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Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 × 10−5; q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.

Background The objective of this randomized controlled trial was to determine whether a goal-setting program integrated into a surgical training curriculum would improve performance on simulation testing times and confidence with laparoscopic operative skills. Methods Beginning in 2013, 36 students and 26 general surgery residents were randomized separately into 3 groups. Trainees were either given no time goals for each of 5 Fundamentals of Laparoscopic Surgery (FLS) tasks or were given time goals that were the mean time scores or the best time scores reported in the literature for passing each FLS task. All trainees were evaluated for each task with time scores and a confidence survey both prior to and after the training program. Results For the students, all confidence scores and task times improved significantly from pre- to post-training. The average percent improvement in task times was greater for all 5 tasks in the 2 groups assigned to the goals compared to the no-goals group with the combined 5-task, mean percent improvement ( P = .02). Overall, the students assigned to the mean-goal group improved more than the best or no-goal groups ( P = .048). In the residents assigned to goals, all task times improved significantly pre/post, although the overall average percent improvement between groups was not different. Residents in both the no-goals and the goals groups improved their confidence with skills pre- to post-training. Conclusion The addition of achievable goals, defined as the average task time for residents who passed the FLS, was beneficial to students, because by achieving these goals, the students were able to achieve faster task times with improved confidence. Setting appropriate goals may improve laparoscopic operative skills in students. Suitable goals were also shown to strengthen accuracy and confidence in residents’ laparoscopic operative skills.

Objective Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case–control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function. Methods A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008–2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function. Results Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11–2.64), ejaculation (OR 2.27; 95% CI 1.32–3.91), and problem assessment (OR 2.36; 95% CI 1.43–3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls. Conclusion This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype.

Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects.We used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score.A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR = 1.42; 95 % CI, 0.51-3.95 and RR = 3.13; 95 % CI, 1.25-7.80 for low and high use compared with no use; p (trend) = 0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a nonsignificant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance.Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.

Developments in science and technology are potentially relevant to the scope of the Biological Weapons Convention (BWC), as well as to its operation and implementation. At the upcoming Seventh Review Conference in December this year, three basic trends are likely to play a part: the rapid pace of relevant advances in science and technology; the global diffusion of science and technology research and its applications; and the breadth of fields now engaged in the “life sciences.” Continued engagement of the scientific community, the authors write, will be important for monitoring ongoing developments in science and technology and for contributing to assessments on the implications of these developments for the BWC. Sustained engagement will enable the Convention to anticipate and respond more effectively to the challenges and opportunities offered by the continuing advances in science and technology.

Dickens World opened at Chatham Maritime Docks in May 2007 and it almost immediately met with widespread criticism. Although it carefully avoided billing itself as a theme park, that did not stop d...

Higher prostate-specific antigen (PSA) velocity (change in PSA over time) measured after diagnosis or treatment is associated with poorer prognosis for prostate cancer patients. However, less is known about the association between PSA velocity measured prior to a diagnosis of cancer and future prostate cancer mortality. We evaluated whether PSA velocity is associated with the risk of prostate cancer mortality among men without a history of prostate cancer in the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. As part of the PLCO trial, men in the screening arm were offered PSA screening at baseline in the trial and annually thereafter for five years. From the screening arm, we included 33,961 men who had at least two prediagnostic trial PSA measurements (to allow for PSA velocity calculation), among whom 167 later died of prostate cancer. We estimated PSA velocity and initial PSA concentration for each participant from the random slope and random intercept terms in a mixed effects model based on up to the first three trial PSA measures per person since participants varied in the number of available measures. We defined our study baseline for survival analysis as the time of the last PSA measurement used to calculate PSA velocity. Participants were 55 to 79 years of age at our study baseline, and we followed them for up to 18 years (through Dec. 31, 2012) for prostate cancer mortality, with a median follow-up time of 12.7 years (interquartile range: 10.7-14.4 years). We dichotomized PSA velocity as Citation Format: Erik Barr, Sonja I. Berndt, John D. Sorkin, Wen-Yi Huang, Kathryn Hughes Barry. Prostate-specific antigen velocity is associated with future prostate cancer mortality among men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2201.

PurposeThis study aims to investigate the attributes that create brand trust in internet retailing extending the work by Ha, and expanding the purchase categories.Design/methodology/approachUsing a two‐phase qualitative and quantitative methodology, 15 in‐depth interviews were conducted followed by written surveys from 199 respondents. Linear regressions were undertaken to test the hypotheses. Further to the empirical research, a new model is proposed.FindingsRegression analysis using Ha's six scales of security, privacy, brand name, word of mouth, information, and (past) experience yielded an R2 of only 0.105 for the dependent variable of web brand trust. Similar results were obtained when adding in extra scales (i.e. website design and navigation, returns policy and country of origin), and when completing regression analysis using only the attributes that had a statistically significant correlation with brand trust. The results for all three types of regressions increased to R2≤ 0.165 when the attributes length of time using the internet, length of time purchasing from the internet and frequency of internet purchase on the internet were included.Research limitations/implicationsA limitation of the study was that the sample included only part‐time graduate students from one Australian university. Therefore future research should include respondents from a wider range of ages, income and educational levels.Originality/valueThe study extends the work of Ha to additional cultural and internet retailing contexts. It also introduces a wider range of factors affecting brand trust.

Evidence suggests that global blood DNA methylation levels may be associated with the risk of various cancers, but no studies have evaluated this relationship for prostate cancer.We used pyrosequencing to quantify DNA methylation levels at the long interspersed nuclear element 1 (LINE-1) and Alu repetitive elements in pre-diagnostic blood samples from 694 prostate cancer cases and 703 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We evaluated prostate cancer risk associated with the mean methylation level for each element using logistic regression, adjusting for potential confounders.We did not observe a significant association with prostate cancer for LINE-1 [odds ratio (OR) for the highest compared to the lowest quartile = 1.01, 95% confidence interval (CI): 0.73-1.39, Ptrend = 0.99] or Alu (OR = 0.94, 95% CI: 0.68-1.29, Ptrend = 0.69) methylation levels overall. However, for Alu, we observed that higher DNA methylation levels were associated with a significant increased risk for those diagnosed 4 or more years after blood draw (OR = 2.26, 95% CI: 1.27-4.00, Ptrend = 4.4 × 10(-3) ). In contrast, there was no association for those diagnosed 2 (OR = 1.13, 95% CI: 0.67-1.90, Ptrend = 0.64) or 3 years after draw (OR = 1.22, 95% CI: 0.71-2.07, Ptrend = 0.32), and a decreased risk for those diagnosed less than 2 years after draw (OR = 0.40, 95% CI: 0.25-0.65, Ptrend = 3.8 × 10(-5) ; Pheterogeneity = 5.3 × 10(-6) ).Although LINE-1 DNA methylation levels were not associated with prostate cancer, we observed an association for Alu that varied by time from blood draw to diagnosis. Our study suggests that elevated Alu blood DNA methylation levels several years before diagnosis may be associated with an increased prostate cancer risk.

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.

Circumferentially stretched polyurethanes, Pellethane 2363-80A and 2363-55D, were studied following exposure to three steroids of differing polarity; cholesterol, cholesteryl acetate and cortisone. Equilibrium uptakes, diffusion kinetics and environmental stress cracking (ESC) were investigated. Cholesterol reached equilibrium uptake by 16 h, whereas cortisone and cholesteryl acetate did not attain equilibrium uptake until 96 h, suggesting different processes. All uptakes were less than 0.6%. The cortisone diffusion curves showed an inflection at 36 h suggesting some sort of structural change in 55D. The glass transition temperature, Tg, of the soft segment as a function of exposure time to cortisone and water shows a steady increase with cortisone content until after 36 h at which time the Tg falls almost to the value for water equilibrated samples. This shows that cortisone is able to affect the mobility of soft segments. The relationship between circumferential strain, steroid uptake and ESC was investigated. Samples were stretched at 50% increments from 0 to 250%; after 12days exposure steroid uptakes were determined and the samples examined with SEM. Cholesterol promoted ESC in 80A and 55D at strains of 200 and 150%, respectively. Pellethane 55D was resistant to ESC in the presence of cortisone at all strains, while 80A cracked only at strains above 200%. The equilibrium uptake of cholesterol acetate was most sensitive to strain, particularly for 55D. Cholesterol acetate was the most effective ESC agent, cracking both 80A and 55D after 12days exposure with an uptake under 0.25% and a strain of only 50%.

Background: Vitamin D and its metabolites are believed to impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation, and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D's anticarcinogenic properties. We hypothesize that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants. Methods: We evaluated interactions between 41 pesticides and 152 single-nucleotide polymorphisms (SNP) in nine vitamin D pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case–control study of Caucasian pesticide applicators within the Agricultural Health Study. We assessed Pinteraction values using likelihood ratio tests from unconditional logistic regression and a false discovery rate (FDR) to account for multiple comparisons. Results: Five significant interactions (P < 0.01) displayed a monotonic increase in prostate cancer risk with individual pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos use and three vitamin D genes (VDR, RXRB, and GC). The exposure–response pattern among participants with increasing parathion use with the homozygous CC genotype for GC rs7041 compared with unexposed participants was noteworthy [low vs. no exposure: OR, 2.58, 95% confidence interval (CI), 1.07–6.25; high vs. no exposure: OR, 3.09, 95% CI, 1.10–8.68; Pinteraction = 3.8 × 10−3]. Conclusions: In this study, genetic variations in vitamin D pathway genes, particularly GC rs7041, an SNP previously linked to lower circulating vitamin D levels, modified pesticide associations with prostate cancer risk. Impact: Because our study is the first to examine this relationship, additional studies are needed to rule out chance findings. Cancer Epidemiol Biomarkers Prev; 22(9); 1557–66. ©2013 AACR.

Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44–8.15) (P-interaction = 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction = 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17; P(trend) < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08, 1.88; P(trend) = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI: 1.02, 1.64; P(trend) = 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed = 1.49, 95% CI: 1.03, 2.18; P(trend) = 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer.

The etiology of prostate cancer remains largely unknown. Cases that occur late in life may have a different etiology than early-onset cases, and their inclusion in epidemiological studies may obscure associations with early-onset prostate cancer, which is often more aggressive and clinically relevant. We evaluated occupation in relation to the risk of prostate cancer separately for early-onset and later-onset disease in a large pooled study. We used census data to code occupations among census participants in five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from 1960-1990. We identified prostate cancer cases diagnosed from 1961-2005 by linkage to national cancer registries and calculated standardized incidence ratios (SIRs) by occupation separately for men aged 30-49 and those aged 50 or older. We also conducted separate analyses by period of cancer follow-up in two categories, 1961-1990 and 1991-2005, based on introduction of the prostate-specific antigen (PSA) screening test in the Nordic countries in 1990 or later. For early-onset prostate cancer, the highest SIRs were observed for public safety workers (e.g., firefighters) [SIR = 1.71, 95% confidence interval (CI): 1.23-2.31] and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than those observed for later-onset disease (pheterogeneity = 0.005 and 0.002), with public safety workers and military personnel demonstrating SIRs of 1.10 (95% CI: 1.07-1.14) and 1.09 (95% CI: 1.05-1.13), respectively. Administrators (SIR = 1.41, 95% CI: 1.13-1.73) and technical workers (SIR = 1.18, 95% CI: 1.01-1.37) also demonstrated significantly increased risk for early-onset prostate cancer, although the SIRs did not significantly differ from those for later-onset disease (for administrators, SIR = 1.17, 95% CI: 1.15-1.19; pheterogeneity = 0.08, and for technical workers, SIR = 1.11, 95% CI: 1.09-1.12; pheterogeneity = 0.40). With the exception of public safety workers, for whom the SIR for early-onset prostate cancer was higher in the later period (for 1961-1990, SIR = 1.45, 95% CI: 0.79-2.43, and for 1991-2005, SIR = 1.87, 95% CI: 1.25-2.71), the observed associations with early-onset disease tended to be restricted to the earlier, pre-PSA period. Our results suggest that occupational exposures among public safety workers and military personnel may contribute to the risk of prostate cancer, particularly for early-onset disease. Citation Format: Kathryn Hughes Barry, Jan Ivar Martinsen, Michael C.R. Alavanja, Gabriella Andreotti, Aaron Blair, Johnni Hansen, Kristina Kjaerheim, Stella Koutros, Elsebeth Lynge, Par Sparen, Laufey Tryggvadottir, Elisabete Weiderpass, Sonja I. Berndt, Eero Pukkala. Occupation and the risk of early- and later-onset prostate cancer in five Nordic countries. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3431.

Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway.Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons.Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was forALOXE3rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association.Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.

Metal-based formulations containing Cu(II) or Fe(III) ions plus a reducing agent, have been shown to be effective microbicidal agents and suggested for liquid disinfection or sterilization of reusable medical devices. In this study, we examined, by optical and scanning electron microscopy, the stability of five polymeric materials, commonly used in the manufacture of implantable, exploratory, and other medical devices, to oxidative challenge by metal-based formulations. No damage of any of the polymers could be attributed to repeated treatment with metal-based formulations under ‘in use’ conditions. However, a poly(vinyl acetate-vinyl chloride) copolymer (PVC) was found to be unstable to 10 wetting/drying cycles. The polymers were also challenged once for a longer time, at higher temperature, and with reagents at concentrations far exceeding those expected to be used in disinfecting medical devices. The only damage observed after this ‘accelerated’ testing consisted in minor pitting, or erosion, observed in polyamide and polyurethane samples exposed to formulations containing Fe(III) ions. Our results after ‘in-use’ and ‘accelerated’ testing indicate that silicone rubber, polyethylene, polyamide, and polyurethane polymers should be stable to treatment with Cu(II) plus hydrogen peroxide or ascorbic acid under conditions likely to be encountered in the decontamination of medical devices. The stability of these polymeric materials suggests the feasibility of using metal-based formulations for repeated disinfection of a broad range of medical devices without deleterious effects on the polymeric components.

Previous research demonstrates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, human biomonitoring studies indicate increased genetic damage (e.g. chromosomal aberrations) with pesticide exposure. Given that the nucleotide excision repair (NER) pathway repairs a broad range of DNA damage, we evaluated interactions between pesticide exposure and 324 single-nucleotide polymorphisms (SNPs) tagging 27 NER genes among 776 prostate cancer cases and 1444 male controls in a nested case-control study of white Agricultural Health Study pesticide applicators. We determined interaction P values using likelihood ratio tests from logistic regression models and three-level pesticide variables (none/low/high) based on lifetime days of use weighted to an intensity score. We adjusted for multiple comparisons using the false discovery rate (FDR) method. Of the 17 interactions that met FDR

To explore associations with prostate cancer and farming, it is important to investigate the relationship between pesticide use and single nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes.[corrected] We evaluated pesticide-SNP interactions between 45 pesticides and 1913 XME SNPs with respect to prostrate cancer among 776 cases and 1444 controls in the Agricultural Health Study.We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test.A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate cysteine ligase (GCLC; P interaction=1.0×10(-4)); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI: 1.9-7.3). Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hydrolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, an increased prostate cancer risk was observed with high, compared with no, petroleum oil/petroleum distillate (OR=1.9, 95% CI: 1.1-3.2, P interaction=0.01; OR=2.1, 95% CI: 1.1-4.0, P interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5-6.0, P interaction=2.0×10(-3)) use, respectively. No interactions were deemed noteworthy at the false discovery rate=0.20 level; the number of observed interactions in XMEs was comparable with the number expected by chance alone.We observed several pesticide-SNP interactions in oxidative stress and phase I/II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk.

Evidence from previous studies has suggested there may be physical and mental changes in health among testicular cancer survivors. No studies have been conducted in the United States, however.Study participants were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT (testicular germ cell tumor) cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Mean time since diagnosis for cases was 14 years, and no less than five for all cases. Component scores determined from responses to questions about physical and mental health on SF36 were tabulated to yield two summary measures, physical component scores (PCS), and mental component scores (MCS). Component and summary scores were normalized to a score of 50 with a standard deviation of 10 by a linear T-score transformation.Overall, cases may not suffer greatly in different quality of life than controls. When all cases and controls are compared, TGCT cases had lower PCS (mean: 51.9 95% CI: 50.6-53.2, P value: 0.037) than controls (mean: 53.6 95% CI: 52.7-54.6). MCS were not significantly different (P value: 0.091). In multivariate analyses, several physical health components were worse for TGCT cases such as role-physical (OR 1.19, 95% CI: 1.01-1.39) and general health (OR 1.26, 95% CI: 1.07-1.49) compared to controls. However, TGCT cases treated with chemotherapy had lower PCS (cases: 50.2, 95% CI: 47.6-52.8; controls: 53.6, 95% CI: 52.7-54.6, P value: 0.0032) and MCS (cases: 49.3, 95% CI: 46.5-52.1; controls: 52.0, 95% CI: 50.9-53.2, P value: 0.039). TGCT cases who received treatments other than chemotherapy did not differ from controls in either PCS or MCS.Physical and general health limitations may affect testicular cancer survivors. Men treated with chemotherapy, however, may be most likely to suffer adverse health outcomes due to a combination of body-wide effects on physical and mental factors which affect various aspects of physical health, mental health, and overall quality of life. And in particular, physical functioning, role-physical, and general health are strongly affected.

Using 1996-2000 data among Connecticut women, the authors evaluated whether genetic variation in 4 metabolic genes modifies organic solvent associations with non-Hodgkin lymphoma and 5 major histologic subtypes. P(interaction) values were determined from cross-product terms between dichotomous (ever/never) solvent variables and genotypes at examined loci in unconditional logistic regression models. The false discovery rate method was used to account for multiple comparisons. Overall associations between the chlorinated solvents dichloromethane (odds ratio (OR) = 1.69, 95% confidence interval (CI): 1.06, 2.69), carbon tetrachloride (OR = 2.33, 95% CI: 1.23, 4.40), and methyl chloride (OR = 1.44, 95% CI: 0.94, 2.20) and total non-Hodgkin lymphoma were increased among women TT for rs2070673 in the cytochrome P4502E1 gene, CYP2E1 (dichloromethane: OR = 4.42, 95% CI: 2.03, 9.62; P(interaction)0.01; carbon tetrachloride: OR = 5.08, 95% CI: 1.82, 14.15; P(interaction) = 0.04; and methyl chloride: OR = 2.37, 95% CI: 1.24, 4.51; P(interaction) = 0.03). In contrast, no effects of these solvents were observed among TA/AA women. Similar patterns were observed for diffuse large B-cell lymphoma and follicular lymphoma, as well as marginal zone lymphoma for dichloromethane. The weak, nonsignificant overall association between benzene and diffuse large B-cell lymphoma (OR = 1.29, 95% CI: 0.84, 1.98) was increased among women AA for rs2234922 in the microsomal epoxide hydrolase gene, EPHX1 (OR = 1.77, 95% CI: 1.06, 2.97; P(interaction) = 0.06). In contrast, no effect was observed among AG/GG women. Additional studies with larger sample size are needed to replicate these findings.

The category of atypical glandular cells (AGC) in gynecologic cytopathology presents many well-documented diagnostic challenges, the most significant related to high interobserver variability, low specificity, and low positive predictive value. The current Bethesda System provides criteria for specific glandular categories including atypical endocervical cells not otherwise specified (AEC-NOS), AEC favor neoplastic, and atypical endometrial cells. The Bethesda System does, however, acknowledge that in some cases AGC cannot be categorized based upon cell of origin, in which case the generic term "atypical glandular cells" (AGC) may be used. We sought to determine whether further refinement of the current Bethesda System criteria for AEC-NOS might increase the positive predictive value of the general category of AGC. Fifty-three cases of AGC with documented histologic follow-up at the University of Illinois Hospital were reviewed. The cases were graded on each of the eight specific cytologic criteria recommended by the current Bethesda System for AEC-NOS using a study-developed three-tier grading system. Multiple regression analysis showed that four of the cytologic criteria in combination--nuclear enlargement, nuclear pleomorphism, increased nuclear-to-cytoplasmic (N/C) ratio, and cells occurring in sheets and strips with cell crowding and nuclear overlap--discriminated positive histologic outcome slightly better than any single criterion alone. In addition, simple logistic regression analysis showed nuclear enlargement to have a marginal independent association with positive histologic outcome (P = 0.0566). No other criterion was independently associated with outcome. Ancillary methods seem indicated to increase the positive predictive value of AGC at this time.

We examined the occurrence of negative transfer in the learning of a novel motor task with regard to the schema theory (Schmidt, 1975) premise that practicing similar movements should have a facilitatory effect on learning. Given that negative transfer is often difficult to produce, an attempt was made to use a design similar to that of Lewis, McAllister, and Adarns (1951), in which the interpolated task was a complete reversal of the original task. Forty-eight university students were tested on a discrete pursuit-tracking task. They completed trials on both the original task and an interpolated reversed task before relearning the original task. The decrement between the first re- learning trial and the last original learning trial was analyzed for a negative transfer effect. Schmidt's (1982) hypothesis that negative transfer is due to temporary cognitive or decision confusion, not the result of a motor control problem, was supported. All evident performance decrements were observed only in the first rele...

Testicular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49 years, when reproduction is typical. Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility.To examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted. The men were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT cases and 236 controls participated in the current study and completed a self-administered questionnaire in 2008-2009.TGCT cases were significantly more likely than controls to experience fertility distress (OR 5.23; 95% CI 1.99-13.76) and difficulty in fathering children (OR 6.41; 2.72-15.13). Cases were also more likely to be tested for infertility (OR 3.65; 95% CI 1.55-8.59). Cases, however, did not differ from controls in actually fathering children (OR 1.37; 95% CI 0.88-2.15). These findings were predominantly observed among nonseminoma cases and cases treated with surgery only or surgery-plus-chemotherapy.While expressing greater fertility distress, higher likelihood of fertility testing, and difficulty fathering children, these data suggest that TGCT survivors are no less likely to father children than are other men. It is possible that treatment for TGCT does not permanently affect fertility or, alternatively, that TGCT survivors attempt to father children with greater persistence or at younger ages than do other men.