Faculty Bibliography

Inference on the time of onset and the duration of a treatment effect is a challenging problem in biomedical research. These studies often generate repeated measurements from subjects in a treated group and a control group during the same time period. We propose a simple approach, called the 'Fishing License' method, to test for a treatment effect occurring during an unspecified time interval. The method is based on a statistic of the largest absolute value of the t statistic between two groups obtained by considering every possible time interval in the observed time period. A bootstrapped null distribution of the test statistic is used to determine the critical value. The method also provides estimates of onset and ending times, when the null hypothesis of no effect is rejected. Simulated and real experimental data sets were generated for assessing the performance of the method

The collapse of the World Trade Center (WTC) on September 11, 2001, generated large amounts of dust and smoke that settled in the surrounding indoor and outdoor environments in southern Manhattan. Sixteen dust samples were collected from undisturbed locations inside two uncleaned buildings that were adjacent to Ground Zero. These samples were analyzed for morphology, metals, and organic compounds, and the results were compared with the previously reported outdoor WTC dust/smoke results. We also analyzed seven additional dust samples provided by residents in the local neighborhoods. The morphologic analyses showed that the indoor WTC dust/smoke samples were similar to the outdoor WTC dust/smoke samples in composition and characteristics but with more than 50% mass in the <53-microm size fraction. This was in contrast to the outdoor samples that contained >50% of mass above >53 microm. Elemental analyses also showed the similarities, but at lower concentrations. Organic compounds present in the outdoor samples were also detected in the indoor samples. Conversely, the resident-provided convenience dust samples were different from either the WTC indoor or outdoor samples in composition and pH, indicating that they were not WTC-affected locations. In summary, the indoor dust/smoke was similar in concentration to the outdoor dust/smoke but had a greater percentage of mass <53 microm in diameter

The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster

The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol impacting many residents, workers, and commuters after September 11, 2001. In all, 12 bulk samples of the settled dust were collected at indoor locations surrounding the epicenter of the disaster, including one sample from a residence that had been cleansed and was once again occupied. Additionally, one sample was collected from just outside a fifth story window on the sill. These samples were analyzed for many components, including inorganic and organic constituents as well as morphology of the various particles. The results of the analyses for persistent organic pollutants on dusts that settled at indoor locations are described herein, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and select organo-chlorine pesticides. The Sigma(86)-PCB concentrations, comprising less than one part per million by mass of the bulk in the two samples analyzed, indicated that PCBs were of limited significance in the dust that settled at indoor locations across lower Manhattan. Likewise, organo-chlorine pesticides, Hexachlorobenzene, Heptachlor, 4,4'-DDE, 2,4'-DDT, 4,4'-DDT and Mirex were found at even lower concentrations in the bulk samples. Conversely, Sigma(37)-PAHs comprised up to 0.04% (<0.005-0.036%) by mass of the bulk indoor dust in the 11 WTC impacted bulk indoor samples. Analysis of one sample of indoor dusts collected from a vacuum cleaner of a rehabilitated home shows markedly lower PAH concentrations (<0.0005 mass%), as well as differing relative contributions for individual compounds. In addition to similar concentrations, comparison of PAH concentration patterns (i.e. chemical fingerprints) shows that dusts that settled indoors are chemically similar to previously measured WTC dusts found at outdoor locations and that these PAH analyses may be used in identifying dusts of WTC origin at indoor locations, along with ascertaining further needs for cleaning

This article reports an extensive program to monitor individual personal exposures of subjects recruited for a study conducted in a Chinese occupational population to determine whether selected biological markers of exposure to benzene are reliable and sensitive enough to detect low-level benzene exposure in people. The monitoring program reported here was to assure an appropriate range of exposure for subject selection as well as to provide data for the exposure response assessment. The overall study resulted in correlation of the measured exposures with the measured concentrations of two minor urinary benzene metabolites, trans,trans-muconic acid and S-phenylmercapturic acid. The study design and evaluation of biological end points are presented in separate publications. Recruitment of 130 exposed subjects was based on personal exposure measurements collected with passive organic vapor monitors at weekly intervals for 3 to 4 weeks prior to collection of biological samples. Two monitors, side by side, were used for all of the personal monitoring in the first year of the study and about 10 percent of subsequent monitoring. One of each pair was analyzed immediately in Beijing at the Institute of Occupational Medicine, and the other was shipped to the United States and analyzed at the New York University Institute of Environmental Medicine. Exposure concentrations measured over 4-5 weeks were reasonably stable with average coefficients of variation of 0.58, 0.59, and 0.46 for benzene, toluene, and xylene, respectively. Benzene exposure averaged 10 +/- 13 ppm benzene with a median of 3.8 ppm for the recruited exposed workers. Excellent correlation was obtained between samples analyzed for benzene at the two laboratories. The extensive effort to document exposures was important to the exposure-response relationship demonstrated in the full study, which concluded that S-phenylmercapturic acid appears to be a good biomarker for detecting and evaluating benzene exposure at concentrations less than 0.25 ppm

The carcinogenic process initiated by nongenotoxic carcinogens involves modulation of gene expression. Nickel compounds have low mutagenic activity, but are highly carcinogenic. In vitro both mouse and human cells can be efficiently transformed by soluble and insoluble nickel compounds to anchorage-independent growth. Because previous studies have shown that carcinogenic nickel compounds silence genes by inhibiting histone acetylation and enhancing DNA methylation, we investigated the effect of enhancing histone acetylation on cell transformation. The exposure of nickel-transformed cells to the histone deacetylase inhibitor trichostatin A (TSA) resulted in the appearance of significant number of revertants measured by their inability to grow in soft agar. Using the Affymetrix GeneChip we found that the level of expression of a significant number of genes was changed (suppressed or upregulated) in nickel-transformed clones but returned to a normal level in revertants obtained following TSA treatment. Moreover, we found that treatment of cells with TSA inhibited the ability of nickel to transform mouse PW cells to anchorage-independent growth. Treatment with TSA also inhibited the ability of nickel to transform human HOS cells, although to a lesser extent. In contrast, treatment with TSA was not able to revert established cancer cell lines as readily as the nickel-transformed cells. These data indicated that modulation of gene expression is important for nickel-induced transformation

There are limited data on the efficacy of procedures for adapting rodents to restraint in nose-only holders. We examined: (1) What effect does restraint in nose-only holders have on heart rate and body temperature? (2) Does a gradual increase in the duration of restraint facilitate adaptation? (3) How long does it take for rodents to become fully adapted to nose-only holders? (4) Do rats and mice respond and adapt similarly to restraint in nose only holders? Heart rate and body temperature were monitored as measures of stress using electrocardiograph (ECG) transmitters in male C57Bl/6J mice and Sprague-Dawley rats. In naive animals during the first hour of restraint, heart rate increased by 58 beats per minute (BPM) (18.6%) in rats and by 174 BPM (32.3%) in mice as compared to cage controls. Temperature increased by 2 degrees C in mice and was unchanged in rats compared to cage controls. Heart rate and temperature values remained within normal physiologic values during restraint. In rats, the response to restraint in nose-only holders was the same after 4 days regardless of whether the duration of restraint was increased gradually to 4 h/day or kept constant at 4 h/day. In mice, the group that was gradually adapted had a statistically significant higher heart rate and temperature after 4 days than the fixed-duration adapted group. Rats and mice restrained for 4 h/day every day showed a gradual decrease in heart rate and temperature over time. Full adaptation to restraint required 14 days of fixed-duration daily restraint