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| 2. |
- Pape Møller, Anders, et al.
(författare)
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Interaction of climate change with effects of conspecific and heterospecific density on reproduction
- 2020
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Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 129:12, s. 1807-1819
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Tidskriftsartikel (refereegranskat)abstract
- We studied the relationship between temperature and the coexistence of great tit Parus major and blue tit Cyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density‐dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.
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| 3. |
- Sundh, Josefin, 1972-, et al.
(författare)
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Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial
- 2020
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.
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| 4. |
- Evengård, Birgitta, 1952-, et al.
(författare)
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Healthy ecosystems for human and animal health : Science diplomacy for responsible development in the Arctic
- 2021
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Ingår i: Polar Record. - : Cambridges Institutes Press. - 0032-2474 .- 1475-3057. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF - a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.
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| 5. |
- Goetz, Charlotte, et al.
(författare)
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The plasma environment of comet 67P/Churyumov-Gerasimenko
- 2022
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Ingår i: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 218:8
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Forskningsöversikt (refereegranskat)abstract
- The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency's Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet's orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future.
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| 6. |
- Nilsson, Jesper, 1984, et al.
(författare)
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Multiphoton characterization and live cell imaging using fluorescent adenine analogue 2CNqA
- 2023
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Ingår i: Physical Chemistry Chemical Physics. - 1463-9084 .- 1463-9076. ; 25:30, s. 20218-20224
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescent nucleobase analogues (FBAs) are established tools for studying oligonucleotide structure, dynamics and interactions, and have recently also emerged as an attractive option for labeling RNA-based therapeutics. A recognized drawback of FBAs, however, is that they typically require excitation in the UV region, which for imaging in biological samples may have disadvantages related to phototoxicity, tissue penetration, and out-of-focus photobleaching. Multiphoton excitation has the potential to alleviate these issues and therefore, in this work, we characterize the multiphoton absorption properties and detectability of the highly fluorescent quadracyclic adenine analogue 2CNqA as a ribonucleotide monomer as well as incorporated, at one or two positions, into a 16mer antisense oligonucleotide (ASO). We found that 2CNqA has a two-photon absorption cross section that, among FBAs, is exceptionally high, with values of & sigma;(2PA)(700 nm) = 5.8 GM, 6.8 GM, and 13 GM for the monomer, single-, and double-labelled oligonucleotide, respectively. Using fluorescence correlation spectroscopy, we show that the 2CNqA has a high 2P brightness as the monomer and when incorporated into the ASO, comparing favorably to other FBAs. We furthermore demonstrate the usefulness of the 2P imaging mode for improving detectability of 2CNqA-labelled ASOs in live cells.
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| 7. |
- Nilsson, Magnus, et al.
(författare)
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Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma
- 2022
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Ingår i: Drug Design, Development and Therapy. - : Informa Healthcare. - 1177-8881. ; 16, s. 2901-2917
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation.Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats. Pharmacokinetic studies performed on rats evaluated AZD0449 at a lung deposited dose of 52 mu g/kg and AZD4604 at 30 mu g/kg. The efficacy of AZD0449 and AZD4604 was assessed by evaluating lung inflammation (cell count and cytokine levels) and the late asthmatic response (average enhanced pause [Penh]).Results: Both compounds inhibited JAK1-dependent cytokine signaling pathways in a dose-dependent manner in human and rat leukocytes. After intratracheal administration in rats, both compounds exhibited low systemic exposures and medium-to-long terminal lung half-lives (AZD0449, 34 hours; AZD4604, 5 hours). Both compounds inhibited STAT3 and STAT5 phosphorylation in lung tissue from ovalbumin (OVA)-challenged rats. AZD0449 and AZD4604 also inhibited eosinophilia in the lung and reduced the late asthmatic response, measured as Penh in the OVA rat model.Conclusion: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.
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| 8. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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Introducing guidelines for publishing DNA-derived occurrence data through biodiversity data platforms
- 2022
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Ingår i: Metabarcoding and Metagenomics. - : Pensoft Publishers. - 2534-9708. ; 6, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- DNA sequencing efforts of environmental and other biological samples disclose unprecedented and largely untapped opportunities for advances in the taxonomy, ecology, and geographical distributions of our living world. To realise this potential, DNA-derived occurrence data (notably sequences with dates and coordinates) – much like traditional specimens and observations – need to be discoverable and interpretable through biodiversity data platforms. The Global Biodiversity Information Facility (GBIF) recently headed a community effort to assemble a set of guidelines for publishing DNA-derived data. These guidelines target the principles and approaches of exposing DNA-derived occurrence data in the context of broader biodiversity data. They cover a choice of terms using a controlled vocabulary, common pitfalls, and good practices, without going into platform-specific details. Our hope is that they will benefit anyone interested in better exposure of DNA-derived occurrence data through general biodiversity data platforms, including national biodiversity portals. This paper provides a brief rationale and an overview of the guidelines, an up-to-date version of which is maintained at https://doi.org/10.35035/doc-vf1a-nr22. User feedback and interaction are encouraged as new techniques and best practices emerge.
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| 9. |
- Ny, Lars, 1967, et al.
(författare)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 10. |
- Sah, Vasu R., et al.
(författare)
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Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
- 2023
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Ingår i: Cancer Research Communications. ; 3:5, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomark-ers needing validation and become hypothesis generating for experimental research.
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