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92 result(s) for "Lamm, Steven"
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A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water
High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1–1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100–150 µg/L arsenic.
Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water
Background: Although inorganic arsenic in drinking water at high levels (100s–1000s μg/L [ppb]) increases cancer risk (skin, bladder, lung, and possibly prostate), the evidence at lower levels is limited. Methods: We conducted an ecologic analysis of the dose-response relationship between prostate cancer incidence and low arsenic levels in drinking water in a large study of U.S. counties (N = 710). County arsenic levels were <200 ug/L with median <100 ug/L and dependency greater than 10%. Groundwater well usage, water arsenic levels, prostate cancer incidence rates (2009–2013), and co-variate data were obtained from various U.S. governmental agencies. Poisson and negative-binomial regression analyses and stratified analysis were performed. Results: The best fitting polynomial analysis yielded a J-shaped linear-quadratic model. Linear and quadratic terms were significant (p < 0.001) in the Poisson model, and the quadratic term was significant (p < 0.05) in the negative binomial model. This model indicated a decreasing risk of prostate cancer with increasing arsenic level in the low range and increasing risk above. Conclusions: This study of prostate cancer incidence in US counties with low levels of arsenic in their well-water arsenic levels finds a j-shaped model with decreasing risk at very low levels and increasing risk at higher levels.
Lung Cancer Risk and Low (≤50 μg/L) Drinking Water Arsenic Levels for US Counties (2009–2013)—A Negative Association
While epidemiologic studies clearly demonstrate drinking water with high levels of arsenic as a significant risk factor for lung cancer, the evidence at low levels (≤50 μg/L) is uncertain. Therefore, we have conducted an ecological analysis of recent lung cancer incidence for US counties with a groundwater supply of <50 μg/L, the historical limit for both the EPA and WHO. Data sources used included USGS for arsenic exposure, NCI for lung cancer outcome, and CDC and US Census Bureau forcovariates. Poisson log-linear models were conducted for male, female, and total populations using for exposure median county arsenic level, maximum arsenic level ≤50 μg/L, and ≥80% population groundwater dependency. Statistically significant negative associations were found in each of the six models in which the exposure was limited to those who had major exposure (≥80% dependency) to low-levels of arsenic (≤50 μg/L). This is the first large ecological study of lung cancer risk from drinking water arsenic levels that specifically examined the dose-response slope for populations whose exposure was below the historical limit of ≤50 μg/L. The models for each of the three populations (total; male; female) demonstrated an association that is both negative and statistically significant.
Arsenic in Drinking Water and Lung Cancer Mortality in the United States: An Analysis Based on US Counties and 30 Years of Observation (1950-1979)
Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10–934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3–59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. The unit risk estimates were nonpositive and not significantly different from zero, and the maximum (95% UCL) unit risk estimates for lung cancer were lower than those in US EPA (2010). Conclusions. These data do not demonstrate an increased risk of lung cancer associated with median drinking water arsenic levels in the range of 3–59 µg/L. The upper-bound estimates of the risks are lower than the risks predicted from the SW Taiwan data and do not support those predictions. These results are consistent with a recent metaregression that indicated no increased lung cancer risk for arsenic exposures below 100–150 µg/L.
Arsenic Cancer Risk Confounder in Southwest Taiwan Data Set
Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD)-endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose-response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 µg/L (95% confidence interval, 42 to 229 µg/L). Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose-response relationship with arsenic exposure by separating out township as a confounding factor.
Arsenic in Drinking Water and Bladder Cancer Mortality in the United States: An Analysis Based on 133 U.S. Counties and 30 Years of Observation
This study analyzes the relationship between arsenic exposure through dunking water and bladder cancer mortality. The county-specific white male bladder cancer mortality data (1950-1979) and county-specific groundwater arsenic concentration data were obtained for 133 U.S. counties known to be exclusively dependent on groundwater for their public dunking water supply. No arsenic-related increase in bladder cancer mortality was found over the exposure range of 3 to 60 µg/L using stratified analysis and regression analyses (both unweighted and weighted by county population and using both mean and median arsenic concentrations). These results, which provide a direct estimate of arsenic-related cancer risk for U.S. residents, exclude the National Research Council's 2001 risk estimate that was based on Southwest Taiwan data and required adjusting for differences between the body mass and water consumption rates of U.S. and Taiwanese residents.
Cortical Tuber Count: A Biomarker Indicating Neurologic Severity of Tuberous Sclerosis Complex
The relationship between the number of cortical tubers observed by magnetic resonance imaging (MRI) and the severity of cerebral dysfunction of tuberous sclerosis patients has been examined in a meta-analysis of the published literature. The literature review has identified five independent studies for examining the association. These studies consistently reveal that the cortical tuber count detected on MRI scans is increased among those with more severe cerebral disease. Severity of the cerebral dysfunction is measured by the seizure status and its control and by the developmental status and the level of mental retardation. Meta-analysis demonstrates that within a study population, the MRI-detected cortical tuber count is six times more likely to be above the median count for tuberous sclerosis patients with severe cerebral dysfunction (poor seizure control or moderate-severe retardation or both) than more mildly affected tuberous sclerosis patients. Similarly, across studies, moderately to severely affected patients are five times more likely to have greater than seven MRI-detected cortical tubers than those more mildly affected. These associations are both statistically significant and strong. The cortical tuber count is a biomarker that reasonably predicts the severity of cerebral dysfunction of tuberous sclerosis. Cortical tubers of tuberous sclerosis form in the early gestational period. The embryologic disruption determining the clinical severity of the cortical dysfunction of tuberous sclerosis is set in the early gestational period. (J Child Neurol 1997;12:85-90).