| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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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| 3. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 4. |
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| 5. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 6. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 7. |
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| 8. |
- Aits, Sonja, et al.
(författare)
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HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:5, s. 1008-1019
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Tidskriftsartikel (refereegranskat)abstract
- HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.
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| 9. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 10. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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| 11. |
- Baudin, Katarina, 1971-
(författare)
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Assistive technology and welfare technology explorations : Aspects of perception, utilisation and decision-making
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims: The overall aim of this thesis was to explore decision makers’ and professionals’ perceptions, utilisation, and decision-making about assistive technology (AT) and welfare technology (WT) within the interprofessional field of care for older adults. Methods: A literature review was conducted, including nine peer-reviewed scientific articles (I), analysed with a qualitative descriptive method. A web-based questionnaire, answered by 393 officials and health care providers in municipal eldercare (II and III), was analysed using content analysis of the open-ended answers (II) and descriptive and inferential statistics of the closed-ended answers (III). A semi-structured interview with 24 decision makers was also conducted and analysed with thematic reflexive analysis. Results: The studies revealed a lack of evidence-based decision models to support assistive and welfare technology decisions, partly due to the context being complex and multifaceted. The technology was perceived as progressive and cutting-edge, while organizational structure and culture were perceived as regressive and resistant to change. The results revealed personnel working with WT were generally very positive toward new technology, although there were age, gender, participation, and professional differences. Study IV results revealed that supportive aspects, technology aspects, patient aspects, and knowledge aspects influence AT-organizations' decision-making. Although AT/WT has been portrayed to have the potential to solve the challenges of an aging population, the decision-making regarding AT/WT is complex and evolving. Increased communication between government, regions, and municipalities to support the development of guidelines would enhance the goal of a person-centred care. Conclusion: This thesis contributes to knowledge of decision-making models, focusing on GATE´s model (Khasnabis et al., 2015) applicable in AT/WT. Further development and deepen knowledge in the area of AT/WT appears as needed due to results showing that there is a lack of structured knowledge about the decision-making processes and evaluations of effects of AT/WT.
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| 12. |
- Berggren, Karolina, et al.
(författare)
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Hydraulic impacts on urban drainage systems due to changes in rainfall, caused by climatic change
- 2012
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Ingår i: Journal of hydrologic engineering. - 1084-0699 .- 1943-5584. ; 17:1, s. 92-98
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Tidskriftsartikel (refereegranskat)abstract
- The changes in climate were of a growing concern in the last decade, and will be even more so in the coming years. When investigating impacts on urban drainage systems due to changes in the climate, two challenges are (1) what type of input rainfall data to use, and (2) what parameters to measure the impacts. The overall objective of this study is to investigate the hydraulic performances ofurban drainage systems related to changes in rainfall, and through these hydraulic parameters describe impacts of climate change. Input rainfall data represents today's climate, as well as three future time periods (2011-2040, 2041-2070, and 2071-2100). The hydraulic parameters used were water levels in nodes (e.g. as the number of floods, frequency and duration of floods), and pipe flow ratio. For the study area, the number of flooded nodes and the geographical distribution of floods will increase in the future, as will both the flooding frequency and the duration of floods.
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| 13. |
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| 14. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 15. |
- Bjursell, Magnus K., et al.
(författare)
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Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 89:4, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (Ado Met), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism.
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| 16. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 17. |
- Borris, Matthias, et al.
(författare)
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Continuous simulations of urban stormwater runoff and total suspended solids loads: influence of varying climatic inputs and catchment imperviousness
- 2014
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Ingår i: Journal of Water and Climate. - : IWA Publishing. - 2040-2244 .- 2408-9354. ; 5:4, s. 593-609
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Tidskriftsartikel (refereegranskat)abstract
- Potential implications of climate change for future stormwater management were addressed by undertaking continuous simulations of runoff and total suspended solids (TSS) loads for three urban catchments, with imperviousness varying from 23 to 63%, which were exposed to five rainfall regimes during the snow-free part of the year: the current climate and four climate change scenarios projecting higher rainfalls. Simulated runoff volumes increased in all the future scenarios, particularly in the sub-arctic climate and the fixed uplift scenario (plus20) indicating appreciable rainfall increases. Simulated runoff volumes increased depending on the projected increases in rainfall and increasing runoff contributions from pervious areas when more intense future rainfalls exceeded hydrologic abstractions. The increased runoff volumes then contributed higher TSS loads, which were highly variable for the rainfall regimes tested. In cold climate regions, residues of solids from winter road maintenance may contribute to high initial accumulations of TSS on the catchment surface and high washed off loads. In general, the study suggests that intermediate design-life stormwater management facilities require flexible design allowing for future step-wise adaptation by gradually increasing design capacities and modifying treatment trains.
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| 18. |
- Borris, Matthias, et al.
(författare)
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Modelling the effects of changes in rainfall event characteristics on TSS loads in urban runoff
- 2014
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Ingår i: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 28:4, s. 1787-1796
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Tidskriftsartikel (refereegranskat)abstract
- The effect of changes in rainfall event characteristics on urban stormwater quality, which was described by total suspended solids (TSS), was studied by means of computer simulations conducted with the Storm Water Management Model for a climate change scenario for northern Sweden. The simulation results showed that TSS event loads depended mainly on rainfall depth and intensity, but not on antecedent conditions. Storms with low-to-intermediate depths and intensities showed the highest sensitivity to changes in rainfall input, both for percentage and absolute changes in TSS wash-off loads, which was explained by the contribution of pervious areas and supply limitations. This has significant implications for stormwater management, because those relatively frequent events generally carry a high percentage of the annual pollutant load
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| 19. |
- Borris, Matthias, et al.
(författare)
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Simulating future trends in urban stormwater quality for changing climate, urban land use and environmental controls
- 2013
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 68:9, s. 2082-2089
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Tidskriftsartikel (refereegranskat)abstract
- The effects of climatic changes, progressing urbanization and improved environmental controls on the simulated urban stormwater quality in a northern Sweden community were studied. Future scenarios accounting for those changes were developed and their effects simulated with the Storm Water Management Model (SWMM). It was observed that the simulated stormwater quality was highly sensitive to the scenarios, mimicking progressing urbanization with varying catchment imperviousness and area. Thus, land use change was identified as one of the most influential factors and in some scenarios, urban growth caused changes in runoff quantity and quality exceeding those caused by a changing climate. Adaptation measures, including the reduction of directly connected impervious surfaces (DCIS) through the integration of more green spaces into the urban landscape, or disconnection of DCIS were effective in reducing runoff volume and pollutant loads. Furthermore, pollutant source control measures, including material substitution, were effective in reducing pollutant loads and significantly improving stormwater quality
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| 20. |
- Borris, Matthias, et al.
(författare)
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Using urban runoff simulations for addressing climate change impacts on urban runoff quality in a Swedish town
- 2012
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Ingår i: Urban Drainage Modelling. - Belgrade : Faculty of Civil Engineering, University of Belgrade. - 9788675181569
-
Konferensbidrag (refereegranskat)abstract
- The effect of climate change on urban stormwater quality was studied by means of computer simulations conducted with the Stormwater Management Model (SWMM) for common climate change scenarios developed for northern Sweden. The simulation results showed that stormwater quality depended on rainfall characteristics; a climate scenario implying increased rainfall depths and intensities produced higher pollutant loads carried by stormwater, but reduced concentrations, particularly for medium to high intensity storm events. This type of stormwater quality response was explained by pollutant supply limited transport processes and the resulting dilution of such pollutants. Medium intensity events showed the highest sensitivity to climatic changes, since such events strongly affected the contributions of pervious surfaces. This has significant implications for stormwater management, because those relatively frequent events generally carry a high percentage of the annual pollutant load.
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| 21. |
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| 22. |
- de Peppo, Giuseppe Maria, et al.
(författare)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role inthe osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenicdifferentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 23. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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Ingår i: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 24. |
- Dellmuth, Lisa Maria, 1981-, et al.
(författare)
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Global adaptation governance : Explaining the governance responses of international organizations to new issue linkages
- 2020
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011 .- 1873-6416. ; 114, s. 204-215
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Tidskriftsartikel (refereegranskat)abstract
- Climate change adaptation is increasingly perceived as a global and interconnected policy challenge among practitioners and academics, making localized solutions insufficient. In parallel to this trend, a growing number of international organizations that do not have climate as their core mandates link adaptation to various issue areas, such as energy, health, and conflict resolution. Yet we still know little about how and why international organizations respond to adaptation challenges. This article develops an innovative theoretical framework to understand the factors that influence the governance responses of international organizations to adaptation challenges in the context of their respective issue areas. Our analysis reveals that there are three main and interrelated factors influencing international governance responses: problem complexity, institutional frag- mentation, and fiscal pressures. We examine our framework by drawing on of two sources of data: first, a yearly large-n dataset at the level of fourteen international organizations from 2007 to 2017 created on the basis of official documents; and second, in-depth case studies of three UN agencies central in addressing three prominent issue linkages: climate-conflict, climate-health, and climate-migration. We conclude by sketching broader im- plications for the theory and practice of global adaptation governance.
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| 25. |
- Dellmuth, Lisa Maria, 1981-, et al.
(författare)
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Global adaptation governance : how intergovernmental organizations mainstream climate change adaptation
- 2021
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Ingår i: Climate Policy. - : Informa UK Limited. - 1469-3062 .- 1752-7457. ; 21:7, s. 868-883
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Tidskriftsartikel (refereegranskat)abstract
- Climate change adaptation is increasingly being mainstreamed into all types of organizations across the world. A large number of intergovernmental organizations (IGOs), such as the European Union, the World Bank, or Food and Agriculture Organization, have already started to mainstream adaptation. Yet, despite a surge in scholarly interest in climate policy integration over the past decade, adaptation is still predominantly studied as a local issue and mainstreaming in IGOs remains poorly understood. In this article, we develop and test an innovative framework for examining adaptation mainstreaming practices in IGOs. Using quantitative and qualitative data derived from extensive fieldwork conducted between 2017 and 2020, we examine mainstreaming practices in a large number of IGOs and arrive at two key findings. First, adaptation has been mainstreamed within the procedures and outputs of IGOs across ten (nonclimate) issue areas, while there is also evidence of important issue-specific variation. Second, there is variation across mainstreaming practices in the sense that discursive mainstreaming is most common, whereas more concrete collaboration, policy change affecting projects and programs, and budget allocations are less common. We conclude with a discussion of how our framework can inform the theory and practice of global adaptation governance.
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| 26. |
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| 27. |
- Ekman, Maria, et al.
(författare)
-
Inte så smakfullt
- 1997
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Ingår i: Dagens Nyheter. ; :27 februari
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 28. |
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| 29. |
- Gustafsson, Anna-Maria, et al.
(författare)
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Metoder för att undersöka extrema regnhändelsers påverkan på dagvattensystemet
- 2014
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Rapport (refereegranskat)abstract
- Detta projekt har genomförts av Luleå Tekniska Universitet i samarbete med 5 kommuner; Arvika, Skellefteå, Sundsvall, Trelleborg samt Växjö. Projektets syfte har varit att studera hur olika metoder kan användas för att utvärdera dagvattensystemets påverkan av extrema regnhändelser. Rapporten har skrivits i syfte att ge en övergripande bild av olika metoder och de osäkerheter som finns när de olika metoderna används. Materialet i rapporten är hämtat från aktuellt projekt samt från parallella studier vid forskningsgruppen Stadens vatten, LTU och från internationella och nationella studier för att ge ett så brett perspektiv på olika metoder som möjligt. De metoder som beskrivs i rapporten går från en väldigt enkel analys baserat på vanliga dimensioneringsekvationer som kan utföras i ett excelark eller för hand till analyser som kräver komplexa modeller som simulerar vattenföringen i ledningsnätet samt ytavrinning kopplat till infiltration. Alla metoder kräver någon form av nederbördsinformation och därför inkluderas i rapporten ett avsnitt om regn och framtida regn kopplat till klimatförändring. För att genomföra en analys krävs även parametrar att studera effekterna av olika körningar och i slutet presenteras ett kort avsnitt om indikationer som är lämpliga att använda vid utvärdering av dagvattensystemet. När en metod ska väljas är det viktigt att syfte med undersökning och resurser i form av tid, existerande data och pengar ställs mot varandra. En avancerad modell har ett större krav på indata, datakapacitet och på mätdata som den kan verifieras mot. I vissa fall är det bättre att använda en enklare modell med kontinuerligt, historiskt regndata medan i andra fall krävs en komplex modell som inkluderar t.ex. infiltration i permeabla ytor och att då använda sig av designregn för att klara av de begränsningar som ev. finns i datakapacitet och simuleringstid. Innan beslut tas om modell eller metod bör det noggrant funderas över varför modellen ska tas fram, hur den ska användas samt vilka data som finns tillgängliga eller kan tas fram med nya mätningar. Om metoderna beskrivna i rapporten används på korrekt sätt och verifieras med tillräckligt data kan dessa utvärderingar av dagvattensystemet ge en bra bild av hur systemet fungerar samt hur det påverkas av olika scenarier.
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| 30. |
- Gustafsson, Håkan, et al.
(författare)
-
Magnetic and Electron Spin Relaxation Properties of (GdxY1-x)(2)O-3 (0 <= x <= 1) Nanoparticles Synthesized by the Combustion Method. Increased Electron Spin Relaxation Times with Increasing Yttrium Content
- 2011
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:13, s. 5469-5477
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Tidskriftsartikel (refereegranskat)abstract
- The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)(2)O-3 (0 <= x <= 1) were prepared by the combustion method and thoroughly characterized (by X-ray diffraction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.
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| 31. |
- Gustafsson, Håkan, 1976-, et al.
(författare)
-
Magnetic and Electron Spin Relaxation Properties of (GdxY1-x)2O3 (0 ≤ x ≤ 1) Nanoparticles Synthesized by the Combustion Method. Increased Electron Spin Relaxation Times with Increasing Yttrium Content
- 2011
-
Ingår i: The Journal of Physical Chemistry C. - United States : American Chemical Society. - 1932-7447 .- 1932-7455. ; 115:13, s. 5469-5477
-
Tidskriftsartikel (refereegranskat)abstract
- The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)2O3 (0 e x e 1) were prepared by the combustion method and thoroughly characterized (by X-ray di.raction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.
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| 32. |
- Gustafsson, Håkan, et al.
(författare)
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Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging
- 2015
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 73:4, s. 1682-1691
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.
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| 33. |
- Gustafsson Lundberg, Johanna, et al.
(författare)
-
Feministisk etik
- 2011
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Ingår i: Kön, teologi och etik : en introduktion. - 9789144057460 ; , s. 107-142
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Bokkapitel (refereegranskat)
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| 34. |
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| 35. |
- Gustafsson, Maria, et al.
(författare)
-
Drug-related hospital admissions among old people with dementia
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Drug treatment associated problems, including medication errors and adverse drug events, are common, and are the cause of a large proportion of hospital admissions in old people. People with dementia are especially at risk of drug-related problems. The objectives of this study were to assess the occurrence and character of drug-related problems that lead to acute hospital admissions among old people with dementia or cognitive impairment. Methods: This study was conducted in orthopedic and internal medicine wards in two hospitals in Northern Sweden. Information about acute admissions was collected from the medical records of the study population. A total of 458 people aged 65 years or older with dementia or cognitive impairment were included in the study. The contribution of drug related problems to each hospitalization was assessed. Results: Of 458 acute hospital admissions, 189 (41.3%) were determined to be drug-related. The most common drug-related problem (86/189; 45.5%) was an adverse drug reaction. In total, 264 drugs were judged to be involved in 189 drug-related admissions, of which cardiovascular (29.5%) and psychotropic (26.9%) drugs were the most commonly involved drug classes. The relationship between the drug-related problem and the admission was judged certain in 25 cases, probable in 78 cases, and possible in 86 cases. Drug-related admissions were more common among people taking more drugs and among younger patients. Conclusion: Drug-related problems appear to be responsible for a major proportion of hospitalizations among old people with dementia or cognitive impairment. Targeted interventions may be warranted to reduce drug-related problems.
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| 36. |
- Gustafsson, Maria, et al.
(författare)
-
Drug-related hospital admissions among old people with dementia
- 2016
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 72:9, s. 1143-1153
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Drug treatment associated problems are common and are the cause of a large proportion of hospitalizations in oldpeople. People with dementia are especially at risk of drug-related problems. The objectives of this study were to assess the occurrence and character of drug-related problems that lead to acute hospital admissions among old people (≥65 years) with dementia or cognitive impairment.METHODS: This study was conducted in orthopedic and internal medicine wards in two hospitals in Northern Sweden. Information about acute admissions was collected from the medical records. A total of 458 people aged 65 years or older with dementia or cognitive impairment were included in the study. The contribution of drug-related problems to each hospitalization was assessed.RESULTS: Of 458 acute hospital admissions, 189 (41.3 %) were determined to be drug-related. The most common drug-relatedproblem (86/189; 45.5 %) was an adverse drug reaction. In total, 264 drugs were judged to be involved in 189 drug-relatedadmissions, of which cardiovascular (29.5 %) and psychotropic (26.9 %) drugs were the most commonly involved drug classes. The relationship between the drug-related problem and the admission was judged certain in 25 cases, probable in 78 cases, and possible in 86 cases. Drug-related admissions were more common among people taking more drugs (p = 0.035) and among younger patients (p = 0.031).CONCLUSION: Drug-related problems appear to be responsible for a major proportion of hospitalizations among old peoplewith dementia or cognitive impairment. Targeted interventions such as education and medication reviews may be warranted to reduce drug-related problems.
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| 37. |
- Gustafsson, Maria, et al.
(författare)
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Effects of pharmacists' interventions on inappropriate drug use and drug-related readmissions in people with dementia : a secondary analysis of a randomized controlled trial
- 2018
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Ingår i: Pharmacy. - Basel : MDPI. - 2226-4787. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- Age-associated physiological changes and extensive drug treatment including use of potentially inappropriate medications (PIMs) pose a significant risk of drug-drug interactions and adverse drug events among elderly people with dementia. This study aimed at analysing the effects of clinical pharmacists' interventions on use of PIMs, risk of emergency department visits, and time to institutionalization. Furthermore, a descriptive analysis was conducted of circumstances associated with drug-related readmissions. This is a secondary analysis of data from a randomized controlled intervention study conducted in two hospitals in Northern Sweden. The study included patients (n = 460) 65 years or older with dementia or cognitive impairment. The intervention consisted of comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team. There was a larger decrease in PIMs in the intervention group compared with the control group (p= 0.011). No significant difference was found in time to first all-cause emergency department visits (HR = 0.994, 95% CI = 0.755-1.307 p = 0.963, simple Cox regression) or time to institutionalization (HR = 0.761, 95% CI = 0.409-1.416 p = 0.389, simple Cox regression) within 180 days. Common reasons for drug-related readmissions were negative effects of sedatives, opioids, antidepressants, and anticholinergic agents, resulting in confusion, falling, and sedation. Drug-related readmissions were associated with living at home, heart failure, and diabetes. Pharmacist-provided interventions were able to reduce PIMs among elderly people with dementia and cognitive impairment.
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| 38. |
- Gustafsson, Margareta, 1952-, et al.
(författare)
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Identifying clinically relevant groups of hip fracture patients at risk of adverse outcomes by using classification tree analysis
- 2012
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Ingår i: International Journal of Orthopaedic and Trauma Nursing. - London, United Kingdom : Elsevier. - 1878-1241 .- 1878-1292. ; 17:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To identify groups of hip fracture patients at risk of adverse utcome by investigating interactions between previously reported risk factors.Methods: A consecutive sample of 338 hip fracture patients was included at admission to the orthopaedic department and followed up 4 months later. Outcomes measured were mortality, failure to regain pre-injury mobility and failure to return home. Data were collected about previously reported risk factors for adverse outcomes in those respects.Results: The highest risk of death occured in males living in institutions for the elderly before the fracture (48%). Lowest risk of death had patients admitted from their own home, without malignancy and below 80 years of age (1%). The overall risk of failure to regain pre-injury mobility at the 4 month follow up was 30%. In patients walking independently before the fracture and age above 85 years, the risk increased to 88%. In patients walking with devices before the fracture, the risk of being confined to bed or wheelchair increased from 10% to 20% if the patient was confused. Confusion also increased the risk of relocation from their own home to an institution for the elderly from 19% to 53%.Conclusion: The results of the study can help nurses in making realistic discharge plans based on risk analyses, employing more than just age as risk factor. Using this information nurses can meet the patient’s individual needs in an improved way.
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| 39. |
- Gustafsson, Maria, 1971-
(författare)
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Optimizing drug therapy among people with dementia : the role of clinical pharmacists
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Drugs are one of the cornerstones in the management of many diseases. In general, drugs are used for diagnosis, prevention, mitigation of symptoms, and, sometimes, to cure disease. However, drug treatment in elderly people, especially those with dementia and cognitive impairments, may involve significant risk of adverse drug events. The aim of this thesis was to identify the extent of potentially inappropriate drug treatment among people with dementia and cognitive impairment and to assess the occurrence and character of drug-related problems that lead to acute hospital admissions. Another aim was to assess the potential impact of a comprehensive medication review conducted by clinical pharmacists as part of a health care team on quality of patients’ drug therapy and drug-related hospital readmission rates.Method: Long-term use of antipsychotic/psychotropic drugs and associated factors were investigated among 344 and 278 people respectively with dementia living in specialized care units. Trends in the prescribing of potentially inappropriate drugs between 2007 and 2013, comprising 2772 and 1902 people, living in nursing homes in the county of Västerbotten, were assessed using six national quality indicators. Data on drug use, function in the activities of daily living, cognitive function and behavioral and psychological symptoms were collected using the Multi-Dimensional Dementia Assessment Scale. Further, an investigation of a separate corresponding population from 2012 was done, where potentially inappropriate drug use was measured before and after a total of 895 medication reviews. Finally, a randomized, controlled trial was carried out among people 65 years or older with dementia or cognitive impairment in internal medicine and orthopedic wards at two hospitals in northern Sweden. The proportion of hospital admissions that were drug-related were estimated, and also whether comprehensive medication reviews conducted by clinical pharmacists as part of a health care team could affect the risk of drug-related hospital readmissions.Results: Antipsychotic and other psychotropic drugs were frequently prescribed to people with dementia living in specialized care units for prolonged periods. Associations were found between behavioral and psychological symptoms and different psychotropic drugs. The extent of potentially inappropriate drug use declined between 2007 and 2013. In the separate corresponding population from 2012, the frequency of potentially inappropriate drug use was significantly reduced among people who underwent medication reviews. Hospitalizations due to drug-related problems among old people with dementia or cognitive impairment were prevalent. We found that inclusion of a clinical pharmacist in the health care team significantly reduced the risk of drug-related 30-day and 180-day readmissions. However, in a subset of patients with concomitant heart failure no effect was seen.Conclusion: Among patients with dementia or cognitive impairment long-term treatment with antipsychotic and other psychotropic drugs is common. The results indicate that these drugs are prescribed to treat behavioral and psychological symptoms among cognitively impaired individuals, despite limited evidence of their efficacy and the high risk of adverse effects. Drug-related problems, such as adverse drug reactions, constituted a major cause of hospital admissions. By reducing potentially inappropriate drug use and optimizing overall drug therapy, inclusion of clinical pharmacists in a health care team might improve the quality of patient care and reduce the risk of hospital readmissions among people with dementia.
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| 40. |
- Gustafsson, Maria, et al.
(författare)
-
Pharmacist participation in hospital ward teams and hospital readmission rates among people with dementia : a randomized controlled trial
- 2017
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 7:73, s. 827-835
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment.Methods: This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years with dementia or cognitive impairment admitted to three wards at two hospitals located in Northern Sweden were included.Results: Of the 473 deemed eligible for participation, 230 were randomized to intervention and 230 to control group by block randomization. The primary outcome, risk of drug-related hospital readmissions, was assessed at 180 days of follow-up by intention-to-treat analysis.During the 180 days of follow-up, 18.9% (40/212) of patients in the intervention group and 23.0% (50/217) of those in the control group were readmitted for drug-related reasons (HR = 0.80, 95% CI = 0.53–1.21, p = 0.28, univariable Cox regression). Heart failure was significantly more common in the intervention group. After adjustment for heart failure as a potential confounder and an interaction term, multiple Cox regression analysis indicated that pharmacist participation significantly reduced the risk of drug-related readmissions (HR = 0.49, 95% CI = 0.27–0.90, p = 0.02). A post-hoc analysis showed a significantly reduced risk of 30-day readmissions due to drug-related problems in the total sample (without adjustment for heart failure).Conclusion: Participation of clinical pharmacists in healthcare team conducting comprehensive medication reviews did not significantly reduce the risk of drug-related readmissions in patients with dementia or cognitive impairment; however, post-hoc and subgroup analyses indicated significant effects favoring the intervention. More research is needed.Trial registration: Clinical trials NCT01504672.
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| 41. |
- Gustafsson, Maria, et al.
(författare)
-
Pharmacological Pain Treatment in 2012 and 2017 Among Older People with Major Neurocognitive Disorder
- 2021
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Ingår i: Drugs & Aging. - : Adis. - 1170-229X .- 1179-1969. ; 38, s. 1017-1023
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Pain is highly prevalent among older people, and treatment is complicated because of comorbidities and polypharmacy. Among people with major neurocognitive disorder additional difficulties might arise. The aim of this study was to describe analgesic drug use in 2012 and 2017 and associated factors among older people with major neurocognitive disorder.Methods: In this register-based study, the Swedish Dementia Registry and the Swedish Prescribed Drug Register were combined in order to obtain data regarding analgesic drug use among older people with major neurocognitive disorder. One or more filled prescriptions during the timeframe of 6 months (1 July–31 December 2012 and 1 July–31 December 2017) defined drug use during the respective period. A comparison between 2012 and 2017 was made, including a total of 56,101 people (20,889 and 35,212 respectively) with a mean age of 81.9 and 82.7 years, respectively.Results: The overall use of analgesic drugs increased significantly from 41.6% of individuals to 46.0% between the years 2012 and 2017. Users of opioid analgesics (15.2% vs 17.3%) and paracetamol (37.0% vs 42.3%) increased, while the users of non-steroidal anti-inflammatory drugs (4.9% vs 2.7%) declined between the two data collections. Multiple logistic regression analyses were performed for different drugs and drug classes, and it was found that the use of opioids and paracetamol was associated with older age and a longer time since diagnosis. In contrast, non-steroidal anti-inflammatory drugs were associated with younger age and a shorter time since diagnosis.Conclusions: The results indicate that on a population level, pharmacological drug treatment has changed in line with guidelines between 2012 and 2017, with an increase in paracetamol and strong opioids and a decrease in non-steroidal anti-inflammatory drugs and tramadol. The relatively high prevalence of opioids warrants concern given the significant risk of adverse effects among older people with major neurocognitive disorder.
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| 42. |
- Gustafsson, Maria, et al.
(författare)
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Prevalence of Drugs and Drug Combinations that Increase Risk of Prolonged QT Time Among People with Major Neurocognitive Disorder Living in Sweden : A Cross-Sectional Registry Study
- 2023
-
Ingår i: Drugs - real world outcomes. - : Springer Nature. - 2199-1154 .- 2198-9788. ; 10, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Background: People with major neurocognitive disorder might be susceptible to drug-induced QT interval prolongation due to the presence of a number of concomitant risk factors.Objective: The aim of this study was to investigate the prevalence of QT-prolonging drugs and QT-prolonging drug–drug interactions and associated factors among older people with major neurocognitive disorder.Methods: In this register-based study, we obtained information regarding QT-prolonging drug use in a large population of older people with major neurocognitive disorder, through record linkage between the Swedish registry for cognitive/dementia disorders, and the Swedish Prescribed Drug Register. QT-prolonging drugs were identified according to the CredibleMeds online database and interactions using the Janusmed interaction database. Drug use was defined as one or more filled prescriptions during a 6-month timeframe, July 01 to December 31, 2017. Associations between people with a QT-prolonging drug and the factors of age and gender were analysed through multiple logistic regression.Results: Of 35,212 people included in the study, 41.6% had one or more QT-prolonging drug prescribed. The most commonly prescribed drug was donepezil, with a prevalence of 25.0%, followed by citalopram and escitalopram, representing 14.5% and 3.9% of prescriptions in the study population, respectively. Significant associations were found between QT-prolonging drug use and the factors of younger age and female gender. The most prevalent interaction was between citalopram and donepezil (2.7%), followed by the combination of escitalopram and donepezil (0.7%).Conclusions: In this population of older people with major neurocognitive disorder, QT-prolonging drugs and interactions that increase the risk of torsade de pointes were prevalent. Due to the presence of many risk factors in this population, it is important to continuously evaluate current QT-prolonging drugs and concomitant drug treatment in each individual.
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| 43. |
- Gustafsson, Maria, et al.
(författare)
-
Reduction in the use of potentially inappropriate drugs among old people living in geriatric care units between 2007 and 2013
- 2015
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 71:4, s. 507-515
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aims of this study were to investigate trends in the prevalence of potentially inappropriate drug use among old people living in geriatric care units in the county of Västerbotten between 2007 and 2013 using six national quality indicators and to assess the impact of medication reviews on those quality indicators.METHODS: Data were collected concerning potentially inappropriate drug use, function in the activities of daily living (ADL) and cognitive function, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). A comparison was made between the years 2007 and 2013, comprising 2772 and 1902 people, respectively, living in geriatric care in the county of Västerbotten, Sweden. We conducted a parallel investigation of a separate corresponding population in Västerbotten County from 2012, where potentially inappropriate drug use was measured before and after 895 medication reviews which involved a clinical pharmacist.RESULTS: After controlling for age, sex, ADL and cognitive impairment, there was a significant improvement in five out of six quality indicators between 2007 and 2013. While 44 % of the people were exposed to one or more potentially inappropriate medications in 2007, this number had declined to 26 % by 2013. In the separate population from 2012, the frequency of potentially inappropriate drug use was significantly reduced amongst the people who had a medication review performed.CONCLUSION: The extent of potentially inappropriate drug use declined between 2007 and 2013 according to the quality indicators used. Medication reviews involving clinical pharmacists might be an important factor in reducing potentially inappropriate drug use and improving drug treatment among old people.
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| 44. |
- Gustafsson, Maria-Therese, 1979-, et al.
(författare)
-
Private adaptation to climate risks : Evidence from the world’s largest mining companies
- 2022
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Ingår i: Climate Risk Management. - : Elsevier BV. - 2212-0963. ; 35
-
Tidskriftsartikel (refereegranskat)abstract
- Private companies have in recent years started to disclose information about their exposure and responses to climate risks. However, we still know little about how and why private actors engage in climate change adaptation, and to what extent they do so in ways that improve societal resilience. This article addresses these questions. It conceptualizes private adaptation as consisting of institutional, infrastructural and community-oriented responses to climate risks. It develops a political-economic framework about the drivers of private adaptation, where private adaptation is expected to be shaped by pressures exerted by governments, investors, and civil society actors. Empirically, the framework is explored by using an original dataset on the adaptation responses of the 37 largest mining companies worldwide. We select the mining sector as mineral extraction plays a critical role in the low-carbon transition, and can, at the same time, exacerbate climate vulnerability in extracting sites. The descriptive findings suggest that the majority of the investigated companies have set up procedures to assess climate impacts on business operations, integrated climate risks in water governance, and adapted their infrastructure. The explanatory results indicate that private adaptation is mainly driven by investor pressures, and not domestic regulations and civil society. By implication, companies rarely engage in community-oriented adaptation responses by cooperating with local communities in ways that would benefit these communities. Taken together, our findings help to better understand the limitations of private adaptation and barriers to achieve transformative change, and identify how private adaptation could help improve societal resilience.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Gustafsson, Robert, et al.
(författare)
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Crystal Structure of the Emerging Cancer Target MTHFD2 in Complex with a Substrate-Based Inhibitor
- 2017
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 77:4, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-carbon metabolism. Because MTHFD2 is expressed normally only during embryonic development, it offers a disease-selective therapeutic target for eradicating cancer cells while sparing healthy cells. Here we report the synthesis and preclinical characterization of the first inhibitor of human MTHFD2. We also disclose the first crystal structure of MTHFD2 in complex with a substrate-based inhibitor and the enzyme cofactors NAD(+) and inorganic phosphate. Our work provides a rationale for continued development of a structural framework for the generation of potent and selective MTHFD2 inhibitors for cancer treatment.
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| 49. |
- Hedlund, Anna, 1973-, et al.
(författare)
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Detection of Gd2O3 Nanoparticles in Hematopoietic Cells for MRI Contrast Enhancement
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3 ) nanoparticles generate higher relaxivity than currently available Gd chelates. The Gd2O3 nanoparticles are also promising for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles and to improve techniques for monitoring hematopoietic stem cell migration by MRI. We studied particle uptake in two cell lines; the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles as well as superparamagnetic iron oxide particles (SPIOs) for comparison. In addition, it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by microscopic techniques, MRI and analyzed for particle content. Results showed that particles were intracellular, however in Ba/F3 only sparsely. The relaxation times were shortened with increasing particle concentration. Overall relaxivities, r1 and r2 for Gd2O3 nanoparticles in all cell samples measured were 5.1 ± 0.3 and 14.9 ± 0.7 (s-1mM-1) respectively. Goodness of fit was 0.97 in both cases. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. Viability of treated cells was not significantly decreased and thus, we conclude that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells.
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- Hedlund, Anna, et al.
(författare)
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Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement
- 2011
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Ingår i: International journal of nano medicine. - Manchester, UK : Dove Medical Press Ltd. - 1178-2013. ; 6, s. 3233-3240
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Tidskriftsartikel (refereegranskat)abstract
- As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s-1 mM-1 and 9.6–17.2 s-1 mM-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.
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