiautomated GIS approaches to estimation of daily air pollution concentrations and their associated estimation errors. The air pollution data estimated using these approaches will support the Environmental Epidemiology of Arrhythmogenesis in WHI study (Whitsel 2006) examining the cardiac effects of air pollution in 68,133 postmenopausal women 50-79 years of age at baseline in the WHI CT (WHI Study Group 1998). Here we describe our experience resolving several important methodologic and practical issues in adopting a systematic, standardized, and semiautomated kriging approach to estimate daily air pollution concentrations and the associated estimation errors at geocoded addresses across the contiguous United States over 10 years.

We successfully downloaded from AQS the P[M.sub.10] and P[M.sub.2.5] raw data from 1993-2004. We then cleaned, calculated, and reconstructed site-specific daily PM concentration data ready for GIS applications. It is well known that the monitoring sites in AQS are not randomly distributed, which is one of the assumptions in kriging estimation, and the density of the monitoring sites is relatively low given the size of the contiguous United States. However, the AQS is the only currently available nationwide database. Our cross-validation studies suggest that the AQS data can be used as source data for kriging estimation of ambient pollution concentrations at various locations across the 48 contiguous states.

In this study, we performed cross-validation to assess the goodness of fit of various semivariogram and spatial models using four major parameters: the average PE, SPE, RMSS, and SE of estimation. Details can be found elsewhere (Webster and Oliver 2001), but it is worth noting that in addition to using the SE as a measure of the goodness of fit of a kriging model, one could improve the health effects models by incorporating SE in the models to account for the error in the estimation of location-specific PM concentrations. We consider this an important advantage of GIS-based estimation over the traditional area-average approach and are performing studies of using SE in health effects models.

We compared the performance of three widely spatial models (spherical, exponential, Gaussian) for P[M.sub.10] and P[M.sub.2.5] estimations using regular ordinary kriging on a national scale (Tables 1 and 2). In general, the cross-validation parameters suggest that all three models performed fairly well. Overall, the spherical model seemed to perform slightly better, consistent with the observation that the spatial distribution pattern of ambient air pollutants is closest to the assumption of the spherical model. The spherical model has been used most often in modeling spatially distributed data, providing a further rationale for its use in our large-scale population-based study of the health effects of PM. Furthermore, from the perspective of the cross-validation results, both average PE and average SPE are very close to 0, with a very narrow range of variation from the 366 daily cross-validations. These data support the overall validity of using kriging-based estimation approaches to estimate location-specific PM concentrations across the contiguous United States.

We completed an empirical analysis to investigate whether manually adjusting semivariogram parameters improves a) cross-validation parameters and b) estimated P[M.sub.10] concentrations and their SEs (Table 3). From these data, we conclude that manually adjusting semivariogram parameters improves cross-validation parameters. However, the application of such "improved" semivariograms to the estimation of P[M.sub.10] concentrations at geocoded locations across the United States did not necessarily provide better estimation of location-specific PM. Therefore, we recommend using the default-calculated semivariogram.

Semivariograms are sensitive to strong positive skewness. As a result, regular ordinary kriging can yield negative predicted values or values exceeding the range of the source data. Kriging works best if the input data have a normal distribution. One solution is to log-transform the input data--using "lognormal kriging." In the ArcView software package, performing lognormal kriging is a standard option. This option log-transforms the input data to normalize its distribution and attenuate the impact of very large values. It also back-transforms the estimated values and the "unbiased" SE of the estimation to the original scale (Cressie 1993b; Johnston 2001). Our results comparing lognormal ordinary kriging versus regular-scale ordinary kriging suggest that lognormal ordinary kriging not only effectively estimated location-specific PM concentrations within the range of the measured data for the days regular ordinary kriging yielded negative or "out of range" PM estimations, but also yielded a smaller average SE than did regular ordinary kriging and estimations. Therefore, our results support the use of lognormal ordinary kriging as an acceptable solution to the problem commonly posed by positively skewed distributions of environmental data.

Our comparisons of national- versus regional-scale kriging indicate that, in terms of cross-validation results, both performed similarly. However, such comparisons are based on krigings using the source data from optimal days (when > 900 sites across the country were reporting data), which account for only 17% of all days in a year. Therefore, there is additional justification for using national-scale kriging: Usually, there were very few operating sites within a region. On typical days--when only about 200 monitoring sites were operating--ability to derive stable and meaningful semivariograms was greatly impaired. Regional kriging also poses problems for estimation at locations near regional borders. For example, at locations within Washington State but near the Washington-Idaho border, regional kriging is based solely on P[M.sub.10] concentrations in the "Washington/Oregon, Northern California" region. It is not based on P[M.sub.10] concentrations measured immediately across the border in Idaho, despite the real possibility that they would have the largest weights in national-scale kriging estimation. For all these reasons, we recommend national-scale kriging.

Considering the number of study participants and the length of study period (1994-2003) for the Environmental Epidemiology of Arrhythmogenesis in WHI study, development of an automated procedure enabling large-scale daily krigings and semivariogram cross-validations was critical. In this study, we decided to use ArcView for predicting individuals' PM exposure concentrations because of the flexibility it offers for automation. Because ArcView GIS relies on either the weighted least-squares method or visual adjustment to create semivariograms, we did not compare the relative performance of semivariograms generated using alternative methods such as maximum likelihood and restricted maximum likelihood. For generating semivariograms, we compared only three popular spatial models (spherical, exponential, and Gaussian). Our results, however, do not invalidate alternative spatial models (e.g., power). In the end, we selected the spherical model for our study because it is the most studied model, and its assumption pertaining to the spatial correlation of data is probably closest to our pollutant data. Furthermore, the spherical model seemed to perform as well as or slightly better than the remaining models in terms of cross-validation parameters.

We chose ordinary kriging instead of universal or simple kriging for several reasons. First, the assumption for simple kriging of a known mean concentration on any given day across space is not practical for our data. Although it may seem more appropriate because of the "varying mean" concentration across the contiguous U.S. assumption, universal kriging requires a predetermined set of "exploratory variables" to explain the varying means. The candidates, many of which are spatial variables, include emissions, land use, population, road network distribution, altitude, rainfall, latitude, climatology, and other quality data. Denby et al. (2005) recently recommended a method that uses measured concentration data in combination with some "exploratory variables" as suggested above. However, their approach may not be feasible for a national-scale study such as ours, because little guiding information is available as to how to identify a set of widely acceptable variables that can be applied to the entire nation. Moreover, even if we could identify a set of exploratory variables, we do not know the forms or shapes of their independent and joint relations to the air pollution measures. Further studies that involve large-scale national data using universal kriging are still needed. In this study, we empirically tested whether the nonconstant mean assumption for universal kriging was needed; we performed five regional ordinary krigings so that different parts of the country would assume a different mean PM concentration. Our data suggested that regional and national ordinary kriging performed similarly. Therefore, our data indirectly validated and supported the use of national ordinary kriging.

Although the primary objective of our study is to assess the short-term relationship between PM and cardiac responses, the proposed kriging method also enables us to calculate the long-term cumulative exposure of an individual by taking into account the change of his or her residences over time, because the WHI study recorded the residential location history over 10 years. Nevertheless, from the environmental perspective, an inherited limitation of the kriging-based approach is that the estimations of the PM concentrations will provide only surrogates, or the best guesses, of the true exposure levels at the locations of interest. Thus, the accuracy of the estimations depends highly on the quality of the measured data and their spatial correlation. Even if the estimations were made with a high level of confidence, they cannot be directly interpreted as the true individual-level exposures. However, to correlate individual level cardiac responses with a surrogate of location-specific exposure, our approach represents one of the best available methods for a large-scale population-based study.

In summary, our investigation of GIS approaches for estimating daily mean geocoded location-specific air pollutant concentrations and their SEs supports the use of a spherical model to perform lognormal ordinary kriging on a national scale. Our findings also support the use of default-generated semivariograms (estimated using the weighted least-squares method) without visual adjustment. We developed a semiautomated program to access and execute ArcView to implement these approaches for large-scale daily kriging estimations and semivariogram cross-validations. Detailed information about this program can be obtained on request.

REFERENCES

Abbey DE, Moore J, Petersen F, Beeson L. 1991. Estimating cumulative ambient concentrations of air pollutants: description and precision of methods used for an epidemiological study. Arch Environ Health 46:281-287.

Abbey DE, Nishino N, McDonnell WF, Burchette RJ, Knutsen SF, Lawrence Beeson W, et al. 1999. Long-term inhalable particles and other air pollutants related to mortality in nonsmokers. Am J Respir Crit Care Med 159:373-382.

Cressie NAC. 1993a. Geostatistics. In: Statistics for Spatial Data (Cressie NAC, ed). New York:John Wiley & Sons, 29-104.

Cressie NAC. 1993b. Spatial prediction and kriging. In: Statistics for Spatial Data (Cressie NAC, ed). New York:John Wiley & Sons, 105-209.

Davis JC. 2002. Analysis of sequences of data. In: Statistics and Data Analysis in Geography (Davis JC, ed). 3rd ed. New York:John Wiley & Sons, 159-292.

Denby B, Walker SE, Horalek OJ, Eben K, Fiala J. 2005. Interpolation and Assimilation Methods for European Scale Air Quality Assessment and Mapping. Part I: Review and Recommendations. European Topic Centre on Air and Climate Change Technical Paper 2005/7. Bilthoven, the Netherlands:European Topic Centre on Air and Climate Change.

Dockery DW, Pope CA III, Xu X, Spengler JD, Ware JH, Fay ME, et al. 1993. An association between air pollution and mortality in six U.S. cities. N Engl J Med 329:1753-1759.

ESRI Inc. 2001. Using analytic tools when generating surfaces. In: Geostatistical Analyst Extension. Redlands, CA:ESRI Inc., 128-167.

Gribov A, Krivoruchko K, Hoef JMV. 2004. Modeling the semivariogram: new approach, methods comparison and case study. In: Stochastic Modeling and Geostatistics--Principles, Methods and Case Studies (Yarus JM, Chambers RL, eds). Vol 2. Bath, UK:American Association of Petroleum Geologists. Available: http://campus.esri.com/campus/library/books/GeostatisticsTeam/Krivoruchko_2001_Modeling.pdf [accessed 31 July 2006].

Jian X, Olea RA, Yu YS. 1996. Semivariogram modeling by weighted least squares. Comput Geosci 22:387-397.

Johnston K. 2001. Lognormal linear kriging. In: Using ArcGIS Geostatistical Analyst (ESRI, ed). Redlands, CA:ESRI Press, 247-273.

Katsouyanni K, Schwartz J, Spix C, Touloumi G, Zmirou D, Zanobetti A, et al. 1996. Short term effects of air pollution on health: a European approach using epidemiologic time series data: the APHEA protocol. J Epidemiol Community Health 50(suppl 1):S12-S18.

Katsouyanni K, Touloumi G, Samoli E, Gryparis A, Le Tertre A, Monopolis Y, et al. 2001. Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 project. Epidemiology 12:521-531.

Krige DG. 1966. Two-dimensional weighted moving average trend surfaces for ore evaluation. J S Afr Inst Min Metall 66:13-38.

Legendre P, Fortin M-J. 1989. Spatial pattern and ecological analysis. Vegetatio 80:107-138.

Liao D, Duan Y, Whitsel EA, Zheng ZJ, Heiss G, Chinchilli VM, et al. 2004. Association of higher levels of ambient criteria pollutants with impaired cardiac autonomic control: a population-based study. Am J Epidemiol 159:768-777.

Liao D, Heiss G, Chinchilli VM, Duan Y, Folsom AR, Lin H, et al. 2005a. Association of criteria pollutants with plasma hemostatic/inflammatory markers--a population-based study. J Expo Anal Environ Epidemiol 15:319-328.

Liao D, Peuquet DJ, Duan Y, Whitsel EA, Dou J, Smith RL, et al. 2005b. Estimation of residential-level ambient PM concentrations from the U.S. EPA's air quality monitoring database [Abstract]. Epidemiology 16(5):S27-S28.

Liao D, Peuquet DJ, Duan Y, Dou J, Smith RL, Whitsel EA, et al. 2005c. GIS approaches for estimation of residential-level ambient PM concentrations [Abstract]. Epidemiology 16(5):S28.

Miller KA, Siscovick DS, Sheppard L, Anderson GL, Kaufman JD. 2004. Air pollution and cardiovascular disease events in the women's health initiative observational (WHI-OS) study [Abstract]. Circulation 109:E189.

Miller KA, Siscovick DS, Sheppard L, Sheppard K, Anderson GL, Kaufman JD. 2005. Effect of traditional risk factors on the association of air pollution and incident cardiovascular disease in the women's health initiative observational study (WHI-OS) [Abstract]. Circulation 111:E228-E229.

Moore DA, Carpenter TE. 1999. Spatial analytical methods and geographic information systems: use in health research and epidemiology. Epidemiol Rev 21:143-161.

Pope CA III, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, et al. 2004. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 109:71-77.

Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. 2000a. Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994. N Engl J Med 343:1742-1749.

Samet JM, Zeger SL, Dominici F, Curriero F, Coursac I, Dockery DW, et al. 2000b. The National Morbidity, Mortality, and Air Pollution Study. Part II: Morbidity and mortality from air pollution in the United States. Res Rep Health Eff Inst 94(pt 2):5-70.

Sullivan J, Sheppard L, Schreuder A, Ishikawa N, Siscovick D, Kaufman J. 2005. Relation between short-term fine-particulate matter exposure and onset of myocardial infarction. Epidemiology 16:41-48.

U.S. EPA. 1995a. Air Quality Criteria for Particulate Matter. Vol 1. EPA/600/p-95/001aF. Research Triangle Park, NC:U.S. Environmental Protection Agency, Environmental Criteria and Assessment Office.

U.S. EPA. 1995b. Office of Air Quality Planning and Standards: Aerometric Information Retrieval System (AIRS). Vol 2. Research Triangle Park, NC:U.S. Environmental Protection Agency.

U.S. EPA. 2005. Air Quality System. Research Triangle Park, NC:U.S. Environmental Protection Agency. Available: http://www.epa.gov/ttn/AQS/AQSaqs/ [accessed 15 December 2005].

Webster R, Oliver MA. 2001. Geostatistics for environmental scientists. In: Statistics in Practice (Barnett V, ed). New York:John Wiley & Sons, 149-192.

Wellenius GA, Schwartz J. Mittleman MA. 2005. Air pollution and hospital admissions for ischemic and hemorrhagic stroke among Medicare beneficiaries. Stroke 36:2549-2553.

WHI Study Group. 1998. Design of the Women's Health Initiative Clinical Trial and Observational Study. Control Clin Trials 19:61-109.

Whitsel EA. 2006. The environmental epidemiology of arrhythmo genesis in WHI [Abstract]. Available: http://crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=6599396&p_grant_num=1R01ES012238-1&p_query=&ticket=6776514&p_audit_session_id=30381838&p_keywords= [accessed 15 December 2005].

Whitsel EA, Rose KM, Wood JL, Henley AC, Liao D, Heiss G. 2004. Accuracy and repeatability of commercial geocoding. Am J Epidemiol 160:1023-1029.

Whitsel EA, Rose KM, Wood JL, Henley AC, Liao D, Smith RL, et al. 2005. Accuracy and repeatability of commercial geocoding [Abstract]. Circulation 111:237.

Zimmerman D. 1999. An experimental comparison of ordinary and universal kriging and inverse distance weighting. Math Geol 31:375-390.

Duanping Liao, (1) Donna J. Peuquet, (2) Yinkang Duan, (1) Eric A. Whitsel, (3,4) Jianwei Dou, (2) Richard L. Smith, (5) Hung-Mo Lin, (1) Jiu-Chiuan Chen, (3) and Gerardo Heiss (3)

(1) Department of Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; USA; (2) Department of Geography, Pennsylvania State University, College Park, Pennsylvania, USA; (3) Department of Epidemiology, (4) Department of Medicine, and (5) Department of Statistics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA

Address correspondence to D. Liao, Department of Health Evaluation Sciences, Pennsylvania State University College of Medicine, 600 Centerview Dr., A210, Hershey, PA 17033 USA. Telephone [phone]. Fax: [phone]. E-mail: [e-mail]

We acknowledge the contributions of WHI investigators and institutions (Appendix).

The National Institute of Environmental Health Sciences funded this ancillary study (5-R01-ES012238). The National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services, funded the Women's Health Initiative (WHI) program.

The authors declare they have no competing financial interests.

Received 15 March 2006; accepted 8 June 2006.

Table 1. Cross-validation summary statistics and semivariogram parameter
estimates for P[M.sub.10] from three different spatial models, year
2000.

Model                    Days (a)  Mean            SD

PE ([micro]g/[m.sup.3])
  Exponential            366               0.2347          1.3212
  Gaussian               366              -0.1097          1.0509
  Spherical              366               0.0629          1.1999
RMSS
  Exponential            366               1.8374          1.5431
  Gaussian               366               1.1709          0.9891
  Spherical              366               1.2549          0.7988
SPE
  Exponential            366               0.0118          0.0330
  Gaussian               366              -0.0094          0.0333
  Spherical              366              -0.0011          0.0212
Nugget ([micro]g/
  [m.sup.3])
  Exponential            366           2,837.28       27,839.3
  Gaussian               366           4,096.10       38,738.9
  Spherical              366           3,515.02       33,349.0
Partial sill ([micro]g/
  [m.sup.3])
  Exponential            366           7,957.38       91,589.2
  Gaussian               366           6,483.31       73,915.9
  Spherical              366           6,374.25       71,024.0
Range (m)
  Exponential            366       2,696,226       2,832,621
  Gaussian               366       2,163,126       2,277,023
  Spherical              366       2,447,936       2,375,933

                                             2.5th           97.5th
Model                          Median      percentile       percentile

PE ([micro]g/[m.sup.3])
  Exponential                    0.0294       -0.6437          1.6690
  Gaussian                      -0.1216       -1.1230          1.0020
  Spherical                     -0.0705       -0.7914          1.4810
RMSS
  Exponential                    1.1410        0.8638          6.0240
  Gaussian                       1.0070        0.8140          2.2660
  Spherical                      1.0270        0.8094          4.1550
SPE
  Exponential                    0.0036       -0.0274          0.1058
  Gaussian                      -0.0071       -0.0418          0.0274
  Spherical                     -0.0034       -0.0318          0.0470
Nugget ([micro]g/
  [m.sup.3])
  Exponential                   93.5230        0.0000      5,332.40
  Gaussian                     181.975        26.6230      7,466.20
  Spherical                    142.955         0.0000      7,143.10
Partial sill ([micro]g/
  [m.sup.3])
  Exponential                  258.515        49.1340     23,007.0
  Gaussian                     176.240        39.4570     23,716.0
  Spherical                    201.215        36.6550     22,736.0
Range (m)
  Exponential            1,392,250       282,500       9,064,200
  Gaussian               1,207,050       262,460       8,958,300
  Spherical              1,424,050       280,820       8,958,300

(a) Daily operating monitoring sites range from 148 to 1,061 sites.

Table 2. Cross-validation summary statistics and semivariogram parameter
estimates for P[M.sub.2.5] from three different spatial models, year
2000.

Model                    Days (a)           Mean            SD

PE ([micro]g/[m.sup.3])
  Exponential            366               0.1067          0.1162
  Gaussian               366              -0.0323          0.0846
  Spherical              366               0.0491          0.0883
  RMSS
  Exponential            366               2.0953          1.6086
  Gaussian               366               0.9562          0.4500
  Spherical              366               1.3887          1.3037
SPE
  Exponential            366               0.0253          0.0356
  Gaussian               366              -0.0102          0.0155
  Spherical              366               0.0085          0.0242
Nugget ([micro]g/
  [m.sup.3])
  Exponential            366               9.4120         14.0622
  Gaussian               366              26.8536         19.8300
  Spherical              366              16.4381         16.5187
Partial sill ([micro]g/
  [m.sup.3])
  Exponential            366              94.0859         81.4191
  Gaussian               366              80.2910        102.183
  Spherical              366              84.3554         82.4740
Range (m)
  Exponential            366       4,944,054       3,364,623
  Gaussian               366       3,137,407       2,199,286
  Spherical              366       3,840,664       2,669,710

                                            2.5th
Model                          Median     percentile   97.5th percentile

PE ([micro]g/[m.sup.3])
  Exponential                    0.0857       -0.0756          0.3835
  Gaussian                      -0.0349       -0.2084          0.1187
  Spherical                      0.0413       -0.1033          0.2571
  RMSS
  Exponential                    1.4365        0.5974          6.1640
  Gaussian                       0.9114        0.5517          1.5960
  Spherical                      1.0014        0.5532          4.5810
SPE
  Exponential                    0.0127       -0.0178          0.1097
  Gaussian                      -0.0096       -0.0379          0.0178
  Spherical                      0.0038       -0.0219          0.0749
Nugget ([micro]g/
  [m.sup.3])
  Exponential                    4.2819        0.0000         46.2270
  Gaussian                      22.2560        3.3694         76.4140
  Spherical                     12.0995        0.0000         64.1640
Partial sill ([micro]g/
  [m.sup.3])
  Exponential                   70.0215       13.0410        304.610
  Gaussian                      49.9360        8.8309        326.550
  Spherical                     56.7625       10.1850        299.980
Range (m)
  Exponential            4,047,800       758,590       9,064,200
  Gaussian               2,683,950       564,450       8,904,000
  Spherical              3,370,250       667,310       8,944,000

(a) Daily operating monitoring sites range from 178 to 1,019 sites.

Table 3. Comparison of estimated P[M.sub.10] ([micro]g/[m.sup.3]) at
94,135 geocoded addresses of WHI CT participant residences and
examination sites using default and manually modified semivariograms.

                     Summary statistics of cross-validations
                   PE                 RMSS               SPE
Date        Default  Modified  Default  Modified  Default  Modified

02/16/2000  0.0122   -0.0099   5.034    1.037     0.0470    0.0021
03/05/2000  0.1660    0.0474   5.134    1.360     0.0469    0.0058
07/15/2000  0.5278    0.0193   5.564    1.180     0.0674   -0.0024
08/07/2000  0.5524   -0.1056   6.183    1.134     0.1417   -0.0053
08/19/2000  0.7609    0.3651   4.744    1.146     0.0963    0.0142
10/28/2000  0.4590    0.0363   4.243    1.276     0.0780    0.0018

                         Summary statistics of estimation
                                                  P[M.sub.10] difference
             Mean P[M.sub.10]       Mean SE       (default--modified)
Date        Default  Modified  Default  Modified  Mean  SD

02/16/2000  31.19    28.76      9.73    14.02     2.43  3.61
03/05/2000  20.85    20.10     10.99    13.80     0.75  4.24
07/15/2000  24.01    23.83      7.57    10.13     0.18  3.11
08/07/2000  34.84    33.79     14.09    17.27     1.06  2.70
08/19/2000  25.07    24.76     13.59    13.54     0.30  3.64
10/28/2000  25.17    24.23      5.57     7.40     0.93  2.16

Table 4. Minima and maxima of measured and estimated P[M.sub.10]
([micro]g/[m.sup.3]) on the 22 days in 2000 when estimated values
exceeded the range of measured values.

                 Estimated from                Estimated from
       Minimum   ordinary krigings   Maximum   ordinary krigings
Date   measured  Regular  Lognormal  measured  Regular   Lognormal

01/11  3.80       -3.135   5.535      712.00    534.814  261.951
01/15  3.00        2.106  11.756      194.88    162.905   88.078
01/16  3.00        2.102   9.150      167.60    107.460   70.224
02/13  1.00       -4.006   5.938      196.13    100.739   33.147
02/28  3.00       -0.005   7.196      138.50    135.518   77.630
03/05  3.68       -5.278   7.281      186.48    103.308   36.171
03/11  4.00        2.945   9.064      109.15    106.438   42.912
03/18  5.29        3.179   8.841      117.35    108.649   43.124
04/08  4.00      -43.540   9.097      690.00    534.630   78.059
04/16  0.14       -3.759   0.901      171.13    164.973   69.290
05/04  5.65       -5.768  14.550     1063.00    808.397   61.646
05/09  2.00      -15.362  10.889     3059.00    895.213   66.493
05/10  3.00      -18.598  13.805     1513.00   1023.12   252.891
05/14  6.00        5.472   6.175       82.00     79.383   79.051
06/07  9.13      -49.164  18.164     1642.00   1234.99    64.426
06/10  8.00        7.456   8.224      111.79     69.293   74.018
06/15  7.22        5.282  12.582      242.42    235.167   83.429
07/04  7.00        6.946   9.128       90.00     80.347   74.346
08/02  3.00       -1.224  16.587      441.00    356.964   76.597
08/17  8.22        5.296   7.132      200.00    194.675  198.473
08/20  5.00        4.244   5.899      135.00    134.182   83.798
08/30  7.00        6.074  11.696      140.00    112.957   83.781

Table 5. Means [+ or -] SDs of the cross-validation summary statistics
from both ordinary and lognormal krigings, year 2000.

                           All days (n = 366)
                      SPE                        RMSS

Ordinary   -0.0011 [+ or -] 0.0212    1.2549 [+ or -] 0.7988
Lognormal  -0.05012 [+ or -] 0.10191  1.390834 [+ or -] 1.56927

                         Out-of-range days (n = 22)
                      SPE                         RMSS

Ordinary    0.018489 [+ or -] 0.04202  3.329227 [+ or -] 1.93762
Lognormal  -0.10918 [+ or -] 0.12434   2.374532 [+ or -] 2.18070

                        Within-range days (n = 344)
                      SPE                        RMSS

Ordinary   -0.00147 [+ or -] 0.02018  1.18206 [+ or -] 0.67478
Lognormal  -0.04635 [+ or -] 0.09933  1.327924 [+ or -] 1.50445

Table 6. Comparisons of goodness of fit between national and regional
scale krigings of the 12 days studied in 2000.

                              SPE
Date    Natl     SW      NW       MN       SE       NE

01/01    0.0106  0.0193  -0.0238   0.0008  -0.0168  -0.0125
02/06    0.0034  0.0320  -0.0013   0.0087   0.0241  -0.0126
03/01    0.0159  0.0089   0.0456   0.0062  -0.0079  -0.0215
04/06   -0.0015  0.0038   0.0286  -0.0032   0.0014   0.0140
05/06   -0.0052  0.0284  -0.0420  -0.0075  -0.0095  -0.0178
06/05   -0.0079  0.0150   0.0105  -0.0228  -0.0086  -0.0058
07/05    0.0031  0.0010   0.0083  -0.0571  -0.0233   0.0054
08/04    0.0108  0.0220  -0.0025   0.0069  -0.0208   0.0165
09/03    0.0053  0.0086  -0.0013  -0.0022   0.0054   0.0130
10/03    0.0055  0.0245   0.0164  -0.0314   0.0287   0.0137
11/02    0.0190  0.0565   0.0364  -0.0155   0.0432   0.0080
12/02    0.0130  0.0193   0.0379  -0.0016   0.0308   0.0010
Mean     0.0060  0.0199   0.0094  -0.0099   0.0039   0.0001
Median   0.0054  0.0193   0.0094  -0.0027  -0.0033   0.0032
SD       0.0083  0.0150   0.0259   0.0192   0.0225   0.0136

                           RMSS
Date    Natl    SW      NW      MN      SE      NE

01/01   0.9843  0.9976  1.0042  1.0064  0.9642  0.8617
02/06   0.9996  1.0034  1.0203  0.9335  1.0370  0.9816
03/01   1.0237  1.0701  1.0505  1.0021  1.0067  1.0397
04/06   0.9992  0.9693  1.0927  0.8644  1.0000  0.9995
05/06   1.0732  1.0027  1.0162  0.9997  0.9938  0.9361
06/05   0.9966  0.9694  1.1046  0.9131  1.1005  1.0638
07/05   0.9938  0.9052  1.1020  0.9489  1.0043  1.0048
08/04   0.9922  0.9990  1.2180  1.0243  0.9932  1.0014
09/03   0.9731  1.0328  1.0393  1.0030  0.8441  1.0008
10/03   0.9692  1.0014  1.0052  0.9925  0.9948  0.9619
11/02   0.9956  0.9984  0.9210  0.9964  0.9933  1.0103
12/02   0.9956  0.9976  1.0037  1.0082  1.0454  1.1159
Mean    0.9997  0.9956  1.0481  0.9744  0.9981  0.9981
Median  0.9956  0.9987  1.0298  0.9981  0.9974  1.0011
SD      0.0269  0.0389  0.0743  0.0485  0.0598  0.0634

Abbreviations: Natl, national-scale kriging; MN, kriging in middle north
region; NE, kriging in northeast region; NW, kriging in northwest
region; SE, kriging in southeast region; SW, kriging in southwest
region.

Appendix 1. WHI Institutions and Investigators

WHI Program Office, National Heart,  Barbara Alving, Jacues Rossouw,
  Lung, and Blood Institute,         Shari Ludlam, Linda Pottern,
  Bethesda, MD                       Joan McGowan, Leslie Ford,
                                     Nancy Geller
Clinical Coordinating Centers
  Fred Hutchinson Cancer Research    Ross Prentice, Garnet Anderson,
    Center, Seattle, WA              Andrea LaCroix,
                                     Charles L. Kooperberg,
                                     Ruth E. Patterson, Anne McTiernan,
                                     Shirley Beresford
  Wake Forest University School of   Sally Shumaker
    Medicine, Winston-Salem, NC
  Medical Research Labs, Highland    Evan Stein
    Heights, KY
  University of California-San       Steven Cummings
    Francisco, San Francisco, CA
Clinical Centers
  Albert Einstein College of         Sylvia Wassertheil-Smoller
    Medicine, Bronx, NY
  Baylor College of Medicine,        Jennifer Hays
    Houston, TX
  Brigham and Women's Hospital,      JoAnn Manson
    Harvard Medical School, Boston,
    MA
  Brown University, Providence, RI   Annlouise R. Assaf
  Emory University, Atlanta, GA      Lawrence Phillips
  George Washington University       Judith Hsia
    Medical Center Washington, DC
  Harbor-UCLA Research and           Rowan Chlebowski
    Education Institute, Torrance,
    CA
  Kaiser Permanente Center for       Evelyn Whitlock
    Health Research, Portland, OR
  Kaiser Permanente Division of      Bette Caan
    Research, Oakland, CA
  Medical College of Wisconsin,      Jane Morley Kotchen
    Milwaukee, WI
  MedStar Research Institute/Howard  Barbara V. Howard
    University, Washington, DC
  Northwestern University,           Linda Van Horn
    Chicago/Evanston, IL
  Ohio State University, Columbus,   Rebecca Jackson
    OH
  Rush Medical Center, Chicago, IL   Henry Black
  Stanford Prevention Research       Marcia L. Stefanick
    Center, Stanford, CA
  State University of New            Dorothy Lane
    York-Stony Brook, Stony Brook,
    NY
  University of Alabama at           Cora E. Lewis
    Birmingham, Birmingham, AL
  University of Arizona,             Tamsen Bassford
    Tucson/Phoenix, AZ
  University at Buffalo, Buffalo,    Jean Wactawski-Wende
    NY
  University of California-Davis,    John Robbins
    Sacramento, CA
  University of California-Irvine,   F. Allan Hubbell
    Irvine, CA
  University of California-Los       Howard Judd
    Angeles, Los Angeles, CA
  University of California-San       Robert D. Langer
    Diego, La Jolla/Chula Vista, CA
  University of Cincinnati,          Margery Gass
    Cincinnati, OH
  University of Florida,             Marian Limacher
  Gainesville/Jacksonville, FL
  University of Hawaii, Honolulu,    David Curb
    HI
  University of Iowa, Iowa           Robert Wallace
    City/Davenport, IA
  University of Massachusetts/       Judith Ockene
    Fallon Clinic, Worcester, MA
  University of Medicine and         Norman Lasser
    Dentistry of New Jersey,
    Newark, NJ
  University of Miami, Miami, FL     Mary Jo O'Sullivan
  University of Minnesota,           Karen Margolis
    Minneapolis, MN
  University of Nevada, Reno, NV     Robert Brunner
  University of North Carolina-      Gerardo Heiss
    Chapel Hill, Chapel Hill, NC
  University of Pittsburgh,          Lewis Kuller
    Pittsburgh, PA
  University of Tennessee, Memphis,  Karen C. Johnson
    TN
  University of Texas Health         Robert Brzyski
    Science Center, San Antonio, TX
  University of Wisconsin, Madison,  Gloria E. Sarto
    WI
  Wake Forest University School of   Denise Bonds
    Medicine, Winston-Salem, NC
  Wayne State University School of   Susan Hendrix
    Medicine/Hutzel Hospital,
    Detroit, MI