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Sökning: WFRF:(Xu Ying) > (2015-2019)

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1.
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2.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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3.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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4.
  • Kato, Norihiro, et al. (författare)
  • Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
  • 2015
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
  • Tidskriftsartikel (refereegranskat)abstract
    • We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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5.
  • Andersson, Eva M., 1968, et al. (författare)
  • High exposure to perfluorinated compounds in drinking water and thyroid disease. A cohort study from Ronneby, Sweden
  • 2019
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 176
  • Tidskriftsartikel (refereegranskat)abstract
    • Per- and polyfluoroalkyl substances (PFAS) are extremely persistent manmade substances. Apart from exposure through food and indoor air and dust, humans can be exposed through drinking water if the surface or groundwater is contaminated. In 2013 very high levels of PFOS and PFHxS were found in the drinking water from one of the two waterworks supplying the municipality of Ronneby, Sweden. A cohort was formed, including all individuals who had lived at least one year in Ronneby during the period 1980–2013 (ñ63,000). Each year, addresses that got their drinking water from the contaminated water works were identified. Through the Swedish personal identity number, each individual was linked to registers providing diagnoses and prescriptions for hyper- and hypothyroidism. In total, 16,150 individuals had ever been exposed. The hazard ratios did not indicate any excess risk of hyperthyroidism among those with contaminated water. For hypothyroidism, the risk of being prescribed medication was significantly increased among women with exposure during the mid part of the study period (but not men). However, the association with period of exposure was non-monotonic, so the significance is considered to be a chance finding. Our research was limited by the relatively simple exposure assessment.
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6.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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7.
  • Luo, Yiqi, et al. (författare)
  • Toward more realistic projections of soil carbon dynamics by Earth system models
  • 2016
  • Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 30:1, s. 40-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Soil carbon (C) is a critical component of Earth system models (ESMs), and its diverse representations are a major source of the large spread across models in the terrestrial C sink from the third to fifth assessment reports of the Intergovernmental Panel on Climate Change (IPCC). Improving soil C projections is of a high priority for Earth system modeling in the future IPCC and other assessments. To achieve this goal, we suggest that (1) model structures should reflect real-world processes, (2) parameters should be calibrated to match model outputs with observations, and (3) external forcing variables should accurately prescribe the environmental conditions that soils experience. First, most soil C cycle models simulate C input from litter production and C release through decomposition. The latter process has traditionally been represented by first-order decay functions, regulated primarily by temperature, moisture, litter quality, and soil texture. While this formulation well captures macroscopic soil organic C (SOC) dynamics, better understanding is needed of their underlying mechanisms as related to microbial processes, depth-dependent environmental controls, and other processes that strongly affect soil C dynamics. Second, incomplete use of observations in model parameterization is a major cause of bias in soil C projections from ESMs. Optimal parameter calibration with both pool- and flux-based data sets through data assimilation is among the highest priorities for near-term research to reduce biases among ESMs. Third, external variables are represented inconsistently among ESMs, leading to differences in modeled soil C dynamics. We recommend the implementation of traceability analyses to identify how external variables and model parameterizations influence SOC dynamics in different ESMs. Overall, projections of the terrestrial C sink can be substantially improved when reliable data sets are available to select the most representative model structure, constrain parameters, and prescribe forcing fields.
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8.
  • Miao, Yanfeng, et al. (författare)
  • Stable and bright formamidinium-based perovskite light-emitting diodes with high energy conversion efficiency
  • 2019
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Solution-processable perovskites show highly emissive and good charge transport, making them attractive for low-cost light-emitting diodes (LEDs) with high energy conversion efficiencies. Despite recent advances in device efficiency, the stability of perovskite LEDs is still a major obstacle. Here, we demonstrate stable and bright perovskite LEDs with high energy conversion efficiencies by optimizing formamidinium lead iodide films. Our LEDs show an energy conversion efficiency of 10.7%, and an external quantum efficiency of 14.2% without outcoupling enhancement through controlling the concentration of the precursor solutions. The device shows low efficiency droop, i.e. 8.3% energy conversion efficiency and 14.0% external quantum efficiency at a current density of 300 mA cm(-2), making the device more efficient than state-of-the-art organic and quantum-dot LEDs at high current densities. Furthermore, the half-lifetime of device with benzylamine treatment is 23.7 hr under a current density of 100 mA cm(-2), comparable to the lifetime of near-infrared organic LEDs.
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9.
  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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10.
  • Skwark, Marcin J., et al. (författare)
  • Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
  • 2017
  • Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in the scale and diversity of population genomic datasets for bacteria now provide the potential for genome-wide patterns of co-evolution to be studied at the resolution of individual bases. Here we describe a new statistical method, genomeDCA, which uses recent advances in computational structural biology to identify the polymorphic loci under the strongest co-evolutionary pressures. We apply genomeDCA to two large population data sets representing the major human pathogens Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A Streptococcus). For pneumococcus we identified 5,199 putative epistatic interactions between 1,936 sites. Over three-quarters of the links were between sites within the pbp2x, pbp1a and pbp2b genes, the sequences of which are critical in determining non-susceptibility to beta-lactam antibiotics. A network-based analysis found these genes were also coupled to that encoding dihydrofolate reductase, changes to which underlie trimethoprim resistance. Distinct from these antibiotic resistance genes, a large network component of 384 protein coding sequences encompassed many genes critical in basic cellular functions, while another distinct component included genes associated with virulence. The group A Streptococcus (GAS) data set population represents a clonal population with relatively little genetic variation and a high level of linkage disequilibrium across the genome. Despite this, we were able to pinpoint two RNA pseudouridine synthases, which were each strongly linked to a separate set of loci across the chromosome, representing biologically plausible targets of co-selection. The population genomic analysis method applied here identifies statistically significantly co-evolving locus pairs, potentially arising from fitness selection interdependence reflecting underlying protein- protein interactions, or genes whose product activities contribute to the same phenotype. This discovery approach greatly enhances the future potential of epistasis analysis for systems biology, and can complement genome-wide association studies as a means of formulating hypotheses for targeted experimental work.
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11.
  • Takeuchi, Fumihiko, et al. (författare)
  • Interethnic analyses of blood pressure loci in populations of East Asian and European descent
  • 2018
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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12.
  • Wheeler, Eleanor, et al. (författare)
  • Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
  • 2017
  • Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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14.
  • Zhao, Ying, et al. (författare)
  • Intramyocardial Dissecting Hematoma after Acute Myocardial Infarction : Echocardiographic Features and Clinical Outcome
  • 2016
  • Ingår i: Echocardiography. - : Wiley-Blackwell. - 0742-2822 .- 1540-8175. ; 33:7, s. 962-969
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Intramyocardial dissecting hematoma (IDH) after acute myocardial infarction (MI) is a rare form of subacute cardiac rupture and hence management uncertainties. The objective of this study was to describe the clinical course of a small series of IDH patients and to review the available evidence for managing similar cases. Methods: Eight IDH patients from our center had echocardiographic, coronary angiographic and clinical outcome data reviewed. PubMed was also searched for IDH following MI. Cases were divided into three groups and compared according to the dissection location. Results: In our 8 patients, 3 had septal, 1 right ventricular (RV), and 4 left ventricular (LV) dissection. Five were medically treated and 3 surgically repaired. Reviewing the literature revealed 68 IDH patients, of mean age 66 +/- 10 years, 43 males. The percentage of IDH involving the LV free wall, septal, and RV free wall were 47%, 26.5%, and 26.5%, respectively. In the cohort as a whole, mortality was not different between surgically and medically treated patients (33.3% vs. 54.3%, P = 0.08), neither based on the IDH location (P = 0.49). While surgical and medical treatment of the LV free wall (20.0% vs. 40.9%, P = 0.25) and septal (46.2% vs. 60.0%, P = 0.60) were not different, surgical repair of RV free wall had significantly better survival (30.0% vs. 87.5%, P = 0.015). The LVEF (P = 0.82), mitral regurgitation (P = 0.49) failed to predict mortality. Conclusion: While survival following medical and surgical treatment of LV IDH is not different, patients with RV free wall dissection benefit significantly from surgical repair.
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15.
  • Bäckhed, Fredrik, 1973, et al. (författare)
  • Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
  • 2015
  • Ingår i: Cell Host & Microbe. - Cambridge : Elsevier BV. - 1931-3128 .- 1934-6069. ; 17:5, s. 690-703
  • Tidskriftsartikel (refereegranskat)abstract
    • The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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17.
  • Chen, Shaoqing, et al. (författare)
  • Anchoring High-Concentration Oxygen Vacancies at Interfaces of CeO2–x/Cu toward Enhanced Activity for Preferential CO Oxidation
  • 2015
  • Ingår i: ACS Applied Materials & Interfaces. - 1944-8252 .- 1944-8244. ; 7:41, s. 22999-23007
  • Tidskriftsartikel (refereegranskat)abstract
    • Catalysts are urgently needed to remove the residual CO in hydrogen feeds through selective oxidation for large-scale applications of hydrogen proton exchange membrane fuel cells. We herein propose a new methodology that anchors high concentration oxygen vacancies at interface by designing a CeO2–x/Cu hybrid catalyst with enhanced preferential CO oxidation activity. This hybrid catalyst, with more than 6.1% oxygen vacancies fixed at the favorable interfacial sites, displays nearly 100% CO conversion efficiency in H2-rich streams over a broad temperature window from 120 to 210 °C, strikingly 5-fold wider than that of conventional CeO2/Cu (i.e., CeO2 supported on Cu) catalyst. Moreover, the catalyst exhibits a highest cycling stability ever reported, showing no deterioration after five cycling tests, and a super long-time stability beyond 100 h in the simulated operation environment that involves CO2 and H2O. On the basis of an arsenal of characterization techniques, we clearly show that the anchored oxygen vacancies are generated as a consequence of electron donation from metal copper atoms to CeO2 acceptor and the subsequent reverse spillover of oxygen induced by electron transfer in well controlled nanoheterojunction. The anchored oxygen vacancies play a bridging role in electron capture or transfer and drive molecule oxygen into active oxygen species to interact with the CO molecules adsorbed at interfaces, thus leading to an excellent preferential CO oxidation performance. This study opens a window to design a vast number of high-performance metal-oxide hybrid catalysts via the concept of anchoring oxygen vacancies at interfaces.
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18.
  • Chen, Ying, et al. (författare)
  • Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
  • 2015
  • Ingår i: Molecular Cancer Therapeutics. - 1538-8514. ; 14:1, s. 259-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and is previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. beta-catenin was determined by immunohistochemistry, PAF levels by ELISA and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared to WT mice. While all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared to WT mice, cytosol expression of beta-catenin was significantly decreased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion lack of alk-SMase markedly increases AOM/DSS induced colonic tumorigenesis associated with decreased ceramide and increased sphingosine-1-phosphate and PAF levels.
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20.
  • de Vries, Paul S., et al. (författare)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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21.
  • Feitosa, Mary F., et al. (författare)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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22.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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23.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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24.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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25.
  • Gan, Zhixing, et al. (författare)
  • Electron transition pathways of photoluminescence from 3C-SiC nanocrystals unraveled by steady-state, blinking and time-resolved photoluminescence measurement
  • 2016
  • Ingår i: Journal of Physics D. - : Institute of Physics (IOP). - 0022-3727 .- 1361-6463. ; 49:27
  • Tidskriftsartikel (refereegranskat)abstract
    • The cubic phase SiC nanocrystals (3C-SiC NCs) have been extensively studied for electronics and photonics applications. In this work we study the electron transition pathways of photoluminescence (PL) from 3C-SiC NCs. It is found through measuring the steady-state, blinking and time-resolved PL spectra that surface passivation by glycerol improved the steady-state PL intensity (it does not modify the emission wavelength) and the NCs fluoresced more steadily. The PL decay lifetimes are shown to be the same when the detection wavelength is modified to scan the broad PL peak, implying that the broad PL peak is originated from the distribution of NCs' sizes. Furthermore, the PL decay lifetimes are not modified by the surface passivation. It is concluded that for PL, the electron is photoexcited from the ground state in the NC to a high-energy excited state, relaxes to the first excited state then radiatively recombines to the ground state to emit a photon. The photoexcited electron at the high-energy excited state could transit to the surface state, resulting in a reduced PL intensity and a decreased on-state dwell time in the blinking trajectory. The PL decay lifetime data implies that the two principal electron transition pathways of (a) high-energy excited state double right arrow the first excited state double right arrow the ground state, and (b) high-energy excited state double right arrow surface state double right arrow the ground state are independent from each other. We strongly believe that such a deep knowledge about 3C-SiC NCs will open new doors to harness them for novel applications.
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26.
  • Gan, Zhixing, et al. (författare)
  • Photon Reabsorption and Nonradiative Energy-Transfer-Induced Quenching of Blue Photoluminescence from Aggregated Graphene Quantum Dots
  • 2016
  • Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 120:51, s. 29432-29438
  • Tidskriftsartikel (refereegranskat)abstract
    • A deep understanding of the photoluminescence (PL) from aggregated graphene quantum dots (GQDs) is very important for their practical applications. Here the PL spectra from GQDs solutions at different concentrations are studied. We find that the intensity of the green emission (ca. 530560 nm) linearly relies on the concentration of GQDs, whereas the blue PL (ca. 425 nm) intensity is below the linear relationship, indicating a concentration-induced partial quenching of blue PL. Confocal fluorescence images explicitly demonstrate the aggregation of GQDs at high concentration. The concentration-induced PL quenching is successfully interpreted by a model of photon reabsorption and nonradiative energy transfer, indicating that, at the aggregated states, the excited electrons of GQDs may nonradiatively relax to ground states through couplings with neighboring ones. Simulated fluorescence decay results show that the energy transfer between neighboring GQDs results in a prolonged dwell time of electron on high-energy state and thus increases the decay time of 425 nm emission, while 550 nm emission remains unaffected, which is consistent with the experimental results. This work will contribute to a deep understanding on PL of GQDs and is also of huge importance to extend GQDs applications.
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27.
  • Ganda, Anjali, et al. (författare)
  • Plasma metabolite profiles, cellular cholesterol efflux, and non-traditional cardiovascular risk in patients with CKD
  • 2017
  • Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 112, s. 114-122
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease.METHODS: We recruited 120 CKD patients (eGFR<30mL/min/1.73m(2)) and 120 control subjects (eGFR ≥60mL/min/1.73m(2)) in order to measure cholesterol efflux using either patients' HDL and THP-1 macrophages or patients' monocytes and a flow cytometry based cholesterol efflux assay. We also measured cell-surface levels of the common β subunit of the IL-3/GM-CSF receptor (IL-3Rβ) which has been linked to defective cholesterol homeostasis and may promote monocytosis. In addition, we measured plasma inflammatory cytokines and plasma metabolite profiles.RESULTS: There was a strong positive correlation between cell-surface IL-3Rβ levels and monocyte counts in CKD (P<0.001). ABCA1 mRNA was reduced in CKD vs. control monocytes (P<0.05), across various etiologies of CKD. Cholesterol efflux to apolipoprotein A1 was impaired in monocytes from CKD patients with diabetic nephropathy (P<0.05), but we found no evidence for a circulating HDL-mediated defect in cholesterol efflux in CKD. Profiling of plasma metabolites showed that medium-chain acylcarnitines were both independently associated with lower levels of cholesterol transporter mRNA in CKD monocytes at baseline (P<0.05), and with cardiovascular events in CKD patients after median 2.6years of follow-up.CONCLUSIONS: Cholesterol efflux in humans varies in terms of cellular components. We report a cellular defect in ABCA1-mediated cholesterol efflux in monocytes from CKD patients with diabetic nephropathy. Unlike several traditional risk factors for atherosclerotic cardiovascular disease, plasma metabolites inversely associated with endogenous cholesterol transporters predicted cardiovascular events in CKD patients. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
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28.
  • He, Wang, et al. (författare)
  • RF Compliance Study of Temperature Elevation in Human Head Model Around 28 GHz for 5G User Equipment Application : Simulation Analysis
  • 2018
  • Ingår i: IEEE Access. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 2169-3536. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The crowdedness of current cellular bands and the demand for higher transmission speed prompt the use of the millimeter-wave spectrum for the next-generation mobile communication. In the millimeter-wave frequencies, the dosimetric quantity for human exposure to electromagnetic fields changes from the specific absorption rate to incident power density. In this paper, we used 28-GHz beam-steering patch arrays, a dipole antenna, and plane waves to investigate the temperature elevation in a multi-layer model of human head and its correlation with power density metrics. The power density averaged over one square-centimeter in free space and the peak temperature elevation in tissue at 28 GHz have good correlation. The peak temperature elevation indicated by the power density averaged one square-centimeter also agrees well with the peak temperature elevation induced by the plane waves. The results show that the averaging area of a few square-centimeters may be a good candidate for the spatial-average power density. The findings provide valuable input to the ongoing revision and updating of relevant safety standards and guidelines.
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29.
  • Huang, Hongyun, et al. (författare)
  • Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
  • 2018
  • Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:2, s. 310-324
  • Forskningsöversikt (refereegranskat)abstract
    • Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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30.
  • Huang, Jing, et al. (författare)
  • Development of a human head and neck muscle activation control model based on BPNN
  • 2018
  • Ingår i: Journal of Intelligent and Fuzzy Systems. - 1875-8967 .- 1064-1246. ; 34:2, s. 1161-1167
  • Tidskriftsartikel (refereegranskat)abstract
    • With the development of vehicle active safety technology and its combination with passive safety technologies, there is a need for an updated tool to assess the performance of vehicle safety systems in both the in-crash and pre-crash phases. Consequently, developing human body models with active muscles is critical to achieve improved bio-fidelity simulation results to evaluate the effects of safety systems. In the present study, an innovative human active muscle control model based on a back-propagation neural network (BPNN) controller was developed, and the active muscle response was modelled using a feedback control strategy with the BPNN algorithm implemented in a human head and neck Sim Mechanics model. The BPNN controller was used to dynamically control the muscle activation level, the most complicated and essential factor in active muscle force calculation based on the Hill equation. Then, the active muscle control model was evaluated by simulating the human response in volunteer sled tests. The results validated the proposed active muscle control method as successful and easily realized. Achieving muscle active control would further improve the bio-fidelity of the human body model.
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31.
  • Huang, Ying-Lai, 1962, et al. (författare)
  • Mechanical ventilation promotes lung metastasis in experimental 4T1 breast cancer lung-metastasized models
  • 2018
  • Ingår i: Cancer Management and Research. - 1179-1322. ; 10, s. 545-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/purpose: The aim of this study was to test the hypothesis that mechanical ventilation (MV) during cancer surgery induces lung stroma/tissue milieu changes, creating a favorable microenvironment for postoperative lung metastatic tumor establishment. Materials and methods: In Protocol A, female BALB/c mice were divided into an MV group and a control (no MV) group, both of which were anesthetized and subjected to intravenous injection of green fluorescent protein (GFP)-labeled mouse mammary carcinoma cell line (4T1) cells. After 24 h, the lung tissue was removed and the number of GFP-labeled 4T1 cells was calculated. In Protocol B, the clinically relevant mouse model of spontaneous breast cancer lung metastasis was used with surgical resection of the primary tumor to investigate the MV event that dictates postoperative lung metastasis. Female BALB/c mice were inoculated in the mammary fat pad with 4T1 cells. After 14-d growth, mice were anesthetized and divided into an MV group and a control (no MV) group during surgical procedures (mastectomy). Metastatic tumor burden was assessed two weeks after mastectomy by both macroscopic metastatic nodule count, hematoxylin–eosin histology, immunohistochemistry for the macrophage marker (CD68), and epithelial cell adhesion molecule (EpCAM). Results: MV was associated with a significant increase in the number of circulating breast tumor cells (GFP-labeled 4T1 cells) remaining in the microvasculature of the lung (P<0.01). Immunohistochemical results showed increased infiltration of CD68-positive macrophages within injured lung parenchyma and metastatic tumor as well as increased expression of EpCAM in metastatic nodules. Postoperative metastases were more prevalent in the mechanically ventilated mice group compared to the non-ventilated group (P<0.05). Conclusion: MV-induced lung metastasis occurs by attracting circulating tumor cells to the site of the lung injury and by accelerating the proliferation of preexisting micro-metastases in the lung. These observations indicate that the metastasis-enhancing effect of MV should be considered in general anesthesia during cancer surgery. © 2018 Huang et al.
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32.
  • Ji, Jiadong, et al. (författare)
  • Detection for pathway effect contributing to disease in systems epidemiology with a case-control design
  • 2015
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 5:1, s. e006721-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Identification of pathway effects responsible for specific diseases has been one of the essential tasks in systems epidemiology. Despite some advance in procedures for distinguishing specific pathway (or network) topology between different disease status, statistical inference at a population level remains unsolved and further development is still needed. To identify the specific pathways contributing to diseases, we attempt to develop powerful statistics which can capture the complex relationship among risk factors. Setting and participants: Acute myeloid leukaemia (AML) data obtained from 133 adults (98 patients and 35 controls; 47% female). Results: Simulation studies indicated that the proposed Pathway Effect Measures (PEM) were stable; bootstrap-based methods outperformed the others, with bias-corrected bootstrap CI method having the highest power. Application to real data of AML successfully identified the specific pathway (Treg -> TGF beta -> Th17) effect contributing to AML with p values less than 0.05 under various methods and the bias-corrected bootstrap CI (-0.214 to -0.020). It demonstrated that Th17-Treg correlation balance was impaired in patients with AML, suggesting that Th17-Treg imbalance potentially plays a role in the pathogenesis of AML. Conclusions: The proposed bootstrap-based PEM are valid and powerful for detecting the specific pathway effect contributing to disease, thus potentially providing new insight into the underlying mechanisms and ways to study the disease effects of specific pathways more comprehensively.
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33.
  • Jin, Zhan-Kui, et al. (författare)
  • Outcomes of total knee arthroplasty in the adult Kashin-Beck disease with severe osteoarthritis.
  • 2019
  • Ingår i: International Orthopaedics. - : Springer. - 0341-2695 .- 1432-5195. ; 43:2, s. 323-331
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and the severe knee pain and functional limitations were seriously affecting the quality of life in patients with end-stage KBD. We retrospectively evaluated the clinical outcomes and the quality of life in KBD patients with total knee arthroplasty (TKA).METHODS: A total of 22 subjects (25 knees) suffered KBD with severe knee pain and underwent primary TKA. Knee pain was measured by visual analogue scale (VAS), and the knee function was evaluated by Knee Society Clinical Rating System Score (KSS). KBD Quality of Life (KBDQOL) was used to evaluate the quality of life in KBD patients before and after TKA.RESULTS: There were no major complications after TKA. The levels of VAS score were obviously deceased in post-operation than that in pre-operation. The levels of KSS score were increased in one year after TKA compared with the pre-operative values, and it maintained a higher level on three years after TKA. The average KBDQOL score level of each domain in pre-operation and one and three years after TKA was increased accordingly. The average scores of physical function, activity limitation, support of society, mental health, and general health in one year after TKA were significantly higher than those in pre-operation.CONCLUSIONS: TKA can reduce knee pain, improve knee function, and improve the quality life in KBD patients. KBDQOL questionnaire may be a promising instrument for assessing the quality life in KBD patients.
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34.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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35.
  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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36.
  • Ke, Ying, et al. (författare)
  • On the use of a novel nanoporous polyethylene (nanoPE) passive cooling material for personal thermal comfort management under uniform indoor environments
  • 2018
  • Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 145, s. 85-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Passive cooling materials such as specially designed nanoporous microfibers are nearly transparent to infrared thermal radiation emitted from the human body. Hence, such passive cooling materials have the potential to help indoor occupants attain thermal comfort through regulating the radiative body heat in indoor conditions. In this work, a regular fit women's business shirt made of the nanoporous polyethylene (nanoPE) material was designed and its cooling performance under four uniform indoor conditions was examined. A cotton shirt (CO) with the same size and pattern as the nanoPE shirt was designed and selected as the control. Eighteen female participants underwent eight 80-min trials at four indoor temperatures: 23, 25, 27 and 29 °C. Trials were performed in simulated indoor environments where RH = 60% and the air velocity was kept below 0.10 m/s. Results have demonstrated that participants had significantly lower mean skin temperatures, mean upper torso temperatures and forearm temperatures in nanoPE as compared to CO at 23, 25 and 27 °C. Participants showed the maximum satisfaction with the thermal environment while wearing the CO clothing at 25 °C, whereas they were mostly satisfied with the thermal environment while wearing the nanoPE clothing at 27 °C. Thus, the acceptable air conditioning setpoint temperature could be extended by 1.5 °C from 25.5 to 27 °C while using the nanoPE clothing and thereby, this saves about 9–15% cooling energy. Finally, it was concluded that the nanoPE passive cooling clothing contributes to enhancing indoor thermal comfort under uniform environments and saving significant cooling energy.
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37.
  • Li, Shu, et al. (författare)
  • Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia : a systematic review and network meta-analysis
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12-0.24) and safer (OR: 0.72, 95% CI: 0.56-0.91) than allopurinol.
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38.
  • Liu, Kaifei, et al. (författare)
  • Asperosaponin VI protects against bone destructions in collagen induced arthritis by inhibiting osteoclastogenesis
  • 2019
  • Ingår i: Phytomedicine. - München : Elsevier. - 0944-7113 .- 1618-095X. ; 63
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Bone destructive diseases like rheumatoid arthritis (RA), osteoporosis and bone metastatic tumors are mainly mediated by over-activated osteoclasts. Asperosaponin VI (AVI), isolated from the rhizome of Dipsacus asper, belongs to triterpenoid saponins. It has multiple physiological activities but its effects on RA, especially on osteoclast differentiation and activation are still unclear.PURPOSE: Explore the protective role of AVI on collagen induced arthritis (CIA) in vivo and RANKL induced osteoclastogenesis in vitro.METHODS: The effects of AVI on cell viability and RANKL-induced osteoclastogenesis, actin ring formation, bone resorption activity as well as on osteoclast specific gene and protein expression were tested using bone marrow derived monocytes (BMMs). Paws from CIA mice were used for micro-CT, HE and TRAP staining, real-time PCR and western blot. Sera were used for cytokine analysis by ELISA. The signaling pathways were detected using western blot, real-time PCR and immunofluorescence assay.RESULTS: AVI significantly inhibited RANKL-induced osteoclast formation and bone resorption activity by suppressing the formation of actin ring. It also inhibited the expression of various osteoclatogenesis marker genes and signaling pathways. AVI protected arthritis in vivo by suppressing inflammation and bone loss.CONCLUSION: AVI exerts its anti-osteoclastogenic activity both in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function. Thus, our studies demonstrate a potential therapeutic role for AVI in preventing or inhibiting RANKL-mediated osteolytic bone diseases.
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39.
  • Liu, Kaifei, et al. (författare)
  • Regulatory role of Golgi brefeldin A resistance factor-1 in amyloid precursor protein trafficking, cleavage and Aβ formation
  • 2019
  • Ingår i: Journal of Cellular Biochemistry. - Hoboken : John Wiley & Sons. - 0730-2312 .- 1097-4644. ; 120:9, s. 15604-15615
  • Tidskriftsartikel (refereegranskat)abstract
    • β-amyloid peptide (Aβ) deposition derived from sequential cleavage of the amyloid precursor protein (APP) through the amyloidogenic pathway is an important characteristic feature of Alzheimer's disease (AD). During this process, cellular trafficking plays a crucial role. A large Sec7-domain containing ADP-ribosylation factor guanine nucleotide exchange factor (ARF-GEF), Golgi brefeldin A resistance factor 1 (GBF1) has been reported to initiate the ADP-ribosylation factor (Arf) activation cascade at trans-Golgi network, which plays a crucial function at the endoplasmic reticulum-Golgi interface. In this study, we investigated the role of GBF1 in APP transmembrane transport and Aβ formation. Using APP/PS1 (presenilin 1) overexpressing transgenic mice, we demonstrate that GBF1 has upregulated the expression of APP, indicating a role for GBF1 in APP physiological process. Knocking down of GBF1 using small interfering has significantly increased the intracellular but not the surface expression of APP. In contrast, overexpression of wild-type (WT) and guanine nucleotide exchange factor (GEF) in the activated form but not the GEF deficient mutation induced continuous activation of GBF1, which subsequently increased the surface level of APP. Interestingly, inhibition of GBF1 by c(BFA) also impaired APP trafficking and induced endoplasmic reticulum (ER) stress in SH-SY5Y cells. Our results thus for identified the role of GBF1 in APP trafficking and cleavage, and provide evidence for GBF1 as a possible therapeutic target in AD. © 2019 Wiley Periodicals, Inc.
  •  
40.
  • Luo, Cong, et al. (författare)
  • Wet mixing combustion synthesis of CaO-based sorbents for high temperature cyclic CO2 capture
  • 2015
  • Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 267, s. 111-116
  • Tidskriftsartikel (refereegranskat)abstract
    • CaO-based sorbents are considered suitable candidates for cyclic CO2 capture at high temperatures. However, the CO2 capture capacities of natural CaO-based sorbents decrease sharply after only a few cycles. This paper presents a novel wet mixing combustion synthesis to improve the cyclic CO2 capture performance of CaO-based sorbents. Results show that preparation conditions significantly affected the cyclic performance of the sorbents. The optimal molar ratios of calcium to magnesium and fuel to metal oxides were 2 and 0.5, respectively, for the preparation process. The wet mixing combustion synthesis did not show the highest CO2 capture capacity in comparison to the sol-gel combustion synthesis, however, the proposed method is still valid due to the low cost of the materials used. The sorbent prepared by the new method could achieve relatively stable cyclic CO2 capture behavior, and showed a porous microstructure that can be maintained during cyclic reactions. The capture capacity of the sorbent obtained a 0.4 g CO2/g sorbent after 50 cycles. (C) 2015 Elsevier B.V. All rights reserved.
  •  
41.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
  •  
42.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
  •  
43.
  • Qin, Danfeng, et al. (författare)
  • Protic salt-based nitrogen-doped mesoporous carbon for simultaneous electrochemical detection of Cd(II) and Pb(II)
  • 2017
  • Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 7:59, s. 36929-36934
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitrogen-doped mesoporous carbon (NMC) derived from a single small-molecule protic salt (p-phenylenediamine bisulfate) is used for sensing toxic heavy metal ions. Using Nafion, bismuth and NMC to anchor the glassy carbon electrode surface, the fabricate electrode shows high sensitivity for detecting Cd(II) and Pb(II). The limits of detection (S/N = 3) are estimated to be 0.3 mu g L-1 for Cd(II) and 0.4 mu g L-1 for Pb(II), respectively, which are 10 and 25 times lower than the maximum acceptable content for drinking water recommended by the WHO. Furthermore, the sensor is successfully used to analyze Cd(II) and Pb(II) in tap-water with high anti-interference capability and good recovery.
  •  
44.
  • Scialacqua, L., et al. (författare)
  • Advanced measurement post-processing by equivalent currents on small 5G antennas
  • 2018
  • Ingår i: 12th European Conference on Antennas and Propagation (EuCAP 2018). - : Institution of Engineering and Technology.
  • Konferensbidrag (refereegranskat)abstract
    • Fifth-Generation (5G) mobile communication demands a wide use of multi beam scanning array antennas, providing effective coverage performances at millimeter waves [1-3]. In particular, when the telecommunication channel is characterized by a reduced signal to noise ratio, an omni like radiation pattern could be generated by the beam scanning antenna system. The testing of the AUT (Antenna Under Test), in such conditions, is typically performed with low directive reference antennas. These antennas can suffer of the interaction with the feeding cable. The measurement post-processing by the equivalent currents approach (EQC) [4-7], implemented in the MVG software INSIGHT [8], can be used for diagnostic investigations on this kind of reference antennas and to filter undesired currents on the feeding cable. In this paper the EQC approach is applied, for the first time, on diagnostic and filtering of feeding cable on a measurement of a low directive antenna for 5G tests.
  •  
45.
  • Shambetova, Nestan, et al. (författare)
  • Acid Dissociation of 3-Mercaptopropionic Acid Coated CdSe-CdS/Cd0.5Zn0.5S/ZnS Core-Multishell Quantum Dot and Strong Ionic Interaction with Ca2+ Ion
  • 2016
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 120:6, s. 3519-3529
  • Tidskriftsartikel (refereegranskat)abstract
    • By devising careful electrophoresis, it was shown that at pH below 7.0, the electrophoretic mobility of 3-mercaptopropionic acid (3MPA) coated CdSe-ZnS core-shell quantum dots (denoted as QD-3MPA) was very small. At pH above 7.0, QD-3MPA migrated toward the anode, implying acid dissociation, and the degree of which was proportional to the pH value. QD-3MPA's electrophoretic mobility was impaired after adding sufficient Ca2+ ions to the QD solution and revived when a similar amount of Ca2+ chelators (ethylene glycol tetraacetic acid, EGTA) was added. This demonstrated that acid dissociation and its pH dependence of 3MPA on the QD surface are critical factors in understanding the electric and optical properties of QDs. The acid dissociated QD-3MPA interacted strongly with Ca2+, forming a charge neutral QD-3MPA Ca2+ complex in the absence of EGTA. First-principles study confirmed the observed experimental evidence. The strong ionic interaction between acid dissociated QD-3MPA and Ca2+ is critical for developing reliable QD-based biosensing assays. Moreover, the strategy and techniques reported in this work are easily applicable to other fluorescent biomarkers and therefore can be important for advancing in vivo and in vitro imaging, sensing, and labeling.
  •  
46.
  • Shang, Ying, et al. (författare)
  • Incidence and Evolution of Prediabetes among Older Adults : A Population-Based Cohort Study
  • 2018
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:suppl 1, s. LB49-LB49
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The incidence and evolution of prediabetes in older adults is still unclear. We aimed to estimate the incidence of prediabetes, the rates of prediabetes reverting to normoglycemia or progressing to type 2 diabetes, and to identify possible prognostic factors among older adults with prediabetes.Methods: In the Swedish National Study on Aging and Care-Kungsholmen Project, 3049 diabetes-free participants aged ≥60 years were examined at baseline (2001-2004), and were followed-up to 12 years (2013-2016). At each wave, type 2 diabetes was ascertained based on self-report, antidiabetic drug use, medical records, or glycated haemoglobin (HbA1c) ≥6.5% (48 mmol/mol). In diabetes-free participants, prediabetes was assessed as HbA1c ≥5.7% (39 mmol/mol), and normoglycemia was defined as HbA1c <5.7%. Data were analysed with Poisson regression and multinomial logistic regression.Results: During 12 years follow-up, among 1972 (64.7%) participants with normoglycemia, 505 (25.6%) developed prediabetes (incidence=4.3/100 person-years, 95% CI 3.9-4.8). Of the 1077 (35.3%) participants with prediabetes at baseline, 204 (18.9%) reverted to normoglycemia (reversion rate=3.1/100 person-years, 95% CI: 2.6-3.6) and 119 (11.0%) progressed to type 2 diabetes (progression rate=1.7/100 person-years, 95% CI: 1.3-2.1). The reversal to normoglycemia was significantly associated with lower systolic blood pressure and weight loss, while, obesity and weight gain were risk factors for progression to type 2 diabetes.Conclusions: The incidence of prediabetes is high (about 26%) among older adults. Around 19% of people with prediabetes may revert to normoglycemia and 11% progress to type 2 diabetes. Weight change and systolic blood pressure may play a role in such evolution.
  •  
47.
  • Shang, Ying, et al. (författare)
  • Natural history of prediabetes in older adults from a population-based longitudinal study
  • 2019
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:3, s. 326-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The natural history of prediabetes in older adults remains unknown.Objectives. To assess the rate at which prediabetes progresses to diabetes, leads to death or reverts to normoglycaemia in older adults and to identify prognostic factors related to different outcomes of prediabetes.Methods. In the Swedish National Study on Aging and Care-Kungsholmen, 2575 diabetes-free participants aged >= 60 years were examined at baseline and followed for up to 12 years. At each wave, diabetes was diagnosed via medical examination, antidiabetic drug use, medical records or glycated haemoglobin (HbA1c) >= 6.5%. Prediabetes was defined as HbA1c >= 5.7% and normoglycaemia as HbA1c <5.7% in diabetes-free participants. Data were analysed with multinomial logistic regression.Results. At baseline, 918 (36%) individuals had prediabetes. Of them, 204 (22%) reverted to normoglycaemia (3.4/100 person-years, 95% CI 5.6-12.3), 119 (13%) developed diabetes (2.0/100 person-years, 95% CI 1.7-2.4) and 215 (23%) died (13.0/100 person-years, 95% CI 11.4-14.9) during the 12-year follow-up. The rates of reversion, progression and mortality were higher in the first 6-year than in the second 6-year follow-up, albeit not statistically significant. Lower systolic blood pressure (SBP), absence of heart diseases and weight loss promoted the reversion from prediabetes to normoglycaemia, whilst obesity accelerated its progression to diabetes.Conclusions. During a 12-year follow-up, most of older adults with prediabetes remained stable or reverted to normoglycaemia, whereas only one-third developed diabetes or died. Lower SBP, no heart diseases and weight management may promote reversion to normoglycaemia, suggesting possible strategies for achieving normoglycaemia in older adults with prediabetes.
  •  
48.
  • Shen, Qiuwan, et al. (författare)
  • Optimize process parameters of microwave-assisted EDTA method using orthogonal experiment for novel BaCoO3-delta perovskite
  • 2016
  • Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388. ; 658, s. 125-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxyfuel process is a promising technique for carbon capture and storage, and a new application of perovskite-type oxide is as oxygen carrier for CO2 capture in oxy-fuel combustion system. This study proposed a novelty process and an optimization study on the synthesis of the BaCoO3-delta perovskite powders using microwave-assisted EDTA method. OA(16) (4(5)) orthogonal experiments were employed to optimize the process parameters such as precursor pH, microwave time, microwave power and calcination temperature. The oxygen production performance of synthesized powders were investigated in a fixed-bed reactor system. It was found that the order of significant factors for oxygen production performance of synthesized perovskite samples is microwave radiation time > pH value of precursor solution > calcination temperature > microwave power. Based on the results of the range analysis, the best oxygen production performance of BaCoO3-delta was found at pH value of precursor solution was 8, microwave radiation time was 30 min, microwave power was 700 W and calcination temperature was 600 degrees C. Finally, the optimized sample was selected as candidate for multiple oxygen adsorption/desorption cycles tests. Results demonstrate that the prepared perovskites via optimized microwave-assisted EDTA process can be used as a potential oxygen carrier for oxyfuel combustion application. (C) 2015 Elsevier B.V. All rights reserved.
  •  
49.
  • Sung, Yun Ju, et al. (författare)
  • A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
  • 2019
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
  •  
50.
  • Tao, Fei, et al. (författare)
  • Manufacturing Service Management in Cloud Manufacturing : Overview and Future Research Directions
  • 2015
  • Ingår i: Journal of manufacturing science and engineering. - : ASME International. - 1087-1357 .- 1528-8935. ; 137:4
  • Tidskriftsartikel (refereegranskat)abstract
    • As a new service-oriented manufacturing paradigm, cloud manufacturing (CMfg) has experienced rapid development in the past five years. The research on its theories, key technologies, developments, and applications still keeps attracting attentions from more and more researchers. One of the most important issues to its improvements and quality of service (QoS) is the manufacturing service management (MSM). CMfg aims to realize the full-scale sharing, free circulation and transaction, and on-demand use of various manufacturing resource and capabilities in the form of manufacturing service. Without the effective operation and technical support of MSM, the implementation of CMfg and its aim cannot be achieved. It is therefore necessary to summarize the existing works and technologies on MSM in CMfg. This paper first provides a brief overview of CMfg and then focuses on the problem of MSM in CMfg from the service lifecycle perspective. The advances on MSM technology from eleven aspects are investigated and summarized. Finally, future research directions are identified and discussed. It is evident that the future MSM in CMfg is closely related to Internet of things (IoT), big data, and cloud computing.
  •  
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