| 31. |
- Fedorowski, Artur, et al.
(author)
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Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.
- 2012
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In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:18, s. 2331-2341
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Journal article (peer-reviewed)abstract
- Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
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| 32. |
- Forouzanfar, Mohammad H, et al.
(author)
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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
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Journal article (peer-reviewed)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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| 33. |
- Hohman, Timothy J, et al.
(author)
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Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau.
- 2018
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 75:8
-
Journal article (peer-reviewed)abstract
- The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neuropathology in a sex-specific manner.To evaluate sex differences in the association between APOE and markers of AD neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy.This multicohort study selected data from 10 longitudinal cohort studies of normal aging and AD. Cohorts had variable recruitment criteria and follow-up intervals and included population-based and clinic-based samples. Inclusion in our analysis required APOE genotype data and either CSF data available for analysis. Analyses began on November 6, 2017, and were completed on December 20, 2017.Biomarker analyses included levels of β-amyloid 42, total tau, and phosphorylated tau measured in CSF. Autopsy analyses included Consortium to Establish a Registry for Alzheimer's Disease staging for neuritic plaques and Braak staging for neurofibrillary tangles.Of the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years. Of the 5109 patients in the autopsy cohort, 2813 were women, 4953 were white, and the mean (SD) age was 84 (9) years. After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β=0.41; 95% CI, 0.27-0.55; P<.001) and phosphorylated tau (β=0.24; 95% CI, 0.09-0.38; P=.001), whereby APOE showed a stronger association among women compared with men. Post hoc analyses suggested this sex difference was present in amyloid-positive individuals (β=0.41; 95% CI, 0.20-0.62; P<.001) but not among amyloid-negative individuals (β=0.06; 95% CI, -0.18 to 0.31; P=.62). We did not observe sex differences in the association between APOE and β-amyloid 42, neuritic plaque burden, or neurofibrillary tangle burden.We provide robust evidence of a stronger association between APOE-ε4 and CSF tau levels among women compared with men across multiple independent data sets. Interestingly, APOE-ε4 is not differentially associated with autopsy measures of neurofibrillary tangles. Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Larson, Greger, et al.
(author)
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Phylogeny and ancient DNA of Sus provides insights into neolithic expansion in island southeast Asia and Oceania
- 2007
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:12, s. 4834-4839
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Journal article (peer-reviewed)abstract
- Human settlement of Oceania marked the culmination of a global colonization process that began when humans first left Africa at least 90,000 years ago. The precise origins and dispersal routes of the Austronesian peoples and the associated Lapita culture remain contentious, and numerous disparate models of dispersal (based primarily on linguistic, genetic, and archeological data) have been proposed. Here, through the use of mtDNA from 781 modern and ancient Sus specimens, we provide evidence for an early human-mediated translocation of the Sulawesi warty pig (Sus celebensis) to Flores and Timor and two later separate human-mediated dispersals of domestic pig (Sus scrofa) through Island Southeast Asia into Oceania. Of the later dispersal routes, one is unequivocally associated with the Neolithic (Lapita) and later Polynesian migrations and links modern and archeological Javan, Sumatran, Wallacean, and oceanic pigs with mainland Southeast Asian S. scrofa. Archeological and genetic evidence shows these pigs were certainly introduced to islands east of the Wallace Line, including New Guinea, and that so-called "wild" pigs within this region are most likely feral descendants of domestic pigs introduced by early agriculturalists. The other later pig dispersal links mainland East Asian pigs to western Micronesia, Taiwan, and the Philippines. These results provide important data with which to test current models for human dispersal in the region.
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| 38. |
- Lee, Crystal, et al.
(author)
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Association of anthropometry and weight change with risk of dementia and its major subtypes: a meta-analysis consisting 2.8 million adults with 57,294 cases of dementia
- 2020
-
In: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 21:4
-
Journal article (peer-reviewed)abstract
- Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5–22.4 kg/m2), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5–24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had non-significant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change and dementia is complex and exhibits nonlinear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.
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| 39. |
- Linden, S. T., et al.
(author)
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GOALS-JWST: Revealing the Buried Star Clusters in the Luminous Infrared Galaxy VV 114
- 2023
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 944:2
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Journal article (peer-reviewed)abstract
- We present the results of a James Webb Space Telescope NIRCam investigation into the young massive star cluster (YMC) population in the luminous infrared galaxy VV 114. We identify 374 compact YMC candidates with signal-to-noise ratios ≥ 3, 5, and 5 at F150W, F200W, and F356W, respectively. A direct comparison with our HST cluster catalog reveals that ∼20% of these sources are undetected at optical wavelengths. Based on yggdrasil stellar population models, we identify 17 YMC candidates in our JWST imaging alone with F150W - F200W and F200W - F356W colors suggesting they are all very young, dusty (A V = 5-15), and massive (105.8 < M ⊙ < 106.1). The discovery of these “hidden” sources, many of which are found in the “overlap” region between the two nuclei, quadruples the number of t < 3 Myr clusters and nearly doubles the number of t < 6 Myr clusters detected in VV 114. Now extending the cluster age distribution ( dN / d τ ∝ τ γ ) to the youngest ages, we find a slope of γ = −1.30 ± 0.39 for 106 < τ(yr) < 107, which is consistent with the previously determined value from 107 < τ(yr) < 108.5, and confirms that VV 114 has a steep age distribution slope for all massive star clusters across the entire range of cluster ages observed. Finally, the consistency between our JWST- and HST-derived age distribution slopes indicates that the balance between cluster formation and destruction has not been significantly altered in VV 114 over the last 0.5 Gyr.
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| 40. |
- Liu, Daizhong, et al.
(author)
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PHANGS–JWST First Results : Stellar-feedback-driven Excitation and Dissociation of Molecular Gas in the Starburst Ring of NGC 1365?
- 2023
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Journal article (peer-reviewed)abstract
- We compare embedded young massive star clusters (YMCs) to (sub-)millimeter line observations tracing the excitation and dissociation of molecular gas in the starburst ring of NGC 1365. This galaxy hosts one of the strongest nuclear starbursts and richest populations of YMCs within 20 Mpc. Here we combine near-/mid-IR PHANGS–JWST imaging with new Atacama Large Millimeter/submillimeter Array multi-J CO (1–0, 2–1 and 4–3) and [C ı] (1–0) mapping, which we use to trace CO excitation via R42 = ICO(4−3)/ICO(2−1) and R21 = ICO(2−1)/ICO(1−0) and dissociation via RCICO = I[CI](1−0)/ICO(2−1) at 330 pc resolution. We find that the gas flowing into the starburst ring from northeast to southwest appears strongly affected by stellar feedback, showing decreased excitation (lower R42) and increased signatures of dissociation (higher RCICO) in the downstream regions. There, radiative-transfer modeling suggests that the molecular gas density decreases and temperature and [CI/CO] abundance ratio increase. We compare R42 and RCICO with local conditions across the regions and find that both correlate with near-IR 2 μm emission tracing the YMCs and with both polycyclic aromatic hydrocarbon (11.3 μm) and dust continuum (21 μm) emission. In general, RCICO exhibits ∼0.1 dex tighter correlations than R42, suggesting C ı to be a more sensitive tracer of changing physical conditions in the NGC 1365 starburst than CO (4–3). Our results are consistent with a scenario where gas flows into the two arm regions along the bar, becomes condensed/shocked, forms YMCs, and then these YMCs heat and dissociate the gas.
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