Neural circuits sit in a dynamic balance between excitation (E) and inhibition (I). Fluctuations in E:I balance have been shown to influence neural computation, working memory, and information flow, ...while more drastic shifts and aberrant E:I patterns are implicated in numerous neurological and psychiatric disorders. Current methods for measuring E:I dynamics require invasive procedures that are difficult to perform in behaving animals, and nearly impossible in humans. This has limited the ability to examine the full impact that E:I shifts have in cognition and disease. In this study, we develop a computational model to show that E:I changes can be estimated from the power law exponent (slope) of the electrophysiological power spectrum. Predictions from the model are validated in published data from two species (rats and macaques). We find that reducing E:I ratio via the administration of general anesthetic in macaques results in steeper power spectra, tracking conscious state over time. This causal result is supported by inference from known anatomical E:I changes across the depth of rat hippocampus, as well as oscillatory theta-modulated dynamic shifts in E:I. Our results provide evidence that E:I ratio may be inferred from electrophysiological recordings at many spatial scales, ranging from the local field potential to surface electrocorticography. This simple method for estimating E:I ratio—one that can be applied retrospectively to existing data—removes a major hurdle in understanding a currently difficult to measure, yet fundamental, aspect of neural computation.
•Computational modeling predicts E:I changes can shift 1/f power law (slope) in PSD.•Rat CA1 PSD slope tracks E & I synapse density across hippocampal layers.•Theta oscillation-modulated E:I changes is reflected in per-cycle PSD slope.•Propofol-induced inhibition in monkey cortex is reflected in ECoG PSD slope.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Since September 2010, more than 10,000 patients have undergone preemptive, panel‐based pharmacogenomic testing through the Vanderbilt Pharmacogenomic Resource for Enhanced Decisions in Care and ...Treatment program. Analysis of the genetic data from the first 9,589 individuals reveals that the frequency of genetic variants is concordant with published allele frequencies. Based on five currently implemented drug–gene interactions, the multiplexed test identified one or more actionable variants in 91% of the genotyped patients and in 96% of African American patients. Using medication exposure data from electronic medical records, we compared a theoretical “reactive,” prescription‐triggered, serial single‐gene testing strategy with our preemptive, multiplexed genotyping approach. Reactive genotyping would have generated 14,656 genetic tests. These data highlight three advantages of preemptive genotyping: (i) the vast majority of patients carry at least one pharmacogenetic variant; (ii) data are available at the point of care; and (iii) there is a substantial reduction in testing burden compared with a reactive strategy.
Clinical Pharmacology & Therapeutics (2014); 95 4, 423–431. doi:10.1038/clpt.2013.229
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Magnetic field amplification by relativistic streaming plasma instabilities is central to a wide variety of high-energy astrophysical environments as well as to laboratory scenarios associated with ...intense lasers and electron beams. We report on a new secondary nonlinear instability that arises for relativistic dilute electron beams after the saturation of the linear Weibel instability. This instability grows due to the transverse magnetic pressure associated with the beam current filaments, which cannot be quickly neutralized due to the inertia of background ions. We show that it can amplify the magnetic field strength and spatial scale by orders of magnitude, leading to large-scale plasma cavities with strong magnetic field and to very efficient conversion of the beam kinetic energy into magnetic energy. The instability growth rate, saturation level, and scale length are derived analytically and shown to be in good agreement with fully kinetic simulations.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
This study examined public perceptions of obesity-related public health media campaigns with specific emphasis on the extent to which campaign messages are perceived to be motivating or stigmatizing.
...In summer 2011, data were collected online from a nationally representative sample of 1014 adults. Participants viewed a random selection of 10 (from a total of 30) messages from major obesity public health campaigns from the United States, the United Kingdom and Australia, and rated each campaign message according to positive and negative descriptors, including whether it was stigmatizing or motivating. Participants also reported their familiarity with each message and their intentions to comply with the message content.
Participants responded most favorably to messages involving themes of increased fruit and vegetable consumption, and general messages involving multiple health behaviors. Messages that have been publicly criticized for their stigmatizing content received the most negative ratings and the lowest intentions to comply with message content. Furthermore, messages that were perceived to be most positive and motivating made no mention of the word 'obesity' at all, and instead focused on making healthy behavioral changes without reference to body weight.
These findings have important implications for framing messages in public health campaigns to address obesity, and suggest that certain types of messages may lead to increased motivation for behavior change among the public, whereas others may be perceived as stigmatizing and instill less motivation to improve health.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) ...generally have decreased dose‐adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Research demonstrates that health providers express negative attitudes toward overweight and obese patients that can be conveyed through weight-related language, yet little is known about people's ...perceptions of weight-related language used by providers. The current study examined public preferences and perceptions of weight-based terminology used by health-care providers to describe excess weight.
A national sample of American adults (N=1064) completed an online survey to assess perceptions and preferences associated with 10 common terms to describe body weight. Participants rated how much they perceived each term to be desirable, stigmatizing, blaming or motivating to lose weight (using five-point Likert scales), and how they would react if stigmatized by their doctor's reference to their weight.
The terms 'weight' (3.43, 95% confidence interval (CI) 3.35-3.50) and 'unhealthy weight' (3.24, 95% CI 3.15-3.33) were rated most desirable, and the terms 'unhealthy weight' (3.77, 95% CI 3.69-3.84) and 'overweight' (3.51, 95% CI 3.43-3.58) were rated most motivating to lose weight. The terms 'morbidly obese', 'fat' and 'obese' were rated as the most undesirable (95% CI 1.61-2.06), stigmatizing (95% CI 3.66-4.05) and blaming (95% CI 3.62-3.94) language used by health providers. Notably, participant ratings were consistent across socio-demographic variables and body weight categories. A total of 19% of participants reported they would avoid future medical appointments and 21% would seek a new doctor if they felt stigmatized about their weight from their doctor.
This study advances our understanding of why individuals prefer particular weight-related terms, and how patients may react if their provider uses stigmatizing language to refer to their weight. It also offers suggestions for practical strategies that providers can use to improve discussions about weight-related health with patients.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
We describe an update of MirGeneDB, the manually curated microRNA gene database. Adhering to uniform and consistent criteria for microRNA annotation and nomenclature, we substantially ...expanded MirGeneDB with 30 additional species representing previously missing metazoan phyla such as sponges, jellyfish, rotifers and flatworms. MirGeneDB 2.1 now consists of 75 species spanning over ∼800 million years of animal evolution, and contains a total number of 16 670 microRNAs from 1549 families. Over 6000 microRNAs were added in this update using ∼550 datasets with ∼7.5 billion sequencing reads. By adding new phylogenetically important species, especially those relevant for the study of whole genome duplication events, and through updating evolutionary nodes of origin for many families and genes, we were able to substantially refine our nomenclature system. All changes are traceable in the specifically developed MirGeneDB version tracker. The performance of read-pages is improved and microRNA expression matrices for all tissues and species are now also downloadable. Altogether, this update represents a significant step toward a complete sampling of all major metazoan phyla, and a widely needed foundation for comparative microRNA genomics and transcriptomics studies. MirGeneDB 2.1 is part of RNAcentral and Elixir Norway, publicly and freely available at http://www.mirgenedb.org/.
We propose a mediation model to explain the relationship between CEO humility and firm performance. Building on upper echelons, power, and paradox theories, we hypothesize that when a more humble CEO ...leads a firm, its top management team (TMT) is more likely to collaborate, share information, jointly make decisions, and possess a shared vision. The firm will also tend to have lower pay disparity between the CEO and the TMT. The humble CEO and TMT, in turn, will be more likely to adopt an ambidextrous strategic orientation, which will be associated with stronger firm performance. We tested the model by using both survey and archival data that were collected at multiple time points from 105 small-to-medium-sized firms in the computer software and hardware industry in the United States. Findings largely support our theoretical assertions, suggesting that CEO humility has important implications for firm processes and outcomes.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
9.
Insulator-metal transition in dense fluid deuterium Celliers, Peter M; Millot, Marius; Brygoo, Stephanie ...
Science (American Association for the Advancement of Science),
08/2018, Volume:
361, Issue:
6403
Journal Article
Peer reviewed
Open access
Dense fluid metallic hydrogen occupies the interiors of Jupiter, Saturn, and many extrasolar planets, where pressures reach millions of atmospheres. Planetary structure models must describe ...accurately the transition from the outer molecular envelopes to the interior metallic regions. We report optical measurements of dynamically compressed fluid deuterium to 600 gigapascals (GPa) that reveal an increasing refractive index, the onset of absorption of visible light near 150 GPa, and a transition to metal-like reflectivity (exceeding 30%) near 200 GPa, all at temperatures below 2000 kelvin. Our measurements and analysis address existing discrepancies between static and dynamic experiments for the insulator-metal transition in dense fluid hydrogen isotopes. They also provide new benchmarks for the theoretical calculations used to construct planetary models.
Inheritance of a coding variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is associated with increased susceptibility to autoimmunity and infection. Efforts to elucidate ...the mechanisms by which the PTPN22-C1858T variant modulates disease risk revealed that PTPN22 performs a signaling function in multiple biochemical pathways and cell types. Capable of both enzymatic activity and adaptor functions, PTPN22 modulates signaling through antigen and innate immune receptors. PTPN22 plays roles in lymphocyte development and activation, establishment of tolerance, and innate immune cell-mediated host defense and immunoregulation. The disease-associated PTPN22-R620W variant protein is likely involved in multiple stages of the pathogenesis of autoimmunity. Establishment of a tolerant B cell repertoire is disrupted by PTPN22-R620W action during immature B cell selection, and PTPN22-R620W alters mature T cell responsiveness. However, after autoimmune attack has initiated tissue injury, PTPN22-R620W may foster inflammation through modulating the balance of myeloid cell-produced cytokines.
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