| 1. |
|
|
| 2. |
|
|
| 3. |
- Estrada, Karol, et al.
(författare)
-
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
|
|
| 4. |
- Foltynie, T, et al.
(författare)
-
MRI-guided STN DBS in Parkinson's disease without microelectrode recording : efficacy and safety
- 2011
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 82:4, s. 358-363
-
Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.
|
|
| 5. |
- Litter, M. I., et al.
(författare)
-
Arsenic in Argentina : Occurrence, human health, legislation and determination
- 2019
-
Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026. ; 676, s. 756-766
-
Tidskriftsartikel (refereegranskat)abstract
- An overview about the presence of arsenic (As) in groundwaters of Argentina, made by a transdisciplinary group of experts is presented. Aspects on As occurrence, effects of As on human health, regulations regarding the maximum allowable amount of As in drinking water as well as bottled water, and analytical techniques for As determination are presented. The most affected region in Argentina is the Chaco-Pampean plain, covering around 10 million km 2 , where approximately 88% of 86 groundwater samples collected in 2007 exceeded the World Health Organization (WHO) guideline value. In the Salí river basin, As concentrations ranged from 11.4 to 1660 μg/L, with 100% of the samples above the WHO guideline value. In the Argentine Altiplano (Puna) and Subandean valleys, 61% of 62 samples collected from surface and groundwaters exceeded the WHO limit. Thus, it can be estimated that, at present, the population at risk in Argentina reaches around four million people. Pathologies derived from the chronic consumption of As, the metabolism of As in the human body and the effects of the different As chemical forms, gathered under the name HACRE (hidroarsenicismo crónico regional endémico in Spanish, for chronic regional endemic hydroarsenicism) are described. Regarding the regulations, the 10 μg/L limit recommended by the WHO and the United States Environmental Protection Agency has been incorporated in the Argentine Food Code, but the application is still on hold. In addition, there is disparity regarding the maximal admitted values in several provinces. Considerations about the As concentrations in bottled water are also presented. A survey indicates that there are several Argentine laboratories with the suitable equipment for As determination at 10 μg/L, although 66% of them are concentrated in Buenos Aires City, and in the Santa Fe, Córdoba and Buenos Aires provinces. Conclusions and recommendations of this first part are provided.
|
|
| 6. |
- Liu, Ching-Ti, et al.
(författare)
-
Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
-
Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
-
Tidskriftsartikel (refereegranskat)abstract
- Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?
|
|
| 7. |
|
|
| 8. |
- Rodes, G A, et al.
(författare)
-
Optical switching for dynamic distribution of wireless-over-fiber signals
- 2012
-
Ingår i: 2012 16th International Conference on Optical Networking Design and Modelling, ONDM 2012. - 9781467314428 ; , s. 1-4
-
Konferensbidrag (refereegranskat)abstract
- In this paper, we report on an experimental validation of dynamic distribution of wireless-over-fiber by employing optical switching using semiconductor optical amplifiers; the rest of the network was designed according to the channel distribution over the optical spectra required by the optical switch. An experimental validation was also conducted. The experiment consists of a four wavelength division multiplexed (WDM) channel system operating on a WiMax frequency band, and employing an orthogonal frequency-division multiplexing (OFDM) modulation at 625 Mbit/s per channel, transmission of the data over 20 km of optical fiber, and active switching in a one-by-sixteen active optical switch. The results show a negligible power penalty on each channel, for both the best and the worst case in terms of inter-channel crosstalk.
|
|
| 9. |
- Scott, Robert A., et al.
(författare)
-
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
-
Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
|
|
| 10. |
- Desta Zahlay, Fitiwi, et al.
(författare)
-
A formulation for large-scale transmission expansion planning problem and a solution strategy
- 2013
-
Ingår i: 2013 10th International Conference on the European Energy Market (EEM). - : IEEE. - 9781479920082 ; , s. 6607393-
-
Konferensbidrag (refereegranskat)abstract
- The expected deployment of massive renewable energy sources (RES, mainly of wind and solar) at a continental or even intercontinental level creates very complex transmission expansion planning (TEP) problems. Both the size of the system and the level of uncertainty are huge. Solving a TEP problem for such big networks under high levels of uncertainty demands an exceptionally huge computational effort when using reasonably precise models. Conventional modeling approaches and solution strategies cannot be directly reproduced in this case due to their computational limitations. In this paper, we show a systematic way of approaching the problem, which deals both with modeling and with solution strategy aspects. We formulate the TEP problem as a two period stochastic linear programming problem characterized by common investment decisions to all scenarios in the first period and scenario-dependent decisions in the second period. In order to make it tractable, we devise a solution strategy based on decomposing the problem into successive optimization phases. Each phase uses the results of the previous one to reduce the search space. This reduction in complexity allows each phase to use more complex models with a similar computational load. Each optimization phase could be defined and solved as an independent problem, thus, allowing the use of specific decomposition techniques, or parallel computation when possible. A modified Garver's system is used to illustrate the methodologies. Test results from IEEE-300 bus system show that the proposed solution strategy is very effective. And, integrating the proposed solution strategy in the solution process contributes to a significant reduction in computational effort while fairly maintaining optimality of the solution.
|
|
