| 1. |
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| 2. |
- Angelin, Bo, et al.
(author)
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Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome
- 2015
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In: Journal of Internal Medicine. - : Wiley: 12 months. - 0954-6820 .- 1365-2796. ; 277:3, s. 331-342
-
Journal article (peer-reviewed)abstract
- BackgroundLiver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia. MethodsWe performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200gday(-1) eprotirome or placebo for 12weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures. ResultsEprotirome treatment at 100 and 200g daily reduced serum LDL cholesterol levels by 235% and 31 +/- 4%, respectively, compared with 2 +/- 6% for placebo (Pless than0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients. ConclusionIn hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.
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| 3. |
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| 4. |
- Betancourt, Lazaro Hiram, et al.
(author)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Journal article (peer-reviewed)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 5. |
- Cheung, Pierre, et al.
(author)
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[18F]MK-7246 for Positron Emission Tomography Imaging of the Beta-Cell Surface Marker GPR44
- 2023
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In: Pharmaceutics. - : MDPI. - 1999-4923. ; 15:2
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Journal article (peer-reviewed)abstract
- The progressive loss of beta-cell mass is a hallmark of diabetes and has been suggested as a complementary approach to studying the progression of diabetes in contrast to the beta-cell function. Non-invasive nuclear medicinal imaging techniques such as Positron Emission Tomography using radiation emitting tracers have thus been suggested as more viable methodologies to visualize and quantify the beta-cell mass with sufficient sensitivity. The transmembrane G protein-coupled receptor GPR44 has been identified as a biomarker for monitoring beta-cell mass. MK-7246 is a GPR44 antagonist that selectively binds to GPR44 with high affinity and good pharmacokinetic properties. Here, we present the synthesis of MK-7246, radiolabeled with the positron emitter fluorine-18 for preclinical evaluation using cell lines, mice, rats and human pancreatic cells. Here, we have described a synthesis and radiolabeling method for producing [18F]MK-7246 and its precursor compound. Preclinical assessments demonstrated the strong affinity and selectivity of [18F]MK-7246 towards GPR44. Additionally, [18F]MK-7246 exhibited excellent metabolic stability, a fast clearance profile from blood and tissues, qualifying it as a promising radioactive probe for GPR44-directed PET imaging.
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| 6. |
- Cheung, Pierre, et al.
(author)
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PET Imaging of GPR44 by Antagonist [C-11]MK-7246 in Pigs
- 2021
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In: Biomedicines. - : MDPI. - 2227-9059. ; 9:4
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Journal article (peer-reviewed)abstract
- A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [C-11]MK-7246 was evaluated in a pig model and in vitro cell lines. The [C-11]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [C-11]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [C-11]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.
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| 7. |
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| 8. |
- Cheung, Pierre, et al.
(author)
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Preclinical evaluation of Affibody molecule for PET imaging of human pancreatic islets derived from stem cells
- 2023
-
In: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 13:1
-
Journal article (peer-reviewed)abstract
- Background: Beta-cell replacement methods such as transplantation of isolated donor islets have been proposed as a curative treatment of type 1 diabetes, but widespread application is challenging due to shortages of donor tissue and the need for continuous immunosuppressive treatments. Stem-cell-derived islets have been suggested as an alternative source of beta cells, but face transplantation protocols optimization difficulties, mainly due to a lack of available methods and markers to directly monitor grafts survival, as well as their localization and function. Molecular imaging techniques and particularly positron emission tomography has been suggested as a tool for monitoring the fate of islets after clinical transplantation. The integral membrane protein DGCR2 has been demonstrated to be a potential pancreatic islet biomarker, with specific expression on insulin-positive human embryonic stem-cell-derived pancreatic progenitor cells. The candidate Affibody molecule ZDGCR2:AM106 was radiolabeled with fluorine-18 using a novel click chemistry-based approach. The resulting positron emission tomography tracer [18F]ZDGCR2:AM106 was evaluated for binding to recombinant human DGCR2 and cryosections of stem-cell-derived islets, as well as in vivo using an immune-deficient mouse model transplanted with stem-cell-derived islets. Biodistribution of the [18F]ZDGCR2:AM106 was also assessed in healthy rats and pigs. Results: [18F]ZDGCR2:AM106 was successfully synthesized with high radiochemical purity and yield via a pretargeting approach. [18F]ZDGCR2:AM106 retained binding to recombinant human DCGR2 as well as to cryosectioned stem-cell-derived islets, but in vivo binding to native pancreatic tissue in both rat and pig was low. However, in vivo uptake of [18F]ZDGCR2:AM106 in stem-cell-derived islets transplanted in the immunodeficient mice was observed, albeit only within the early imaging frames after injection of the radiotracer. Conclusion: Targeting of DGCR2 is a promising approach for in vivo detection of stem-cell-derived islets grafts by molecular imaging. The synthesis of [18F]ZDGCR2:AM106 was successfully performed via a pretargeting method to label a site-specific covalently bonded fluorine-18 to the Affibody molecule. However, the rapid washout of [18F]ZDGCR2:AM106 from the stem-cell-derived islets graft indicates that dissociation kinetics can be improved. Further studies using alternative binders of similar classes with improved binding potential are warranted.
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| 9. |
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| 10. |
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| 11. |
- Eriksson, Andrea, et al.
(author)
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How is health promotion research undertaken in a Nordic context? : A scoping review on doctoral dissertations from 2008-2018
- 2020
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In: Socialmedicinsk Tidskrift. - 0037-833X. ; 97:3, s. 488-502
-
Journal article (peer-reviewed)abstract
- This scoping review was commenced as a collaboration within the NordicHealth Promotion Research Network (NHPRN). The overall aim was to explore how research under the label ‘health promotion’ was undertaken in a Nordic context. The search for dissertations published in Denmark, Finland, Iceland, Norway and Sweden was limited to the years 2008 to 2018. Manual searches of university websites, as well as different databases in the Nordic countries, were required for collecting dissertations from all universities. The collection of dissertations was more difficult than expected. There were 56 published PhD dissertations from 6 universities in Denmark, 51 from 8 universities in Finland, 0 from Iceland, 53 from 7 universities in Norway and 193 from 22 universities in Sweden. Almost half of the analysed dissertations combined qualitative and quantitative methods. About one-third of the dissertations had a settings approach, followed by a societal approach and individual approach. Finland and Sweden presented more intervention studies than the other countries. A majority of the intervention studies included individual lifestyle issues. Based on the analysis of the research approaches, more dissertations embracing societal perspectives and broader determinants of health may be recommended for future Nordic dissertations.
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| 12. |
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| 13. |
- Eriksson, Johan, et al.
(author)
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Utilisation of oily mill scale sludge as scrap resource
- 1999
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In: REWAS '99. ; , s. 1423-1430
-
Conference paper (peer-reviewed)abstract
- This paper presents the results of reduction trials of oily mill scale sludge. Laboratory experiments and two campaigns in a pilot plant rotary kiln have been carried out. The results indicate that it's possible to reduce oily mill scale sludge to sponge iron in the rotary kiln. The first pilot plant campaign was carried out with a mix of 75 wt-% mill scales and 25 wt-% mill scale sludge. During the second campaign 100 wt-% oily mill scale sludge were mixed with blast furnace flue dust and reduced. Petroleum coke has been used as the main reductant in both campaigns. Smelting trials of the sponge iron product have also been carried out in a production EAF. The sponge iron was charged into the scrap bin in big-bags. These trials showed that the degree of metallization of the sponge iron must be higher than 55% to avoid an increased iron oxide content in the slag, i.e. a low iron yield to the metal
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| 14. |
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| 15. |
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| 16. |
- Erlinge, D., et al.
(author)
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Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
- 2017
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In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
-
Journal article (peer-reviewed)abstract
- Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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| 17. |
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| 18. |
- Frennby, Bo, et al.
(author)
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Determination of the relative glomerular filtration rate of each kidney in man : Comparison between iohexol CT and 99mTc-DTPA scintigraphy
- 1995
-
In: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 36:4, s. 410-417
-
Journal article (peer-reviewed)abstract
- Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.
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| 19. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
-
Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 20. |
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| 21. |
- Smith, Jennifer A, et al.
(author)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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In: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
Journal article (peer-reviewed)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 22. |
- Taddei, C, et al.
(author)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
-
Journal article (peer-reviewed)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 23. |
- van der Valk, Ralf J P, et al.
(author)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
-
Journal article (peer-reviewed)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 24. |
- Vogelezang, Suzanne, et al.
(author)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
-
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
-
Journal article (peer-reviewed)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 25. |
- Wegrzyniak, Olivia, et al.
(author)
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Imaging of fibrogenesis in the liver by [18F]TZ-Z0959 : an Affibody molecule targeting platelet derived growth factor receptor β
- 2023
-
In: EJNMMI Radiopharmacy and Chemistry. - : Springer Nature. - 2365-421X. ; 8:1
-
Journal article (peer-reviewed)abstract
- Background: Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([18F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis. Results: In vitro specificity studies demonstrated that the trans-Cyclooctenes (TCO) conjugated Z09591 Affibody molecule had a picomolar affinity for human PDGFRβ. Biodistribution performed on healthy rats showed rapid clearance of [18F]TZ-Z09591 through the kidneys and low liver background uptake. Autoradiography (ARG) studies on fibrotic livers from mice or humans correlated with histopathology results. Ex vivo biodistribution and ARG revealed that [18F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars. Conclusions: Our study highlights [18F]TZ-Z09591 as a specific tracer for fibrogenic cells in the fibrotic liver, thus offering the potential to assess fibrogenesis clearly. Graphical abstract: [Figure not available: see fulltext.]
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Adermark, Louise, 1974, et al.
(author)
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Region-specific depression of striatal activity in Wistar rat by modest ethanol consumption over a ten-month period
- 2013
-
In: Alcohol. - : Elsevier BV. - 0741-8329. ; 47:4, s. 289-298
-
Journal article (peer-reviewed)abstract
- The nucleus accumbens (nAc) is the primary target for the mesolimbic dopamine system and a key brain region for the reinforcing effects displayed by drugs of abuse, including ethanol. During the. transition from recreational to compulsive consumption of reinforcing drugs, however, the dorsal striatum seems to be recruited. Understanding how synaptic activity is altered in a sub-region specific manner in the striatum during the course of long-term drug consumption thus could be essential for understanding the long-lasting changes produced by addictive substances, including ethanol. Here we evaluated synaptic activity in the dorsolateral striatum (DLS) and ventral Striatum (nucleus accumbens, nAc) of single-housed Wistar rats consuming water, or water and ethanol, for up to 10 months. Even though ethanol intake was moderate, it was sufficient to decrease input/output function in response to stimulation intensity in the DLS, while recorded population spike (PS) amplitudes in the nAc were unaffected. Striatal disinhibition induced by the GABA(A) receptor antagonist bicuculline had a slower onset in rats that had consumed ethanol for 2 months, and was significantly depressed in slices from rats that had Consumed ethanol for 4 months. Bicuculline-induced disinhibition in the nAc, on the other hand, was not significantly altered by long-term ethanol intake. Changes in PS amplitude induced by taurine or the glycine receptor antagonist strychnine were not significantly altered by ethanol in any brain region. Even though input/output function was not significantly affected by age, there was a significant decline in antagonist-induced disinhibition in brain slices from aged rats. The data presented here suggest that even modest consumption of ethanol is sufficient to alter neurotransmission in the striatum, while synaptic activity appears to be relatively well-preserved in the nAc during the course of long-term ethanol consumption. (C) 2013 Elsevier Inc. All rights reserved.
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| 30. |
- Adman, Per, et al.
(author)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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In: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 31. |
- Ahrén, Bo, et al.
(author)
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Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
- 2002
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:5, s. 869-75
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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| 32. |
- Albinsson, Bo, 1963, et al.
(author)
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The Electronically Excited-States of 2-Phenylindole
- 1991
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In: Chemical Physics. - 0301-0104. ; 151:1, s. 149-157
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Journal article (peer-reviewed)abstract
- The light absorption of 2-phenylindole (2PI) in the UV region (210-350 nm) is investigated by means of linear dichroism in stretched polyethylene film and fluorescence polarization anisotropy in a propylene glycol glass. Experimentally, 2PI is found to have five distinct electronic transitions located above 200 nm for which the transition moments are determined. The conclusions are supported by quantum chemical calculations and the origin of the so-called composite band is discussed. Comparison with the absorption spectrum of the fluorescent DNA binding probe DAPI is also made and 2PI is found to be an appropriate model system for the electronic transitions of DAPI.
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| 33. |
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| 34. |
- Almby, Kristina, 1985-
(author)
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Brain-gut-adipose interplay in the antidiabetic effects of gastric bypass surgery
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Gastric bypass surgery (GBP) leads not only to considerable and consistent weight loss but to a number of beneficial metabolic effects, often including a swift remission of type 2 diabetes (T2DM). Increases in the gut hormone GLP-1 are considered central to this effect, although several other mechanism are likely involved. One complication to GBP is post-bariatric hypoglycaemia (PBH), where the individual suffers from episodes of low blood sugar after meals. The mechanism behind this is incompletely understood. Previous research has reported an attenuation of the counterregulatory response to hypoglycaemia in patients after GBP. Many hypoglycaemic episodes also appear to be asymptomatic. Together, this has led to the hypothesis that GBP and PBH may involve an adaptation to lower blood glucose levels, a lowered glycaemic set point. As much of hypoglycaemia counterregulation involves the central nervous system (CNS), such an adaptation would presumably involve neuroendocrine mechanism. Experimental treatment with GLP-1 receptor agonists (GLP-1RA) has been reported as successful against PBH, which is paradoxical as GLP-1RA stimulate insulin release. The aim of this thesis is to further explore the metabolic changes after GBP that may influence glycaemic control. In Paper I, euglycaemic-hypoglycaemic clamps were used to assess whether infusion with GLP-1RA affects the counterregulatory response to hypoglycaemia after GBP. In Paper II, normoglycaemic-hypoglycaemic clamps were performed before and after GBP during simultaneous brain imaging with fMRI and FDG-PET techniques, cognitive testing and assessment of counterregulatory hormones. Paper III details the time course of metabolic changes after GBP in patients with previous T2DM with focus on adipose tissue, including gene expression, and possible anti-inflammatory effects. Paper IV approaches the same question as Paper I, this time in the setting of a standardized meal test. All papers include assessment of heart rate variability (HRV) as a potential reflection of autonomic nervous system (ANS) activity. In Paper I, we do not find indications that GLP-1RA affects counterregulatory hormones, but that it may affect ANS activation during hypoglycaemia. In contrast, Paper IV reports higher cortisol levels with GLP1-RA after a meal, and indications of ANS effects, but no effect on post-prandial glucose levels. Results from Paper II support the hypothesis that GBP attenuates hormonal counterregulatory responses and affects how the CNS responds to hypoglycaemia. In Paper III we report sustained improvements in glucose uptake in adipocytes, potentially indications of decreased low-grade inflammation and signs of transient increases in parasympathetic activity.
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| 35. |
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| 36. |
- Andersson, Anne-Marie, et al.
(author)
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LvU-utredningar : kritisk granskning och utveckling
- 1984
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Reports (other academic/artistic)abstract
- Syftet är att utveckla en problemfokuserad arbetsmodell för LVU-utredningar. Åtta utredningar efter 82-01-01 granskades och fem kunniga informanter som representerade olika perspektiv intervjuades om LVU-utredande. De granskade utredningarna bedömdes uppvisa brister. En perspektiv- och problemfokuserad arbetsmodell framläggs.
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| 37. |
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| 38. |
- Andersson, Sören, et al.
(author)
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Säsongslagring av värme i berg
- 1981
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In: Byggnadskonst. - 0007-7593. ; 73:11, s. 45-47
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Journal article (pop. science, debate, etc.)
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| 39. |
- Andersson Schaeffer, Jennie, 1974-
(author)
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Spaces for innovation
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- Workspace design, as an enabling factor in innovation, is an emerging topic for innovation and design research. However, little research has been done on users’ experience on workspaces for innovation in a manufacturing industrial context. The aim of the dissertation is to develop knowledge and understanding of workspaces for innovation from a user perspective.The dissertation is based on studies done in four manufacturing industries and in one design and innovation consultancy, with a focus on the employees' experience of the physical space in relation to innovation. The research method used was the photo elicitation interview. The 31 participants made photographs that served as a basis for verbal interviews to communicate the relationship they experienced between their workspace and innovation. The analysis and the interpretation of the material, supported by information, cultural and phenomenological theoretical perspectives, intend to contribute to the current scientific discourse in innovation and design.A pattern was found in the results. In the manufacturing industrial companies, the majority of workspaces that users described as supporting or hindering innovation were motifs showing aculture promoting innovation in small steps. Their examples were found to be in close similarity to what previous research describe as characteristics of exploitative innovation. In the design company, the most photographed motifs were workspaces and objects that supported different variations of what previousresearch defines as characteristics for a culture supporting radical, explorative innovation.The dissertation presents results contributing to the research on ambidexterity, with focus on a possible coexistence between different innovation cultures. The results indicate that spatial differentiation creates possibilities for coexistence between the two innovation cultures. Six spatial characteristics were found in the descriptions of the workspaces related to the marginalised explorative culture in the manufacturing companies.The dissertation discusses the possibilities of creating spaces for explorative innovation (SEIs) and space as a tool for innovation. An initial version of a support for design is presented.
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| 40. |
- Appelros, Peter, et al.
(author)
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Trends in baseline patient characteristics during the years 1995-2008 : observations from Riks-Stroke, the Swedish Stroke Register.
- 2010
-
In: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 30:2, s. 114-119
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Reported improvements in outcome in stroke patients treated in hospital are often attributed to advances in stroke care. However, secular trends in patient characteristics that are present already on admission to hospital may also contribute to improved outcome. METHODS: Time trends for baseline data (289,854 stroke admittances) in Riks-Stroke, the Swedish national quality register for stroke care, were analyzed for the years 1995 through 2008. The following data were included: number of strokes for each year, age, sex, risk factors, stroke subtype, stroke severity, functional status and need of external home service before the stroke. RESULTS: The number of annually reported strokes increased until 2005. The proportion of recurrent strokes decreased from 28.0 to 25.9%. The mean age at first-ever stroke increased in women, but not in men. The proportion of smokers dropped, and the proportion of patients who had treated hypertension increased. The stroke severity decreased in men. The prestroke functional status (walking, dressing, toileting) improved in both sexes over these years. More patients lived alone in 2008 than in 1995, and more had home help service. CONCLUSIONS: Many baseline parameters in Riks-Stroke have changed over the years. This has consequences for the interpretation of outcome data. Some changes may be due to inclusion bias, others due to alterations in general health, evolution of vascular risk factors or demographics.
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| 41. |
- Arshad, W., et al.
(author)
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Incorporating lamination processing and component manufacturing in electrical machine design tools
- 2007
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In: Conference Record. - : IEEE. - 9781424403646 - 1424403642 ; , s. 94-102
-
Conference paper (peer-reviewed)abstract
- Measures to improve the modeling of steel-sheet laminations in electrical machine design tools are studied. Only the magnetic properties, namely, the permeability (BH curves) and the iron losses are addressed. The sensitivity of these properties upon dimensional, directional (anisotropy) and excitation variations, as well as upon the electrical machines manufacturing steps is evaluated. The studied electrical machines manufacturing step are: guillotine, laser-cutting, welding, pressing and punching. The properties of the delivered lamination coils and the various associated loss figures are also statistically benchmarked. The focus is on finding guidelines for incorporation of these sensitivities in design tools when needed. For this purpose, 5 Hz to 10 kHz tests are conducted on Epstein strips, on L-shaped segments and on standard stator laminations. Two different steel grades are studied. It is shown that the lateral dimension, anisotropy and welding influences are much more pronounced then those for punching, pressing and laser cutting and hence, need to be addressed in design tools. It is found that the commonly used Epstein test results of the coils are slightly inferior to the mean loss value of the online-testing (losses that are measured at every 1 m of the entire coil length). It is also noted that, the delivered laminations are almost always better than those ordered and the losses for each individual lamination coil are nearly constant.
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| 42. |
- Arvidsson, Alf, et al.
(author)
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För Sverige i tiden?
- 2009
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In: Kulturella perspektiv - Svensk etnologisk tidskrift. - Umeå. - 1102-7908. ; 18:2, s. 2-8
-
Journal article (peer-reviewed)
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| 43. |
- Asplund, Kjell, et al.
(author)
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Effects of Extending the Time Window of Thrombolysis to 4.5 Hours : Observations in the Swedish Stroke Register (Riks-Stroke)
- 2011
-
In: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 42:9, s. 2492-2497
-
Journal article (peer-reviewed)abstract
- Background and Purpose: The European Cooperative Acute Stroke Study (ECASS) III trial and Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) data were published in 2008. Riks-Stroke, the Swedish Stroke Register, was used to explore how thrombolysis in the 3- to 4.5-hour window has been spread in different hospitals and patient groups and what effects this has had on treatment within 3 hours.Methods: All 76 hospitals in Sweden admitting patients with acute stroke participate in Riks-Stroke. During the study period, January 2003 to June 2010, 92 150 18- to 80-year-old patients were hospitalized for acute ischemic stroke.Results: After the publication of the ECASS III results in the third quarter of 2008, thrombolysis in the 3- to 4.5-hour window increased from 0.5% before publication to 2.1% in 2010. Thrombolysis in the 3- to 4.5-hour window spread somewhat faster in men than women (P=0.04) but at a similar rate in different age groups. The use of thrombolysis within 3 hours after onset of symptoms increased successively from 0.9% in 2003 to 6.6% in late 2008 and then it stabilized at 6%. The median time from arrival to the hospital to start of treatment remained unchanged at 66 to 69 minutes before and after 2008 (P=0.06).Conclusions: Since the end of 2008, there has been a rapid nationwide dissemination of thrombolysis in the 3- to 4.5-hour window, whereas rates in the <3-hour window have leveled off. The extended time window has not affected door-to-needle time.
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| 44. |
- Asplund, Kjell, et al.
(author)
-
Patient dissatisfaction with acute stroke care
- 2009
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In: Stroke. - : American Heart Association, Inc.. - 0039-2499 .- 1524-4628. ; 40:12, s. 3851-3856
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Riks-Stroke, the Swedish Stroke Register, was used to explore patient characteristics and stroke services as determinants of patient dissatisfaction with acute in-hospital care. METHODS: All 79 hospitals in Sweden admitting acute stroke patients participate in Riks-Stroke. During 2001 to 2007, 104,876 patients (87% of survivors) responded to a follow-up questionnaire 3 months after acute stroke; this included questions on satisfaction with various aspects of stroke care. RESULTS: The majority (>90%) were satisfied with acute in-hospital stroke care. Dissatisfaction was closely associated with outcome at 3 months. Patient who were dependent regarding activities of daily living, felt depressed, or had poor self-perceived general health were more likely to be dissatisfied. Dissatisfaction with global acute stroke care was linked to dissatisfaction with other aspects of care, including rehabilitation and support by community services. Patients treated in stroke units were less often dissatisfied than patients in general wards, as were patients who had been treated in a small hospital (vs medium or large hospitals) and patient who had participated in discharge planning. In multivariate analyses, the strongest predictor of dissatisfaction with acute care was poor outcome (dependency regarding activities of daily living, depressed mood, poor self-perceived health). CONCLUSIONS: Dissatisfaction with in-hospital acute stroke care is part of a more extensive complex comprising poor functional outcome, depressive mood, poor self-perceived general health, and dissatisfaction not only with acute care but also with health care and social services at large. Several aspects of stroke care organization are associated with a lower risk of dissatisfaction.
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| 45. |
- Asplund, Kjell, et al.
(author)
-
The Riks-Stroke story : building a sustainable national register for quality assessment of stroke care
- 2011
-
In: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 6:2, s. 99-108
-
Journal article (peer-reviewed)abstract
- Background Riks-Stroke, the Swedish Stroke Register, is the world's longest-running national stroke quality register (established in 1994) and includes all 76 hospitals in Sweden admitting acute stroke patients. The development and maintenance of this sustainable national register is described. Methods Riks-Stroke includes information on the quality of care during the acute phase, rehabilitation and secondary prevention of stroke, as well as data on community support. Riks-Stroke is unique among stroke quality registers in that patients are followed during the first year after stroke. The data collected describe processes, and medical and patient-reported outcome measurements. The register embraces most of the dimensions of health-care quality (evidence-based, safe, provided in time, distributed fairly and patient oriented). Result Annually, approximately 25 000 patients are included. In 2009, approximately 320 000 patients had been accumulated (mean age 76-years). The register is estimated to cover 82% of all stroke patients treated in Swedish hospitals. Among critical issues when building a national stroke quality register, the delicate balance between simplicity and comprehensiveness is emphasised. Future developments include direct transfer of data from digital medical records to Riks-Stroke and comprehensive strategies to use the information collected to rapidly implement new evidence-based techniques and to eliminate outdated methods in stroke care. Conclusions It is possible to establish a sustainable quality register for stroke at the national level covering all hospitals admitting acute stroke patients. Riks-Stroke is fulfilling its main goals to support continuous quality improvement of Swedish stroke services and serve as an instrument for following up national stroke guidelines.
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| 46. |
- Asztely, Mats, et al.
(author)
-
Is ultrasonography useful for population studies on schistosomiasis mansoni? An evaluation based on a survey on a population from Kome Island, Tanzania
- 2016
-
In: Acta Radiologica Open. - : SAGE Publications. - 2058-4601. ; 5:12
-
Journal article (peer-reviewed)abstract
- BackgroundObservation of characteristic alterations at liver ultrasonography in clinical schistosomiasis mansoni cases has initiated utilization of this examination method in population surveys in areas where this disease is endemic.PurposeTo present results of liver ultrasonography and their relation to epidemiological data of a population in an area endemic for S. mansoni, to estimate the precision of classification of periportal anatomy changes known as periportal fibrosis (PPF), and to evaluate the relevance of ultrasonography in epidemiological studies on S. mansoni.Material and MethodsA total of 459 inhabitants on Kome Island, Lake Victoria, Tanzania were examined by ultrasound with image documentation by locally trained personnel. A subsample of this population, 116 individuals, was subject to ultrasonography by two examiners independently. Separately, the images were classified for PPF according to the Managil protocol, twice for the subsample.ResultsPPF could be classified for 458 individuals; 64% and 36% were classified as I or II, respectively; none was classified as 0; only one as III. Results were similar for the subsample examined twice. Comparing the two separate classifications of all 232 sets of images of the subsample gave a Kappa (K) value of 0.50. When comparing the classifications of each of the two different examinations of the same individuals of the subsample, K values of 0.29 and 0.34 for the first and second classification, respectively, were obtained.ConclusionUltrasonography does not appear to correlate well with disease stage. Presently, it should not be utilized for staging of schistosoma mansoni-related liver damage in population surveys.
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| 47. |
- Augustsson, Olga, et al.
(author)
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Social and medical risk indicators for 8-year mortality in a Swedish urban elderly population
- 2003
-
In: Archives of Gerontology and Geriatrics. ; 36:2, s. 155-171
-
Journal article (peer-reviewed)abstract
- The aim of this study was to identify and evaluate social and medical risk indicators for mortality in an urban elderly population. Altogether 217 subjects (144 women and 73 men, mean age 78 years, range 69–96 years of age) participated in an examination 1990/91. Eighty-eight persons (55 women and 33 men) had died, and 129 subjects (89 women and 40 men) were alive January 1, 1999. Several risk indicators were found and those with the highest statistical explanatory power to predict mortality were: tremor, inability for heavy housework, a pathological second heart sound, low triceps skinfold, low diastolic blood pressure and decreased appetite. A multivariate model (MVM) utililizing both social and medical risk indicators, and a clinical model (CM) based on the judgement of a registered nurse identified 49 and 34%, respectively, of those who died during the 8-year period (n=88). A third risk group, the intervention group, comprising individuals selected by either the MVM or CM models, identified 56% of those who died. The latter procedure could be used to define risk groups for mortality in future intervention studies. The combination of social and medical risk indicators in MVM, and a CM might be used in studies with larger sample sizes in order to increase the knowledge in this field.
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| 48. |
- Augustsson, Olga, et al.
(author)
-
The Johanneberg Study: a Social Survey in an Urban Elderly Population. I. General presentation of the study including an analysis of non-response and identification of risk groups
- 1993
-
In: Scandinavian Journal of Social Medicin. ; 22:4, s. 283-92
-
Journal article (peer-reviewed)abstract
- This study is the Swedish part of a world-wide transcultural and interdisciplinary study in elderly populations which addresses food habits, health and life-style. The aim of this paper is to present the general design including an analysis of non-response, and to identify risk-groups for intervention programmes. The study comprised 217 noninstitutionalized males (n = 73) and females (n = 144), aged 70 and over (mean age 78 years) in a small urban area. Home visits and clinical examinations with standard methods were used. The participation rate was 76%. Significant differences between non-respondents and respondents could be seen, which may be important when planning health promotion. On the basis of experience during the examinations, a risk-group was identified for prospective and intervention study purpose, based on a multiple variable model and a clinical model.
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| 49. |
- Axelsson, Malin, 1964, et al.
(author)
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Chronic bronchitis in West Sweden - a matter of smoking and social class
- 2016
-
In: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 3
-
Journal article (peer-reviewed)abstract
- Background: Although chronic bronchitis is associated with impaired quality of life, hospitalisations and increased mortality, it has been less in focus after the introduction of the term chronic obstructive pulmonary disease (COPD). There are no recent published data on the prevalence of chronic bronchitis from the Scandinavian countries. Aim: The main aim of the present study was to estimate the prevalence of chronic bronchitis in West Sweden by using data from a large-scale epidemiological study of the general population. A further aim was to identify current risk factors for chronic bronchitis in a population with a major decrease in the proportion of smokers. Methods: From the 18,087 questionnaire responders out of 30,000 invited to participate at the West Sweden Asthma Study, 2,000 subjects were randomly selected and invited to detailed clinical examinations performed during 2009-2013. A total of 1,172 subjects aged 17-79 participated in the examinations which included, among others, spirometry and structured interviews. Chronic bronchitis was defined according to reported symptoms. Results: The overall prevalence of chronic bronchitis was 7.2% (men 7.6%; women 6.8% ns), and it was 8.7% in subjects older than age 60. Chronic bronchitis was strongly associated with smoking, defined both as current smoking status and pack-years. Other risk factors were increasing age, low socio-economic class and urban living. Of those with chronic bronchitis, 22% fulfilled the GOLD criteria of COPD. Conclusion: The prevalence of chronic bronchitis was somewhat lower than found by studies in Sweden in the 1980s and the prevalence was now similar in men and women. Although smoking was still the dominating risk factor for chronic bronchitis, the relative importance of smoking had decreased parallel with a decreasing smoking prevalence, while the relative importance of other factors than smoking had increased compared to previous studies.
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| 50. |
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