| 11. |
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| 12. |
- Furberg, Helena, et al.
(author)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Journal article (peer-reviewed)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 13. |
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| 14. |
- Green, Anders, et al.
(author)
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Incidence of Cancer and Mortality in Patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Trial.
- 2014
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In: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 114:10, s. 1518-1522
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Journal article (peer-reviewed)abstract
- The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.
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| 15. |
- Naylor, Mary D, et al.
(author)
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Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit.
- 2012
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 8:5, s. 445-52
-
Journal article (peer-reviewed)abstract
- To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article.
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| 16. |
- Postmus, Iris, et al.
(author)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
-
Journal article (peer-reviewed)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 17. |
- Silfverskiöld, Stefan, et al.
(author)
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Technology Forecast 2013 Military Utility of Six Technologies : a Report from Seminars at the SNDC Department of Military-Technology
- 2013
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Reports (other academic/artistic)abstract
- Four technology forecast reports from the Fraunhofer Institute and two internet based search reports from Recorded Future have been reviewed by staff at the Department of Military- Technology at the Swedish National Defence College (Note that there probably are other technology areas, equally interesting, but not included in this study). The task given by FMV was to assess the military utility of the chosen technologies in a time frame from 2025 to 2030, from a SwAF viewpoint.We assess the military utility of a certain technology, as its contribution to the operational capabilities of the SwAF, within identified relevant scenarios.The technologies were grouped in three classes; technologies with potentially significant, uncertain or negligible military utility.The following technologies were assessed to have a potential for significant military utility;Alternative fuelsHigh altitude platformsUnmanned Aerial VehiclesCyber DefenceThe forecasting and analysis technology described in the report "Future of Cyber Threats" if the tool is combined with advanced artificial intelligence algorithmsThe following technology was assessed to have uncertain military utility;The forecasting and analysis technology described in the report "Future of Cyber Threats" in its present formThe following technology was assessed to have negligible military utility;Walking machinesThe method used was first to make a summary of each forecast report. The technology was then put into one or more scenarios that are assessed to be the best in order to show possible military utility as well as possibilities and drawbacks of the technologies. Based on a SWOT-analysis, the contribution to SwAF capabilities and the cost in terms of acquisition, C2 footprint, logistic footprint, doctrine/TTP, training, facilities and R&D were assessed. Conclusions regarding the military utility of the technology were drawn.Our evaluation of the method used shows that there is a risk that the assessment is biased by the participating experts’ presumptions and experiences from their own field of research. The scenarios that were chosen do not cover all aspects of the technology and their possible contribution to operational capabilities. It should be stressed that we have assessed the six technologies’ potential military utility within the presented scenarios, not the technology itself.The chosen definition of military utility clearly affects the result of the study. The definition (the military utility of a certain technology is its contribution to the operational capabilities of the SwAF, within identified relevant scenarios) has been slightly modified from the one used in the Technology Forecast 2012. It is believed to be good enough for this report, but could be further elaborated in the future.The greatest value of the method used is its simplicity, cost effectiveness and the tradeoff that it promotes learning within the working group. The composition of the working group and the methodology used is believed to provide for a broad and balanced coverage of the technologies under study. This report provides executive summaries of the Fraunhofer and Recorded Future reports and helps the SwAF Headquarter to evaluate the military utility of emerging technologies within identified relevant scenarios.Given the limited quantitative base (only 2 reports) for assessing the potential value of using the tool Temporal Analytics™ used by Recorded Future, our conclusion is nevertheless that the overall value of using the tool for technology forecasting is rather poor. Our assessment is that Recorded Future at present can’t be used as an alternative to the Fraunhofer Institute. Overall, the quality of the Fraunhofer reports is considered to be balanced and of a high level of critical analysis regarding technology development. These reports are in line with our task to evaluate the military utility of the emerging technologies. In the case of Recorded Future’s technology forecast, the sources that are relevant for making military predictions are considered to be ill-suited for aggregation in the form the tool in focus, Temporal Analytics™, provides. The tool requires further development to fit military purposes. Further use of Recorded Future in the technology forecast process is therefore not recommended, at least not until the tool has been combined with advanced artificial intelligence algorithms.We propose that the Department of Military Technology at SNDC could be involved in the early phase of the Technology Forecast process giving support to FMV in choosing which technology areas that should be selected to be studied by the Fraunhofer Institute within the framework of the Technology Forecast project (Teknisk Prognos).
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| 18. |
- Torkzad, Michael R., et al.
(author)
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Magnetic resonance imaging and ultrasonography in diagnosis of pelvic vein thrombosis during pregnancy
- 2010
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 126:2, s. 107-112
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Pelvic deep vein thrombosis (DVT) is difficult to diagnose during pregnancy. In a two-center trial, we evaluated the agreement between ultrasonography and magnetic resonance imaging (MRI) in diagnosing the extent of DVT into the pelvic veins during pregnancy. MATERIALS AND METHODS: Pregnant women with proximal DVT were examined both with ultrasound and MRI as part of a study designed for treatment of DVT during pregnancy. Ultrasound was performed using color flow by specialist in vascular ultrasound with Doppler and compression techniques. The MRI sequences consisted of a 2D Time of Flight angiography with arterial flow suppression and maximum intensity projection reconstructions; a 3D, T1-w-prepared gradient echo sequence with fat saturation for thrombus imaging; a steady-state free precession sequence; and a Turbo-Spin-Echo. No contrast agent was used. Proportion of agreement (kappa) for detection of DVT in individual veins was measured for different ipsilateral veins and inferior vena cava. RESULTS: All 27 patients were imaged with both techniques at an average gestational age of 29 weeks (range 23-39). Three cases (11.5%) of DVT in the pelvic veins were missed on ultrasound but detected by MRI. The upper limit of the DVT was always depicted at a higher (20 cases, 65.4%) or the same level (seven cases, 34.6%) on MRI than on ultrasound. Agreement expressed as kappa was 0.33 (95% CI 0.27-0.40) demonstrating only fair agreement. In one woman the thrombus had propagated into the inferior vena cava, shown only on MRI. CONCLUSION: Our study suggests that in pregnant women there is only fair agreement between ultrasound and MRI for determination of extent of DVT into pelvic veins, with MRI showing consistently more detailed depiction of extension. Our results indicate that MRI has an important role as a complementary technique in the diagnosis of DVT during pregnancy.
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