Neural activity associated with the passive prediction of ambiguity and risk for aversive events

In economic decision making, outcomes are described in terms of risk (uncertain outcomes with certain probabilities) and ambiguity (uncertain outcomes with uncertain probabilities). Humans are more averse to ambiguity than to risk, with a distinct neural system suggested as mediating this effect. However, there has been no clear disambiguation of activity related to decisions themselves from perceptual processing of ambiguity. In a functional magnetic resonance imaging (fMRI) experiment, we contrasted ambiguity, defined as a lack of information about outcome probabilities, to risk, where outcome probabilities are known, or ignorance, where outcomes are completely unknown and unknowable.Wemodified previously learned pavlovian CSstimuli such that they became an ambiguous cue and contrasted evoked brain activity both with an unmodified predictive CS(risky cue), and a cue that conveyed no information about outcome probabilities (ignorance cue). Compared with risk, ambiguous cues elicited activity in posterior inferior frontal gyrus and posterior parietal cortex during outcome anticipation. Furthermore, a similar set of regions was activated when ambiguous cues were compared with ignorance cues. Thus, regions previously shown to be engaged by decisions about ambiguous rewarding outcomes are also engaged by ambiguous outcome prediction in the context of aversive outcomes. Moreover, activation in these regions was seen even when no actual decision is made. Our findings suggest that these regions subserve a general function of contextual analysis when search for hidden information during outcome anticipation is both necessary and meaningful

The California coastal wave monitoring and prediction system

AbstractA decade-long effort to estimate nearshore (20m depth) wave conditions based on offshore buoy observations along the California coast is described. Offshore, deep water directional wave buoys are used to initialize a non-stationary, linear, spectral refraction wave model. Model hindcasts of spectral parameters commonly used in nearshore process studies and engineering design are validated against nearshore buoy observations seaward of the surfzone. The buoy-driven wave model shows significant skill at most validation sites, but prediction errors for individual swell or sea events can be large. Model skill is high in north San Diego County, and low in the Santa Barbara Channel and along the southern Monterey Bay coast. Overall, the buoy-driven model hindcasts have relatively low bias and therefore are best suited for quantifying mean (e.g. monthly or annual) nearshore wave climate conditions rather than extreme or individual wave events. Model error correlation with the incident offshore wave energy, and between neighboring validation sites, may be useful in identifying sources of regional modeling errors

A standardized framing for reporting protein identifications in mzIdentML 1.2

Inferring which protein species have been detected in bottom-up proteomics experiments has been a challenging problem for which solutions have been maturing over the past decade. While many inference approaches now function well in isolation, comparing and reconciling the results generated across different tools remains difficult. It presently stands as one of the greatest barriers in collaborative efforts such as the Human Proteome Project and public repositories such as the PRoteomics IDEntifications (PRIDE) database. Here we present a framework for reporting protein identifications that seeks to improve capabilities for comparing results generated by different inference tools. This framework standardizes the terminology for describing protein identification results, associated with the HUPO-Proteomics Standards Initiative (PSI) mzIdentML standard, while still allowing for differing methodologies to reach that final state. It is proposed that developers of software for reporting identification results will adopt this terminology in their outputs. While the new terminology does not require any changes to the core mzIdentML model, it represents a significant change in practice, and, as such, the rules will be released via a new version of the mzIdentML specification (version 1.2) so that consumers of files are able to determine whether the new guidelines have been adopted by export software

CO(1-0) detection of molecular gas in the massive Spiderweb Galaxy (z=2)

The high-redshift radio galaxy MRC 1138−262 (‘Spiderweb Galaxy’; z = 2.16) is one of the most massive systems in the early Universe and surrounded by a dense ‘web’ of proto-cluster galaxies. Using the Australia Telescope Compact Array, we detected CO(1–0) emission from cold molecular gas – the raw ingredient for star formation – across the Spiderweb Galaxy. We infer a molecular gas mass of MH2 = 6 × 1010 M⊙ (for MH2/L′CO = 0.8). While the bulk of the molecular gas coincides with the central radio galaxy, there are indications that a substantial fraction of this gas is associated with satellite galaxies or spread across the intergalactic medium on scales of tens of kpc. In addition, we tentatively detect CO(1–0) in the star-forming proto-cluster galaxy HAE 229, 250 kpc to the West. Our observations are consistent with the fact that the Spiderweb Galaxy is building up its stellar mass through a massive burst of widespread star formation. At maximum star formation efficiency, the molecular gas will be able to sustain the current star formation rate (SFR ≈ 1400 M⊙ yr−1, as traced by Seymour et al.) for about 40 Myr. This is similar to the estimated typical lifetime of a major starburst event in infrared luminous merger systems

Definition and recommendations for advance care planning: an international consensus supported by the European Association for Palliative Care

Advance care planning (ACP) is increasingly implemented in oncology and beyond, but a definition of ACP and recommendations concerning its use are lacking. We used a formal Delphi consensus process to help develop a definition of ACP and provide recommendations for its application. Of the 109 experts (82 from Europe, 16 from North America, and 11 from Australia) who rated the ACP definitions and its 41 recommendations, agreement for each definition or recommendation was between 68–100%. ACP was defined as the ability to enable individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and health-care providers, and to record and review these preferences if appropriate. Recommendations included the adaptation of ACP based on the readiness of the individual; targeting ACP content as the individual's health condition worsens; and, using trained non-physician facilitators to support the ACP process. We present a list of outcome measures to enable the pooling and comparison of results of ACP studies. We believe that our recommendations can provide guidance for clinical practice, ACP policy, and research

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma

BackgroundAn improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.Materials and methodsTranscriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).ResultsIn the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.ConclusionsOur results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours

CO(1-0) survey of high-z radio galaxies: alignment of molecular halo gas with distant radio sources

We present a CO(1–0) survey for cold molecular gas in a representative sample of 13 highz radio galaxies (HzRGs) at 1.4 <z< 2.8, using the Australia Telescope Compact Array. We detect CO(1–0) emission associated with five sources: MRC 0114-211, MRC 0152-209, MRC 0156-252, MRC 1138-262 and MRC 2048-272. The CO(1–0) luminosities are in the range L CO ∼ (5–9) × 1010 K km s−1 pc2. For MRC 0152-209 and MRC 1138-262, part of the CO(1–0) emission coincides with the radio galaxy, while part is spread on scales of tens of kpc and likely associated with galaxy mergers. The molecular gas mass derived for these two systems is MH2 ∼ 6 × 1010 M� (MH2/L CO = 0.8). For the remaining three CO-detected sources, the CO(1–0) emission is located in the halo (∼50-kpc) environment. These three HzRGs are among the fainter far-IR emitters in our sample, suggesting that similar reservoirs of cold molecular halo gas may have been missed in earlier studies due to pre-selection of IR-bright sources. In all three cases, the CO(1–0) is aligned along the radio axis and found beyond the brightest radio hotspot, in a region devoid of 4.5 µm emission in Spitzerimaging. The CO(1–0) profiles are broad, with velocity widths of ∼1000–3600 km s−1. We discuss several possible scenarios to explain these halo reservoirs of CO(1–0). Following these results, we complement our CO(1–0) study with detections of extended CO from the literature and find at marginal statistical significance (95 per cent level) that CO in HzRGs is preferentially aligned towards the radio jet axis. For the eight sources in which we do not detect CO(1–0), we set realistic upper limits of L CO ∼ 3–4 × 1010 K km s−1 pc2. Our survey reveals a CO(1–0) detection rate of 38 per cent, allowing us to compare the CO(1–0) content of HzRGs with that of other types of high-z galaxies

Critical Review of Methods for Sampling, Analysis, and Monitoring of Vapor-Phase Toluene Diisocyanate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91959/1/TLVpaper2002.pd