34 research outputs found

    To Each According to their Needs: Anarchist Praxis as a Resource for Byzantine Theological Ethics

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    I argue that anarchist ideas for organising human communities could be a useful practical resource for Christian ethics. I demonstrate this firstly by introducing the main theological ideas underlying Maximus the Confessor’s ethics, a theologian respected and important in a number of Christian denominations. I compare practical similarities in the way in which ‘love’ and ‘well-being’ are interpreted as the telos of Maximus and Peter Kropotkin’s ethics respectively. I further highlight these similarities by demonstrating them in action when it comes attitudes towards property. I consequently suggest that there are enough similarities in practical aims, for Kropotkin’s ideas for human organising to be useful to Christian ethicists

    The Cosmology of St Maximus the Confessor as a Basis for Ecological and Humanitarian Ethics

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    This paper explores the cosmology of St Maximus the Confessor and its relevance for contemporary ethics. It takes as it’s starting point two papers on Maximus’ cosmology and environmental ethics (Bordeianu, 2009; Munteanu, 2010) and from there argues that we can not consider environmental ethics in isolation from other ethical issues. This, as both Ware and Keselopoulos have also pointed out, is because the environmental crisis is actually a crisis in the human heart and in human attitudes toward everything about us. The paper goes through some key areas in Maximus’ cosmology according to his own formula of creation – movement – rest and considers at each stage the implications of this theology for the way the human should be living and treating other beings. The main sources for this exploration are Ambiguum 7, Ambiguum 41, and The Mystagogia with especial focus on the doctrine of the logoi and the divisions of nature. The paper concludes that Bordeianu and Munteanu are right to consider Maximus’ theology to be of ecological relevance, but that this relevance comes from the radical ethical statement being made about human activity. Maximus’ theology points the human toward becoming in the likeness of Christ who unites heaven and earth through love. The love of Christ when considered in an ethical context stands as a formidable challenge to current attitudes and institutions that advocate the exploitation and destruction of human or non-human creation

    Revolution in the Microcosm: Love and Virtue in the Cosmological Ethics of St Maximus the Confessor

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    I explore virtue and love in Maximus the Confessor’s theology with an aim to drawing an ethics from it relevant to the present day. I use a meta-ethical framework derived from contemporary virtue ethics and look at virtue as an instance of love within the context of Maximus’ cosmic theology. Virtue becomes a path that leads us towards love – who is God Himself. Virtue is thus about movement towards theosis. I describe virtue as a relationship between humans and God, brought about through the mutual practice of a life of ascesis from humans and grace from God. I look at the mediatoral role of humans as microcosms gathering up the universe in an image of Christ’s activity. In particular I analyse the way that human activity is simultaneously cosmic and ascetic; personal and communal. The ethic of virtue that we pursue is always caught up in a conversation about what creation gathered in love looks like. Using a number of tools derived from Maximus’ thought, I suggest that this ethics will necessarily transform our current communities and personal practices. Recognising the cosmic dimension of personal behaviour means that our communities must be scrutinised as extensions of our actions. As an example, I critique the state as an inadequate form of loving relationship, illustrating its systemic reliance on violence and ideologies of alienation and hatred. I give examples of alternative ways of human organising drawn from anarchist thought that might better enable us to love and, more importantly, enable us to call to account failures to love. I conclude that to seek theosis after the manner Maximus describes involves recognising our personal and communal failures to love. His holistic understanding of human purpose can help us see the cosmic dimension to personal ascetic practice and consequently set our sights on a more cosmic vision of love here in the present world

    Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

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    Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM\textit{CHM} in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

    Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

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    BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

    Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

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    Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

    Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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    Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype
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