309 research outputs found

    Development of a multivariable risk model integrating urinary cell DNA methylation and cell-free RNA data for the detection of significant prostate cancer

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    Background: Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naïve patients. Methods: Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207). A robust feature selection framework, based on bootstrap resampling and permutation, was utilized to find the optimal combination of clinical and urinary markers in a random forest model, deemed ExoMeth. Out-of-bag predictions from ExoMeth were used for diagnostic evaluation in men with a clinical suspicion of prostate cancer (PSA ≥ 4 ng/mL, adverse digital rectal examination, age, or lower urinary tract symptoms). Results: As ExoMeth risk score (range, 0-1) increased, the likelihood of high-grade disease being detected on biopsy was significantly greater (odds ratio = 2.04 per 0.1 ExoMeth increase, 95% confidence interval [CI]: 1.78-2.35). On an initial TRUS biopsy, ExoMeth accurately predicted the presence of Gleason score ≥3 + 4, area under the receiver-operator characteristic curve (AUC) = 0.89 (95% CI: 0.84-0.93) and was additionally capable of detecting any cancer on biopsy, AUC = 0.91 (95% CI: 0.87-0.95). Application of ExoMeth provided a net benefit over current standards of care and has the potential to reduce unnecessary biopsies by 66% when a risk threshold of 0.25 is accepted. Conclusion: Integration of urinary biomarkers across multiple assay methods has greater diagnostic ability than either method in isolation, providing superior predictive ability of biopsy outcomes. ExoMeth represents a more holistic view of urinary biomarkers and has the potential to result in substantial changes to how patients suspected of harboring prostate cancer are diagnosed

    Scaling of the F_2 structure function in nuclei and quark distributions at x>1

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    We present new data on electron scattering from a range of nuclei taken in Hall C at Jefferson Lab. For heavy nuclei, we observe a rapid falloff in the cross section for x>1x>1, which is sensitive to short range contributions to the nuclear wave-function, and in deep inelastic scattering corresponds to probing extremely high momentum quarks. This result agrees with higher energy muon scattering measurements, but is in sharp contrast to neutrino scattering measurements which suggested a dramatic enhancement in the distribution of the `super-fast' quarks probed at x>1. The falloff at x>1 is noticeably stronger in ^2H and ^3He, but nearly identical for all heavier nuclei.Comment: 5 pages, 4 figures, to be submitted to physical revie

    A controlled evaluation of an enhanced self-directed behavioural family intervention for parents of children with conduct problems in rural and remote areas.

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    Few studies have examined the impact of parenting interventions for families in rural and isolated areas who have children with conduct problems, where-access to professional services can be difficult. The present investigation compared the effects of three conditions, two levels of self-directed behavioral family intervention: an enhanced self-directed program that combined a self-help program using written materials and a weekly telephone consultation (ESD), a self-help program (SD) and a waitlist control group (WL). At postintervention the ESD group reported significantly lower levels of disruptive behaviour, and lower levels of dysfunctional parenting than the SD and WL controls, and higher levels of consumer satisfaction. At 6 months follow-up the main effects for the ESD group had been maintained. The SD group continued to evidence improvement from postintervention to follow-up such that 65% of children in the ESD condition and 57% of children in the SD condition showed clinical reliable change on measures of disruptive behaviour. Implications of findings and directions for future research are discussed
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