| 1. |
- Jallow, Muminatou, et al.
(författare)
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Genome-wide and fine-resolution association analysis of malaria in West Africa.
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
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| 2. |
- Prokopenko, Inga, et al.
(författare)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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| 3. |
- Lynch, Sean R., et al.
(författare)
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A comparison of physical properties, screening procedures and a human efficacy trial for predicting the bioavailability of commercial elemental iron powders used for food fortification
- 2007
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Ingår i: INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH. - : Hogrefe Publishing Group. - 0300-9831 .- 1664-2821. ; 77:2, s. 107-124
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Tidskriftsartikel (refereegranskat)abstract
- Elemental iron powders are widely used to fortify staple foods. Experimental evidence indicates that there is considerable variation in the bioavailability of different products. For some powders, it may be too low to permit a significant impact on iron status. This study was designed to evaluate possible approaches to screening commercial iron powders for predicted bioavailability, to identify products that have the potential to improve iron status, and to ascertain whether bioavailability is related to the method of manufacture. Nine commercial iron powders were allocated to one of five types based on the production process; carbonyl, electrolytic, hydrogen-reduced (H-reduced), carbon monoxide-reduced (CO-reduced), and other reduced. Structure by scanning electron microscopy and physical properties (pycnometric and apparent density, particle size distribution, Fisher subsieve size, and surface area) were determined on all samples. Selected samples (one or more of each type depending on the cost of the assay) were then subjected to five screening procedures that have previously been advocated for predicting bioavailability in humans - dissolution rate in 0.1 mol/L HCl, dialyzability and Caco-2 cell iron uptake, both after simulated in vitro gastrointestinal digestion, relative bioavailability (RBV) with respect to ferrous sulfate by the AOAC rat hemoglobin repletion method, and plasma iron tolerance tests in human volunteers. The results for particle size distribution, surface area, Fisher subsieve size, dissolution rate in 0.1 mol/L HCl, and RBV in rats were significantly correlated and consistent for powders of the same type. However, values for different powder types were significantly different. There was no correlation between either dialyzability or Caco-2 cell uptake and the predicted bioavailability estimates based on the physical properties, dissolution rates, RBV in rats, or human efficacy data. Although human plasma iron tolerance tests were in general agreement with the other measures of predicted bioavailability, they did not provide information that would have improved the precision of bioavailability estimates based on physical properties, dissolution in HCl and/or RBV in rats. Our observations indicate that the dissolution rate in 0.1 mol/L HCl under standardized conditions is highly predictive of potential bioavailability and that it would be the most practical approach to developing a reliable and sensitive screening procedure for predicting and monitoring the bioavailability of commercial elemental iron powder products. Some, but not all, of the carbonyl and electrolytic iron powders had the highest predicted bioavailability values. The predicted bioavailability for the reduced iron products was lower and variable, with the lowest values being recorded for the carbon monoxide and other reduced iron products. Two powder types were selected for a human efficacy trial, electrolytic (because it is the iron powder type recommended by WHO) and hydrogen-reduced (because of its widespread use). Electrolytic/A131 and H-reduced/AC-325 had relative efficacies compared with ferrous sulfate monohydrate of 77% and 49%, respectively, based on the change in body iron stores in Thai women with low iron stores, who received an additional 12 mg iron per day, six days per week for 35 weeks in wheat-based snacks. We conclude that there is significant variability in the bioavailability of the commercial iron powders that we evaluated (those used for food fortification at the time that our studies were initiated), and that bioavailability is related in part to production method. The bioavailability of some carbonyl and electrolytic iron powders may be adequate for effective food fortification. The reduced iron powders that we tested are unlikely to have an adequate impact on iron nutrition at the fortification levels currently employed, although preliminary analysis of a new H-reduced product indicates that it may be possible to improve the bioavailability of individual powders of this type of product. We did find significant differences among products in both the electrolytic and carbonyl categories. Therefore, all products should be screened rigorously.
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| 4. |
- Dance, D, et al.
(författare)
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Breast dosimetry using high-resolution voxel phantoms
- 2005
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 359-363
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Tidskriftsartikel (refereegranskat)abstract
- A computer model of X-ray mammography has been developed, which uses quasi-realistic high-resolution voxel phantoms to simulate the breast. The phantoms have 400 μm voxels and simulate the three-dimensional distributions of adipose and fibroglandular tissues, Cooper's ligaments, ducts and skin and allow the estimation of dose to individual tissues. Calculations of the incident air kerma to mean glandular dose conversion factor, g, were made using a Mo/Mo spectrum at 28 kV for eight phantoms in the thickness range 40-80 mm and of varying glandularity. The values differed from standard tabulations used for breast dosimetry by up to 43%, because of the different spatial distribution of glandular tissue within the breast. To study this further, additional voxel phantoms were constructed, which gave variations of between 9 and 59% compared with standard values. For accurate breast dosimetry, it is therefore very important to take the distribution of glandular tissues into account. © The Author 2005. Published by Oxford University Press. All rights reserved.
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| 5. |
- Hunt, R, et al.
(författare)
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Calculation of the properties of digital mammograms using a computer simulation
- 2005
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 395-398
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Tidskriftsartikel (refereegranskat)abstract
- A Mote Carlo computer model of mammography has been developed to study and optimise the performance of digital mammographic systems. The program uses high-resolution voxel phantoms to model the breast, which simulate the adipose and fibroglandular tissues, Cooper's ligaments, ducts and skin in three dimensions. The model calculates the dose to each tissue, and also the quantities such as energy imparted to image pixels, noise per image pixel and scatter-to-primary (S/P) ratios. It allows studies of the dependence of image properties on breast structure and on position within the image. The program has been calibrated by calculating and measuring the pixel values and noise for a digital mammographic system. The thicknesses of two components of this system were unknown, and were adjusted to obtain a good agreement between measurement and calculation. The utility of the program is demonstrated with the calculations of the variation of the S/P ratio with and without a grid, and of the image contrast across the image of a 50-mm-thick breast phantom. © The Author 2005. Published by Oxford University Press. All rights reserved.
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| 6. |
- Hunt, R, et al.
(författare)
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Monte Carlo simulation of a mammographic test phantom
- 2005
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 432-435
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Tidskriftsartikel (refereegranskat)abstract
- A test phantom, including a wide range of mammographic tissue equivalent materials and test details, was imaged on a digital mammographic system. In order to quantify the effect of scatter on the contrast obtained for the test details, calculations of the scatter-to-primary ratio (S/P) have been made using a Monte Carlo simulation of the digital mammographic imaging chain, grid and test phantom. The results show that the S/P values corresponding to the imaging conditions used were in the range 0.084-0.126. Calculated and measured pixel values in different regions of the image were compared as a validation of the model and showed excellent agreement. The results indicate the potential of Monte Carlo methods in the image quality-patient dose process optimisation, especially in the assessment of imaging conditions not available on standard mammographic units. © The Author 2005. Published by Oxford University Press. All rights reserved.
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| 7. |
- Loos, Ruth J. F., et al.
(författare)
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Common variants near MC4R are associated with fat mass, weight and risk of obesity
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
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Tidskriftsartikel (refereegranskat)abstract
- To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
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| 8. |
- Macovez, Roberto, et al.
(författare)
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Metal-to-insulator transition in thin-film polymeric AC(60)
- 2009
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 11, s. 023035-
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Tidskriftsartikel (refereegranskat)abstract
- We present an electron spectroscopy study of phase-pure AC(60) thin films (A = Rb, Cs) in their monomer (face-centred cubic (fcc)) and polymer phases. A surface electronic reconstruction is observed in polymeric RbC60, analogous to that reported for the fcc phase. As for pristine C-60, the occupied electronic states of AC(60) fullerides are not dramatically affected by polymerization. The energy separation between the leading feature in photoemission and inverse photoemission is similar in both stable AC(60) phases. These observations suggest that electron correlation effects are similar in the two phases, and that their different electronic behaviour is mainly related to the reduction of degeneracy of the polymer frontier states. Photoemission and electron-energy loss spectroscopy data show that the thin-film form of the RbC60 polymer is metallic at room temperature, and that it undergoes a metal-insulator transition at around 100 K. This transition temperature is much higher than that reported for the corresponding bulk phase and signals a poorer screening of Coulomb interactions at the film surface.
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| 9. |
- Ullman, Gustaf, et al.
(författare)
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Distributions of scatter to primary ratios and signal to noise ratios per pixel in digital chest imaging
- 2005
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 355-358
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to calculate distributions of scatter-to-primary ratios (s/p) and signal-to-noise ratios per pixel (SNRp) in chest images. Such distributions may provide useful information on how physical image quality (contrast, SNR) is distributed over the posterior/anterior (PA) chest image. A Monte Carlo computer program was used for the calculations, including a model of both the patient (voxel phantom) and the imaging system (X-ray tube, anti-scatter grid and image detector). The calculations were performed for three PA thicknesses 20, 24 and 28 cm. For a 24 cm patient, the s/p varies between 0.5 in the lung to 2.5 behind the spine and heart. The corresponding variation of the SNRp is a factor of 3, with the highest values in the lung. Increasing the patient thickness from 20 to 28 cm increases the s/p by a factor of 2.2 behind the spine and heart.
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| 10. |
- Ullman, Gustaf, 1977-, et al.
(författare)
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The influence of patient thickness and imaging system on patient dose and physical image quality in digital chest imaging
- 2005
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 294-297
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to study the influence of patient thickness, tube voltage and image detector on patient dose, contrast and ideal observer signal-to-noise ratio (SNRI), for pathological details positioned at different regions in the image in posterior-anterior (PA) chest radiology. A Monte Carlo computational model was used to compute measures of physical image quality (contrast, SNRI) and patient effective dose, E. Two metastasis-like details positioned in the central right lung and right lung near the spine, respectively, were studied. The tube voltage was varied between 100 and 150 kV and the patient thickness between 20 and 28 cm. Both, a computed radiography (CR) system and a direct radiography (DR) system, were investigated. The DR system provides both lower doses and better image quality compared with the CR system. The SNRI2/E is ∼2.9 times higher for the DR system compared with the CR system. © The Author 2005. Published by Oxford University Press. All rights reserved.
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