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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 4. |
- Graham, Jesse R., et al.
(författare)
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The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline
- 2016
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Ingår i: Journal of Experimental Social Psychology. - : Elsevier. - 1096-0465 .- 0022-1031. ; 66, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed.
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| 5. |
- Palin, K, et al.
(författare)
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Contribution of allelic imbalance to colorectal cancer
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3664-
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
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| 6. |
- Washburn, Anthony N., et al.
(författare)
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Data from a pre-publication independent replication initiative examining ten moral judgement effects
- 2016
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Ingår i: Scientific Data. - : Nature Research (part of Springer Nature): Fully open access journals / Nature Publishing Group. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires.
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| 8. |
- Callaghan, Terry V., et al.
(författare)
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Improving dialogue among researchers, local and indigenous peoples and decision-makers to address issues of climate change in the North
- 2020
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Ingår i: Ambio: a Journal of the Human Environment. - : Springer Science and Business Media LLC. - 0044-7447. ; 49:6, s. 1161-1178
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Tidskriftsartikel (refereegranskat)abstract
- The Circumpolar North has been changing rapidly within the last decades, and the socioeconomic systems of the Eurasian Arctic and Siberia in particular have displayed the most dramatic changes. Here, anthropogenic drivers of environmental change such as migration and industrialization are added to climate-induced changes in the natural environment such as permafrost thawing and increased frequency of extreme events. Understanding and adapting to both types of changes are important to local and indigenous peoples in the Arctic and for the wider global community due to transboundary connectivity. As local and indigenous peoples, decision-makers and scientists perceive changes and impacts differently and often fail to communicate efficiently to respond to changes adequately, we convened a meeting of the three groups in Salekhard in 2017. The outcomes of the meeting include perceptions of how the three groups each perceive the main issues affecting health and well-being and recommendations for working together better.
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| 10. |
- Drobysheva, Arina V., et al.
(författare)
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Structure and function of virion RNA polymerase of a crAss-like phage
- 2021
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 589:7841, s. 306-309
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Tidskriftsartikel (refereegranskat)abstract
- The RNA polymerase from the crAss-like bacteriophage phi14:2, which is translocated into the host cell with phage DNA and transcribes early phage genes, is structurally most similar to eukaryotic RNA interference polymerases, suggesting that the latter have a phage origin. CrAss-like phages are a recently described expansive group of viruses that includes the most abundant virus in the human gut(1-3). The genomes of all crAss-like phages encode a large virion-packaged protein(2,4) that contains a DFDxD sequence motif, which forms the catalytic site in cellular multisubunit RNA polymerases (RNAPs)(5). Here, using Cellulophaga baltica crAss-like phage phi14:2 as a model system, we show that this protein is a DNA-dependent RNAP that is translocated into the host cell along with the phage DNA and transcribes early phage genes. We determined the crystal structure of this 2,180-residue enzyme in a self-inhibited state, which probably occurs before virion packaging. This conformation is attained with the help of a cleft-blocking domain that interacts with the active site and occupies the cavity in which the RNA-DNA hybrid binds. Structurally, phi14:2 RNAP is most similar to eukaryotic RNAPs that are involved in RNA interference(6,7), although most of the phi14:2 RNAP structure (nearly 1,600 residues) maps to a new region of the protein fold space. Considering this structural similarity, we propose that eukaryal RNA interference polymerases have their origins in phage, which parallels the emergence of the mitochondrial transcription apparatus(8).
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| 13. |
- Gallardo-Fernández, Gloria L., 1953-, et al.
(författare)
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We adapt … but is it good or bad? Locating the political ecology and social-ecological systems debate in reindeer herding in the Swedish Sub-Arctic : Locating the political ecology and social-ecological systems debate in reindeer herding in the Swedish Sub-Arctic
- 2017
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Ingår i: Journal of Political Ecology. - : University of Arizona Press. - 1073-0451. ; 24, s. 667-691
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Tidskriftsartikel (refereegranskat)abstract
- Reindeer herding (RDH) is a livelihood strategy deeply connected to Sami cultural tradition. This article explores the implications of two theoretical and methodological approaches for grasping complex socio-environmental relationships of RDH in Subarctic Sweden. Based on joint fieldwork, two teams – one that aligns itself with political ecology (PE) and the other with social-ecological systems (SES) – compared PE and SES approaches of understanding RDH. Our purpose was twofold: 1) to describe the situation of Sami RDH through the lenses of PE and SES, exploring how the two approaches interpret the same empirical data; 2) to present an analytical comparison of the ontological and epistemological assumptions of this work, also inferring different courses of action to instigate change for the sustainability of RDH. Key informants from four sameby in the Kiruna region expressed strong support for the continuation of RDH as a cultural andeconomic practice. Concerns about the current situation raised by Sami representatives centered on the cumulative negative impacts on RDH from mining, forestry and tourism. PE and SES researchers offered dissimilar interpretations of the key aspects of the RDH socio-economic situation, namely: the nature and scale of RDH systems; the ubiquitous role of conflict; and conceptualizations of responses to changing socio-environmental conditions. Due to these disparities, PE and SES analyses have radically divergent socio-political implications for what ought to be done to redress the current RDH situation.
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| 15. |
- Parfenova, L. N., et al.
(författare)
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Influence of climatic and hydrological factors on structure and composition of peat from northern wetland territories with low anthropogenic impact
- 2016
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 551, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- Northern wetlands ecosystems play an important role in the hydrological balance of neighboring areas, where they act as chemical barriers against anthropogenic and technogenic contaminations. Studied region is well known for quantity of peat deposits and the volume of peat resources. Peat can be considered as a highly informative marker for assessing change in environmental conditions. The study presents the results of the first investigation of peat samples, collected from representative ecosystems of northern wetland territories with low anthropogenic impact. Component and element composition of various peat types were studied in a relation to hydrologic, climate and sampling conditions. It was found out that organic and ash contents are more dependent on the type of the bog, than geographic location. Climatic factors are more important for the formation of bitumen. The degradation degree in peat increases proportionally to content of humates. High content of biogenic and lithogenic elements was observed in transition-and low-moor peat. The content of trace elements in peat samples do not depend on the type of the peat. The structural properties of peat were studied by the light microscopy, AFM and dynamic light scattering. It was determined that the conformation of studied peat samples is characterized by elements of asymmetry. The observed particles in the solutions exist in dynamic equilibrium with separated globular macromolecules. The size of these nanoparticles is comparable with the size of the particles of other biopolymers of similar nature. Swelling of peat in liquid water was studied. The relationship between structural specificities, origin of peat and its maximum degree of swelling was found. The degree of swelling can be used as structural-sensitive parameter in further research. (C) 2016 Elsevier B.V. All rights reserved.
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| 17. |
- Rheubottom, Sarah, I, et al.
(författare)
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Hiding in the background : community-level patterns in invertebrate herbivory across the tundra biome
- 2019
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Ingår i: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 42:10, s. 1881-1897
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Tidskriftsartikel (refereegranskat)abstract
- Invertebrate herbivores depend on external temperature for growth and metabolism. Continued warming in tundra ecosystems is proposed to result in increased invertebrate herbivory. However, empirical data about how current levels of invertebrate herbivory vary across the Arctic is limited and generally restricted to a single host plant or a small group of species, so predicting future change remains challenging. We investigated large-scale patterns of invertebrate herbivory across the tundra biome at the community level and explored how these patterns are related to long-term climatic conditions and year-of-sampling weather, habitat characteristics, and aboveground biomass production. Utilizing a standardized protocol, we collected samples from 92 plots nested within 20 tundra sites during summer 2015. We estimated the community-weighted biomass lost based on the total leaf area consumed by invertebrates for the most common plant species within each plot. Overall, invertebrate herbivory was prevalent at low intensities across the tundra, with estimates averaging 0.94% and ranging between 0.02 and 5.69% of plant biomass. Our results suggest that mid-summer temperature influences the intensity of invertebrate herbivory at the community level, consistent with the hypothesis that climate warming should increase plant losses to invertebrates in the tundra. However, most of the observed variation in herbivory was associated with other site level characteristics, indicating that other local ecological factors also play an important role. More details about the local drivers of invertebrate herbivory are necessary to predict the consequences for rapidly changing tundra ecosystems.
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| 19. |
- Ugarte-Gil, Manuel Francisco, et al.
(författare)
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Impact of glucocorticoids on the incidence of lupus-related major organ damage : A systematic literature review and meta-regression analysis of longitudinal observational studies
- 2021
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 8:1
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Forskningsöversikt (refereegranskat)abstract
- Objective In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. Methods We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. Results We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. Conclusions We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.
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| 20. |
- Vuorinen, Katariina E.M., et al.
(författare)
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Growth rings show limited evidence for ungulates' potential to suppress shrubs across the Arctic
- 2022
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Global warming has pronounced effects on tundra vegetation, and rising mean temperatures increase plant growth potential across the Arctic biome. Herbivores may counteract the warming impacts by reducing plant growth, but the strength of this effect may depend on prevailing regional climatic conditions. To study how ungulates interact with temperature to influence growth of tundra shrubs across the Arctic tundra biome, we assembled dendroecological data from 20 sites, comprising 1153 individual shrubs and 223 63 annual growth rings. Evidence for ungulates suppressing shrub radial growth was only observed at intermediate summer temperatures (6.5 °C-9 °C), and even at these temperatures the effect was not strong. Multiple factors, including forage preferences and landscape use by the ungulates, and favourable climatic conditions enabling effective compensatory growth of shrubs, may weaken the effects of ungulates on shrubs, possibly explaining the weakness of observed ungulate effects. Earlier local studies have shown that ungulates may counteract the impacts of warming on tundra shrub growth, but we demonstrate that ungulates' potential to suppress shrub radial growth is not always evident, and may be limited to certain climatic conditions.
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