Component Neural Systems for the Creation of Emotional Memories during Free Viewing of a Complex, Real-World Event

To investigate the neural systems that contribute to the formation of complex, self-relevant emotional memories, dedicated fans of rival college basketball teams watched a competitive game while undergoing functional magnetic resonance imaging (fMRI). During a subsequent recognition memory task, participants were shown video clips depicting plays of the game, stemming either from previously-viewed game segments (targets) or from non-viewed portions of the same game (foils). After an old–new judgment, participants provided emotional valence and intensity ratings of the clips. A data driven approach was first used to decompose the fMRI signal acquired during free viewing of the game into spatially independent components. Correlations were then calculated between the identified components and post-scanning emotion ratings for successfully encoded targets. Two components were correlated with intensity ratings, including temporal lobe regions implicated in memory and emotional functions, such as the hippocampus and amygdala, as well as a midline fronto-cingulo-parietal network implicated in social cognition and self-relevant processing. These data were supported by a general linear model analysis, which revealed additional valence effects in fronto-striatal-insular regions when plays were divided into positive and negative events according to the fan's perspective. Overall, these findings contribute to our understanding of how emotional factors impact distributed neural systems to successfully encode dynamic, personally-relevant event sequences

Participation in an innovative patient support program reduces prescription abandonment for adalimumab-treated patients in a commercial population.

Purpose: Nonadherence to indicated therapy reduces treatment effectiveness and may increase cost of care. HUMIRA Complete, a Patient Support Program (PSP), aims to reduce nonadherence in patients prescribed adalimumab (ADA). The objective of this study was to assess the relationship between participation in the PSP and prescription abandonment rates among ADA-treated patients. Patients and methods: This longitudinal study using patient-level data from AbbVie\u27s PSP linked with medical and pharmacy claims data included patients ≥18 years with an ADA-approved indication, ≥1 pharmacy claim for ADA, and available data ≥3 months before and ≥6 months after the index date (defined as the initial ADA claim [01/2015 to 02/2017]). Abandonment was defined as reversal of initial ADA prescription with no paid claim during 3-month follow-up. Abandonment rates were compared between PSP and non-PSP cohorts using multivariable logistic regression controlling for potentially confounding baseline characteristics. Results: In 17,371 patients (9,851 PSP; 7,520 non-PSP), the overall abandonment rate was 10.8-16.8% across indications. The odds of ADA abandonment were 70% less for PSP vs non-PSP patients (5.6% vs 20.4%, odds ratio [OR]=0.30, [95% confidence interval (CI)=0.27-0.33] Conclusion: Participation in the PSP, higher income, and using a specialty pharmacy were associated with lower odds of abandoning ADA therapy, whereas increased copayments were associated with greater abandonment. PSPs should be considered to improve initiation of ADA therapy

Long Term Effects of Radiation and Combined Modalities on Mouse Lung

The lung appears to be the major dose-limiting organ in radiation of the thorax. Early responses (\u3c1 week) involve the type II pneumocyte and increased surfactant biosynthesis and secretion. Later changes, which appear to be related to the surfactant response, lead to classical radiation pneumonitis, which is often fatal. Animals which survive radiation pneumonitis develop progressive fibrosis, a late-appearing response, which reduces compliance and available air space, and is usually fatal. This study centers on the fine structural changes in the lungs of LAF1 mice, 63 weeks following various radiation exposures (5-13 Gy). Doses which are subthreshold in evoking surfactant and pneumonitic responses precipitate fibrosis and atelectasis by 63 weeks, and involve type II pneumocyte sloughing and degeneration. Of the two major deterrents to lung irradiation (pneumonitis and fibrosis), these results suggest that fibrosis always follows pneumonitis, but pneumonitis is not a necessary preliminary step to fibrosis. Bleomycin elicits several morphological alterations characteristic of radiation, and, when combined with the latter, appears to exacerbate radiation effects

The SWELLS Survey. I. A large spectroscopically selected sample of edge-on late-type lens galaxies

The relative contribution of baryons and dark matter to the inner regions of spiral galaxies provides critical clues to their formation and evolution, but it is generally difficult to determine. For spiral galaxies that are strong gravitational lenses, however, the combination of lensing and kinematic observations can be used to break the disk-halo degeneracy. In turn, such data constrain fundamental parameters such as i) the mass density profile slope and axis ratio of the dark matter halo, and by comparison with dark matter-only numerical simulations the modifications imposed by baryons; ii) the mass in stars and therefore the overall star formation efficiency, and the amount of feedback; iii) by comparison with stellar population synthesis models, the normalization of the stellar initial mass function. In this first paper of a series, we present a sample of 16 secure, 1 probable, and 6 possible strong lensing spiral galaxies, for which multi-band high-resolution images and rotation curves were obtained using the Hubble Space Telescope and Keck-II Telescope as part of the Sloan WFC Edge-on Late-type Lens Survey (SWELLS). The sample includes 8 newly discovered secure systems. [abridged] We find that the SWELLS sample of secure lenses spans a broad range of morphologies (from lenticular to late-type spiral), spectral types (quantified by Halpha emission), and bulge to total stellar mass ratio (0.22-0.85), while being limited to M_*>10^{10.5} M_sun. The SWELLS sample is thus well-suited for exploring the relationship between dark and luminous matter in a broad range of galaxies. We find that the deflector galaxies obey the same size-mass relation as that of a comparison sample of elongated non-lens galaxies selected from the SDSS survey. We conclude that the SWELLS sample is consistent with being representative of the overall population of high-mass high-inclination disky galaxies.Comment: 21 pages, 6 figures, MNRAS, in pres

Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma

The molecular basis for the inverse relationship between differentiation and tumorigenesis is unknown. The function of runx2, a master regulator of osteoblast differentiation belonging to the runt family of tumor suppressor genes, is consistently disrupted in osteosarcoma cell lines. Ectopic expression of runx2 induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and leading to the dephosphorylation of the retinoblastoma tumor suppressor protein (pRb) and a G1 cell cycle arrest. Runx2 physically interacts with the hypophosphorylated form of pRb, a known coactivator of runx2, thereby completing a feed-forward loop in which progressive cell cycle exit promotes increased expression of the osteoblast phenotype. Loss of p27KIP1 perturbs transient and terminal cell cycle exit in osteoblasts. Consistent with the incompatibility of malignant transformation and permanent cell cycle exit, loss of p27KIP1 expression correlates with dedifferentiation in high-grade human osteosarcomas. Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is mediated through runx2 and p27KIP1, and these processes are disrupted in osteosarcoma

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Earliest rock fabric formed in the Solar System preserved in a chondrule rim

Rock fabrics – the preferred orientation of grains – provide a window into the history of rock formation, deformation and compaction. Chondritic meteorites are among the oldest materials in the Solar System1 and their fabrics should record a range of processes occurring in the nebula and in asteroids, but due to abundant fine-grained material these samples have largely resisted traditional in situ fabric analysis. Here we use high resolution electron backscatter diffraction to map the orientation of sub-micrometre grains in the Allende CV carbonaceous chondrite: the matrix material that is interstitial to the mm-sized spherical chondrules that give chondrites their name, and fine-grained rims which surround those chondrules. Although Allende matrix exhibits a bulk uniaxial fabric relating to a significant compressive event in the parent asteroid, we find that fine-grained rims preserve a spherically symmetric fabric centred on the chondrule. We define a method that quantitatively relates fabric intensity to net compression, and reconstruct an initial porosity for the rims of 70-80% - a value very close to model estimates for the earliest uncompacted aggregates2,3. We conclude that the chondrule rim textures formed in a nebula setting and may therefore be the first rock fabric to have formed in the Solar System

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin