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| 2. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 3. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 4. |
- Harvey, N. C., et al.
(författare)
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Predictive Value of DXA Appendicular Lean Mass for Incident Fractures, Falls, and Mortality, Independent of Prior Falls, FRAX, and BMD: Findings from the Women's Health Initiative (WHI)
- 2021
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:4, s. 654-661
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Tidskriftsartikel (refereegranskat)abstract
- In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX(R)) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height(2)) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height(2) (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height(2) was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83-0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98-1.14). There were no associations between ALM/height(2) and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height(2), depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height(2) and mortality remain robust. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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| 5. |
- Zweegman, Sonja, et al.
(författare)
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Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 127:9, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- The combination of melphalan, prednisone and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for stem-cell transplantation. Long term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone and lenalidomide, followed by lenalidomide maintenance therapy showed promising results, without severe neuropathy emerging. We randomly assigned 668 NDMM patients, ineligible for stem-cell transplantation, between nine 4-weekly cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomised phase 3 trial was undertaken by HOVON and the NMSG. The primary endpoint was progression-free survival (PFS). The accrual for the study was completed in October 19, 2012. 318 patients were randomly assigned to receive MPT-T and 319 MPR-R. After a median follow up of 36 months PFS with MPT-T was 20 months (95% CI 18-23 months) versus 23 months (95% CI 19-27 months) with MPR-R (HR 0.87 [0.72-1.04], p=0.12). Response rates were similar, with ≥VGPR 47% and 45% respectively. Hematological toxicity was more pronounced with MPR-R, especially grade 3 and 4 neutropenia: 64 versus 27%. Neuropathy ≥ grade 3 was significantly higher in the MPT-T arm; 16% versus 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 versus 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance versus myelosuppression with MPR.
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| 6. |
- Mantovani Nardes, Alexandre, et al.
(författare)
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Microscopic understanding of the anisotropic conductivity of PEDOT : PSS thin films
- 2007
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Ingår i: Advanced Materials. - : Wiley-VCH Verlag. - 0935-9648 .- 1521-4095. ; 19:9, s. 1196-
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Tidskriftsartikel (refereegranskat)abstract
- The amsotropic conductivity of thin films of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is correlated to the film morphology as obtained from scanning tunneling and atomic force microscopy images. The material was found to consist of layers of flattened PEDOT-rich particles that are separated by quasi-continuous PSS lamella (see figure).
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| 7. |
- Kabat, G. C., et al.
(författare)
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Metabolic phenotypes of obesity : frequency, correlates and change over time in a cohort of postmenopausal women
- 2017
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 41:1, s. 170-177
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The possibility that a subset of persons who are obese may be metabolically healthy—referred to as the ‘metabolically healthy obese’ (MHO) phenotype—has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS).Methods: We used repeated measurements available for a subcohort of participants enrolled in the Women’s Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5–<25.0, 25.0–<30.0, 30.0 kg m−2) by MetS (yes, no). A continuous-time Markov model was used to estimate 6-year transition probabilities from one state to another.Results: Over the 6 years of follow-up, one-third of women with the healthy obese phenotype transitioned to the metabolically unhealthy obese (MUO) phenotype. Overall, there was a marked tendency toward increased metabolic deterioration with increasing BMI and toward metabolic improvement with lower BMI. Among MHO women, the 6-year probability of becoming MUO was 34%, whereas among unhealthy normal-weight women, the probability of ‘regressing’ to the metabolically healthy normal-weight phenotype was 52%.Conclusions: The present study demonstrated substantial change in metabolic obesity phenotypes over a 6-year period. There was a marked tendency toward metabolic deterioration with greater BMI and toward metabolic improvement with lower BMI.
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| 8. |
- Law, PJ, et al.
(författare)
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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 14175-
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Tidskriftsartikel (refereegranskat)abstract
- Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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| 9. |
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| 10. |
- Cordero, Gerardo A., et al.
(författare)
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Physiological plasticity in lizard embryos exposed to high-altitude hypoxia
- 2017
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Ingår i: JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY. - : Wiley. - 2471-5646 .- 2471-5638. ; 327:7, s. 423-432
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Tidskriftsartikel (refereegranskat)abstract
- Coping with novel environments may be facilitated by plastic physiological responses that enable survival during environmentally sensitive life stages. We tested the capacity for embryos of the common wall lizard (Podarcis muralis) from low altitude to cope with low-oxygen partial pressure (hypoxia) in an alpine environment. Developing embryos subjected to hypoxic atmospheric conditions (15-16% O-2 sea-level equivalent) at 2,877m above sea level exhibited responses common to vertebrates acclimatized to or evolutionarily adapted to high altitude: suppressed metabolism, cardiac hypertrophy, and hyperventilation. These responses might have contributed to the unaltered incubation duration and hatching success relative to the ancestral, low-altitude, condition. Even so, hypoxia constrained egg energy utilization such that larger eggs produced hatchlings with relatively low mass. These findings highlight the role of physiological plasticity in maintaining fitness-relevant phenotypes in high-altitude environments, providing impetus to further explore altitudinal limits to ecological diversification in ectothermic vertebrates.
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