| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 6. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 11. |
- Solmi, M, et al.
(författare)
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- 2022
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Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Zhang, X., et al.
(författare)
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Human total, basal and activity energy expenditures are independent of ambient environmental temperature
- 2022
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Ingår i: iScience. - : Elsevier Inc.. - 2589-0042. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.
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| 13. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 14. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 19. |
- Chen, Hao Yu, et al.
(författare)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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| 20. |
- Fortier, A., et al.
(författare)
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CHEOPS in-flight performance: A comprehensive look at the first 3.5 yr of operations
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- Context. Since the discovery of the first exoplanet almost three decades ago, the number of known exoplanets has increased dramatically. By beginning of the 2000s it was clear that dedicated facilities to advance our studies in this field were needed. The CHaracterising ExOPlanet Satellite (CHEOPS) is a space telescope specifically designed to monitor transiting exoplanets orbiting bright stars. In September 2023, CHEOPS completed its nominal mission duration of 3.5 yr and remains in excellent operational conditions. As a testament to this, the mission has been extended until the end of 2026. Aims. Scientific and instrumental data have been collected throughout in-orbit commissioning and nominal operations, enabling a comprehensive analysis of the missiona's performance. In this article, we present the results of this analysis with a twofold goal. First, we aim to inform the scientific community about the present status of the mission and what can be expected as the instrument ages. Secondly, we intend for this publication to serve as a legacy document for future missions, providing insights and lessons learned from the successful operation of CHEOPS. Methods. To evaluate the instrument performance in flight, we developed a comprehensive monitoring and characterisation (M&C) programme. It consists of dedicated observations that allow us to characterise the instrumenta's response and continuously monitor its behaviour. In addition to the standard collection of nominal science and housekeeping data, these observations provide valuable input for detecting, modelling, and correcting instrument systematics, discovering and addressing anomalies, and comparing the instrumenta's actual performance with expectations. Results. The precision of the CHEOPS measurements has enabled the mission objectives to be met and exceeded. The satellitea's performance remains stable and reliable, ensuring accurate data collection throughout its operational life. Careful modelling of the instrumental systematics allows the data quality to be significantly improved during the light curve analysis phase, resulting in more precise scientific measurements. Conclusions. CHEOPS is compliant with the driving scientific requirements of the mission. Although visible, the ageing of the instrument has not affected the missiona's performance. The satellitea's capabilities remain robust, and we are confident that we will continue to acquire high-quality data during the mission extension.
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| 21. |
- Urquhart, J. S., et al.
(författare)
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SEDIGISM-ATLASGAL: Dense gas fraction and star formation efficiency across the Galactic disc
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 500:3, s. 3050-3063
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Tidskriftsartikel (refereegranskat)abstract
- By combining two surveys covering a large fraction of the molecular material in the Galactic disc, we investigate the role spiral arms play in the star formation process. We have matched clumps identified by APEX Telescope Large Area Survey of the Galaxy (ATLASGAL) with their parental giant molecular clouds (GMCs) as identified by SEDIGISM, and use these GMC masses, the bolometric luminosities, and integrated clump masses obtained in a concurrent paper to estimate the dense gas fractions (DGFgmc = ΣMclump/Mgmc) and the instantaneous star formation efficiencies (i.e. SFEgmc = ΣLclump/Mgmc). We find that the molecular material associated with ATLASGAL clumps is concentrated in the spiral arms (∼60 per cent found within ±10 km s-1 of an arm).We have searched for variations in the values of these physical parameters with respect to their proximity to the spiral arms, but find no evidence for any enhancement that might be attributable to the spiral arms. The combined results from a number of similar studies based on different surveys indicate that, while spiral-arm location plays a role in cloud formation and HI to H2 conversion, the subsequent star formation processes appear to depend more on local environment effects. This leads us to conclude that the enhanced star formation activity seen towards the spiral arms is the result of source crowding rather than the consequence of any physical process.
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| 22. |
- Chen, H. Y., et al.
(författare)
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Genome-wide association meta-analysis in 652,134 participants identifies 9 novel susceptibility loci for aortic stenosis
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:Suppl 2, s. 1862-1862
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Aortic stenosis (AS) is the most common form of incident valvular heart disease. While valve replacement is effective, the absence of an approved medical therapy provides no alternatives to patients with contraindications or mild disease. An improved understanding of the genetics of AS could identify targets for pharmacological intervention.Methods: An inverse variance-weighted, fixed effects meta-analysis of the association of 11,591,806 variants with AS was undertaken using data from 10 European cohorts totalling 652,134 participants (13,758 cases of AS). We queried publicly available datasets to characterize the functional consequences of genome-wide significant variants, conducted a phenome-wide association study to assess their association with other outcomes, and constructed polygenic risk scores to examine their association with AS. We also performed gene- and gene-set enrichment analyses, estimated genetic correlation with cardiovascular traits, and assessed whether five lipid or immunological biomarkers were causally associated with AS using Mendelian randomization.Results: Eighteen independent variants at 16 loci attained genome-wide significance in the meta-analysis, including variants at all seven previously reported loci. Many of the significant variants were intronic or intergenic, and the phenome-wide association study revealed extensive pleiotropy with apolipoprotein B, C-reactive protein, and other cardiovascular and immunological traits. A weighted polygenic risk score composed of the 18 variants was strongly associated with AS (adjusted OR per SD, 1.38; 95% CI, 1.33 to 1.44; p=4.6×10–57), and improved the discriminatory ability for AS when added to a model that contained clinical risk factors (difference in the area under the curve p=2.0×10–11). Gene-based approaches indicated higher IL6R expression in the blood among AS cases compared to controls (p=3.1×10–6), and the association of LDLR with AS (p=2.3×10–10). Gene set analyses revealed that genes bound by the transcription factor TCF7 or micro-RNAs miR-21, miR-219, miR-491, and miR-19 were differentially expressed in the liver depending on AS status (p≤5.7×10–4), suggesting disease development may be mediated by tissue-specific transcriptional and post-transcriptional regulation. Mendelian randomization supported a causal association of five lipid and immunological biomarkers with AS, including low-density lipoprotein cholesterol (OR per mmol/L, 1.61; 95% CI, 1.48 to 1.75; p=1.3×10–30).Conclusions: Evidence from large-scale genetic analyses indicate that lipid metabolism, inflammation, and calcification are key contributors to AS.
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| 23. |
- Osborn, H. P., et al.
(författare)
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Uncovering the true periods of the young sub-Neptunes orbiting TOI-2076
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664
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Tidskriftsartikel (refereegranskat)abstract
- Context. TOI-2076 is a transiting three-planet system of sub-Neptunes orbiting a bright (G = 8.9 mag), young (340 +/- 80 Myr) K-type star. Although a validated planetary system, the orbits of the two outer planets were unconstrained as only two non-consecutive transits were seen in TESS photometry. This left 11 and 7 possible period aliases for each. Aims. To reveal the true orbits of these two long-period planets, precise photometry targeted on the highest-probability period aliases is required. Long-term monitoring of transits in multi-planet systems can also help constrain planetary masses through TTV measurements. Methods. We used the MonoTools package to determine which aliases to follow, and then performed space-based and ground-based photometric follow-up of TOI-2076 c and d with CHEOPS, SAINT-EX, and LCO telescopes. Results. CHEOPS observations revealed a clear detection for TOI-2076 c at P = 21.01538(-0.00074)(+0.00084) d, and allowed us to rule out three of the most likely period aliases for TOI-2076 d. Ground-based photometry further enabled us to rule out remaining aliases and confirm the P = 35.12537 +/- 0.00067 d alias. These observations also improved the radius precision of all three sub-Neptunes to 2.518 +/- 0.036, 3.497 +/- 0.043, and 3.232 +/- 0.063 R-circle plus. Our observations also revealed a clear anti-correlated TTV signal between planets b and c likely caused by their proximity to the 2:1 resonance, while planets c and d appear close to a 5:3 period commensurability, although model degeneracy meant we were unable to retrieve robust TTV masses. Their inflated radii, likely due to extended H-He atmospheres, combined with low insolation makes all three planets excellent candidates for future comparative transmission spectroscopy with JWST.
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| 24. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 25. |
- Grigoroglou, C., et al.
(författare)
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Effectiveness of collaborative care in reducing suicidal ideation: An individual participant data meta-analysis
- 2021
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Ingår i: General Hospital Psychiatry. - : Elsevier BV. - 0163-8343. ; 71, s. 27-35
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Tidskriftsartikel (refereegranskat)abstract
- To assess whether CC is more effective at reducing suicidal ideation in people with depression compared with usual care, and whether study and patient factors moderate treatment effects. Method: We searched Medline, Embase, PubMed, PsycINFO, CINAHL, CENTRAL from inception to March 2020 for Randomised Controlled Trials (RCTs) that compared the effectiveness of CC with usual care in depressed adults, and reported changes in suicidal ideation at 4 to 6 months post-randomisation. Mixed-effects models accounted for clustering of participants within trials and heterogeneity across trials. This study is registered with PROSPERO, CRD42020201747. Results: We extracted data from 28 RCTs (11,165 patients) of 83 eligible studies. We observed a small significant clinical improvement of CC on suicidal ideation, compared with usual care (SMD, 0.11 [95%CI, 0.15 to 0.08]; I-2, 0.47% [95%CI 0.04% to 4.90%]). CC interventions with a recognised psychological treatment were associated with small reductions in suicidal ideation (SMD, 0.15 [95%CI -0.19 to 0.11]). CC was more effective for reducing suicidal ideation among patients aged over 65 years (SMD, 0.18 [95%CI -0.25 to 0.11]). Conclusion: Primary care based CC with an embedded psychological intervention is the most effective CC framework for reducing suicidal ideation and older patients may benefit the most.
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| 26. |
- Hayes, A., et al.
(författare)
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A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts
- 2020
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 92:8, s. 1065-1074
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Tidskriftsartikel (refereegranskat)abstract
- Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
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| 27. |
- Tran, Thao Thanh, et al.
(författare)
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Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
- 2022
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Ingår i: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.
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| 28. |
- Reed, B. P., et al.
(författare)
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Diamond (111) surface reconstruction and epitaxial graphene interface
- 2022
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Ingår i: Physical Review B. - 2469-9950. ; 105:20
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of the diamond (111) surface as it undergoes reconstruction and subsequent graphene formation is investigated with angle-resolved photoemission spectroscopy, low energy electron diffraction, and complementary density functional theory calculations. The process is examined starting at the C(111)-(2×1) surface reconstruction that occurs following detachment of the surface adatoms at 920 ∘C, and continues through to the liberation of the reconstructed surface atoms into a freestanding monolayer of epitaxial graphene at temperatures above 1000 ∘C. Our results show that the C(111)-(2×1) surface is metallic as it has electronic states that intersect the Fermi level. This is in strong agreement with a symmetrically π-bonded chain model and should contribute to resolving the controversies that exist in the literature surrounding the electronic nature of this surface. The graphene formed at higher temperatures exists above a newly formed C(111)-(2×1) surface and appears to have little substrate interaction as the Dirac point is observed at the Fermi level. Finally, we demonstrate that it is possible to hydrogen-terminate the underlying diamond surface by means of plasma processing without removing the graphene layer, forming a graphene-semiconductor interface. This could have particular relevance for doping the graphene formed on the diamond (111) surface via tuneable substrate interactions as a result of changing the terminating species at the diamond-graphene interface by plasma processing.
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| 29. |
- Farnocchia, Davide, et al.
(författare)
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International Asteroid Warning Network Timing Campaign: 2019 XS
- 2022
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Ingår i: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- As part of the International Asteroid Warning Network's observational exercises, we conducted a campaign to observe near-Earth asteroid 2019 XS around its close approach to Earth on 2021 November 9. The goal of the campaign was to characterize errors in the observation times reported to the Minor Planet Center, which become an increasingly important consideration as astrometric accuracy improves and more fast-moving asteroids are observed. As part of the exercise, a total of 957 astrometric observations of 2019 XS during the encounter were reported and subsequently were analyzed to obtain the corresponding residuals. While the timing errors are typically smaller than 1 s, the reported times appear to be negatively biased, i.e., they are generally earlier than they should be. We also compared the observer-provided position uncertainty with the cross-track residuals, which are independent of timing errors. A large fraction of the estimated uncertainties appear to be optimistic, especially when <0 2. We compiled individual reports for each observer to help identify and remove the root cause of any possible timing error and improve the uncertainty quantification process. We suggest possible sources of timing errors and describe a simple procedure to derive reliable, conservative position uncertainties.
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| 30. |
- Lindgren, Erik, 1993, et al.
(författare)
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Dural arteriovenous fistulas in cerebral venous thrombosis Data from the International Cerebral Venous Thrombosis Consortium
- 2022
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:3, s. 761-770
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population. Methods We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up. Results dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8 (5-23) months. Patients with dAVF were older (median [IQR] 53 [44-61] vs. 41 [29-53] years; p < 0.001), more frequently male (69% vs. 33%; p < 0.001), more often had chronic clinical CVT onset (>30 days: 39% vs. 7%; p < 0.001) and sigmoid sinus thrombosis (86% vs. 51%; p < 0.001), and less frequently had parenchymal lesions (31% vs. 55%; p = 0.013) at baseline imaging. Clinical outcome at last follow-up did not differ between patients with and without dAVF. Additionally, five patients were confirmed with dAVF from non-consecutive CVT cohorts. Among all patients with CVT and dAVF, 17/34 (50%) had multiple fistulas and 23/34 (68%) had cortical venous drainage. Of 34 patients with dAVF with 36 separate CVT events, 3/36 fistulas (8%) were diagnosed prior to, 20/36 (56%) simultaneously and 13/36 after (36%, median 115 [IQR 38-337] days) diagnosis of CVT. Conclusions Dural arteriovenous fistulas occur in at least 2% of CVT patients and are associated with chronic CVT onset, older age and male sex. Most CVT-related dAVFs are detected simultaneously or subsequently to diagnosis of CVT.
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| 31. |
- Perez-Escobar, O. A., et al.
(författare)
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Molecular Clocks and Archeogenomics of a Late Period Egyptian Date Palm Leaf Reveal Introgression from Wild Relatives and Add Timestamps on the Domestication
- 2021
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Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:10, s. 4475-4492
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Tidskriftsartikel (refereegranskat)abstract
- The date palm, Phoenix dactylifera, has been a cornerstone of Middle Eastern and North African agriculture for millennia. It was first domesticated in the Persian Gulf, and its evolution appears to have been influenced by gene flow from two wild relatives, P. theophrasti, currently restricted to Crete and Turkey, and P. sylvestris, widespread from Bangladesh to the West Himalayas. Genomes of ancient date palm seeds show that gene flow from P. theophrasti to P. dactylifera may have occurred by similar to 2,200years ago, but traces of P. sylvestris could not be detected. We here integrate archeogenomics of a similar to 2,100-year-old P. dactylifera leaf from Saqqara (Egypt), molecular-clock dating, and coalescence approaches with population genomic tests, to probe the hybridization between the date palm and its two closest relatives and provide minimum and maximum timestamps for its reticulated evolution. The Saqqara date palm shares a close genetic affinity with North African date palm populations, and we find clear genomic admixture from both P. theophrasti, and P. sylvestris, indicating that both had contributed to the date palm genome by 2,100years ago. Molecular-clocks placed the divergence of P. theophrasti from P. dactylifera/P. sylvestris and that of P. dactylifera from P. sylvestris in the Upper Miocene, but strongly supported, conflicting topologies point to older gene flow between P. theophrasti and P. dactylifera, and P. sylvestris and P. dactylifera. Our work highlights the ancient hybrid origin of the date palms, and prompts the investigation of the functional significance of genetic material introgressed from both close relatives, which in turn could prove useful for modern date palm breeding.
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| 32. |
- Pluta, J, et al.
(författare)
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Identification of 22 susceptibility loci associated with testicular germ cell tumors
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 4487-
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Tidskriftsartikel (refereegranskat)abstract
- Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.
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| 33. |
- Plymale, Andrew E., et al.
(författare)
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Niche Partitioning of Microbial Communities at an Ancient Vitrified Hillfort : Implications for Vitrified Radioactive Waste Disposal
- 2021
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Ingår i: Geomicrobiology Journal. - : Taylor & Francis. - 0149-0451 .- 1521-0529. ; 38:1, s. 36-56
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Tidskriftsartikel (refereegranskat)abstract
- Because microbes cannot be eliminated from radioactive waste disposal facilities, the consequences of bio-colonization must be understood. At a pre-Viking era vitrified hillfort, Broborg, Sweden, anthropogenic glass has been subjected to bio-colonization for over 1,500 years. Broborg is used as a habitat analogue for disposed radioactive waste glass to inform how microbial processes might influence long-term glass durability. Electron microscopy and DNA sequencing of surficial material from the Broborg vitrified wall, adjacent soil, and general topsoil show that the ancient glass supports a niche microbial community of bacteria, fungi, and protists potentially involved in glass alteration. Communities associated with the vitrified wall are distinct and less diverse than soil communities. The vitrified niche of the wall and adjacent soil are dominated by lichens, lichen-associated microbes, and other epilithic, endolithic, and epigeic organisms. These organisms exhibit potential bio-corrosive properties, including silicate dissolution, extraction of essential elements, and secretion of geochemically reactive organic acids, that could be detrimental to glass durability. However, long-term biofilms can also possess a homeostatic function that could limit glass alteration. This study documents potential impacts that microbial colonization and niche partitioning can have on glass alteration, and subsequent release of radionuclides from a disposal facility for vitrified radioactive waste.
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| 34. |
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| 35. |
- Daw, Tim M., et al.
(författare)
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Life satisfaction in coastal Kenya and Mozambique reflects culture, gendered relationships and security of basic needs : Implications for ecosystem services
- 2023
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Ingår i: Ecosystem Services. - 2212-0416. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Life satisfaction is both a desirable 'end' for sustainable development, and a means to understand the priorities, and behaviour of people towards local ecosystems. Ecosystem-services research on life satisfaction has focused on cultural services in wealthy, Western contexts, although ecosystem services are essential for poor people's livelihoods in the Global South. We examined reported life satisfaction from a survey of over 2000 people in rural and urban settings of coastal Kenya and Mozambique. We coded respondents' open-ended reasons for their reported satisfaction, and used multiple correspondence analysis to explore the characteristics of people who mentioned different reasons. We tested associations between satisfaction and the meeting of basic needs and income, with binary logistic regression, accounting for site and gender. Life satisfaction was lower in Kenya, for men, and in the most urbanised site. Respondents explained high, and low, satisfaction in terms of social relationships, basic needs, money and employment. They rarely mentioned the ecosystem services and related livelihoods that underpin those, suggesting an instrumental relation to nature. Meeting basic needs, including economic security better predicted satisfaction than household income. Life satisfaction reflected material differences in people's lives but also different evaluative criteria and national cultures. For example, family reasons more commonly explained women's satisfaction, while money was more important for urban-dwelling men. We propose that the holistic perspective offered by life-satisfaction research can inform environmental management alongside more focused ecosystem-service research. For example, our results suggest that a) interventions should recognise immediate needs and social relationships, b) the role of ecosystem services for subjective wellbeing varies by local culture and individual identities and c) secure and fair access to ecosystem services may support life satisfaction better than high incomes that are insecure or ineq-uitably distributed.
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| 36. |
- Farnocchia, Davide, et al.
(författare)
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The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
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Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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| 37. |
- Fecchio, Alan, et al.
(författare)
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Global drivers of avian haemosporidian infections vary across zoogeographical regions
- 2021
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 30:12, s. 2393-2406
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Macroecological analyses provide valuable insights into factors that influence how parasites are distributed across space and among hosts. Amid large uncertainties that arise when generalizing from local and regional findings, hierarchical approaches applied to global datasets are required to determine whether drivers of parasite infection patterns vary across scales. We assessed global patterns of haemosporidian infections across a broad diversity of avian host clades and zoogeographical realms to depict hotspots of prevalence and to identify possible underlying drivers. Location: Global. Time period: 1994–2019. Major taxa studied: Avian haemosporidian parasites (genera Plasmodium, Haemoproteus, Leucocytozoon and Parahaemoproteus). Methods: We amalgamated infection data from 53,669 individual birds representing 2,445 species world-wide. Spatio-phylogenetic hierarchical Bayesian models were built to disentangle potential landscape, climatic and biotic drivers of infection probability while accounting for spatial context and avian host phylogenetic relationships. Results: Idiosyncratic responses of the three most common haemosporidian genera to climate, habitat, host relatedness and host ecological traits indicated marked variation in host infection rates from local to global scales. Notably, host ecological drivers, such as migration distance for Plasmodium and Parahaemoproteus, exhibited predominantly varying or even opposite effects on infection rates across regions, whereas climatic effects on infection rates were more consistent across realms. Moreover, infections in some low-prevalence realms were disproportionately concentrated in a few local hotspots, suggesting that regional-scale variation in habitat and microclimate might influence transmission, in addition to global drivers. Main conclusions: Our hierarchical global analysis supports regional-scale findings showing the synergistic effects of landscape, climate and host ecological traits on parasite transmission for a cosmopolitan and diverse group of avian parasites. Our results underscore the need to account for such interactions, in addition to possible variation in drivers across regions, to produce the robust inference required to predict changes in infection risk under future scenarios.
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| 38. |
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| 39. |
- Kiragu, J. M., et al.
(författare)
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Costs and intermediate outcomes for the implementation of evidence-based practices of midwifery under a MIDWIZE framework in an urban health facility in Nairobi, Kenya
- 2023
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier. - 1877-5756 .- 1877-5764. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Background: Three evidence-based midwife-led care practices: dynamic birth positions (DBP), immediate skin-to-skin contact (SSC) with zero separation between mother and newborn, and delayed cord clamping (DCC), were implemented in four sub-Saharan African countries after an internet-based capacity building program for midwifery leadership in quality improvement (QI). Knowledge on costs of this QI initiative can inform resource mobilization for scale up and sustainability. Methods: We estimated the costs and intermediate outcomes from the implementation of the three evidence-based practices under the midwife-led care (MIDWIZE) framework in a single facility in Kenya through a pre- and post-test implementation design. Daily observations for the level of practice on DBP, SSC and DCC was done at baseline for 1 week and continued during the 11 weeks of the training intervention. Three cost scenarios from the health facility perspective included: scenario 1; staff participation time costs ($515 USD), scenario 2; staff participation time costs plus hired trainer time costs, training material and logistical costs ($1318 USD) and scenario 3; staff participation time costs plus total program costs for the head trainer as the QI leader from the capacity building midwifery program ($8548 USD). Results: At baseline, the level of DBP and SSC practices per the guidelines was at 0 % while that of DCC was at 80 %. After 11 weeks, we observed an adoption of DBP practice of 36 % (N = 111 births), SSC practice of 79 % (N = 241 births), and no change in DCC practice. Major cost driver(s) were midwives’ participation time costs (56 %) for scenario 1 (collaborative), trainers’ material and logistic costs (55 %) in scenario 2(collaborative) and capacity building program costs for the trainer (QI lead) (94 %) in scenario 3 (programmatic). Costs per intermediate outcome were $2.3 USD per birth and $0.5 USD per birth adopting DBP and SSC respectively in Scenario 1; $6.0 USD per birth adopting DBP and $1.4 USD per birth adopting SSC in Scenario 2; $38.5 USD per birth adopting DBP and $8.8 USD per birth adopting SSC in scenario 3. The average hourly wage of the facility midwife was $4.7 USD. Conclusion: Improving adoption of DBP and SSC practices can be done at reasonable facility costs under a collaborative MIDWIZE QI approach. In a programmatic approach, higher facility costs would be needed. This can inform resource mobilization for future QI in similar resource-constrained settings. © 2023
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| 40. |
- Rubia-Rodríguez, Irene, et al.
(författare)
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Whither Magnetic Hyperthermia? : A Tentative Roadmap
- 2021
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.
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| 41. |
- Stoop, Thomas F., et al.
(författare)
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Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
- 2024
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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| 42. |
- Widdicombe, S., et al.
(författare)
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Unifying biological field observations to detect and compare oceanacidification impacts across marine species and ecosystems: what to monitorand why
- 2023
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Ingår i: Ocean Science. - : Copernicus GmbH. - 1812-0784 .- 1812-0792. ; 19:1, s. 101-119
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Tidskriftsartikel (refereegranskat)abstract
- Approximately one-quarter of the CO2 emitted to the atmosphere annually from human activities is absorbed by the ocean, resulting in a reduction of seawater pH and shifts in seawater carbonate chemistry. This multi-decadal process, termed "anthropogenic ocean acidification " (OA), has been shown to have detrimental impacts on marine ecosystems. Recent years have seen a globally coordinated effort to measure the changes in seawater chemistry caused by OA, with best practices now available for these measurements. In contrast to these substantial advances in observing physicochemical changes due to OA, quantifying their biological consequences remains challenging, especially from in situ observations under real-world conditions. Results from 2 decades of controlled laboratory experiments on OA have given insight into the likely processes and mechanisms by which elevated CO2 levels affect biological process, but the manifestation of these process across a plethora of natural situations has yet to be fully explored. This challenge requires us to identify a set of fundamental biological and ecological indicators that are (i) relevant across all marine ecosystems, (ii) have a strongly demonstrated link to OA, and (iii) have implications for ocean health and the provision of ecosystem services with impacts on local marine management strategies and economies. This paper draws on the understanding of biological impacts provided by the wealth of previous experiments, as well as the findings of recent meta-analyses, to propose five broad classes of biological indicators that, when coupled with environmental observations including carbonate chemistry, would allow the rate and severity of biological change in response to OA to be observed and compared. These broad indicators are applicable to different ecological systems, and the methods for data analysis suggested here would allow researchers to combine biological response data across regional and global scales by correlating rates of biological change with the rate of change in carbonate chemistry parameters. Moreover, a method using laboratory observation to design an optimal observing strategy (frequency and duration) and observe meaningful biological rates of change highlights the factors that need to be considered when applying our proposed observation strategy. This innovative observing methodology allows inclusion of a wide diversity of marine ecosystems in regional and global assessments and has the potential to increase the contribution of OA observations from countries with developing OA science capacity.
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| 43. |
- Blomgren, J., et al.
(författare)
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Putting co-creation into practice : lessons learned from developing a midwife-led quality improvement intervention
- 2023
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Ingår i: Global Health Action. - : Taylor and Francis Ltd.. - 1654-9716 .- 1654-9880. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Integrating evidence-based midwifery practices improves healthcare quality for women and newborns, but an evidence-to-practice gap exists. Co-created quality improvement initiatives led by midwives could bridge this gap, prevent resource waste and ensure intervention relevance. However, how to co-create a midwife-led quality improvement intervention has not been scientifically explored. Objective: The objective of this study is to describe the co-creation process and explore the needs and determinants of a midwife-led quality improvement targeting evidence-based midwifery practices. Methods: A qualitative deductive approach using the Consolidated Framework for Advancing Implementation Science was employed. An analysis matrix based on the framework was developed, and the data were coded according to categories. Data were gathered from interviews, focus group discussions, observations and workshops. New mothers and birth companions (n = 19) were included through convenience sampling. Midwives (n = 26), professional association representatives, educators, policymakers, managers, and doctors (n = 7) were purposely sampled. Results: The co-creation process of the midwife-led Quality Improvement intervention took place in four stages. Firstly, core elements of the intervention were established, featuring a group of midwife champions leading a quality improvement initiative using a train-the-trainers approach. Secondly, the intervention needs, context and determinants were explored, which showed knowledge and skills gaps, a lack of shared goals among staff, and limited resources. However, there was clear relevance, compatibility, and mission alignment for a midwife-led quality improvement at all levels. Thirdly, during co-creation workshops with new mothers and companions, the consensus was to prioritise improved intrapartum support, while workshops with midwives identified enhancing the use of birth positions and perineal protection as key focus areas for the forthcoming Quality Improvement intervention. Lastly, the findings guided intervention strategies, including peer-assisted learning, using existing structures, developing educational material, and building stakeholder relationships. Conclusions: This study provides a practical example of a co-creation process for a midwife-led quality improvement intervention, which can be relevant in different maternity care settings. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 44. |
- Bondarenko, Vasyl, et al.
(författare)
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Structures of highly flexible intracellular domain of human alpha 7 nicotinic acetylcholine receptor
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular domain (ICD) of Cys-loop receptors mediates diverse functions. To date, no structure of a full-length ICD is available due to challenges stemming from its dynamic nature. Here, combining nuclear magnetic resonance (NMR) and electron spin resonance experiments with Rosetta computations, we determine full-length ICD structures of the human alpha 7 nicotinic acetylcholine receptor in a resting state. We show that similar to 57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning similar to 50 angstrom from the central channel axis. Loop L is anchored onto the MA helix and virtually forms two smaller loops, thereby increasing its stability. Previously known motifs for cytoplasmic binding, regulation, and signaling are found in both the helices and disordered flexible regions, supporting the essential role of the ICD conformational plasticity in orchestrating a broad range of biological processes.
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| 45. |
- Brooks, William, et al.
(författare)
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Historically Authentic Truths (the HAT trick) : Facts, fancies and footnotes
- 2021. - 1
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Ingår i: Music and Heritage. - : Taylor & Francis. ; , s. 183-193
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Bokkapitel (refereegranskat)abstract
- Footnotes, a composition written between 1983 and 1985 by a composer allegedly named William Brooks, was recorded between 2011 and 2018 by guitarist Stefan Östersjö and sound engineer Jez Wells, with the help of William Brooks, musicologist. It became evident to the three collaborators that the overall project required the construction of a set of different identities for each participant: guitar, guitarist; score, composer; hardware, engineer. This chapter traces the construction of, distinction between and eventual representation of those identities. It considers the extent to which a single entity – personality, place, artifact or historical event – can be regarded as a collection of irreconcilable differences, whether those differences can be constituted as a series of masks or persona and whether anything can truly be said to reside behind those masks.
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| 46. |
- Cesano, A, et al.
(författare)
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Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II-practical challenges
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated with the infrastructure, technology, workforce, and sustainability required for clinical biomarker data sharing. To provide guidance and assist in the navigation of these challenges, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to outline the challenges that researchers currently face, both at the conceptual level (Volume I) and at the technical level (Volume II). The committee also suggests possible solutions to these problems in the form of professional standards and harmonized requirements for data sharing, assisting in continued progress toward effective, clinically relevant biomarkers in the IO setting.
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| 47. |
- Christiansen, Colette, et al.
(författare)
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Adipose methylome integrative-omic analyses reveal genetic and dietary metabolic health drivers and insulin resistance classifiers
- 2022
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is considerable evidence for the importance of the DNA methylome in metabolic health, for example, a robust methylation signature has been associated with body mass index (BMI). However, visceral fat (VF) mass accumulation is a greater risk factor for metabolic disease than BMI alone. In this study, we dissect the subcutaneous adipose tissue (SAT) methylome signature relevant to metabolic health by focusing on VF as the major risk factor of metabolic disease. We integrate results with genetic, blood methylation, SAT gene expression, blood metabolomic, dietary intake and metabolic phenotype data to assess and quantify genetic and environmental drivers of the identified signals, as well as their potential functional roles. Methods: Epigenome-wide association analyses were carried out to determine visceral fat mass-associated differentially methylated positions (VF-DMPs) in SAT samples from 538 TwinsUK participants. Validation and replication were performed in 333 individuals from 3 independent cohorts. To assess functional impacts of the VF-DMPs, the association between VF and gene expression was determined at the genes annotated to the VF-DMPs and an association analysis was carried out to determine whether methylation at the VF-DMPs is associated with gene expression. Further epigenetic analyses were carried out to compare methylation levels at the VF-DMPs as the response variables and a range of different metabolic health phenotypes including android:gynoid fat ratio (AGR), lipids, blood metabolomic profiles, insulin resistance, T2D and dietary intake variables. The results from all analyses were integrated to identify signals that exhibit altered SAT function and have strong relevance to metabolic health. Results: We identified 1181 CpG positions in 788 genes to be differentially methylated with VF (VF-DMPs) with significant enrichment in the insulin signalling pathway. Follow-up cross-omic analysis of VF-DMPs integrating genetics, gene expression, metabolomics, diet, and metabolic traits highlighted VF-DMPs located in 9 genes with strong relevance to metabolic disease mechanisms, with replication of signals in FASN, SREBF1, TAGLN2, PC and CFAP410. PC methylation showed evidence for mediating effects of diet on VF. FASN DNA methylation exhibited putative causal effects on VF that were also strongly associated with insulin resistance and methylation levels in FASN better classified insulin resistance (AUC=0.91) than BMI or VF alone. Conclusions: Our findings help characterise the adiposity-associated methylation signature of SAT, with insights for metabolic disease risk.
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| 48. |
- Depelsenaire, Alexandra C. I., et al.
(författare)
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Cellular responses at the application site of a high-density microarray patch delivering an influenza vaccine in a randomized, controlled phase I clinical trial
- 2021
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 16:7
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Tidskriftsartikel (refereegranskat)abstract
- Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use and more cost-effective method for administration of vaccines when compared to the needle and syringe. Since MAPs deliver vaccine to the dermis and epidermis, a degree of local immune response at the site of application is expected. In a phase 1 clinical trial (ACTRN 12618000112268), the Vaxxas high-density MAP (HD-MAP) was used to deliver a monovalent, split inactivated influenza virus vaccine into the skin. HD-MAP immunisation led to significantly enhanced humoral responses on day 8, 22 and 61 compared with IM injection of a quadrivalent commercial seasonal influenza vaccine (Afluria Quadrivalent (R)). Here, the aim was to analyse cellular responses to HD-MAPs in the skin of trial subjects, using flow cytometry and immunohistochemistry. HD-MAPs were coated with a split inactivated influenza virus vaccine (A/Singapore/GP1908/2015 [H1N1]), to deliver 5 mu g haemagglutinin (HA) per HD-MAP. Three HD-MAPs were applied to the volar forearm (FA) of five healthy volunteers (to achieve the required 15 mu g HA dose), whilst five control subjects received three uncoated HD-MAPs (placebo). Local skin response was recorded for over 61 days and haemagglutination inhibition antibody titres (HAI) were assessed on days 1, 4, 8, 22, and 61. Skin biopsies were taken before (day 1), and three days after HD-MAP application (day 4) and analysed by flow-cytometry and immunohistochemistry to compare local immune subset infiltration. HD-MAP vaccination with 15 mu g HA resulted in significant HAI antibody titres compared to the placebo group. Application of uncoated placebo HD-MAPs resulted in mild erythema and oedema in most subjects, that resolved by day 4 in 80% of subjects. Active, HA-coated HD-MAP application resulted in stronger erythema responses on day 4, which resolved between days 22-61. Overall, these erythema responses were accompanied by an influx of immune cells in all subjects. Increased cell infiltration of CD3(+), CD4(+), CD8(+) T cells as well as myeloid CD11b(+) CD11c(+) and non-myeloid CD11b(-) dendritic cells were observed in all subjects, but more pronounced in active HD-MAP groups. In contrast, CD19(+)/CD20(+) B cell counts remained unchanged. Key limitations include the use of an influenza vaccine, to which the subjects may have had previous exposure. Different results might have been obtained with HD-MAPs inducing a primary immune response. In conclusion, influenza vaccine administered to the forearm (FA) using the HD-MAP was well-tolerated and induced a mild to moderate skin response with lymphocytic infiltrate at the site of application.
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| 49. |
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| 50. |
- Erlandsson, Kerstin, 1961-, et al.
(författare)
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Implementing an internet-based capacity building program for interdisciplinary midwifery-lead teams in Ethiopia, Kenya Malawi and Somalia
- 2021
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier B.V.. - 1877-5756 .- 1877-5764. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish care model MIDWIZE defined as midwife-led interdisciplinary care and zero separation between mother and newborn, was implemented in 2020–21 in Ethiopia, Kenya, Malawi, and Somalia in a capacity building programme funded by the Swedish Institute. Objective: To determine the feasibility of using an internet-based capacity building programme contributing to effective midwifery practices in the labour rooms through implementation of dynamic birthing positions, delayed umbilical cord clamping and skin-to-skin care of newborns in the immediate postnatal period. Methods: The design is inspired by process evaluation. Focus group discussions with policy leaders, academicians, and clinicians who participated in the capacity building programme were carried out. Before and after the intervention, the numbers for dynamic birthing positions, delayed umbilical cord clamping and skin-to-skin care of the newborn in the immediate postnatal period were detected. Results: Participants believed the internet-based programme was appropriate for their countries’ contexts based on their need for improved leadership and collaboration, the need for strengthened human resources, and the vast need for improved outcomes of maternal and newborn health. Conclusion: The findings provide insight into the feasibility to expand similar online capacity building programmes in collaboration with onsite policy leaders, academicians, and clinicians in sub-Saharan African countries with an agenda for improvements in maternal and child health. © 2021
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