A prospective adaptive utility trial to validate performance of a novel urine exosome gene expression assay to predict high-grade prostate cancer in patients with prostate-specific antigen 2-10ng/ml at initial biopsy

BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption. OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI performance assessment during phase I, a clinical implementation document (ie, CarePath) was developed for utilizing the EPI test in phase II, where the biopsy decision is uncertain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance evaluation of the EPI test in patients enrolled in phase I and publication of a consensus CarePath for phase II. RESULTS AND LIMITATIONS: In a total of 503 patients, with median age of 64 yr, median PSA 5.4ng/ml, 14% African American, 70% Caucasian, 53% positive biopsy rate (22% GG1, 17% GG2, and 15% ≥ GG3), EPI was superior to an optimized model of standard clinical parameters with an area under the curve (AUC) 0.70 versus 0.62, respectively, comparable with previously published results (n=519 patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary prostate biopsies and 20% of total biopsies, with negative predictive value (NPV) 89% and missing 7% of ≥GG2 PCa. Alternative cut-point 20 would avoid 40% of unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of ≥GG2 PCa. The clinical investigators reached consensus recommending use of the 15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II will be reported separately. CONCLUSIONS: EPI is a noninvasive, easy-to-use, gene expression urine assay, which has now been successfully validated in over 1000 patients across two prospective validation trials to stratify risk of ≥GG2 from GG1 cancer and benign disease. The test improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies. PATIENT SUMMARY: It is challenging to predict which men are likely to have high-grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2-10ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore) test can predict ≥GG2 PCa at initial biopsy and defer unnecessary biopsies better than existing risk calculator\u27s and standard clinical data

Relativistic Meson Spectroscopy and In-Medium Effects

We extend our earlier model of $q\bar q$ mesons using relativistic quasipotential (QP) wave equations to include open-flavor states and running quark-gluon coupling effects. Global fits to meson spectra are achieved with rms deviations from experiment of 43-50 MeV. We examine in-medium effects through their influence on the confining interaction and predict the confining strength at which the masses of certain mesons fall below the threshold of their dominant decay channel.Comment: 12 Pages, 2 Postscript figures (appended at the end with instructions, available also from [email protected]

Prevalência de brucelose bovina no Estado da Paraíba

A serosurvey was conducted to estimate the prevalence of bovine brucellosis in the State of Paraíba, Brazil. A random sample of six municipalities was selected from each of three ecoregions of the State: the Agreste/Litoral region (1), the Cariri/Curimatau region (2) and the Sertão region (3). These 18 municipalities were divided in quadrants and one herd was selected at random from each quadrant. The sampling scheme included herds with more than 50 bovines, which excludes small-holder subsistence livestock production. At least 32 animals were sampled within each herd, stratified in four age categories, as follows: (1) at least 8 animals under 6 months of age, (2) at least 8 animals of 7 to 18 months of age, (3) at least 8 animals of 19 to 30 months of age and (4) at least 8 animals over 30 months of age. Antibodies to Brucella abortus were observed in 8 out of 18 municipalities (44.44%),in 8 out of 72 herds included in this study (11.11%) and in 8 animals out of 2343 samples collected (0.34%). The prevalence of test positive cattle by ecoregion/cattle production regions in the state showed no significant differences of risk among them. Likewise, there was no significant difference of risk among the different age categories studied. It was observed that brucellosis is widely spread across the state albeit with low animal prevalence. These results may be used in the design of a strategy for controlling bovine brucellosis in the State of Paraíba.Foi realizado um estudo para a determinação da prevalência sorológica de brucelose bovina no Estado da Paraíba. Seis municípios foram selecionados aleatoriamente em cada uma das três ecorregiões do Estado: a região do Agreste/Litoral (1), a região do Cariri/Curimatau (2) e a região do Sertão (3). Estes 18 municípios foram divididos em quadrantes e uma propriedade foi selecionada em cada quadrante. Foram amostradas propriedades com mais de 50 animais, o que exclui as pequenas propriedades de subsistência. Pelo menos 32 animais foram amostrados de cada rebanho, estratificados nas quatro faixas etárias seguintes: (1) no mínimo 8 animais até 6 meses de idade, (2) no mínimo 8 animais com 7 a 18 meses de idade, (3) no mínimo 8 animais com 19 a 30 meses de idade e (4) no mínimo 8 animais com mais de 30 meses de idade. Anticorpos anti-B. abortus foram observados em 8 de 18 municípios (44,44%), em 8 de 72 rebanhos (11,11%) e em 8 animais dos 2343 amostrados (0,34%). A análise dos resultados de prevalência por ecorregião do Estado não revelou diferença significativa de risco entre elas. A análise dos resultados por categorias de faixa etária também não evidenciaram diferença significativa de risco entre as mesmas. Foi observado que a brucelose está amplamente disseminada no estado embora com uma baixa prevalência animal. Estes resultados podem ser úteis no delineamento de estratégias de controle da brucelose bovina no estado da Paraíba

Exploring the NRO Opportunity for a Hubble-sized Wide-field Near-IR Space Telescope -- NEW WFIRST

We discuss scientific, technical and programmatic issues related to the use of an NRO 2.4m telescope for the WFIRST initiative of the 2010 Decadal Survey. We show that this implementation of WFIRST, which we call "NEW WFIRST," would achieve the goals of the NWNH Decadal Survey for the WFIRST core programs of Dark Energy and Microlensing Planet Finding, with the crucial benefit of deeper and/or wider near-IR surveys for GO science and a potentially Hubble-like Guest Observer program. NEW WFIRST could also include a coronagraphic imager for direct detection of dust disks and planets around neighboring stars, a high-priority science and technology precursor for future ambitious programs to image Earth-like planets around neighboring stars.Comment: 76 pages, 26 figures -- associated with the Princeton "New Telescope Meeting

Advanced EFL learners' beliefs about language learning and teaching: a comparison between grammar, pronunciation, and vocabulary

This paper reports on the results of a study exploring learners’ beliefs on the learning and teaching of English grammar, pronunciation and vocabulary at tertiary level. While the importance of learners’ beliefs on the acquisition process is generally recognized, few studies have focussed on and compared learners’ views on different components of the language system. A questionnaire containing semantic scale and Likert scale items probing learners’ views on grammar, pronunciation and vocabulary was designed and completed by 117 native speakers of Dutch in Flanders, who were studying English at university. The analysis of the responses revealed that (i) vocabulary was considered to be different from grammar and pronunciation, both in the extent to which an incorrect use could lead to communication breakdown and with respect to the learners’ language learning strategies, (ii) learners believed in the feasibility of achieving a native-like proficiency in all three components, and (iii) in-class grammar, pronunciation and vocabulary exercises were considered to be useful, even at tertiary level. The results are discussed in light of pedagogical approaches to language teaching

Three steps towards metrological traceability for ballistics signature measurements.

Abstract The National Institute of Standards and Technology (NIST) in collaboration with the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF) has developed the Standard Reference Material (SRM) bullets and casings. NIST and ATF are proposing to establish a National Ballistics Measurement Traceability and Quality System for ballistics signature measurements and correlations using these materials. In this paper, three key steps towards metrological traceability for ballistics signature measurements are discussed that include: 1) Establishing a reference standard; 2) Establishing an unbroken chain of calibrations; and 3) Evaluating measurement uncertainty

Toward a second-person neuroscience

LS & BT : equal contributions (shared first-authorship)Peer reviewedPreprin

Prevalência de Brucelose bovina no Estado da Paraíba

Foi realizado um estudo para a determinação da prevalência sorológica de brucelose bovina no Estado da Paraíba. Seis municípios foram selecionados aleatoriamente em cada uma das três ecorregiões do Estado: a região do Agreste/Litoral (1), a região do Cariri/Curimatau (2) e a região do Sertão (3). Estes 18 municípios foram divididos em quadrantes e uma propriedade foi selecionada em cada quadrante. Foram amostradas propriedades com mais de 50 animais, o que exclui as pequenas propriedades de subsistência. Pelo menos 32 animais foram amostrados de cada rebanho, estratificados nas quatro faixas etárias seguintes: (1) no mínimo 8 animais até 6 meses de idade, (2) no mínimo 8 animais com 7 a 18 meses de idade, (3) no mínimo 8 animais com 19 a 30 meses de idade e (4) no mínimo 8 animais com mais de 30 meses de idade. Anticorpos anti-B. abortus foram observados em 8 de 18 municípios (44,44%), em 8 de 72 rebanhos (11,11%) e em 8 animais dos 2343 amostrados (0,34%). A análise dos resultados de prevalência por ecorregião do Estado não revelou diferença significativa de risco entre elas. A análise dos resultados por categorias de faixa etária também não evidenciaram diferença significativa de risco entre as mesmas. Foi observado que a brucelose está amplamente disseminada no estado embora com uma baixa prevalência animal. Estes resultados podem ser úteis no delineamento de estratégias de controle da brucelose bovina no estado da Paraíba.A serosurvey was conducted to estimate the prevalence of bovine brucellosis in the State of Paraíba, Brazil. A random sample of six municipalities was selected from each of three ecoregions of the State: the Agreste/Litoral region (1), the Cariri/Curimatau region (2) and the Sertão region (3). These 18 municipalities were divided in quadrants and one herd was selected at random from each quadrant. The sampling scheme included herds with more than 50 bovines, which excludes small-holder subsistence livestock production. At least 32 animals were sampled within each herd, stratified in four age categories, as follows: (1) at least 8 animals under 6 months of age, (2) at least 8 animals of 7 to 18 months of age, (3) at least 8 animals of 19 to 30 months of age and (4) at least 8 animals over 30 months of age. Antibodies to Brucella abortus were observed in 8 out of 18 municipalities (44.44%),in 8 out of 72 herds included in this study (11.11%) and in 8 animals out of 2343 samples collected (0.34%). The prevalence of test positive cattle by ecoregion/cattle production regions in the state showed no significant differences of risk among them. Likewise, there was no significant difference of risk among the different age categories studied. It was observed that brucellosis is widely spread across the state albeit with low animal prevalence. These results may be used in the design of a strategy for controlling bovine brucellosis in the State of Paraíba

Atmospheric Acetaldehyde: Importance of Air-Sea Exchange and a Missing Source in the Remote Troposphere.

We report airborne measurements of acetaldehyde (CH3CHO) during the first and second deployments of the National Aeronautics and Space Administration (NASA) Atmospheric Tomography Mission (ATom). The budget of CH3CHO is examined using the Community Atmospheric Model with chemistry (CAM-chem), with a newly-developed online air-sea exchange module. The upper limit of the global ocean net emission of CH3CHO is estimated to be 34 Tg a-1 (42 Tg a-1 if considering bubble-mediated transfer), and the ocean impacts on tropospheric CH3CHO are mostly confined to the marine boundary layer. Our analysis suggests that there is an unaccounted CH3CHO source in the remote troposphere and that organic aerosols can only provide a fraction of this missing source. We propose that peroxyacetic acid (PAA) is an ideal indicator of the rapid CH3CHO production in the remote troposphere. The higher-than-expected CH3CHO measurements represent a missing sink of hydroxyl radicals (and halogen radical) in current chemistry-climate models