| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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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.
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- McGurnaghan, S. J., et al.
(författare)
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Development and validation of a cardiovascular risk prediction model in type 1 diabetes
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2001-2011
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis We aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes. Methods A cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., >= 10%) using the model with the percentage eligible for statins using current guidelines by age. Results The age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer- Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic foam 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and >= 60 years, respectively (alp values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those >= 40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD >= 10% in 10 years. Conclusions/interpretation A prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention. the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.
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| 4. |
- Patterson, Brooke E., et al.
(författare)
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Evaluation of an injury prevention programme (Prep-to-Play) in women and girls playing Australian Football : design of a pragmatic, type III, hybrid implementation-effectiveness, stepped-wedge, cluster randomised controlled trial
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Due to the increase in participation and risk of anterior cruciate ligament (ACL) injuries and concussion in womens Australian Football, an injury prevention programme (Prep-to-Play) was codesigned with consumers (eg, coaches, players) and stakeholders (eg, the Australian Football League). The impact of supported and unsupported interventions on the use of Prep-to-Play (primary aim) and injury rates (secondary aim) will be evaluated in women and girls playing community Australian Football. Methods and analysis This stepped-wedge, cluster randomised controlled trial will include >= 140 teams from U16, U18 or senior womens competitions. All 10 geographically separated clusters (each containing >= 14 teams) will start in the control (unsupported) phase and be randomised to one of five dates (or wedges) during the 2021 or 2022 season to sequentially transition to the intervention (supported Prep-to-Play), until all teams receive the intervention. Prep-to-Play includes four elements: a neuromuscular training warm-up, contact-focussed football skills (eg, tackling), strength exercises and education (eg, technique cues). When transitioning to supported interventions, study physiotherapists will deliver a workshop to coaches and player leaders on how to use Prep-to-Play, attend team training at least two times and provide ongoing support. In the unsupported phase, team will continue usual routines and may freely access available Prep-to-Play resources online (eg, posters and videos about the four elements), but without additional face-to-face support. Outcomes will be evaluated throughout the 2021 and 2022 seasons (similar to 14 weeks per season). Primary outcome: use of Prep-to-Play will be reported via a team designate (weekly) and an independent observer (five visits over the two seasons) and defined as the team completing 75% of the programme, two-thirds (67%) of the time. Secondary outcomes: injuries will be reported by the team sports trainer and/or players. Injury definition: any injury occurring during a football match or training that results in: (1) being unable to return to the field of play for that match or (2) missing >= one match. Outcomes in the supported and unsupported phases will be compared using a generalised linear mixed model adjusting for clustering and time. Due to the type III hybrid implementation-effectiveness design, the study is powered to detect a improvement in use of Prep-to-Play and a reduction in ACL injuries. Ethics and dissemination La Trobe University Ethics Committee (HREC 20488) approved. Coaches provided informed consent to receive the supported intervention and players provided consent to be contacted if they sustained a head or knee injury. Results will be disseminated through partner organisations, peer-reviewed publications and scientific conferences.
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