279 research outputs found

    Positive words carry less information than negative words

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    We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

    Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

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    © 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

    DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification.

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    AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology that resolved 17/22 and 15/21, respectively, where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach

    A morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation.

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    OBJECTIVE: The purpose of this study was to evaluate the possible structural changes of the macula in patients with unilateral amblyopia using optical coherence tomography (OCT) image segmentation. PATIENTS AND METHODS: 38 consecutive patients (16 male; mean age 32.4+/-17.6 years; range 6-67 years) with unilateral amblyopia were involved in this study. OCT examinations were performed with a time-domain OCT device, and a custom-built OCT image analysis software (OCTRIMA) was used for OCT image segmentation. The axial length (AL) was measured by a LenStar LS 900 device. Macular layer thickness, AL and manifest spherical equivalent refraction (MRSE) of the amblyopic eye were compared to that of the fellow eye. We studied if the type of amblyopia (strabismus without anisometropia, anisometropia without strabismus, strabismus with anisometropia) had any influence on macular layer thickness values. RESULTS: There was significant difference between the amblyopic and fellow eyes in MRSE and AL in all subgroups. Comparing the amblyopic and fellow eyes, we found a statistically significant difference only in the thickness of the outer nuclear layer in the central region using linear mixed model analysis keeping AL and age under control (p = 0.032). There was no significant difference in interocular difference in the thickness of any macular layers between the subgroups with one-way between-groups ANCOVA while statistically controlling for interocular difference in AL and age. CONCLUSIONS: According to our results there are subtle changes in amblyopic eyes affecting the outer nuclear layer of the fovea suggesting the possible involvement of the photoreceptors. However, further studies are warranted to support this hypothesis

    Embryology and bony malformations of the craniovertebral junction

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    BACKGROUND: The embryology of the bony craniovertebral junction (CVJ) is reviewed with the purpose of explaining the genesis and unusual configurations of the numerous congenital malformations in this region. Functionally, the bony CVJ can be divided into a central pillar consisting of the basiocciput and dental pivot and a two-tiered ring revolving round the central pivot, comprising the foramen magnum rim and occipital condyles above and the atlantal ring below. Embryologically, the central pillar and the surrounding rings descend from different primordia, and accordingly, developmental anomalies at the CVJ can also be segregated into those affecting the central pillar and those affecting the surrounding rings, respectively. DISCUSSION: A logical classification of this seemingly unwieldy group of malformations is thus possible based on their ontogenetic lineage, morbid anatomy, and clinical relevance. Representative examples of the main constituents of this classification scheme are given, and their surgical treatments are selectively discussed

    Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

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    Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. © 2009 Nascimento et al

    Molecular Mechanisms of Fiber Differential Development between G. barbadense and G. hirsutum Revealed by Genetical Genomics

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    Cotton fiber qualities including length, strength and fineness are known to be controlled by genes affecting cell elongation and secondary cell wall (SCW) biosynthesis, but the molecular mechanisms that govern development of fiber traits are largely unknown. Here, we evaluated an interspecific backcrossed population from G. barbadense cv. Hai7124 and G. hirsutum acc. TM-1 for fiber characteristics in four-year environments under field conditions, and detected 12 quantitative trait loci (QTL) and QTL-by-environment interactions by multi-QTL joint analysis. Further analysis of fiber growth and gene expression between TM-1 and Hai7124 showed greater differences at 10 and 25 days post-anthesis (DPA). In this two period important for fiber performances, we integrated genome-wide expression profiling with linkage analysis using the same genetic materials and identified in total 916 expression QTL (eQTL) significantly (P<0.05) affecting the expression of 394 differential genes. Many positional cis-/trans-acting eQTL and eQTL hotspots were detected across the genome. By comparative mapping of eQTL and fiber QTL, a dataset of candidate genes affecting fiber qualities was generated. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed the major differential genes regulating fiber cell elongation or SCW synthesis. These data collectively support molecular mechanism for G. hirsutum and G. barbadense through differential gene regulation causing difference of fiber qualities. The down-regulated expression of abscisic acid (ABA) and ethylene signaling pathway genes and high-level and long-term expression of positive regulators including auxin and cell wall enzyme genes for fiber cell elongation at the fiber developmental transition stage may account for superior fiber qualities
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