Playing the odds in clinical decision making: lessons from berry aneurysms undetected by magnetic resonance angiography

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Modulation of frontal effective connectivity during speech

Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change

Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. >30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com

Tomographic Separation of Composite Spectra. VIII. The Physical Properties of the Massive Compact Binary in the Triple Star System HD 36486 (delta Orionis A)

Double-lined spectroscopic orbital elements have recently been found for the central binary in the massive triple, delta Orionis A based on radial velocities from cross-correlation techniques applied to IUE high dispersion spectra and He I 6678 spectra obtained at Kitt Peak. The primary and secondary velocity amplitudes were found to be 94.9 +/- 0.6 km/s and 186 +/- 9 km/s respectively. Tomographic reconstructions of the primary and secondary stars' spectra confirm the O9.5 II classification of the primary and indicate a B0.5 III type for the secondary. The widths of the UV cross-correlation functions are used to estimate the projected rotational velocities, Vsin i = 157 +/- 6 km/s and 138 +/- 16 km/s for the primary and secondary, respectively implying that both stars rotate faster than their orbital motion. We used the spectroscopic results to make a constrained fit of the Hipparcos light curve of this eclipsing binary, and the model fits limit the inclination to the range between 67 and 77 degrees. The i = 67 degrees solution, which corresponds to a near Roche-filling configuration, results in a primary mass of 11.2 solar masses and a secondary mass of 5.6 solar masses, both of which are substantially below the expected masses for stars of their luminosity. This binary may have experienced a mass ratio reversal caused by Case A Roche lobe overflow, or the system may have suffered extensive mass loss through a binary interaction, perhaps during a common envelope phase, in which most of the primary's mass was lost from the system rather than transferred to the secondary.Comment: 27 pages, 15 figures in press, the Astrophysical Journal, February 1, 200

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

Graphical Perception of Continuous Quantitative Maps: the Effects of Spatial Frequency and Colormap Design

Continuous 'pseudocolor' maps visualize how a quantitative attribute varies smoothly over space. These maps are widely used by experts and lay citizens alike for communicating scientific and geographical data. A critical challenge for designers of these maps is selecting a color scheme that is both effective and aesthetically pleasing. Although there exist empirically grounded guidelines for color choice in segmented maps (e.g., choropleths), continuous maps are significantly understudied, and their color-coding guidelines are largely based on expert opinion and design heuristics--many of these guidelines have yet to be verified experimentally. We conducted a series of crowdsourced experiments to investigate how the perception of continuous maps is affected by colormap characteristics and spatial frequency (a measure of data complexity). We find that spatial frequency significantly impacts the effectiveness of color encodes, but the precise effect is task-dependent. While rainbow schemes afforded the highest accuracy in quantity estimation irrespective of spatial complexity, divergent colormaps significantly outperformed other schemes in tasks requiring the perception of high-frequency patterns. We interpret these results in relation to current practices and devise new and more granular guidelines for color mapping in continuous maps

Efficient posterior probability mapping using savage-dickey ratios.

Statistical Parametric Mapping (SPM) is the dominant paradigm for mass-univariate analysis of neuroimaging data. More recently, a Bayesian approach termed Posterior Probability Mapping (PPM) has been proposed as an alternative. PPM offers two advantages: (i) inferences can be made about effect size thus lending a precise physiological meaning to activated regions, (ii) regions can be declared inactive. This latter facility is most parsimoniously provided by PPMs based on Bayesian model comparisons. To date these comparisons have been implemented by an Independent Model Optimization (IMO) procedure which separately fits null and alternative models. This paper proposes a more computationally efficient procedure based on Savage-Dickey approximations to the Bayes factor, and Taylor-series approximations to the voxel-wise posterior covariance matrices. Simulations show the accuracy of this Savage-Dickey-Taylor (SDT) method to be comparable to that of IMO. Results on fMRI data show excellent agreement between SDT and IMO for second-level models, and reasonable agreement for first-level models. This Savage-Dickey test is a Bayesian analogue of the classical SPM-F and allows users to implement model comparison in a truly interactive manner

Phylogenomics: Gene Duplication, Unrecognized Paralogy and Outgroup Choice

Comparative genomics has revealed the ubiquity of gene and genome duplication and subsequent gene loss. In the case of gene duplication and subsequent loss, gene trees can differ from species trees, thus frequent gene duplication poses a challenge for reconstruction of species relationships. Here I address the case of multi-gene sets of putative orthologs that include some unrecognized paralogs due to ancestral gene duplication, and ask how outgroups should best be chosen to reduce the degree of non-species tree (NST) signal. Consideration of expected internal branch lengths supports several conclusions: (i) when a single outgroup is used, the degree of NST signal arising from gene duplication is either independent of outgroup choice, or is minimized by use of a maximally closely related post-duplication (MCRPD) outgroup; (ii) when two outgroups are used, NST signal is minimized by using one MCRPD outgroup, while the position of the second outgroup is of lesser importance; and (iii) when two outgroups are used, the ability to detect gene trees that are inconsistent with known aspects of the species tree is maximized by use of one MCRPD, and is either independent of the position of the second outgroup, or is maximized for a more distantly related second outgroup. Overall, these results generalize the utility of closely-related outgroups for phylogenetic analysis

The High Angular Resolution Multiplicity of Massive Stars

We present the results of a speckle interferometric survey of Galactic massive stars that complements and expands upon a similar survey made over a decade ago. The speckle observations were made with the KPNO and CTIO 4 m telescopes and USNO speckle camera, and they are sensitive to the detection of binaries in the angular separation regime between 0.03" and 5" with relatively bright companions (Delta V < 3). We report on the discovery of companions to 14 OB stars. In total we resolved companions of 41 of 385 O-stars (11%), 4 of 37 Wolf-Rayet stars (11%), and 89 of 139 B-stars (64%; an enriched visual binary sample that we selected for future orbital determinations). We made a statistical analysis of the binary frequency among the subsample that are listed in the Galactic O Star Catalog by compiling published data on other visual companions detected through adaptive optics studies and/or noted in the Washington Double Star Catalog and by collecting published information on radial velocities and spectroscopic binaries. We find that the binary frequency is much higher among O-stars in clusters and associations compared to the numbers for field and runaway O-stars, consistent with predictions for the ejection processes for runaway stars. We present a first orbit for the O-star Delta Orionis, a linear solution of the close, apparently optical, companion of the O-star Iota Orionis, and an improved orbit of the Be star Delta Scorpii. Finally, we list astrometric data for another 249 resolved and 221 unresolved targets that are lower mass stars that we observed for various other science programs.Comment: 76 pages, 6 figures, 11 table