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| 2. |
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| 3. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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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.
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| 4. |
- Foltynie, T, et al.
(författare)
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MRI-guided STN DBS in Parkinson's disease without microelectrode recording : efficacy and safety
- 2011
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 82:4, s. 358-363
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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.
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| 5. |
- Litter, M. I., et al.
(författare)
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Arsenic in Argentina : Occurrence, human health, legislation and determination
- 2019
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Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026. ; 676, s. 756-766
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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.
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| 6. |
- Liu, Ching-Ti, et al.
(författare)
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Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
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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?
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| 7. |
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| 8. |
- Rodes, G A, et al.
(författare)
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Optical switching for dynamic distribution of wireless-over-fiber signals
- 2012
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Ingår i: 2012 16th International Conference on Optical Networking Design and Modelling, ONDM 2012. - 9781467314428 ; , s. 1-4
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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.
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| 9. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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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.
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| 10. |
- Desta Zahlay, Fitiwi, et al.
(författare)
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A formulation for large-scale transmission expansion planning problem and a solution strategy
- 2013
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Ingår i: 2013 10th International Conference on the European Energy Market (EEM). - : IEEE. - 9781479920082 ; , s. 6607393-
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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.
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| 11. |
- Garcia, J, et al.
(författare)
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Remote processing server for ECG-based clinical diagnosis support
- 2002
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Ingår i: IEEE Transactions on Information Technology in Biomedicine. - 1089-7771. ; 6:4, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present the development of a remote server that provides a user-friendly access to advanced electrocardiographic (ECG) signal processing techniques. The prototype supplies telemedicine facilities to doctors for clinical indexes remote computation to support diagnosis through the Internet. The user-friendly interface is based on the selection of the desired ECG signal processing tools on a Web browser window. The centralized structure of the system permits unique and user-independent update and management of the software and, therefore, is especially suitable for remote or rural regions to have access to the new ECG information techniques.
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| 12. |
- Hariz, Gun-Marie, et al.
(författare)
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Gender differences in quality of life following subthalamic stimulation for Parkinson's disease
- 2013
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 128:4, s. 281-285
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - Surveys of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) have shown that this procedure is roughly twice more common in men than in women. Here, we investigate possible differences between women and men undergoing STN DBS, with respect to health-related quality of life.Materials and methods - Forty-nine consecutive patients (18 women) received STN DBS. The impact of PD and its surgical treatment was compared between women and men, before and at mean of 19 +/- 11months after surgery, using the Unified Parkinson Disease Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire-39 (PDQ-39).Results - Duration of disease at surgery and off-medication scores of the motor part of the UPDRS were similar in women and men. At baseline, women had lower doses of dopaminergic medication than men, experienced more disability due to dyskinesias, had more sensory symptoms and perceived more difficulties in mobility. Following DBS, both men and women showed equal and significant (P<0.001) improvement in off-medication scores on the UPDRS III. On the PDQ-39, women expressed improvement in ADL to a greater extent than men. Moreover, women but not men showed a positive effect on mobility, stigma and cognition as well as on the summary score of PDQ-39.Conclusions - Although STN DBS results in equal degree of motor improvement between women and men, health-related quality of life seems to improve to a greater extent in women.
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| 13. |
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| 14. |
- Horimoto, Yoshiya, et al.
(författare)
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ERβ1 represses FOXM1 expression through targeting ERα to control cell proliferation in breast cancer.
- 2011
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Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 179:3, s. 1148-56
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated the effects of ectopic estrogen receptor (ER)β1 expression in breast cancer cell lines and nude mice xenografts and observed that ERβ1 expression suppresses tumor growth and represses FOXM1 mRNA and protein expression in ERα-positive but not ERα-negative breast cancer cells. Furthermore, a significant inverse correlation exists between ERβ1 and FOXM1 expression at both protein and mRNA transcript levels in ERα-positive breast cancer patient samples. Ectopic ERβ1 expression resulted in decreased FOXM1 protein and mRNA expression only in ERα-positive but not ERα-negative breast carcinoma cell lines, suggesting that ERβ1 represses ERα-dependent FOXM1 transcription. Reporter gene assays showed that ERβ1 represses FOXM1 transcription through an estrogen-response element located within the proximal promoter region that is also targeted by ERα. The direct binding of ERβ1 to the FOXM1 promoter was confirmed by chromatin immunoprecipitation analysis, which also showed that ectopic expression of ERβ1 displaces ERα from the endogenous FOXM1 promoter. Forced expression of ERβ1 promoted growth suppression in MCF-7 cells, but the anti-proliferative effects of ERβ1 could be overridden by overexpression of FOXM1, indicating that FOXM1 is an important downstream target of ERβ1 signaling. Together, these findings define a key anti-proliferative role for ERβ1 in breast cancer development through negatively regulating FOXM1 expression.
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| 15. |
- Litter, Marta I., et al.
(författare)
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Arsenic in Argentina : Technologies for arsenic removal from groundwater sources, investment costs and waste management practices
- 2019
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Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 690, s. 778-789
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Tidskriftsartikel (refereegranskat)abstract
- An overview about the presence of arsenic (As) in groundwaters of Argentina, made by a transdisciplinary group of experts is presented. In this second part, the conventional and emerging technologies for As removal, management of wastes, and the initial investment costs of the proposed technologies, with emphasis on developments of local groups are described. Successful examples of real application of conventional and emerging technologies for As removal in waters for human consumption, for medium, small and rural and periurban communities are reported. In the country, the two most applied technologies for arsenic removal at a real scale are reverse osmosis and coagulation-adsorption-filtration processes using iron or aluminum salts or polyelectrolytes as coagulants. A decision tree to evaluate the possible technologies to be applied, based on the population size, the quality of the water and its intended use, is presented, including preliminary and indicative investment costs. Finally, a section discussing the treatment and final disposal of the liquid, semiliquid and solid wastes, generated by the application of the most used technologies, is included. Conclusions and recommendations, especially for isolated rural and periurban regions, have been added.
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| 16. |
- Nakajima, Takeshi, et al.
(författare)
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MRI-Guided subthalamic nucleus deep brain stimulation without microelectrode recording : can we dispense with surgery under local anaesthesia?
- 2011
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Ingår i: Stereotactic and Functional Neurosurgery. - Basel : Karger. - 1011-6125 .- 1423-0372. ; 89:5, s. 318-325
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is traditionally performed under local anaesthetic (LA). STN visualization and routine validation of electrode location on stereotactic MRI may allow surgery under general anaesthesia (GA). This study compares the clinical outcome of MRI-guided STN DBS performed under LA or GA in a consecutive patient series. Methods: Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III) in 14 GA patients (mean age 56.1 years, disease duration 13.8 years) were compared with those of 68 LA patients (mean age 57.5 years, disease duration 15.2 years). Results: Baseline UPDRS-III were worse in the GA group, both on medication (GA: 20.9 +/- 10.8; LA: 13.2 +/- 7.8, p < 0.01) and off medication (GA: 57.9 +/- 16.6; LA: 48.2 +/- 15.7, p < 0.05). On stimulation off medication motor scores significantly improved in both groups (GA: 27.3 +/- 11.8, mean 12-month follow-up; LA: 23.7 +/- 11.8, mean 14-month follow-up). The percentage improvement was similar in both groups (GA: 52.8%; LA: 50.8%, p = 0.96). Transient surgical complications occurred in 1 GA and 7 LA patients. Conclusions: MRI-guided STN DBS under GA with routine stereotactic verification of lead location did not have a negative effect on efficacy or safety. Surgery under GA is a viable option in patients who would find it hard to tolerate awake surgery due to disease severity, comorbidities or anxiety. Copyright (C) 2011 S. Karger AG, Basel
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| 17. |
- Olmos, JJ Vegas, et al.
(författare)
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E-and W-Band High-Capacity Hybrid Fiber-Wireless Links
- 2014
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Ingår i: IEICE transactions on communications. - : Institute of Electronics, Information and Communication, Engineers, IEICE. - 0916-8516 .- 1745-1345. ; 97:7, s. 1290-1294
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we summarize the work conducted in our group in the area of E- and W-band optical high-capacity fiber-wireless links. We present performance evaluations of E- and W-band mm-wave signal generation using photonic frequency upconversion employing both VCSELs and ECLs, along with transmission over different type of optical fibers and for a number of values for the wireless link distance. Hybrid wireless-optical links can be composed of mature and resilient technology available off-the-shelf, and provide functionalities that can add value to optical access networks, specifically in mobile backhaul/fronthaul applications, dense distributed antenna systems and fiber-over-radio scenarios.
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| 18. |
- Olmos, JJ Vegas, et al.
(författare)
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VCSEL sources for optical fiber-wireless composite data links at 60GHz
- 2013
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Ingår i: 2013 18th OptoElectronics and Communications Conference Held Jointly with 2013 International Conference on Photonics in Switching, OECC/PS 2013. - 9784885522710
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Konferensbidrag (refereegranskat)abstract
- This paper presents a performance assessment of 60-GHz mm-wave signal generation using photonic upconversion employing a VCSEL as source. The system reaches 10-9 BER over a variety of optical fibers for data rates of 1.25-Gbit/s.
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| 19. |
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| 20. |
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| 21. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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