| 1. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- de Groot, P. F., et al.
(författare)
-
Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
- 2017
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.
|
|
| 8. |
|
|
| 9. |
- Main, Chris J., et al.
(författare)
-
Implementation Science and Employer Disability Practices : Embedding Implementation Factors in Research Designs
- 2016
-
Ingår i: Journal of occupational rehabilitation. - : Springer-Verlag New York. - 1053-0487 .- 1573-3688. ; 26:4, s. 448-464
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: For work disability research to have an impact on employer policies and practices it is important for such research to acknowledge and incorporate relevant aspects of the workplace. The goal of this article is to summarize recent theoretical and methodological advances in the field of Implementation Science, relate these to research of employer disability management practices, and recommend future research priorities.Methods: The authors participated in a year-long collaboration culminating in an invited 3-day conference, “Improving Research of Employer Practices to Prevent Disability”, held October 14–16, 2015, in Hopkinton, MA, USA. The collaboration included a topical review of the literature, group conference calls to identify key areas and challenges, drafting of initial documents, review of industry publications, and a conference presentation that included feedback from peer researchers and a question/answer session with a special panel of knowledge experts with direct employer experience.Results: A 4-phase implementation model including both outer and inner contexts was adopted as the most appropriate conceptual framework, and aligned well with the set of process evaluation factors described in both the work disability prevention literature and the grey literature. Innovative interventions involving disability risk screening and psychologically-based interventions have been slow to gain traction among employers and insurers. Research recommendations to address this are : (1) to assess organizational culture and readiness for change in addition to individual factors; (2) to conduct process evaluations alongside controlled trials; (3) to analyze decision-making factors among stakeholders; and (4) to solicit input from employers and insurers during early phases of study design.Conclusions: Future research interventions involving workplace support and involvement to prevent disability may be more feasible for implementation if organizational decision-making factors are imbedded in research designs and interventions are developed to take account of these influences.
|
|
| 10. |
- Den Ouden, M. A. G., et al.
(författare)
-
Stand-alone single-frequency GPS ice velocity observations on Nordenskiöldbreen, Svalbard
- 2010
-
Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 4:4, s. 593-604
-
Tidskriftsartikel (refereegranskat)abstract
- Precise measurements of ice-flow velocities are necessary for a proper understanding of the dynamics of glaciers and their response to climate change. We use stand-alone single-frequency GPS receivers for this purpose. They are designed to operate unattended for 1–3 years, allowing uninterrupted measurements for long periods with hourly temporal resolution. We present the system and illustrate its functioning using data from 9 GPS receivers deployed on Nordenskiöldbreen, Svalbard, for the period 2006–2009. The accuracy of the receivers is 1.62 m based on the standard deviation in the average location of a stationary reference station (NBRef). Both the location of NBRef and the observed flow velocities agree within one standard deviation with DGPS measurements. Periodicity (6, 8, 12, 24 h) in the NBRef data is largely explained by the atmospheric, mainly ionospheric, influence on the GPS signal. A (weighed) running-average on the observed locations significantly reduces the standard deviation and removes high frequency periodicities, but also reduces the temporal resolution. Results show annual average velocities varying between 40 and 55 m yr−1 at stations on the central flow-line. On weekly to monthly time-scales we observe a peak in the flow velocities (from 60 to 90 m yr−1) at the beginning of July related to increased melt-rates. No significant lag is observed between the timing of the maximum speed between different stations. This is likely due to the limited temporal resolution after averaging in combination with the relatively small distance (max. ±13 km) between the stations.
|
|
