Remote sensing of glacier change (1965 - 2021) and identification of surge-type glaciers on Severnaya Zemlya, Russian High Arctic

Glaciers in the Russian High Arctic have undergone accelerated mass loss due to atmospheric and oceanic warming in the Barents-Kara Seas region. Most studies have concentrated on the western Barents-Kara sector, despite evidence of accelerating mass loss as far east as Severnaya Zemlya. However, long-term trends in glacier change on Severnaya Zemlya are largely unknown and this record may be complicated by surge-type glaciers. Here, we present a long-term assessment of glacier change (1965-2021) on Severnaya Zemlya and a new inventory of surge-type glaciers using declassified spy-satellite photography (KH-7/9 Hexagon) and optical satellite imagery (ASTER, Sentinel-2A, Landsat 4/5 TM & 8 OLI). Glacier area reduced from 17,053 km2 in 1965 to 16,275 in 2021 (-5%; mean: -18%, max: -100%), with areal shrinkage most pronounced at land-terminating glaciers on southern Severnaya Zemlya, where there is a recent (post-2010s) increase in summer atmospheric temperatures. We find that surging may be more widespread than previously thought, with three glaciers classified confirmed as surge-type, eight as likely to have surged and nine as possible, comprising 11% of Severnaya Zemlya’s 190 glaciers (37% by area). Under continued warming, we anticipate accelerated retreat and increased likelihood of surging as basal thermal regimes shift

Remote sensing of glacier change (1965–2021) and identification of surge-type glaciers on Severnaya Zemlya, Russian High Arctic

Glaciers in the Russian High Arctic have undergone accelerated mass loss due to atmospheric and oceanic warming in the Barents–Kara Sea region. Most studies have concentrated on the western Barents–Kara sector, despite evidence of accelerating mass loss as far east as Severnaya Zemlya. However, long-term trends in glacier change on Severnaya Zemlya are largely unknown and this record may be complicated by surge-type glaciers. Here, we present a long-term assessment of glacier change (1965–2021) on Severnaya Zemlya and a new inventory of surge-type glaciers using declassified spy-satellite photography (KH-7/9 Hexagon) and optical satellite imagery (ASTER, Sentinel-2A, Landsat-4/5 TM and 8 OLI). Glacier area reduced from 17 053 km2 in 1965 to 16 275 in 2021 (−5%; mean: −18%, max: −100%), with areal shrinkage most pronounced at land-terminating glaciers on southern Severnaya Zemlya, where there is a recent (post-2010s) increase in summer atmospheric temperatures. We find that surging may be more widespread than previously thought, with three glaciers classified confirmed as surge-type, eight as likely to have surged and nine as possible, comprising 11% of Severnaya Zemlya's 190 glaciers (37% by area). Under continued warming, we anticipate accelerated retreat and increased likelihood of surging as basal thermal regimes shift

Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

From absent to present pasts: civil society, democracy and the shifting place of memory in Brazil

This paper takes Alexis de Tocqueville’s concern with the emotional life of citizens as a cue for exploring the role of collective memory within ‘the self-organizing sphere’ and asking how the invocation of memory affects progress towards democracy. The paper hones in on the Brazilian experience, re-assessing Brazil’s amnesiac past as well as its much lauded ‘turn to memory’. Against common assertions that Brazil’s ‘turn to memory’ will enhance the country’s democratic credentials, this paper argues that the move from an ‘absent’ to a ‘present’ past in Brazil in fact bodes rather mixed prospects for the country’s democratic deepening

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis,independent of RANK ligand, which disrupts normal bone homeostasisleading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications

Stable Cytotoxic T Cell Escape Mutation in Hepatitis C Virus Is Linked to Maintenance of Viral Fitness

Mechanisms by which hepatitis C virus (HCV) evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA) class I-restricted epitopes targeted by CD8+ T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood. Previous work showed that the HCV quasispecies in a persistently infected chimpanzee accumulated multiple mutations in numerous class I epitopes over a period of 7 years. During the acute phase of infection, one representative epitope in the C-terminal region of the NS3/4A helicase, NS31629-1637, displayed multiple serial amino acid substitutions in major histocompatibility complex (MHC) anchor and T cell receptor (TCR) contact residues. Only one of these amino acid substitutions at position 9 (P9) of the epitope was stable in the quasispecies. We therefore assessed the effect of each mutation observed during in vivo infection on viral fitness and T cell responses using an HCV subgenomic replicon system and a recently developed in vitro infectious virus cell culture model. Mutation of a position 7 (P7) TCR-contact residue, I1635T, expectedly ablated the T cell response without affecting viral RNA replication or virion production. In contrast, two mutations at the P9 MHC-anchor residue abrogated antigen-specific T cell responses, but additionally decreased viral RNA replication and virion production. The first escape mutation, L1637P, detected in vivo only transiently at 3 mo after infection, decreased viral production, and reverted to the parental sequence in vitro. The second P9 variant, L1637S, which was stable in vivo through 7 years of follow-up, evaded the antigen-specific T cell response and did not revert in vitro despite being less optimal in virion production compared to the parental virus. These studies suggest that HCV escape mutants emerging early in infection are not necessarily stable, but are eventually replaced with variants that achieve a balance between immune evasion and fitness for replication

Assessing robustness of carotid artery CT angiography radiomics in the identification of culprit lesions in cerebrovascular events

Funder: School of Clinical Medicine, University of Cambridge; doi: http://dx.doi.org/10.13039/501100007552Funder: Frank Edward Elmore FundFunder: National Institute for Health Research (NIHR) Imperial Biomedical Research CentreFunder: British Heart Foundation Cambridge Centre of Research ExcellenceFunder: Royal College of Surgeons of England; doi: http://dx.doi.org/10.13039/501100000297Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Funder: AstraZeneca Oncology RFunder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Funder: Leverhulme Trust; doi: http://dx.doi.org/10.13039/501100000275Funder: Cantab Capital Institute for the Mathematics of InformationFunder: Alan Turing Institute; doi: http://dx.doi.org/10.13039/100012338Funder: NIHR Cambridge Biomedical Research CentreFunder: Higher Education Funding Council for England; doi: http://dx.doi.org/10.13039/501100000384Abstract: Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk

Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens

This is the final version of the article. Available from the publisher via the DOI in this record.Background: Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses. Results: We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses. Conclusions: Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.This article is a joint effort of the working group TRANSBEE and an outcome of two workshops kindly supported by sDiv, the Synthesis Centre for Biodiversity Sciences within the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Science Foundation (FZT 118). New datasets were performed thanks to the Insect Pollinators Initiative (IPI grant BB/I000100/1 and BB/I000151/1), with participation of the UK-USA exchange funded by the BBSRC BB/I025220/1 (datasets #4, 11 and 14). The IPI is funded jointly by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government and the Wellcome Trust, under the Living with Environmental Change Partnershi