152 research outputs found

    Construyendo Una Frontera Comun O Desconstruyendo Una Identidad Nacional?: Un Analisis Del Esfuerzo De Centralizar Control De Inmigracion De Tercer Pais En La Union Europea

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    Lejos de los ataques espantosos sobre las torres gemelas y el Pentdgono, una pared al lado de una mezquita en Inglaterra del Norte lee, Vengue EE. UU - maten a un Musulmin ahora

    Building A Common Frontier Or Deconstructing National Identity?: An Analysis Of The Effort To Centralize Control Of Third Country Immigration In The European Union

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    Faraway from the frightening attacks on the World Trade Center and the Pentagon, a wall next to a mosque in Northern England reads, Avenge USA - kill a Muslim now

    White matter microstructural abnormalities in children with severe congenital hypothyroidism.

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    This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.This work was supported by a NIHR/CSO Healthcare Science Doctoral Research Fellowship, Hannah Cooper, NIHR-HCS-D12-03-05. We also acknowledge funding from the NIHR Biomedical Research Centre at Great Ormond Street Hospital and the Great Ormond Street Institute of Child Health, University College London, as well as at University College London Hospitals. Enrico Kaden was supported by grants UK EPSRCEP/M020533/1, EP/N018702/1 and EU H2020 634541-2

    FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

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    Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

    Reactions to Brexit in images : a multimodal content analysis of shared visual content on Flickr

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    In this article, the authors analyze citizens’ reactions to Brexit on social media after the referendum results by performing a content analysis of 5877 posts collected from the social media platform Flickr, written in English, German, French, Spanish or Italian. Their research aims to answer the three following questions: What multimodal practices are adopted by citizens when they react to societal events like Brexit? To what extent do these practices illustrate types of citizenship that are specific to social networks? Can we observe different reactions to Brexit according to the languages used by the citizens? The authors focus on the types of visual content the citizens used to react to Brexit, as well as on what types of social relations this content can particularly create between their authors and the other members of the Flick community. Their article also highlights to what extent these posts shared on Flickr show content that is in favour of, or against, Brexit

    Psychophysics with children: Investigating the effects of attentional lapses on threshold estimates

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    When assessing the perceptual abilities of children, researchers tend to use psychophysical techniques designed for use with adults. However, children’s poorer attentiveness might bias the threshold estimates obtained by these methods. Here, we obtained speed discrimination threshold estimates in 6- to 7-year-old children in UK Key Stage 1 (KS1), 7- to 9-year-old children in Key Stage 2 (KS2), and adults using three psychophysical procedures: QUEST, a 1-up 2-down Levitt staircase, and Method of Constant Stimuli (MCS). We estimated inattentiveness using responses to “easy” catch trials. As expected, children had higher threshold estimates and made more errors on catch trials than adults. Lower threshold estimates were obtained from psychometric functions fit to the data in the QUEST condition than the MCS and Levitt staircases, and the threshold estimates obtained when fitting a psychometric function to the QUEST data were also lower than when using the QUEST mode. This suggests that threshold estimates cannot be compared directly across methods. Differences between the procedures did not vary significantly with age group. Simulations indicated that inattentiveness biased threshold estimates particularly when threshold estimates were computed as the QUEST mode or the average of staircase reversals. In contrast, thresholds estimated by post-hoc psychometric function fitting were less biased by attentional lapses. Our results suggest that some psychophysical methods are more robust to attentiveness, which has important implications for assessing the perception of children and clinical groups

    Improving experiences of neglected tropical diseases of the skin: Mixed methods formative research for development of a complex intervention in Atwima Mponua District, Ghana.

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    Integrated approaches to managing co-endemic neglected tropical diseases (NTDs) of the skin within primary healthcare services are complex and require tailoring to local contexts. We describe formative research in Atwima Mponua District in Ghana's Ashanti Region designed to inform the development of a sustainable intervention to improve access to skin NTD care. We employed a convergent, parallel, mixed-methods design, collecting data from February 2021 to February 2022. We quantitatively assessed service readiness using a standardised checklist and reviewed outpatient department registers and condition-specific case records in all government health facilities in the district. Alongside a review of policy documents, we conducted 49 interviews and 7 focus group discussions with purposively selected affected persons, caregivers, community members, health workers, and policy-makers to understand skin NTD care-seeking practices and the policy landscape. Outside the district hospital, skin NTD reporting rates in the surveyed facilities were low; supply chains for skin NTD diagnostics, consumables, and medicines had gaps; and health worker knowledge of skin NTDs was limited. Affected people described fragmented care, provided mostly by hospitals (often outside the district) or traditional healers, resulting in challenges obtaining timely diagnosis and treatment and high care-seeking costs. Affected people experienced stigma, although the extent to which stigma influenced care-seeking behaviour was unclear. National actors were more optimistic than district-level actors about local resource availability for skin NTD care and were sceptical of including traditional healers in interventions. Our findings indicate that improvement of the care cascade for affected individuals to reduce the clinical, economic, and psychosocial impact of skin NTDs is likely to require a complementary set of interventions. These findings have informed the design of a strategy to support high-quality, integrated, decentralised care for skin NTDs in Atwima Mponua, which will be assessed through a multidisciplinary evaluation

    Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

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    Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer
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