| 1. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 2. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 3. |
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| 4. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
- 2014
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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| 5. |
- Adolph, Thorsten, et al.
(författare)
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Comparison of the dummy response in two different restraint system crash tests
- 2014
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Ingår i: 2014 IRCOBI Conference Proceedings - International Research Council on the Biomechanics of Injury. ; , s. 545-561
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Konferensbidrag (refereegranskat)abstract
- In the European Project FIMCAR, a proposal for a frontal impact test configuration was developed which included an additional full width deformable barrier (FWDB) test. Motivation for the deformable element was partly to measure structural forces as well as to produce a severe crash pulse different from that in the offset test. The objective of this study was to analyse the safety performance of vehicles:in the full width rigid barrier test (FWRB) andin the full width deformable barrier test (FWDB)In total, 12 vehicles were crashed in both configurations. Comparison of these tests to real world accident data was used to identify the crash barrier most representative of real world crashes. For all vehicles, the airbag visible times were later in the FWDB configuration. This was attributed to the attenuation of the initial acceleration peak, observed in FWRB tests, by the addition of the deformable element. These findings were in alignment with airbag triggering times seen in real world crash data. Also, the dummy loadings were slightly worse in FWDB compared to FWRB tests, which is possibly linked to the airbag firing and a more realistic loading of the vehicle crash structures in the FWDB configuration. Evaluations of the lower extremities have shown a general increasing of the tibia index with the crash pulse severity.
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| 6. |
- Adolph, T., et al.
(författare)
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Development of compatibility assessments for full-width and offset frontal impact test procedures in FIMCAR
- 2014
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Ingår i: International Journal of Crashworthiness. - : Informa UK Limited. - 1358-8265 .- 1754-2111. ; 19:4, s. 414-430
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Tidskriftsartikel (refereegranskat)abstract
- The goal of the project FIMCAR (Frontal Impact and Compatibility Assessment Research) was to define an integrated set of test procedures and associated metrics to assess a vehicle's frontal impact protection, which includes self-And partner-protection. For the development of the set, two different full-width tests (full-width deformable barrier [FWDB] test, full-width rigid barrier test) and three different offset tests (offset deformable barrier [ODB] test, progressive deformable barrier [PDB] test, moveable deformable barrier with the PDB barrier face [MPDB] test) have been investigated. Different compatibility assessment procedures were analysed and metrics for assessing structural interaction (structural alignment, vertical and horizontal load spreading) as well as several promising metrics for the PDB/MPDB barrier were developed.The final assessment approach consists of a combination of the most suitable full-width and offset tests. For the full-width test (FWDB), a metric was developed to address structural alignment based on load cell wall information in the first 40 ms of the test. For the offset test (ODB), the existing ECE R94 was chosen. Within the paper, an overview of the final assessment approach for the frontal impact test procedures and their development is given.
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| 7. |
- del Poso de Dios, Eduardo, et al.
(författare)
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Development of a Structural Interaction Assessment Criteria Using Progressive Deformable Barrier Data
- 2013
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Ingår i: Proceedings of the 23rd Conference of the Enhanced Safety of Vehicles.
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Konferensbidrag (refereegranskat)abstract
- Structural interaction has been one of the critical issues for improved frontal impact protection. An evaluation procedure for structural interaction has been difficult to develop using objective test data procedures. While previous research with the PDB barrier has been promising based on subjective evaluations, an objective assessment criteria has been elusive. Part of the EU project FIMCAR focused on the development of an assessment procedure to assess important frontal impact characteristics like load spreading.Test and simulation data from vehicle impacts with the PDB or MPDB were collected for different vehicle models, spanning a range of vehicle masses and vehicle classes. Available car-to-car crash tests were also collected for reference. The main information analyzed w.r.t. the assessment of load spreading was the deformation pattern of the PDB barrier after a test. These deformation plots were reviewed and subjectively assessed by experts. The subjective assessments were used to develop key characteristics that should be detected by a numerical assessment of the 3D data. These subjective assessments were then compared to different objective (numerical) assessments for the barriers to ensure correlation of the results and then validated with available car-car data. Assessment of the influence of assessment area and scanning resolution were also performed.
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| 8. |
- Harris, Simon R., et al.
(författare)
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Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing
- 2012
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:4, s. 413-419
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.
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