Cosmic dust grains strike again

A detailed simulation of air showers produced by dust grains has been performed by means of the {\sc aires} Monte Carlo code with the aim of comparing with experimental data. Our analysis indicates that extensive dust grain air showers must yet be regarded as highly speculative but they cannot be completely ruled out.Comment: Improved revised version with comments by an anonymous referee. Accepted for publication in Physical review

Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance

AbstractPurpose:Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers.Materials and Methods:Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort.Results:PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001).Conclusions:Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.Active surveillance (AS) is recommended for men with low- and favorable intermediate–risk prostate cancer.1 Compared to AS for low-risk men, AS for intermediate-risk men would likely benefit from more intensive surveillance to stave off disease progression. Despite increased use of advanced imaging tools, risk calculators, and molecular biomarkers, a third or more of men initially classified as low risk actually have intermediate or higher risk, heralded by subsequent detection of occult Gleason pattern 4.2,3 Strategies to identify such men have limited accuracy. They include attention to traditional risk factors such as age, tumor size and extent, and PSA level, measured by tests such as digital rectal examination, multiparametric (mp) MRI, and biopsy and blood analyses. Despite its increasing use in prostate cancer risk assessment, expert prostate mpMRI is a limited resource with low (circa 59%) sensitivity for intermediate-risk cases.4 A biomarker that more accurately distinguishes between grade group (GG) 1 and GG ≥2 could be helpful in deintensifying AS for men with truly low-risk cancers.Several commercially available and guideline-approved tests use gene (mRNA or protein) expression levels in prostate cancer biopsies to detect adverse pathology (AP; ie, GG ≥3 or nonorgan-confined disease) in the subsequent prostatectomy. However, no existing molecular test has been adopted in current guidelines as standard of care to distinguish between GG1 and GG ≥2 cancers.1,5,6 Despite indications that such tests could be useful,6,7 uptake has been limited, perhaps because of low accuracy, which in turn may derive from limitations in the number and types of molecular features included in each test. Since cardinal molecular features of early prostate carcinogenesis include not only altered gene expression but also DNA methylation events and copy number alterations (CNAs),8-10 we hypothesized that tests combining these features could provide superior performance in separating low-grade (GG1) cancers from their higher-grade (GG ≥2) counterparts.The personalized risk stratification for patients with early prostate cancer (PRONTO) program is a pan-Canadian effort that aims to develop a GG classifier to stratify risk in prostate cancer and achieve technical and clinical validation in statistically powered cohorts. Here, we report the development of 2 candidate classifiers comprising different types of molecular features. These classifiers, developed and independently validated, achieve superior performance by integrating tumor mRNA abundance, DNA copy number, and/or DNA methylation profiles. We demonstrate that these classifiers could add value above and beyond routinely captured clinical data and are remarkably resistant to sampling error. We discuss how adoption of classifiers with these attributes has the potential to improve current AS approaches without increasing patient morbidity. By identifying men at increased risk of occult GG ≥2 cancer, surveillance biopsies could be taken earlier to confirm the presence and extent of Gleason pattern 4 cancer. By confirming GG1 cancers, such biomarkers could identify men for whom it would be safe to forgo MRI or increase the intervals between surveillance biopsies, reducing burdens on health care systems and patients

Machina ex Deus? From Distributed to Orchestrated Agency

In this chapter, the author draws on a historical case study of the Australian wine industry to explore variations in collective agency. The inductively derived process model illustrates the emergence of a new profession of scientific win- emaking, which unfolds in three phases. Each phase is characterized by a dis- tinct form of agency: distributed agency during the earliest phase, coordinated agency during later phases, and orchestrated agency during consolidation. In addition to exploring the temporal shifts in agency, the study includes a detailed analysis of the early stages of distributed agency, examining how col- lective agency is achieved in the absence of shared intentions

Getting a grip on sensorimotor effects in lexical-semantic processing

One of the strategies that researchers have used to investigate the role of sensorimotor information in lexical-semantic processing is to examine effects of words’ rated body-object interaction (BOI; the ease with which the human body can interact with a word’s referent). Processing tends to be facilitated for words with high BOI compared to words with low BOI, across a wide variety of tasks. Such effects have been referenced in debates over the nature of semantic representations, but their theoretical import has been limited by the fact that BOI is a fairly coarse measure of sensorimotor experience with words’ referents. In the present study we collected ratings for 621 words on seven semantic dimensions (graspability, ease of pantomime, number of actions, animacy, size, danger, and usefulness) in order to investigate which attributes are most strongly related to BOI ratings, and to lexical-semantic processing. BOI ratings were obtained from previous norming studies (Bennett, Burnett, Siakaluk, & Pexman, 2011; Tillotson, Siakaluk, & Pexman, 2008) and measures of lexical-semantic processing were obtained from previous behavioural megastudies involving the semantic categorization task (concrete/abstract decision; Pexman, Heard, Lloyd, & Yap, 2017) and the lexical decision task (Balota et al., 2007). Results showed that the motor dimension of graspability, ease of pantomime, and number of actions were all related to BOI and that these dimensions together explained more variance in semantic processing than did BOI ratings alone. These ratings will be useful for researchers who wish to study how different kinds of bodily interactions influence lexical-semantic processing and cognition

Investigation into the formation of the scrape-off layer density shoulder in JET ITER-like wall L-mode and H-mode plasmas

The low temperature boundary layer plasma (Scrape-Off-Layer or SOL) between the hot core and the surrounding vessel determines the level of power-loading, erosion and implantation of material surfaces, and thus the viability of tokamak-based fusion as an energy source. This study explores mechanisms affecting the formation of flattened density profiles, so-called ‘density shoulders’, in the low-field side (LFS) SOL, which modify ion and neutral fluxes to surfaces – and subsequent erosion. There is evidence against local enhancement of ionization inducing shoulder formation. We find that increases in SOL parallel resistivity, Λdiv (=[L||νei Ωi ]/cs Ωe), postulated to lead to shoulder growth through changes in SOL turbulence characteristics, correlates with increases in upstream SOL shoulder amplitude, As only under a subset of conditions (D2-fuelled L-mode density scans with outer strike point on the horizontal target). Λdiv fails to correlate with As for cases of N2 seeding or during sweeping of the strike point across the horizontal target. The limited correlation of Λdiv with As was also found for H-mode discharges. Thus, while Λdiv above a threshold of ~1 may be necessary for shoulder formation and/or growth, another shoulder mechanism is required. More significantly we find that in contrast to parallel resistivity, outer divertor recycling as quantified by the total outer divertor Balmer Dα emission, I-Dα, does scale with shoulder amplitude where Λdiv does and even where Λdiv fails. Divertor recycling could lead to SOL density shoulder formation through: a) reducing the parallel to the field flow (loss) of ions out of the SOL to the divertor; and b) changes in radial electric fields which lead to ExB poloidal flows as well as potentially affecting the SOL turbulence birth characteristics. Thus changes in divertor recycling may be the sole process in bringing about SOL density shoulders or in tandem with parallel resistivity

Neutral pathways and heat flux widths in vertical- and horizontal-target EDGE2D-EIRENE simulations of JET

This paper further analyses the EDGE2D-EIRENE simulations presented by Chankin et al (2017 Nucl. Mater. Energy 12 273), of L-mode JET plasmas in vertical-vertical (VV) and Vertical-horizontal (VH) divertor configurations. As expected, the simulated outer divertor ionisation source peaks near the separatrix in VV and radially further out in VH. We identify the reflections of recycled neutrals from lower divertor tiles as the primary mechanism by which ionisation is concentrated on the outer divertor separatrix in the VV configuration. These lower tile reflection pathways (of neutrals from the outer divertor, and to an even greater extent from the inner divertor) dominate the outer divertor separatrix ionisation. In contrast, the lower-tile-reflection pathways are much weaker in the VH simulation and its outer divertor ionisation is dominated by neutrals which do not reflect from any surfaces. Interestingly, these differences in neutral pathways give rise to strong differences in the heat flux density width λq at the outer divertor entrance: λq = 3.2 mm in VH compared to λq = 11.8 mm in VV. In VH, a narrow channel exists in the near scrape-off-layer (SOL) where the convected heat flux, driven by strong Er × B flow and thermoelectric current, dominates over the conducted heat flux. The width of this channel sets λq and is determined by the radial distance between the separatrix and the ionisation peak in the outer divertor

Observations and modelling of ion cyclotron emission observed in JET plasmas using a sub-harmonic arc detection system during ion cyclotron resonance heating

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