18,581 research outputs found
Cardiovascular Medicine and Genomics
No full textClinicians have always personalised patient management.
There is a growing momentum to improve this further
through the integration of genomic information into
clinical care. Here we present an overview of the current
role of genetics and genomics in cardiovascular medicine,
alongside our expectations for the future
Emergence of a novel lineage containing a prophage in emm/M3 group A Streptococcus associated with upsurge in invasive disease in the UK
No full textA sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isolates during the winter of 2008/09 prompted the initiation of enhanced surveillance in England. In order to characterise the population of emm/M3 GAS within the UK and determine bacterial factors that might be responsible for this upsurge, 442 emm/M3 isolates from cases of invasive and non-invasive infections during the period 2001 to 2013 were subjected to whole genome sequencing. MLST analysis differentiated emm/M3 isolates into three sequence types (STs): ST15, ST315 and ST406. Analysis of the whole genome SNP-based phylogeny showed that the majority of isolates from the 2008-2009 upsurge period belonged to a distinct lineage characterised by the presence of a prophage carrying the speC exotoxin and spd1 DNAase genes but loss of two other prophages considered typical of the emm/M3 lineage. This lineage was significantly associated with the upsurge in iGAS cases and we postulate that the upsurge could be attributed in part to expansion of this novel prophage-containing lineage within the population. The study underlines the importance of prompt genomic analysis of changes in the GAS population, providing an advanced public health warning systems for newly emergent, pathogenic strains
Musica Viva concert Thursday 2nd November 2023 - Taikoz, Side By Side
No full textThe author was invited to provide a concert review of Taikoz's Side By Side performance in November 2023 at Lazenby Hall, the University of New England which was touring with the National Musica Viva concert series. Artistic director, Ian Cleworth describes their new Side By Side program as a response to the pandemic through 'an emotional and intimate exploration of shared human experience: our hopes, anxieties, contentment, and desires'. Based on the Hachijō-style of taiko playing, Side By Side takes on further meanings in this program, including the two-player method of playing a single drum, where one provides the underlying beat and the other builds on this rhythmical foundation with unique and improvised rhythms. This collaborative and improvisatory ingenuity was displayed throughout
155.03 / A Letter to the author of an Address to all rationalists in Great Britain, published in the Old-England-journal, Nov. the 30th, 1745. With an appendix...
No full textA Letter to the author of an Address to all rationalists in Great Britain, published in the Old-England-journal, Nov. the 30th, 1745. With an appendix..
‘A School Under Scrutiny: A Personal Account of The Impact of Inclusion on a Small Primary School in England’
No full textThis paper presents a personal account of a teacher who has
responsibility for the coordination of pupils with special educational
needs. In this paper she has been referred to as Sally. Sally teaches in a
school in England with a significantly high proportion of pupils with
special educational needs. The account demonstrates how current
measures of school effectiveness in England have disadvantaged a small
school which has an outstanding local reputation for inclusion. This has
led to increased levels of surveillance for the teachers who have chosen
to work in this school, whilst other local schools enjoy the benefits of
having good reputations. The paper raises questions about whether
inclusion is too much of a risk for schools given that they operate within
a climate of performativity. Additionally, it raises questions about
whether current measures of school effectiveness are fair on those
schools with more diverse populations
Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
No full textHuman 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays
Utopia Ltd. : Ideologies of Social Dreaming in England 1870-1900 /
No full textThis book uncovers the historical preconditions for the explosive revival of utopian literature at the nineteenth-century fin de siècle , and excavates its ideological content. It marks a contribution not only to the literary and cultural history of the late-Victorian period, and to the expanding field of utopian studies, but to the development of a Marxist critique of utopianism. The book is particularly concerned with three kinds of political utopia or anti-utopia, those of 'state socialism', feminism, and anti-communism (the characteristic expression of this last example being the cacotopia ). After an extensive contextual account of the politics of utopia in late-nineteenth century England, it devotes a chapter to each of these topics before developing an original reinterpretation of William Morris's seminal Marxist utopia, News from Nowhere .Includes bibliographical references and index.Preliminary Material -- Introduction -- History and Utopia at the Fin de Siècle -- State Socialism and Utopia -- Feminism and Utopia -- Anti-Communism and the Cacotopia -- Utopia and the Present in News from Nowhere -- Conclusion -- References -- Index -- Historicalmaterialism Book Series.This book uncovers the historical preconditions for the explosive revival of utopian literature at the nineteenth-century fin de siècle , and excavates its ideological content. It marks a contribution not only to the literary and cultural history of the late-Victorian period, and to the expanding field of utopian studies, but to the development of a Marxist critique of utopianism. The book is particularly concerned with three kinds of political utopia or anti-utopia, those of 'state socialism', feminism, and anti-communism (the characteristic expression of this last example being the cacotopia ). After an extensive contextual account of the politics of utopia in late-nineteenth century England, it devotes a chapter to each of these topics before developing an original reinterpretation of William Morris's seminal Marxist utopia, News from Nowhere .Description based on print version record
Increased COVID-19 mortality rate in rare disease patients:a retrospective cohort study in participants of the Genomics England 100,000 Genomes project
No full textBACKGROUND: Several common conditions have been widely recognised as risk factors for COVID-19 related death, but risks borne by people with rare diseases are largely unknown. Therefore, we aim to estimate the difference of risk for people with rare diseases comparing to the unaffected.METHOD: To estimate the correlation between rare diseases and COVID-19 related death, we performed a retrospective cohort study in Genomics England 100k Genomes participants, who tested positive for Sars-Cov-2 during the first wave (16-03-2020 until 31-July-2020) of COVID-19 pandemic in the UK (n = 283). COVID-19 related mortality rates were calculated in two groups: rare disease patients (n = 158) and unaffected relatives (n = 125). Fisher's exact test and logistic regression was used for univariable and multivariable analysis, respectively.RESULTS: People with rare diseases had increased risk of COVID19-related deaths compared to the unaffected relatives (OR [95% CI] = 3.47 [1.21- 12.2]). Although, the effect was insignificant after adjusting for age and number of comorbidities (OR [95% CI] = 1.94 [0.65-5.80]). Neurology and neurodevelopmental diseases was significantly associated with COVID19-related death in both univariable (OR [95% CI] = 4.07 [1.61-10.38]) and multivariable analysis (OR [95% CI] = 4.22 [1.60-11.08]).CONCLUSIONS: Our results showed that rare disease patients, especially ones affected by neurology and neurodevelopmental disorders, in the Genomics England cohort had increased risk of COVID-19 related death during the first wave of the pandemic in UK. The high risk is likely associated with rare diseases themselves, while we cannot rule out possible mediators due to the small sample size. We would like to raise the awareness that rare disease patients may face increased risk for COVID-19 related death. Proper considerations for rare disease patients should be taken when relevant policies (e.g., returning to workplace) are made
Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease
No full textMonoallelic mutations of DNAJB11 were recently described in seven pedigrees with atypical clinical presentations of autosomal dominant polycystic kidney disease. DNAJB11 encodes one of the main cofactors of the endoplasmic reticulum chaperon BiP, a heat-shock protein required for efficient protein folding and trafficking. Here we conducted an international collaborative study to better characterize the DNAJB11-associated phenotype. Thirteen different loss-of-function variants were identified in 20 new pedigrees (54 affected individuals) by targeted next-generation sequencing, whole-exome sequencing or whole-genome sequencing. Amongst the 77 patients (27 pedigrees) now in total reported, 32 reached end stage kidney disease (range, 55-89 years, median age 75); without a significant difference between males and females. While a majority of patients presented with non-enlarged polycystic kidneys, renal cysts were inconsistently identified in patients under age 45. Vascular phenotypes, including intracranial aneurysms, dilatation of the thoracic aorta and dissection of a carotid artery were present in four pedigrees. We accessed Genomics England 100,000 genomes project data, and identified pathogenic variants of DNAJB11 in nine of 3934 probands with various kidney and urinary tract disorders. The clinical diagnosis was cystic kidney disease for eight probands and nephrocalcinosis for one proband. No additional pathogenic variants likely explaining the kidney disease were identified. Using the publicly available GnomAD database, DNAJB11 genetic prevalence was calculated at 0.85/10.000 individuals. Thus, establishing a precise diagnosis in atypical cystic or interstitial kidney disease is crucial, with important implications in terms of follow-up, genetic counseling, prognostic evaluation, therapeutic management, and for selection of living kidney donors
First Impressions Count: Serious detections arising from Criminal Justice Samples
No full textDNA samples on the England and Wales national database matching those found at scenes of serious violent or sexual crimes were identified. The earlier offence leading the sample to appear on the database was noted. The bulk (60-84% according to inclusion criteria) involved theft, drug or other offending. The result, indicating offender versatility, is consistent with most research on criminal careers. Its importance for operational police lies in identifying the contribution made by DNA samples taken after less serious offences in clearing subsequent serious crime, and the importance of taking such samples from as wide a list of apparently 'trivial' crime types as possible. Examining specific relationships between early and later offences revealed a significant link between providing a DNA sample following a drug offence and subsequently committing murder.Full Tex
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