| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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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. |
- de Jong, Roelof S., et al.
(författare)
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4MOST-4-metre Multi-Object Spectroscopic Telescope
- 2014
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Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147
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Konferensbidrag (refereegranskat)abstract
- 4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the fields of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO and from ground-based facilities like VISTA, VST, DES, LSST and SKA. The 4MOST baseline concept features a 2.5 degree diameter field-of-view with similar to 2400 fibres in the focal surface that are configured by a fibre positioner based on the tilting spine principle. The fibres feed two types of spectrographs; similar to 1600 fibres go to two spectrographs with resolution R> 5000 (lambda similar to 390-930 nm) and similar to 800 fibres to a spectrograph with R> 18,000 (lambda similar to 392-437 nm & 515-572 nm & 605-675 nm). Both types of spectrographs are fixed-configuration, three-channel spectrographs. 4MOST will have an unique operations concept in which 5 year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept. 4MOST has been accepted for implementation by ESO with operations expected to start by the end of 2020. This paper provides a top-level overview of the 4MOST facility, while other papers in these proceedings provide more detailed descriptions of the instrument concept[1], the instrument requirements development[2], the systems engineering implementation[3], the instrument model[4], the fibre positioner concepts[5], the fibre feed[6], and the spectrographs[7].
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| 4. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 5. |
- Ingelsson, Erik, et al.
(författare)
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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans
- 2010
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010
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| 6. |
- Ingelsson, Erik, et al.
(författare)
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Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
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| 7. |
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| 8. |
- Lind, Thomas, et al.
(författare)
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High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats
- 2011
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 48:3, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.
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| 9. |
- Lind, Thomas, et al.
(författare)
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Microarray Profiling of Diaphyseal Bone of Rats Suffering from Hypervitaminosis A
- 2012
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 90:3, s. 219-229
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young male rats high doses of vitamin A and performed microarray analysis of diaphyseal bone with and without marrow after 1 week, i.e., just before the first fractures appeared. Of the differentially expressed genes in cortical bone, including marrow, 98% were upregulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene ontology (GO) analysis revealed that only samples containing bone marrow were associated with a GO term, which principally represented extracellular matrix. This is consistent with the histological findings of increased endosteal/marrow osteoblast number. Fourteen genes, including Cyp26b1, which is known to be upregulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule osteoadherin was upregulated. Further analysis of the major gene-expression changes revealed apparent augmented Wnt signaling in the sample containing bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was found only in samples containing bone marrow. Together, these results highlight the importance of compartment-specific analysis of bone and corroborate previous observations of compartment-specific effects of vitamin A, with reduced activity in cortical bone but increased activity in the endosteal/marrow compartment. We specifically identify potential key osteoblast-, Wnt signaling-, and hypoxia-associated genes in the processes leading to spontaneous fractures.
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| 10. |
- Silajdzic, Edina, et al.
(författare)
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A Critical Evaluation of Inflammatory Markers in Huntington’s Disease Plasma
- 2013
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Ingår i: Journal of Huntington's disease. - 1879-6397. ; 2:1, s. 125-134
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Huntington’s Disease (HD) is a hereditary, progressive neurodegenerative disorder characterised by both neurological and systemic symptoms. In HD, immune changes can be observed before the onset of overt clinical features raising the possibility that immune markers in plasma could be used to track disease progression. It has previously been demonstrated that a widespread, progressive innate immune response is detectable in plasma throughout the course of HD. OBJECTIVE: The aim of the present study was to investigate the potential of several components of innate immunity as plasma biomarkers in HD. METHODS: We utilised antibody-based detection technologies as well as mass spectrometric quantification, multiple reaction monitoring (MRM-MS). RESULTS: Levels of several markers previously described as altered in HD, such as clusterin, complement component 4, complement component 9 and α-2 macroglobulin did not differ between healthy controls and HD subjects as measured by Luminex, ELISA or MRM-MS. C-reactive protein was decreased in early HD, while the other immune markers tested were unaltered. CONCLUSIONS: Of the immune markers tested in this study, none showed potential to track with HD disease progression.
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| 11. |
- Smiljanic, R., et al.
(författare)
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The Gaia-ESO Survey: The analysis of high-resolution UVES spectra of FGK-type stars
- 2014
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570
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Tidskriftsartikel (refereegranskat)abstract
- Context. The ongoing Gaia-ESO Public Spectroscopic Survey is using FLAMES at the VLT to obtain high-quality medium-resolution Giraffe spectra for about 10(5) stars and high-resolution UVES spectra for about 5000 stars. With UVES, the Survey has already observed 1447 FGK-type stars. Aims. These UVES spectra are analyzed in parallel by several state-of-the-art methodologies. Our aim is to present how these analyses were implemented, to discuss their results, and to describe how a final recommended parameter scale is defined. We also discuss the precision (method-to-method dispersion) and accuracy (biases with respect to the reference values) of the final parameters. These results are part of the Gaia-ESO second internal release and will be part of its first public release of advanced data products. Methods. The final parameter scale is tied to the scale defined by the Gaia benchmark stars, a set of stars with fundamental atmospheric parameters. In addition, a set of open and globular clusters is used to evaluate the physical soundness of the results. Each of the implemented methodologies is judged against the benchmark stars to define weights in three different regions of the parameter space. The final recommended results are the weighted medians of those from the individual methods. Results. The recommended results successfully reproduce the atmospheric parameters of the benchmark stars and the expected T-eff-log g relation of the calibrating clusters. Atmospheric parameters and abundances have been determined for 1301 FGK-type stars observed with UVES. The median of the method-to-method dispersion of the atmospheric parameters is 55K for T-eff, 0.13dex for log g and 0.07 dex for [Fe/H]. Systematic biases are estimated to be between 50-100 K for T-eff, 0.10-0.25 dex for log g and 0.05-0.10 dex for [Fe/H]. Abundances for 24 elements were derived: C, N, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ba, Nd, and Eu. The typical method-to-method dispersion of the abundances varies between 0.10 and 0.20 dex. Conclusions. The Gaia-ESO sample of high-resolution spectra of FGK-type stars will be among the largest of its kind analyzed in a homogeneous way. The extensive list of elemental abundances derived in these stars will enable significant advances in the areas of stellar evolution and Milky Way formation and evolution.
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| 12. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 13. |
- Bergemann, M., et al.
(författare)
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The Gaia-ESO Survey : radial metallicity gradients and age-metallicity relation of stars in the Milky Way disk
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 565, s. A89-
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Tidskriftsartikel (refereegranskat)abstract
- We study the relationship between age, metallicity, and alpha-enhancement of FGK stars in the Galactic disk. The results are based upon the analysis of high-resolution UVES spectra from the Gaia-ESO large stellar survey. We explore the limitations of the observed dataset, i.e. the accuracy of stellar parameters and the selection effects that are caused by the photometric target preselection. We find that the colour and magnitude cuts in the survey suppress old metal-rich stars and young metal-poor stars. This suppression may be as high as 97% in some regions of the age-metallicity relationship. The dataset consists of 144 stars with a wide range of ages from 0.5 Gyr to 13.5 Gyr, Galactocentric distances from 6 kpc to 9.5 kpc, and vertical distances from the plane 0 < vertical bar Z vertical bar < 1.5 kpc. On this basis, we find that i) the observed age-metallicity relation is nearly flat in the range of ages between 0 Gyr and 8 Gyr; ii) at ages older than 9 Gyr, we see a decrease in [Fe/H] and a clear absence of metal-rich stars; this cannot be explained by the survey selection functions; iii) there is a significant scatter of [Fe/H] at any age; and iv) [Mg/Fe] increases with age, but the dispersion of [Mg/Fe] at ages > 9 Gyr is not as small as advocated by some other studies. In agreement with earlier work, we find that radial abundance gradients change as a function of vertical distance from the plane. The [Mg/Fe] gradient steepens and becomes negative. In addition, we show that the inner disk is not only more alpha-rich compared to the outer disk, but also older, as traced independently by the ages and Mg abundances of stars.
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| 14. |
- Bergman, Åke, et al.
(författare)
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Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 15. |
- Caesar, Carl, et al.
(författare)
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Bäste herren på täppan : En ESO-rapport om bostadsbyggande och kommunala markanvisningar
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Stora delar av den mark som kan användas för bostadsbebyggelse ägs av kommunerna. Hur kommunerna hanterar sina markområden är därför en central bostadspolitisk fråga.- Finns det brister i kommunernas markhantering som begränsar bostadsmarknadens effektivitet?- Vad kan kommunerna göra för att främja konkurrensen bland byggherrarna och förbättra bostadsbyggandet?
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Cui, Tao, et al.
(författare)
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Olfactory receptor 51E1 protein as a potential novel tissue biomarker for small intestine neuroendocrine carcinomas
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168:2, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded protein may be a novel SI-NEC clinical biomarker.DESIGN: OR51E1 coding sequence was cloned using total RNA from SI-NEC patient specimens. Quantitative real-time PCR analysis explored OR51E1 expression in laser capture microdissected SI-NEC cells and adjacent microenvironment cells. Moreover, immunohistochemistry investigated OR51E1 protein expression on operation and biopsy material from primary SI-NECs, mesentery, and liver metastases from 70 patients. Furthermore, double immunofluorescence studies explored the potential co-localization of the vesicular monoamine transporter 1 (SLC18A1, generally referred to as VMAT1) and OR51E1 in the neoplastic cells and in the intestinal mucosa adjacent to the tumor.RESULTS: OR51E1 coding sequence analysis showed absence of mutation in SI-NEC patients at different stages of disease. OR51E1 expression was higher in microdissected SI-NEC cells than in the adjacent microenvironment cells. Furthermore, both membranous and cytoplasmic OR51E1 immunostaining patterns were detected in both primary SI-NECs and metastases. Briefly, 18/43 primary tumors, 7/28 mesentery metastases, and 6/18 liver metastases were 'positive' for OR51E1 in more than 50% of the tumor cells. In addition, co-localization studies showed that OR51E1 was expressed in >50% of the VMAT1 immunoreactive tumor cells and of the enterochromaffin cells in the intestinal mucosa adjacent to the tumor.CONCLUSION: OR51E1 protein is a potential novel clinical tissue biomarker for SI-NECs. Moreover, we suggest its potential therapeutic molecular target development using solid tumor radioimmunotherapy.
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| 20. |
- Dalenbäck, Jan-Olof, 1954, et al.
(författare)
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Ställ tekniska egenskapskrav och använd deklarationerna
- 2014
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Ingår i: Energi & Miljö. - 1101-0568. ; 2014:4, s. 40-41
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Ta bort energikraven i BBR och ersätt dem med ändamålsenliga egenskaps¬krav. Gör sedan energideklarationerna värda namnet genom att inkludera hushålls- och verk¬sam¬hets¬el så att de kan användas för att följa upp energi¬användningen. I anslutning till Boverkets regeringsuppdrag (N2014/75/E) att definiera nya energihus¬håll¬ningskrav, finns det all anledning att diskutera om vi är på rätt väg med de krav på bygg¬naders energi¬prestanda som ställs i Boverkets Byggregler (BBR). Speciellt om dess uppfyllelse ska vara juridiskt bindande.
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| 21. |
- Damiani, F., et al.
(författare)
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Gaia-ESO Survey: Empirical classification of VLT/Giraffe stellar spectra in the wavelength range 6440-6810 angstrom in the gamma Velorum cluster, and calibration of spectral indices
- 2014
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566
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Tidskriftsartikel (refereegranskat)abstract
- We present a study of spectral diagnostics available from optical spectra with R = 17 000 obtained with the VLT/Giraffe HR15n setup, using observations from the Gaia-ESO Survey, on the gamma Vel young cluster, with the purpose of classifying these stars and finding their fundamental parameters. We define several spectroscopic indices, sampling the amplitude of TiO bands, the H alpha line core and wings, and temperature- and gravity-sensitive sets of lines, each useful as a T-eff or log g indicator over a limited range of stellar spectral types. H alpha line indices are also useful as chromospheric activity or accretion indicators. Furthermore, we use all indices to define additional global T-eff - and logg-sensitive indices tau and gamma, valid for the entire range of types in the observed sample. We find a clear difference between gravity indices of main-sequence and pre-main-sequence stars, as well as a much larger difference between these and giant stars. The potentially great usefulness of the (gamma, t) diagram as a distance-independent age measurement tool for young clusters is discussed. We discuss the effect on the defined indices of classical T Tauri star veiling, which is however detected in only a few stars in the present sample. Then, we present tests and calibrations of these indices, on the basis of both photometry and literature reference spectra, from the UVES Paranal Observatory Project and the ELODIE 3.1 Library. The known properties of these stars, spanning a wide range of stellar parameters, enable us to obtain a good understanding of the performances of our new spectral indices. For non-peculiar stars with known temperature, gravity, and metallicity, we are able to calibrate quantitatively our indices, and derive stellar parameters for a wide range of stellar types. To this aim, a new composite index is defined, providing a good metallicity indicator. The ability of our indices to select peculiar, or otherwise rare classes of stars is also established. For pre-main-sequence stars outside the parameter range of the ELODIE dataset, index calibration relies on model isochrones. We check our calibrations against current Gaia-ESO UVES results, plus a number of Survey benchmark stars, and also against Gaia-ESO observations of young clusters, which contribute to establishing the good performance of our method across a wide range of stellar parameters. Our gravity determination for late-type PMS stars is found to be accurate enough to let us obtain gravity-based age estimates for PMS clusters. Finally, our gravity determinations support the existence of an older pre-main-sequence population in the gamma Vel sky region, in agreement with evidence obtained from the lithium depletion pattern of the same stars.
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| 22. |
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| 23. |
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| 24. |
- Dimas, Antigone S, et al.
(författare)
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Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 63:6, s. 2158-2171
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Tidskriftsartikel (refereegranskat)abstract
- Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci and indices of proinsulin processing, insulin secretion and insulin sensitivity. We included data from up to 58,614 non-diabetic subjects with basal measures, and 17,327 with dynamic measures. We employed additive genetic models with adjustment for sex, age and BMI, followed by fixed-effects inverse variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (including TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without detectable change in fasting glucose. The final group contained twenty risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
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| 25. |
- Erhag, Thomas, 1970, et al.
(författare)
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Retroaktivitet i social trygghetsreglering
- 2013
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Ingår i: I Ketscher, K. Lilleholt, K. Smith, E & Syse, A (Red) Velferd og rettferd, Festskrift til Asbjörn Kjönstad 70 år. - Oslo : Gyldendal. - 9788205424432 ; , s. 139-153
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 26. |
- Fall, Tove, et al.
(författare)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 27. |
- Flannick, Jason, et al.
(författare)
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Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:4, s. 357-357
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
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| 28. |
- Friel, E. D., et al.
(författare)
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Gaia-ESO Survey : Properties of the intermediate age open cluster NGC 4815
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 563, s. A117-
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Tidskriftsartikel (refereegranskat)abstract
- Context. NGC 4815 is a populous similar to 500 Myr open cluster at R-gc similar to 7 kpc observed in the first six months of the Gaia-ESO Survey. Located in the inner Galactic disk, NGC 4815 is an important potential tracer of the abundance gradient, where relatively few intermediate age open clusters are found. Aims. The Gaia-ESO Survey data can provide an improved characterization of the cluster properties, such as age, distance, reddening, and abundance profile. Methods. We use the survey derived radial velocities, stellar atmospheric parameters, metallicity, and elemental abundances for stars targeted as potential members of this cluster to carry out an analysis of cluster properties. The radial velocity distribution of stars in the cluster field is used to define the cluster systemic velocity and derive likely cluster membership for stars observed by the Gaia-ESO Survey. We investigate the distributions of Fe and Fe-peak elements, alpha-elements, and the light elements Na and Al and characterize the cluster's internal chemical homogeneity comparing it to the properties of radial velocity non-member stars. Utilizing these cluster properties, the cluster color-magnitude diagram is analyzed and theoretical isochrones are fit to derive cluster reddening, distance, and age. Results. NGC 4815 is found to have a mean metallicity of [Fe/H] = +0.03 +/- 0.05 dex (s.d.). Elemental abundances of cluster members show typically very small internal variation, with internal dispersions of similar to 0.05 dex. The alpha-elements [Ca/Fe] and [Si/Fe] show solar ratios, but [Mg/Fe] is moderately enhanced, while [Ti/Fe] appears slightly deficient. As with many open clusters, the light elements [Na/Fe] and [Al/Fe] are enhanced, [Na/Fe] significantly so, although the role of internal mixing and the assumption of local thermodynamical equilibrium in the analysis remain to be investigated. From isochrone fits to color-magnitude diagrams, we find a cluster age of 0.5 to 0.63 Gyr, a reddening of E(B-V) = 0.59 to 0.65, and a distance modulus (m -M)(0) = 11.95 to 12.20, depending on the choice of theoretical models, leading to a Galactocentric distance of 6.9 kpc.
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| 29. |
- Hall, Lars, et al.
(författare)
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How the polls can be both spot on and dead wrong: using choice blindness to shift political attitudes and voter intentions.
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Political candidates often believe they must focus their campaign efforts on a small number of swing voters open for ideological change. Based on the wisdom of opinion polls, this might seem like a good idea. But do most voters really hold their political attitudes so firmly that they are unreceptive to persuasion? We tested this premise during the most recent general election in Sweden, in which a left- and a right-wing coalition were locked in a close race. We asked our participants to state their voter intention, and presented them with a political survey of wedge issues between the two coalitions. Using a sleight-of-hand we then altered their replies to place them in the opposite political camp, and invited them to reason about their attitudes on the manipulated issues. Finally, we summarized their survey score, and asked for their voter intention again. The results showed that no more than 22% of the manipulated replies were detected, and that a full 92% of the participants accepted and endorsed our altered political survey score. Furthermore, the final voter intention question indicated that as many as 48% (±9.2%) were willing to consider a left-right coalition shift. This can be contrasted with the established polls tracking the Swedish election, which registered maximally 10% voters open for a swing. Our results indicate that political attitudes and partisan divisions can be far more flexible than what is assumed by the polls, and that people can reason about the factual issues of the campaign with considerable openness to change.
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| 30. |
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| 31. |
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| 32. |
- Hedner, Thomas, et al.
(författare)
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Stora förändringar i den globala läkemedelsindustrin
- 2012
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Ingår i: Läkartidningen. - Stockholm. - 0023-7205 .- 1652-7518. ; 109:7, s. 324-325
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Den globala läkemedelsindustrin är under kraftig för- ändring. Under de senaste tio åren har 300 000 arbets- tillfällen lagts ner i »Big Pharma«. I stället utvecklas mindre, kreativa och »öppna« innovationsnätverk och organisationsstrukturer för att ta fram nya läkemedel, skriver Thomas Hedner och medförfattare.
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| 33. |
- Howes, Louise, et al.
(författare)
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The Gaia-ESO Survey: the most metal-poor stars in the Galactic bulge
- 2014
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 445:4, s. 4241-4246
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results of the EMBLA survey (Extremely Metal-poor BuLge stars with AAOmega), aimed at finding metal-poor stars in the Milky Way bulge, where the oldest stars should now preferentially reside. EMBLA utilizes SkyMapper photometry to pre-select metal-poor candidates, which are subsequently confirmed using AAOmega spectroscopy. We describe the discovery and analysis of four bulge giants with -2.72 <= [Fe/H] <= -2.48, the lowest metallicity bulge stars studied with high-resolution spectroscopy to date. Using FLAMES/UVES spectra through the Gaia-ESO Survey we have derived abundances of twelve elements. Given the uncertainties, we find a chemical similarity between these bulge stars and halo stars of the same metallicity, although the abundance scatter may be larger, with some of the stars showing unusual [alpha/Fe] ratios.
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| 34. |
- Hu, Lijuan, et al.
(författare)
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Adamts1 is highly induced in rachitic bones of FGF23 transgenic mice and participates in degradation of non-mineralized bone matrix collagen
- 2013
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 430:3, s. 901-906
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Tidskriftsartikel (refereegranskat)abstract
- Transgenic mice overexpressing fibroblast growth factor 23 (FGF23) in osteoblasts have a rachitic bone phenotype. These mice display hypomineralized bones, increased expression of osteoblast markers, but osteoclast numbers are unaltered or slightly reduced. Paradoxically, they show increased serum levels of the bone resorption marker CTX, a type I collagen degradation fragment. Here we analyzed a matrix metalloproteinase- (MMP-) like secreted protease, Adamts1, that has previously been associated with osteoblastic type I collagen breakdown in vitro. Bones from FGF23 transgenic (tg) mice displayed increased Adamts1 protein upon both immunohistological staining and Western blotting. We further found Adamts1 protein together with excessively degraded type I collagen in the non-mineralized bone fraction of FGF23 tg mice. A similar degradation pattern of type I collagen was noticed upon forced expression of Adamts1 in osteoblastic cells in vitro. Importantly, these Adamts1-expressing osteoblastic cells exhibited increased release of CTX fragments when cultured on demineralized bone discs. Together, these results demonstrate for the first time that Adamts1 can be highly induced in bone tissue and that this MMP-like protease can increase osteoblastic release of CTX fragments from non-mineralized bone. Thus, Adamts1 potentially contributes to the increased serum levels of CTX in rickets/osteomalacia.
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| 35. |
- Hu, Lijuan, et al.
(författare)
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Over-expression of Adamts1 in mice alters bone mineral density
- 2012
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Ingår i: Journal of Bone and Mineral Metabolism. - : Springer Science and Business Media LLC. - 0914-8779 .- 1435-5604. ; 30:3, s. 304-311
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Tidskriftsartikel (refereegranskat)abstract
- ADAMTS1, a secreted multifunctional metalloproteinase with disintegrin and thrombospondin motifs, is an early response gene of parathyroid hormone (PTH) in osteoblasts. Mice engineered to lack Adamts1 are smaller compared to wild-type (WT) mice and ADAMTS1 metalloproteinase activity has been shown to increase osteoblastic growth in collagen gels. However, there are no reports investigating the consequence of Adamts1 over-expression on bone tissue in vivo. Here, we analyze bones of female and male transgenic (TG) mice over-expressing mouse Adamts1 using peripheral quantitative computed tomography to evaluate its effect on bone shape and mineral density. Western blotting of protein extracts and immunohistochemistry of bone sections reveal increased presence of Adamts1 protein in TG bones compared to WT bones. Phenotypic analyses of femur show that female TG mice have reduced metaphyseal total density, trabecular bone mineral density and trabecular mineral content. In contrast, male TG mice which were without changes in the metaphysis showed increased total density and cortical density at the mid-diaphysis cortical site. Female TG mice showed no significant changes at the cortical site compared to WT mice. Furthermore, diaphyseal endosteal compartment was only affected in male TG mice. Along these lines, Adamts1 increased blood levels of PTH only in females whereas it reduced osteocalcin levels only in males. These results reveal that Adamts1 has an impact on bone mineral density and thus further confirm Adamts1 as a potent regulator of bone remodeling.
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| 36. |
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| 37. |
- Hu, Lijuan, et al.
(författare)
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Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:10, s. e13305-
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown that high vitamin A intake is associated with bone fragility and fractures in both animals and humans. However, the mechanism by which vitamin A affects bones is unclear. In the present study, the direct effects of retinoic acid (RA) on human and murine osteoclastogenesis were evaluated using cultured peripheral blood CD14(+) monocytes and RAW264.7 cells. Both the activity of the osteoclast marker tartrate resistant acid phosphatase (TRAP) in culture supernatant and the expression of the genes involved in osteoclast differentiation together with bone resorption were measured. To our knowledge, this is the first time that the effects of RA on human osteoclast progenitors and mature osteoclasts have been studied in vitro. RA stimulated proliferation of osteoclast progenitors both from humans and mice. In contrast, RA inhibited differentiation of the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis of human and murine osteoclast progenitors via retinoic acid receptors (RARs). We also show that the mRNA levels of receptor activator of nuclear factor κB (RANK), the key initiating factor and osteoclast associated receptor for RANKL, were potently suppressed by RA in osteoclast progenitors. More importantly, RA abolished the RANK protein in osteoclast progenitors. This inhibition could be partially reversed by a RAR pan-antagonist. Furthermore, RA treatment suppressed the expression of the transcription factor nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and increased the expression of interferon regulatory factor-8 (IRF-8) in osteoclast progenitors via RARs. Also, RA demonstrated differential effects depending on the material supporting the cell culture. RA did not affect TRAP activity in the culture supernatant in the bone slice culture system, but inhibited the release of TRAP activity if cells were cultured on plastic. In conclusion, our results suggest that retinoic acid increases proliferation of human osteoclast progenitors and that it inhibits RANK-stimulated osteoclast differentiation by suppressing RANK.
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| 38. |
- Hultenheim Klintberg, Ingrid, 1959, et al.
(författare)
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Western Ontario Osteoarthritis Shoulder (WOOS) index: a cross-cultural adaptation into Swedish, including evaluation of reliability, validity, and responsiveness in patients with subacromial pain
- 2012
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Ingår i: Journal of Shoulder and Elbow Surgery. - : Elsevier BV. - 1058-2746. ; 21:12, s. 1698-1705
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to translate the Western Ontario Osteoarthritis Shoulder (WOOS) index into Swedish and to test its validity, reliability, and responsiveness in patients with subacromial pain. Methods: The validity of the WOOS translation was tested in 54 patients who completed the WOOS and the Shoulder Rating Questionnaire, Swedish version (SRQs). Of these patients, 46 were retested to assess reliability. Responsiveness was evaluated in 29 subjects who completed the WOOS and SRQs before surgery and again at 3 months after surgery, when they also rated perceived change in shoulder function. The relationship between the questionnaires and patient-perceived improvement was assessed. Results: A high correlation was found between the Swedish version of WOOS and the SRQs. The correlations were similar in a group of working patients (r = -0.832) and in all patients (r = -0.843; P<.001). A high degree of agreement between WOOS at test and retest was also observed. A Bland-Altman plot showed a small mean difference and no trend across the range of WOOS values. A strong significant agreement was also shown by a kappa value of 0.649 (P<.001) and an intraclass correlation coefficient of 0.95 (95% confidence interval, 0.92-0.97, P<.001) as well as by a low difference between the test and retest means. Responsiveness, calculated by standardized response mean, was excellent (1.02). Conclusion: The results of the present study provide evidence that the Swedish version of WOOS is valid, reliable, and responsive in patients with subacromial pain and performs similarly to the original Canadian version. Level of evidence: Development or Validation of Outcomes Instruments Study. (C) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees.
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| 39. |
- Janols, Rebecka, et al.
(författare)
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Användarnas synpunkter på IT-lösningar i vården - Sammanfattande erfarenheter från utvärderingar vid Landstinget i Uppsala län (2008-2012)
- 2013
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det ständigt pågående IT-förändringsarbetet inom vården har potentialen att bidra till ökad vårdkvalitet, effektivitet, patientsäkerhet, patientservice och en förbättrad arbetsmiljö. Om man lyckas med detta är IT-investeringar nyttiga för vården, patienterna och landstinget. Idag finns emellertid en dålig kunskap om vilken nyttan är och det saknas modeller för att beräkna den. All erfarenhet från det hittills genomförda arbetet, liksom från mycket annan tidigare forskning, pekar på att det finns stora problem med utveckling och införande av IT i vården. Problemen består dels i att man inte förmår utnyttja den nyttopotential som finns, dels att såväl IT-system som förändringsprocesserna inte håller nog hög kvalitet, vilket resulterar i negativa reaktioner och effekter hos användarna, dvs. hos vårdpersonalen. Denna rapport presenterar en sammanfattning av användarnas synpunkter på IT lösningar i vården. Innehållet i rapporten är grundat i både kvalitativa och kvantitativa studier genomfört inom ramen for projektet IVAN. Projektet IVAN (Informationssystem i vården Användbarhet och Nytta) är ett samarbetsprojekt mellan Landstinget Uppsala Län (LUL) och forskare vid avdelningen for visuell information och interaktion, Institutionen för informationsteknologi vid Uppsala universitet. Projektet startade med en 6 månaders förstudie på Akademiska sjukhuset hösten 2008 och har mellan jan 2010- dec 2011 fungerat som ett Landstingsprojekt. Projektet var ett IVAN har till stor del fokuserat på kartläggningar och analyser av de system, processer och organisation som finns runt dagens IT-system. Bilden av de problem som finns idag, särskilt när det gäller vårdpersonalens upplevda situation, har klarnat. Många behov av förändringar och förbättringar har framkommit.
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| 40. |
- Janols, Rebecka, et al.
(författare)
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Evaluation of User Adoption during Three Module Deployments of Region-wide Electronic Patient Record Systems
- 2014
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Ingår i: International Journal of Medical Informatics. - : Elsevier BV. - 1386-5056 .- 1872-8243. ; 83:6, s. 438-449
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:In Sweden there are modular region-wide EPR systems that are implemented at various health organisations in the region. The market is dominated by four IT systems that have been procured and deployed in 18 out of 21 regions.METHODS:In a 2.5-year research study, deployments of three region-wide EPR modules: a patient administration system, eReferral module and eMedication module were followed and evaluated. Health professionals, EPR maintenance organisation, IT and health care managers were observed, interviewed and responded to questionnaires.RESULTS:Although the same deployment process was used during the three deployments, large variations in the units' adoptions were observed. The variations were due to: (1) expectation and attitude, (2) management and steering, (3) end-user involvement, (4) EPR learning, and (5) usability and the possibility of changing and improving the EPR.CONCLUSIONS:If changes in work processes are not considered in development and deployment, the potential benefits will not be achieved. It is therefore crucial that EPR deployment is conceived as organisational development. Users must be supported not just before and during the go-live phase, but also in the post-period. A problem often encountered is that it is difficult to make late changes in a region-wide EPR, and it is an open question whether it is possible to talk about a successful deployment if the usability of the introduced system is low.
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| 41. |
- Jeffries, R. D., et al.
(författare)
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The Gaia-ESO Survey: Kinematic structure in the Gamma Velorum cluster
- 2014
-
Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 563
-
Tidskriftsartikel (refereegranskat)abstract
- Context. A key science goal of the Gaia-ESO survey (GES) at the VLT is to use the kinematics of low-mass stars in young clusters and star forming regions to probe their dynamical histories and how they populate the field as they become unbound. The clustering of low-mass stars around the massive Wolf-Rayet binary system gamma(2) Velorum was one of the first GES targets. Aims. We empirically determine the radial velocity precision of GES data, construct a kinematically unbiased sample of cluster members and characterise their dynamical state. Methods. Targets were selected from colour-magnitude diagrams and intermediate resolution spectroscopy was used to derive radial velocities and assess membership from the strength of the Li I 6708 angstrom line. The radial velocity distribution was analysed using a maximum likelihood technique that accounts for unresolved binaries. Results. The GES radial velocity precision is about 0.25 km s(-1) and sufficient to resolve velocity structure in the low-mass population around gamma(2) Vel. The structure is well fitted by two kinematic components with roughly equal numbers of stars; the first has an intrinsic dispersion of 0.34 +/- 0.16 km s(-1), consistent with virial equilibrium. The second has a broader dispersion of 1.60 +/- 0.37 km s(-1) and is offset from the first by congruent to 2 kms(-1). The first population is older by 1-2 Myr based on a greater level of Li depletion seen among its M-type stars and is probably more centrally concentrated around gamma(2) Vel. Conclusions. We consider several formation scenarios, concluding that the two kinematic components are a bound remnant of the original, denser cluster that formed gamma(2) Vel, and a dispersed population from the wider Vela OB2 association, of which gamma(2) Vel is the most massive member. The apparent youth of gamma(2) Vel compared to the older (>= 10 Myr) low-mass population surrounding it suggests a scenario in which the massive binary formed in a clustered environment after the formation of the bulk of the low-mass stars.
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| 42. |
- Jofre, P., et al.
(författare)
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Gaia FGK benchmark stars : Metallicity
- 2014
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 564, s. A133-
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Tidskriftsartikel (refereegranskat)abstract
- Context. To calibrate automatic pipelines that determine atmospheric parameters of stars, one needs a sample of stars, or "benchmark stars", with well-defined parameters to be used as a reference. Aims. We provide detailed documentation of the iron abundance determination of the 34 FGK-type benchmark stars that are selected to be the pillars for calibration of the one billion Gaia stars. They cover a wide range of temperatures, surface gravities, and metallicities. Methods. Up to seven different methods were used to analyze an observed spectral library of high resolutions and high signal-to-noise ratios. The metallicity was determined by assuming a value of effective temperature and surface gravity obtained from fundamental relations; that is, these parameters were known a priori and independently from the spectra. Results. We present a set of metallicity values obtained in a homogeneous way for our sample of benchmark stars. In addition to this value, we provide detailed documentation of the associated uncertainties.Finally, we report a value of the metallicity of the cool giant psi Phe for the first time.
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| 43. |
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| 44. |
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| 45. |
- Kwan, Wanda, et al.
(författare)
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Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease.
- 2012
-
Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:1, s. 133-142
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is caused by an expanded polyglutamine tract in the protein huntingtin (htt). Although HD has historically been viewed as a brain-specific disease, htt is expressed ubiquitously, and recent studies indicate that mutant htt might cause changes to the immune system that could contribute to pathogenesis. Monocytes from HD patients and mouse models are hyperactive in response to stimulation, and increased levels of inflammatory cytokines and chemokines are found in pre-manifest patients that correlate with pathogenesis. In this study, wild-type (WT) bone marrow cells were transplanted into two lethally irradiated transgenic mouse models of HD that ubiquitously express full-length htt (YAC128 and BACHD mice). Bone marrow transplantation partially attenuated hypokinetic and motor deficits in HD mice. Increased levels of synapses in the cortex were found in HD mice that received bone marrow transplants. Importantly, serum levels of interleukin-6, interleukin-10, CXC chemokine ligand 1, and interferon-γ were significantly higher in HD than WT mice but were normalized in mice that received a bone marrow transplant. These results suggest that immune cell dysfunction might be an important modifier of pathogenesis in HD.
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| 46. |
- Lind, Mårten, et al.
(författare)
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A Picea abies Linkage Map Based on SNP Markers Identifies QTLs for Four Aspects of Resistance to Heterobasidion parviporum Infection
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7, s. e101049-
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Tidskriftsartikel (refereegranskat)abstract
- A consensus linkage map of Picea abies, an economically important conifer, was constructed based on the segregation of 686 SNP markers in a F-1 progeny population consisting of 247 individuals. The total length of 1889.2 cM covered 96.5% of the estimated genome length and comprised 12 large linkage groups, corresponding to the number of haploid P. abies chromosomes. The sizes of the groups (from 5.9 to 9.9% of the total map length) correlated well with previous estimates of chromosome sizes (from 5.8 to 10.8% of total genome size). Any locus in the genome has a 97% probability to be within 10 cM from a mapped marker, which makes the map suited for QTL mapping. Infecting the progeny trees with the root rot pathogen Heterobasidion parviporum allowed for mapping of four different resistance traits: lesion length at the inoculation site, fungal spread within the sapwood, exclusion of the pathogen from the host after initial infection, and ability to prevent the infection from establishing at all. These four traits were associated with two, four, four and three QTL regions respectively of which none overlapped between the traits. Each QTL explained between 4.6 and 10.1% of the respective traits phenotypic variation. Although the QTL regions contain many more genes than the ones represented by the SNP markers, at least four markers within the confidence intervals originated from genes with known function in conifer defence; a leucoanthocyanidine reductase, which has previously been shown to upregulate during H. parviporum infection, and three intermediates of the lignification process; a hydroxycinnamoyl CoA shikimate/quinate hydroxycinnamoyltransferase, a 4-coumarate CoA ligase, and a R2R3-MYB transcription factor.
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| 47. |
- Lind, Thomas, 1986-
(författare)
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Change and resistance to change in health care : Inertia in sociotechnical systems
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores change and resistance to change of IT systems in organisations from a sociotechnical perspective. The work is drawing on empirical data gathered during two Action Research projects in Swedish Health Care: one regarding the deployment of electronic patient record systems within health care organisations, and the other regarding the deployment of eHealth services geared towards patients and citizens. Resistance to change is classified as an indicator of social inertia, and the concept of counter-implementation, comprising three general strategies to obstruct change initiatives, is used to highlight the political aspects of social inertia. For the analysis, the concept of social inertia is used as a point of departure towards inertia in sociotechnical systems by applying values and principles from sociotechnical systems research, most prominently the interdependence-characteristic. This extended concept is used to show and discuss how IT systems can either enforce change or be a source of inertia preventing change in organisations, and such planned or inadvertent effects of implementing IT systems are discussed as a significant source of user resistance.
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| 48. |
- Lind, Thomas, et al.
(författare)
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Evaluation of the Uppsala University ROLE Prototype
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report presents an evaluation of a prototype of a personal learning environment, the ROLE prototype testbed at Uppsala University. The foci of the evaluation was the usability of the system and providing feedback to the ROLE project on the users’ impression of how well the system functioned as a personal learning environment. Two HCI researchers conducted the usability evaluation in the spring of 2012. The context of the evaluation was a course in Social Media and Web 2.0 at Uppsala University, and a survey was used for the assessment. The survey consisted of 28 questions and was answered by 16 of approximately 20 students attending the course (~80%). The report contains results from the analysis of data and some interesting results are that the students felt like they were part of a team while working with the system, and that the advanced inter-widget communication introduced in the system did not create conceptual difficulties for them. Furthermore, the best predictor for the value of the system seem to be how well it supports collaboration between peers. This implies that in online education it is important to focus on supporting collaboration.
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| 49. |
- Lind, Thomas, et al.
(författare)
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Förstudierapport : Införande av verksamhetsstödjande IT-system. Problem, effekter och nytta
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under hösten 2011 har en förstudie genomförts för att kartlägga och analysera dagens processer för utveckling, anskaffande, införande och utvärdering av administrativa IT-system vid Uppsala universitet (UU). Förstudien, Införande av verksamhetsstödjande IT-system. Problem, effekter och nytta, har genomförts av forskare vid avdelningen för människa-datorinteraktion (MDI) vid institutionen för informationsteknologi, UU. Förstudien har gjorts på uppdrag av universitetsdirektör Ann Fust och kontaktperson har varit Britta Nyberg, enheten för planering, uppföljning och stöd för verksamhetsutveckling.Arbetet har dels bestått av en kartläggning och analys av dagens utvecklings- och införandeprocesser och de problem man upplever i samband med dessa, dels några analyser av hur användare uppfattar de IT-system man idag har.Sammanfattningsvis har kartläggningen och analysen visat att det finns en stor förbättringspotential när det gäller processer för verksamhets- och IT-utveckling samt hur användbarhetsaspekter beaktas i utveckling, anskaffande, införande och utvärdering av IT-system. Kartläggningen av processer som används vid UU visar att det inte finns några enhetliga processer som används generellt inom UU, men att det lokalt finns fungerande sådana. Några exempel är förvaltningen som sedan några år arbetar enligt PM3, och avdelningen för IT och inköp som använder sig av ITIL. I de idag pågående IT-projekten varierar arbetssättet mycket. Det finns inga rekommenderade processer eller arbetssätt utan projektledaren lägger upp arbetet baserat på egna erfarenheter.Inom UU arbetar man generellt inte med användarcentrerade processer, och användbarhetsaspekter är inte prioriterade. Inom vissa projekt och i viss förvaltning förekommer en del arbete med fokus på användbarhet. Referensgrupper används som en form av användarmedverkan, men med olika mål och syften. Införandeprocesser upplevs generellt som problematiska inom UU och här finns påtagliga problem. Den upplevda användbarheten i de administrativa IT-systemen varierar, men generellt anser förstudiens intervjupersoner att det finns stor förbättringspotential.Fallstudien av Raindanceportalen visar att olika användargrupper upplever systemet på helt olika sätt. De som har utbildning i Raindance (ekonomiadministratörer) och använder det i sina kärnuppgifter upplever att systemet i ganska stor utsträckning stöder arbetet. Övriga användare som använder systemet mer sällan och som administrativt stödsystem har klart större problem med systemet.I en avslutande diskussion ger vi en sammanställning av de observerade problemen, ger förslag på vad som fordras för att utveckla kunskaper kring problem och möjligheter och för att införa förbättrade processer, samt för att på sikt få bättre och effektivare administrativa IT-system inom UU.
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| 50. |
- Lind, Thomas, et al.
(författare)
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Införandet av Raindance Bokföringsportal vid Uppsala universitet - En kortfattad rapport från KiA-projektet
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under senvåren och hösten 2013 genomfördes en studie för att dra lärdomar av införandet som skedde inför årsskiftet 2012-2013 utav Bokföringsportalen, en del av ekonomisystemet Raindance vid Uppsala universitet. Utöver Bokföringsportalen har studien även berört frågor om införande av IT kopplat till avdelningen för ekonomi och upphandling mer generellt. Studien har utförts inom ramen för KiA-projektet och baseras på fyra intervjuer med personal vid universitetsförvaltningens avdelning för ekonomi och upphandling samt sex intervjuer med ekonomiadministratörer från olika institutioner vid universitetet. Intervjuerna visar på ett brett spektra av uppfattningar och inställningar till införandet av Bokföringsportalen, där vissa anser att hela deras arbetssituation har förändrats medan andra ser förändringen som knappt märkbar. Synen på förändringen som positiv eller negativ varierar också bland respondenterna. Vitt skilda förhållanden i organisationen av ekonomiadministratörernas roller och arbetsuppgifter, samt faktorer rörande institutionerna i övrigt, bidrar till att skapa väldigt olika förutsättningar vid förändring av IT som påverkar administratörernas arbetsmiljö.
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