| 1. |
- Morris, John A, et al.
(författare)
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An atlas of genetic influences on osteoporosis in humans and mice.
- 2019
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
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| 2. |
- Baldock, Paul A., et al.
(författare)
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Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 282:26, s. 19092-19102
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Tidskriftsartikel (refereegranskat)abstract
- The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y receptors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1(-/-) mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1(-/-) mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, conditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Furthermore, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by nonhypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors.
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| 3. |
- Hill, Brendan, et al.
(författare)
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Investigation and analysis of ferrous sulfate polyvinyl alcohol (PVA) gel dosimeter
- 2002
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 47:23, s. 4233-4246
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Tidskriftsartikel (refereegranskat)abstract
- Ferrous sulfate (Fe(SO4)2) PVA gels were investigated for a range of absorbed doses up to 20 Gy using both magnetic resonance imaging (MRI) and spectrophotometry to determine R1 and optical density (OD) dose responses and G values. It was found that R1- and OD-dose sensitivities increased with O2 saturation or by the introduction of a freeze-thaw cycle during preparation of the PVA gel. The storage temperature of the Fe(SO4)2 PVA gel at -18 degrees C increased R1-dose sensitivity above that of gels stored at 5 degrees C. The addition of sucrose to the formulation was found to result in the largest increase in both R1- and OD-dose sensitivities. Fe(SO4)2 PVA gel with and without the addition of xylenol orange was demonstrated to have a G value of approximately 20 ions/100 eV and with sucrose approximately 24 ions/100 eV.
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| 4. |
- Trydegård, Gun-Britt, 1937-
(författare)
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Tradition, change and variation : past and present trends in public old-age care
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this dissertation is to describe and analyse how public old-age care in Sweden has developed and changed during the last century. The study applies a provider perspective on how care has been planned and professionally carried out. A broader social policy perspective, studying old-age care at central/national as well as local/municipal level, is also developed. A special focus is directed at the large local variation in care and services for the elderly. The empirical base is comprised of official documents and other public sources, survey data from interviews with elderly recipients of public old-age care, and official statistics on publicly financed and controlled old-age care and services.Study I addresses the development of old-age care in Sweden during the twentieth century by studying an important occupation in this field – the supervisors and their professional roles, tasks and working conditions. Throughout, the roles of supervisors have followed the prevailing official policy on the proper way to provide care for elderly people in Sweden; from poor relief at the beginning of the 1900s, via a generous level of services in the 1960s and 1970s, to today’s restricted and economy-controlled mode of operation.Study II describes and compares two main forms of public old-age care in Sweden today, home help services and institutional care. The care-load found in home-based care was comparable to and sometimes even larger than in service-homes and other institutions, indicating that large care needs among elderly people in Sweden today can be met in their homes as well as in institutional settings.Studies III and IV analyse the local variation in public old-age care in Sweden. During the last decades there has been an overall decline in home help services. The coverage of home help for elderly people shows large differences between municipalities throughout this period, and the relative variation has increased. The local disparity seems to depend more on historical factors, e.g., previous coverage rates, than on the present municipal situation in levels of need or local economy and politics.In an introductory part the four papers are linked together by an outline of the demographic situation and the social policy model for old-age care in Sweden. Trends that have been apparent over time, e.g. professionalisation and market orientation, are traced and discussed. Conflicts between prevailing ideologies are analysed, in regards to for instance home-based and institution-based care, social and medical culture, and local and central levels of decision-making. ’Welfare municipality’, ‘path dependency’, and ‘decentralisation’ are suggested as a conceptual framework for describing the large and increasing local variations in old-age care. Finally, implications of the four studies with regard to old-age care policy and further research are discussed.
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