Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007).

Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association

Respiratory Cancer and Inhaled Inorganic Arsenic in Copper Smelters Workers: A Linear Relationship with Cumulative Exposure that Increases with Concentration

BACKGROUND: Inhalation of high levels of airborne inorganic arsenic is a recognized cause of respiratory cancer. Although multiple epidemiologic studies have demonstrated this association, there have been few analyses of the mathematical relationship between cumulative arsenic exposure and risk of respiratory cancer, and no assessment as to whether and how arsenic concentration may modify this association. OBJECTIVES: The objective is an evaluation of the shape of the relationship between respiratory cancer mortality and cumulative inhaled arsenic exposure among copper smelter workers, and the modification of that relationship by arsenic concentration. METHODS: We used Poisson regression methods to analyze data from a cohort of arsenic-exposed copper smelter workers under a linear-exponential model for the excess relative risk. RESULTS: Within categories of arsenic concentration, the association between respiratory cancer and cumulative arsenic exposure was consistent with linearity. The slope of the linear relationship with cumulative exposure increased with increasing arsenic concentration category. CONCLUSIONS: Our results suggested a direct concentration effect from inhaled inorganic arsenic, whereby the excess relative risk for a fixed cumulative exposure was greater when delivered at a higher concentration and shorter duration than when delivered at a lower concentration and longer duration. KEY WORDS: arsenic, dose–response relationship, lung neoplasms, occupational diseases. Environ Health Perspect 116:1661–1665 (2008). doi:10.1289/ehp.11515 available vi

Safeguarding human–wildlife cooperation

Human–wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human–honeyguide and human–dolphin cooperation, but these are at risk of joining several inactive forms (including human–wolf and human–orca cooperation). Human–wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components—a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge—which face threats from ecological and cultural changes. To safeguard human–wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures

A Systematic Review of the Prevalence of Schizophrenia

BACKGROUND: Understanding the prevalence of schizophrenia has important implications for both health service planning and risk factor epidemiology. The aims of this review are to systematically identify and collate studies describing the prevalence of schizophrenia, to summarize the findings of these studies, and to explore selected factors that may influence prevalence estimates. METHODS AND FINDINGS: Studies with original data related to the prevalence of schizophrenia (published 1965–2002) were identified via searching electronic databases, reviewing citations, and writing to authors. These studies were divided into “core” studies, “migrant” studies, and studies based on “other special groups.” Between- and within-study filters were applied in order to identify discrete prevalence estimates. Cumulative plots of prevalence estimates were made and the distributions described when the underlying estimates were sorted according to prevalence type (point, period, lifetime, and lifetime morbid risk). Based on combined prevalence estimates, the influence of selected key variables was examined (sex, urbanicity, migrant status, country economic index, and study quality). A total of 1,721 prevalence estimates from 188 studies were identified. These estimates were drawn from 46 countries, and were based on an estimated 154,140 potentially overlapping prevalent cases. We identified 132 core studies, 15 migrant studies, and 41 studies based on other special groups. The median values per 1,000 persons (10%–90% quantiles) for the distributions for point, period, lifetime, and lifetime morbid risk were 4.6 (1.9–10.0), 3.3 (1.3–8.2), 4.0 (1.6–12.1), and 7.2 (3.1–27.1), respectively. Based on combined prevalence estimates, we found no significant difference (a) between males and females, or (b) between urban, rural, and mixed sites. The prevalence of schizophrenia in migrants was higher compared to native-born individuals: the migrant-to-native-born ratio median (10%–90% quantile) was 1.8 (0.9–6.4). When sites were grouped by economic status, prevalence estimates from “least developed” countries were significantly lower than those from both “emerging” and “developed” sites (p = 0.04). Studies that scored higher on a quality score had significantly higher prevalence estimates (p = 0.02). CONCLUSIONS: There is a wealth of data about the prevalence of schizophrenia. These gradients, and the variability found in prevalence estimate distributions, can provide direction for future hypothesis-driven research

All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1−FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci