| 61. |
- Balabanski, Anna H., et al.
(författare)
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The Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index : A Systematic Review Protocol
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations.Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including <10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research.Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this.Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.
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| 62. |
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| 63. |
- Beard, David J., et al.
(författare)
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Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
- 2020
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Ingår i: The Lancet. - 0140-6736. ; 395:10226, s. 828-838
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Forskningsöversikt (refereegranskat)abstract
- Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.
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| 64. |
- Beard, David J., et al.
(författare)
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Placebo comparator group selection and use in surgical trials : The aspire project including expert workshop
- 2021
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Ingår i: Health Technology Assessment. - 1366-5278. ; 25:53
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space.
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| 65. |
- Bedard, Jean H., et al.
(författare)
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Geochemical Systematics of High Arctic Large Igneous Province Continental Tholeiites from Canada-Evidence for Progressive Crustal Contamination in the Plumbing System
- 2021
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Ingår i: Journal of Petrology. - : Oxford University Press. - 0022-3530 .- 1460-2415. ; 62:9
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Tidskriftsartikel (refereegranskat)abstract
- Cretaceous High Arctic large igneous province (HALIP) sub-alkaline magmatic rocks in Canada are mostly evolved (MgO 2-7 wt%), sparsely plagioclase + clinopyroxene +/- olivine-phyric tholeiitic basalts. There were two main HALIP continental flood basalt (CFB) eruption episodes: 135-120 Ma (Isachsen Fm.) and 105-90 Ma (Strand Fiord Fm.), both associated with cogenetic doleritic sills and dykes. Building on a large modern database, 16 HALIP tholeiite types are defined and grouped into genetic series using Ce vs Sm/Yb-NMORB distributions. Comparison with model melting curves implies that higher-Sm/Yb HALIP basalt types record low-degree melting of garnet-bearing mantle sources. More voluminous intermediate- and low-Sm/Yb HALIP basalt types separated from the mantle at shallower levels after further extensive melting in the spinel-peridotite field. Within a given Sm/Yb range, increases in incompatible elements such as Ce are coupled with progressive clockwise rotation of normalized incompatible trace element profiles. Trace element modeling implies this cannot be due to closed-system fractional crystallization but requires progressive and ubiquitous incorporation of a component resembling continental crust. The fractionation models imply that low-Sm/Yb HALIP basalts (similar to 7 wt% MgO) initially crystallized olivine gabbro assemblages, with lower-MgO basalts successively crystallizing gabbro and ilmenite-gabbro assemblages. In contrast, higher-Sm/Yb basalts fractionated more clinopyroxene and ilmenite, but extensive plagioclase fractionation is still required to explain developing negative Sr-Eu anomalies. Backfractionation models require about 40% addition of olivine to bring the most primitive HALIP basalts (similar to 7% MgO) into equilibrium with Fo(89) mantle. Inverse fractionation-assimilation modeling shrinks the CFB signature, making decontaminated model parental melts more similar to enriched mid-ocean ridge basalt. The progressive increase of the contamination signature within each HALIP tholeiitic differentiation series is not consistent with models involving derivation of HALIP basalts from a mantle source previously enriched by subduction. Strong interaction of basalt with Sverdrup Basin sedimentary rocks may cause localized over-enrichment in K-Rb-Th-U, but cannot explain strong Ba enrichment in the absence of concomitant K-Rb-Th-U enrichment. The localized Ba enrichment could reflect either a Ba-rich lithospheric mantle component that is strongly manifested in the coeval HALIP alkaline suites, or syn- to post-emplacement fluid-mediated transfer from Ba-rich host rocks.
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| 66. |
- Bedard, Jean H., et al.
(författare)
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High Arctic Large Igneous Province Alkaline Rocks in Canada : Evidence for Multiple Mantle Components
- 2021
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Ingår i: Journal of Petrology. - : Oxford University Press. - 0022-3530 .- 1460-2415. ; 62:9
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Tidskriftsartikel (refereegranskat)abstract
- The Cretaceous High Arctic Large Igneous Province (HALIP) in Canada, although dominated by tholeiites (135-90 Ma), contains two main groups of alkaline igneous rocks. The older alkaline rocks (similar to 96 Ma) scatter around major fault and basement structures. They are represented by the newly defined Fulmar Suite alkaline basalt dykes and sills, and include Hassel Formation volcanic rocks. The younger alkaline group is represented by the Wootton Intrusive Complex (92.2-92.7 Ma), and the Audhild Bay Suite (83-73 Ma), both emplaced near the northern coast of Ellesmere Island. Fulmar Suite rocks resemble EM-type ocean island basalts (OIB) and most show limited crustal contamination. The Fulmar Suite shows increases of P2O5 at near-constant Ba-K-Zr-Ti that are nearly orthogonal to predicted fractionation- or melting-related variations, which we interpret as the result of melting composite mantle sources containing a regionally widespread apatite-bearing enriched component (P1). Low-P2O5 Fulmar Suite variants overlap compositionally with enriched HALIP tholeiites, and fall on common garnet Iherzolite trace element melting trajectories, suggesting variable degrees of melting of a geochemically similar source. High-P2O5 Hassel Formation basalts are unusual among Fulmar rocks, because they are strongly contaminated with depleted lower crust; and because they involve a high-P2O5-Ba-Eu mantle component (P2), similar to that seen in alkali basalt dykes from Greenland. The P2 component may have contained Ba-Eu-rich hawthorneite and/or carbonate minerals as well as apatite, and may typify parts of the Greenlandic sub-continental lithospheric mantle (SCLM). Mafic alkaline Audhild Bay Suite (ABS) rocks are volcanic and hypabyssal basanites, alkaline basalts and trachy-andesites, and resemble HIMU ocean island basalts in having high Nb, low Zr/Nb and low Sr-87/Sr-86(i). These mafic alkaline rocks are associated with felsic alkaline lavas and syenitic intrusions, but crustally derived rhyodacites and rhyolites also exist. The Wootton Intrusive Complex (WIC) contains geochemically similar plutonic rocks (alkali gabbros, diorites and anatectic granites), and may represent a more deeply eroded, slightly older equivalent of the ABS. Low-P2O5 ABS and WIC alkaline mafic rocks have flat heavy rare earth element (HREE) profiles suggesting shallow mantle melting; whereas High-P2O5 variants have steep HREE profiles indicating deeper separation from garnet-bearing residues. Some High-P2O5 mafic ABS rocks seem to contain the P1 and P2 components identified in Fulmar-Hassel rocks, whereas other samples trend towards possible High-P2O5 + Zr (PZr) and High-P2O5 + K2O (PK) components. We argue that the strongly alkaline northern Ellesmere Island magmas sampled mineralogically heterogeneous veins or metasomes in Greenlandic-type SCLM, which contained trace phases such as apatite, carbonates, hawthorneite, zircon, mica or richterite. The geographically more widespread apatite-bearing component (P1) could have formed part of a heterogeneous plume or upwelling mantle current that also generated HALIP tholeiites when melted more extensively, but may also have resided in the SCLM as relics of older events. Rare HALIP alkaline rocks with high K-Rb-U-Th fall on mixing paths implying strong local contamination from either Sverdrup Basin sedimentary rocks or granitic upper crust. However, the scarcity of potassic alkaline HALIP facies, together with the other trace element and isotopic signatures, provides little support for a ubiquitous fossil sedimentary subduction-zone component in the HALIP mantle source.
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| 67. |
- Bernhardson, Britt-Marie, et al.
(författare)
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Sensations, symptoms, and then what? : Early bodily experiences prior to diagnosis of lung cancer
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer (LC) generally lacks unique core symptoms or signs. However, there are a multitude of bodily sensations that are often non-specific, not easily understood, and many times initially not recognized as indicative of LC by the affected person, which often leads to late diagnosis. In this international qualitative study, we inductively analyzed retrospective accounts of 61 people diagnosed with LC in Denmark, England and Sweden. Using the bodily sensations they most commonly spoke about (tiredness, breathlessness, pain, and cough), we constructed four sensation-based cases to understand the pre-diagnostic processes of reasoning and practice triggered by these key indicators of LC. We thereafter critically applied Hay's model of sensations to symptoms transformation, examining its central concepts of duration, disability and vulnerability, to support understanding of these processes. We found that while duration and disability are clearly relevant, vulnerability is more implicitly expressed in relation to perceived threat. Tiredness, even when of long duration and causing disability, was often related to normal aging, rather than a health threat. Regardless of duration, breathlessness was disturbing and threatening enough to lead to care-seeking. Pain varied by location, duration and degree of disability, and thus also varied in degree of threat perceived. Preconceived, but unmet expectations of what LC-related cough and pain would entail could cause delays by misleading participants; if cough lasted long enough, it could trigger health care contact. Duration, disability, and sense of threat, rather than vulnerability, were found to be relevant concepts for understanding the trajectory to diagnosis for LC among these participants. The process by which an individual, their family and health care providers legitimize sensations, allowing them to be seen as potential symptoms of disease, is also an essential, but varying part of the diagnostic processes described here.
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| 68. |
- Blom, Anna M, et al.
(författare)
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A Novel Non-Synonymous Polymorphism (p.Arg240His) in C4b-Binding Protein Is Associated with Atypical Hemolytic Uremic Syndrome and Leads to Impaired Alternative Pathway Cofactor Activity.
- 2008
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Ingår i: Journal of Immunology. - 1550-6606. ; 180:9, s. 6385-6391
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Tidskriftsartikel (refereegranskat)abstract
- Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) alpha-chain (c.719G>A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (chi2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.
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| 69. |
- Boccaletti, Anthony, et al.
(författare)
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Fast-moving features in the debris disk around AU Microscopii
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7572, s. 230-
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Tidskriftsartikel (refereegranskat)abstract
- In the 1980s, excess infrared emission was discovered around main-sequence stars; subsequent direct-imaging observations revealed orbiting disks of cold dust to be the source(1). These 'debris disks' were thought to be by-products of planet formation because they often exhibited morphological and brightness asymmetries that may result from gravitational perturbation by planets. This was proved to be true for the beta Pictoris system, in which the known planet generates an observable warp in the disk(2-5). The nearby, young, unusually active late-type star AU Microscopii hosts a well-studied edge-on debris disk; earlier observations in the visible and near-infrared found asymmetric localized structures in the form of intensity variations along the midplane of the disk beyond a distance of 20 astronomical units(6-9). Here we report high-contrast imaging that reveals a series of five large-scale features in the southeast side of the disk, at projected separations of 10-60 astronomical units, persisting over intervals of 1-4 years. All these features appear to move away from the star at projected speeds of 4-10 kilometres per second, suggesting highly eccentric or unbound trajectories if they are associated with physical entities. The origin, localization, morphology and rapid evolution of these features are difficult to reconcile with current theories.
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| 70. |
- Butler, Geraldine, et al.
(författare)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Tidskriftsartikel (refereegranskat)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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