INCORPORATING LOW-DOSE EPIDEMIOLOGY DATA IN A CHLORPYRIFOS RISK ASSESSMENT

USEPA assessed whether epidemiology data suggest that fetal or early-life chlorpyrifos exposure causes neurodevelopmental effects and, if so, whether they occur at exposures below those causing the current most sensitive endpoint, 10% inhibition of blood acetylcholinesterase (AChE). We previously conducted a hypothesis-based weight-of-evidence analysis and found that a proposed causal association between chlorpyrifos exposure and neurodevelopmental effects in the absence of AChE inhibition does not have a substantial basis in existing animal or in vitro studies, and there is no plausible basis for invoking such effects in humans at their far lower exposure levels. The epidemiology studies fail to show consistent patterns; the few associations are likely attributable to alternative explanations. Human data are inappropriate for a dose-response assessment because biomarkers were only measured at one time point, may reflect exposure to other pesticides, and many values are at or below limits of quantification. When considered with pharmacokinetic data, however, these biomarkers provide information on exposure levels relative to those in experimental studies and indicate a margin of exposure of at least 1,000. Because animal data take into account the most sensitive lifestages, the use of AChE inhibition as a regulatory endpoint is protective of adverse effects in sensitive populations

Drinking Behaviors Versus Perceived Norms of Kentucky College Students

Accidents and unintentional injury are the number one cause of death in college-aged adults. More than 1,500 college-aged students die from alcohol-related unintentional injuries per year, including motor-vehicle crashes. Other alcohol-related problems for college students include physical assault, sexual assault, and poor academic performance. In the state of Kentucky 17% of adults report binge drinking habits, and 1 in 4 deaths are due to vehicular accidents involving alcohol consumption. This is in line with the stats for the rest of the country. The purpose of the study is to assess the drinking habits versus perceived drinking norms of students attending a regional Kentucky university. Data will be gathered using a self-reported survey known as the Drinking Behaviors vs. Perceived Norms of Kentucky College Students Survey, consisting of 8 questions asking about their drinking habits versus what they perceive the drinking habits of their peers to be, and 6 demographic questions. The data will be analyzed using frequencies, percentages, and means for demographic results and chi-square analysis comparing self-reported drinking habits and perceived drinking norms. Results will be forthcoming. Keywords: alcohol, norms, drinking behaviors, college student

Improving Patient Decision-Making in Health Care

Outlines regional variations within Minnesota in rates of patients with similar conditions receiving elective surgery, the concept of shared decision making, treatment choices for eight conditions, and steps for ensuring patients make informed decisions

The Global Burden of Ozone on Respiratory Mortality: No Clear Evidence for Association

The correspondence section is a public forum and, as such, is not peer-reviewed. EHP is not responsible for the accuracy, currency, or reliability of personal opinion expressed herein; it is the sole responsibility of the authors. EHP neither endorses nor disputes their published commentary

Polymorphism Interaction Analysis (PIA): a method for investigating complex gene-gene interactions

<p>Abstract</p> <p>Background</p> <p>The risk of common diseases is likely determined by the complex interplay between environmental and genetic factors, including single nucleotide polymorphisms (SNPs). Traditional methods of data analysis are poorly suited for detecting complex interactions due to sparseness of data in high dimensions, which often occurs when data are available for a large number of SNPs for a relatively small number of samples. Validation of associations observed using multiple methods should be implemented to minimize likelihood of false-positive associations. Moreover, high-throughput genotyping methods allow investigators to genotype thousands of SNPs at one time. Investigating associations for each individual SNP or interactions between SNPs using traditional approaches is inefficient and prone to false positives.</p> <p>Results</p> <p>We developed the Polymorphism Interaction Analysis tool (PIA version 2.0) to include different approaches for ranking and scoring SNP combinations, to account for imbalances between case and control ratios, stratify on particular factors, and examine associations of user-defined pathways (based on SNP or gene) with case status. PIA v. 2.0 detected 2-SNP interactions as the highest ranking model 77% of the time, using simulated data sets of genetic models of interaction (minor allele frequency = 0.2; heritability = 0.01; N = 1600) generated previously [Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH: A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol 2007, 31:306–315.]. Interacting SNPs were detected in both balanced (20 SNPs) and imbalanced data (case:control 1:2 and 1:4, 10 SNPs) in the context of non-interacting SNPs.</p> <p>Conclusion</p> <p>PIA v. 2.0 is a useful tool for exploring gene*gene or gene*environment interactions and identifying a small number of putative associations which may be investigated further using other statistical methods and in replication study populations.</p

Wild Buckwheat Is Unlikely to Pose a Risk to Buckwheat-Allergic Individuals

Buckwheat (Fagopyrum esculentum) is a commonly allergenic food especially in Asia where buckwheat is more commonly consumed. Wild buckwheat (Polygonum convolvulus, recently changed to Fallopia convolvulus) is an annual weed prevalent in grain-growing areas of the United States. Wild buckwheat is not closely related to edible buckwheat although the seeds do have some physical resemblance. A large shipment of wheat into Japan was halted by the discovery of the adventitious presence of wild buckwheat seeds over possible concerns for buckwheat-allergic consumers. However, IgE-binding was not observed to an extract of wild buckwheat using sera from 3 buckwheat-allergic individuals either by radio-allergosorbent test inhibition or by immunoblotting after protein separation by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Furthermore, the extract of wild buckwheat was not detected in a buckwheat enzyme-linked immunosorbent assay developed with antisera against common buckwheat. Thus, wild buckwheat is highly unlikely to pose any risk to buckwheat-allergic individuals. The common names of plants should not be a factor in the risk assessment for possible cross-allergenicity

Association of MTHFR gene polymorphisms with breast cancer survival

BACKGROUND: Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. METHODS: African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival. RESULTS: We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C) had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR) = 2.05; 95% confidence interval (CI), 1.05–4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31–1.35). The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17–6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12–1.04 for C/T or T/T versus C/C at codon 677). Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, p(interaction )= 0.088; C677T, p(interaction )= 0.026). CONCLUSION: We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

BACKGROUND Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.Financial support for IMPACT-Tz came primarily from CDC, the U.S. Agency for International Development and the Wellcome Trust

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM. Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM. We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58–3.77) and MMA% (aOR = 1.95 (95% CI 0.81–4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25–1.52), though the confidence intervals included the null value. While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM