| 1. |
- Winslow, S., et al.
(author)
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Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and Haemophilus infection in COPD
- 2021
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:4
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Journal article (peer-reviewed)abstract
- Background: Interleukin (IL)-6 trans-signalling (IL-6TS) is emerging as a pathogenic mechanism in chronic respiratory diseases; however, the drivers of IL-6TS in the airways and the phenotypic characteristic of patients with increased IL-6TS pathway activation remain poorly understood. Objective: Our aim was to identify and characterise COPD patients with increased airway IL-6TS and to elucidate the biological drivers of IL-6TS pathway activation. Methods: We used an IL-6TS-specific sputum biomarker profile (soluble IL-6 receptor (sIL-6R), IL-6, IL1 beta, IL-8, macrophage inflammatory protein-1 beta) to stratify sputum data from patients with COPD (n=74; Biomarkers to Target Antibiotic and Systemic Corticosteroid Therapy in COPD Exacerbation (BEAT-COPD)) by hierarchical clustering. The IL-6TS signature was related to clinical characteristics and sputum microbiome profiles. The induction of neutrophil extracellular trap formation (NETosis) and IL-6TS by Haemophilus influenzae were studied in human neutrophils. Results: Hierarchical clustering revealed an IL-6TS-high subset (n=24) of COPD patients, who shared phenotypic traits with an IL-6TS-high subset previously identified in asthma. The subset was characterised by increased sputum cell counts (p=0.0001), persistent sputum neutrophilia (p=0.0004), reduced quality of life (Chronic Respiratory Questionnaire total score; p=0.008), and increased levels of pro-inflammatory mediators and matrix metalloproteinases in sputum. IL-6TS-high COPD patients showed an increase in Proteobacteria, with Haemophilus as the dominating genus. NETosis induced by H. influenzae was identified as a potential mechanism for increased sIL-6R levels. This was supported by a significant positive correlation between sIL-6R and NETosis markers in bronchoalveolar lavage fluid from COPD patients. Conclusion: IL-6TS pathway activation due to chronic colonisation with Haemophilus may be an important disease driver in a subset of COPD patients.
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| 2. |
- Fu, Michael, 1963, et al.
(author)
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Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822.
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Journal article (peer-reviewed)abstract
- Aims The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation. Methods and results A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with >= 1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%. Conclusions Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high.
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| 3. |
- Karason, Kristjan, 1962, et al.
(author)
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Randomized trial of a left ventricular assist device as destination therapy versus guideline-directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial
- 2020
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:2, s. 739-50
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Journal article (peer-reviewed)abstract
- Aims Patients with advanced heart failure (AdHF) who are ineligible for heart transplantation (HTx) can become candidates for treatment with a left ventricular assist device (LVAD) in some countries, but not others. This reflects the lack of a systematic analysis of the usefulness of LVAD systems in this context, and of their benefits, limitations and cost-effectiveness. The SWEdish evaluation of left Ventricular Assist Device (SweVAD) study is a Phase IV, prospective, 1:1 randomized, non-blinded, multicentre trial that will examine the impact of assignment to mechanical circulatory support with guideline-directed LVAD destination therapy (GD-LVAD-DT) using the HeartMate 3 (HM3) continuous flow pump vs. guideline-directed medical therapy (GDMT) on survival in a population of AdHF patients ineligible for HTx. Methods A total of 80 patients will be recruited to SweVAD at the seven university hospitals in Sweden. The study population will comprise patients with AdHF (New York Heart Association class IIIB-IV, INTERMACS profile 2-6) who display signs of poor prognosis despite GDMT and who are not considered eligible for HTx. Participants will be followed for 2 years or until death occurs. Other endpoints will be determined by blinded adjudication. Patients who remain on study-assigned interventions beyond 2 years will be asked to continue follow-up for outcomes and adverse events for up to 5 years. Conclusion The SweVAD study will compare survival, medium-term benefits, costs and potential hazards between GD-LVAD-DT and GDMT and will provide a valuable reference point to guide destination therapy strategies for patients with AdHF ineligible for HTx.
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| 5. |
- Lindmark, Matilda, et al.
(author)
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Protecting forest edges using trap logs – Limited effects of associated push-pull strategies targeting Ips typographus
- 2022
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In: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 505
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Journal article (peer-reviewed)abstract
- Bark beetles can cause epidemic outbreaks and kill millions of cubic meters of economical and ecologically important forests around the world. It is well known what attracts and what repels different species of bark beetle, and these chemical cues can be used to protect trees and catch the beetles without using pesticides. Applying this knowledge, we investigated the use of push–pull strategies with trap logs along susceptible edges of a Swedish boreal spruce forest. The repellents (push) used were non-host volatiles (NHV) attached to tree trunks at the forest edge, and the attractants (pull) was a commercial aggregation pheromone attached to trap logs. The aim was to test whether the Ips typographus catch could be significantly increased by combining a push–pull system with traditional trap logs, thereby providing additional protection. The experiment was performed over two years and included the main flight period of I. typographus. The study sites were clear-cuts that had been harvested the preceding winter, and sun-exposed forest edges of mature spruce were targeted for protection. A full factorial setup was used comprising two treatments (repellent and attractant) and a control. Seven replicates of the trap logs were used, three during the first year and four during the second. The number of established I. typographus maternal galleries per square meter of log surface was used as the response variable. The trap logs captured large numbers of I. typographus, at an average density of 353 and 169 maternal galleries per m2 during year 1 and year 2, respectively, over all treatments. Based on the catch data, with a sufficient number of trap logs, the risk of tree mortality at forest edges may be reduced and we recommend its general use. However, we did not see any significant effect of either the repellent or the attractant on the density of maternal galleries. Hence, we cannot recommend the addition of chemical cues to improve the efficiency of trap logs. Although trap logs are efficient in capturing bark beetles and hence may protect forest edges, it does not imply that they can provide protection on a larger scale. In line with other studies, we hence recommend that forest management to target nature-based solutions that strengthen the resilience of forest stands, by using mixed forest stands and resistant plant species, and nurture habitats for natural predators of I. typographus.
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| 6. |
- Lindmark, Matilda, et al.
(author)
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Semiochemicals produced by fungal bark beetle symbiont Endoconidiophora rufipennis and the discovery of an anti-attractant for Ips typographus
- 2023
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 18:4
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Journal article (peer-reviewed)abstract
- Bark beetles vector symbiotic fungal species into their host trees during mass attacks. The symbiotic relationship with blue stain fungi of the Ascomycetes, including genera of Endoconidiophora (syn. = Ceratocystis), promotes successful establishment whereby the microbes help to overcome the host trees' defence and degrade toxic resins. This is the first study to evaluate both the volatile emissions from an insect-associated blue stain fungus over time and the insect response in a field trapping experiment. Volatile emissions from isolates of Endoconidiophora rufipennis (ER) were collected by solid-phase microextraction (SPME) and analysed by gas chromatography-mass spectroscopy (GC-MS) over a period of 30 days. This virulent North American fungus is closely related to E. polonica, a symbiotic fungus known from Eurasian spruce bark beetle Ips typographus.Nine volatiles were emitted by ER in substantial amounts: isoamyl acetate, sulcatone, 2-phenethyl acetate, geranyl acetone, geranyl acetate, citronellyl acetate, (R)- and (S)-sulcatol, and (R)-sulcatol acetate. A late peaking compound was geranyl acetone. In the field trapping experiment, three of the fungal volatiles (geranyl acetone, 2-phenethyl acetate and sulcatone) were tested in combination with a synthetic aggregation pheromone for I. typographus. Traps with geranyl acetone attracted lower numbers of I. typographus compared to traps with 2-phenethyl acetate, sulcatone or the pheromone alone as a control. The results showed that geranyl acetone acts as an anti-attractant and may act naturally on I. typographus as a cue from an associated fungus to signal an overexploited host.
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| 7. |
- Seekell, David A., et al.
(author)
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The Fractal Scaling Relationship for River Inlets to Lakes
- 2021
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 48:9
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Journal article (peer-reviewed)abstract
- Scaling relationships provide simple rules for understanding complex hydrographic patterns. Globally, river inlet abundance varies among lakes by about three orders of magnitude, but few scaling relationships describe this aspect of lake-river connectivity. In this study, we describe a simple theoretical scaling relationship between lake surface area and river inlet abundance, and test this theory using data from Scandinavia. On average, the number of inlets increases by 67% for each doubling of lake area. However, lakes of vastly different areas can have the same number of inlets with relatively small variations of drainage density, lake shape, or junction angle - characteristics that can often be linked to specific geological processes. Our approach bridges the gap between the detailed understanding of geomorphic processes and large-scale statistical relationships, and engenders predictions about additional patterns including the relationship between lake area and water residence time.
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