A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya

On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders >20 m in diameter, and scoured the valley walls up to 220 m above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

GENCODE reference annotation for the human and mouse genomes

The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.National Human Genome Research Institute of the National Institutes of Healt

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Imagination, theology, and literature (D. W. D. Shaw memorial lecture 2022)

In the first annual D. W. D. Shaw memorial lecture, delivered on 9 February 2022 Prof Paul Fiddes considers the human capacity for imagination, theology, and the literary arts. Looking at the interplay between creativity and order, Fiddes underscores the indispensable role that images play in theology alongside its commitment to concepts, and argues for the necessity of imagination for the work of theology as a response to God’s self-revelation. Without it, he contends, theology finds itself devoid of movement and life, stuck in an attempt to enforce complete conceptual control on imagination’s creations

Divine authority and covenant community in contemporary culture

The question I address is: how might a theology of authority be conceived in the light of questions raised by what is termed 'post-modernity'? Is it possible to articulate a theology of authority coming to the church community 'from God' that avoids an oppressive and alienating heteronomy? The thesis explores the question of authority as of vital importance in the sociological dimension of religion, calling for legitimisation (in light of claims made for itself) and as obligatory in the theological sphere. For this reason the project involves two methodologies (theological and sociological/ethnographic). While this investigation is relevant to all sections of the Christian church, particular attention is paid to Baptist churches in the UK, since they hold a concept in their tradition that I suggest is valuable in answering the question of the thesis, namely that of covenant. Within the Christian tradition there is an inner 'problematic' relating the personal authority of Christ to the forms of institution (church) and text (scripture). I explore this with a brief survey of theological authority as found in the fourfold foundation of scripture, tradition, reason and experience. From this is developed a brief theological and Christological reflection on divine authority and covenant theology as found in Karl Barth and his response to the 'inner problematic'. Within contemporary culture I view authority through the lens of so-called 'postmodernism', identifying four challenges to the notion of 'external authority' (all of which exemplify a move from the external to internal, and objective to subjective approaches to authority). This is further explored by means of qualitative research with one-to-one interviews conducted in a Baptist church in York. This data is reflected upon by means of ethnography and 'judicious narratives', especially in dialogue with material from Guest ('congregational study'), Heelas and Woodhead ('subjectivised-self') and Healy ('theodramatic horizon' and 'practical-prophetic ecclesiology'), providing an intersection between the language of theology and sociology. The concept of church as covenant community is explored in Baptist and (more briefly) Anglican traditions, leading to a constructive proposal that both the inner-church 'problematic' and the 'postmodern' challenge to authority might begin to be resolved with the notion of covenant. It is within this context of relationship, human and divine, that the authoritative and revelatory Word of God, the story that is Christ, is found in community and praxis. Here is a 'triangulating' relationship between authority, story and covenant revealing divine authority in a non-coercive way and relevant to contemporary culture.This thesis is not currently available in ORA

Selfless love and human flourishing : a theological and a secular perspective in dialogue

The point of departure of this thesis is derived from a modern tendency to create a dichotomy between selfless love and human flourishing. Modern attempts to liberate the human being from heteronomous oppression and the moral norms promoting this have sometimes led to the conclusion that selfless love is harmful to human flourishing. Such a conclusion has gained momentum also through modernist re-conceptualisations of the self as an autonomous but empty consciousness which must guard itself against determination by the other. In effect, significant thinkers have replaced the notion of selfless love with a call for self-assertion over against the other, as key to the individual person’s well-being. This has been matched by Christian dismissals of the individual’s pursuit of human flourishing. In the face of modern insights into the ‘desirous’ nature of the human being, modern Christian theology has equally struggled to sustain the tension between the traditional Christian notion of selfless or self-giving love and human beings’ desire to affirm themselves and to find personal fulfilment in this world. Strands of Christian theology have, for instance, affirmed a self-surrendering love at the cost of dismissing the individual’s worldly desires entirely. In this thesis, I outline this situation in modern thought and its problematic consequences. With a view to discerning whether selfless love and human flourishing can be re-connected, I then undertake close studies of the theologian Paul Tillich’s and the moral philosopher and novelist Iris Murdoch’s conceptualisations of the self and of love. As I will argue, Tillich’s and Murdoch’s engagement with modern thought leads them to develop accounts of the self, which correspond with understandings of love as both selfless and conducive to human flourishing. On the basis of their thought I thus argue that selfless love and human flourishing can be understood as interdependent even today.EThOS - Electronic Theses Online ServiceGBUnited Kingdo