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Sökning: WFRF:(Eric Katarina)

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2.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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3.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Sator, Lea, et al. (författare)
  • Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
  • 2019
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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8.
  • Adewumi, Oluseun, et al. (författare)
  • Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
  • 2007
  • Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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9.
  • Akselsson, Roland, et al. (författare)
  • Luftföroreningar vid svetsning
  • 1977
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • PIXE-analyser kan utföras med utvecklad analysuppställning med noggrannhet och precision av c:a 10 % och med hög analyskapacitet. Ett dataprogram för evaluering av räntgenspektra presenteras. Inverkan av provtjocklek vid PIXE-analys av inhomogena prov har studerats och korrektioner föreslås. Fluorinnehållet i filterprov har bestämts, samtidigt med PIXE-analys, genom utnyttjande av en kärnfysikalisk reaktion som ger resultat med god noggrannhet och precision. Svetsaerosoler har karakteriserats m.h.a. PIXE, ESCA och TEM/EDAX. En uppställning för insamling av svetsaerosoler under utveckling och hittillsvarande resultat indikerar representativ provinsamling med god reproducerbarhet.
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11.
  • Albers, Eva, 1966, et al. (författare)
  • Influence of preservation methods on biochemical composition and downstream processing of cultivated Saccharina latissima biomass
  • 2021
  • Ingår i: Algal Research. - : Elsevier BV. - 2211-9264. ; 55
  • Tidskriftsartikel (refereegranskat)abstract
    • Saccharina latissima biomass cultivated along the Swedish west coast was subjected to four different scalable preservation methods after harvest; freezing, sun-drying, oven-drying and ensiling. Freeze-drying and freezing at -80 ?C were also included to provide dry and wet references. The effects of the different preservation methods on the composition of Saccharina biomass (on dry weight, DW, basis), and the recovery as well as properties of high-quality protein, alginate and biogas were evaluated. Sun-drying significantly reduced protein, alginate and fatty acid content of the seaweeds and thereby concentrated ash in the biomass compared to the other methods. Protein/amino acids and fatty acids were significantly concentrated in ensiled biomass, while mannitol and laminarin were reduced compared to the other biomasses. Oven-drying and -20 ?C freezing affected the composition the least, with lower ash content and alterations in some specific amino and fatty acids. Sun-drying and ensiling resulted in significantly lower protein solubility at high pH compared to the other biomasses which translated into the lowest total seaweed protein recovery using the pH-shift process. Highest protein yield was obtained with the freeze-dried reference. Ensiling lead to a significant decrease in the molecular weight of alginate, while sun-drying caused a negative effect on alginate by inducing a shift in the guluronic and mannuronic acids composition of alginate. Sun-drying gave the lowest methane yield in the anaerobic digestion experiments while freezing at -80 ?C gave the highest yield, closely followed by freezing at -20 ?C and ensiling. To conclude, preservation methods must be carefully chosen to protect the valuable component in Saccharina latissima, and to achieve an efficient downstream processing ultimately yielding high quality products as part of a seaweed biorefinery.
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12.
  • Conti, David, V, et al. (författare)
  • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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13.
  • Eklund, D. Magnus, et al. (författare)
  • Homologues of the Arabidopsis thaliana SHI/STY/LRP1 genes control auxin biosynthesis and affect growth and development in the moss Physcomitrella patens
  • 2010
  • Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 137:8, s. 1275-1284
  • Tidskriftsartikel (refereegranskat)abstract
    • The plant hormone auxin plays fundamental roles in vascular plants. Although exogenous auxin also stimulates developmental transitions and growth in non-vascular plants, the effects of manipulating endogenous auxin levels have thus far not been reported. Here, we have altered the levels and sites of auxin production and accumulation in the moss Physcomitrella patens by changing the expression level of homologues of the Arabidopsis SHI/STY family proteins, which are positive regulators of auxin biosynthesis genes. Constitutive expression of PpSHI1 resulted in elevated auxin levels, increased and ectopic expression of the auxin response reporter GmGH3pro:GUS, and in an increased caulonema/chloronema ratio, an effect also induced by exogenous auxin application. In addition, we observed premature ageing and necrosis in cells ectopically expressing PpSHI1. Knockout of either of the two PpSHI genes resulted in reduced auxin levels and auxin biosynthesis rates in leafy shoots, reduced internode elongation, delayed ageing, a decreased caulonema/chloronema ratio and an increased number of axillary hairs, which constitute potential auxin biosynthesis sites. Some of the identified auxin functions appear to be analogous in vascular and non-vascular plants. Furthermore, the spatiotemporal expression of the PpSHI genes and GmGH3pro:GUS strongly overlap, suggesting that local auxin biosynthesis is important for the regulation of auxin peak formation in non-vascular plants.
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14.
  • Ferreira, Daniel, et al. (författare)
  • The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
  • 2017
  • Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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15.
  • Hendriksen, Rene S., et al. (författare)
  • Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019, The Author(s). Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
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16.
  • Holm, Åsa, et al. (författare)
  • Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation : correlation with impaired translocation of PKCα and defective phagosome maturation
  • 2001
  • Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 3:7, s. 439-447
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes. The repeating disaccharide–phosphate units of LPG are crucial for promastigote survival inside macrophages and establishment of infection. LPG has a number of effects on the host cell, including inhibition of PKC activity, inhibition of nitric oxide production and altered expression of cytokines. LPG also inhibits phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin. In the present study, we have characterized the dynamics of F-actin during the phagocytosis of L. donovani promastigotes in J774 macrophages. We observed that F-actin accumulated progressively around phagosomes containing wild-type L. donovani promastigotes during the first hour of phagocytosis. Using LPG-defective mutants and yeast particles coated with purified LPG, we obtained evidence that this effect could be attributed to the repeating units of LPG. LPG also disturbed cortical actin turnover during phagocytosis. The LPG-dependent accumulation of periphagosomal F-actin correlated with an impaired recruitment of the lysosomal marker LAMP1 and PKCα to the phagosome. Accumulation of periphagosomal F-actin during phagocytosis of L. donovani promastigotes may contribute to the inhibition of phagosomal maturation by physically preventing vesicular trafficking to and from the phagosome.
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17.
  • Holm, Åsa, et al. (författare)
  • Protein C α regulates phagocytosis actin dynamics and phagosomal maturation in macrophages
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Promastigotes of the protozoan parasite Leishmania donovani cause an accumulation of periphagosomal F-actin instead of the normal decrease seen with other prey [1]. This accumulation is dependent on promastigote lipophosphoglycan (LPG), which has several detrimental effects on the cell including inhibition of PKCα activity.To directly address the role of PKCα and LPG for actin remodeling in macrophages, we investigated F-actin dynamics in RAW 264.7 macrophages overexpressing a dominant-negative mutant of PKCα (DN PKCα). We found that DN PKCα-overexpressing cells displayed increased levels of cortical F-actin and decreased phagocytic capacity, which was augmented when the cells were subjected to LPG-coated prey. The DN PKCα-overexpressing cells also showed defective breakdown of periphagosomal F-actin and inhibition of phagosomal maturation. The level of periphagosomal F-actin was similar to that of controls subjected to LPG-coated prey. Our results show that PKCα regulates phagocytosis and F-actin turnover in macrophages, and that PKCα-dependent breakdown of periphagosomal F-actin is required for normal phagosomal maturation.
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18.
  • Holm, Åsa, et al. (författare)
  • Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages
  • 2003
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 302:4, s. 653-658
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the dissassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKCα. To investigate a possible connection between PKCα and LPG’s effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PKCα (DN PKCα). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKCα-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKCα is involved in F-actin turnover in macrophages and that PKCα-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKCα by LPG.
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19.
  • Huyghe, Jeroen R., et al. (författare)
  • Discovery of common and rare genetic risk variants for colorectal cancer
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
  • Tidskriftsartikel (refereegranskat)abstract
    • To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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20.
  • Hvidtfeldt, Ulla A., et al. (författare)
  • Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults
  • 2010
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 121:14, s. 1589-1597
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. Methods and Results-In this pooled analysis of 8 prospective studies from North America and Europe including 192 067 women and 74 919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >= 60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100 000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100 000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100 000; 90% CI, 44 to 140) adults. Similar results were observed in women. Conclusion-Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults. (Circulation. 2010; 121: 1589-1597.)
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21.
  • Johansson, Gerd, et al. (författare)
  • Luftföroreningar vid svetsning
  • 1978
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Beskrivning ges av utveckling av analysuppställning för PIXE-analys, kombinerad med metod för analys av fluor. Vidareutveckling av spektrumevalueringsprogram, HEX, presenteras. Beskrivning av utförda svetsröskarakteriseringar ges. Resultat redovisas för följande belagda elektroder: OK 48.00, OK 38.65 samt OK 61.41. För sistnämnda, rostfria elektrod, presenteras procedur för bestämning av kroms valenstal och löslighet.
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22.
  • Kapun, Martin, et al. (författare)
  • Drosophila Evolution over Space and Time (DEST) : A New Population Genomics Resource
  • 2021
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5782-5805
  • Tidskriftsartikel (refereegranskat)abstract
    • Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
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23.
  • Kitutu, Freddy Eric, et al. (författare)
  • Integrated community case management by drug sellers influences appropriate treatment of paediatric febrile illness in South Western Uganda : a quasi-experimental study.
  • 2017
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Fever case management is a major challenge for improved child health globally, despite existence of cheap and effective child survival health technologies. The integrated Community Case Management (iCCM) intervention of paediatric febrile illnesses though adopted by Uganda's Ministry of Health to be implemented by community health workers, has not addressed the inaccess to life-saving medicines and diagnostics. Therefore, the iCCM intervention was implemented in private drug shops and evaluated for its effect on appropriate treatment of paediatric fever in a low malaria transmission setting in South Western Uganda.METHODS: From June 2013 to September 2015, the effect of the iCCM intervention on drug seller paediatric fever management and adherence to iCCM guidelines was assessed in a quasi-experimental study in South Western Uganda. A total of 212 care-seeker exit interviews were done before and 285 after in the intervention arm as compared to 216 before and 268 care-seeker interviews at the end of the study period in the comparison arm. The intervention effect was assessed by difference-in-difference analysis of drug seller treatment practices against national treatment recommendations between the intervention and comparison arms. Observed proportions among care-seeker interviews were compared with corresponding proportions from 5795 child visits recorded in patient registries and 49 direct observations of drug seller-care-seeker encounters in intervention drug shops.RESULTS: The iCCM intervention increased the appropriate treatment of uncomplicated malaria, pneumonia symptoms and non-bloody diarrhoea by 80.2% (95% CI 53.2-107.2), 65.5% (95% CI 51.6-79.4) and 31.4% (95% CI 1.6-61.2), respectively. Within the intervention arm, drug seller scores on appropriate treatment for pneumonia symptoms and diagnostic test use were the same among care-seeker exit interviews and direct observation. A linear trend (negative slope, - 0.009 p value < 0.001) was observed for proportions of child cases prescribed any antimicrobial medicine in the intervention arm drug shops.CONCLUSIONS: The iCCM intervention improved appropriate treatment for uncomplicated malaria, pneumonia symptoms and diarrhoea. Drug seller adherence to iCCM guidelines was high, without causing excessive prescription of antimicrobial medicines in this study. Further research should assess whether this effect is sustained over time and under routine supervision models.
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25.
  • Kraljic, Katarina, et al. (författare)
  • Emergence and cosmic evolution of the Kennicutt- Schmidt relation driven by interstellar turbulence
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 682
  • Tidskriftsartikel (refereegranskat)abstract
    • The scaling relations between the gas content and star formation rate of galaxies provide useful insights into the processes governing their formation and evolution. We investigated the emergence and the physical drivers of the global Kennicutt-Schmidt (KS) relation at 0:25 ≤ z ≤ 4 in the cosmological hydrodynamic simulation NewHorizon, capturing the evolution of a few hundred galaxies with a resolution down to 34 pc. The details of this relation vary strongly with the stellar mass of galaxies and the redshift. A power-law relation ΣSFR / Σa gas with a ≈ 1:4, like that found empirically, emerges at z ≈ 2..3 for the more massive half of the galaxy population. However, no such convergence is found in the lower-mass galaxies, for which the relation gets shallower with decreasing redshift. At galactic scales, the star formation activity correlates with the level of turbulence of the interstellar medium, quantified by the Mach number, rather than with the gas fraction (neutral or molecular), confirming the conclusions found in previous works. With decreasing redshift, the number of outliers with short depletion times diminishes, reducing the scatter of the KS relation, while the overall population of galaxies shifts toward low densities. Our results, from parsec-scale star formation models calibrated with local Universe physics, demonstrate that the cosmological evolution of the environmental (e.g., mergers) and internal conditions (e.g., gas fractions) conspire to shape the KS relation. This is an illustration of how the interplay of global and local processes leaves a detectable imprint on galactic-scale observables and scaling relations.
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26.
  • Landberg, Katarina, et al. (författare)
  • The Moss Physcomitrella patens Reproductive Organ Development Is Highly Organized, Affected by the Two SHI/STY Genes and by the Level of Active Auxin in the SHI/STY Expression Domain
  • 2013
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 1532-2548 .- 0032-0889. ; 162:3, s. 1406-1419
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3(pro):GUS and PpPINA(pro): GFP-GUS, and the auxin-conjugating transgene PpSHI2(pro):IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
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27.
  • Lindahl, Katarina, et al. (författare)
  • Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk.
  • 2009
  • Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 384:4, s. 501-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variation plays an important role in osteoporosis and a prime candidate gene is Collagen alpha2(I) (COL1A2). A coding polymorphism (rs42524) in COL1A2 has previously been associated with intracranial aneurysms. Here the effects of this polymorphism have been studied in relation to bone mineral density (BMD) and prevalences of stroke and myocardial infarction (MI). rs42524 was genotyped in elderly men (n = 2004) from the Swedish MrOS cohort. Genotypes were analysed for association to BMD and certain health parameters. Significant associations (overall P < 0.05), were observed between rs42524 genotype and BMD at several skeletal sites. Surprisingly, the heterozygote genotype class exhibited lower BMD than either homozygote group. When subjects were classified as heterozygotes or homozygotes, the heterozygous genotype was found to confer a lower BMD at total hip, femoral neck and trochanter Furthermore, the heterozygote genotype had an increased risk of stroke and MI, with population Attributable Risks being 0.12 and 0.08, respectively.
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28.
  • Lindblom, Anders, et al. (författare)
  • Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Åland Islands
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Tick-transmitted diseases are an emerging health problem, and the hard tick Ixodes ricinus is the main vector for Borrelia spp., tick-borne encephalitis virus and most of the spotted fever Rickettsiae in Europe. The aim of the present study was to examine the incidence of rickettsial infection in the southernmost and south central parts of Sweden and the Aland Islands in Finland the risk of infection in humans and its correlation with a bite of a Rickettsia-infected tick, the self-reported symptoms of rickettsial disease, and the prevalence of co-infection between Rickettsia spp. and Borrelia spp. Persons with a recent tick bite were enrolled through public media and asked to answer a questionnaire, provide a blood sample and bring detached ticks at enlistment and at follow-up three months later. Blood samples were previously analysed for Borrelia spp. antibodies and, for this report, analysed for antibodies to Rickettsia spp. by immunofluorescence and in 16 cases also using Western Blot. Ninety-six (44.0%) of the 218 participants were seropositive for IgG antibodies to Rickettsia spp. Forty (18.3%) of the seropositive participants had increased titres at the follow-up, indicating recent/current infection, while four (1.8%) had titres indicating probable recent/current infection (>= 1: 256). Of 472 ticks, 39 (8.3%) were Rickettsia sp. positive. Five (31.3%) of 16 participants bitten by a Rickettsia-infected tick seroconverted. Experience of the selfreported symptoms nausea (p = 0.006) and radiating pain (p = 0.041) was more common among those with recent, current or probable infection compared to those who did not seroconvert. Participants who showed seroreactivity or seroconversion to Rickettsia spp. had more symptoms than those who were seronegative. Seven (3.2%) participants showed seroconversion to Borrelia spp., and three (1.4%) of these showed seroconversion to both Rickettsia spp. and Borrelia spp., in accordance with previous studies in Sweden. Symptoms of rickettsial disease were in most of the cases vague and general that were difficult to differentiate from other tick-borne diseases.
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29.
  • Ljungberg, Michael, et al. (författare)
  • A 3-dimensional absorbed dose calculation method based on quantitative SPECT for radionuclide therapy: evaluation for (131)I using monte carlo simulation.
  • 2002
  • Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 43:8, s. 1101-1109
  • Tidskriftsartikel (refereegranskat)abstract
    • A general method is presented for patient-specific 3-dimensional absorbed dose calculations based on quantitative SPECT activity measurements. METHODS: The computational scheme includes a method for registration of the CT image to the SPECT image and position-dependent compensation for attenuation, scatter, and collimator detector response performed as part of an iterative reconstruction method. A method for conversion of the measured activity distribution to a 3-dimensional absorbed dose distribution, based on the EGS4 (electron-gamma shower, version 4) Monte Carlo code, is also included. The accuracy of the activity quantification and the absorbed dose calculation is evaluated on the basis of realistic Monte Carlo-simulated SPECT data, using the SIMIND (simulation of imaging nuclear detectors) program and a voxel-based computer phantom. CT images are obtained from the computer phantom, and realistic patient movements are added relative to the SPECT image. The SPECT-based activity concentration and absorbed dose distributions are compared with the true ones. RESULTS: Correction could be made for object scatter, photon attenuation, and scatter penetration in the collimator. However, inaccuracies were imposed by the limited spatial resolution of the SPECT system, for which the collimator response correction did not fully compensate. CONCLUSION: The presented method includes compensation for most parameters degrading the quantitative image information. The compensation methods are based on physical models and therefore are generally applicable to other radionuclides. The proposed evaluation methodology may be used as a basis for future intercomparison of different methods.
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30.
  • Lundberg, Stellan, et al. (författare)
  • Femton hinder förhållbar stadsutveckling : Delegationen för hållbara städer
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Femton hinder för hållbar stadsutvecklingDelegationen för hållbara städer tillsattes av regeringen för perioden 2008–2012 för att genomföra olika åtgärder som bidrar till förbättrade förutsättningar för utveckling av hållbara städer. I delegationens uppdrag ingick att undersöka vilka eventuella system och strukturer som kan utgöra hinder för hållbar stadsutveckling och identifiera förslag till åtgärder och lösningar. Den 28 juni 2012 lämnade delegationen denna rapport till regeringen.
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31.
  • Mattsson, Katarina (författare)
  • (O)likhetens geografier : Marknaden, forskningen och de Andra
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The dissertation examines representations and discourses of the Others in the field of immigration and labour market studies from a critical discourse analysis perspective. The theoretical discussions rely on theories of post-colonialism, racial and colonial discourse, as well as theories of nationalism, culture and identity. Firstly, empirical material, i.e., editorials, newspaper articles, and news reporting, on issues of immigration and labour market collected from a wide range of Swedish newspapers covering the period 1996-1999 has been studied. The purpose was to identify dominant themes and representations as well as suggested policy recommendations, with particular emphasis on the debates on ethnic discrimination and anti-discrimination laws. Secondly, a critical and detailed analysis has been carried out of a scientific discourse that claims that culturally defined deficiencies in skills account for the low rates of gainful employment among "culturally distant" immigrants. This discourse - expressed in the conceptual framework of human capital theory - is laballed the "cultural skill deficiency discourse". The analyses reveal the discursive relationships between geographical imaginations of origins, cultural identity, and politics in labour market and immigration studies. The discourse includes racialized assumptions about culture, nation and skills, and reproduces a spatial hierarchy of (dis)similarity earlier expressed in racial and colonial discourses. The study also analyses the assumption that non-western immigrants have a self-evident place at the bottom of labour market hierarchies. Finally, the scientific discourse claiming that immigrants lack culturally specific skills, is in the dissertation conceptualised as a form of economic racism, since it expresses culturally racist ideas in an economic rhetoric and conceptual frame. It also legitimises ethnic hierachies in the labour market and the economy.
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32.
  • Nilsson, Niklas, et al. (författare)
  • The economic cost and patient-reported outcomes of chronic Achilles tendon ruptures.
  • 2020
  • Ingår i: Journal of experimental orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • While most Achilles tendon ruptures are dramatic and diagnosed quickly, some are missed, with a risk of becoming chronic. A chronic Achilles tendon rupture is defined as a rupture that has been left untreated for more than 4 weeks. By mapping the health economic cost of chronic Achilles tendon ruptures the health-care system might be able to better distribute resources to detect these ruptures at an earlier time.All patients with a chronic Achilles tendon rupture who were treated surgically at Sahlgrenska University Hospital or Kungsbacka Hospital between 2013 and 2018 were invited to participate in the study. The patients were evaluated postoperatively using the validated Achilles tendon Total Rupture Score (ATRS). The health-care costs were assessed using clinical records. The production-loss costs were extracted from the Swedish Social Insurance Agency. The cost of chronic Achilles tendon ruptures was then compared with the cost of acute ruptures in a previous study by Westin et.al.Forty patients with a median (range) age of 66 (28-86) were included in the study. The mean total cost (± SD) for the patients with a chronic Achilles tendon rupture was 6494 EUR±6508, which is 1276 EUR higher than the mean total cost of acute ruptures. Patients with chronic Achilles tendon ruptures reported a mean (min-max) postoperative ATRS of 73 (14-100).Missing an Achilles tendon rupture will entail higher health-care costs compared with acute ruptures. Health-care resources can be saved if Achilles tendon ruptures are detected at an early stage.
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33.
  • Nordenholm, Anna, et al. (författare)
  • Disappointment and frustration, but long-term satisfaction: patient experiences undergoing treatment for a chronic Achilles tendon rupture-a qualitative study.
  • 2022
  • Ingår i: Journal of orthopaedic surgery and research. - : Springer Science and Business Media LLC. - 1749-799X. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Delayed treatment of Achilles tendon ruptures is generally due to either misdiagnosis or patient delay. When the treatment is delayed more than 4weeks, the rupture is defined as "chronic", and almost always requires more invasive surgery and longer rehabilitation time compared with acute Achilles tendon ruptures. There is insufficient knowledge of patient experiences of sustaining and recovering from a chronic Achilles tendon rupture.To evaluate patients' experiences of suffering a chronic Achilles tendon rupture, semi-structured group interviews were conducted 4-6years after surgical treatment using a semi-structured interview guide. The data were analyzed using qualitative content analysis described by Graneheim and Lundman.The experiences of ten patients (65±14years, 7 males and 3 females) were summarized into four main categories: (1) "The injury", where the patients described immediate functional impairments, following either traumatic or non-traumatic injury mechanisms that were misinterpreted by themselves or the health-care system; (2) "The diagnosis", where the patients expressed relief in receiving the diagnosis, but also disappointment and/or frustration related to the prior misdiagnosis and delay; (3) "The treatment", where the patients expressed high expectations, consistent satisfaction with the surgical treatment, and addressed the importance of the physical therapist having the right expertise; and (4) "The outcomes", where the patients expressed an overall satisfaction with the long-term outcome and no obvious limitations in physical activity, although some fear of re-injury emerged.An Achilles tendon rupture can occur during both major and minor trauma and be misinterpreted by both the assessing health-care professional as well as the patient themselves. Surgical treatment and postoperative rehabilitation for chronic Achilles tendon rupture results in overall patient satisfaction in terms of the long-term outcomes. We emphasize the need for increased awareness of the occurrence of Achilles tendon rupture in patients with an atypical patient history.
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34.
  • Nordenholm, Anna, et al. (författare)
  • Greater heel-rise endurance is related to better gait biomechanics in patients surgically treated for chronic Achilles tendon rupture
  • 2022
  • Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 30, s. 3898-3906
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To determine the relationships among calf muscle function, tendon length and gait biomechanics in patients surgically treated for chronic Achilles tendon rupture. Methods Twenty-one patients with chronic Achilles tendon rupture (mean age 62 +/- 13 years) were evaluated by heel-rise endurance test, Achilles Tendon Resting Angle (ATRA), ultrasound measurement of tendon length and three-dimensional gait analysis. A bivariate two-sided correlation test was performed on all variables in all patients. Results Better performance across all parameters of the heel-rise endurance test correlated with faster walking speed (r = 0.52-0.55), greater peak ankle power (r = 0.56-0.64), shorter stance phase (r = -0.52 to -0.76) and less peak ankle dorsiflexion angle (r = -0.49 to -0.64) during gait. Greater ATRA correlated with longer stance time (r = 0.47), greater peak ankle dorsiflexion angle (r = 0.48), less heel-rise repetitions (r = -0.52) and less heel-rise total work LSI (r = -0.44 to -0.59). Conclusion Greater calf muscle endurance, especially heel-rise total work, is moderately correlated (r = 0.49-0.76) to better ankle biomechanics during gait in patients surgically treated for CATR. The heel-rise endurance test may be a clinical proxy for power development in the ankle joint during gait.
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35.
  • Nordenholm, Anna, et al. (författare)
  • Patients with chronic Achilles tendon rupture have persistent limitations in patient-reported function and calf muscle function one year after surgical treatment - a case series
  • 2022
  • Ingår i: Journal of Experimental Orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Evaluate the one-year postoperative outcomes in patients with Chronic Achilles tendon rupture. Methods Patients surgically treated for Chronic Achilles tendon rupture (n = 22, 14 males and 8 females, mean age 61 +/- 15) were evaluated by Achilles tendon Total Rupture Score, The Physical Activity Scale, The Foot and Ankle Outcome Score, Calf muscle endurance test, counter movement jump, Hopping, ultrasound measurement of tendon length, Achilles Tendon Resting Angle, dorsi flexion range of motion and calf muscle circumference. Muscle function and tendon length outcomes on the injured side were compared with the healthy side. Results The patients scored a mean of 62 +/- 26 on the Achilles tendon Total Rupture Score. Median scores on the injured compared with the healthy side were lower in heel-rise repetitions (20 vs 24 cm, p = 0.004), hel-rise height (8 vs 10 cm, p < 0.001), heel-rise total work (872 vs 1590 joule, p < 0.001) and hopping ratio (0.37 vs 0.48, p = 0.005). Median calf circumference was smaller (37 vs 38 cm, p = 0.001) and the mean tendon elongation greater on the injured side; Achilles tendon resting angle (55 vs 50 degrees, p < 0.001) and ultrasound (22.4 vs 20.5 cm, p = 0.006). Conclusions At one year postoperatively, patients with chronic Achilles tendon rupture reported persistent limitations in subjective foot and ankle function. Heel-rise height and total work as well as hopping ratio were not recovered, and there was an elongation of the injured Achilles tendon compared with the healthy tendon.
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36.
  • Nordenholm, Anna, et al. (författare)
  • Surgical treatment of chronic Achilles tendon rupture results in improved gait biomechanics
  • 2022
  • Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic Achilles tendon rupture is associated with persistent weakness at push-off with the affected foot and poor balance, resulting in significant alterations to normal gait. Surgical repair is the most common treatment for improving gait in patients with a Chronic Achilles tendon rupture, but, to date, the outcomes have not been quantified in the literature. Methods: A total of 23 patients with a Chronic Achilles tendon rupture (mean age 61 ± 15years) underwent three-dimensional gait analysis according to a standardized protocol using an optical tracking system. Data of spatiotemporal, kinematic and kinetic variables were collected preoperatively and one year postoperatively. In addition, the postoperative gait biomechanics were compared with the gait biomechanics of a control group consisting of 70 healthy individuals (mean age 49 ± 20years). The prospectively collected data were analyzed by an independent t test. Results: Postoperatively, increments were found in gait speed (mean difference − 0.12m/s), stride length (− 0.12m), peak ankle moment (− 0.64 Nm/kg), peak ankle power (− 1.38W/kg), peak knee power (− 0.36m) and reduced step width (0.01m), compared with preoperative gait biomechanics (p < 0.014). Compared with the control group, patients with a Chronic Achilles tendon rupture exhibited slower postoperative gait speed (mean difference 0.24m/s), wider step width (− 0.02m), shorter stride length (0.16m), longer relative stance phase (− 2.15%), lower peak knee flexion (17.03 degrees), greater peak knee extension (2.58 degrees), lower peak ankle moment (0.35 Nm/kg), peak ankle power (1.22W/kg) and peak knee power (1.62W/kg), (p < 0.010). Conclusion: Surgical intervention and postoperative rehabilitation can be an effective treatment for alterations in gait after a Chronic rupture of the Achilles tendon. However, at one year postoperatively, patients still exhibit impairments in spatiotemporal variables and knee and ankle power compared with healthy controls. © 2022, The Author(s).
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37.
  • Rundqvist, Helene, et al. (författare)
  • Activation of the erythropoietin receptor in human skeletal muscle
  • 2009
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 161:3, s. 427-434
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise. Design and methods: Ten healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated. Results: The EPOR proteinwas localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased. Conclusions: Interaction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.
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38.
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39.
  • Scutelnic, Adrian, et al. (författare)
  • Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
  • 2022
  • Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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40.
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41.
  • Sigvant, Birgitta, et al. (författare)
  • Risk factor profile and use of cardiovascular drugprevention in women and men with peripheral artery disease
  • 2009
  • Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267 .- 1741-8275. ; 16:1, s. 39-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To determine cardiovascular comorbidities and use of cardiovascular disease preventive drugs in patients with peripheral arterial disease (PAD), with special attention to sex differences. Design A cross-sectional point-prevalence study. Patients A population sample of patients that are 60-90 years old. Setting Primary care areas in four Swedish regions. Main outcome measures Prevalence of PAD stages, comorbidities and medication use. Results The prevalence of any type of PAD was 18.0% (range 16-20), of asymptomatic peripheral arterial disease (APAD) was 11.1% (range 9-13), intermittent claudication was 6.8% (range 6.5-7.1), and of critical limb ischemia (CLI) was 1.2% (range 1.0-1.5). APAD and CLI were more common in women. Statins were used by 17.5% (range 16.9-18.2), 29.4% (range 29.0-30.1), and 30.3% (range 29.9-30.8) of the patients with APAD, intermittent claudication, and CLI, respectively, and antiplatelet therapy was reported by 34.1% (range 33.7-34.3), 47.6% (range 47.3-47.9), and 60.2% (range 59.1-60.7). The odds ratio for having APAD was 1.7 (range 1.2-2.4) for women with a smoking history of 10 years in relation to nonsmokers. This association was observed only in men who had smoked for at least 30 years or more. Preventive drug use was more common in men with PAD. Compared with women they had an odds ratio of 1.3 (range 1.1-1.5) for lipid-lowering therapy, 1.3 (range 1.0-1.7) for β-blockers or angiotensin-converting enzyme inhibitors, and 1.5 (range 1.2-1.9) for antiplatelet therapy. Conclusion The patients' risk factor profiles differed among the PAD stages. Smoking duration already seemed to be a risk factor for women with PAD after 10 years of smoking, as compared with 30 years for men, and fewer women reported use of preventive medication. These observations may partly explain the sex differences in prevalence that were observed.
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42.
  • Skogman, Barbro Hedin, 1967-, et al. (författare)
  • Lyme neuroborreliosis in Swedish children-PCR as a complementary diagnostic method for detection of Borrelia burgdorferi sensu lato in cerebrospinal fluid
  • 2021
  • Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 40:5, s. 1003-1012
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate polymerase chain reaction (PCR) as a diagnostic method for the detection of Borrelia burgdorferi s.l. in CSF of Swedish children with LNB. This study was performed retrospectively on CSF and serum samples collected from children evaluated for LNB (n = 233) and controls with other specific neurological disorders (n = 59) in a Swedish Lyme endemic area. For anti-Borrelia antibody index, the IDEIA Lyme Neuroborreliosis kit (Oxoid) was used. Two in-house real-time PCR assays targeting the 16S rRNA gene were evaluated (TaqMan® and LUX™). Among patients classified as LNB cases (n = 102), five children (5%) were Borrelia PCR-positive in CSF with the TaqMan® assay. In the Non-LNB group (n = 131), one patient was Borrelia PCR positive with the TaqMan® assay. Among controls (n = 59), all CSF samples were PCR negative. When amplifying and sequencing ospA, we found B. garinii (n = 2), B. afzelii (n = 2), B. bavariensis (n = 1), and one untypable (n = 1). With the LUX™ technology, all CSF samples were PCR negative. The TaqMan® assay could detect only few cases (n = 6) of B. burgdorferi s.l. in CSF among children with LNB and the sensitivity was very low (5%). However, using larger CSF volumes and centrifugation of samples, the PCR technique could still be useful as a complementary diagnostic method when evaluating LNB. Furthermore, detection of spirochete DNA in clinical matrices, including CSF, is the method of choice for studying epidemiological aspects of LNB, a tick-borne emerging disease.
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43.
  • Studnicka, Michael, et al. (författare)
  • COPD : Should Diagnosis Match Physiology?
  • 2020
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 157:2, s. 473-475
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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44.
  • Tejle, Katarina, 1945- (författare)
  • Leishmania donovani Lipophosphoglycan : Modulation of Macrophage and Dendritic Cell Function
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Leishmania donovani is a blood-borne tropicial parasite, which infects humans through bites by Phlebotomus sandflies. The parasite survives and multiplies inside macrophages in inner organs, and causes the deadly disease visceral leishmaniasis (Kala-Azar).Macrophages and dendritic cells (DC) are professional antigen-presenting cells involved in the initiation of immune responses. Immature DC are present in all tissues where they internalise and process antigen, in response to which they migrate from tissue, into draining lymphoid organs, undergo maturation and present antigens to lymphocytes. Control measures for leishmaniasis include testing of new diagnostics and development of affordable and effective vaccines for humans.Lipophosphoglycan (LPG) is the major surface component of Leishmania donovani promastigotes. LPG comprises a membrane-anchoring lysophosphatidylinositol part and an extracellular chain of disaccharide phosphates. These repetitions are crucial for parasite survival inside macrophages following phagocytosis. LPG has several specific effects on the host cell including inhibition of protein kinase C (PKC) activity, and inhibition of phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin.Confocal microscopy and image analysis were used to follow F-actin dynamics in single macrophages during phagocytosis of L. donovani promastigotes and LPG-coated particles. F-actin did not depolymerize, but instead progressively polymerized around phagosomes with LPG-containing prey. This correlated with reduced translocation of PKCα to the phagosome and blocked phagosomal maturation. LPG also inhibited cortical actin turnover, which could be the underlying cause of the reduced uptake of LPG-containing prey. Extracellular- and intracellular calcium was necessary for phagocytosis, periphagosomal F-actin breakdown and phagosomal maturation in macrophages interacting with unopsonized prey,and for the action of LPG.We also studied F-actin turnover in macrophages overexpressing dominant-negative (DN) PKCα. DN PKCα macrophages showed increased amounts of cortical F-actin, decreased phagocytic capacity, inhibition of periphagosomal F-actin breakdown and defective phagosomal maturation. When DN PKCα macrophages interacted with LPG-containing prey, phagocytosis was almost completely blocked.Moreover, we found that Leishmania promastigotes and particularly LPG inhibit DC maturation and detachment from distinct surfaces. Thus, LPG from Leishmania donovani could directly inhibit DC migration to lymphoid organs, antigen-presentation and development of immunity.
  •  
45.
  • Tejle, Katarina, et al. (författare)
  • Phagocytosis and phagosome maturation are regulated by calcium in J774 macrophages interacting with un-opsonized prey
  • 2002
  • Ingår i: Bioscience Reports. - 0144-8463 .- 1573-4935. ; 22:5-6, s. 529-540
  • Tidskriftsartikel (refereegranskat)abstract
    • Phagocytosis by neutrophils, macrophages, and other professional phagocytes requires rapid remodeling of actin. Early phagosomes are surrounded by a rim of F-actin that is disassembled during phagosomoal maturation. Breakdown of periphagosomal F-actin and phagolysosome fusion are calcium dependent processes in neutrophils interacting with serum-opsonized prey, but appears to be calcium independent in macrophages interacting with serum- or IgG-opsonized prey. In the present study, we found that calcium was necessary for phagocytosis, breakdown of periphagosomal F-actin, and phagosomal maturation in J774 macrophages interacting with unopsonized prey. We also observed that lipophosphoglycan (LPG) from Leishmania donovani promastigotes required calcium to exert its inhibitory effect on macrophage phagocytosis and periphagosomal F-actin breakdown. We conclude that calcium is essential for phagocytosis, depolymerization of periphagosomal F-actin, and phagosomal maturation in J774 macrophages interacting with unopsonized prey, as well as for proper functioning of LPG.
  •  
46.
  • Tejle, Katarina, 1945-, et al. (författare)
  • Wild-type Leishmania donovani promastigotes block maturation, increase integrin expression and inhibit detachment of human monocyte-derived dendritic cells - The influence of phosphoglycans
  • 2008
  • Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 0378-1097 .- 1574-6968. ; 279:1, s. 92-102
  • Tidskriftsartikel (refereegranskat)abstract
    • The protective immune response against the parasite, including the role of dendritic cells (DC) in the course of infection, plays a fundamental role. This study shows that wild-type (WT) Leishmania promastigotes and specifically the phosphoglycans family of virulence-associated antigens inhibit human monocyte-derived dendritic cells (MoDC) maturation and detachment to distinct surfaces. Immature phagocytosis of Leishmania donovani promastigotes by immature MoDC results in the increased expression of CD11b and CD51, and inhibition of cell detachment to distinct surfaces, which was dependent on the presence of phosphoglycans. These findings demonstrate that phosphoglycans of WT L. donovani might also inhibit human DC migration to lymphoid organs. © 2007 Federation of European Microbiological Societies.
  •  
47.
  • Tengvall, Katarina, 1980-, et al. (författare)
  • Bayesian model and selection signature analyses reveal risk factors for canine atopic dermatitis
  • 2022
  • Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus (Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated.
  •  
48.
  • Thorsén, Frida, et al. (författare)
  • Digital nerve injuries: Epidemiology, results, costs, and impact on daily life.
  • 2012
  • Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; 46:3-4, s. 184-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiology, results of treatment, impact on activity of daily living (ADL), and costs for treatment of digital nerve injuries have not been considered consistently. Case notes of patients of 0-99 years of age living in Malmö municipality, Sweden, who presented with a digital nerve injury and were referred to the Department of Hand Surgery in 1995-2005 were analysed retrospectively. The incidence was 6.2/100 000 inhabitants and year. Most commonly men (75%; median age 29 years) were injured. Isolated nerve injuries and concomitant tendon injuries were equally common. The direct costs (hospital stay, operation, outpatient visits, visits to a nurse and/or a hand therapist) for a concomitant tendon injury was almost double compared with an isolated digital nerve injury (6136 EUR [range, 744-29 689 EUR] vs 2653 EUR [range, 468-6949 EUR]). More than 50% of the patients who worked were injured at work and 79% lost time from work (median 59 days [range 3-337]). Permanent nerve dysfunction for the individual patient with ADL problems and subjective complaints of fumbleness, cold sensitivity, and pain occur in the patients despite surgery. It is concluded that digital nerve injuries, often considered as a minor injury and that affect young people at productive age, cause costs, and disability. Focus should be directed against prevention of the injury and to improve nerve regeneration from different aspects.
  •  
49.
  • Vallejo-Vaz, Antonio J., et al. (författare)
  • Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
  • 2018
  • Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 277, s. 234-255
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in similar to 2/3 countries. Lipoprotein-apheresis is offered in similar to 60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.
  •  
50.
  • Viaene, Tom, et al. (författare)
  • Directional Auxin Transport Mechanisms in Early Diverging Land Plants
  • 2014
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24, s. 2786-2791
  • Tidskriftsartikel (refereegranskat)abstract
    • The emergence and radiation of multicellular land plants was driven by crucial innovations to their body plans [1]. The directional transport of the phytohormone auxin represents a key, plant-specific mechanism for polarization and patterning in complex seed plants [2-5]. Here, we show that already in the early diverging land plant lineage, as exemplified by the moss Physcomitrella patens, auxin transport by PIN transporters is operational and diversified into ER-localized and plasma membrane-localized PIN proteins. Gain-of-function and loss-of-function analyses revealed that PIN-dependent intercellular auxin transport in Physcomitrella mediates crucial developmental transitions in tip-growing filaments and waves of polarization and differentiation in leaf-like structures. Plasma membrane PIN proteins localize in a polar manner to the tips of moss filaments, revealing an unexpected relation between polarization mechanisms in moss tip-growing cells and multicellular tissues of seed plants. Our results trace the origins of polarization and auxin-mediated patterning mechanisms and highlight the crucial role of polarized auxin transport during the evolution of multicellular land plants.
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