| 1. |
- Brehony, Carina, et al.
(författare)
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Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development
- 2014
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Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:6, s. 847-853
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Tidskriftsartikel (refereegranskat)abstract
- New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
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| 2. |
- Burr, H., et al.
(författare)
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The demand–control model as a predictor of depressive symptoms—interaction and differential subscale effects : Prospective analyses of 2212 German employees
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:16
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Tidskriftsartikel (refereegranskat)abstract
- Testing assumptions of the widely used demand–control (DC) model in occupational psychosocial epidemiology, we investigated (a) interaction, i.e., whether the combined effect of low job control and high psychological demands on depressive symptoms was stronger than the sum of their single effects (i.e., superadditivity) and (b) whether subscales of psychological demands and job control had similar associations with depressive symptoms. Logistic longitudinal regression analyses of the 5-year cohort of the German Study of Mental Health at Work (S-MGA) 2011/12–2017 of 2212 employees were conducted. The observed combined effect of low job control and high psychological demands on depressive symptoms did not indicate interaction (RERI = −0.26, 95% CI = −0.91; 0.40). When dichotomizing subscales at the median, differential effects of subscales were not found. When dividing subscales into categories based on value ranges, differential effects for job control subscales (namely, decision authority and skill discretion) were found (p = 0.04). This study does not support all assumptions of the DC model: (1) it corroborates previous studies not finding an interaction of psychological demands and job control; and (2) signs of differential subscale effects were found regarding job control. Too few prospective studies have been carried out regarding differential subscale effects.
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| 3. |
- Gylvin, T., et al.
(författare)
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Functional SOCS1 polymorphisms are associated with variation in obesity in whites
- 2009
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:3, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- The suppressor of cytokine signalling 1 (SOCS1) is a natural inhibitor of cytokine and insulin signalling pathways and may also play a role in obesity. In addition, SOCS1 is considered a candidate gene in the pathogenesis of both type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective was to perform mutation analysis of SOCS1 and to test the identified variations for association to T2D-related quantitative traits, T2D or T1D. Mutation scanning was performed by direct sequencing in 27 white Danish subjects. Genotyping was carried out by TaqMan allelic discrimination. A total of more than 8100 individuals were genotyped. Eight variations were identified in the 5' untranslated region (UTR) region. Two of these had allele frequencies below 1% and were not further examined. The six other variants were analysed in groups of T1D families (n = 1461 subjects) and T2D patients (n = 1430), glucose tolerant first-degree relatives of T2D patients (n = 212) and normal glucose tolerant (NGT) subjects. The rs33977706 polymorphism (-820G > T) was associated with a lower body mass index (BMI) (p = 0.004). In a second study (n = 4625 NGT subjects), significant associations of both the rs33977706 and the rs243330 (-1656G > A) variants to obesity were found (p = 0.047 and p = 0.015) respectively. The rs33977706 affected both binding of a nuclear protein to and the transcriptional activity of the SOCS1 promoter, indicating a relationship between this polymorphism and gene regulation. This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Abramovitz, T, et al.
(författare)
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MONA LISA : Deep seismic investigations of the lithosphere in the southeastern North Sea
- 1997
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Ingår i: TECTONOPHYSICS. - : ELSEVIER SCIENCE BV. - 0040-1951. ; 269:1-2, s. 1-19
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The MONA LISA collaborative project has collected 1112 km of seismic normal-incidence reflection data (recorded to 26 s) and wide-angle data from 26 onshore and 2 offshore locations along 4 profiles in the southeastern North Sea. The seismic data clearly
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| 8. |
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| 9. |
- Berthelsen, A., et al.
(författare)
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Recording marine airgun shots at offsets between 300 and 700 km
- 1991
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 18:4, s. 645-648
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates that - under favorable conditions - by using multichannel recording and subsequent stacking of adjacent records marine airgun shots have been detected at offset distances up to 700 km, the maximum offset at which the authors attempted to record data.^Besides a powerful airgun array, a low noise environment at the recording site and the elimination of static shifts are the prerequisites to obtain refracted and reflected arrivals from the crust and upper mantle at such large offsets.^Primary arrivals detected at offsets between 400 and 700 km image the upper mantle from 70 to about 120 km depth.^Stacking of neighboring shots and/or receivers successfully increases the signal-to-noise ratio, if the traces have been corrected for offset differences, which requires knowledge of the apparent phase velocities.^The data presented here were collected in autumn 1989 during the BABEL Project on the Baltic Shield.
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| 10. |
- England, RW, et al.
(författare)
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Closure of the Tornquist sea: Constraints from MONA LISA deep seismic reflection data
- 1997
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Ingår i: GEOLOGY. - : GEOLOGICAL SOC AMERICA. - 0091-7613. ; 25:12, s. 1071-1074
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Deep seismic reflection profiles west of Denmark across the suture between Baltica and Eastern Avalonia reveal weak, southward-dipping reflectors within the crystalline basement. These reflectors are interpreted as thrusts resulting from emplacement of Ea
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| 11. |
- Fjeldsoe-Nielsen, H, et al.
(författare)
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Phenotypic and genotypic characterization of prolyliminopeptidase-negative Neisseria gonorrhoeae isolates in Denmark.
- 2005
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 24:4, s. 280-283
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Tidskriftsartikel (refereegranskat)abstract
- In the study presented here 26 recent Danish clinical isolates of prolyliminopeptidase (PIP)-negative Neisseria gonorrhoeae were phenotypically and genotypically characterized to investigate whether one or more PIP-negative strains are circulating in the Danish community. The profiles of these isolates were compared with those of three isolates from a recent outbreak of PIP-negative N. gonorrhoeae infection in the UK. Twenty-five of the Danish isolates and all three UK isolates had similar antibiograms and were designated serovar IB-4. Genotypic characterization by pulsed-field gel electrophoresis, porB1b gene sequencing, and opa-typing revealed that these isolates were indistinguishable or closely related. The results indicate that at least one PIP-negative N. gonorrhoeae strain is currently circulating in the Danish community, and this strain is indistinguishable from the one that caused an outbreak in the UK.
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| 12. |
- Hempel, Nele-Johanna, et al.
(författare)
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The Effect of the Molecular Weight of Polyvinylpyrrolidone and the Model Drug on Laser-Induced In Situ Amorphization
- 2021
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 26:13
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Tidskriftsartikel (refereegranskat)abstract
- Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (T-g) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (M-w) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug. Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different M-w of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer M-w on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant. In perfect correlation to the Noyes-Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest M-w (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.
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| 13. |
- Hempel, Nele-Johanna, et al.
(författare)
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The Influence of Drug-Polymer Solubility on Laser-Induced In Situ Drug Amorphization Using Photothermal Plasmonic Nanoparticles
- 2021
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- In this study, laser-induced in situ amorphization (i.e., amorphization inside the final dosage form) of the model drug celecoxib (CCX) with six different polymers was investigated. The drug-polymer combinations were studied with regard to the influence of (i) the physicochemical properties of the polymer, e.g., the glass transition temperature (T-g) and (ii) the drug-polymer solubility on the rate and degree of in situ drug amorphization. Compacts were prepared containing 30 wt% CCX, 69.25 wt% polymer, 0.5 wt% lubricant, and 0.25 wt% plasmonic nanoparticles (PNs) and exposed to near-infrared laser radiation. Upon exposure to laser radiation, the PNs generated heat, which allowed drug dissolution into the polymer at temperatures above its T-g, yielding an amorphous solid dispersion. It was found that in situ drug amorphization was possible for drug-polymer combinations, where the temperature reached during exposure to laser radiation was above the onset temperature for a dissolution process of the drug into the polymer, i.e., T-DStart. The findings of this study showed that the concept of laser-induced in situ drug amorphization is applicable to a range of polymers if the drug is soluble in the polymer and temperatures during the process are above T-DStart.
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| 14. |
- Hempel, Nele-Johanna, et al.
(författare)
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Utilizing Laser Activation of Photothermal Plasmonic Nanoparticles to Induce On-Demand Drug Amorphization inside a Tablet
- 2021
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 18:6, s. 2254-2262
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Tidskriftsartikel (refereegranskat)abstract
- Poor aqueous drug solubility represents a major challenge in oral drug delivery. A novel approach to overcome this challenge is drug amorphization inside a tablet, that is, on-demand drug amorphization. The amorphous form is a thermodynamically instable, disordered solid-state with increased dissolution rate and solubility compared to its crystalline counterpart. During on-demand drug amorphization, the drug molecularly disperses into a polymer to form an amorphous solid at elevated temperatures inside a tablet. This study investigates, for the first time, the utilization of photothermal plasmonic nanoparticles for on-demand drug amorphization as a new pharmaceutical application. For this, near-IR photothermal plasmonic nanoparticles were tableted together with a crystalline drug (celecoxib) and a polymer (polyvinylpyrrolidone). The tablets were subjected to a near-IR laser at different intensities and durations to study the rate of drug amorphization under each condition. During laser irradiation, the plasmonic nanoparticles homogeneously heated the tablet. The temperature was directly related to the rate and degree of amorphization. Exposure times as low as 180 s at 1.12 W cm(-2) laser intensity with only 0.25 wt % plasmonic nanoparticles and up to 50 wt % drug load resulted in complete drug amorphization. Therefore, near-IR photothermal plasmonic nanoparticles are promising excipients for on-demand drug amorphization with laser irradiation.
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| 15. |
- Hobbs, R. W., et al.
(författare)
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Integrated seismic studies of the Baltic shield using data in the Gulf of Bothnia region
- 1993
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Ingår i: Geophysical Journal International. - 0956-540X .- 1365-246X. ; 112:3, s. 305-324
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Tidskriftsartikel (refereegranskat)abstract
- In the autumn of 1989 a co-operative experiment involving 12 research institutions in northwestern Europe collected 2268 km of deep seismic reflection profiles in the Gulf of Bothnia and the Baltic Sea. the 121 litre airgun array used for this profiling was also recorded by 62 muiticomponent land stations to provide coincident refraction surveys, fan-spreads, and 3-D seismic coverage of much of the Gulf of Bothnia. We thus have potentially both high-resolution impedance contrast images as well as more regional 3-D velocity models in both P- and S-waves. In the Bothnian Bay a south-dipping, non-reflective zone coincides with the conductive Archaean-Proterozoic boundary onshore in Finland. Between the Bothnian Bay and Bothnian Sea observed reflectivity geometries and velocity models at Moho depths suggest structures inherited from a 1.9Ga subduction zone; the upper crust here appears to have anomalously low velocity. Within the Bothnian Sea, reflectivity varies considerably beneath the metasedimentary/granitoid rocks of the Central Svecofennian Province (CSP) and the surrounding metavolcanic-arc rocks. Numerous dipping reflectors appear throughout the metavolcanic crust, whereas the CSP has little reflectivity. Wide-angle reflections indicate that the metasedimentary crust of the Bothnian Basin is 10 km thicker than the neighbouring Svecofennian subprovinces. Near the Åland archipelago Rapakivi granite plutons exhibit bright reflections, a contrast to the usual non-reflective plutons elsewhere in western Europe. Additional dipping reflections deep in the crust of this area may support models of rifting and crustal thinning during emplacement of the 1.70-1.54 Ga Rapakivi granites. Coeval gabbroic/anorthositic magmatism may explain the high reflectivity and high velocity of these plutons. the c. 1.25 Ga mafic sills and feeder dykes of the Central Scandinavian Dolerite Group also produce clear reflections on both near- and far-offset seismic sections. Continued modelling will produce better velocity models of the crust and better constrained contour maps of crustal thickness in this part of the Baltic shield.
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| 16. |
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| 19. |
- Öhlander, Björn, et al.
(författare)
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Delineation and character of the Archaean-Proterozoic boundary in northern Sweden
- 1993
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Ingår i: Precambrian Research. - 0301-9268 .- 1872-7433. ; 64:1-4, s. 67-84
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Tidskriftsartikel (refereegranskat)abstract
- Before the deposition of a Proterozoic cover and the repeated Proterozoic reworking of the older rocks, the presently exposed Archaean areas in northern Sweden formed part of a coherent craton. In the present study, we have used Sm---Nd isotopic analyses of Proterozoic granitoids and metavolcanics to delineate the Archaean palaeoboundary. In a regional context, the transition from strongly negative εNd(t) values in the northeast to positive values in the southwest is distinct, and approximately defines the border of the old craton. The Archaean palaeoboundary extends in a WNW direction, and is subparallel to the longitudinal axis of the Skellefte sulphide ore district but it is situated ≈ 100 km farther to the north. The ≈ 1.9 Ga old granitoids on the two sides of the palaeoboundary were all formed in compressional environments, but those situated to the north have higher contents of LILE and LREE at similar contents of Si. This indicates that they were generated in an area with thicker crust and supports the location of the Archaean-Proterozoic palaeoboundary. There is no simple correlation between the Archaean palaeoboundary, as defined by the isotopic results, and any of the major fracture systems as interpreted from regional geophysical measurements. Reflection seismic work indicates that juvenile volcanic-arc terrains to the south have been thrust onto the Archaean craton. Possible thrust faults have been identified from aeromagnetic measurements. Rifting of the Archaean craton created a passive margin ≈ 2.0 Ga ago. Spreading shifted to convergence with subduction beneath the Archaean continent ≈ 1.9 Ga ago. Subsequently, the resulting juvenile volcanic arc collided with the old continent, and the Archaean palaeoboundary as existing today was formed by a collision characterized by overthrusting. The boundary then was disturbed by later deformation predominantly along NNE-trending fracture systems.
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