| 1. |
- Heymer, Emma J., et al.
(author)
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Cumulative Absolute Risk of Subsequent Colorectal Cancer After Abdominopelvic Radiotherapy Among Childhood Cancer Survivors : A PanCareSurFup Study
- 2024
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In: Journal of Clinical Oncology. - 0732-183X. ; 42:3, s. 336-347
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Journal article (peer-reviewed)abstract
- PURPOSE Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study. METHODS Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area. RESULTS Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected). CONCLUSION We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.
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| 2. |
- Heymer, Emma J., et al.
(author)
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Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study
- 2024
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In: British Journal of Cancer. - 0007-0920. ; 130:6, s. 976-986
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Journal article (peer-reviewed)abstract
- Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.
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| 3. |
- Becker, Joel, et al.
(author)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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In: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Journal article (peer-reviewed)abstract
- Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 4. |
- Sugden, David E., et al.
(author)
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Plucking enhanced beneath ice sheet margins : evidence from the Grampian Mountains, Scotland
- 2019
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In: Geografiska Annaler. Series A, Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 101:1, s. 34-44
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Journal article (peer-reviewed)abstract
- Concentrations of boulders are a common feature of landscapes modified by former mid-latitude ice sheets. In many cases, the origin of the boulders can be traced in the up-ice direction to a cliff only tens to hundreds of metres distant. The implication is that a pulse of plucking and short boulder transport occurred beneath thin ice at the end of the last glacial cycle. Here we use a case study in granite bedrock in the Dee Valley, Scotland, to constrain theory and explore the factors involved in such a late phase of plucking. Plucking is influenced by ice velocity, hydrology, effective ice pressure, the extent of subglacial cavities and bedrock characteristics. The balance between these factors favours block removal beneath thin ice near a glacier margin. At Ripe Hill in the Dee Valley, a mean exposure age of 14.2 ka on blocks supports the view that the boulder train formed at the end of ice sheet glaciation. The late pulse of plucking was further enhanced by ice flowing obliquely across vertical joints and by fluctuations in sub-marginal meltwater conditions. An implication of the study is that there is the potential for a wave of ice-marginal plucking to sweep across a landscape as an ice sheet retreats.
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| 5. |
- Bentley, Michael J., et al.
(author)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Journal article (peer-reviewed)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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