Citizenship, community, and counter-terrorism : UK security discourse, 2001-2011

This paper analyses a corpus of UK policy documents which sets out national security policy as an exemplar of the contemporary discourse of counter-terrorism in Europe, the USA and worldwide. A corpus of 148 documents (c. 2.8 million words) was assembled to reflect the security discourse produced by the UK government before and after the 7/7 attacks on the London Transport system. To enable a chronological comparison, the two sub-corpora were defined: one relating to a discourse of citizenship and community cohesion (2001-2006); and one relating to the ‘Preventing Violent Extremism’ discourse (2007-2011). Wordsmith Tools (Scott 2008) was used to investigate keywords and patterns of collocation. The results present themes emerging from a comparative analysis of the 100 strongest keywords in each sub- corpus; as well as a qualitative analysis of related patterns of the collocation, focusing inparticular on features of connotation and semantic prosody

Global English and Political Economy

In this book, John O’Regan examines the role of political economy in the worldwide spread of English and traces the origins and development of the dominance of English to the endless accumulation of capital in a capitalist world-system. O’Regan combines Marxist perspectives of capital accumulation with world-systems analysis, international political economy, and studies of imperialism and empire to present a historical account of the ‘free riding’ of English upon the global capital networks of the capitalist world-system. Relevant disciplinary perspectives on global English are examined in this light, including superdiversity, translanguaging, translingual practice, trans-spatiality, language commodification, World Englishes and English as a Lingua Franca. Global English and Political Economy presents an original historical and interdisciplinary interpretation of the global ascent of English, while also raising important theoretical and practical questions for perspectives which suggest that the time of the traditional models of English is past. Providing an introduction to key theoretical perspectives in political economy, this book is essential reading for advanced students and researchers in applied linguistics, World Englishes and related fields of study

Swiss Multilingualism and Global English: Bourdieusian Capitals in Contestation

This paper reports on a small-scale research study into the beliefs of teenagers in Switzerland on Swiss national languages and their status relative to English. High school students (n = 232) in the French-speaking city of Lausanne completed a questionnaire about the economic, social, cultural and symbolic value of German, Italian and English. The data was then analysed quantitatively by computing the means, standard deviations, significance, and effect sizes, and interpreted in relation to the capitals of Bourdieu. The findings corroborate previous studies on the widespread and shared high value ascribed to English for economic, social, cultural and symbolic purposes. They also reveal, however, a solid respect and support for Swiss multilingualism. The study thus suggests that the students’ high estimation of English is not at the expense of the national languages, German and Italian. Even though students value Swiss multilingualism, they nevertheless rank the economic capital of German higher than Italian. Finally, the apparent accommodation of English beside national languages is explained in regard to the Swiss multilingual tradition

Patterns of psychotropic prescribing and polypharmacy in older hospitalized patients in Ireland: the influence of dementia on prescribing

Neuropsychiatric Symptoms (NPS) are ubiquitous in dementia and are often treated pharmacologically. The objectives of this study were to describe the use of psychotropic, anti-cholinergic, and deliriogenic medications and to identify the prevalence of polypharmacy and psychotropic polypharmacy, among older hospitalized patients in Ireland, with and without dementia. All older patients (≥ 70 years old) that had elective or emergency admissions to six Irish study hospitals were eligible for inclusion in a longitudinal observational study. Of 676 eligible patients, 598 patients were recruited and diagnosed as having dementia, or not, by medical experts. These 598 patients were assessed for delirium, medication use, co-morbidity, functional ability, and nutritional status. We conducted a retrospective cross-sectional analysis of medication data on admission for 583/598 patients with complete medication data, and controlled for age, sex, and co-morbidity. Of 149 patients diagnosed with dementia, only 53 had a previous diagnosis. At hospital admission, 458/583 patients experienced polypharmacy (≥ 5 medications). People with dementia (PwD) were significantly more likely to be prescribed at least one psychotropic medication than patients without dementia (99/147 vs. 182/436; p < 0.001). PwD were also more likely to experience psychotropic polypharmacy (≥ two psychotropics) than those without dementia (54/147 vs. 61/436; p < 0.001). There were no significant differences in the prescribing patterns of anti-cholinergics (23/147 vs. 42/436; p = 0.18) or deliriogenics (79/147 vs. 235/436; p = 0.62). Polypharmacy and psychotropic drug use is highly prevalent in older Irish hospitalized patients, especially in PwD. Hospital admission presents an ideal time for medication reviews in PwD

Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis. AIM: The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis. RESULTS: DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement. Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis

Cultural relativism and the discourse of intercultural communication: aporias of praxis in the intercultural public sphere

The premise of much intercultural communication pedagogy and research is to educate people from different cultures towards open and transformative positions of mutual understanding and respect. This discourse in the instance of its articulation realises and sustains Intercultural Communication epistemologically – as an academic field of social enquiry, and judgementally – as one which locates itself on a moral terrain. By adopting an ethical stance towards difference, the discourse of intercultural communication finds itself caught in a series of aporias, or performative contradictions, where interculturalists are projected simultaneously into positions of cultural relativism on the one hand and ideological totalism on the other. Such aporias arise because the theoretical premises upon which the discourse relies are problematic. We trace these thematics to a politics of presence operating within the discourse of intercultural communication and links this to questions of judgement and truth in the intercultural public sphere. We propose that the politics of presence be set aside in favour of an intercultural praxis which is oriented to responsibility rather than to truth

Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. OBJECTIVES: The goal of this study was to compare lifetime outcomes and cardiovascular phenotypes according to the presence of rare variants in sarcomere-encoding genes among middle-aged adults. METHODS: This study analyzed whole exome sequencing and cardiac magnetic resonance imaging in UK Biobank participants stratified according to sarcomere-encoding variant status. RESULTS: The prevalence of rare variants (allele frequency <0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n = 5,712; 1 in 35), and the prevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was 0.25% (n = 493; 1 in 407). SARC-HCM-P/LP variants were associated with an increased risk of death or major adverse cardiac events compared with controls (hazard ratio: 1.69; 95% confidence interval [CI]: 1.38-2.07; P < 0.001), mainly due to heart failure endpoints (hazard ratio: 4.23; 95% CI: 3.07-5.83; P < 0.001). In 21,322 participants with both cardiac magnetic resonance imaging and whole exome sequencing, SARC-HCM-P/LP variants were associated with an asymmetric increase in left ventricular maximum wall thickness (10.9 ± 2.7 mm vs 9.4 ± 1.6 mm; P < 0.001), but hypertrophy (≥13 mm) was only present in 18.4% (n = 9 of 49; 95% CI: 9%-32%). SARC-HCM-P/LP variants were still associated with heart failure after adjustment for wall thickness (hazard ratio: 6.74; 95% CI: 2.43-18.7; P < 0.001). CONCLUSIONS: In this population of middle-aged adults, SARC-HCM-P/LP variants have low aggregate penetrance for overt HCM but are associated with an increased risk of adverse cardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease

Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy

BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.This work was supported in part by grants from the Instituto de Salud Carlos III (ISCIII) (PI15/01551, PI17/01941 and CB16/11/00432 to P.G-P. and L.A-P.), the Spanish Ministry of Economy and Competitiveness (SAF2015-71863-REDT to P.G-P.), the John S. LaDue Memorial Fellowship at Harvard Medical School (Y.K.), Wellcome Trust (107469/Z/15/Z to J.S.W.), Medical Research Council (intramural awards to S.A.C. and J.S.W; MR/M003191/1 to U.T), National Institute for Health Research Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London (P.J.B., S.A.C., J.S.W.), National Institute for Health Research Biomedical Research Centre at Imperial College London Healthcare National Health Service Trust and Imperial College London (D.O.R., S.A.C., S.P., J.S.W.), Sir Henry Wellcome Postdoctoral Fellowship (C.N.T.), Rosetrees and Stoneygate Imperial College Research Fellowship (N.W.), Fondation Leducq (S.A.C., C.E.S., J.G.S.), Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health (UK; HICF-R6-373; S.A.C., P.J.B., J.S. W.), the British Heart Foundation (NH/17/1/32725 to D.O.R.; SP/10/10/28431 to S.A.C), Alex’s Lemonade Stand Foundation (K.G.), National Institutes of Health (R.A.: U01CA097452, R01CA133881, and U01CA097452; Z.A.: R01 HL126797; B.K.: R01 HL118018 and K23-HL095661; J.G.S. and C.E.S.: 5R01HL080494, R01HL084553), and the Howard Hughes Medical Institute (C.E.S.). The Universitario Puerta de Hierro and Virgen de la Arrixaca Hospitals are members of the European Reference Network on Rare and Complex Diseases of the Heart (Guard-Heart; http://guard-heart.ern-net.eu). This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe”.S