| 1. |
- Perez-Nadales, Elena, et al.
(författare)
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Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
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Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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| 2. |
- Gu, Y, et al.
(författare)
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Quick Hot Shot & Young Surgeon Presentation
- 2015
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Ingår i: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S77-84
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Biscaia, S. M. P., et al.
(författare)
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Safe therapeutics of murine melanoma model using a novel antineoplasic, the partially methylated mannogalactan from Pleurotus eryngii
- 2017
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Ingår i: Carbohydrate Polymers. - : ELSEVIER SCI LTD. - 0144-8617 .- 1879-1344. ; 178, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono-and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A man-nogalactan having a main chain of (1 -> 6)-linked alpha-D-galactopyranosyl and 3-O-methyl-alpha-D-galactopyranosyl residues, both partially substituted at OH-2 by beta-D-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50 mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10 days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.
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| 4. |
- Evans, D. A D, et al.
(författare)
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Return to Rodinia? Moderate to high palaeolatitude of the São Francisco/Congo craton at 920 Ma
- 2015. - 1
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Ingår i: Geological Society Special Publication. - 0305-8719. ; 424:1, s. 167-190
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Bokkapitel (refereegranskat)abstract
- Moderate to high palaeolatitudes recorded in mafic dykes, exposed along the coast of Bahia, Brazil, are partly responsible for some interpretations that the São Francisco/Congo craton was separate from the low-latitude Rodinia supercontinent at about 1050 Ma. We report new palaeomagnetic data that replicate the previous results. However, we obtain substantially younger U-Pb baddeleyite ages from five dykes previously thought to be 1.02-1.01 Ga according to the 40Ar/39Ar method. Specifically, the so-called «A-normal» remanence direction from Salvador is dated at 924.2±3.8 Ma, within error of the age for the «C» remanence direction at 921.5±4.3 Ma. An «A-normal» dyke at Ilh»us is dated at 926.1±4.6 Ma, and two «A-normal» dykes at Olivença have indistinguishable ages with best estimate of emplacement at 918.2±6.7 Ma. We attribute the palaeomagnetic variance of the «A-normal» and «C» directions to lack of averaging of geomagnetic palaeosecular variation in some regions. Our results render previous 40Ar/39Ar ages from the dykes suspect, leaving late Mesoproterozoic palaeolatitudes of the São Francisco/Congo craton unconstrained. The combined «A-normal» palaeomagnetic pole from coastal Bahia places the São Francisco/Congo craton in moderate to high palaeolatitudes at c. 920 Ma, allowing various possible positions of that block within Rodinia.
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| 5. |
- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X. ; 8, s. 901-911
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 6. |
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| 7. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699. ; 51:7, s. 1163-1184
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 8. |
- Martins, Inês S., et al.
(författare)
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Widespread shifts in body size within populations and assemblages
- 2023
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 381:6662, s. 1067-1071
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Tidskriftsartikel (refereegranskat)abstract
- Biotic responses to global change include directional shifts in organismal traits. Body size, an integrative trait that determines demographic rates and ecosystem functions, is thought to be shrinking in the Anthropocene. Here, we assessed the prevalence of body size change in six taxon groups across 5025 assemblage time series spanning 1960 to 2020. Using the Price equation to partition this change into within-species body size versus compositional changes, we detected prevailing decreases in body size through time driven primarily by fish, with more variable patterns in other taxa. We found that change in assemblage composition contributes more to body size changes than within-species trends, but both components show substantial variation in magnitude and direction. The biomass of assemblages remains quite stable as decreases in body size trade off with increases in abundance.
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| 9. |
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| 10. |
- ter Steege, Hans, et al.
(författare)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 11. |
- Allison, J, et al.
(författare)
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Geant4 developments and applications
- 2006
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Ingår i: IEEE TRANSACTIONS ON NUCLEAR SCIENCE. - 0018-9499. ; 53:1, s. 270-278
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Bispo-Santos, Franklin, et al.
(författare)
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Columbia revisited : paleomagnetic results from the 1790 Ma colider volcanics (SW Amazonian Craton, Brazil)
- 2008
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Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268 .- 1872-7433. ; 164:1-2, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- In an attempt to improve our understanding of the Paleoproterozoic geodynamic evolution, a paleomagnetic study was performed on 10 sites of acid volcanic rocks of the Colider Suite, southwestern Amazonian Craton. These rocks have a well-dated zircon U-Pb mean age of 1789 +/- 7 Ma. Alternating field and thermal demagnetization revealed northern (southern) directions with moderate to high upward (downward) inclinations. Rock magnetism experiments and magnetic mineralogy show that this characteristic magnetization is carried by Ti-poor magnetite or by hematite that replaces magnetite by late-magmatic cleuteric alteration. Both magnetite and hematite carry the same characteristic component. The mean direction (Dm = 183.0 degrees, Im = 53.5 degrees, N = 10, alpha(95) = 9.8 degrees, K = 25.2) yielded a paleomagnetic pole located at 298.8 degrees E, 63.3 degrees S (alpha(95) = 10.2 degrees, K = 23.6), which is classified with a quality factor Q = 5. Paleogeographic reconstructions using this pole and other reliable Paleoproterozoic poles suggest that Laurentia, Baltica, North China Craton and Amazonian Craton were located in laterally contiguous positions forming a large continental mass at 1790 Ma ago. This is reinforced by geological evidence which support the existence of the supercontinent Columbia in Paleoproterozoic times.
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| 13. |
- Carvalho, S. A., et al.
(författare)
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Self-compassion in Acceptance and Commitment Therapy for chronic pain: a pilot study
- 2022
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 22:3, s. 631-638
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Evidence shows that Acceptance and Commitment Therapy (ACT) is an empirically supported psychological approach for chronic pain (CP) management. Although self-compassion is not explicitly a target of ACT, it seems to be one mechanism of change in ACT for CP. However, research is lacking on the benefits of including explicit self-compassionate exercises in ACT for CP. The current study pilot tested a Compassionate ACT 8-session group program (COMP.ACT; n=9), as well as an ACT-only 8-session group program (ACT; n=7), in a sample of women with CP. Methods: The current study follows a quasi-experimental design, and conducts Reliable and Significant Change analyses comparing pre- to post-intervention scores of self-report measures. Results: No differences were found between conditions at baseline, nor between completers and drop-outs. Although preliminary, results showed COMP.ACT led to greater clinical improvements in depression and anxiety, while ACT led to greater improvements in stress and uncompassionate self-responding. Reliable and Significant Change analysis showed that some participants improved significantly (in psychopathological symptoms, valued living and uncompassionate self-responding) in both conditions, while the majority did not change significantly. Conclusions: More research is needed to conclude whether explicit self-compassion exercises are useful in ACT for CP. Limitations and implications are further discussed.
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| 14. |
- de Ridder, Lissy, et al.
(författare)
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Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease : A Multinational Study from the Porto Pediatric IBD Group
- 2014
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Ingår i: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 20:2, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. Results: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Conclusions: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.
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| 15. |
- Elming, Sten-åke, et al.
(författare)
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A palaeomagnetic and Ar-40/Ar-39 study of late precambrian sills in the SW part of the Amazonian craton: Amazonia in the Rodinia reconstruction
- 2009
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Ingår i: Geophysical Journal International. - 0956-540X .- 1365-246X. ; 178:1, s. 106-122
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Forskningsöversikt (refereegranskat)abstract
- A new key palaeomagnetic pole (Plat. = 64.3 degrees S, Plon. = 271.0 degrees E, N = 14, A(95) = 9.2 degrees; Q = 5) is calculated from a primary magnetization isolated in early Neoproterozoic Aguapei basic sills and dykes hosted by 1.3-1.0 Ga sedimentary rocks from the southwestern part of the Amazon craton. The characteristic remanence carried by stable, pseudo-single domain titanomagnetite shows two antipodal polarities that pass a reversals test. Magnetic anisotropy for most sites shows fabric orientations that are typical of sills, with horizontal magnetic foliations concordant to the flat-lying bedding of the host sedimentary rocks. Ar-40/Ar-39 analyses for one of the sills reveal a well-defined plateau age at 981 +/- 2 Myr. A tectonic reconstruction for Amazonia relative Laurentia based on this new pole 'is consistent with' a position of the present northwestern part of Amazonia attached with eastern Laurentia close to Greenland at ca. 981 Ma. On basis of palaeomagnetic and geological data, we propose a scenario where Amazonia moved northeastwards along the present southeast coast of Laurentia from ca. 1200 to 980 Ma. By 980 Ma, Amazonia is placed alongside Laurentia and Baltica, in a position similar to other reconstructions of Rodinia but with a significantly different orientation.
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| 16. |
- Peripato, Vinicius, et al.
(författare)
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More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia
- 2023
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Ingår i: Science (New York, N.Y.). - 1095-9203. ; 382:6666, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.
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| 17. |
- Salminen, Johanna, et al.
(författare)
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Congo-São Francisco craton in Paleoproterozoic-Mesoproterozoic supercontinent Nuna
- 2024
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Ingår i: Precambrian Research. - 0301-9268. ; 406
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Tidskriftsartikel (refereegranskat)abstract
- The location of the Congo-São Francisco (CSF) craton, one of the largest cratons in Proterozoic paleogeography, has been poorly constrained for the supercontinent Nuna interval (ca. 1800–1300 Ma). Initial models of Nuna suggested that the CSF craton was part of the Atlantica continent, together with Amazonia, West Africa, and perhaps Río de la Plata, as a separate continental block from other Nuna constituents. In other Nuna models the CSF craton has been placed adjacent to Baltica and Siberia, the core of Nuna, based mainly on ages of mafic magmatism and sparse paleomagnetic data. Through a geochemical, geochronological and paleomagnetic study of the WNW-trending Virei mafic dykes, which extend outward from the Mesoproterozoic Kunene Igneous Complex in southwest Angola, we provide a U-Pb baddeleyite age of 1385 ± 5 Ma, geochemical signatures, and a robust Mesoproterozoic paleomagnetic pole to test the CSF craton's placement within Nuna. Including our new pole with quality-filtered poles from the other cratons during the Nuna interval, we propose a refined Nuna model with (1) southwest Congo / west Siberia cratonic connection at 1700–1500 Ma, (2) proximity of Amazonia and West Africa cratons, and (3) connection of southwest Congo craton with northwest West Africa at 1380 Ma. Our proposed 1500–1380 Ma reconstructions are further supported by matching large igneous province (LIP) records from these crustal blocks. The new 1385 Ma Virei pole, when considered relative to an earlier CSF pole at ca. 1500 Ma, requires substantial azimuthal rotation (∼85°) of CSF in the intervening time interval. To accommodate both the matching LIP records and paleomagnetic data from CSF and neighboring cratons in Nuna, we propose an interval of transform motion near the supercontinent's periphery prior to more widespread mid-Mesoproterozoic supercontinental breakup.
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| 18. |
- Schiffer, Christian, et al.
(författare)
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Vp/Vs ratios in the Parnaíba Basin from joint active-passive seismic analysis : Implications for continental amalgamation and basin formation
- 2021
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Ingår i: Tectonophysics. - : Elsevier. - 0040-1951 .- 1879-3266. ; 801
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Tidskriftsartikel (refereegranskat)abstract
- The Phanerozoic intracontinental Parnaíba Basin in northeast Brazil lies atop crust composed of Archaean to Mesoproterozoic cratonic blocks and Neoproterozoic mobile belts. Recently, active and passive source geophysical surveys characterised the crustal structure beneath the basin. We use information from published active-source seismic and new, coincident receiver function (RF) data to obtain Vp/Vs ratios for sedimentary and crustal structure and make inferences about crustal compositions and tectonic evolution. In our approach, sedimentary and crustal Vp/Vs ratios are adjusted to match common conversion point (CCP) images of RFs and known Moho and basement geometry. We use a P-wave model from published wide-angle reflection/refraction (WARR) seismics, and structural features from a deep seismic reflection (DSR) profile. CCP images of the primary RF conversions were used to model the crust, whilst conversions of multiples were used for the sediment-basement interface. The maximum uncertainties in Vp/Vs are estimated to be 0.15 for the basin and 0.03 for the crust. Vp/Vs ratios in the basin were estimated between 1.7 and 2.2. Lower values correlate with the exposure of older units primarily in the east of the basin, whilst higher values coincide with exposed younger units of the Parnaíba Basin. The obtained crustal Vp/Vs ratios between 1.73 and 1.81 support the previously published segmentation of the crust. In particular, we identified three regions of elevated Vp/Vs ratios, which can be related to proposed Neoproterozoic suture zones underlying the Parnaíba Basin, as well as high velocity lower crust beneath. The high Vp/Vs ratios can be explained by mafic compositions, for example metamorphosed or intruded crust, or fluids and sedimentary rocks entrained into highly deformed crust, typical for modifications related to suture zones. These new deep geophysical models provide important and complementary evidence for crustal amalgamation and the formation of the Parnaíba Basin.
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| 19. |
- Shaw, W, et al.
(författare)
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Timing Of Primary Surgery for cleft palate (TOPS): protocol for a randomised trial of palate surgery at 6 months versus 12 months of age
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, speech, hearing, dental development and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. This has led to palatal closure in one-stage procedures being carried out around the age of 12 months, but in some cases as early as 6 months. The primary objective of the Timing Of Primary Surgery for Cleft Palate (TOPS)trial is to determine whether surgery for cleft palate performed at 6 or 12 months of age is most beneficial for speech outcomes. Methods and analysis Infants with a diagnosis of non-syndromic isolated cleft palate will be randomised to receive standardised primary surgery (Sommerlad technique) for closure of the cleft at either 6 months or 12 months, corrected for gestational age. The primary outcome will be perceived insufficient velopharyngeal function at 5 years of age. Secondary outcomes measured across 12 months, 3 years and 5 years will include growth, safety of the procedure, dentofacial development, speech, hearing level and middle ear function. Video and audio recordings of speech will be collected in a standardised age-appropriate manner and analysed independently by multiple speech and language therapists. The trial aims to recruit and follow-up 300 participants per arm. Data will be analysed according to the intention-to-treat principle using a 5% significance level. All analyses will be prespecified within a full and detailed statistical analysis plan. Ethics and dissemination Ethical approval has been sought in each participating country according to country-specific procedures. Trial results will be presented at conferences, published in peer-reviewed journals and disseminated through relevant patient support groups.
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| 20. |
- Tavella, T A, et al.
(författare)
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Yeast-based high-throughput screens for discovery of kinase inhibitors for neglected diseases.
- 2021
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Ingår i: Advances in Protein Chemistry and Structural Biology. - : Elsevier. - 1876-1631. ; 124, s. 275-309
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Forskningsöversikt (refereegranskat)abstract
- The discovery and development of a new drug is a complex, time consuming and costly process that typically takes over 10 years and costs around 1 billion dollars from bench to market. This scenario makes the discovery of novel drugs targeting neglected tropical diseases (NTDs), which afflict in particular people in low-income countries, prohibitive. Despite the intensive use of High-Throughput Screening (HTS) in the past decades, the speed with which new drugs come to the market has remained constant, generating doubts about the efficacy of this approach. Here we review a few of the yeast-based high-throughput approaches that can work synergistically with parasite-based, in vitro, or in silico methods to identify and optimize novel antiparasitic compounds. These yeast-based methods range from HTP screens to identify novel hits against promising parasite kinase targets to the identification of potential antiparasitic kinase inhibitors extracted from databases of yeast chemical genetic screens.
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| 21. |
- Tohver, E., et al.
(författare)
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Paleomagnetic evidence for a transpressional Grenville Orogen : sinistral offsets between Amazonia and Laurentia point to an evolving Rodinia
- 2005
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Ingår i: EOS. - 0096-3941 .- 2324-9250. ; 86:52 Suppl
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We report three new paleomagnetic poles from the Amazon craton for the Meso/Neoproterozoic Grenvillian interval, a period notable for the eponymous continental collision that affected the eastern margin of Laurentia. The poles were derived from study of ca.1230 Ma mafic sills (Figueira Branca -V 40Ar/39Ar biotite), the 1149 , b7 Ma sediments of the Aguapeà Gp. (U-Pb SHRIMP analysis of authigenic xenotime) and the ca.980 Ma basaltic dykes and flat-lying flows (40Ar/39Ar biotite) that intrude and overlie the Aguapeà Gp. sediments. These new data define a skeletal apparent polar wander path marked by a counterclockwise loop, similar to that observed for North America and Baltica. A pole-by-pole comparison of the Amazon and North American data demonstrates the evolving paleogeographic affinity of these two continents, marked by the large-scale strike-slip movement of Amazonia relative to Laurentia. The 3000 km of sinistral offset between these two continents is substantiated by a 200 Ma record of sinistral transpression recorded in the 1.2-1.15 Ga deformation of basement rocks of the Amazon craton, the 1.1 Ga Nova Brasil\^{a}ndia belt, and the 1.05-1.0 Ga Sunsas belt of eastern Bolivia. Our observations suggest that transpressional collision of the Amazon craton and Laurentia was responsible for the bulk of Grenvillian deformation, as opposed to the multiple continents required by other Rodinia models.
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| 22. |
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| 23. |
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| 24. |
- Wang, Minxian, et al.
(författare)
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Rare, Damaging DNA Variants in CORIN and Risk of Coronary Artery Disease : Insights From Functional Genomics and Large-Scale Sequencing Analyses
- 2021
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Ingår i: Circulation. Genomic and precision medicine. - 2574-8300. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Corin is a protease expressed in cardiomyocytes that plays a key role in salt handling and intravascular volume homeostasis via activation of natriuretic peptides. It is unknown if Corin loss-of-function (LOF) is causally associated with risk of coronary artery disease (CAD). METHODS: We analyzed all coding CORIN variants in an Italian case-control study of CAD. We functionally tested all 64 rare missense mutations in Western Blot and Mass Spectroscopy assays for proatrial natriuretic peptide cleavage. An expanded rare variant association analysis for Corin LOF mutations was conducted in whole exome sequencing data from 37 799 CAD cases and 212 184 controls. RESULTS: We observed LOF variants in CORIN in 8 of 1803 (0.4%) CAD cases versus 0 of 1725 controls (P, 0.007). Of 64 rare missense variants profiled, 21 (33%) demonstrated <30% of wild-type activity and were deemed damaging in the 2 functional assays for Corin activity. In a rare variant association study that aggregated rare LOF and functionally validated damaging missense variants from the Italian study, we observed no association with CAD-21 of 1803 CAD cases versus 12 of 1725 controls with adjusted odds ratio of 1.61 ([95% CI, 0.79-3.29]; P=0.17). In the expanded sequencing dataset, there was no relationship between rare LOF variants with CAD was also observed (odds ratio, 1.15 [95% CI, 0.89-1.49]; P=0.30). Consistent with the genetic analysis, we observed no relationship between circulating Corin concentrations with incident CAD events among 4744 participants of a prospective cohort study-sex-stratified hazard ratio per SD increment of 0.96 ([95% CI, 0.87-1.07], P=0.48). CONCLUSIONS: Functional testing of missense mutations improved the accuracy of rare variant association analysis. Despite compelling pathophysiology and a preliminary observation suggesting association, we observed no relationship between rare damaging variants in CORIN or circulating Corin concentrations with risk of CAD.
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