We present evidence for localized deviations from Keplerian rotation, i.e., velocity "kinks," in 8 of the 18 circumstellar disks observed by the DSHARP program: DoAr 25, Elias 2-27, GW Lup, HD ...143006, HD 163296, IM Lup, Sz 129, and WaOph 6. Most of the kinks are detected over a small range in both radial extent and velocity, suggesting a planetary origin, but for some of them foreground contamination prevents us from measuring their spatial and velocity extent. Because of the DSHARP limited spectral resolution and signal to noise in the 12CO J = 2−1 line, as well as cloud contamination, the kinks are usually detected in only one spectral channel, and will require confirmation. The strongest circumstantial evidence for protoplanets in the absence of higher spectral resolution data and additional tracers is that, upon deprojection, we find that all of the candidate planets lie within a gap and/or at the end of a spiral detected in dust continuum emission. This suggests that a significant fraction of the dust gaps and spirals observed by Atacama Large Millimeter/submillimeter Array in disks are caused by embedded protoplanets.
Cetuximab-induced hypomagnesemia has been associated with improved clinical outcomes in advanced colorectal cancer (CRC). We explored this relationship from a randomized clinical trial of cetuximab ...plus best supportive care (BSC) versus BSC alone in patients with pretreated advanced CRC.
Day 28 hypomagnesemia grade (0 versus ≥1) and percent reduction (<20% versus ≥20%) of Mg from baseline was correlated with outcome.
The median percentage Mg reduction at day 28 was 10% (-42.4% to 63.0%) for cetuximab (N = 260) versus 0% (-21.1% to 25%) for BSC (N = 251) P < 0.0001. Grade ≥1 hypomagnesemia and ≥20% reduction from baseline at day 28 were associated with worse overall survival (OS) hazard ratio, HR 1.61 (95% CI 1.12–2.33), P = 0.01 and 2.08 (95% CI 1.32–3.29), P = 0.002, respectively in multivariate analysis including grade of rash (0–1 versus 2+). Dyspnea (grade ≥3) was more common in patients with ≥20% versus < 20% Mg reduction (68% versus 45%; P = 0.02) and grade 3/4 anorexia were higher in patients with grade ≥1 hypomagnesemia (81% versus 63%; P = 0.02).
In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Long-duration gamma-ray bursts (GRBs) are widely believed to be highly collimated explosions (bipolar conical outflows with half-opening angle theta{approx} 1{sup 0}-10{sup 0}). As a result of this ...beaming factor, the true energy release from a GRB is usually several orders of magnitude smaller than the observed isotropic value. Measuring this opening angle, typically inferred from an achromatic steepening in the afterglow light curve (a 'jet' break), has proven exceedingly difficult in the Swift era. Here, we undertake a study of five of the brightest (in terms of the isotropic prompt gamma-ray energy release, E{sub g}amma{sub ,iso}) GRBs in the Swift era to search for jet breaks and hence constrain the collimation-corrected energy release. We present multi-wavelength (radio through X-ray) observations of GRBs 050820A, 060418, and 080319B, and construct afterglow models to extract the opening angle and beaming-corrected energy release for all three events. Together with results from previous analyses of GRBs 050904 and 070125, we find evidence for an achromatic jet break in all five events, strongly supporting the canonical picture of GRBs as collimated explosions. The most natural explanation for the lack of observed jet breaks from most Swift GRBs is therefore selection effects. However, the opening angles for the events in our sample are larger than would be expected if all GRBs had a canonical energy release of {approx}10{sup 51} erg. The total energy release we measure for the 'hyper-energetic' (E{sub tot} {approx}> 10{sup 52} erg) events in our sample is large enough to start challenging models with a magnetar as the compact central remnant.
Roughly 3% of the Earth's land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat ...fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels-namely plants and their litter-that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences.
The Pan-STARRS1 (PS1) survey has obtained imaging in five bands (griz
y
P1) over 10 Medium Deep Survey (MDS) fields covering a total of 70 square degrees. This paper describes the search for ...apparently hostless supernovae (SNe) within the first year of PS1 MDS data with an aim of discovering superluminous supernovae (SLSNe). A total of 249 hostless transients were discovered down to a limiting magnitude of M
AB ∼ 23.5, of which 76 were classified as Type Ia supernovae (SNe Ia). There were 57 SNe with complete light curves that are likely core-collapse SNe (CCSNe) or type Ic SLSNe and 12 of these have had spectra taken. Of these 12 hostless, non-Type Ia SNe, 7 were SLSNe of type Ic at redshifts between 0.5 and 1.4. This illustrates that the discovery rate of type Ic SLSNe can be maximized by concentrating on hostless transients and removing normal SNe Ia. We present data for two possible SLSNe; PS1-10pm (z = 1.206) and PS1-10ahf (z = 1.1), and estimate the rate of type Ic SLSNe to be between
$3^{+3}_{-2}\times 10^{-5}$
and
$8^{+2}_{-1}\times 10^{-5}$
that of the CCSN rate within 0.3 ≤ z ≤ 1.4 by applying a Monte Carlo technique. The rate of slowly evolving, type Ic SLSNe (such as SN2007bi) is estimated as a factor of 10 lower than this range.
Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. ...We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ∼19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal.
Whole-genome sequencing (WGS) could potentially provide a single platform for extracting all the information required to predict an organism's phenotype. However, its ability to provide accurate ...predictions has not yet been demonstrated in large independent studies of specific organisms. In this study, we aimed to develop a genotypic prediction method for antimicrobial susceptibilities. The whole genomes of 501 unrelated Staphylococcus aureus isolates were sequenced, and the assembled genomes were interrogated using BLASTn for a panel of known resistance determinants (chromosomal mutations and genes carried on plasmids). Results were compared with phenotypic susceptibility testing for 12 commonly used antimicrobial agents (penicillin, methicillin, erythromycin, clindamycin, tetracycline, ciprofloxacin, vancomycin, trimethoprim, gentamicin, fusidic acid, rifampin, and mupirocin) performed by the routine clinical laboratory. We investigated discrepancies by repeat susceptibility testing and manual inspection of the sequences and used this information to optimize the resistance determinant panel and BLASTn algorithm. We then tested performance of the optimized tool in an independent validation set of 491 unrelated isolates, with phenotypic results obtained in duplicate by automated broth dilution (BD Phoenix) and disc diffusion. In the validation set, the overall sensitivity and specificity of the genomic prediction method were 0.97 (95% confidence interval 95% CI, 0.95 to 0.98) and 0.99 (95% CI, 0.99 to 1), respectively, compared to standard susceptibility testing methods. The very major error rate was 0.5%, and the major error rate was 0.7%. WGS was as sensitive and specific as routine antimicrobial susceptibility testing methods. WGS is a promising alternative to culture methods for resistance prediction in S. aureus and ultimately other major bacterial pathogens.
Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other ...psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ~15% (s.e. = 0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P = 1.5 x 10.sup.-15) spanning 4Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ~1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes. Molecular Psychiatry (2016) 21, 749-757; doi: 10.1038/mp.2016.49; published online 12 April 2016
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) ...band. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.
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