| 1. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Brodic, Bojan, et al.
(author)
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Innovative seismic imaging of volcanogenic massive sulfide deposits, Neves-Corvo, Portugal - Part 1 : In-mine array
- 2021
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In: Geophysics. - : Society of Exploration Geophysicists. - 0016-8033 .- 1942-2156. ; 86:3, s. B165-B179
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Journal article (peer-reviewed)abstract
- To evaluate and upscale the feasibility of using exploration tunnels in an operating mine for active-source seismic imaging, a seismic experiment was conducted at the Neves-Corvo mine, in southern Portugal. Four seismic profiles were deployed in exploration drifts approximately 650 m beneath the ground surface, above the world-class Lombador volcanogenic massive sulfide deposit. In addition to the tunnel profiles, two perpendicular surface seismic profiles were deployed above the exploration tunnels. The survey was possible due to a newly developed prototype global positioning system (GPS) time transmitter enabling accurate GPS synchronization of cabled and nodal seismic recorders, below and on the surface. Another innovative acquisition aspect was a 1.65 t broadband, linear synchronous motor (LSM) driven - electric seismic vibrator (e-vib) used as the seismic source along two of the exploration tunnels. We have evaluated the challenges and innovations necessary for active-source tunnel seismic acquisition, characterized by high levels of vibrational noise from the mining activities. In addition, we evaluated the LSM vibrator's signal and overall seismic-data quality in this hard rock mining environment. Our processing results from the tunnel data and 3D reflection imaging of the Lombador deposit below the exploration tunnels were checked for consistency through constant-velocity 3D ray-tracing traveltime forward modeling. For imaging purposes, 3D Kirchhoff prestack depth and poststack time-migration algorithms were used, with both successfully imaging the targeted deposit. The results obtained show that active-source-seismic imaging using subsurface mining infrastructure of operational mines is possible. However, it requires innovative exploration strategies, a broadband seismic source, an accurate GPS-time system capable of transmitting GPS-time hundreds of meters below the surface, and careful processing. The results obtained open up possibilities for similar studies in different mining or tunneling projects.
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| 3. |
- Carvalho, Joao, et al.
(author)
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A drill-hole, geological and geophysical data-based 3D model for target generation in Neves-Corvo mine region, Portugal
- 2022
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In: International journal of earth sciences. - : Springer Nature. - 1437-3254 .- 1437-3262. ; 111, s. 403-424
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Journal article (peer-reviewed)abstract
- The Neves-Corvo world class Iberian Pyrite Belt volcanogenic massive sulphide (VMS) deposit located in southern Portugal, constitutes an important Cu-Zn-Pb active mine. Seven deposits are currently known, among which the Lombador deposit alone has estimated 150 Mt of massive sulphides. The life-time of the mine is dependent on the discovery of new exploration targets and it is vital to have accurate 3D geological models, not only to guide drilling campaigns but also to drive a winning/new strategy, which in the past has led to Semblana and Monte Branco discoveries: geophysical inversion and modelling. Furthermore, 3D geological models can contribute to the understanding of the tectonic and stratigraphic evolution of the region. Therefore, the goal of this study is to produce a realistic 3D geological model of the Neves-Corvo region, as only one model is presently publicly available: the PROMINE model, which includes the study area of this work and extends from Aljustrel to the border with Spain. Lundin Mining has also produced two unpublished, confidential models in 2007 and 2017. The latest Lundin model incorporates the same geophysical data used in this work (2D and 3D seismic reflection and time-domain electromagnetic (TEM) ground loop data) and approximately 7500 surface and underground drill-holes. The model presented in this research has much more detail than the 2012 PROMINE model in the Neves-Corvo region and uses an updated and revised drill-hole database with approximately 8000 drill-holes, revised geological cross-sections built from surface geology and drill-hole logs, new geological outcrop data, petrophysical and reprocessed geophysical data, and is therefore more detailed and accurate than any of the previous models, in particular the 2007 and PROMINE models. Land gravimetric and aeromagnetic data are also available in the study area but were not directly used to build the geological model but rather to investigate and check the model produced. Modelling was performed with industry standard software and the 3D curves resulting from the geological/geophysical interpretation were interpolated using different approaches to respect the hard data (interpretation lines and drill-holes). The resulting 3D stratigraphic surfaces required strong manual editing to respect the interpretation, due to the presence of folds, thrusts and tectonic nappes in the study area. The surfaces were afterwards tied to the drill-holes, resulting in a 3D model with great accuracy and detail in the near mining area and covering a larger area than previously available 3D geological models. The model has three major stratigraphic layers: the Mertola Flysch Formation and the Volcano-Sedimentary Complex (VSC), overlying the Phyllite-Quartzite Formation basement, and also the known VMS deposits (underlying the top of the Lower VSC) geometries according to drill-hole data. In the central part of the study area, where more drill-holes are available, the top of the Lower VSC sequence surface was also built. This approach will contribute to a better exploration drill-hole planning and the generation of new targets for exploration.
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| 4. |
- Dias, Pedro, et al.
(author)
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Geophysical investigation of the down-dip extension of the Lombador massive sulphide deposit, Neves-Corvo, Portugal
- 2021
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In: International journal of earth sciences. - : Springer Nature. - 1437-3254 .- 1437-3262. ; 110:3, s. 911-922
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Journal article (peer-reviewed)abstract
- The 150 Mt Lombador massive sulphide deposit is one of the seven known deposits of the Neves-Corvo mine. The deposit dips approximately 30o-35o to the NE and is open down dip, with current exploitation reaching down at 1 km depth. To investigate the possible downwards continuation of the deposit, a 1D constrained inversion of time-domain electromagnetic (TEM) ground loop data was conducted, followed by 3D electromagnetic (EM) forward modeling and a constrained 3D gravimetric inversion over the same area. To perform the EM and gravity modeling/inversion, a 3D geologic model was built using a density database comprising of approximately 300 drill-holes, and an electrical conductivity database with measurements from resistivity surveys and 1D inversion of the TEM data. The EM modeling shows that the Neves Formation shales are a regional conductive layer extending down to approximately 1.6 km depth in the Lombador area. This layer, often topped by massive sulphides, has an average density of 2.83 g/cm(3), whereas stockwork and massive sulphide reach on average 3.1 g/cm(3) and 4.5 g/cm(3), respectively. The 3D constrained gravity inversion results do not support the hypothesis of the presence of massive sulphides located in the down-dip direction of the Lombador deposit in the immediate vicinity of the known deposit. The lack of spatial resolution of the gravity grid, the study area limited size and the lack of information from within the basement suggest further studies are required to confirm the presence and amount of stockwork mineralization down-dip the Lombador deposit inside the Neves-Formation or the Phyllite-Quartzite basement.
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| 5. |
- Donoso, George A., et al.
(author)
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Innovative seismic imaging of volcanogenic massive sulfide deposits, Neves-Corvo, Portugal – Part 2 : Surface array
- 2021
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In: Geophysics. - : Society of Exploration Geophysicists. - 0016-8033 .- 1942-2156. ; 86:3, s. B181-B191
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Journal article (peer-reviewed)abstract
- Seismic methods are an affordable and effective way of studying the subsurface for mineral exploration. With the goal of testing new technologies for mineral exploration in highly challenging mining areas, in early 2019, an innovative seismic survey was conducted at the Neves-Corvo mine, south Portugal. We have focused on the data and results from the surface array data, whereas other work deals with the underground seismic data. The surface seismic survey consisted of two perpendicular 2D profiles positioned above the known world-class tier-1 Lombador deposit. Simultaneously, a survey inside the active underground mine took place, being unique because it included the testing of a prototype system that enabled accurate GPS-time (microsecond accuracy) synchronization inside the mine tunnels, approximately 650 m below the surface profiles. Due to the active mining operations, the surface data are noisy. To handle this, a carefully tailored processing algorithm was developed and applied to enhance reflections in the data, interpreted to originate from lithologic contacts and the Lombador deposit. The results and interpretations from 2D processing were validated taking advantage of the known deposit geometry using 3D exploding reflector modeling and pseudo-3D cross-dip analysis. These analyses suggest that there is an out-of-plane signature of the Lombador deposit on the surface data. Additionally, source points activated in the exploration tunnels and simultaneously recorded on the surface profiles allowed for the creation of a 2D velocity model that was used for migration and time-to depth conversion, providing a reliable 2D seismic section of the subsurface under the surface profiles. We determine that limited surface coverage 2D surveys and a velocity model derived from the tunnel-to-surface seismic recordings allow for imaging of key subsurface geologic structures and delineating mineral deposits of economic interest.
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| 6. |
- Donoso, George A., et al.
(author)
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Potential of legacy 2D seismic data for deep targeting and structural imaging at the Neves-Corvo massive sulphide-bearing deposit, Portugal
- 2020
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In: Geophysical Prospecting. - : WILEY. - 0016-8025 .- 1365-2478. ; 68:1, s. 44-61
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Journal article (peer-reviewed)abstract
- Seismic methods are becoming an established choice for deep mineral exploration after being extensively tested and employed for the past two decades. To investigate whether the early European mineral-exploration datasets had potential for seismic imaging that was overlooked, we recovered a low-fold legacy seismic dataset from the Neves-Corvo mine site in the Iberian Pyrite Belt in southern Portugal. This dataset comprises six 4-6 km long profiles acquired in 1996 for deep targeting. Using today's industry-scale processing algorithms, the world-class, ca. 150 Mt, Lombador massive sulphide and other smaller deposits were better imaged. Additionally, we also reveal a number of shallow but steeply dipping reflections that were absent in the original processing results. This study highlights that legacy seismic data are valuable and should be revisited regularly to take advantage of new processing algorithms and the experiences gained from processing such data in hard-rock environments elsewhere. Remembering that an initial processing job in hard rock should always aim to first obtain an overall image of the subsurface and make reflections visible, and then subsequent goals of the workflow could be set to, for example understanding relative amplitude ratios. The imaging of the known mineralization implies that this survey could likely have been among one of the pioneer studies in the world that demonstrated the capability of directly imaging massive sulphide deposits using the seismic method.
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| 7. |
- Feng, Shaohong, et al.
(author)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 8. |
- Gelabert, Pere, et al.
(author)
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Evolutionary History, Genomic Adaptation to Toxic Diet, and Extinction of the Carolina Parakeet
- 2020
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 30:1, s. 108-114
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Journal article (peer-reviewed)abstract
- As the only endemic neotropical parrot to have recently lived in the northern hemisphere, the Carolina parakeet (Conuropsis carolinensis) was an iconic North American bird. The last surviving specimen died in the Cincinnati Zoo in 1918 [1]. The cause of its extinction remains contentious: besides excessive mortality associated to habitat destruction and active hunting, their survival could have been negatively affected by its range having become increasingly patchy [2] or by the exposure to poultry pathogens [3, 4]. In addition, the Carolina parakeet showed a pre-dilection for cockleburs, an herbaceousplant that contains a powerful toxin, carboxyatractyloside, or CAT [5], which did not seem to affect them but made the birds notoriously toxic to most predators [3]. To explore the demographic history of this bird, we generated the complete genomic sequence of a preserved specimen held in a private collection in Espinelves (Girona, Spain), as well as of a close extant relative, Aratinga solstitialis. We identified two non-synonymous genetic changes in two highly conserved proteins known to interact with CAT that could underlie a specific dietary adaptation to this toxin. Our genomic analyses did not reveal evidence of a dramatic past demographic decline in the Carolina parakeet; also, its genome did not exhibit the long runs of homozygosity that are signals of recent inbreeding and are typically found in endangered species. As such, our results suggest its extinction was an abrupt process and thus likely solely attributable to human causes.
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| 9. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 10. |
- Witjes, J. Alfred, et al.
(author)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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