| 1. |
- Chang-Claude, Jenny, et al.
(författare)
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Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965. ; 16:4, s. 740-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. Methods: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. Results: Breast cancer risk was not significantly related to age at menopause {hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; ≥55 years, 1.12 [0.12-5.02], as compared with premenopausal women}. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. Conclusions: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
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| 2. |
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| 3. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 4. |
- Axelsson, Erik Marcus Kristian, 1974, et al.
(författare)
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Opportunities for Process Integrated Evaporation in a Eucalyptus Pulp Mill and Comparison with a Softwood Mill Study
- 2007
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Ingår i: Conference PRES 07, Ischia Island, Italy. ; , s. 727-732
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Konferensbidrag (refereegranskat)abstract
- Significant energy savings can be made in the pulp and paper industry by implementing process-integrated evaporation (PIvap). The concept of PIvap has been evaluated for a Eucalyptus mill producing bleached kraft market pulp in Portugal and the results were compared to the ones from an earlier model mill study of a soft wood mill. In the eucalyptus mill there were, theoretically, 0.86 GJ/ADt of excess heat suitable for a PIvap besides the 2.6 GJ/ADt of pinch violations. The pinch violations could be transferred to excess heat, but some pinch violations were cost effective to solve. A suggestion where 1.1 GJ/ADt of pinch violations are solved and 1.6 GJ/ADt of excess heat are extracted is presented. If the excess heat is used in a 7 effect PIvap with integrated stripper and increased dry solids content, steam savings of 2.7 GJ/ADt could be made in the evaporation plant. Together with the pinch violations and opportunities for improved soot blowing, the total steam savings from the suggested measures were 4.5 GJ/ADt or 35%. The amount of steam savings and associated costs were similar to the ones in the soft-wood model-mill. Hence, no significant differences could be found for the opportunities to implement PIvap in the hardwood mill compared to in the soft wood mill. The existence of a pre-evaporation plant, however, showed to hinder introduction of PIvap, since a pre-evaporation plant uses excess heat, and uses it ineffectively compared to a PIvap. Hence, the pre-evaporation has been removed in the suggestion for integration presented here.
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| 5. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 6. |
- Bernin, Diana, 1979, et al.
(författare)
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Real time MRI to elucidate the functionality of coating films intended for modified release
- 2019
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 311-312, s. 117-124
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Tidskriftsartikel (refereegranskat)abstract
- Polymer films based on mixtures of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) have been widely used to coat pellets and tablets to modify the release profile of drugs. For three different EC/HPC films we used 1H and 19F MRI in combination with a designed release cell to monitor the drug, polymer and water in 5 dimensional (5D) datasets; three spatial, one diffusion or relaxation and a temporal dimension, in real time. We observed that the water inflow through the films correlated with the initiation of the dissolution of the drug in the tablet beneath the film. Leaching of the pore forming HPC further accelerated water penetration and resulted in a drug release onset after a hydrostatic pressure was generated below the film indicated by positional changes of the film. For the more permeable film, both water ingress and drug egress showed a large variability of release over the film surface indicating the heterogeneity of the system. Furthermore, the 1H diffusion dataset revealed the formation of a gel layer of HPC at the film surface. We conclude that the setup presented provides a significant level of details, which are not achieved with traditional methods.
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| 7. |
- Boisvert, Catherine Anne, 1978-
(författare)
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The Origin of Tetrapod Limbs and Girdles: Fossil and Developmental Evidence
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Around 375 million years ago, the first tetrapods appeared, marking one of the most important events in vertebrate evolutionary history. The fin to limb transition saw the appearance of fingers and a weight bearing pelvic girdle. While very little research has been done on the evolution of the tetrapod pelvic girdle, a fair amount has been done on the origins of fingers but some aspects remained controversial. A combination of palaeontology, developmental biology and comparative morphology was therefore used in this thesis to better understand the fin to limb transition. The pectoral fin of Panderichthys, a sarcopterygian fish closely related to tetrapods was CT-scanned and modeled in three dimensions and its pelvic girdle and fin were examined with traditional techniques. This information from the fossil record was integrated with comparisons of the development of the Australian lungfish, Neoceratodus forsteri, our closest living fish relative and the axolotl (Ambystoma mexicanum), a salamander representing well the condition of early tetrapods. Development of bone and cartilage was studied through clearing and staining and development of skeletal muscles through immunostaining. In situ hybridizations were performed on the lungfish to study the expression of Hoxd13, associated with the formation of digits in tetrapods. This work shows that the late expression phase of Hoxd13 is present in Neoceratodus and is associated with the formation of radials. Redescription of the pectoral fin of Panderichthys reveals that distal radials are present, which, in addition to other information, lead us to conclude that digits are not novelties in tetrapods but rather have evolved from the distal radials present in the fins of all sarcopterygian fish. The earliest tetrapods lack a full set of wrist + carpals/ankle + tarsal bones. Here, we propose that this region of the limbs evolved after fingers and toes through an expansion of the region between the proximal limb bones and the digits. As for the pelvic girdle, it is very primitive in Panderichthys but comparison of its development in Neoceratodus and Ambystoma suggest that the ischium evolved through the posterior expansion of the pubis and the ilium, through an elongation of the iliac process already present in sarcopterygian fishes. The results of this thesis help to better understand the fin to limb transition and show that it is more gradual than previously believed.
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| 8. |
- Bonaïti, Bernard, et al.
(författare)
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TTR familial amyloid polyneuropathy : does a mitochondrial polymorphism entirely explain the parent-of-origin difference in penetrance?
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438.
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Tidskriftsartikel (refereegranskat)abstract
- The Val30Met transthyretin familial amyloid polyneuropathy (TTR-V30M-FAP) is the most frequent familial amyloidosis, with autosomal dominant transmission. This severe disease shows important differences in age of onset and penetrance. Recently, a difference in penetrance according to the gender of the transmitting parent was elicited in different geographic areas with a higher penetrance in case of maternal transmission of the trait. In addition, differences in mitochondrial haplogroup distribution in early and late onset Swedish and French cases of TTR-V30M-FAP suggested that a polymorphism of mitochondrial DNA could be one underlying mechanism of the phenotypic variation. We further investigated this hypothesis by modeling the penetrance function with a parent-of-origin and/or a mitochondrial polymorphism effect in samples of Portuguese (n=33) and Swedish families (n=86) with TTR-V30M-FAP in which several individuals had been tested for mitochondrial haplogroups. Our analysis showed that a mitochondrial polymorphism effect was sufficient to explain the observed difference in penetrance according to gender of the transmitting parent in the Portuguese sample, whereas, in the Swedish sample, a clear residual parent-of-origin effect remained. This study further supported the role of a mitochondrial polymorphism effect that might induce a higher penetrance in case of maternal inheritance of the disease. In clinical practice, these results might help to better delineate the individual disease risk and have a significant impact on the management of both patients and carriers.
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| 9. |
- Brohet, Richard M., et al.
(författare)
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Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: A report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group
- 2007
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 25:25, s. 3831-3836
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/ 2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/ 2 carriers. Patients and Methods In the International BRCA1/ 2 Carrier Cohort study ( IBCCS), a retrospective cohort of 1,593 BRCA1/ 2 mutation carriers was analyzed with a weighted Cox regression analysis. Results We found an increased risk of breast cancer for BRCA1/ 2 mutation carriers who ever used oral contraceptives ( adjusted hazard ratio [ HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full- term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers ( 4 or more years of use before first full-term pregnancy: HR = 1.49 [ 95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [ 95% CI, 1.21 to 5.49] for BRCA2 carriers). Conclusion No evidence was found among BRCA1/ 2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full- term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.
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| 10. |
- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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