| 1. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 2. |
- Hoffmann, Henry, et al.
(författare)
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Self-aware computing in the Angstrom processor
- 2012
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Ingår i: Proceedings of the 49th Annual Design Automation Conference. - New York, NY, USA : ACM. - 9781450311991 ; , s. 259-264
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Konferensbidrag (refereegranskat)abstract
- Addressing the challenges of extreme scale computing re- quires holistic design of new programming models and sys- tems that support those models. This paper discusses the Angstrom processor, which is designed to support a new Self-aware Computing (SEEC) model. In SEEC, applications explicitly state goals, while other systems components provide actions that the SEEC runtime system can use to meet those goals. Angstrom supports this model by ex- posing sensors and adaptations that traditionally would be managed independently by hardware. This exposure allows SEEC to coordinate hardware actions with actions specified by other parts of the system, and allows the SEEC runtime system to meet application goals while reducing costs (e.g., power consumption).
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| 3. |
- Kaiser, Matthias J., et al.
(författare)
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Frequency of Malnutrition in Older Adults : A Multinational Perspective Using the Mini Nutritional Assessment
- 2010
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 58:9, s. 1734-1738
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To provide pooled data on the prevalence of malnutrition in elderly people as evaluated using the Mini Nutritional Assessment (MNA). DESIGN Retrospective pooled analysis of previously published datasets. SETTING Hospital, rehabilitation, nursing home, community. PARTICIPANTS Four thousand five hundred seven people (75.2% female) with a mean age of 82.3. MEASUREMENTS The prevalence of malnutrition in the combined database and in the four settings was examined. RESULTS Twenty-four data sets with information on full MNA classification from researchers from 12 countries were submitted. In the combined database, the prevalence of malnutrition was 22.8%, with considerable differences between the settings (rehabilitation, 50.5%; hospital, 38.7%; nursing home, 13.8%; community, 5.8%). In the combined database, the "at risk" group had a prevalence of 46.2%. Consequently, approximately two-thirds of study participants were at nutritional risk or malnourished. CONCLUSION The MNA has gained worldwide acceptance and shows a high prevalence of malnutrition in different settings, except for the community. Because of its specific geriatric focus, the MNA should be recommended as the basis for nutritional evaluation in older people.
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