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- Christenson, A., et al.
(författare)
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The Swedish Youth with Obesity cohort: Profile of an ongoing prospective study
- 2023
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Ingår i: Obesity. - 1930-7381. ; 31:6, s. 1678-1685
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAs there is a lack of studies on adolescents and young adults with obesity, the Swedish Youth with Obesity cohort was set up to describe the long-term results of medical, as well as surgical, obesity interventions in youth. This article describes the study protocol. MethodsSince 2018, the study has continuously recruited patients aged between 16 and 25 years who have been admitted for obesity treatment at a specialist obesity clinic in Stockholm, Sweden. Participants provide data from blood tests, questionnaires, and anthropometric measurements. Data are collected longitudinally at enrollment and after 18 months and 3, 4, 5, and 10 years. ResultsIn the first 500 participants (76% female), the mean age was 21 (SD 3.0) years and the mean BMI was 41.3 (SD 6.1) kg/m(2) at enrollment. Almost half of the participants (44.4%) reported that both parents were born outside the Nordic countries. The proportion of participants who smoked at least sometimes was 28.4%. ConclusionsThe longitudinally collected data from the Swedish Youth with Obesity cohort will become a valuable source for answering various research questions regarding long-term results of medical and surgical obesity treatment in adolescents and young adults with obesity.
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| 2. |
- Das, Anirban, et al.
(författare)
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Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium.
- 2024
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Ingår i: Cancer discovery. - 2159-8290. ; 14:2, s. 258-273
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Tidskriftsartikel (refereegranskat)abstract
- Immune-checkpoint inhibition (ICI) is effective for replication-repair deficient, high-grade gliomas (RRD-HGG). Clinical/biologic impact of immune-directed approaches after failing ICI-monotherapy are unknown. We performed an international study on 75 patients treated with anti-PD1; 20 are progression-free (median follow-up: 3.7-years). After 2nd-progression/recurrence (n=55), continuing ICI-based salvage prolonged survival to 11.6-months (n=38; p<0.001), particularly for those with extreme mutation burden (p=0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and immune-microenvironment. Response to re-irradiation was explained by an absence of deleterious post-radiation indel signatures (ID8). Increased CTLA4-expression over time, and subsequent CTLA4-inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to reinvigoration of peripheral immune and radiological responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/ synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology.
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| 3. |
- Ercan, Ayse Bahar, et al.
(författare)
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Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
- 2024
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Ingår i: The Lancet. Oncology. - 1474-5488. ; 25:5, s. 668-682
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Tidskriftsartikel (refereegranskat)abstract
- Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
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| 5. |
- Håkansson, Lena, et al.
(författare)
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Cosmogenic Be-10-ages from the Store Koldewey island, NE Greenland
- 2007
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Ingår i: Geografiska Annaler. Series A. Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 89A:3, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Earlier work in northeast Greenland has suggested a limited advance of the Greenland Ice Sheet during the Last Glacial Maximum (LGM). However, this concept has recently been challenged by marine geological studies, indicating grounded ice on the continental shelf at this time. New Be-10-ages from the Store Koldewey island, northeast Greenland, suggest that unscoured mountain plateaus at the outer coast were covered at least partly by cold-based ice during the LGM. It is, however, still inconclusive whether this ice was dynamically connected to the Greenland Ice Sheet or not. Regardless of the LGM ice sheet extent, the Be-10 results from Store Koldewey add to a growing body of evidence suggesting considerable antiquity of crystalline unscoured terrain near present and Pleistocene ice sheet margins.
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| 8. |
- Webb, J. L., et al.
(författare)
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Imaging Atomic Scale Dynamics on III-V Nanowire Surfaces during Electrical Operation
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- As semiconductor electronics keep shrinking, functionality depends on individual atomic scale surface and interface features that may change as voltages are applied. In this work we demonstrate a novel device platform that allows scanning tunneling microscopy (STM) imaging with atomic scale resolution across a device simultaneously with full electrical operation. The platform presents a significant step forward as it allows STM to be performed everywhere on the device surface and high temperature processing in reactive gases of the complete device. We demonstrate the new method through proof of principle measurements on both InAs and GaAs nanowire devices with variable biases up to 4 V. On InAs nanowires we observe a surprising removal of atomic defects and smoothing of the surface morphology under applied bias, in contrast to the expected increase in defects and electromigration-related failure. As we use only standard fabrication and scanning instrumentation our concept is widely applicable and opens up the possibility of fundamental investigations of device surface reliability as well as new electronic functionality based on restructuring during operation.
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| 10. |
- Alexanderson, Helena, et al.
(författare)
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Depositional history of the North Taymyr ice-marginal zone, Siberia - a landsystem approach
- 2002
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Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 17:4, s. 361-382
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Tidskriftsartikel (refereegranskat)abstract
- The sediment-landform associations of the northern Taymyr Peninsula in Arctic Siberia tell a tale of ice sheets advancing from the Kara Sea shelf and inundating the peninsula, probably three times during the Weichselian. In each case the ice sheet had a margin frozen to its bed and an interior moving over a deforming bed. The North Taymyr ice-marginal zone (NTZ) comprises ice-marginal and supraglacial landsystems dominated by thrust-block moraines 2-3 km wide and large-scale deformation of sediments and ice. Large areas are still underlain by remnant glacier ice and a supraglacial landscape with numerous ice-walled lakes and kames is forming even today. The proglacial landsystem is characterised by subaqueous (e.g. deltas) or terrestrial (e.g. sandar) environments, depending on location/altitude and time of formation. Dating results (OSL, C-14) indicate that the NTZ was initiated ca. 80 kyr BP during the retreat of the Early Weichselian ice sheet and that it records the maximum limit of a Middle Weichselian glaciation (ca. 65 kyr BP). During both these events, proglacial lakes were dammed by the ice sheets. Part of the NTZ was occupied by a thin Late Weichselian ice sheet (20-12 kyr BP), resulting in subaerial proglacial drainage. Copyright (C) 2002 John Wiley Sons, Ltd.
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