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- Albrechtsen, A., et al.
(author)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Journal article (peer-reviewed)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 4. |
- Ingason, Haukur, et al.
(author)
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The Metro Project: Final Report
- 2012
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Reports (other academic/artistic)abstract
- The report compiles the results from the METRO-project. The different parts of the project; design fires, evacuation, integrated fire control, smoke control, extraordinary strain on constructions and fire- and rescue operations are presented separately. The most complicated and expensive part of the project was the performance of the large scale fire and explosion tests in the Brunsberg tunnel. The maximum heat release rates measured from the metro carriage was 77 MW. The maximum ceiling gas temperatures was 1118 °C. These values are high, and should be put into a perspective of the situation and the type of carriages used. The project is not recommending the highest values as the design fire, but values reflected in conditions. The egress study confirm that one of the major issues related to fire evacuation in underground transportation systems is that people often are reluctant to initiate an evacuation. New data show that participants moved with an average of 0.9 meters per second in the smoke filled environment (average visibility of 1.5–3.5 meters). A way-finding installation at the emergency exit, which consisted of a loudspeaker, was found to perform particularly well in terms of attracting people to the door. Two smoke control systems were simulated for a single exit metro station. The systems consisted of a pressurizing supply air system and mechanical exhaust ventilation system with and without platform screen doors. The results show that both the pressurizing supply air system and the mechanical exhaust air system provide effective smoke control for one exit metro station. The significance of the platform screen doors was shown to be important in relation to smoke control. Experiments and simulations have provided increased confidence in ability to simulate explosion scenarios to determine the pressure inside and outside a carriage and to be able to study variations of conditions such as carriage geometry and window designs. The explosion test performed show that an explosion with a relatively minor charge can significantly change the conditions for both evacuees and the rescue service. The results show that the conditions for evacuation and rescue operations can change dramatically as a result of a relatively minor explosion. Evaluation of methods and fire and rescue tactics in metros is given. Mapping of IR imaging as a tactical resource at tunnel fires was presented.
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| 5. |
- Isomaa, B., et al.
(author)
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A family history of diabetes is associated with reduced physical fitness in the Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia study
- 2010
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:8, s. 1709-1713
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Journal article (peer-reviewed)abstract
- We studied the impact of a family history of type 2 diabetes on physical fitness, lifestyle factors and diabetes-related metabolic factors. The Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia study is a population-based study in Western Finland, which includes a random sample of 5,208 individuals aged 18 to 75 years identified through the national Finnish Population Registry. Physical activity, dietary habits and family history of type 2 diabetes were assessed by questionnaires and physical fitness by a validated 2 km walking test. Insulin secretion and action were assessed based upon OGTT measurements of insulin and glucose. A family history of type 2 diabetes was associated with a 2.4-fold risk of diabetes and lower physical fitness (maximal aerobic capacity 29.2 +/- 7.2 vs 32.1 +/- 7.0, p = 0.01) despite having similar reported physical activity to that of individuals with no family history. The same individuals also had reduced insulin secretion adjusted for insulin resistance, i.e. disposition index (p < 0.001) despite having higher BMI (27.4 +/- 4.6 vs 26.0 +/- 4.3 kg/m(2), p < 0.001). Individuals with a family history of type 2 diabetes are characterised by lower physical fitness, which cannot solely be explained by lower physical activity. They also have an impaired capacity of beta cells to compensate for an increase in insulin resistance imposed by an increase in BMI. These defects should be important targets for interventions aiming at preventing type 2 diabetes in individuals with inherited susceptibility to the disease.
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