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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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4. |
- Yao, W-M, et al.
(författare)
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Review of Particle Physics
- 2006
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 33:1, s. 1-1
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Tidskriftsartikel (refereegranskat)
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5. |
- Hagiwara, K, et al.
(författare)
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Review of particle physics
- 2002
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Ingår i: Physical Review D (Particles and Fields). - 0556-2821. ; 66:1
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Forskningsöversikt (refereegranskat)abstract
- This biennial Review summarizes much of Particle Physics Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles All the particle properties and search limits are listed in Summary Tables We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review) Another new review is on Grand Unified Theories A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review All tables, listings, and reviews (and errata) are also available on the Particle Data Group website http //pdg 1b1 gov.
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6. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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9. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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10. |
- Scott, G. D., et al.
(författare)
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Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.
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12. |
- Brown, C.L, et al.
(författare)
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Social Activity and Cognitive Functioning Over Time
- 2012
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Ingår i: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212.
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Tidskriftsartikel (refereegranskat)abstract
- Social activity is typically viewed as part of an engaged lifestyle that may help mitigate the deleterious effects of advanced age on cognitive function. As such, social activity has been examined in relation to cognitive abilities later in life. However, longitudinal evidence for this hypothesis thus far remains inconclusive. The current study sought to clarify the relationship between social activity and cognitive function over time using a coordinated data analysis approach across four longitudinal studies. A series of multilevel growth models with social activity included as a covariate is presented. Four domains of cognitive function were assessed: reasoning, memory, fluency, and semantic knowledge. Results suggest that baseline social activity is related to some, but not all, cognitive functions. Baseline social activity levels failed to predict rate of decline in most cognitive abilities. Changes in social activity were not consistently associated with cognitive functioning. Our findings do not provide consistent evidence that changes in social activity correspond to immediate benefits in cognitive functioning, except perhaps for verbal fluency.
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13. |
- Mitchell, M.B, et al.
(författare)
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Cognitively stimulating activities: Effects on cognition across four studies with up to 21 years of longitudinal data
- 2012
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Ingår i: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2012
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Tidskriftsartikel (refereegranskat)abstract
- Engagement in cognitively stimulating activities has been considered to maintain or strengthen cognitive skills, thereby minimizing age-related cognitive decline. While the idea that there may be a modifiable behavior that could lower risk for cognitive decline is appealing and potentially empowering for older adults, research findings have not consistently supported the beneficial effects of engaging in cognitively stimulating tasks. Using observational studies of naturalistic cognitive activities, we report a series of mixed effects models that include baseline and change in cognitive activity predicting cognitive outcomes over up to 21 years in four longitudinal studies of aging. Consistent evidence was found for cross-sectional relationships between level of cognitive activity and cognitive test performance. Baseline activity at an earlier age did not, however, predict rate of decline later in life, thus not supporting the concept that engaging in cognitive activity at an earlier point in time increases one's ability to mitigate future age-related cognitive decline. In contrast, change in activity was associated with relative change in cognitive performance. Results therefore suggest that change in cognitive activity from one's previous level has at least a transitory association with cognitive performance measured at the same point in time.
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14. |
- Thompson, Luke R., et al.
(författare)
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A communal catalogue reveals Earth's multiscale microbial diversity
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.
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20. |
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21. |
- Lindwall, Magnus, 1975, et al.
(författare)
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Dynamic associations of change in physical activity and change in cognitive function: Coordinated analyses of four longitudinal studies
- 2012
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Ingår i: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2012
-
Tidskriftsartikel (refereegranskat)abstract
- The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person) and time-varying (within-person) predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge) was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency.
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22. |
- Raininko, Raili, et al.
(författare)
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Observer variability in the assessment of disc degeneration on MRI of the lumbar and thoracic spine
- 1995
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 20:9, s. 1029-35
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN. Intraobserver and interobserver reproducibility study. OBJECTIVE. This study investigates the variability in the interpretation of degenerative disc findings using magnetic resonance imaging. SUMMARY OF BACKGROUND DATA. Magnetic resonance imaging has been used for years in clinical diagnostics, primarily to investigate disc herniation and spinal stenosis. Less attention has been paid to other disc findings and their assessment reliability. METHODS. Three independent readers evaluated magnetic resonance images of the lumbar and the lower and middle thoracic spines of 122 subjects by grading 12 aspects of the intervertebral discs and adjacent endplates using written definitions and example images. Images of 20 subjects were reevaluated for the assessment of intraobserver agreement. RESULTS. Agreement was highest in the lower lumbar and poorest in the middle thoracic spine. Intraobserver agreement was generally fair to excellent for almost all variables in the lumbar and lower thoracic spine (most intraclass correlation and kappa coefficients for these regions were above 0.70). Interobserver agreement was notably lower than intraobserver agreement, except for osteophytes and endplate defects in some regions. CONCLUSIONS. Intraobserver agreement in the evaluation of disc degeneration was at an acceptable level, in general, in the lumbar and lower thoracic spine. However, assessments were substantially more variable between readers, which limits comparisons of evaluations between different readers.
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23. |
- Rubin, D., et al.
(författare)
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Precision Measurement of The Most Distant Spectroscopically Confirmed Supernova Ia with the Hubble Space Telescope
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:1, s. 35-
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a redshift 1.71 supernova in the GOODS-North field. The Hubble Space Telescope (HST) ACS spectrum has almost negligible contamination from the host or neighboring galaxies. Although the rest-frame-sampled range is too blue to include any Si II line, a principal component analysis allows us to confirm it as a Type Ia supernova with 92% confidence. A recent serendipitous archival HST WFC3 grism spectrum contributed a key element of the confirmation by giving a host-galaxy redshift of 1.713 +/- 0.007. In addition to being the most distant SN Ia with spectroscopic confirmation, this is the most distant Ia with a precision color measurement. We present the ACS WFC and NICMOS 2 photometry and ACS and WFC3 spectroscopy. Our derived supernova distance is in agreement with the prediction of CDM.
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24. |
- Sawyer, L. M., et al.
(författare)
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Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response
- 2019
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : WILEY. - 0926-9959 .- 1468-3083. ; 33:2, s. 355-366
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Forskningsöversikt (refereegranskat)abstract
- Background Patients with moderate-to-severe psoriasis require long-term treatment, yet few trials compare outcomes beyond a short-term induction period. Quantitative comparisons of long-term outcomes in patients with psoriasis are limited. To our knowledge, no network meta-analysis (NMA) of such data has been performed. Objective To compare novel systemic therapies, both biologic and non-biologic, approved for moderate-to-severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year. Methods An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention-to-treat approach with non-responder imputation were used. Results Twenty-four studies reporting outcomes at 40-64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52-week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long-term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long-term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded. Conclusion Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long-term active-comparator RCT data are required to better assess relative efficacy across therapies.
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25. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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26. |
- Appendino, G, et al.
(författare)
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Antibacterial galloylated alkylphloroglucinol glucosides from myrtle (Myrtus communis)
- 2006
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 69:2, s. 251-254
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Tidskriftsartikel (refereegranskat)abstract
- An investigation of the polar glycosidic fraction from the leaves of myrtle afforded four galloylated nonprenylated phloroglucinol glucosides (3a-d) related to the endoperoxide hormone G3 (4) in terms of structure and biogenesis. Despite their close similarity, significant antibacterial activity was shown only by one of these compounds (3b, gallomyrtucommulone B), while the G3 hormone (4) was inactive.
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27. |
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28. |
- Armstrong, Chelsey, et al.
(författare)
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Anthropological contributions to historical ecology : 50 questions, infinite prospects
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.
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30. |
- Ellis, Gemma L, et al.
(författare)
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Two-Step synthesis of Achiral Dispiro-1,2,4,5-tetraoxanes with outstanding antimalarial activity, low toxicity, and high-stability profiles
- 2008
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:7, s. 2170-2177
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Tidskriftsartikel (refereegranskat)abstract
- A rapid, two step synthesis of a range of dispiro-1,2,4,5-tetraoxanes with potent antimalarial activity both in vitro and in vivo has been achieved. These 1,2,4,5-tetraoxanes have been proven to be superior to 1,2,4-trioxolanes in terms of stability and to be superior to trioxane analogues in terms of both stability and activity. Selected analogues have in vitro nanomolar antimalarial activity, good oral activity and are non-toxic in screens for both cytotoxicity and genotoxicity. The synthesis of a fluorescent NBD-tagged tetraoxane probe has allowed investigation into the mechanism of accumulation of these drugs using laser scanning confocal microscopy techniques.
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31. |
- Fuller, M., et al.
(författare)
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The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis
- 2015
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 309:10, s. 840-851
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2−/−mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2−/−and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2−/−mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis. © 2015 the American Physiological Society.
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32. |
- Gangannagaripalli, J., et al.
(författare)
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A Standard Set of Value-Based Patient-Centered Outcomes and Measures of Overall Health in Adults
- 2022
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Ingår i: Patient-Patient Centered Outcomes Research. - : Springer Science and Business Media LLC. - 1178-1653 .- 1178-1661. ; 15:3, s. 341-351
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Tidskriftsartikel (refereegranskat)abstract
- Background The definition of population-specific outcomes is an essential precondition for the implementation of value-based health care. We developed a minimum standard outcome set for overall adult health (OAH) to facilitate the implementation of value-based health care in tracking, comparing, and improving overall health care outcomes of adults across multiple conditions, which would be of particular relevance for primary care and public health populations. Methods The International Consortium for Health Outcomes Measurement (ICHOM) convened an international panel (patients, clinicians, and topic experts). Following the development of a conceptual framework, a modified Delphi method (supported by public consultations) was implemented to identify, in sequence, the relevant domains, the best instruments for measuring them, the timing of measurement, and the relevant adjustment variables. Findings Outcomes were identified in relation to overall health status and the domains of physical, mental, and social health. Three instruments covering these domains were identified: PROMIS Scale v1.2-Global Health (10 items), WHO Wellbeing Index (5 items), and the WHO Disability Assessment Schedule 2.0 (12 items). Case-mix variables included a range of sociodemographic and biometric measures. Yearly measurement was proposed for all outcomes and most case-mix variables. Interpretation The ICHOM OAH Standard Set has been developed through consensus-based methods based on predefined criteria following high standards for the identification and selection of high-quality measures The involvements of a wide range of stakeholders supports the acceptability of the set, which is readily available for use and feasibility testing in clinical settings.
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33. |
- Hirani, Nikhil, et al.
(författare)
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Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:5
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Tidskriftsartikel (refereegranskat)abstract
- Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139: placebo ratio) with once-daily doses of TD139 (0.3–10 mg) for 14 days. Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration (Cmax) values ranging from 0.6 to 3 h and a plasma half-life (T1/2) of 8 h. The concentration of TD139 in the lung was >567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-dependent inhibition demonstrated. Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (platelet-derived growth factor-BB, plasminogen activator inhibitor-1, Gal-3, CCL18 and YKL-40). TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on bronchoalveolar lavage macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression.
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34. |
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35. |
- Jandrić, P., et al.
(författare)
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Collective Writing : The Continuous Struggle for Meaning-Making
- 2023
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Ingår i: Postdigital Science and Education. - : Springer Nature. - 2524-485X .- 2524-4868. ; 5:3, s. 851-893
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Tidskriftsartikel (refereegranskat)abstract
- This paper is a summary of philosophy, theory, and practice arising from collective writing experiments conducted between 2016 and 2022 in the community associated with the Editors’ Collective and more than 20 scholarly journals. The main body of the paper summarises the community’s insights into the many faces of collective writing. Appendix 1 presents the workflow of the article’s development. Appendix 2 lists approximately 100 collectively written scholarly articles published between 2016 and 2022. Collective writing is a continuous struggle for meaning-making, and our research insights merely represent one milestone in this struggle. Collective writing can be designed in many different ways, and our workflow merely shows one possible design that we found useful. There are many more collectively written scholarly articles than we could gather, and our reading list merely offers sources that the co-authors could think of. While our research insights and our attempts at synthesis are inevitably incomplete, ‘Collective Writing: The Continuous Struggle for Meaning-Making’ is a tiny theoretical steppingstone and a useful overview of sources for those interested in theory and practice of collective writing.
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37. |
- MacKinnon, Alison C., et al.
(författare)
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Regulation of Transforming Growth Factor-beta 1-driven Lung Fibrosis by Galectin-3
- 2012
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 185:5, s. 537-546
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic dysregulated response to alveolar epithelial injury with differentiation of epithelial cells and fibroblasts into matrix-secreting myofibroblasts resulting in lung scaring. The prognosis is poor and there are no effective therapies or reliable biomarkers. Galectin-3 is a beta-galactoside binding lectin that is highly expressed in fibrotic tissue of diverse etiologies. Objectives: To examine the role of galectin-3 in pulmonary fibrosis. Methods: We used genetic deletion and pharmacologic inhibition in well-characterized murine models of lung fibrosis. Further mechanistic studies were performed in vitro and on samples from patients with IPF. Measurements and Main Results: Transforming growth factor (TGF)-beta and bleomycin-induced lung fibrosis was dramatically reduced in mice deficient in galectin-3, manifest by reduced TGF-beta 1 induced EMT and myofibroblast activation and collagen production. Galectin-3 reduced phosphorylation and nuclear translocation of beta-catenin but had no effect on Smad2/3 phosphorylation. A novel inhibitor of galectin -3, TD139, blocked TGF-beta-induced beta-catenin activation in vitro and in vivo and attenuated the late-stage progression of lung fibrosis after bleomycin. There was increased expression of galectin-3 in the bronchoalveolar lavage fluid and serum from patients with stable IPF compared with nonspecific interstitial pneumonitis and controls, which rose sharply during an acute exacerbation suggesting that. galectin-3 may be a marker of active fibrosis in IPF and that strategies that block galectin-3 may be effective in treating acute fibrotic exacerbations of IPF. Conclusions: This study identifies galectin-3 as an important regulator of lung fibrosis and provides a proof of principle for galectin-3 inhibition as a potential novel therapeutic strategy for IPF.
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38. |
- Montorsi, Lucia, et al.
(författare)
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Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1, s. 4051-4051
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.
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- Santana, M. J., et al.
(författare)
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Improving the quality of person-centred healthcare from the patient perspective: development of person-centred quality indicators
- 2020
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Importance International efforts are being made towards a person-centred care (PCC) model, but there are currently no standardised mechanisms to measure and monitor PCC at a healthcare system level. The use of metrics to measure PCC can help to drive the changes needed to improve the quality of healthcare that is person centred. Objective To develop and validate person-centred care quality indicators (PC-QIs) measuring PCC at a healthcare system level through a synthesis of the evidence and a person-centred consensus approach to ensure the PC-QIs reflect what matters most to people in their care. Methods Existing indicators were first identified through a scoping review of the literature and an international environmental scan. Focus group discussions with diverse patients and caregivers and interviews with clinicians and experts in quality improvement allowed us to identify gaps in current measurement of PCC and inform the development of new PC-QIs. A set of identified and newly developed PC-QIs were subsequently refined by Delphi consensus process using a modified RAND/UCLA Appropriateness Method. The international consensus panel consisted of patients, family members, community representatives, clinicians, researchers and healthcare quality experts. Results From an initial 39 unique evidence-based PC-QIs identified and developed, the consensus process yielded 26 final PC-QIs. These included 7 related to structure, 16 related to process, 2 related to outcome and 1 overall global PC-QI. Conclusions The final 26 evidence-based and person-informed PC-QIs can be used to measure and evaluate quality incorporating patient perspectives, empowering jurisdictions to monitor healthcare system performance and evaluate policy and practice related to PCC.
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- Videman, Tapio, et al.
(författare)
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Disc degeneration and bone density in monozygotic twins discordant forinsulin-dependent diabetes mellitus
- 2000
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 18:5, s. 768-72
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Tidskriftsartikel (refereegranskat)abstract
- The effects of insulin-dependent diabetes mellitus on bone density and connective tissue degeneration have theoretical interest and practical relevance. Several experimental studies in animals have demonstrated the harmful effects of insulin deficiency on connective tissues. However, clinical studies in humans have produced somewhat contradictory results, most likely due to difficulties controlling for general degeneration and factors associated with diabetes. In nine pairs of monozygotic twins discordant for insulin-dependent diabetes mellitus, we compared femoral and lumbar bone mineral density (assessed by dual-energy x-ray absorptiometry) and spinal degeneration (assessed by magnetic resonance imaging). The bone densities were, on average, 0.1-0.3% lower (p = 0.87-0.96) in diabetic patients. However, after controlling for smoking, we found that the bone density in the femoral neck was 2.5% (0.025 g/cm2) lower in diabetic individuals than in their twins (p = 0.09). The five magnetic resonance imaging parameters used to evaluate disc degeneration did not differ between diabetic patients and their twins. In conclusion, our results provide no evidence that insulin-dependent diabetes mellitus has any major effect on bone density or disc degeneration.
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- Østergaard, Søren D, et al.
(författare)
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Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study.
- 2015
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Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR).METHODS AND FINDINGS: We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses.CONCLUSIONS: Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure--or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications--may reduce AD risk.
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