| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Gutierrez-Suarez, R., et al.
(författare)
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Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO multinational quality of life cohort study
- 2007
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Ingår i: Rheumatology (Oxford). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 46:2, s. 314-320
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare health-related quality of life (HRQL) and to identify clinical determinants for poor HRQL of patients with juvenile idiopathic arthritis (JIA) coming from three geographic areas.METHODS: The HRQL was assessed through the Child Health Questionnaire (CHQ). A total of 30 countries were included grouped in three geographic areas: 16 countries in Western Europe; 10 in Eastern Europe; and four in Latin America. Potential determinants of poor HRQL included demographic data, physician's and parent's global assessments, measures of joint inflammation, disability as measured by Childhood Health Assessment Questionnaire (CHAQ) and erythrocyte sedimentation rate. Poor HRQL was defined as a CHQ physical summary score (PhS) or psychosocial summary score (PsS) <2 S.D. from that of healthy children.RESULTS: A total of 3167 patients with JIA, younger than 18 yrs, were included in this study. The most affected health concepts (<2 S.D. from healthy children) that differentiate the three geographic areas include physical functioning, bodily pain/discomfort, global health, general health perception, change in health with respect to the previous year, self-esteem and family cohesion. Determinants for poor HRQL were similar across geographic areas with physical well-being mostly affected by the level of disability while the psychosocial well-being by the intensity of pain.CONCLUSION: We found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin.
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| 3. |
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| 4. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 5. |
- Miller, M R, et al.
(författare)
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General considerations for lung function testing.
- 2005
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 0903-1936. ; 26:1, s. 153-61
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Miller, M R, et al.
(författare)
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Standardisation of spirometry.
- 2005
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 0903-1936. ; 26:2, s. 319-38
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Pellegrino, R, et al.
(författare)
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Definition of COPD: based on evidence or opinion?
- 2008
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003. ; 31:3, s. 681-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Pellegrino, R, et al.
(författare)
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Interpretative strategies for lung function tests.
- 2005
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 0903-1936. ; 26:5, s. 948-68
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Power, Deborah M, et al.
(författare)
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The molecular and endocrine basis of flatfish metamorphosis
- 2008
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Ingår i: Reviews in Fisheries Science. - : Informa UK Limited. - 1064-1262 .- 1547-6553. ; 16:S1, s. 93-109
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Tidskriftsartikel (refereegranskat)abstract
- A significant component of aquaculture is the production of good quality larvae, and, in the case of flatfish, this is tied up with the change from a symmetric larva to an asymmetric juvenile. Despite the pioneering work carried out on the metamorphosis of the Japanese flounder (Paralichthys olivaceus) and summer flounder (Paralichthys dentatus), the underlying molecular basis of flatfish metamorphosis is still relatively poorly characterized. It is a thyroid hormone (TH) driven process, and the role of other hormones in the regulation of the process along with the interplay of abiotic factors are still relatively poorly characterized as is the extent of tissue and organ remodeling, which underlie the profound structural and functional modifications that accompany the larval/juvenile transition. The isolation of genes for hormones, receptors, binding proteins, and other accessory factors has provided powerful tools with which to pursue this question. The application of molecular methodologies such as candidate gene approaches and microarray analysis coupled to functional genomics has started to contribute to understanding the complexity of tissue and organ modifications that accompany flatfish metamorphosis. A better understanding of the biology of normal metamorphosis is essential to identify factors contributing to abnormal metamorphosis.
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| 10. |
- Ruperto, N., et al.
(författare)
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The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus : prospective validation of the definition of improvement
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 55:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.RESULTS: The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.CONCLUSION: PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.
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| 11. |
- Wanger, J, et al.
(författare)
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Standardisation of the measurement of lung volumes.
- 2005
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 0903-1936. ; 26:3, s. 511-22
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Tidskriftsartikel (refereegranskat)
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