No abstract

Purpose Liquid biopsies that noninvasively detect molecular correlates of aggressive prostate cancer (PCa) could be used to triage patients, reducing the burdens of unnecessary invasive prostate biopsy and enabling early detection of high-risk disease. DNA hypermethylation is among the earliest and most frequent aberrations in PCa. We investigated the accuracy of a six-gene DNA methylation panel (Epigenetic Cancer of the Prostate Test in Urine [epiCaPture]) at detecting PCa, high-grade (Gleason score greater than or equal to 8) and high-risk (D’Amico and Cancer of the Prostate Risk Assessment] PCa from urine. Patients and Methods Prognostic utility of epiCaPture genes was first validated in two independent prostate tissue cohorts. epiCaPture was assessed in a multicenter prospective study of 463 men undergoing prostate biopsy. epiCaPture was performed by quantitative methylation-specific polymerase chain reaction in DNA isolated from prebiopsy urine sediments and evaluated by receiver operating characteristic and decision curves (clinical benefit). The epiCaPture score was developed and validated on a two thirds training set to one third test set. Results Higher methylation of epiCaPture genes was significantly associated with increasing aggressiveness in PCa tissues. In urine, area under the receiver operating characteristic curve was 0.64, 0.86, and 0.83 for detecting PCa, high-grade PCa, and high-risk PCa, respectively. Decision curves revealed a net benefit across relevant threshold probabilities. Independent analysis of two epiCaPture genes in the same clinical cohort provided analytical validation. Parallel epiCaPture analysis in urine and matched biopsy cores showed added value of a liquid biopsy. Conclusion epiCaPture is a urine DNA methylation test for high-risk PCa. Its tumor specificity out-performs that of prostate-specific antigen (greater than 3 ng/mL). Used as an adjunct to prostate-specific antigen, epiCaPture could aid patient stratification to determine need for biopsy.

No abstract

Polymodal fault systems are sets of faults in three or more orientations that formed in relation to a common state of strain. The importance of polymodal fault systems was first demonstrated by Oertel (1965) in a series of remarkable experiments on clay deformed in a three-dimensional strain state, including measurements of both displacements and stress. He outlined a theoretical framework for the development of four sets of faults, which were related to the principal strain rate axes by symmetry arguments and tensor geometry. Oertel''s work was followed up a decade later by Reches (1978Reches ( , 1983, Aydin and Reches (1982) and Reches and Dieterich (1983), who produced field and experimental evidence for polymodal fault sets, and analysed the strain associated with their formation. Krantz (1988) documented polymodal faults and showed how strain states could be inferred from field measurements by the "Odd Axis" method. Subsequently, Healy et al. (2006a, b) drew attention to the existence of non-Andersonian, polymodal fault sets, and proposed a model for their formation based in crack tip interactions. Fig. 1 displays the differences between conjugate faults predicted by Andersonian fault theory, and a polymodal fault geometry.Scaling, kinematics and evolution of a polymodal fault system: Hail Creek Mine, NE Australia AbstractWe analyse a system of normal faults that cut cuts sandstone , siltstone , mudstone, coal, and tuff at Hail Creek Coal Mine in the Bowen Basin, NE Australia. Our detailed mapping utilized utilised the dense borehole network and strip mining operations. The fault surfaces have complex geometries, yet the components of the individual faults show similar orientation variability to the whole fault system. The faults and their components dip to the SE, NW, NNW, and SSE with an orthorhombic symmetry that we refer to as polymodal. There are multiple displacement peaks, with complementary changes on adjacent faults. This observation suggests kinematic coherence between neighbouring faults.Twin displacement peaks on some faults suggest that segment linkage occurred on a scale of hundreds of m. These polymodal faults follow the same displacement --length scaling laws as other normal faults. Fault dip is affected by lithology, with steeper dips in more competent (sandstone) beds. An 'odd axis' construction using whole fault planes suggests that they formed in a triaxial strain state (three different principal strains) with vertical shortening, and horizontal extension along principal directions of 148° and 058°. Odd axis constructions using individual fault components, as opposed to whole faults, give similar principal strain orientations and maximum strain ratios. The variable component orientations, and the consistency of fault kinematics on different scales, suggest that the faults evolved by the propagation or linkage of smaller components with variable orientations, within the same bulk strain state.Keywords: Normal fault; Orthorhombic fault; Polymodal fault; Displacement--length scaling; Coal...

The Ertsberg district hosts multiple skarn and porphyry-related deposits, which together comprise one of the largest Cu-Au resources in the world. Earlier skarn Cu-Au deposits at Big Gossan and 2 km along strike to the northwest at Wanagon Gold are overprinted by distinctive late-stage pyrite, sphalerite, arsenopyrite, and native gold with local Bi and Te minerals. The Wanagon Gold deposit contains an estimated 2 million ounces (Moz) of gold; reserves at Big Gossan are 33 million tonnes (Mt) at 2.63 percent Cu, 0.92 g/t Au, and 15.72 g/t Ag. Phlogopite from the Big Gossan occurrence is younger than 2.82 ± 0.04 Ma, based on a new 40 Ar/ 39 Ar age from the Big Gossan skarn, and K-feldspar from the Wanagon Gold deposit has a 40 Ar/ 39 Ar age of 3.62 ± 0.05 Ma. A K-Ar date (3.81 ± 0.06 Ma) from the Wanagon sill constrains formation of the overprinting skarn Cu-Au and late-stage Wanagon Gold deposit to a period of ca. 0.2 m.y. At Big Gossan, earlier skarn Cu-Au mineralization displays three-dimensional mineralogical, chemical, and temperature zonation. The high-temperature core (defined by low Zn/Cu) plunges to the northwest and is open at depth. Highest Cu grades and greatest development of the overprinting pyrite-Au-As-Zn-BiTe association occur to the northwest coincident with northeast-striking faults. Pyrite-Au-As-Zn-BiTe occurrences are also distributed in faults and fractures to the north and south of the Big Gossan skarn Cu-Au deposit. At Wanagon Gold, leaching of skarn and sandstone preceded introduction of the pyrite-Au-As-Zn-BiTe occurrences. In the sandstone, the pyrite-Au-As-Zn-BiTe mineralization was accompanied by K-feldspar (adularia) and minor quartz gangue. In carbonate rocks, no leaching or secondary K-feldspar is apparent; instead, sulfides are accompanied by quartz and dolomite gangue. The δ 34 S of sulfide from skarn Cu-Au and overprinting pyrite-Au-As-Zn-BiTe occurrences at both deposits range from-0.7 to +5.1 per mil. Laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) analyses show that later pyrite overprinting both occurrences is distinct from that in the earlier skarn Cu-Au deposits and contains up to 60 ppm Au, 2 percent As, 680 ppm Bi, and 40 ppm Te. The mineralogy of the overprinting occurrences includes native gold, argentian tetrahedrite and tennantite, a silver-antimony sulfide, and Bi and Te-(Ag-Au) minerals including cosalite, bismuthinite, petzite, hessite, altaite, and tetradymite. The fineness of native gold varies with sulfide association. The lowest fineness gold (737-863) occurs with Pb minerals (galena and sulfosalts), and the higher fineness gold (904-974) occurs trapped within pyrite or in association with bismuthinite. Fluid inclusions in sphalerite and quartz in the Big Gossan pyrite-Au-As-Zn-BiTe occurrence have an average salinity of 8 wt percent NaCl equiv and an average homogenization temperature of 245°C. Stable isotopes indicate that the inclusion fluids were magmatic. However, a direct genetic relationship to earlier skarn Cu-Au mineralization is ...