| 1. |
- Bergh, Anders, et al.
(författare)
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Didecyl squarate — A practical amino-reactive cross-linking reagent for neoglycoconjugate synthesis
- 2001
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Ingår i: Glycoconjugate Journal. - 1573-4986. ; 18:8, s. 615-621
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Tidskriftsartikel (refereegranskat)abstract
- The present paper describes the synthesis and use of the hydrophobic squaric decyl ester glycosides in neoglycoconjugate chemistry. The 2-aminoethyl glycosides of agr-D-mannopyranose, lactose, globotriose, globotetraose, GM3, and sialyl Lewisx, as well as the 2-(2-aminoethylthio)ethyl glycoside of agr-D-mannopyranose, beta-D-glucopyranose, and galabiose were reacted with squaric acid didecyl ester to afford the hydrophobic squaric decyl ester glycosides. These glycosides were efficient reagents for the conjugation to amino-functional microtiter plates, BSA and aminated Sepharose EAH 4B. The decyl ester moiety of the squaric decyl ester glycosides constitutes a traceless hydrophobic tag, which has the major advantage, as compared to the corresponding ethyl esters, that it enables easy purification of the glycosides with silica chromatography and that unreacted excesses glycosides from conjugation reaction mixtures can easily be recovered by means of C18 solid phase extraction.
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| 2. |
- 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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| 3. |
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| 4. |
- Ekelund, Ulf, et al.
(författare)
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The skåne emergency medicine (SEM) cohort
- 2024
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - London : BioMed Central (BMC). - 1757-7241. ; 32, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the European Union alone, more than 100 million people present to the emergency department (ED) each year, and this has increased steadily year-on-year by 2-3%. Better patient management decisions have the potential to reduce ED crowding, the number of diagnostic tests, the use of inpatient beds, and healthcare costs.METHODS: We have established the Skåne Emergency Medicine (SEM) cohort for developing clinical decision support systems (CDSS) based on artificial intelligence or machine learning as well as traditional statistical methods. The SEM cohort consists of 325 539 unselected unique patients with 630 275 visits from January 1st, 2017 to December 31st, 2018 at eight EDs in the region Skåne in southern Sweden. Data on sociodemographics, previous diseases and current medication are available for each ED patient visit, as well as their chief complaint, test results, disposition and the outcome in the form of subsequent diagnoses, treatments, healthcare costs and mortality within a follow-up period of at least 30 days, and up to 3 years.DISCUSSION: The SEM cohort provides a platform for CDSS research, and we welcome collaboration. In addition, SEM's large amount of real-world patient data with almost complete short-term follow-up will allow research in epidemiology, patient management, diagnostics, prognostics, ED crowding, resource allocation, and social medicine.
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| 5. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 6. |
- Johansson, Helena, 1981, et al.
(författare)
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High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:6, s. 1390-1396
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Tidskriftsartikel (refereegranskat)abstract
- Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 mu g/mL (interquartile range, 7.714.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.231.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.091.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men. (C) 2012 American Society for Bone and Mineral Research.
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| 7. |
- Lewerin, Catharina, 1961, et al.
(författare)
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High plasma osteocalcin is associated with low blood haemoglobin in elderly men: the MrOS Sweden Study
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known. OBJECTIVE: To determine whether plasma osteocalcin is a determinant of Hb in elderly men. METHODS: A total of 993 men (mean age 75.3 +/- 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C). RESULTS: Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb <130 g L-1 ) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 mug L-1 , P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05). CONCLUSIONS: These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis.
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| 8. |
- Lewerin, Catharina, 1961, et al.
(författare)
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High serum adiponectin is associated with low blood haemoglobin in elderly men: the Swedish MrOS study
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 278:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-derived protein adiponectin increases with age. The association between erythropoiesis and adiponectin in elderly men is unclear. The aim of this study was to determine whether adipokines such as adiponectin and leptin are associated with anaemia and Hb concentration in elderly community-dwelling men. Design and setting: The Gothenburg part of the population-based Swedish Osteoporotic Fractures in Men (MrOS) cohort (n=1010; median age 75.3years, range 69-81). Main outcome measures: We investigated the associations between levels of adiponectin and Hb before and after adjusting for potential confounders [i.e. age, body composition, erythropoietin (EPO), total oestradiol, leptin, cystatin C and iron and B vitamin status]. Results: In these elderly men, age was negatively associated with Hb (r=-0.12, P<0.001) and positively associated with adiponectin level (r=0.13, P<0.001). In age-adjusted partial correlations, Hb and adiponectin levels were negatively correlated (r=-0.20, P<0.001); this association remained significant after multivariable adjustment for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Age-adjusted mean adiponectin concentrations were significantly higher in anaemic men (66/1005; Hb <130gL(-1)) compared to nonanaemic men (14.0 vs. 11.7 gmL(-1), P<0.05). In multivariate analysis, adiponectin together with EPO, total oestradiol, insulin, albumin, transferrin saturation, HDL cholesterol, cystatin C, total body fat mass and free thyroxine, but not leptin, explained 35% of the variation in Hb level. These results remained essentially unchanged after exclusion of men with diabetes. Conclusions: Serum adiponectin, but not leptin, was negatively and independently associated with Hb. This finding suggests a possible role of adiponectin in the age-related decline in Hb level observed in apparently healthy elderly men.
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| 9. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 10. |
- Ohlsson, H, et al.
(författare)
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Understanding adherence to official guidelines on statin prescribing in primary health care-a multi-level methodological approach.
- 2005
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 61:Aug 25, s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to investigate the role that municipalities and out-patient health care centres (HCCs) have in understanding adherence to official guidelines on statin prescribing. Our hypothesis was that after guideline publication, adherence to recommended statin prescription would increase and variance among HCCs and municipalities would decrease. Since multi-level regression analysis (MLRA) is a relatively new methodology in pharmacoepidemiology, we also aimed to explore the application of MLRA in our investigation. Methods: We obtained data from the Swedish Corporation of Pharmacies record of sales regarding all initial prescriptions of statins issued between April and December 2003. We applied multi-level analysis on 34,514 individual prescriptions (level 1) nested within 226 HCCs (level 2), which in turn were nested within 33 municipalities (level 3). Temporal trends and gender differences were investigated by means of random slope analysis. Variance was expressed using median odds ratio (MOR) and interval odds ratio. Results: HCCs appeared to be more relevant than municipalities for understanding the physicians' propensity to prescribe a recommended statin (MORHCC=1.96 and MORMunicipality=1.41). Overall prevalence of adherence was very low (about 20%). After publication of the guidelines, prescription of recommended statins increased, and variance among HCCs decreased but only during the first 4 months of the observation period. Conclusion: The publication of official guidelines in the county of Scania exerted a positive influence on statin prescription but, at the end of the observation period, adherence was still low and practice variation high. These facts may reflect inefficient therapeutic traditions and suggest that more intensive interventions may be necessary to promote rational statin prescription.
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