Using response surface methods to explore and optimize mating disruption of the leafminer Phyllocnistis citrella (Lepidoptera: Gracillariidae).

The application of synthetic sex pheromones to disrupt mating of agricultural pests can be an effective and environmentally friendly alternative to pesticide applications. Optimizing mating disruption through examination of multiple interrelated variables may contribute to wider adoption in agriculture, especially in situations where pheromone synthesis is expensive. Simulations and field experiments designed to produce response surfaces by varying the distribution and number of pheromone dispensers suggested procedures whereby understanding optimization might be increased over that resulting from more common experiments focusing on one factor at a time. Monte Carlo simulations of a spatially explicit agent-based model resulted in nonlinear disruption profiles with increasing point source density. Field trials conducted in citrus infested by the leafminer Phyllocnistis citrella varied the amount of pheromone applied at each point source and point source density using attractive and non-attractive disruption blends. Trap catch disruption in the field resulted in nonlinear disruption profiles similar to those observed with simulations. Response surfaces showed an interaction between the amount of pheromone applied and the number of point sources for the attractive blend, but not for the non-attractive blend. Disruption surfaces were combined with cost curves to optimize trap catch disruption under real world cost constraints. The methods used here highlight the importance of experiment design for understanding the underlying biological dynamics governing mating disruption and optimizing its implementation

Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia

Specific genes, such as BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC) tissue compared to normal colon tissue specimens. Such DNA may leak into blood and be present as cell-free circulating DNA. We have evaluated the accuracy of a novel blood test for these two markers across the spectrum of benign and neoplastic conditions encountered in the colon and rectum. Circulating DNA was extracted from plasma obtained from volunteers scheduled for colonoscopy for any reason, or for colonic surgery, at Australian and Dutch hospitals. The extracted DNA was bisulphite converted and analysed by methylation specific real-time quantitative PCR (qPCR). A specimen was deemed positive if one or more qPCR replicates were positive for either methylated BCAT1 or IKZF1 DNA. Sensitivity and specificity for CRC were estimated as the primary outcome measures. Plasma samples were collected from 2105 enrolled volunteers (mean age 62 years, 54 % male), including 26 additional samples taken after surgical removal of cancers. The two-marker blood test was run successfully on 2127 samples. The test identified 85 of 129 CRC cases (sensitivity of 66 %, 95 % CI: 57-74). For CRC stages I-IV, respective positivity rates were 38 % (95 % CI: 21-58), 69 % (95 % CI: 53-82), 73 % (95 % CI: 56-85) and 94 % (95 % CI: 70-100). A positive trend was observed between positivity rate and degree of invasiveness. The colonic location of cancer did not influence assay positivity rates. Gender, age, smoking and family history were not significant predictors of marker positivity. Twelve methylation-positive cancer cases with paired pre- and post-surgery plasma showed reduction in methylation signal after surgery, with complete disappearance of signal in 10 subjects. Sensitivity for advanced adenoma (n = 338) was 6 % (95 % CI: 4-9). Specificity was 94 % (95 % CI: 92-95) in all 838 non-neoplastic pathology cases and 95 % (95 % CI: 92-97) in those with no colonic pathology detected (n = 450). The sensitivity for cancer of this two-marker blood test justifies prospective evaluation in a true screening population relative to a proven screening test. Given the high rate of marker disappearance after cancer resection, this blood test might also be useful to monitor tumour recurrence. ACTRN1261100031898

Additional file 4: of Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia

Age versus assay positivity. Figure S1. The proportion of positive blood results were calculated for <50, 50-54, 55-59, 60-64, 65-69, 70-74, 75-80 and >80 years of age. The binomial standard deviation was calculated using the formula S E p = p 1 ‐ p / n $$\mathrm{S}\mathrm{E}\mathrm{p}=\sqrt{\mathrm{p}\left(1\hbox{-} \mathrm{p}\right)/\mathrm{n}}$$ , where p = proportion of positive results, n = sample size ( https://www.easycalculation.com/statistics/standard-error-sample-proportion.php ). A two-sample Z-test two-tailed, 95 % significant level was performed on the terminal groups less than 50yrs of age versus more than 80yrs of age (the age span in study cohort) and 50-54yrs vs 75-80yrs (screen-eligible age) based on the assumption that if there was an age trend then that would be most pronounced in ‘young’ versus ‘old’. (A) non-neoplastic controls (n = 1288); (B) cancer (n = 129). (TIFF 2521 kb

Additional file 2: of Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia

Recruitment details for participating clinical sites. Table S3. Distribution of recruits from the four hospitals participating in the study. (PDF 97 kb

The Molecular Taxonomy of Primary Prostate Cancer

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defectsclose