| 1. |
- Becker, Joel, et al.
(författare)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Bentley, Michael J., et al.
(författare)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Blank, Rainer, et al.
(författare)
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International clinical practice recommendations on the definition, diagnosis, assessment, intervention, and psychosocial aspects of developmental coordination disorder
- 2019
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Ingår i: Developmental Medicine & Child Neurology. - : John Wiley & Sons. - 0012-1622 .- 1469-8749. ; 61:3, s. 242-285
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Tidskriftsartikel (refereegranskat)abstract
- AIM: These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD), initiated by the European Academy of Childhood Disability (EACD), aim to address key questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice.METHOD: Key questions in five areas were considered through literature reviews and formal expert consensus. For recommendations based on evidence, literature searches on 'mechanisms', 'assessment', and 'intervention' were updated since the last recommendations in 2012. New searches were conducted for 'psychosocial issues' and 'adolescents/adults'. Evidence was rated according to the Oxford Centre for Evidence-Based Medicine (level of evidence [LOE] 1-4) and transferred into recommendations. For recommendations based on formal consensus, two meetings of an international, multidisciplinary expert panel were conducted with a further five Delphi rounds to develop good clinical practice (GCP) recommendations.RESULTS: Thirty-five recommendations were made. Eight were based on the evidence from literature reviews (three on 'assessment', five on 'intervention'). Twenty-two were updated from the 2012 recommendations. New recommendations relate to diagnosis and assessment (two GCPs) and psychosocial issues (three GCPs). Additionally, one new recommendation (LOE) reflects active video games as adjuncts to more traditional activity-oriented and participation-oriented interventions, and two new recommendations (one GCP, one LOE) were made for adolescents and adults with DCD.INTERPRETATION: The CPR-DCD is a comprehensive overview of DCD and current understanding based on research evidence and expert consensus. It reflects the state of the art for clinicians and scientists of varied disciplines. The international CPR-DCD may serve as a basis for national guidelines.WHAT THIS PAPER ADDS:Updated international clinical practice guidelines on developmental coordination disorder (DCD).Refined and extended recommendations on clinical assessment and intervention for DCD.A critical synopsis of current research on mechanisms of DCD.A critical synopsis of psychosocial issues in DCD, with implications for clinical practice.The first international recommendations to consider adolescents and adults with DCD.
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| 4. |
- Hall, Adrian M., et al.
(författare)
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Late readvance and rapid final deglaciation of the last ice sheet in the Grampian Mountains, Scotland
- 2016
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 31:8, s. 869-878
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Tidskriftsartikel (refereegranskat)abstract
- Towards the end of the last glaciation, ice sourced from the western Grampian Mountains of Scotland flowed down Strath Spey to encroach on the northern flanks of the Cairngorm Mountains. The maximum of this late advance and its subsequent retreat is recorded by moraines, ice-marginal meltwater channels, and kame terraces that can be traced for 60 km along Strath Spey. New cosmogenic Be-10 exposure ages from moraines indicate deglaciation at 15.1 +/- 1.1 ka. This timing matches closely the recalibrated mean ages of 14.7 +/- 0.7 and 15.2 +/- 0.7 ka for the Wester Ross Readvance in the North-West Highlands. A synchronous readvance of the British-Irish Ice Sheet (BIIS) towards the end of Greenland Stadial 2a (GS-2a) (16.9-14.7 ka) is indicated. Thereafter active ice retreat from the flanks of Strath Spey was rapid, occurring within the similar to 1 ka uncertainty of the cosmogenic exposure ages. We suggest the advance followed the collapse of the marine parts of the BIIS at similar to 16 ka due to conditions of increased precipitation occurring at a time of low temperatures. The rapidity of deglaciation may reflect enhanced Fohn effects caused by the ice dome in the western Grampians.
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| 5. |
- Heymer, Emma J., et al.
(författare)
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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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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 42:3, s. 336-347
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Heymer, Emma J., et al.
(författare)
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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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Ingår i: British Journal of Cancer. - 0007-0920. ; 130:6, s. 976-986
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Hubbard, Alun, et al.
(författare)
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Dynamic cycles, ice streams and their impact on the extent, chronology and deglaciation of the British–Irish ice sheet
- 2009
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 28:7-8, s. 758-776
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Tidskriftsartikel (refereegranskat)abstract
- We present results from a suite of forward transient numerical modelling experiments of the British and Irish Ice Sheet (BIIS), consisting of Scottish, Welsh and Irish accumulation centres, spanning the last Glacial period from 38 to 10 ka BP. The 3D thermomechanical model employed uses higher-order physics to solve longitudinal (membrane) stresses and to reproduce grounding-line dynamics. Surface mass balance is derived using a distributed degree-day calculation based on a reference climatology from mean (1961–1990) precipitation and temperature patterns. The model is perturbed from this reference state by a scaled NGRIP oxygen isotope curve and the SPECMAP sea-level reconstruction. Isostatic response to ice loading is computed using an elastic lithosphere/relaxed asthenosphere scheme. A suite of 350 simulations were designed to explore the parameter space of model uncertainties and sensitivities, to yield a subset of experiments that showed close correspondence to offshore and onshore ice-directional indicators, broad BIIS chronology, and the relative sea-level record. Three of these simulations are described in further detail and indicate that the separate ice centres of the modelled BIIS complex are dynamically interdependent during the build up to maximum conditions, but remain largely independent throughout much of the simulation. The modelled BIIS is extremely dynamic, drained mainly by a number of transient but recurrent ice streams which dynamically switch and fluctuate in extent and intensity on a centennial time-scale. A series of binge/purge, advance/retreat, cycles are identified which correspond to alternating periods of relatively cold-based ice, (associated with a high aspect ratio and net growth), and wet-based ice with a lower aspect ratio, characterised by streaming. The timing and dynamics of these events are determined through a combination of basal thermomechanical switching spatially propagated and amplified through longitudinal coupling, but are modulated and phase-lagged to the oscillations within the NGRIP record of climate forcing. Phases of predominant streaming activity coincide with periods of maximum ice extent and are triggered by abrupt transitions from a cold to relatively warm climate, resulting in major iceberg/melt discharge events into the North Sea and Atlantic Ocean. The broad chronology of the modelled BIIS indicates a maximum extent at 20 ka, with fast-flowing ice across its western and northern sectors that extended to the continental shelf edge. Fast-flowing streams also dominate the Irish Sea and North Sea Basin sectors and impinge onto SW England and East Anglia. From 19 ka BP deglaciation is achieved in less than 2000 years, discharging the freshwater equivalent of 2 m global sea-level rise. A much reduced ice sheet centred on Scotland undergoes subsequent retrenchment and a series of advance/retreat cycles into the North Sea Basin from 17 ka onwards, culminating in a sustained Younger Dryas event from 13 to 11.5 ka BP. Modelled ice cover is persistent across the Western and Central Highlands until the last remnant glaciers disappear around 10.5 ka BP.
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| 8. |
- Nilsson, Harriet
(författare)
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The role of nitric oxide in cytoskeleton-mediated organelle transport and cell adhesion
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nitric oxide (NO) is a signaling molecule that is produced by many different kinds of cells, and it is known to mediate actions such as blood vessel dilation, communication between nerve cells, and killing of bacteria in infections. The cytoskeleton is involved in many important cellular functions, among them intracellular transport of organelles, migration, and cell division. The aim of the present studies was to examine the effects of NO on some of the indicated functions. Homotypic adhesion of human neutrophils, which is mediated by ß2 integrins, is an early step in the inflammatory process. Addition of L-argiriine (the substrate of NO production) to fMLP-stimulated neutrophils increased and prolonged aggregation of the cells. Stimulation of L-arginine-pretreated neutrophils by cross-linking of ß2 integrins attenuated the increase in F-actin, as compared to control cells. These results suggest that the aggregation is prolonged by activation of ß2 integrins and endogenous NO production, two events that together seem to inhibit actin polymerization, possibly via ADP ribosylation.The effect of NO on intracellular translocation of organelles along the cytoskeleton was studied in Xenopus laevis pigment cells. Inhibition of NO production induced by the drug L-NAME was found to inhibit aggregation of the pigment organelles (melanosomes) and to induce dispersion. Activation of PKC, MEK, and ERKl, but not PKA, was associated with the dispersion, thus NO may negatively regulate these kinases, which, when activated, would induce movement of melanosomes. During melanosome aggregation, the cell center increases in height by approximately 30%. Experiments were performed to determine whether the cell membrane is pushed upwards by actin polymerization and water influx through HgCl2-sensitive aquaporins. The results gave no evidence that either two of these mechanisms affects the upward movement. However, L-NAME caused dispersion and a decrease in cell height, thus NO may play a role in maintaining an aggregated, elevated state. In conclusion, many factors regulate both homotypic aggregation and intracellular organelle transport, and NO seems to prolong homotypic aggregation of neutrophils and regulate melanosome transport by inhibiting PKC, MEK and ERKl.
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| 9. |
- Näslund, Jens-Ove, 1965-
(författare)
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Ice Sheet, Climate, and Landscape Interactions in Dronning Maud Land, Antarctica
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The impact of glaciers and ice sheets on the subglacial landscape are of fundamental importance for studies of glacial history and landscape development, both in previously glaciated areas and in areas that are glaciated today. The thesis concerns the present and past erosive capacity of the ice sheet in Dronning Maud Land, East Antarctica. Large-scale subglacial landforms, mainly glacial valleys and cirques, were mapped by radar soundings and basal ice temperatures were calculated. The hypothesis that the alpine landscape in western and central Dronning Maud Land predates the ice sheet was tested. It was found that the ice sheet covering localities at high altitudes within the landscape today are covered by cold-based, and thus non-erosive, ice and that this probably also was the case during late Cenozoic glacial/interglacial cycles. It was concluded that the high-altitude alpine landscape commonly found within the coastal mountain ranges of Dronning Maud Land was formed by local wet-based mountain glaciers during the middle Cenozoic. In the late Cenozoic, the high-altitude alpine landscape has been preserved by cold-based ice coverage. Glacial preservation of a subglacial large-scale sediment accumulation, interpreted as a pre-glacial floodplain or valley delta, was also inferred. Intermediate altitudes within the landscape may have experienced alternating phases of cold-based and wet-based conditions during the late Cenozoic. The lowest parts of the Dronning Maud Land landscape constitute troughs of tectonic origin, exemplified by the prominent Penck-Jutul Trough. In these depressions wet-based conditions have prevailed up to the present day due to the presence of fast flowing ice streams such as Jutulstraumen and Veststraumen. Ice stream erosion has probably been important for the continued deepening of these troughs, and it is feasible that erosion by ice streams today still increases the already significant landscape relief. The alpine landscape of Dronning Maud Land is incised in considerably older large-scale morphology consisting of an elevated Paleozoic planation surface and a passive continental margin escarpment. An attempt is made to synthesise major events in the long-term landscape development of central and western Dronning Maud Land since the time of break-up of the Gondwana continent. The role of glacial erosion in the development of this passive continental margin is assessed.
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| 10. |
- Sugden, David, et al.
(författare)
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Antarctic blue-ice moraines : Analogue for Northern Hemisphere ice sheets?
- 2020
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- This paper reviews the distribution, character and age of blue-ice moraines in Antarctica and asks whether there are implications for the study of former Pleistocene ice sheets in the Northern Hemisphere. Blue-ice forms where acceleration of downslope katabatic winds removes snow and causes ice to ablate. Upward ice flow compensates for the surface ablation and in some places brings rock debris to the surface to form a blue-ice moraine. Blue-ice moraines occur where topography focuses katabatic winds, notably outlet glaciers cutting through mountains and in the lee of nunataks and escarpments nearer the coast. Many Antarctic blue-ice moraines have been accumulating for millions of years. The cyclic growth and decay of Pleistocene ice sheets and the dominance of surface ablation near the ice-sheet margins are clearly different, yet there are aspects that apply to Pleistocene ice sheets. Based on Antarctic blue-ice deposits, equivalent deposits associated with former Pleistocene ice sheets are likely to: (1) lie in topographic sediment traps such as in side valleys or embayments next to outlet glaciers, (2) occur in the lee of mountains, (3) display a morphology indicating ice flow into the embayment or towards the mountain front, (4) include a wide range of lithologies derived from the inland ice sheet, yet consist wholly of local debris in places, (5) accumulate a thick deposit perhaps over successive glaciations. Further, (6) the location and intensity of moraine formation will change spatially and vertically in response to changes in the relative elevation of the surrounding mountains and its effect on ice flow. The extent to which these criteria will help in interpreting the behaviour of Pleistocene ice sheets is uncertain. But we use examples from the Greenland, Laurentide and Eurasian ice sheets to suggest that the concept of enhanced ablation by katabatic winds encouraging surface moraine formation helps resolve several puzzles.
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