111 research outputs found
Liquid Urbanisms: Dublin's Loose Networks and Provisional Places
My PhD thesis contributes to the disciplines of Geography and Urban Studies by adding the vocabulary, typology and conceptual framework of what I call ‘Liquid Urbanisms’ (LU). My LU typology invites scholars to investigate a range of provisional places and projects in their city initiatives, largely overlooked in the ‘temporary urbanisms’ literature, including autonomous social centres and direct-action occupations, and highlights the need to include these lesser-known projects in our understandings of how the neoliberal city is made and how groups, artists and activists contribute to the complex and fluid timespaces of the lived, rhythmic city and emphasises the nuanced everyday experiences of those creating more liveable spaces in post-austerity cities. It introduces an innovative methodological approach which I describe as a ‘Flexible Activist Case Study Approach’, which includes mixed qualitative methods across numerous case studies over a period of three years, to capture a range of case studies. The fourteen case studies I examined in the PhD varied, but I classified them into three broad types: Creative, Community-Based and Autonomous Liquid Urbanisms. These case studies include: a pop-up urban park, a squat, a networking group, community urban gardens, exhibitions, occupations, an art and cultural centre, projects in annual festivals, among others. I also identified four tributaries, or characteristics, which intersect and flow with the types of LU: networks and place, timespaces and rhythms, use value and urban commons, and political beliefs and institutional relationships. When combined, the LU types and tributaries form a typology and illustrate the ecology of provisional places in Dublin
Liquid Urbanisms: Dublin's Loose Networks and Provisional Places
My PhD thesis contributes to the disciplines of Geography and Urban Studies by adding the vocabulary, typology and conceptual framework of what I call ‘Liquid Urbanisms’ (LU). My LU typology invites scholars to investigate a range of provisional places and projects in their city initiatives, largely overlooked in the ‘temporary urbanisms’ literature, including autonomous social centres and direct-action occupations, and highlights the need to include these lesser-known projects in our understandings of how the neoliberal city is made and how groups, artists and activists contribute to the complex and fluid timespaces of the lived, rhythmic city and emphasises the nuanced everyday experiences of those creating more liveable spaces in post-austerity cities. It introduces an innovative methodological approach which I describe as a ‘Flexible Activist Case Study Approach’, which includes mixed qualitative methods across numerous case studies over a period of three years, to capture a range of case studies. The fourteen case studies I examined in the PhD varied, but I classified them into three broad types: Creative, Community-Based and Autonomous Liquid Urbanisms. These case studies include: a pop-up urban park, a squat, a networking group, community urban gardens, exhibitions, occupations, an art and cultural centre, projects in annual festivals, among others. I also identified four tributaries, or characteristics, which intersect and flow with the types of LU: networks and place, timespaces and rhythms, use value and urban commons, and political beliefs and institutional relationships. When combined, the LU types and tributaries form a typology and illustrate the ecology of provisional places in Dublin
Age-related Changes in miR-143-3p:Igfbp5 Interactions Affect Muscle Regeneration
A common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age-related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA-143-3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR-143 as a regulator of the insulin growth factor-binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR-143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR-143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR-143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR-143-3p:Igfbp5 interactions in satellite cells with age may be responsible for age-related changes in satellite cell function
The WHO-DAS II: Psychometric Properties in the Measurement of Functional Health Status in Adults With Acquired Hearing Loss
The World Health Organization\u27s (WHO) Disability Assessment Scale II (WHO-DAS II) is a generic health-status instrument firmly grounded in the WHO\u27s International Classification of Functioning, Disability and Health (WHO-ICF). As such, it assesses functioning for six domains: communication, mobility, self-care, interpersonal, life activities, and participation. Domain scores aggregate to a total score. Because the WHO-DAS II contains questions relevant to hearing and communication, it has good face validity for use as an outcome measure for audiologic intervention. The purpose of the present study was to determine the psychometric properties of the WHO-DAS II on a sample of individuals with adult-onset hearing loss, including convergent validity, internal consistency, and test-retest stability. Convergent validity was established by examining correlations between the WHO-DAS II (domain and total scores) and the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Hearing Aid Handicap for the Elderly (HHIE), two disease-specific measures, as well as with the Short Form-36 for veterans (SF-36V), a second generic measure. Data on all four measures were collected from 380 older individuals with adult-onset hearing loss who were not hearing aid users. The results of the convergent validity analysis revealed that the WHO-DAS II communication domain score was moderately and significantly correlated with scores on the APHAB and the HHIE. WHO-DAS II interpersonal and participation domain scores and the total scores were also moderately and significantly correlated with HHIE scores. These findings support the validity of using the WHO-DAS II for assessing activity limitations and participation restrictions of adult-onset hearing loss. Several WHO-DAS II domain scores and the total score were also significantly and moderately-markedly correlated with scores from the SF-36V. These findings support the validity of the WHO-DAS II as a generic health-status instrument. Internal consistency reliability for all the domain scores was adequate for all but the interpersonal domain. Test-retest stability for all the domain scores was adequate. Critical difference values were calculated for use in clinical application of the WHO-DAS II. From these findings, we concluded that the WHO-DAS II communication, participation, and total scores can be used to examine the effects of adult-onset hearing loss on functional health status. Further work examining the utility of the WHO-DAS II as an outcome measure for hearing aid intervention is warranted
Building Information Modelling (BIM): a route for geological models to have real world impact
The rapid rise of Building Information Modelling (BIM) represents a major opportunity for Geological
Survey Organisations (GSO) to make their data and in particular three-dimensional geological models
accessible to the civil engineering and construction industry. The paper presents how GSOs and the
private sector are preparing themselves for a possible paradigm shift with the vision of a ‘live’ ground
model becoming a possibility, leading to real efficiency gains and risk reduction during construction and
throughout the life time of an asset
Genetic Diversity of Near Genome-Wide Hepatitis C Virus Sequences during Chronic Infection: Evidence for Protein Structural Conservation Over Time
Infection with hepatitis C virus (HCV) is one of the leading causes of chronic hepatitis, liver cirrhosis and end-stage liver disease worldwide. The genetics of HCV infection in humans and the disease course of chronic hepatitis C are both remarkably variable. Although the response to interferon treatment is largely dependent on HCV genotypes, whether or not a relationship exists between HCV genome variability and clinical course of hepatitis C disease still remains unknown. To more thoroughly understand HCV genome evolution over time in association with disease course, near genome-wide HCV genomes present in 9 chronically infected participants over 83 total study years were sequenced. Overall, within HCV genomes, the number of synonymous substitutions per synonymous site (dS) significantly exceeded the number of non-synonymous substitutions per site (dN). Although both dS and dN significantly increased with duration of chronic infection, there was a highly significant decrease in dN/dS ratio in HCV genomes over time. These results indicate that purifying selection acted to conserve viral protein structure despite persistence of high level of nucleotide mutagenesis inherent to HCV replication. Based on liver biopsy fibrosis scores, HCV genomes from participants with advanced fibrosis had significantly greater dS values and lower dN/dS ratios compared to participants with mild liver disease. Over time, viral genomes from participants with mild disease had significantly greater annual changes in dN, along with higher dN/dS ratios, compared to participants with advanced fibrosis. Yearly amino acid variations in the HCV p7, NS2, NS3 and NS5B genes were all significantly lower in participants with severe versus mild disease, suggesting possible pathogenic importance of protein structural conservation for these viral gene products
Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
The aetiology of Kawasaki disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host ‘omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple ‘omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering, and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infections at the transcriptomic and proteomic levels through comparison of ‘omic profiles from children with KD to those with bacterial and viral infections. Pathways activated in patients with KD included those involved in anti-viral and anti-bacterial responses. Unsupervised clustering showed that the majority of KD patients clustered with bacterial patients on both ‘omic levels, whilst application of diagnostic signatures specific for bacterial and viral infections revealed that many transcriptomic KD samples had low probabilities of having bacterial or viral infections, suggesting that KD may be triggered by a different process not typical of either common bacterial or viral infections. Clustering based on the transcriptomic and proteomic responses during KD revealed three clusters of KD patients on both ‘omic levels, suggesting heterogeneity within the inflammatory response during KD. The observed heterogeneity may reflect differences in the host response to a common trigger, or variation dependent on different triggers of the condition
Genomic investigations of unexplained acute hepatitis in children
Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK. Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells. Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Genomic investigations of unexplained acute hepatitis in children
Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1. Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells. Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
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