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Sökning: WFRF:(Ng Siew C.)

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  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • 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.
  • King, James A., et al. (författare)
  • Incidence of Celiac Disease Is Increasing Over Time : A Systematic Review and Meta-analysis
  • 2020
  • Ingår i: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 115:4, s. 507-525
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVES: To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends.METHODS: MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time.RESULTS: Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I-2= 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I-2= 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I-2= 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I-2= 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I-2= 79.6%) per year over the past several decades.DISCUSSION: Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.
  • King, James A., et al. (författare)
  • Trends in hospitalisation rates for inflammatory bowel disease in western versus newly industrialised countries : a population-based study of countries in the Organisation for Economic Co-operation and Development
  • 2019
  • Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 4:4, s. 287-295
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hospitalisation rates for inflammatory bowel disease (IBD) vary across the world. We aimed to investigate temporal patterns of hospitalisation for IBD in member countries of the Organisation for Economic Co-operation and Development (OECD).Methods: From the OECD database, we assessed IBD-related hospitalisation rates (expressed as annual rates per 100 000 inhabitants) for 34 countries from 1990 to 2016. We calculated mean hospitalisation rates for the period 2010-15 and used joinpoint regression models to calculate average annual percentage changes with 95% CIs.Findings: Mean hospitalisation rates for IBD from 2010 to 2015 were highest in North America (eg, 33.9 per 100 000 in the USA), Europe (eg, 72.9 per 100 000 in Austria), and Oceania (eg, 31.5 per 100 000 in Australia). Hospitalisation rates for IBD were stabilising or decreasing over time in many countries in these regions but increasing in others. Countries in Asia and Latin America and the Caribbean had the lowest IBD-related hospitalisation rates but the greatest increases in rates over time. For example, Turkey had an annual hospitalisation rate of 10.8 per 100 000 inhabitants and an average annual percentage change of 10.4% (95% CI 5.2-15.9). Similarly, Chile had an annual hospitalisation rate of 9.0 per 100 000 inhabitants and an average annual percentage change of 5.9% (4.9-7.0).Interpretation: Hospitalisation rates for IBD are high in western countries but are typically stabilising or decreasing, whereas rates in many newly industrialised countries are rapidly increasing, which reflects the known increase in IBD prevalence in these countries. Potential explanations for these trends include changes in the epidemiology of IBD, health-care delivery, and infrastructure in these countries, as well as overall country-specific patterns in hospitalisations and differences between countries in data collection methods.
  • Ng, Siew C., et al. (författare)
  • Geographical variability and environmental risk factors in inflammatory bowel disease
  • 2013
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 62:4, s. 630-649
  • Tidskriftsartikel (refereegranskat)abstract
    • The changing epidemiology of inflammatory bowel disease (IBD) across time and geography suggests that environmental factors play a major role in modifying disease expression. Disease emergence in developing nations suggests that epidemiological evolution is related to westernisation of lifestyle and industrialisation. The strongest environmental associations identified are cigarette smoking and appendectomy, although neither alone explains the variation in incidence of IBD worldwide. Urbanisation of societies, associated with changes in diet, antibiotic use, hygiene status, microbial exposures and pollution have been implicated as potential environmental risk factors for IBD. Changes in socioeconomic status might occur differently in different geographical areas and populations and, consequently, it is important to consider the heterogeneity of risk factors applicable to the individual patient. Environmental risk factors of individual, familial, community-based, country-based and regionally based origin may all contribute to the pathogenesis of IBD. The geographical variation of IBD provides clues for researchers to investigate possible environmental aetiological factors. The present review aims to provide an update of the literature exploring geographical variability in IBD and to explore the environmental risk factors that may account for this variability.
  • Siegel, Corey A., et al. (författare)
  • Development of an index to define overall disease severity in IBD
  • 2018
  • Ingår i: Gut. - London, United Kingdom : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 67:2, s. 244-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.Methods: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.Results: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.Conclusions: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.
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