3,656 research outputs found

    International Centre for Guidance Studies (iCeGS) Annual Review 2023 - 25th Anniversary

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    This publication offers a brief insight into the wide range of activities the iCeGS team has been involved with over the year and the last 25 years. It explores our contribution to policy, research and practice within the career development sector both in the UK and wider afield. iCeGS Annual Review also allows the team to reflect on our many achievements over the last year. Like other years, we feel particularly proud of several activities this year

    A functional variant on 20q13.33 related to glioma risk alters enhancer activity and modulates expression of multiple genes.

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    Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with glioma risk on 20q13.33, but the biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 20q13.33 impacted the activity of an enhancer, leading to an altered expression of nearby genes. To identify candidate functional SNPs, we identified all SNPs in linkage disequilibrium with the risk-associated SNP rs2297440 that mapped to putative enhancers. Putative enhancers containing candidate functional SNPs were tested for allele-specific effects in luciferase enhancer activity assays against glioblastoma multiforme (GBM) cell lines. An enhancer containing SNP rs3761124 exhibited allele-specific effects on activity. Deletion of this enhancer by CRISPR-Cas9 editing in GBM cell lines correlated with an altered expression of multiple genes, including STMN3, RTEL1, RTEL1-TNFRSF6B, GMEB2, and SRMS. Expression quantitative trait loci (eQTL) analyses using nondiseased brain samples, isocitrate dehydrogenase 1 (IDH1) wild-type glioma, and neurodevelopmental tissues showed STMN3 to be a consistent significant eQTL with rs3761124. RTEL1 and GMEB2 were also significant eQTLs in the context of early CNS development and/or in IDH1 wild-type glioma. We provide evidence that rs3761124 is a functional variant on 20q13.33 related to glioma/GBM risk that modulates the expression of STMN3 and potentially other genes across diverse cellular contexts

    Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

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    Background: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. Methods: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. Results: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain. Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). Conclusion: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain

    A Multi-wavelength View of the TeV Blazar Markarian 421: Correlated Variability, Flaring, and Spectral Evolution

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    We report results from a multi-wavelength monitoring campaign on Mrk 421 over the period of 2003-2004. The source was observed simultaneously at TeV and X-ray energies, with supporting observations frequently carried out at optical and radio wavelengths. The large amount of simultaneous data has allowed us to examine the variability of Mrk 421 in detail. The variabilities are generally correlated between the X-ray and gamma-ray bands, although the correlation appears to be fairly loose. The light curves show the presence of flares with varying amplitudes on a wide range of timescales both at X-ray and TeV energies. Of particular interest is the presence of TeV flares that have no coincident counterparts at longer wavelengths, because the phenomenon seems difficult to understand in the context of the proposed emission models for TeV blazars. We have also found that the TeV flux reached its peak days before the X-ray flux during a giant flare in 2004. Such a difference in the development of the flare presents a further challenge to the emission models. Mrk 421 varied much less at optical and radio wavelengths. Surprisingly, the normalized variability amplitude in optical seems to be comparable to that in radio, perhaps suggesting the presence of different populations of emitting electrons in the jet. The spectral energy distribution (SED) of Mrk 421 is seen to vary with flux, with the two characteristic peaks moving toward higher energies at higher fluxes. We have failed to fit the measured SEDs with a one-zone SSC model; introducing additional zones greatly improves the fits. We have derived constraints on the physical properties of the X-ray/gamma-ray flaring regions from the observed variability (and SED) of the source. The implications of the results are discussed. (Abridged)Comment: 32 pages, 12 figures, to appear in Ap

    Class talk: habitus and class in parental narratives of school choice

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    © 2016 Westburn Publishers Ltd. This article explores how social class is linguistically negotiated and contested in parental narratives of school choice in the British education marketplace. Our study reveals prevalent yet obscured vestiges of ‘class talk’, and in doing so, unmasks ‘micro-political’ acts of status claiming. Using interactional narrative interviewing with 30 parents, we explore how inter- and intra-class differences are emotionally expressed, thus exposing the embodied dispositions of parents’ habitus and its’ subtle influence on school choice. The parental narratives also unveil a moral and political tension between the neoliberal ideal of entrepreneurial self-advancement and an egalitarian sentiment for social equality. Our study therefore challenges the neoliberal educational policy of market choice in closing the attainment gap

    Modeling electromagnetic form factors of light and heavy pseudoscalar mesons

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    The electromagnetic form factors of light and heavy pseudoscalar mesons are calculated within two covariant constituent-quark models, a light-front and a dispersion relation approach. We investigate the details and physical origins of the model dependence of various hadronic observables: the weak decay constant, the charge radius and the elastic electromagnetic form factor.Comment: 6 pages, 4 figures, use revtex4. Figure 2 and references are corrected. Acknoledgments are adde

    Tissue-specific transcriptome profiling of the citrus fruit epidermis and subepidermis using laser capture microdissection

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    Most studies of the biochemical and regulatory pathways that are associated with, and control, fruit expansion and ripening are based on homogenized bulk tissues, and do not take into consideration the multiplicity of different cell types from which the analytes, be they transcripts, proteins or metabolites, are extracted. Consequently, potentially valuable spatial information is lost and the lower abundance cellular components that are expressed only in certain cell types can be diluted below the level of detection. In this study, laser microdissection (LMD) was used to isolate epidermal and subepidermal cells from green, expanding Citrus clementina fruit and their transcriptomes were compared using a 20k citrus cDNA microarray and quantitative real-time PCR. The results show striking differences in gene expression profiles between the two cell types, revealing specific metabolic pathways that can be related to their respective organelle composition and cell wall specialization. Microscopy provided additional evidence of tissue specialization that could be associated with the transcript profiles with distinct differences in organelle and metabolite accumulation. Subepidermis predominant genes are primarily involved in photosynthesis- and energy-related processes, as well as cell wall biosynthesis and restructuring. By contrast, the most epidermis predominant genes are related to the biosynthesis of the cuticle, flavonoids, and defence responses. Furthermore, the epidermis transcript profile showed a high proportion of genes with no known function, supporting the original hypothesis that analysis at the tissue/cell specific levels can promote gene discovery and lead to a better understanding of the specialized contribution of each tissue to fruit physiology

    Review of Clinical Features, Microbiological Spectrum, and Treatment Outcomes of Endogenous Endophthalmitis over an 8-Year Period

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    Purpose. To evaluate the clinical features, microbiological spectrum, and treatment outcomes of endogenous endophthalmitis. Methods. Retrospective review of consecutive cases with infective endogenous endophthalmitis presenting from 2000 to 2007. The main outcome measure was the visual outcome at the latest follow-up visit. Other outcome measures included microbiological investigations, anatomical and clinical outcomes. Results. 22 eyes of 21 patients were included, and the mean follow-up duration was 2.7 years. Eyes with fungal endogenous endophthalmitis were more likely to have visual acuity of finger counting or better at presentation compared with those with bacterial endogenous endophthalmitis (odds ratio=15.0, =0.013). Gram-negative microorganisms accounted for 50% of infections, while fungal and gram-positive organisms accounted for 27.3% and 22.7%, respectively. Despite treatment, the visual outcome was poor in general as 10 (45.5%) eyes had no light perception at the latest follow-up visit and 6 (27.3%) eyes required enucleation or evisceration. Contrary to previous studies, fungal endogenous endophthalmitis did not appear to have better visual outcome compared with bacterial endogenous endophthalmitis. Conclusion. Gram-negative microorganisms were the main causative pathogens of endogenous endophthalmitis in Hong Kong. The visual prognosis of endogenous endophthalmitis is generally poor as almost 50% of eyes were blind despite treatment
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