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- Kaptoge, S., et al.
(author)
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C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction
- 2012
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:14, s. 1310-1320
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Journal article (peer-reviewed)abstract
- Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P < 0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (< 10%), " intermediate" (10% to < 20%), and "high" (>= 20%) (P < 0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of >= 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)
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| 2. |
- Lomnytska, M. I., et al.
(author)
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Impact of genomic stability on protein expression in endometrioid endometrial cancer
- 2012
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106:7, s. 1297-1305
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established.METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry.RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70.CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.
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| 3. |
- Mitrovic, I. Z., et al.
(author)
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On the nature of the interfacial layer in ultra-thin TiN/LaluO3 gate stacks
- 2012
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 112:4, s. 044102-
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Journal article (peer-reviewed)abstract
- We present a detailed investigation on the nature of the interfacial layer (IL) in ultra-thin TiN/LaLuO3 (LLO) gate stacks, which is of importance to facilitate CMOS scaling. The molecular beam deposited LaLuO3 films are found to be amorphous by high-resolution transmission electron microscopy. A similar to 9 angstrom thick LaLuO3/interlayer transition observed by medium energy ion scattering correlates with the presence of a dual silicate/SiO2-like interfacial layer derived from the analysis of photoelectron line positions and electron energy loss spectra. A theoretical model is used for the dielectric transition in a bi-layer LaLuO3/IL structure, linking physical and electrical characterization data. The obtained leakage current of 10(-3) A/cm(2) at 1.5 V and equivalent oxide thickness of 0.75 nm for TiN/LaLuO3 gate stacks are adequate for scaling in the 14-12 nm node.
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| 4. |
- van der Harst, Pim, et al.
(author)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Journal article (peer-reviewed)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 7. |
- Engström, David, 1976, et al.
(author)
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Three-dimensional imaging of liquid crystal structures and defects by means of holographic manipulation of colloidal nanowires with faceted sidewalls
- 2011
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In: Soft Matter. ; 7, s. 6304-6312
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Journal article (peer-reviewed)abstract
- We use nanowires with faceted sidewalls for mapping of the patterns of three-dimensional orientational order and defect structures. In chiral nematics, the nanowires follow the local average orientation of rod-shaped molecules. When spatially translated by use of holographic optical tweezers in three dimensions, they mediate direct nondestructive visualization of the helicoidal ground-state structures, edge and screw dislocations, and kinks, as well as enable non-contact manipulation of these defects. We probe interactions of faceted nanowires with different defects and demonstrate their spontaneous self-alignment along the cores of singular defect lines.
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| 8. |
- Engström, David, 1976, et al.
(author)
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Unconventional structure-assisted optical manipulation of high-index nanowires in liquid crystals
- 2012
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In: Optics Express. - 1094-4087. ; 20:7, s. 7741-7748
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Journal article (peer-reviewed)abstract
- Stable optical trapping and manipulation of high-index particles in low-index host media is often impossible due to the dominance of scattering forces over gradient forces. Here we explore optical manipulation in liquid crystalline structured hosts and show that robust optical manipulation of high-index particles, such as GaN nanowires, is enabled by laser-induced distortions in long-range molecular alignment, via coupling of translational and rotational motions due to helicoidal molecular arrangement, or due to elastic repulsive interactions with confining substrates. Anisotropy of the viscoelastic liquid crystal medium and particle shape give rise to a number of robust unconventional trapping capabilities, which we use to characterize defect structures and study rheological properties of various thermotropic liquid crystals.
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