| 1. |
|
|
| 2. |
-
- 2019
-
Journal article (peer-reviewed)
|
|
| 3. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 4. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 5. |
|
|
| 6. |
- Danaei, Goodarz, et al.
(author)
-
Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
-
In: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
-
Journal article (peer-reviewed)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
|
|
| 7. |
- Wheeler, Eleanor, et al.
(author)
-
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
-
In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
-
Journal article (peer-reviewed)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.
|
|
| 8. |
- Zhou, Bin, et al.
(author)
-
Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
-
In: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
-
Journal article (peer-reviewed)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
|
|
| 9. |
- Ablikim, M., et al.
(author)
-
Search for h(c) -> pi(+)pi(-) J/psi via psi(3686) -> pi(0)pi(+)pi(-) J/psi
- 2018
-
In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 97:5
-
Journal article (peer-reviewed)abstract
- Using a data sample of 448.1 x 10(6) psi(3686) events collected with the BESIII detector operating at the BEPCII, we perform search for the hadronic transition h(c)-> pi(+)pi(-) J/psi via psi (3686) -> pi(0)hc. No signals of the transition are observed, and the upper limit on the product branching fraction B(sigma(3686) -> pi(0)h(c))B(h(c) -> pi(+)pi(-) J/psi) at the 90% confidence level (C. L.) is determined to be 2.0 x 10(-6). This is the most stringent upper limit to date.
|
|
| 10. |
- Chew, Andrew, et al.
(author)
-
Attosecond transient absorption spectrum of argon at the L-2,L-3 edge
- 2018
-
In: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 97:3
-
Journal article (peer-reviewed)abstract
- Progress in high-harmonic generation has led to high-energy attosecond pulses with cutoff above the carbon 1s edge (283.8 eV). These pulses are essential to extend time-resolved spectroscopies to the water window in order to control electron dynamics in solvated organic species. Here we report a step towards this goal: the measurement, with subcycle time resolution, of the attosecond transient absorption spectrum of argon at the 2p(-1) L-2,L-3 edge (similar to 250 eV) in the presence of a short-wave infrared control pulse. The measurements, supported by theoretical simulations, demonstrate the concurrent role of Auger decay and tunnel ionization in the driven evolution of inner-valence holes of polyelectronic atoms.
|
|
| 11. |
- Cloern, James E., et al.
(author)
-
Human activities and climate variability drive fast-paced change across the world's estuarine-coastal ecosystems
- 2016
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 22:2, s. 513-529
-
Research review (peer-reviewed)abstract
- Time series of environmental measurements are essential for detecting, measuring and understanding changes in the Earth system and its biological communities. Observational series have accumulated over the past 2-5 decades from measurements across the world's estuaries, bays, lagoons, inland seas and shelf waters influenced by runoff. We synthesize information contained in these time series to develop a global view of changes occurring in marine systems influenced by connectivity to land. Our review is organized around four themes: (i) human activities as drivers of change; (ii) variability of the climate system as a driver of change; (iii) successes, disappointments and challenges of managing change at the sea-land interface; and (iv) discoveries made from observations over time. Multidecadal time series reveal that many of the world's estuarine-coastal ecosystems are in a continuing state of change, and the pace of change is faster than we could have imagined a decade ago. Some have been transformed into novel ecosystems with habitats, biogeochemistry and biological communities outside the natural range of variability. Change takes many forms including linear and nonlinear trends, abrupt state changes and oscillations. The challenge of managing change is daunting in the coastal zone where diverse human pressures are concentrated and intersect with different responses to climate variability over land and over ocean basins. The pace of change in estuarine-coastal ecosystems will likely accelerate as the human population and economies continue to grow and as global climate change accelerates. Wise stewardship of the resources upon which we depend is critically dependent upon a continuing flow of information from observations to measure, understand and anticipate future changes along the world's coastlines.
|
|
| 12. |
- de Vries, Paul S., et al.
(author)
-
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
-
In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
-
Journal article (peer-reviewed)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.
|
|
| 13. |
- Feitosa, Mary F., et al.
(author)
-
Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
-
In: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
-
Journal article (peer-reviewed)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.
|
|
| 14. |
- Fu, Lixin, et al.
(author)
-
Nanocoating inside porous PE separator enables enhanced ionic transport of GPE and stable cycling of Li-metal anode
- 2019
-
In: Research on chemical intermediates (Print). - : Springer Science and Business Media LLC. - 0922-6168 .- 1568-5675. ; 45:10, s. 4959-4973
-
Journal article (peer-reviewed)abstract
- In this paper, a simple and feasible method for preparing gel polymer electrolyte (GPE) with good ionic transport properties and mechanical stability is proposed. A ZrO2/KH570/PU/P123 layer was formed on the outer and inner pore surfaces of PE separator before in situ polymerization by a simple one-step dipping coating process. This coating layer changes the PE separator surface from hydrophobic to hydrophilic, and therefore facilitates the uniform spreading of the GPE precursor solution on the PE surface to enable the formation of highly uniform GPE. Moreover, it effectively compensates the negative effects of in situ gelatinization on the ionic transport behavior of the final PE-supported GPE. This GPE possesses excellent ion transport properties and mechanical stability, as well as improves the static and dynamic interfacial stability with lithium metal anode. When using metallic lithium and LiCoO2 to assemble cells, this PE-supported GPE affords improved C-rate capability, cycling performance and effective dendrite inhibition. [GRAPHICS] .
|
|
| 15. |
- Haycock, Philip C., et al.
(author)
-
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
-
In: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
-
Journal article (peer-reviewed)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
|
|
| 16. |
- Keasar, Chen, et al.
(author)
-
An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12
- 2018
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
-
Journal article (peer-reviewed)abstract
- Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.
|
|
| 17. |
- Lubitz, Steven A, et al.
(author)
-
Genetic Risk Prediction of Atrial Fibrillation
- 2017
-
In: Circulation. - 0009-7322. ; 135:14, s. 1311-1320
-
Journal article (peer-reviewed)abstract
- BACKGROUND—: Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. METHODS—: To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10 to <1x10 in a prior independent genetic association study. RESULTS—: Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). CONCLUSIONS—: Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms.
|
|
| 18. |
- Ma, Tan, et al.
(author)
-
Effects of In Utero Exposure to Di-n-Butyl Phthalate on Testicular Development in Rat
- 2017
-
In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 14:10
-
Journal article (peer-reviewed)abstract
- Humans are inevitably exposed to ubiquitous phthalate esters (PAEs). In utero exposure to di-n-butyl phthalate (DBP) induces abnormal development of the testis and reproductive tract in male offspring, which correspond closely with the human condition of testicular dysgenesis syndrome (TDS)-like syndrome. However, the underlying mechanisms have not been elucidated in detail. In this study, pregnant rats were orally exposed to either corn oil (controls) or DBP at three different doses by gavage during Gestational Days 12.5-21.5. Pathological examinations were performed for toxicity evaluation. Proliferation and apoptosis related proteins (ras related dexamethasone induced 1 (Rasd1), mitogen-activated protein kinase kinases1/2 (MEK1/2), Bcl-2, and Bax) were measured for mechanisms exploration. The results showed that different doses of DBP caused male developmental and reproductive toxicity in rats, including the decrease of anogenital distance (AGD), the histological damage of testis, and apoptosis of seminiferous tubule cells. Our data suggested that DBP played chronic and continuous toxic roles on male reproductive system by disrupting expression of Rasd1 and MEK1/2 as well as Bcl-2/Bax ratio. Further research is warranted.
|
|
| 19. |
- Qiu, Zhengfu, et al.
(author)
-
Surface activated polyethylene separator promoting Li+ ion transport in gel polymer electrolytes and cycling stability of Li-metal anode
- 2019
-
In: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947 .- 1873-3212. ; 368, s. 321-330
-
Journal article (peer-reviewed)abstract
- This paper proposes a strategy to fabricate surface activated polyethylene (PE)-supported gel polymer electrolyte (GPE) with high ion transport ability, excellent electrolyte retention and mechanical properties to stabilize lithium (Li)-metal anodes. The inert outer and inner pore surface activation of polyethylene is demonstrated by coating an ultrathin zirconium oxide nanocrystal (ZrO2)/polyhedral oligomeric silsesquioxane (POSS) composite layer through a simple layer by layer (LBL) assembly method prior to the in situ polymerization. It is found that the activation layer may improve the Li+ ion transference number and induce the formation of GPE with a gradient structure by the interaction with the initiator system, giving rise to higher ion transport ability of final GPE. On the other hand, the GPE using the activated PE separator as support improves the Li/electrolyte interfacial stability during storage and repeated lithium plating/stripping cycling. A stable voltage profile with cycling for more than 800 h in a Li/Li symmetric cell was obtained by using surface activated PE-supported GPE. When it is assembled into the cells with metallic lithium anodes and lithium cobalt oxide (LiCoO2) cathodes, the cells show excellent rate capability and cycling performance, as well as effective dendrite inhibition.
|
|
| 20. |
- Shen, Erxia, et al.
(author)
-
Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor
- 2019
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 29:7
-
Journal article (peer-reviewed)abstract
- © 2019 The Author(s) Follicular regulatory T (TFR) cells are a specialized suppressive subset that controls the germinal center (GC) response and maintains humoral self-tolerance. The mechanisms that maintain TFR lineage identity and suppressive activity remain largely unknown. Here, we show that expression of Blimp1 by FoxP3+ TFR cells is essential for TFR lineage stability, entry into the GC, and expression of regulatory activity. Deletion of Blimp1 in TFR cells reduced FoxP3 and CTLA-4 expression and increased pro-inflammatory cytokines and spontaneous production of autoantibodies, including elevated IgE. Maintenance of TFR stability reflected Blimp1-dependent repression of the IL-23R-STAT3 axis and activation of the CD25-STAT5 pathway, while silenced IL-23R-STAT3 or increased STAT5 activation rescued the Blimp1-deficient TFR phenotype. Blimp1-dependent control of CXCR5/CCR7 expression also regulated TFR homing into the GC. These findings uncover a Blimp1-dependent TFR checkpoint that enforces suppressive activity and acts as a gatekeeper of GC entry.
|
|
| 21. |
- Sung, Yun Ju, et al.
(author)
-
A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
-
In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
-
Journal article (peer-reviewed)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.
|
|
| 22. |
|
|
| 23. |
- Wang, Shuai, et al.
(author)
-
In Situ Synthesis of Tungsten-Doped SnO2 and Graphene Nanocomposites for High-Performance Anode Materials of Lithium-Ion Batteries
- 2017
-
In: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 9:20, s. 17163-17171
-
Journal article (peer-reviewed)abstract
- The composite of tungsten-doped SnO2 and reduced graphene oxide was synthesized through a simple one pot hydrothermal method. According to the structural characterization of the composite, tungsten ions were doped in the unit cells of tin dioxide rather than simply attaching to the surface. Tungsten-doped SnO2 was in situ grown on the surface of graphene sheet to form a three-dimensional conductive network that enhanced the electron transportation and lithium-ion diffusion effectively. The issues of SnO2 agglomeration and volume expansion could be also avoided because the, tungsten-doped SnO2 nanoparticles were homogeneously distributed on a graphene sheet. As a result, the nanocomposite electrodes of tungsten-doped SnO2 and reduced graphene oxide exhibited an excellent long-term cycling performance. The residual capacity was still as high as 1100 mA h g(-1) at 0.1 A g(-1) after 100 cycles. It still remained at 776 mA h g(-1) after 2000 cycles at the current density of lA g(-1).
|
|
| 24. |
- Wang, Yanan, et al.
(author)
-
Gel Polymer Electrolyte with High Li+ Transference Number Enhancing the Cycling Stability of Lithium Anodes
- 2019
-
In: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 11:5, s. 5168-5175
-
Journal article (peer-reviewed)abstract
- Lithium anodes suffer from severe safety problems in liquid electrolyte systems that result from an unstable Li plating/stripping process and Li dendrite growth, leading to rapid degradation of Li metal batteries. A polyethylene (PE)-supported gel polymer electrolyte (GPE) with excellent electrolyte uptake/retention capability was simply prepared in this paper by the construction of cross-linked polymer networks (PNs) on the surface of a poly(ethylenimine)-primed PE separator to stabilize the lithium anode. The highly delocalized negative charge of p-styrene sulfonate groups on PNs plays a role in regulating the Li+ and anion transport, giving rise to a high Li+ transference number. This GPE extended the electrochemical stability to 4.8 V and improved the stability of interface between the electrolyte and lithium metal anode (reduced overpotential and suppressed lithium dendrites) during storage and repeated lithium plating/stripping cycling. The Li metal anode-based battery employing this GPE exhibits excellent cycling stability and C-rate capability.
|
|
| 25. |
- Wu, Yuan, et al.
(author)
-
In situ constructed Ag/C conductive network enhancing the C-rate performance of Si based anode
- 2018
-
In: Journal of Energy Storage. - : ELSEVIER SCIENCE BV. - 2352-152X .- 2352-1538. ; 17, s. 102-108
-
Journal article (peer-reviewed)abstract
- Poor intrinsic electrical conductivity as well as considerable volume change during lithium alloying/dealloying process has been a critical defect for high theoretical capacity silicon-based anodes. In our work, we demonstrate the synthesis design of multiscale recombined dendritic Si/Ag/C anode for high energy density LIBs via compositing bulky silicon with uniformly distributed Ag NPs, followed by a carbon source PDA (polydopamine) coating step. Here Ag NPs are generated by an in situ redox reaction between Ag+ and PDA, no need for additional reducing agents. According to the characterization analysis, the robust porous Si/Ag/C structure can provide channels for fast Li+ diffusion and electron conduction, promoting the formation of a thinner and more stable SEI film. As a result, the Si/Ag/C composite anode still yields a relatively high residual capacity of 1422.1 mAh g (1) after 100 cycles at 0.2 A g (1). In addition, it remains 633.1 mAh g (1) after 500 cycles at a high current density of 8 A g (1).
|
|
| 26. |
- Yin, Ming-Jie, et al.
(author)
-
Precise Micropatterning of a Porous Poly(ionic liquid) via Maskless Photolithography for High-Performance Nonenzymatic H2O2 Sensing
- 2018
-
In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 12:12, s. 12551-12557
-
Journal article (peer-reviewed)abstract
- Porous poly(ionic liquid)s (PILs) recently have been serving as a multifunctional, interdisciplinary materials platform in quite a few research areas, including separation, catalysis, actuator, sensor, and energy storage, just to name a few. In this context, the capability of photopatterning PIL microstructures in a porous state on a substrate is still missing but is a crucial step for their real industrial usage. Here, we developed a method for in situ rapid patterning of porous PIL microstructures via a maskless photolithography approach coupled with a simple electrostatic complexation treatment. This breakthrough enables design of miniaturized sensors. As exemplified in this work, upon loading Pt nanoparticles into porous PIL microstructures, the hybrid sensor showed outstanding performance, bearing both a high sensitivity and a wide detection range.
|
|
| 27. |
- Yin, Xiaoqin, et al.
(author)
-
MiR-301b-3p/3584-5p enhances low-dose mono-n-butyl phthalate (MBP) induced proliferation by targeting Rasd1 in Sertoli cells
- 2018
-
In: Toxicology in Vitro. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0887-2333 .- 1879-3177. ; 47, s. 79-88
-
Journal article (peer-reviewed)abstract
- To investigate the possible molecular mechanism of low concentration plasticizer mono-n-butyl phthalate (MBP)-induced juvenile Sertoli cells (SCs) proliferation, we evaluated global alterations of miRNA and mRNA expression in rat SCs treated with 0.1 mM MBP. Microarray analysis revealed that miR-3584-5p and miR-301b-3p were up-regulated and their common target gene Dexamethasone-induced Ras-related protein 1 (Rasd1) was down-regulated. Further work suggested that SCs proliferation induced by low concentration MBP in vitro might be mediated by Rasd1 regulating ERK1/2 signaling pathway. The present study is first to investigate the effect of low-dose MBP on SCs proliferation and may enhance our understanding on the modes of action of low concentration MBP on male reproductive system. We hope the results will contribute to explain the causes of precocious puberty and testicular tumors induced by exogenous chemicals.
|
|
| 28. |
- Zhang, Hao, et al.
(author)
-
A simple method to enhance the lifetime of Ni-rich cathode by using low-temperature dehydratable molecular sieve as water scavenger
- 2019
-
In: Journal of Power Sources. - : ELSEVIER. - 0378-7753 .- 1873-2755. ; 435
-
Journal article (peer-reviewed)abstract
- Ni-rich cathode materials have received much attention because of their high specific capacity, low cost and environmentally friendly characteristic. However, the nickel-rich cathode is extremely sensitive to moisture, which results in poor structure stability and electrochemical performance. Herein, we demonstrate an efficient and simple route to prolong the lifetime of nickel-rich cathode by introducing a low-temperature dehydratable molecular sieve as water scavenger. The residual water content in electrolyte measurement and nuclear magnetic resonance test manifest that molecular sieve can effectively fix the trace H2O and reduce the decomposition rate of electrolyte from 16.6% to 4.0%, respectively. Transmission electron microscopy, scanning electron microscopy and X-ray photoelectron spectroscopy confirm that the molecular sieve inhibits the fragmentation of the electrode and the side reactions on the surface of the cathode. This approach improves structural integrity and stabilizes surface structure of the cathode, which increases the capacity retention without sacrificing rate performance. This effective strategy can be extended to other cathode materials which are sensitive to moisture to realize good cycling stability.
|
|
| 29. |
- Zhou, Suhan, et al.
(author)
-
ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function
- 2019
-
In: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:1, s. F134-F145
-
Journal article (peer-reviewed)abstract
- Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Set(473) and eNOS at Ser(1177). Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis. and improving microvascular endothelial dysfunction. rhADAMIS13 could be a promising strategy to treat AKI in clinical settings.
|
|
