| 1. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 2. |
- Shupe, M. D., et al.
(författare)
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Overview of the MOSAiC expedition : Atmosphere
- 2022
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Ingår i: Elementa. - : University of California Press. - 2325-1026. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic.
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| 3. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 4. |
- Norbäck, Dan, et al.
(författare)
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Asthma, eczema, and reports on pollen and cat allergy among pupils in Shanxi province, China
- 2007
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 80:3, s. 207-216
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study self-reported asthma, eczema, and pollen and furry pet allergy among pupils (9-20 years) in Shanxi province, China, in relation to dietary and environmental factors. METHODS: A standardised questionnaire was distributed to pupils in two primary and two secondary schools, one in Taiyuan city (3.0 milj. inhabitants), the others in Qingxu county, a rural area 30 km outside Taiyuan. Totally, 2,116 pupils (90%) participated. RESULTS: Fifty percent were girls, 61% had been growing up on the countryside, 18% lived in Taiyuan now, 1.7% had ever had asthma, 0.8% had doctor's diagnosed asthma, 1.4% pollen allergy, 1.7% cat allergy, and 0% had dog allergy. Multiple logistic regression was applied, controlling for age, gender, diet, indoor exposures, rural childhood, and current urban residency. Girls had less eczema (OR = 0.51; 95%CI 0.28-0.92). Pupils in the city had more eczema (OR = 5.05; 95% CI 1.11-23.3). Those with a rural childhood had less asthma (OR = 0.17; 95% CI 0.05-0.60), eczema (OR = 0.15; 95% CI 0.13-0.66) and pollen/cat allergy (OR = 0.50; 95%CI 0.25-0.99). None of the indoor variables was related to asthma or allergy. Children with frequent fruit consumption had less asthma (OR = 0.40; 95% CI 0.19-0.82) and pollen/cat allergy (OR = 0.49; 95% CI 0.29-0.84). Those with frequent fish consumption had less asthma (OR = 0.32; 95% CI 0.11-0.97). Those with frequent hamburgers consumption had more asthma (OR = 2.05; 95% CI 1.09-3.87) and eczema (OR = 1.85; 95% CI 1.12-3.04). CONCLUSION: Asthma, eczema, and pollen or pet allergy was uncommon, compared with western countries and other areas in China. Pupils with a rural childhood had less asthma and allergy, which is consistent with the "hygiene hypothesis". Fruit and fish consumption may reduce, and fast food consumption may increase the risk for asthma. Finally, the higher prevalence of asthma and eczema among younger children, born in the 1990s, indicates a cohort effect similar to that observed in western countries.
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| 5. |
- Bohlin, Maria, et al.
(författare)
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Estimation of the amount of β2-glycoprotein I adsorbed at the inner surface of fused silica capillaries after acidic, neutral and alkaline pretreatment
- 2012
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Ingår i: Electrophoresis. - Weinheim, Germany : John Wiley & Sons. - 0173-0835 .- 1522-2683. ; 33:12, s. 1695-1702
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Tidskriftsartikel (refereegranskat)abstract
- Sample adsorption to the inner surface of fused silica capillaries is a common problem inCE when analyzingmacromolecules and is harmful to the analysis. We previously utilizedthe pH hysteresis effect of fused silica to facilitate electrophoresis of the strongly adsorbingprotein β2gpI in plain-fused silica capillaries at neutral pH. In the present paper, theeffect of different pretreatments of the capillary on the adsorption of the β2-glycoproteinI has been investigated using electroosmosis markers, SDS mobilization, and imagingbased on indirect immunofluorescence microscopy for direct visualization. The amountof β2gpI adsorbed on the surface was probed using all these independent techniques afterelectrophoresis at neutral pH on capillaries pretreated with HCl, background electrolyte(BGE), and NaOH. BGE pretreatment was included as a positive control. We found that80% or more of the starting material was adsorbed to the inner surface of the silicacapillaries during electrophoresis after pretreatment with only BGE or with NaOH, butafter acidic pretreatment the loss was consistently less than 20%. NaOH most efficientlyremoves adsorbed protein between runs. A theoretical calculation of the pH change ofthe BGE showed that electrolysis affects the pH more than the deprotonation of silanolsduring electrophoresis. We conclude that acidic pretreatment of fused silica capillariesdiminishes adsorption of β2gpI by decreasing charge-dependent wall adsorption.
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| 6. |
- Cable, Jennifer, et al.
(författare)
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Progress in vaccine development for infectious diseases : a Keystone Symposia report
- 2023
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Ingår i: Annals of the New York Academy of Sciences. - : John Wiley & Sons. - 0077-8923 .- 1749-6632. ; 1524:1, s. 65-86
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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| 7. |
- Engelen, A. H., et al.
(författare)
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Circumglobal invasion by the brown seaweed Sargassum muticum
- 2015
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Ingår i: Oceanography and Marine Biology: An Annual Review. R. N. Hughes, D. J. Hughes, I. P. Smith, and A. C. Dale (eds.). - Boca Raton : Crc Press-Taylor & Francis Group. - 9781498705455 ; 53, s. 81-126
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Hundreds of macroalgal species have been spread outside their natural range by human activities, and many of these introductions are occurring at a worldwide scale. This review considers one of the best-studied and most widespread invasive macroalgae, Sargassum muticum, to determine the traits and processes important in marine invasions and to identify important lines of future research. Particular emphasis is placed on the ecology of S. muticum in its native range and on the four stages of invasion transport, colonization, establishment, and spread integrating taxonomy, invasion history, dispersal, impact, invasiveness and invasibility, and general ecology. Although S. muticum has received a lot of scientific attention, with more than 650 papers on this species, key information on its taxonomy, invasive biology, and evolutionary potential is still lacking. Most previous studies have been local or descriptive or provide circumstantial evidence, and too few have been hypothesis driven. Only by local-scale research conducted in different geographical regions, especially including the native range, and developed in an eco-evolutionary framework, will it be possible to greatly improve our understanding of the complex of factors, traits, and processes involved in macroalgal invasions. ERG P, 1992, ECOLOGY, V73, P1488 ERG P, 1992, ECOLOGY, V73, P1473
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| 8. |
- Fernö, Mårten, et al.
(författare)
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Cathepsin D, both a prognostic factor and a predictive factor for the effect of adjuvant tamoxifen in breast cancer. South Sweden Breast Cancer Group
- 1994
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Ingår i: European Journal of Cancer. - 1879-0852. ; 30a:14, s. 2042-2048
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Tidskriftsartikel (refereegranskat)abstract
- Cathepsin D is a lysosomal protease implicated in cancer metastasis. Its concentration in breast tumours has also been shown to be of prognostic importance, although to what extent this is subject to lymph node status, the use of adjuvant therapy and menopausal status has not been clearly evaluated. At a cut-off level of 45 pmol/mg protein (61% of the 623 samples were classified as high cathepsin D tumours; immunoradiometric assay), we found cathepsin D to be of prognostic importance only among breast cancer patients with lymph node-positive (N+) disease not treated with adjuvant tamoxifen. When the series was stratified according to cathepsin D content of their tumours, progesterone receptor (PgR) status and lymph node involvement, adjuvant tamoxifen was found to have a significant beneficial effect only among patients with N+ and PgR-positive breast cancer whose tumours had a high cathepsin D content.
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| 9. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Mejàre, Ingegerd A., et al.
(författare)
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A Systematic Map of Systematic Reviews in Pediatric Dentistry : What Do We Really Know?
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To identify, appraise and summarize existing knowledge and knowledge gaps in practice-relevant questions in pediatric dentistry. Methods A systematic mapping of systematic reviews was undertaken for domains considered important in daily clinical practice. The literature search covered questions in the following domains: behavior management problems/dental anxiety; caries risk assessment and caries detection including radiographic technologies; prevention and non-operative treatment of caries in primary and young permanent teeth; operative treatment of caries in primary and young permanent teeth; prevention and treatment of periodontal disease; management of tooth developmental and mineralization disturbances; prevention and treatment of oral conditions in children with chronic diseases/developmental disturbances/obesity; diagnosis, prevention and treatment of dental erosion and tooth wear; treatment of traumatic injuries in primary and young permanent teeth and cost-effectiveness of these interventions. Abstracts and full text reviews were assessed independently by two reviewers and any differences were solved by consensus. AMSTAR was used to assess the risk of bias of each included systematic review. Reviews judged as having a low or moderate risk of bias were used to formulate existing knowledge and knowledge gaps. Results Out of 81 systematic reviews meeting the inclusion criteria, 38 were judged to have a low or moderate risk of bias. Half of them concerned caries prevention. The quality of evidence was high for a caries-preventive effect of daily use of fluoride toothpaste and moderate for fissure sealing with resin-based materials. For the rest the quality of evidence for the effects of interventions was low or very low. Conclusion There is an urgent need for primary clinical research of good quality in most clinically-relevant domains in pediatric dentistry.
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| 11. |
- Pettersson, Gunilla, et al.
(författare)
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Strong and bulky paperboard plies from low energy CTMP
- 2014
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Ingår i: International Mechanical Pulping Conference, IMPC 2014. - 9780000000002
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Konferensbidrag (refereegranskat)abstract
- A description is given regarding methods used to manufacture strong and bulky sheets from furnishes based on a broad range of surface modified CTMP qualities. Starch and CMC are adsorbed on the fibre surfaces using a multilayer or a MIX concept. It is shown that both the in-plane and out-of-plane strength for the CTMP based sheets after such surface treatment can be more than doubled at a maintained density. This can be utilized to improve bending stiffness or to reduce the basis weight in multi-ply paperboards.
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| 12. |
- Westergren-Thorsson, Gunilla, et al.
(författare)
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Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis
- 2017
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Ingår i: International Journal of Biochemistry & Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 83, s. 27-38
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects. GAGs in lung samples from severe IPF patients and donor lungs were analyzed with HPLC. HS was assessed by immunohistochemistry and collagen was quantified as hydroxyproline content. The total amount of HS, CS/DS and HA was increased in IPF lungs but there was no significant difference in the total collagen content. We found a relative increase in total sulfation of HS due to increment of 2-O, 6-O and N-sulfation and a higher proportion of sulfation in CS/DS. Highly sulfated HS was located in the border zone between denser areas and more normal looking alveolar parenchyma in basement membranes of blood vessels and airways, that were immuno-positive for perlecan, as well as on the cell surface of spindle-shaped cells in the alveolar interstitium. These findings show for the first time that both the amount and structure of glycosaminoglycans are altered in IPF. These changes may contribute to the tissue remodelling in IPF by altering growth factor retention and activity, creating a pro-fibrotic ECM landscape. (C) 2016 The Authors. Published by Elsevier Ltd.
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| 13. |
- Abarenkov, Kessy, et al.
(författare)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 14. |
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| 15. |
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| 16. |
- Benoni, Henrik, et al.
(författare)
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Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study
- 2020
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Ingår i: Transplant International. - : WILEY. - 0934-0874 .- 1432-2277. ; 33:12, s. 1700-1710
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Tidskriftsartikel (refereegranskat)abstract
- Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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| 17. |
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| 18. |
- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 19. |
- Björkbacka, Harry, et al.
(författare)
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Weak associations between human leucocyte antigen genotype and acute myocardial infarction
- 2010
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Ingår i: Journal of Internal Medicine. - : Blackwell Publishing Ltd. - 0954-6820 .- 1365-2796. ; 268:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. The importance of such studies is stressed by recent experimental findings of an involvement of autoimmunity in the atherosclerotic disease process. Results: An SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1, -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188 acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The HLA-DRB1*0101 allele, as well as the HLA-DRB1*0101-DQA1*01-DQB1*05 haplotype, was found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00–1.54 for both). In contrast, the DRB1*07 and DQA*02 alleles (OR 0.78; 95% CI 0.65–0.95 for both), as well as the DRB1*07-DQA*02-DQB*02 haplotype, conferred protection (OR 0.79; 95% CI 0.63–0.98). An HLA risk score taking each individual’s both haplotypes into account was higher amongst cases (2.43 ± 0.92 vs. 2.29 ± 0.95, P = 0.001). The association between HLA risk score and AMI was independent of other cardiovascular riskfactors assessed. Conclusions: This study demonstrates that the associations between HLA-DRB1 and DQA1 loci and cardiovascular disease exists but that they are considerably weaker than those previously reported for other diseases with an established autoimmune aetiology such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.
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| 20. |
- Björling, Gunilla, Docent, et al.
(författare)
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Risk Evaluation of Therapy Medical Devices and Implants for Increased Patient Safety : REMISS Horizon 2020 Research and Innovation Action
- 2017
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Konferensbidrag (refereegranskat)abstract
- Current knowledge in the area of medical devices remains insufficiently complete, and many of the established test methods and international standards (ISO (International Organization for Standardization) standards) open up to individual interpretation on how the test should be performed and the results reported. Treating long-term diseases such as cancer imposes a stringent sequence of various treatments on patients. For instance, cancer may be treated with radiation and chemotherapy; the latter in many treatment protocols requiring the implantation of an intravascular catheter during a prolonged period of time. To maximize the effect of such measures, as well as issues related to the patient Health Related Quality of Life (HRQoL), integrated and validated methodologies are needed as decisional basis for appropriate risk management and patient safety with regard to clinical use of intravascular catheters.The ambition of the REMISS project is to: Establish integrated and validated methodologies for risk management of the clinical use of intravascular catheters with respect to the clinical service lifetime, improved patient treatment, safety and HRQoL. This is assumed to reduce patient suffering due to complications associated with material deployment and degradation associated side effects for e.g. cancer patients receiving treatment with chemotherapeutical drugs using an intravascular catheter.The main vision is to improve the standards for eliminating side effects (complications) caused by deployment from and degradation of intravascular catheters, as well as loss of performance due to material-drug-biological system interactions, compared to the current state-of-the-art. Realising the project goals the rate of catheter-associated complications can be lowered by 40-50%, which in turn will improve patient treatment, safety and HRQoL, as well as health care related costs.Package integrally developed methodologies, predictive models, databases, and other project findings, as a potential product with a holistic coverage. It is believed that commercialisation of (selected) results will be the best option in order to create sustainable availability of this service based on continued research on intravascular catheters according to integrated and validated methodologies.REMISS answer the call NMBP-12-2017 Development of a Reliable Methodology for Better Risk Management of Engineered Biomaterials Advanced Therapy Medicinal Products and/or Medical Devices Marcy, P. Central venous access: techniques and indications in oncology. European Society of Radiology, 2008; 18; 2333-44 Maki DG, et al The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc 2006: 81 (9): 1159-71. Frostell, C., Björling, G., Strömberg, E., Karlsson, S., and Aune, R. E., Tracheal Implants Revisited, The Lancet (2017), 389(10075) pp.1191
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| 21. |
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| 22. |
- Borg, Åsa A., et al.
(författare)
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Interactions Among Female Guppies (Poecilia reticulata) Affect Growth and Reproduction
- 2012
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Ingår i: Ethology. - : Wiley. - 0179-1613 .- 1439-0310. ; 118:8, s. 752-765
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Tidskriftsartikel (refereegranskat)abstract
- Competition among females over resources may have consequences for their resource budgets and thereby the resource allocation between growth and reproduction. In addition, the consequences of femalefemale interactions may differ for dominant and subordinate individuals, with the dominant ones being at an advantage. In this study, we investigated the consequences of femalefemale competition in guppies by manipulating the competitive environment of females. We found that large guppy females dominated smaller females and that interactions between females likely are costly because females exposed to competition grew less. These females compensated by growing at a higher rate when no longer subjected to competition. The higher growth rate might in turn be the cause of the reduced reproductive effort in the more competitive treatments. Furthermore, interactions were more costly for females when they were in the subordinate role than in the dominant role, because the reduction in growth and reproductive effort was highest in females exposed to larger competitors. Whether there was a differential allocation of resources into growth and reproduction depending on dominance status needs further investigation. However, in general, smaller females had a higher growth rate than larger females, independent of competitive level. We also found a negative relationship between reproduction and growth in all treatments, indicating a cost of reproduction.
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| 23. |
- Brink, Eva, 1952, et al.
(författare)
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Constructing grounded theory : A practical guide through qualitative analysis
- 2006
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - Järfälla : CoAction Publishing. - 1748-2623 .- 1748-2631. ; 1:3, s. 188-192
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Recension (refereegranskat)abstract
- BOOK REVIEW: Constructing grounded theory. A practical guide through qualitative analysis Kathy Charmaz, 2006, 208 pp. London: Sage. ISBN 2005928035
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| 24. |
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| 25. |
- Broman, M, et al.
(författare)
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Mutation screening of the RYR1-cDNA from peripheral B-lymphocytes in 15 Swedish malignant hyperthermia index cases.
- 2009
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 102:5, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignant hyperthermia (MH), linked to the ryanodine receptor 1 gene (RYR1) on chromosome 19, is a potentially lethal pharmacogenetic disorder which may lead to a disturbance of intracellular calcium homeostasis when susceptible individuals are exposed to halogenated anaesthetics, suxamethonium, or both. Central core disease (CCD) is a rare dominantly inherited congenital myopathy allelic to MH-susceptibility. METHODS: In this study, 14 unrelated MH-susceptible probands and one CCD patient from Sweden were screened for mutations in the RYR1. Since the RYR1 is also expressed in B-lymphocytes, RYR1-cDNA was transcribed from total RNA extracted from white blood cells. RESULTS: We detected two known RYR1 mutations and two previously described unclassified sequence variants. In addition, six novel sequence variants were detected. All mutations or sequence variants were verified on genomic DNA. Seven of the probands did not show any candidate mutation, although the total coding region of RYR1 was sequenced. Segregation data in in vitro contracture tested family members of three probands support a causative role of three of the novel sequence variants. CONCLUSIONS: Our study contributes to the genetic aetiology of MH in Sweden, but also raises questions about the involvement of genes other than RYR1 since nearly half of the probands did not show any sequence variants in the total coding region of the RYR1.
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| 26. |
- Brynhildsen, Jan, et al.
(författare)
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Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers
- 2013
-
Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 102:6, s. 620-624
-
Tidskriftsartikel (refereegranskat)abstract
- Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.
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| 27. |
- Bülow, Pia H., et al.
(författare)
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Grön rehabilitering i praktiken : En kvalitativ studie av realiserandet och upplevelsen av en terapeutisk verksamhet i landstinget i Jönköpings län
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den studie som redovisas i denna rapport har genomförts av forskare vid Hälsohögskolan i Jönköping på uppdrag av Landstinget i Jönköpings län. Rapporten utgör den kvalitativa delen av utvärderingen av projektverksamheten Grön rehab som landstinget på försök driver sedan årsskiftet 2012-2013. Studiens övergripande syfte var att studera hur grön rehabilitering realiseras i mötet mellan deltagare och natur, deltagare och personal, och mellan deltagarna, samt undersöka deltagarnas motiv och mål för sitt deltagande i Grön rehab, deras upplevelse av att delta och vilken betydelse de tillskriver att deltagandet har haft i deras rehabiliteringsprocess och för deras arbetsförmåga och hälsa.Verksamheter under namn som grön rehabilitering har växt fram ur teorier om sambanden mellan naturens egenskaper och dess betydelse för människans hälsa. Tre olika discipliner har lämnat viktigt bidrag till den vidare utvecklingen mot användning av natur och trädgård i behandlande sammanhang. Hit hör design- och landskapsteorier som formulerat vissa grundantaganden om den gröna miljöns utformning. Aktivitetsteorier, som utgår från att människan är en aktiv varelse med behov av aktivitet och rörelse, har bidragit med forskning om hur olika slags aktiviteter kan användas i terapeutiskt syfte. Slutligen har miljöpsykologin bidragit med kunskaper om hur och varför människan uppfattar gröna miljöer som lugnande och stress-lindrande.Grön rehab i Jönköpings län bedrivs som ett tidsbegränsat projekt med placering vid ett av landstingets naturbruksgymnasier. Det innebär att man delar på resurser som växthus och djurstallar. I projektet Grön rehab ingår arbetsterapeut (100 %), psykolog (50 %) samt trädgårdsmästare och djurinstruktör på 20 % vardera. De båda senare arbetar också på naturbruksgymnasiet där de har sin ordinarie anställning. Verksamheten är organiserad som en kurs där deltagarna kommer till Grön rehab tre timmar per dag, två dagar i veckan under tio veckor. Den övergripande organiseringen av Grön rehab innebar att Dag ett varje vecka hade fokus på gruppsamtalet och att dag två innehöll ett ”grönt” inslag. Som gröna aktiviteter räknades både sådana i trädgården/växthuset och sådana med djur. Grön rehab räknas som en behandlande insats och deltagarna kommer på läkarremiss från vårdcentraler och liknande.Den kvalitativa studien bygger på en serie individuella intervjuer med samtlig personal i projektet samt på individuella intervjuer med personer som deltagit i Grön rehab under hösten 2013. Totalt ingår 12 intervjuer med personal och 12 intervjuer med deltagare. Personalen intervjuades mellan två och fyra gånger per person under olika tidpunkter i två olika kurser. Deltagarna intervjuades mellan en och fyra månader efter kurstidens slut. Utöver intervjuer ingår i studien data från besök i de miljöer som ingår i Grön rehab. Dessa besök genomfördes utanför kurstid och med personal som guide. Som data räknas även projektbeskrivning och broschyren med rubriken ”Grön rehabilitering” som Landstinget i Jönköpings län har producerat och som distribueras via bland annat landstingets hemsida.Analysen av personalintervjuerna visar att skogspromenaden är den aktivitet som förekommer mest frekvent (i princip varje kursdag) och att gruppsamtalet av samtlig personal betraktas som den överordnade aktiviteten i Grön rehab. Gruppsamtalen förs primärt inne i ”Lillstugan” en gång varje vecka. De leds av psykolog och arbetsterapeut gemensamt. Genom att båda samtalsledarna medverkar i samtliga aktiviteter den kursdagen hände det att samtalet fortsatte eller flyttades till exempelvis skogen. Under skogspromenaderna eftersträvade personalen ett fokus på medveten närvaro (mindfulness). Påbjuden tystnad varvades med korta samtal och reflektioner omkring det som kunde erfaras med olika sinnen. Deltagarna uppmanades att känna på bark och mossa, notera lukten av regn, lyssna till vinden och att iaktta naturens växlingar över tid och i förhållande till olika väderlek, samt att gå långsamt. Andra ”gröna” aktiviteter som genomfördes i växthuset eller i trädgården, liksom aktiviteter med djur utgjorde en mindre del av verksamheten. Arrangemanget med en samtalsdag och en ”grön” dag per vecka, betyder att deltagarna var engagerade i trädgårdssysslor omkring en timme vid fem olika tillfällen, och att lika mycket tid lades på aktiviteter med djur. Deltagarna möttes för gruppsamtal vid totalt tio tillfällen. Dessa beskrevs oftast pågå i mer än en timme.Sammanfattningsvis framgår av studien att det behövs• en tydlig programförklaring med uttalat stöd i befintlig nationell och internationell forskning och med beskrivning av vad behandlingsinsatsen Grön rehab syftar till.• en diskussion om Grön rehab’s möjliga betydelse för olika målgrupper.• följeforskning kvantitativt och kvalitativt för att kunna bedöma värdet av behandlingsinsatsen Grön rehab på kort och lång sikt. Alternativt att under en två-årsperiod driva Grön rehab som ett forskningsprojekt.• handledning av erfaren trädgårdsterapeut som resurs i behandlings-verksamheten.• utvecklas en strategi för att hantera krockar med naturbruksgymnasiets verksamhet.
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| 28. |
- Burgess, Janette K, et al.
(författare)
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Extracellular Matrix as a Driver of Chronic Lung Diseases
-
Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1535-4989.
-
Tidskriftsartikel (refereegranskat)abstract
- The extracellular matrix (ECM) is not just a 3 dimensional scaffold that provides stable support for all cells in the lungs but is also an important component of chronic fibrotic airways, vascular, and interstitial diseases. It is a bioactive entity that is dynamically modulated during tissue homeostasis and disease, which controls structural and immune cell functions, drug responses, and which can release fragments that have biological activity and that can be used to monitor disease activity. There is a growing recognition of the importance of considering ECM changes in chronic airways, vascular, and interstitial diseases including (i) compositional changes, (ii) structural and organizational changes, and (iii) mechanical changes -and how these impact on disease pathogenesis. Since altered ECM biology is an important component of many lung diseases, disease models must incorporate this factor to fully recapitulate disease-driver pathways and to study potential novel therapeutic interventions. While novel models are evolving that capture some or all of the elements of the altered ECM microenvironment in lung diseases, opportunities exist to more fully understand cell-ECM interactions that will help devise future therapeutic targets to restore function in chronic lung diseases. In this perspective article, we review evolving knowledge about the ECM's role in homeostasis and disease in the lung.
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| 29. |
- Cantoni, Claudia, et al.
(författare)
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TREM2 regulates microglial cell activation in response to demyelination in vivo
- 2015
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 129:3, s. 429-447
-
Tidskriftsartikel (refereegranskat)abstract
- Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2(-/-)) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2(-/-) microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2(-/-) microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage.
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| 30. |
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| 31. |
- Carlsson, Gunilla, et al.
(författare)
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Falls and Fear of Falling among Persons Who Receive Housing Adaptations-Results from a Quasi-Experimental Study in Sweden
- 2017
-
Ingår i: Healthcare. - : MDPI AG. - 2227-9032. ; 5:4
-
Tidskriftsartikel (refereegranskat)abstract
- While health might deteriorate through the ageing and disablement process, the impacts of disability can be reduced by adapting the environment. This study aimed to investigate the effects of applying a standardized research-based strategy to housing adaptation as compared to ordinary practice with respect to falls and fear of falling. Another aim was to investigate the overall effects of housing adaptations on fall-related outcomes over time. In total, 196 clients were included at baseline, with follow-up at 3 and 6 months after the housing adaptation was implemented. The only significant difference between the two approaches was identified with respect to fear of falling at 3 months after the housing adaptation, but not after 6 months. The number of clients reporting actual falls increased over time in both sites, whereas the number of reported near-falls decreased most in the intervention site, but without significant differences. Thus, the patterns of differences between the sites are inconsistent, as are the patterns of change in fall-related outcomes. An overall conclusion is that if the goal is to improve fall-related outcomes, housing adaptation should be complemented with other interventions preventing falls and explicitly address the clients' activity limitations. In addition, longer follow-up times are necessary.
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| 32. |
- Carlsson, Gunilla H., et al.
(författare)
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Complexes of horseradish peroxidase with formate, acetate and carbon monoxide
- 2005
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 44:2, s. 635-642
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Tidskriftsartikel (refereegranskat)abstract
- Carbon monoxide, formate, and acetate interact with horseradish peroxidase (HRP) by binding to subsites within the active site. These ligands also bind to catalases, but their interactions are different in the two types of enzymes. Formate (notionally the “hydrated” form of carbon monoxide) is oxidized to carbon dioxide by compound I in catalase, while no such reaction is reported to occur in HRP, and the CO complex of ferrocatalase can only be obtained indirectly. Here we describe high-resolution crystal structures for HRP in its complexes with carbon monoxide and with formate, and compare these with the previously determined HRP−acetate structure [Berglund, G. I., et al. (2002) Nature 417, 463−468]. A multicrystal X-ray data collection strategy preserved the correct oxidation state of the iron during the experiments. Absorption spectra of the crystals and electron paramagnetic resonance data for the acetate and formate complexes in solution correlate electronic states with the structural results. Formate in ferric HRP and CO in ferrous HRP bind directly to the heme iron with iron−ligand distances of 2.3 and 1.8 Å, respectively. CO does not bind to the ferric iron in the crystal. Acetate bound to ferric HRP stacks parallel with the heme plane with its carboxylate group 3.6 Å from the heme iron, and without an intervening solvent molecule between the iron and acetate. The positions of the oxygen atoms in the bound ligands outline a potential access route for hydrogen peroxide to the iron. We propose that interactions in this channel ensure deprotonation of the proximal oxygen before binding to the heme iron.
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| 33. |
- Carlsson, Gunilla H., et al.
(författare)
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The elusive ligand complexes of the DWARF14 strigolactone receptor
- 2018
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Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 69:9, s. 2345-2354
-
Tidskriftsartikel (refereegranskat)abstract
- Strigolactones, a group of terpenoid lactones, control many aspects of plant growth and development, but the active forms of these plant hormones and their mode of action at the molecular level are still unknown. The strigolactone protein receptor is unusual because it has been shown to cleave the hormone and supposedly forms a covalent bond with the cleaved hormone fragment. This interaction is suggested to induce a conformational change in the receptor that primes it for subsequent interaction with partners in the signalling pathway. Substantial efforts have been invested into describing the interaction of synthetic strigolactone analogues with the receptor, resulting in a number of crystal structures. This investigation combines a re-evaluation of models in the Protein Data Bank with a search for new conditions that may permit the capture of a receptor-ligand complex. While weak difference density is frequently observed in the binding cavity, possibly due to a low-occupancy compound, the models often contain features not supported by the X-ray data. Thus, at this stage, we do not believe that any detailed deductions about the nature, conformation, or binding mode of the ligand can be made with any confidence.
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| 34. |
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| 35. |
- Christiansen, Ilse, et al.
(författare)
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Soluble ICAM-1 in Hodgkin´s disease : a promising independent predictive marker for survival
- 1995
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 19:3-4, s. 243-51
-
Tidskriftsartikel (refereegranskat)abstract
- The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.
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| 36. |
- Christiansen, Ilse, et al.
(författare)
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Soluble vascular cell adhesion molecule-1 (sVCAM-1) is an independent prognostic marker in Hodgkin's disease
- 1998
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 102:3, s. 701-9
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Tidskriftsartikel (refereegranskat)abstract
- Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1. sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n= 31) (P<0.0001). sVCAM-1 correlated with histology, stage, B-symptoms, and prognostic markers (sICAM-1, sCD30, sIL-2R, LDH). sVCAM-1, sICAM-1 and sCD30 added independent prognostic information for both disease-free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM-1 and ICAM-1. The vascular endothelium stained positive for VCAM-1 in 10/12 evaluable biopsies and for ICAM-1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS-cells. This led us to investigate VCAM-1 (and ICAM-1) expression in six Hodgkin cell lines (HDLM-2, L428, L540, L591, DEV, KM-H2). Two cell lines stained positive for VCAM-1 (HDLM-2, L591). All cell lines stained positive for ICAM-1. sVCAM-1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM-1. Furthermore, two Hodgkin cell lines stained positive for VCAM-1. This indicates that VCAM-1 may be expressed by some HD tumour cells in vivo.
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| 37. |
- da Rocha-Schmidt, L., et al.
(författare)
-
Progress Towards Adaptive Aircraft Engine Nacelles
- 2014
-
Ingår i: 29th Congress of the International Council of the Aeronautical Sciences, ICAS. - : International Council of the Aeronautical Sciences.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Emissions and noise of aircraft engineshave to be significantly further reduced andefficiency further increased in the future. Onemeans is the improvement of airflow though theengine and especially so in its inlet region byproper shapes. Due to changes in the flightconditions, the optimal nacelle shape varies. Itwould thus be beneficial to be able to change thenacelle shape. Evaluations on system and enginelevels including related flow simulations supportthe identification of proper shaping parameters.Initial concepts of possible morphingtechnologies are discussed as well.
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| 38. |
- Daurer, Benedikt J., et al.
(författare)
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Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses
- 2017
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Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4, s. 251-262
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of similar to 40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from similar to 35 to similar to 300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 * 10(12) photons per mu m(2) per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.
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| 39. |
- Davies, Brandon S J, et al.
(författare)
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GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries.
- 2010
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Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 12:1, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries.
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| 40. |
- de Boer, J., et al.
(författare)
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United Nations Environment Programme Capacity Building Pilot Project : training and interlaboratory study on persistent organic pollutant analysis under the Stockholm Convention
- 2008
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 617:1-2, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Within the framework of a United Nations Environment Programme (UNEP) Capacity Building Project for training of laboratory staff in developing countries on persistent organic pollutant (POP) analysis, an interlaboratory study was organised following an initial evaluation of the performance of laboratories (reality check) and a series of training sessions. The target compounds were polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP). Seven laboratories from five countries (Ecuador, Uruguay, Kenya, Moldova, and Fiji) participated. Most of the laboratories had no experience in determining PCBs. Although chromatograms improved considerably after the training and installation of new gas chromatographic (GC) columns at participating laboratories, the level of performance in the interlaboratory study was essentially on par with the moderate performance level achieved by European POP laboratories in the 1980s. Only some individual results were within +/-20% of the target values. The relative standard deviations (R.S.D.s) in POP concentrations determined by laboratories in a sediment sample were >200% in a number of cases. The results for a certified herring sample were better with at least some R.S.D. values below 50% and most below 100%. Clean up was as one of the main sources of error. After inspection it was ascertained that training of laboratory staff and investments in simple consumables such as glassware and GC columns would help to improve the quality of the analysis more than major investments in expensive instrumentation. Creating an effective network of POP laboratories at different continents together with a series of interlaboratory studies and workshops is suggested to improve the measurements of POPs in these countries.
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| 41. |
- Düringer, Caroline, et al.
(författare)
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Agonist-specific patterns of beta(2)-adrenoceptor responses in human airway cells during prolonged exposure.
- 2009
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 158, s. 169-179
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi-effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro. Key results: There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of beta(2)-agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists. Conclusions and implications: There were clear differences in the ability of different beta(2) agonists to induce loss of receptor responsiveness at equi-effective concentrations.
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| 42. |
- Ekstam, Lisa, et al.
(författare)
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A research-based strategy for managing housing adaptations: study protocol for a quasi-experimental trial
- 2014
-
Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The primary aim of this paper is to describe the design of a project evaluating the effects of using a research-based strategy for managing housing adaptations (HAs). The evaluation targets clients' perspectives in terms of activity, participation, usability, fear of falling, fall incidence, use of mobility devices, and health-related quality of life, and determines the societal effects of HAs in terms of costs. Additional aims of the project are to explore and describe this strategy in relation to experiences and expectations (a) among clients and cohabitants and (b) occupational therapists in ordinary practice. Methods/design: This study is a quasi-experimental trial applying a multiphase design, combining quantitative and qualitative data. At the experimental sites, the occupational therapists (OTs) apply the intervention, i.e. a standardized research-based strategy for HA case management. At the control site, the occupational therapists are following their regular routine in relation to HA. Three municipalities in south Sweden will be included based on their population, their geographical dispersion, and their similar organizational structures for HA administration. Identical data on outcomes is being collected at all the sites at the same four time points: before the HA and then 3, 6, and 12 months after the HA. The data-collection methods are semi-structured qualitative interviews, observations, clinical assessments, and certificates related to each client's HA. Primary outcomes are the usability of the home and the client's independence in daily activities (ADL). Cross-sectional and longitudinal data analyses will be conducted as well as statistical analyses, health-economic analyses, and qualitative analyses. Qualitative and quantitative data will be sequentially analyzed, and case studies will be developed. Discussion: The intervention in this study has been developed and tested through many years of research and in collaboration with practitioners. This process includes methodological development and testing research aimed at identifying the most important outcomes and research targeting current HA case-management procedures in Swedish municipalities. When the study is completed, the results will be used for further optimization of the practice strategy for HA, in close collaboration with the data-collecting OTs.
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| 43. |
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| 44. |
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| 45. |
- Fagerberg, Jonas H., et al.
(författare)
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Computational Prediction of Drug Solubility in Fasted Simulated and Aspirated Human Intestinal Fluid
- 2015
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Ingår i: Pharmaceutical research. - : Springer. - 0724-8741 .- 1573-904X. ; 32:2, s. 578-589
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo develop predictive models of apparent solubility (Sapp) of lipophilic drugs in fasted state simulated intestinal fluid (FaSSIF) and aspirated human intestinal fluid (HIF).MethodsMeasured Sapp values in FaSSIF, HIF and phosphate buffer pH 6.5 (PhBpH6.5) for 86 lipophilic drugs were compiled and divided into training (Tr) and test (Te) sets. Projection to latent structure (PLS) models were developed through variable selection of calculated molecular descriptors. Experimentally determined properties were included to investigate their contribution to the predictions.ResultsModest relationships between Sapp in PhBpH6.5 and FaSSIF (R2 = 0.61) or HIF (R2 = 0.62) were found. As expected, there was a stronger correlation obtained between FaSSIF and HIF (R2 = 0.78). Computational models were developed using calculated descriptors alone (FaSSIF, R2 = 0.69 and RMSEte of 0.77; HIF, R2 = 0.84 and RMSEte of 0.81). Accuracy improved when solubility in PhBpH6.5 was added as a descriptor (FaSSIF, R2 = 0.76 and RMSETe of 0.65; HIF, R2 = 0.86 and RMSETe of 0.69), whereas no improvement was seen when melting point (Tm) or logDpH 6.5 were included in the models.ConclusionComputational models were developed, that reliably predicted Sapp of lipophilic compounds in intestinal fluid, from molecular structures alone. If experimentally determined pH-dependent solubility values were available, this further improved the accuracy of the predictions.
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| 46. |
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| 47. |
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| 48. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 49. |
- Gong, Jing, 1971-
(författare)
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Hybrid Methods for Unsteady Fluid Flow Problems in Complex Geometries
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, stable and efficient hybrid methods which combine high order finite difference methods and unstructured finite volume methods for time-dependent initial boundary value problems have been developed. The hybrid methods make it possible to combine the efficiency of the finite difference method and the flexibility of the finite volume method.We carry out a detailed analysis of the stability of the hybrid methods, and in particular the stability of interface treatments between structured and unstructured blocks. Both the methods employ so called summation-by-parts operators and impose boundary and interface conditions weakly, which lead to an energy estimate and stability.We have constructed and analyzed first-, second- and fourth-order Laplacian based artificial dissipation operators for finite volume methods on unstructured grids. The first-order artificial dissipation can handle shock waves, and the fourth-order artificial dissipation eliminates non-physical numerical oscillations efficiently.A stable hybrid method for hyperbolic problems has been developed. It is shown that the stability at the interface can be obtained by modifying the dual grid of the unstructured finite volume method close to the interface. The hybrid method is applied to the Euler equation by the coupling of two stand-alone CFD codes. Since the coupling is administered by a third separate coupling code, the hybrid method allows for individual development of the stand-alone codes. It is shown that the hybrid method is an accurate, efficient and practically useful computational tool that can handle complex geometries and wave propagation phenomena.Stable and accurate interface treatments for the linear advection–diffusion equation have been studied. Accurate high-order calculation are achieved in multiple blocks with interfaces. Three stable interface procedures — the Baumann–Oden method, the “borrowing” method and the local discontinuous Galerkin method, have been investigated. The analysis shows that only minor differences separate the different interface handling procedures.A conservative stable and efficient hybrid method for a parabolic model problem has been developed. The hybrid method has been applied to the full Navier–Stokes equations. The numerical experiments support the theoretical conclusions and show that the interface coupling is stable and converges at the correct order for the Navier–Stokes equations.
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| 50. |
- Gustafsson, Susanne, et al.
(författare)
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Health-promoting interventions for persons aged 80 and older are successful in the short term : results from the randomized and three-armed Elderly Persons in the Risk Zone study
- 2012
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Ingår i: Journal of The American Geriatrics Society. - 0002-8614 .- 1532-5415. ; 60:3, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the outcomes of the Elderly Persons in the Risk Zone study, which was designed to evaluate whether it is possible to delay deterioration if a health-promoting intervention is made when an older adult (≥80) is at risk of becoming frail and whether a multiprofessional group intervention is more effective in delaying deterioration than a single preventive home visit with regard to frailty, self-rated health, and activities of daily living (ADLs) at 3-month follow-up.DESIGN: Randomized, three-armed, single-blind, controlled trial performed between November 2007 and May 2011.SETTING: Two urban districts of Gothenburg, Sweden.PARTICIPANTS: Four hundred fifty-nine community-living adults aged 80 and older not dependent on the municipal home help service.INTERVENTION: A preventive home visit or four weekly multiprofessional senior group meetings with one follow-up home visit.MEASUREMENTS: Change in frailty, self-rated health, and ADLs between baseline and 3-month follow-up.RESULTS: Both interventions delayed deterioration of self-rated health (odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.12-3.54). Senior meetings were the most beneficial intervention for postponing dependence in ADLs (OR = 1.95, 95% CI = 1.14-3.33). No effect on frailty could be demonstrated.CONCLUSION: Health-promoting interventions made when older adults are at risk of becoming frail can delay deterioration in self-rated health and ADLs in the short term. A multiprofessional group intervention such as the senior meetings described seems to have a greater effect on delaying deterioration in ADLs than a single preventive home visit. Further research is needed to examine the outcome in the long term and in different contexts.
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