| 1. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 2. |
- Fitzmauric, C., et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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| 3. |
- Savage, J. E., et al.
(författare)
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
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Tidskriftsartikel (refereegranskat)abstract
- Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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| 4. |
- Silventoinen, K., et al.
(författare)
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The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- 2019
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
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Tidskriftsartikel (refereegranskat)abstract
- The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
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| 5. |
- Komatsu, Kimberly J., et al.
(författare)
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Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
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Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
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| 6. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 7. |
- Du, Andong, et al.
(författare)
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On the efficient particle dispersion and transfer in the fabrication of SiC-particle-reinforced aluminum matrix composite
- 2023
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Ingår i: Crystals. - : MDPI. - 2073-4352. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Lightweight SiC-particle-reinforced aluminum composites have the potential to replace cast iron in brake discs, especially for electric vehicles. This study investigates the effect of SiC particle size and matrix alloy composition on the resulting transfer efficiency and particle distribution. The performance of a specially designed stirring head was studied using a water model, and the stirring head conditions were assessed to understand the particle transfer and dispersion mechanisms in the molten aluminum. The standard practice of thermal pre-treatment promotes the wetting of the reinforcing particles and commonly causes clustering before the addition to the melt. This early clustering affects the transfer efficiency and particle dispersion, where their interaction with the melt top-surface oxide skin plays an important role. In addition, the transfer efficiency was linked to the particle size and the chemical composition of the matrix alloy. Smaller particles aggravated the degree of clustering, and the addition of rare earth elements as alloying elements in the matrix alloy affected the particle dispersion. The stirring parameters should be selected to ensure cluster disruption when the carbides are added to the melt.
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| 8. |
- Du, A., et al.
(författare)
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On the hardness and elastic modulus of phases in SiC-reinforced Al composite : Role of La and Ce addition
- 2021
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Ingår i: Materials. - : MDPI. - 1996-1944 .- 1996-1944. ; 14:21
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Tidskriftsartikel (refereegranskat)abstract
- The use of silicon carbide particles (SiCp) as reinforcement in aluminium (Al)-based composites (Al/SiCp) can offer high hardness and high stiffness. The rare-earth elements like lanthanum (La) and cerium (Ce) and transition metals like nickel (Ni) and copper (Cu) were added into the matrix to form intermetallic phases; this is one way to improve the mechanical property of the composite at elevated temperatures. The α-Al15 (Fe,Mn)3 Si2, Al20 (La,Ce)Ti2, and Al11 (La,Ce)3, π-Al8 FeMg3 Si6 phases are formed. Nanoindentation was employed to measure the hardness and elastic modulus of the phases formed in the composite alloys. The rule of mixture was used to predict the modulus of the matrix alloys. The Halpin–Tsai model was applied to calculate the elastic modulus of the particle-reinforced composites. The transition metals (Ni and Cu) and rare-earth elements (La and Ce) determined a 5–15% increase of the elastic modulus of the matrix alloy. The SiC particles increased the elastic modulus of the matrix alloy by 10–15% in composite materials.
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| 9. |
- Du, A., et al.
(författare)
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Role of matrix alloy, reinforcement size and fraction in the sliding wear behaviour of Al-SiCp MMCs against brake pad material
- 2023
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Ingår i: Wear. - : Elsevier. - 0043-1648 .- 1873-2577. ; 530-531
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Tidskriftsartikel (refereegranskat)abstract
- Aluminium metal matrix composites were produced by a newly developed stirring device for stir casting with different matrix alloys, SiC particle fractions and sizes to investigate these parameters' influence on the materials' wear performance. The wear performance of the composites was evaluated with dry sliding pin-on-plate tests against a high-speed train brake pad, and the study of wear surfaces was completed by electron microscopy. The formation of an iron-based tribolayer during wear protected the metal matrix composite from further wear damage. The composite reinforced with 19% SiC particles sized 32 μm showed an increasing coefficient of friction during wear, and the wear surface showed traces of third body wear. The rare earth and transition metal added to the matrix alloy increased the hardness of the composite, and the intermetallic phases reduced the development of the Fe-based tribolayer. The composites with small SiC particles presented the Fe transfer on the exposed aluminium surface, with a lower wear rate and friction coefficient than other composites. The direct comparison of composites produced with different sizes of SiC particles highlighted that the relationship between the wear rate and the coefficient of friction of the composites and the brake pad showed a linear trend.
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| 10. |
- Du, Andong, et al.
(författare)
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The Influence of Ce, La, and SiC Particles Addition on the Formability of an Al-Si-Cu-Mg-Fe SiCp-MMC
- 2022
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Ingår i: Materials. - : MDPI. - 1996-1944 .- 1996-1944. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- Road transport and the associated fuel consumption plays a primary role in emissions. Weight reduction is critical to reaching the targeted reduction of 34% in 2025. Weight reduction in moving parts, such as pistons and brake disc rotors, provide a high-impact route to achieve this goal. The current study aims to investigate the formability of Al–Si alloys reinforced with different fractions and different sizes of SiCp to create an efficient and lightweight Al-MMC brake disk. Lanthanum (La) and cerium (Ce) were added to strengthen the aluminium matrix alloy and to improve the capability of the Al-MMC brake discs to withstand elevated temperature conditions, such as more extended braking periods. La and Ce formed intermetallic phases that further strengthened the composite. The analysis showed the processability and thermal stability of the different material’s combinations: increased particle sizes and broader size range mixture supported the formation of the SiCp particle interactions, acting as an internal scaffolding. In conclusion, the additions of Ce and La strengthened the softer matrix regions and resulted in a doubled compression peak strength of the material without affecting the formability, as demonstrated by the processing maps.
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