71 research outputs found

    "Migrants, States, and EU Citizenship's Unfulfilled Promise"

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    A constant aim of EU citizenship, and indeed the entire project of European integration, has always been to lower barriers and create a common space. If the complete elimination of national borders remains elusive, their importance has been diminished in striking ways by the development of EU citizenship and the ban against nationality based discrimination. Yet the barriers to free movement have been lowered in differential ways. Most citizens of EU member states now enjoy residence, employment and other rights throughout Europe. The extension of some rights to some categories of citizens of some new member states is admittedly sometimes subject to transition periods, but these expire. By contrast, third country nationals -- individuals who do not hold citizenship of one of the member states, even though they may have resided for many years, or even been born in Europe -- remain largely excluded from the benefits of EU citizenship. Various initiatives over the years have opened up limited rights for third country nationals. But the difficulty of enacting these rights, and current moves to more restrictive immigration and naturalization policies, highlight the continuing exclusivity of EU citizenship: immigrants migrate to national polities, and they become European only by virtue of incorporation into national states. This means that EU citizenship's transformative potential remains unrealized.Glendon College (York University

    A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk

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    Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-a macrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 x 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 x 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D

    Neuroimaging-based classification of PTSD using data-driven computational approaches: a multisite big data study from the ENIGMA-PGC PTSD consortium

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    Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.Stress-related psychiatric disorders across the life spa

    Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

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    Background: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. Methods: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. Findings: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. Interpretation: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. Funding: The UK National Institute for Health Research Health Technology Assessment Programme

    Mortality after discharge from intensive care

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    Nuclear singlet relaxation by scalar relaxation of the second kind in the slow-fluctuation regime

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    The singlet state of nuclear spin-1/2 pairs is protected against many common relaxation mechanisms. Singlet order, which is defined as the population difference between the nuclear singlet and triplet states, usually decays more slowly than the nuclear magnetization. Nevertheless, some decay mechanisms for nuclear singlet order persist. One such mechanism is called scalar relaxation of the second kind (SR2K) and involves the relaxation of additional nuclei ("third spins") which have scalar couplings to the spin-1/2 pair. This mechanism requires a difference between the couplings of at least one third spin with the two members of the spin-1/2 pair, and depends on the longitudinal relaxation time of the third spin. The SR2K mechanism of nuclear singlet relaxation has previously been examined in the case where the relaxation rate of the additional spins is on the time scale of the nuclear Larmor frequency. In this paper, we consider a different regime, in which the longitudinal relaxation of the third spins is on a similar time scale to the J-coupling between the members of the spin pair. This regime is often encountered when the spin-1/2 pair has scalar couplings to nearby deuterium nuclei. We show that the SR2K mechanism may be suppressed in this regime by applying a radiofrequency field which is resonant either with the members of the spin pair, or with the third spins. These phenomena are analyzed theoretically and by numerical simulations, and demonstrated experimentally on a diester of [13C2,2H2]-labeled fumarate in solution. </p

    Alcohol consumption in a general antenatal population and child neurodevelopment at 2 years

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    BACKGROUND:Prenatal alcohol exposure (PAE) is a community health problem with up to 50% of pregnant women drinking alcohol. The relationship between low or sporadic binge PAE and adverse child outcomes is not clear. This study examines the association between PAE in the general antenatal population and child neurodevelopment at 2 years, accounting for relevant contributing factors. METHODS:This prospective population-based cohort recruited 1570 pregnant women, providing sociodemographic, psychological and lifestyle information and alcohol use for five time periods. PAE categories were 'low', 'moderate/high', 'binge', in trimester 1 or throughout pregnancy. Measures of cognitive, language and motor development (Bayley Scales of Infant and Toddler Development) were available for 554 children, while measures of sensory processing (Infant/Toddler Sensory Profile) and social-emotional development (Brief Infant Toddler Social Emotional Assessment) were available for 948. RESULTS:A positive association in univariate analysis with low-level PAE throughout pregnancy and cognition (β=4.1, 95% CI -0.02 to 8.22, p=0.05) was attenuated by adjusting for environmental/social deprivation risk factors (β=3.06 (-1.19 to 7.30), p=0.16). Early binge drinking, plus continued PAE at lower levels, was associated with the child being more likely to score low in sensation avoidance (adjusted OR 1.88 (1.03 to 3.41), p=0.04). CONCLUSION:Early binge exposure, followed by lower-level PAE, demonstrated an increase in sensation-avoiding behaviour. There were, however, no significant associations between PAE and neurodevelopment following adjustment for important confounders and modifiers. Follow-up is paramount to investigate subtle or later onset problems.Jane L Halliday, Evelyne Muggli, Sharon Lewis, Elizabeth J Elliott, David J Amor, Colleen O’Leary ... et al
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