| 1. |
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| 2. |
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| 3. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 4. |
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| 5. |
- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 6. |
- Jami, E. S., et al.
(författare)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 7. |
- Thompson, PM, et al.
(författare)
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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| 8. |
- Boutet, S., et al.
(författare)
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High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6092, s. 362-364
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Tidskriftsartikel (refereegranskat)abstract
- Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.
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| 9. |
- Hillier, J. K., et al.
(författare)
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Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness
- 2015
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Ingår i: Journal of Maps. - : Informa UK Limited. - 1744-5647. ; 11:5, s. 719-729
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Tidskriftsartikel (refereegranskat)abstract
- Mapped topographic features are important for understanding processes that sculpt the Earth's surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34-40%), but reliability of mapping is higher (72-86%). The maps form a reference dataset.
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| 10. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 11. |
- Stack, K. M., et al.
(författare)
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Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
- 2024
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 129:2
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low-angle cross stratified sandstone, thin-bedded granule sandstone, and thick-bedded granule-pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment-deformed sandstone interbedded with broad, unconfined coarser-grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft-sediment deformed laminated, sulfate-bearing mudstone with lenses of low-angle cross-stratified and scoured sandstone; and FA3, comprised of dipping planar, thin-bedded sand-gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand-dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long-lived, habitable lacustrine and deltaic environment within Jezero crater.
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| 12. |
- Dorschel, Boris, et al.
(författare)
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The International Bathymetric Chart of the Southern Ocean Version 2
- 2022
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60 degrees S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50 degrees S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50 degrees S.
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| 13. |
- Finn, Robert D., et al.
(författare)
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Pfam : the protein families database
- 2014
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 42:D1, s. d222-D230
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Tidskriftsartikel (refereegranskat)abstract
- Pfam, available via servers in the UK (http://pfam.sanger.ac.uk/) and the USA (http://pfam.janelia.org/), is a widely used database of protein families, containing 14 831 manually curated entries in the current release, version 27.0. Since the last update article 2 years ago, we have generated 1182 new families and maintained sequence coverage of the UniProt Knowledgebase (UniProtKB) at nearly 80%, despite a 50% increase in the size of the underlying sequence database. Since our 2012 article describing Pfam, we have also undertaken a comprehensive review of the features that are provided by Pfam over and above the basic family data. For each feature, we determined the relevance, computational burden, usage statistics and the functionality of the feature in a website context. As a consequence of this review, we have removed some features, enhanced others and developed new ones to meet the changing demands of computational biology. Here, we describe the changes to Pfam content. Notably, we now provide family alignments based on four different representative proteome sequence data sets and a new interactive DNA search interface. We also discuss the mapping between Pfam and known 3D structures.
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| 14. |
- Finn, Robert D., et al.
(författare)
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The Pfam protein families database
- 2010
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 38, s. d211-d222
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Tidskriftsartikel (refereegranskat)abstract
- Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is similar to 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11 912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).
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| 15. |
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| 16. |
- Litvak, M.L., et al.
(författare)
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Local variations of bulk hydrogen and chlorine-equivalent neutron absorption content measured at the contact between the Sheepbed and Gillespie Lake units in Yellowknife Bay, Gale Crater, using the DAN instrument onboard Curiosity
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1259-1275
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Tidskriftsartikel (refereegranskat)abstract
- Data gathered with the Dynamic Albedo of Neutron (DAN) instrument onboard rover Curiosity were analyzed for variations in subsurface neutron flux and tested for possible correlation with local geological context. A special DAN observation campaign was executed, in which 18 adjacent DAN active measurements were acquired every 0.75–1.0 m to search for the variations of subsurface hydrogen content along a 15 m traverse across geologic contacts between the Sheepbed and Gillespie Lake members of the Yellowknife Bay formation. It was found that several subunits in Sheepbed and Gillespie Lake could be characterized with different depth distributions of water-equivalent hydrogen (WEH) and different chlorine-equivalent abundance responsible for the distribution of neutron absorption elements. The variations of the average WEH at the top 60 cm of the subsurface are estimated at up to 2–3%. Chlorine-equivalent neutron absorption abundances ranged within 0.8–1.5%. The largest difference in WEH and chlorine-equivalent neutron absorption distribution is found between Sheepbed and Gillespie Lake.
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| 17. |
- Punta, Marco, et al.
(författare)
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The Pfam protein families database
- 2012
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 40:D1, s. D290-D301
-
Tidskriftsartikel (refereegranskat)abstract
- Pfam is a widely used database of protein families, currently containing more than 13 000 manually curated protein families as of release 26.0. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/). Here, we report on changes that have occurred since our 2010 NAR paper (release 24.0). Over the last 2 years, we have generated 1840 new families and increased coverage of the UniProt Knowledgebase (UniProtKB) to nearly 80%. Notably, we have taken the step of opening up the annotation of our families to the Wikipedia community, by linking Pfam families to relevant Wikipedia pages and encouraging the Pfam and Wikipedia communities to improve and expand those pages. We continue to improve the Pfam website and add new visualizations, such as the 'sunburst' representation of taxonomic distribution of families. In this work we additionally address two topics that will be of particular interest to the Pfam community. First, we explain the definition and use of family-specific, manually curated gathering thresholds. Second, we discuss some of the features of domains of unknown function (also known as DUFs), which constitute a rapidly growing class of families within Pfam.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Braae, Ellen, et al.
(författare)
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A conversation on education
- 2018
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Ingår i: Routledge Research Companion to Landscape Architecture. - : Routledge. ; , s. 324-334
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Landscape architecture today is becoming increasingly professionalized as a quasi-global profession—not least through the successful expansion of academic research efforts within the discipline. This includes the kinds of effort to which this volume as a whole contributes, and this chapter broadens our understanding of the institutional structures within which we operate. Indeed, education may be one of the most important realms for the engagement and transmission of knowledge that moves back and forth and connects practice and research in intricate ways—with the added benefit that education remains a dialogical and personal setting for exchange, not least in studio-driven design programmes. We therefore have asked significant educators from Landscape Architecture programmes in Europe and North America to reflect on the tensions and challenges the profession currently faces, and on what we can do to prepare new generations of landscape architects who are now part of the educational system or will be so in the future. Moreover, we wished to inspire a discussion of how the aesthetic and ethical dimensions of landscape architecture potentially impact on the discipline, and of the role they should play in future landscape architecture education.
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| 24. |
- Chaplin, E., et al.
(författare)
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Severe mental illness, common mental disorders, and neurodevelopmental conditions amongst 9088 lower court attendees in London, UK
- 2022
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Ingår i: Bmc Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Court Mental Health Liaison and Diversion Services (CMHLDS) have developed in some countries as a response to the over-representation of mental illness and other vulnerabilities amongst defendants presenting to criminal justice (or correctional) systems. This study examined the characteristics and rates of mental disorder of 9088 defendants referred to CMHLDS. Method The study analysed service level data, obtained from the National Health Service's mental health data set, to examine characteristics relating to gender, ethnicity and comorbidity of common mental and neurodevelopmental disorders at five CMHLDS across London between September 2015 and April 2017. Results The sample included 7186 males (79.1%) and 1719 females (18.9%), the gender of 183 (2%) were not recorded. Of those referred, 6616 (72.8%) presented with an identifiable mental disorder and 503 (5.5%) with a neurodevelopmental disorder (NDD). Significantly higher rates of schizophrenia were reported amongst Black defendants (n = 681; 37.2%) and Asian defendants (n = 315; 29%), while higher rates of depression were found amongst White defendants (n = 1007; 22.1%). Substance misuse was reported amongst 2813 defendants (31%), and alcohol misuse amongst 2111 (23.2%), with significantly high rates of substance and alcohol misuse amongst defendants presenting with schizophrenia or personality disorder. Conclusions This is one of the largest studies to examine mental health needs and vulnerabilities amongst defendants presenting to CMHLDS. It will enable an improved understanding of the required service designs and resources required to manage the healthcare pathways for people attending CMHLDS.
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| 25. |
- Deutsch, Eric W., et al.
(författare)
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Expanding the Use of Spectral Libraries in Proteomics
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:12, s. 4051-4060
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Tidskriftsartikel (refereegranskat)abstract
- The 2017 Dagstuhl Seminar on Computational Proteomics provided an opportunity for a broad discussion on ABSTRACT: The 2017 Dagstuhl Seminar on Computational the current state and future directions of the generation and use of peptide tandem mass spectrometry spectral libraries. Their use in proteomics is growing slowly, but there are multiple challenges in the field that must be addressed to further increase the adoption of spectral libraries and related techniques. The primary bottlenecks are the paucity of high quality and comprehensive libraries and the general difficulty of adopting spectral library searching into existing workflows. There are several existing spectral library formats, but none captures a satisfactory level of metadata; therefore, a logical next improvement is to design a more advanced, Proteomics Standards Initiative-approved spectral library format that can encode all of the desired metadata. The group discussed a series of metadata requirements organized into three designations of completeness or quality, tentatively dubbed bronze, silver, and gold. The metadata can be organized at four different levels of granularity: at the collection (library) level, at the individual entry (peptide ion) level, at the peak (fragment ion) level, and at the peak annotation level. Strategies for encoding mass modifications in a consistent manner and the requirement for encoding high-quality and commonly seen but as-yet-unidentified spectra were discussed. The group also discussed related topics, including strategies for comparing two spectra, techniques for generating representative spectra for a library, approaches for selection of optimal signature ions for targeted workflows, and issues surrounding the merging of two or more libraries into one. We present here a review of this field and the challenges that the community must address in order to accelerate the adoption of spectral libraries in routine analysis of proteomics datasets.
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| 26. |
- Eriksson, David, et al.
(författare)
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Critical Manufacturing Prerequisites for Successful Reshoring
- 2021
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Ingår i: Operations and Supply Chain Management. - : OSCM FORUM. - 1979-3561 .- 2579-9363. ; 14:2, s. 249-260
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Tidskriftsartikel (refereegranskat)abstract
- Reshoring is an emergent theme in research and practice. It is important for researchers to understand the motivating force and prerequisites for these reshoring activities, and to develop a method that supports sustainable reshoring decisions. The purpose of this study is to shed light on the prerequisites for successful reshoring. The preparation for this study consists of a systematic literature review. The findings presented here, however, are revelatory and emerged during a workshop. The findings were further researched at a total of four companies, which were part of data collection in a larger project. This research identified three scenarios, in which preceding manufacturing step, creation of parallel steps, or exploration of overcapacity are central. The paper also presents a stage-gateprocess for reshoring decisions as well as a typology of reshoring alternatives. This research sheds light on prerequisites and contextual factors that enable companies to reshore. The importance of manufacturing capabilities can be seen in literature, but has not yet, to our knowledge, been given sufficient attention. The main practical implication is related to offshoring. Overly-aggressive offshoring can complicate future reshoring. As such, reshoring needs to be considered during offshoring, specifically what manufacturing capabilities that are kept at the domestic location.
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| 27. |
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| 28. |
- Hickman, PE, et al.
(författare)
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Decision limits and the reporting of cardiac troponin : Meeting the needs of both the cardiologist and the ED physician
- 2015
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Ingår i: Critical reviews in clinical laboratory sciences. - : Informa UK Limited. - 1040-8363 .- 1549-781X. ; 52:1, s. 28-44
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Forskningsöversikt (refereegranskat)abstract
- Cardiac troponin is the preferred biomarker for defining the acute coronary syndrome and acute myocardial infarction. Currently, the only decision limit formally endorsed with regard to the cardiac troponins is the 99th percentile. This is a "rule-in" criterion, intended to ensure that only persons with the acute coronary syndrome are reviewed. The 99th percentile is an arbitrary cut point and there are many problems associated with its application, including defining a truly healthy population, the difficulty of standardisation of cardiac troponin assays, especially but not only cardiac troponin I, and the effects of age and sex on this parameter. The Emergency Department (ED) screens many more persons for possible acute coronary syndromes than actually have the condition and their needs are best met by a "rule-out" test that enables them to clear their busy departments of the many persons who do not actually have the condition. The needs of the ED are not optimally met using the 99th percentile. The index of individuality for the cardiac troponins is small and significant changes consistent with an acute coronary syndrome can occur without the 99th percentile being exceeded. It appears that the ED may be better served by use of delta troponin changes rather than the 99th percentile, but there are problems with this approach, particularly in persons who present late when troponin release has plateaued. In addition, there are many non-acute coronary syndrome causes for cardiac troponin release. The needs of the cardiologist and the ED physician are so different that it may be inappropriate for both groups to use the same diagnostic criteria for cardiac troponin, and it is of great importance that cardiac troponin measurement be used as only one part of the assessment of the person presenting with possible acute coronary syndrome.
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| 29. |
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| 30. |
- Mansten, Erik, et al.
(författare)
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Spectral signature of short attosecond pulse trains.
- 2009
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Ingår i: Physical Review Letters. - 1079-7114. ; 102:8
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Tidskriftsartikel (refereegranskat)abstract
- We report experimental measurements of high-order harmonic spectra generated in Ar using a carrier-envelope-offset (CEO) stabilized 12 fs, 800 nm laser field and a fraction (less than 10%) of its second harmonic. Additional spectral peaks are observed between the harmonic peaks, which are due to interferences between multiple pulses in the train. The position of these peaks varies with the CEO and their number is directly related to the number of pulses in the train. An analytical model, as well as numerical simulations, support our interpretation.
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| 31. |
- Messner, Christoph B., et al.
(författare)
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Ultra-fast proteomics with Scanning SWATH
- 2021
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 39:7, s. 846-854
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Tidskriftsartikel (refereegranskat)abstract
- Accurate quantification of the proteome remains challenging for large sample series and longitudinal experiments. We report a data-independent acquisition method, Scanning SWATH, that accelerates mass spectrometric (MS) duty cycles, yielding quantitative proteomes in combination with short gradients and high-flow (800 µl min ) chromatography. Exploiting a continuous movement of the precursor isolation window to assign precursor masses to tandem mass spectrometry (MS/MS) fragment traces, Scanning SWATH increases precursor identifications by ~70% compared to conventional data-independent acquisition (DIA) methods on 0.5–5-min chromatographic gradients. We demonstrate the application of ultra-fast proteomics in drug mode-of-action screening and plasma proteomics. Scanning SWATH proteomes capture the mode of action of fungistatic azoles and statins. Moreover, we confirm 43 and identify 11 new plasma proteome biomarkers of COVID-19 severity, advancing patient classification and biomarker discovery. Thus, our results demonstrate a substantial acceleration and increased depth in fast proteomic experiments that facilitate proteomic drug screens and clinical studies. –1
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| 32. |
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| 33. |
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| 34. |
- Tate, A. E., et al.
(författare)
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Association and Familial Coaggregation of Type 1 Diabetes and Eating Disorders: A Register-Based Cohort Study in Denmark and Sweden
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:5, s. 1143-1150
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To ascertain the association and coaggregation of eating disorders and childhood-onset type 1 diabetes in families. RESEARCH DESIGN AND METHODS Using population samples from national registers in Sweden (n = 2,517,277) and Demark (n = 1,825,920), we investigated the within-individual association between type 1 diabetes and eating disorders and their familial coaggregation among full siblings, half siblings, full cousins, and half cousins. On the basis of clinical diagnoses, we classified eating disorders into any eating disorder (AED), anorexia nervosa (AN) and atypical AN, and other eating disorder (OED). Associations were determined with hazard ratios (HRs) with 95% CIs from Cox regressions. RESULTS Swedish and Danish individuals with a type 1 diabetes diagnosis had a greater risk of receiving an eating disorder diagnosis (HR [95% CI] Sweden: AED 2.02 [1.80-2.27], AN 1.63 [1.36-1.96], OED 2.34 [2.07-2.63]; Denmark: AED 2.19 [1.84-2.61], AN 1.78 [1.36-2.33], OED 2.65 [2.20-3.21]). We also meta-analyzed the results: AED 2.07 (1.88-2.28), AN 1.68 (1.44-1.95), OED 2.44 (2.17-2.72). There was an increased risk of receiving an eating disorder diagnosis in full siblings in the Swedish cohort (AED 1.25 [1.07-1.46], AN 1.28 [1.04-1.57], OED 1.28 [1.07-1.52]); these results were nonsignificant in the Danish cohort. CONCLUSIONS Patients with type 1 diabetes are at a higher risk of subsequent eating disorders; however, there is conflicting support for the relationship between having a sibling with type 1 diabetes and an eating disorder diagnosis. Diabetes health care teams should be vigilant about disordered eating behaviors in children and adolescents with type 1 diabetes.
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| 37. |
- Tate, D., et al.
(författare)
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The development of the Cognitive Behavioural Social Competence Therapeutic Intervention for Adults with Autism: A mixed methods report
- 2023
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Ingår i: Counselling & Psychotherapy Research. - 1473-3145.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many young people with autism can have an average or above average IQ, yet they still struggle with the social competencies needed to successfully navigate into adulthood. Despite many individuals with autism experiencing significant challenges during their transition into adulthood, evidence-based therapeutic interventions to support individuals with autism during this transition are limited. The current literature suggests that cognitive behavioural therapy interventions can help improve social skills and the mental health of individuals with autism. However, little is known about the benefits for young adults with autism transitioning or who have transitioned into adulthood. Aims and Method: The aim of this research was to deliver a newly developed Cognitive Behavioural Social Competence Therapeutic Intervention for Adults with Autism (CBSCTI-A) to five young adults with autism. Research aims were to evaluate intervention feasibility and efficacy by triangulating data findings using a mixed methods approach. Results: Results support feasibility, with CBSCTI-A receiving very high user satisfaction ratings, and adherence to the intervention was high, recorded at similar to 90%. Fidelity to treatment was also high, ranging from similar to 86% to similar to 100%. Quantitative findings indicate that over an eight-week time period, a small sample of young adults with autism experienced significant improvements with regard to their social motivation, non-verbal conversation, emotional empathy, assertiveness, interpersonal relationships and self-control. Qualitative findings provide further anecdotal support for intervention feasibility and efficacy. After the completion of the intervention, participants and their parents were invited to complete semistructured interviews. Thematic analysis (TA) revealed four main themes: user satisfaction, important components of therapeutic intervention, challenges and critiques, and recommendations. Conclusions: CBSCTI-A appears to be a feasible intervention; however, future research with larger samples and more rigorous controlled trials is needed before efficacy can be established.
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| 39. |
- Taylor, AJ, et al.
(författare)
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Cost-effectiveness of reduction mammaplasty
- 2004
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Ingår i: International journal of technology assessment in health care. - 0266-4623. ; 20:3, s. 269-273
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Tidskriftsartikel (refereegranskat)
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| 40. |
- Vlaeyen, Johan W. S., et al.
(författare)
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From Boulder to Stockholm in 70 Years : Single Case Experimental Designs in Clinical Research
- 2020
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Ingår i: The Psychological Record. - : Springer. - 0033-2933 .- 2163-3452. ; 70:4, s. 659-670
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Tidskriftsartikel (refereegranskat)abstract
- With the objective of increasing the magnitude of treatment effects in behavioral health, there is steadily growing interest in tailoring assessments and interventions to better match individual needs. This aligns with the central idea that behavior can be adequately understood by considering the unique characteristics of the individual and context. Thus, data collected at an individual level provides critical evidence that can be used to inform health care decisions, improve treatment, or refine theories. Yet, the majority of research in behavioral health is based on group-level analyses. Recent developments in the field of single-case experimental design (SCED) has provided new opportunities to utilize individual data. The present article provides a state-of-the art overview regarding key aspects of SCED, including a historical background to why and how SCED emerged, declined, and recently reemerged as well as methodological aspects such as design issues, challenges related to reliability and validity of repeated observations, innovations in visual and statistical analyses of individual data, strategies to deal with missing values, methodology to examine effect size, and approaches to summarize data from a large number of SCEDs using multilevel models and meta-analyses of replication data. Finally, the article discusses key concerns and actions needed to move the field forward.
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| 41. |
- Yeung, A T Y, et al.
(författare)
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Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The ability to differentiate genetically modified mouse embryonic stem (ES) cells into functional macrophages provides a potentially attractive resource to study host-pathogen interactions without the need for animal experimentation. This is particularly useful in instances where the gene of interest is essential and a knockout mouse is not available. Here we differentiated mouse ES cells into macrophages in vitro and showed, through a combination of flow cytometry, microscopic imaging and RNA-Seq, that ES cell-derived macrophages responded to S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages. We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is known to play a role in tumour necrosis factor-α signalling but has not been studied for its role in infections or response to Toll-like receptor agonists. Interestingly, traf2-deficient macrophages produced reduced levels of inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin stimulation and exhibited increased susceptibility to S. Typhimurium infection.
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