| 1. |
- Escala-Garcia, Maria, et al.
(författare)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 4. |
- Hirao, Yuki, et al.
(författare)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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| 5. |
- Yang, Xin, et al.
(författare)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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| 6. |
- Chandler, Benjamin M. P., et al.
(författare)
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Sub‐annual moraine formation at an active temperate Icelandic glacier
- 2020
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Ingår i: Earth Surface Processes and Landforms. - : Wiley. - 0197-9337 .- 1096-9837. ; 45:7, s. 1622-1643
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents detailed geomorphological and sedimentological investigations of small recessional moraines at Fjallsjökull, an active temperate outlet of Öræfajökull, southeast Iceland. The moraines are characterised by striking sawtooth or hairpin planforms, which are locally superimposed, giving rise to a complex spatial pattern. We recognise two distinct populations of moraines, namely a group of relatively prominent moraine ridges (mean height ~1.2 m) and a group of comparatively low‐relief moraines (mean height ~0.4 m). These two groups often occur in sets/systems, comprising one pronounced outer ridge and several inset smaller moraines. Using a representative subsample of the moraines, we establish that they form by either (i) submarginal deformation and squeezing of subglacial till or (ii) pushing of extruded tills. Locally, proglacial (glaciofluvial) sediments are also incorporated within the moraines during pushing. For the first time, to our knowledge, we demonstrate categorically that these moraines formed sub‐annually using repeat uncrewed aerial vehicle (UAV) imagery. We present a conceptual model for sub‐annual moraine formation at Fjallsjökull that proposes the sawtooth moraine sequence comprises (i) sets of small squeeze moraines formed during melt‐driven squeeze events and (ii) larger push moraines formed during winter re‐advances. We suggest the development of this process‐form regime is linked to a combination of elevated temperatures, high surface meltwater fluxes to the bed, and emerging basal topography (a depositional overdeepening). These factors result in highly saturated subglacial sediments and high porewater pressures, which induces submarginal deformation and ice‐marginal squeezing during the melt season. Strong glacier recession during the summer, driven by elevated temperatures, allows several squeeze moraines to be emplaced. This process‐form regime may be characteristic of active temperate glaciers receding into overdeepenings during phases of elevated temperatures, especially where their englacial drainage systems allow efficient transfer of surface meltwater to the glacier bed near the snout margin.
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| 7. |
- Chandler, Benjamin M. P., et al.
(författare)
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The glacial landsystem of Fjallsjökull, Iceland : Spatial and temporal evolution of process-form regimes at an active temperate glacier
- 2020
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Ingår i: Geomorphology. - : Elsevier BV. - 0169-555X .- 1872-695X. ; 361
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Tidskriftsartikel (refereegranskat)abstract
- This study assesses the spatial and temporal evolution of the glacial landsystem signature at Fjallsjiikull, southeast Iceland, using (a) mapping of the glacial geomorphology and surficial geology and (b) repeat uncrewed aerial vehicle (UAV) surveys. A small-scale (1: 15,000 scale) landsystem map has been compiled using LiDAR data (2011-2012) and historical aerial photographs (1945-1998), along with a large-scale (1: 2000 scale) map based on UAV imagery from May 2019. From our mapping and UAV surveys, we identify sediment-landform assemblages that are typical of active temperate glacial landsystems, including recessional push/squeeze moraines and intervening flutings, overridden moraine arcs, proglacial outwash (sandur) fans and linear/ribbon sandar. We recognize three landform zones that are defined by changes in moraine morphology and the nature of proglacial outwash deposition: (1) the outer foreland is characterized by proglacial outwash fans, overridden moraine arcs and broadly linear recessional moraines; (2) the middle foreland contains sawtooth moraines and linear sandar; and (3) the innermost zone comprises extremely sawtooth and hairpin moraines as well as associated crevasse-squeeze ridge limbs. This landform zonation reflects spatio-temporal changes in moraineforming processes and outwash deposition as determined by changes in snout morphology arid proglacial drainage characteristics. Within this general tripartite zonation, we also identify localized (atonal/intrazonal) sediment-landform assemblages that are not typically found at active temperate glaciers, including ice-cored/hummocky terrain and localized kame and kettle topography. Repeat UAV surveying in 2016-2019 has allowed us to capture and quantify recent intrazonal landsystem change at the southern glacier margin. We identify a switch from moraine formation to the development of ice-cored terrain and an ice-cored esker complex in association with the uncovering of a depositional overdeepening,. Our study demonstrates the important role that variations in local boundary conditions (e.g. topography) can play in the process-form response of individual active temperate outlet glaciers, contributing to the expanding database on modern glacial landsystems.
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| 8. |
- Inglis, Gordon N., et al.
(författare)
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Global mean surface temperature and climate sensitivity of the early Eocene Climatic Optimum (EECO), Paleocene-Eocene Thermal Maximum (PETM), and latest Paleocene
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1953-1968
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Tidskriftsartikel (refereegranskat)abstract
- Accurate estimates of past global mean surface temperature (GMST) help to contextualise future climate change and are required to estimate the sensitivity of the climate system to CO2 forcing through Earth's history. Previous GMST estimates for the latest Paleocene and early Eocene (similar to 57 to 48 million years ago) span a wide range (similar to 9 to 23 degrees C higher than pre-industrial) and prevent an accurate assessment of climate sensitivity during this extreme greenhouse climate interval. Using the most recent data compilations, we employ a multi-method experimen- tal framework to calculate GMST during the three DeepMIP target intervals: (1) the latest Paleocene (similar to 57 Ma), (2) the Paleocene-Eocene Thermal Maximum (PETM; 56 Ma), and (3) the early Eocene Climatic Optimum (EECO; 53.3 to 49.1 Ma). Using six different methodologies, we find that the average GMST estimate (66% confidence) during the latest Paleocene, PETM, and EECO was 26.3 degrees C (22.3 to 28.3 degrees C), 31.6 degrees C (27.2 to 34.5 degrees C), and 27.0 degrees C (23.2 to 29.7 degrees C), respectively. GMST estimates from the EECO are similar to 10 to 16 degrees C warmer than pre-industrial, higher than the estimate given by the Intergovernmental Panel on Climate Change (IPCC) 5th Assessment Report (9 to 14 degrees C higher than pre-industrial). Leveraging the large signal associated with these extreme warm climates, we combine estimates of GMST and CO2 from the latest Paleocene, PETM, and EECO to calculate gross estimates of the average climate sensitivity between the early Paleogene and today. We demonstrate that bulk equilibrium climate sensitivity (ECS; 66% confidence) during the latest Paleocene, PETM, and EECO is 4.5 degrees C (2.4 to 6.8 degrees C), 3.6 degrees C (2.3 to 4.7 degrees C), and 3.1 degrees C (1.8 to 4.4 degrees C) per doubling of CO2. These values are generally similar to those assessed by the IPCC (1.5 to 4.5 ffiC per doubling CO2) but appear incompatible with low ECS values (< 1 :5 per doubling CO2).
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| 9. |
- Strom, Peter, et al.
(författare)
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Artificial intelligence for diagnosis and grading of prostate cancer in biopsies : a population-based, diagnostic study
- 2020
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 21:2, s. 222-232
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAn increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading.MethodsWe digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50–69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa.FindingsThe AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994–0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972–0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95–0·97) for the independent test dataset and 0·87 (0·84–0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60–0·73).InterpretationAn AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist.
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| 10. |
- Denault, Vincent, et al.
(författare)
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The Analysis of Nonverbal Communication: The Dangers of Pseudoscience in Security and Justice Contexts : Análisis de la comunicación no verbal: los peligros de la pseudociencia en entornos de seguridad y justicia
- 2020
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Ingår i: Anuario de Psicología Jurídica. - : Colegio Oficial de la Psicologia de Madrid. - 1133-0740 .- 2174-0542. ; 30:1, s. 1-12
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Forskningsöversikt (refereegranskat)abstract
- For security and justice professionals (e.g., police officers, lawyers, judges), the thousands of peer-reviewed articles on nonverbal communication represent important sources of knowledge. However, despite the scope of the scientific work carried out on this subject, professionals can turn to programs, methods, and approaches that fail to reflect the state of science. The objective of this article is to examine (i) concepts of nonverbal communication conveyed by these programs, methods, and approaches, but also (ii) the consequences of their use (e.g., on the life or liberty of individuals). To achieve this objective, we describe the scope of scientific research on nonverbal communication. A program (SPOT; Screening of Passengers by Observation Techniques), a method (the BAI; Behavior Analysis Interview) and an approach (synergology) that each run counter to the state of science are examined. Finally, we outline five hypotheses to explain why some organizations in the fields of security and justice are turning to pseudoscience and pseudoscientific techniques. We conclude the article by inviting these organizations to work with the international community of scholars who have scientific expertise in nonverbal communication and lie (and truth) detection to implement evidence-based practices.
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