| 1. |
- Aad, G., et al.
(author)
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- 2012
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In: The European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6052. ; 72:10
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Journal article (peer-reviewed)
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| 2. |
- 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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| 3. |
- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 4. |
- Rodriguez-Palmero, Agusti, et al.
(author)
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DLG4-related synaptopathy : a new rare brain disorder
- 2021
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In: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:5, s. 888-899
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Journal article (peer-reviewed)abstract
- PurposePostsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.MethodsThe clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.ResultsThe clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.ConclusionThe present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.
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| 5. |
- Gaudet, Mia M., et al.
(author)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Journal article (peer-reviewed)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 6. |
- Kirchhoff, Tomas, et al.
(author)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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In: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Journal article (peer-reviewed)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 7. |
- Voight, Benjamin F., et al.
(author)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Journal article (peer-reviewed)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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| 8. |
- Gordin, D., et al.
(author)
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The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study
- 2017
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In: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 26:5, s. 294-302
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Journal article (peer-reviewed)abstract
- Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension.Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of 145mm Hg, and/or a daytime diastolic ABPM of 95mm Hg after witnessed drug intake (including 3 antihypertensive drugs, preferably including a diuretic).Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety.Conclusions: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.
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| 9. |
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| 10. |
- Maasri, Alain, et al.
(author)
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A global agenda for advancing freshwater biodiversity research
- 2022
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 255-263
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Journal article (peer-reviewed)abstract
- Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.
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| 11. |
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| 12. |
- Yi, Chuixiang, et al.
(author)
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Climate control of terrestrial carbon exchange across biomes and continents
- 2010
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
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Journal article (peer-reviewed)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
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| 13. |
- Andersson-Sköld, Yvonne, et al.
(author)
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Developing and validating a practical decision support tool (DST) for biomass selection on marginal land
- 2014
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In: Journal of Environmental Management. - : Elsevier BV. - 0301-4797. ; 145, s. 113-121
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Journal article (peer-reviewed)abstract
- Marginal, often contaminated, sites exist in large areas across the world as a result of historic activities such as industry, transportation and mineral extraction. Remediation, or other improvements, of these sites is typically only considered for sites with high exploitation pressure and those posing the highest risks to human health or the environment. At the same time there is increasing competition for land resources for different needs such as biofuel production. Potentially some of this land requirement could be met by production of biomass on brownfield or other marginal land, thereby improving the land while applying the crop cultivation as part of an integrated management strategy. The design and decision making for such a strategy will be site specific. A decision support framework, the Rejuvenate DST (decision support tool) has been developed with the aim of supporting such site specific decision making. This tool is presented here, and has been tested by applying it to a number of case study sites. The consequent SWOT (strength, weakness, opportunities and threats) analysis is discussed and evaluated. The DST was found to be systematic, transparent, and applicable for diverse sites in France, Romania and Sweden, in addition to the sites to which it was applied through its development. The DST is regarded as especially useful if applied as a checklist in an iterative way throughout the decision process, from identifying potential crops to identifying knowledge gaps, working/non-working management strategies and potential risks. The DST also provides a structure promoting effective stakeholder engagement. (C) 2014 Elsevier Ltd. All rights reserved.
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| 14. |
- Barrett, Jennifer H., et al.
(author)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Journal article (peer-reviewed)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 15. |
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| 16. |
- Berry, C, et al.
(author)
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The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis.
- 2012
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In: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:14, s. 1750-7
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Journal article (peer-reviewed)abstract
- A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF).We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%.Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.
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| 17. |
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| 18. |
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| 19. |
- Downing, Andrea S., et al.
(author)
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Unlocking the unsustainable rice-wheat system of Indian Punjab : Assessing alternatives to crop-residue burning from a systems perspective
- 2022
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In: Ecological Economics. - : Elsevier BV. - 0921-8009 .- 1873-6106. ; 195
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Journal article (peer-reviewed)abstract
- Crop residue burning in Indian Punjab emits particulate matter with detrimental impacts on health, climate and that threaten agricultural production. Though legal and technological barriers to residue burning exist – and alternatives considered more profitable to farmers – residue burning continues. We review black carbon (BC) emissions from residue burning in Punjab, analyse social-ecological processes driving residue burning, and rice and wheat value-chains. Our aims are to a) understand system feedbacks driving agricultural practices in Punjab; b) identify systemic effects of alternatives to residue burning and c) identify companies and financial actors investing in agricultural production in Punjab. We find feedbacks locking the system into crop residue burning. The Government of India has greatest financial leverage and risk in the current system. Corporate stakeholders have little financial incentive to enact change, but sufficient stakes in the value chains to influence change. Agricultural policy changes are necessary to reduce harmful impacts of current practices, but insufficient to bringing about sustainability. Transformative changes will require crop diversification, circular business models and green financing. Intermediating financial institutions setting sustainability conditions on loans could leverage these changes. Sustainability requires the systems perspective we provide, to reconnect production with demand and with supporting environmental conditions.
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| 20. |
- Enarsson, Karin, 1975, et al.
(author)
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Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma.
- 2006
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In: Clinical immunology (Orlando, Fla.). - : Elsevier BV. - 1521-6616. ; 121:3, s. 358-68
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Journal article (peer-reviewed)abstract
- CD4(+)CD25(high) FOXP3-expressing regulatory T cells (Treg) can suppress immune responses to infections and tumors, thereby promoting microbial persistence and tumor progression. However, little is known about the phenotype and function of human mucosal Treg. Therefore, we analyzed the suppressive activity and homing phenotype of Treg in gastric mucosa of Helicobacter pylori-infected gastric adenocarcinoma patients. We found increased numbers of CD4(+)FOXP3(+) Treg in the tumor compared to tumor-free gastric mucosa. Gastric Treg cells were able to suppress H. pylori-induced T cell proliferation and IFN-gamma production. Furthermore, gastric Treg expressed increased levels of l-selectin and CCR4, compared to non-Treg cells, suggesting that these receptors contribute to Treg recruitment. The presence of functional antigen-specific Treg in H. pylori-infected gastric mucosa supports an important role for these cells in suppression of mucosal effector T cell responses, which probably contribute to bacterial persistence and possibly also to gastric tumor progression.
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| 21. |
- Fergelot, Patricia, et al.
(author)
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Phenotype and genotype in 52 patients with Rubinstein–Taybi syndrome caused by EP300 mutations
- 2016
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In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 170:12, s. 3069-3082
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Journal article (peer-reviewed)abstract
- Rubinstein–Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8–10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype–phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia.
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| 22. |
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| 23. |
- Fuks, Kateryna B., et al.
(author)
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Arterial blood pressure and long-term exposure to traffic-related air pollution : an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2014
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In: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
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Research review (peer-reviewed)abstract
- BACKGROUND: Long-term exposure to air pollution is hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country-specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated with BP lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in non-medicated participants (0.35 mmHg [95% CI: 0.02-0.68] and 0.22 mmHg [95% CI: 0.04-0.40] per 4,000,000 vehicles × m/day, respectively). The estimated odds ratio for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts we observed a weak positive association of high residential traffic exposure with BP in non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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| 24. |
- Fuks, Kateryna B., et al.
(author)
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Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE)
- 2017
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:13, s. 983-990
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Journal article (peer-reviewed)abstract
- Aims We investigated whether traffic-related air pollution and noise are associated with incident hypertension in European cohorts. Methods and results We included seven cohorts of the European study of cohorts for air pollution effects (ESCAPE). We modelled concentrations of particulate matter with aerodynamic diameter <= 2.5 mu m (PM2.5), <= 10 mu m (PM10), >2.5, and <= 10 mu m (PMcoarse), soot (PM2.5 absorbance), and nitrogen oxides at the addresses of participants with land use regression. Residential exposure to traffic noise was modelled at the facade according to the EU Directive 2002/49/EC. We assessed hypertension as (i) self-reported and (ii) measured (systolic BP >= 140mmHg or diastolic BP >= 90mmHg or intake of BP lowering medication (BPLM). We used Poisson regression with robust variance estimation to analyse associations of traffic-related exposures with incidence of hypertension, controlling for relevant confounders, and combined the results from individual studies with random-effects meta-analysis. Among 41 072 participants free of self-reported hypertension at baseline, 6207 (15.1%) incident cases occurred within 5-9 years of follow-up. Incidence of self-reported hypertension was positively associated with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI): 1.08; 1.37] per 5 mu g/m(3)) and PM2.5 absorbance (RR 1.13 [95% CI: 1.02; 1.24] per 10(-5) m(-1)). These estimates decreased slightly upon adjustment for road traffic noise. Road traffic noise was weakly positively associated with the incidence of self-reported hypertension. Among 10 896 participants at risk, 3549 new cases of measured hypertension occurred. We found no clear associations with measured hypertension. Conclusion Long-term residential exposures to air pollution and noise are associated with increased incidence of self-reported hypertension.
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| 25. |
- Helsmoortel, Celine, et al.
(author)
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A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:4, s. 380-
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Journal article (peer-reviewed)abstract
- Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date.
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| 26. |
- Hop, Paul J., et al.
(author)
-
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
-
In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 27. |
- Hub, Jochen S., et al.
(author)
-
Spontaneous Quaternary and Tertiary T-R Transitions of Human Hemoglobin in Molecular Dynamics Simulation
- 2010
-
In: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 6:5, s. e1000774-
-
Journal article (peer-reviewed)abstract
- We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(beta)146, and they sum up to a total length of 5.6 mu s. We observe spontaneous and reproducible T-->R quaternary transitions of the Hb tetramer and tertiary transitions of the alpha and beta subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the alpha and beta subunits. Using the mutual information as correlation measure, we find that the beta subunits are substantially more strongly linked to the quaternary transition than the alpha subunits. In addition, the tertiary populations of the alpha and beta subunits differ substantially, with the beta subunits showing a tendency towards R, and the alpha subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb.
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| 28. |
- Hörnsten, Rolf, et al.
(author)
-
Arrhythmia - a pitfall in tests of cardiac autonomic function after liver transplantation for familial amyloidotic polyneuropathy : a long-term follow-up of Swedish patients
- 2012
-
In: Amyloid. - London : Informa Healthcare. - 1350-6129 .- 1744-2818. ; 19:2, s. 81-86
-
Journal article (peer-reviewed)abstract
- Liver transplantation (LT) is a potentially curative treatment for hereditary transthyretin amyloidosis, of which familial amyloid polyneuropathy (FAP) is the most common form in Sweden. This study investigated the long-term development in heart rate variability (HRV) after LT in Swedish FAP patients. HRV was analyzed before LT, and during a first (<40 months) and a second (>40 months) follow-up recording after transplantation, respectively. Power spectrum analysis was performed on 2-min sequences in the supine position and after passive tilt, after careful identification of patients with arrhythmia. Data were obtained from 33 patients, but 18 patients had developed cardiac arrhythmia or were pacemaker-treated (4 before LT and 14 after LT) and three patients had not performed the first follow-up recording. In the remaining 12 patients, HRV decreased between the pretransplant evaluation and the first follow-up, thereafter no significant changes were found. In conclusion, our study showed that the progressive development of cardiac arrhythmias after LT is a major pitfall when assessing cardiac autonomic function in FAP patients, especially in patients older than 40 years. In the minority of patients with sinus rhythm in all recordings, cardiac autonomic modulation remained stable after transplantation and no improvement was noted.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Johannsson, Gudmundur, 1960, et al.
(author)
-
Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients.
- 1996
-
In: Clinical endocrinology. - 0300-0664. ; 45:3, s. 305-14
-
Journal article (peer-reviewed)abstract
- The long-term cardiovascular effects of GH administration in adults are of major clinical importance, given the increasing use of such treatment. We have evaluated long-term cardiovascular effects of recombinant human GH (rhGH) substitution in GH deficient men.S.c. rhGH 0.5 U/kg/week or placebo was administered in a 6-month double-blind, cross-over study, followed (after a year without substitution) by a 42-month period of open GH substitution.We evaluated 7 GH-deficient men serially and compared the results with 21 men matched in terms of age and height.Investigations included exercise tests and Doppler-echocardiography to determine exercise capacity and cardiovascular performance.Heart rate and systolic blood pressure at rest increased with GH substitution to the level of the controls, as did diastolic blood pressure after an initial reduction. Age-adjusted exercise capacity increased during the study and we found no evidence of ischaemic heart disease on exercise ECG. Stroke volume increased with GH substitution, thereby normalizing the initially reduced cardiac index. There was no significant change in left atrial or ventricular internal dimensions, systolic function as measured by fractional shortening, or diastolic function as measured by isovolumic relaxation time and left ventricular filling (A/E ratio). However, a lower atrial emptying index than that seen among controls might indicate some diastolic disturbance and there was a definite increase in left ventricular wall thickness compared with controls (to 25.1 +/- 1.5 vs 19.7 +/- 0.4 mm, P < 0.001).We found that GH substitution in GH-deficient adults had a beneficial effect on physical performance and cardiac output. The concomitant increase in left ventricular mass index might be an effect of an excessive substitution dose.
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| 33. |
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| 34. |
- Killela, Patrick J., et al.
(author)
-
TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
- 2013
-
In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:15, s. 6021-6026
-
Journal article (peer-reviewed)abstract
- Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (>= 15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
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| 35. |
- Kindlund, Bert, 1969, et al.
(author)
-
CD4(+) regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β.
- 2017
-
In: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 20:1
-
Journal article (peer-reviewed)abstract
- An increase of regulatory T cells, defined as CD25(high)- and/or FOXP3(+)-expressing CD4(+) T cells, within tumors has been reported in several studies. Tregs promote tumor growth by modulating the antitumor immune response, mainly through inhibition of T-cell-mediated tumor cell killing: this has been suggested to be dependent on IL-10 and/or TGF-β. In stomach cancer, the mechanisms behind the accumulation of Tregs in tumor tissue has not been fully elucidated, and neither has Treg gene expression in situ.
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| 36. |
- Kindlund, Bert, 1969, et al.
(author)
-
FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients.
- 2009
-
In: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 14:3, s. 192-201
-
Journal article (peer-reviewed)abstract
- BACKGROUND: We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H. pylori eradication. METHODS: Cellular FOXP3 expression was studied by immunofluorescence and flow cytometry, and transcription levels of FOXP3, interleukin (IL)-10, transforming growth factor-beta, CD4, and interferon-gamma were analyzed by real-time reverse transcription-polymerase chain reaction. RESULTS: We found an increased (6-fold) frequency of CD4(+)FOXP3(+) T cells in H. pylori-infected gastric mucosa; interestingly 26% of these cells did not co-express CD25. The increase of FOXP3-expressing T cells in the antrum of infected individuals was dependent on the presence of H. pylori, since eradication therapy resulted in 4-fold lower levels of FOXP3 and IL-10 mRNA in the antrum. Furthermore, higher numbers of CD4(+)FOXP3(+) T cells were found in areas of duodenal gastric metaplasia in the duodenum of duodenal ulcer patients compared to duodenal gastric metaplasia of asymptomatic individuals and healthy mucosa in both patient groups. In duodenal ulcer patients, the CD4(+)FOXP3(+) T cells were more highly associated to aggregates in the duodenal mucosa. CONCLUSION: The numbers of CD4(+)FOXP3(+) T cells are increased and localized in CD4(+) T-cell aggregates in areas of duodenal gastric metaplasia in duodenal ulcer patients.
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| 37. |
- Knudsen, Lisa B., et al.
(author)
-
Halogenated organic contaminants and mercury in northern fulmars (Fulmarus glacialis) : levels, relationships to dietary descriptors and blood to liver comparison
- 2007
-
In: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 146:1, s. 25-33
-
Journal article (peer-reviewed)abstract
- The northern fulmar (Fulmarus glacialis) is an interesting candidate for the study of patterns and levels of halogenated organic contaminants (HOCs) since they accumulate high levels of certain HOCs. In the present study we characterized a suite of established and novel HOCs in northern fulmars breeding on Bjørnøya in the Norwegian Arctic. A comparison between blood and liver HOC levels was made, and the levels were related to the ratios of heavier to lighter stable isotopes of nitrogen (15)N/(14)N (delta(15)N) and carbon (13)C/(12)C (delta(13)C) in muscle. A significant difference in congener patterns between blood and liver was found. The delta(13)C was not related to HOCs, neither in liver nor in blood. Weak correlations were found between delta(15)N and liver HOC levels. The 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) in northern fulmars were well above thresholds for reproductive effects in seabirds.
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| 38. |
- Lindelöw, B, et al.
(author)
-
Graft coronary artery disease is strongly related to the aetiology of heart failure and cellular rejections.
- 1999
-
In: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 20:18, s. 1326-34
-
Journal article (peer-reviewed)abstract
- To identify risk factors for the development of coronary artery disease after heart transplantation.In consecutive heart transplanted patients, who underwent coronary angiography at the first year follow-up, the aetiology of heart failure in 113 was ischaemic heart disease or dilated cardiomyopathy. Development of clinically significant graft coronary artery disease was analysed vs recipient and donor pre- and post-transplantation variables. At 1, 5 and 9 years follow-up, coronary artery disease had developed in 4%, 16%, and 20% of the included patients, respectively. Among patients with ischaemic heart disease as the aetiology of heart failure, 38% developed graft coronary artery disease, while the corresponding figure for patients with dilated cardiomyopathy was 9% (P<0.001) during 9 years of follow-up. In multivariate regression analysis, the aetiology of ischaemic heart disease and the number of cellular rejections were independent predictors of developing graft coronary artery disease, with risk ratios of 5.8, (95% confidence interval of 2.2-14.8 (P=0.0003)) and 3.3, (95% confidence interval of 1.7-6.5 (P=0.0004)), respectively. Classical risk factors for coronary artery disease did not influence the development of graft coronary artery disease.Ischaemic heart disease as the aetiology of heart failure and the number of cellular rejections were powerful independent predictors of development of graft coronary artery disease following heart transplantation. The low incidence of graft coronary artery disease among patients with dilated cardiomyopathy implies that coronary angiography after heart transplantation can be made on a more selective basis.
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| 39. |
- Lindelöw, B, et al.
(author)
-
Prognosis of alternative therapies in patients with heart failure not accepted for heart transplantation.
- 1995
-
In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - 1053-2498. ; 14:6 Pt 1, s. 1204-11
-
Journal article (peer-reviewed)abstract
- This article describes the outcome of alternative therapies in patients with end-stage heart failure, New York Heart Association class III-IV, referred for heart transplantation evaluation but not accepted for the procedure. From January 1988 through September 1992, 233 consecutive patients with severe heart failure were admitted to the thoracic transplantation center at Sahlgrenska University Hospital. At the time of admission all patients received standard medical treatment for heart failure. During the pretransplantation evaluation, an attempt to optimize the medical therapy was made in all patients.Eighteen patients (8%) died before a decision concerning transplantation was made, and 146 patients (63%) were accepted for heart transplantation. There were 69 patients (30%) who were denied heart transplantation for various reasons, and they were subgrouped: patients with contraindications (group 1, n = 23) or without indication (group 2, n = 10) for heart transplantation, patients with a positive response to intensified medical therapy (group 3, n = 25), and patients who underwent coronary artery bypass grafting and/or valvular heart surgery (group 4, n = 11). The 1-, 3-, and 5-year actuarial survival rates were as follows: group 1, 26%, 16%, and 8%; group 2, 100%, 77%, and 39%; group 3, 96%, 67%, and 53%; and group 4, 64%, 36%, and 27%, respectively. The corresponding figures for patients who had a heart transplantation were 85%, 79%, and 75%, respectively. During the first 2 to 3 years of follow-up the survival of group 2 and group 3 patients was similar to that of patients who underwent transplantation. However, late survival was worse compared with the heart transplant group.These results suggest that by close follow-up it may be possible to postpone heart transplantation in a selected group of patients.
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| 40. |
- Lindqvist, Per, et al.
(author)
-
Pulsed tissue Doppler and strain imaging discloses early signs of infiltrative cardiac disease: a study on patients with familial amyloidotic polyneuropathy.
- 2006
-
In: Eur J Echocardiogr. ; 7:1, s. 22-30
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis with cardiac involvement. As early identification of the cardiac involvement is of major clinical interest we performed this study to test the hypothesis that tissue Doppler imaging (TDI) and strain imaging (SI) might disclose cardiac involvement in patients with early stages of FAP. METHODS: Twenty-two patients with FAP and 36 healthy controls were studied. Standard M-mode and Doppler echocardiography were performed. TDI and SI were used to assess the regional longitudinal left ventricular (LV) lateral and septal and right ventricular (RV) wall functions. All time intervals were corrected for heart rate by dividing with R-R interval and presented as percentage. RESULTS: We found that patients in comparison with controls had increased LV and RV wall thickness and by using TDI a prolonged isovolumic relaxation time (IVRt) at the septal segment (15.0+/-7.0 vs 10.7+/-4.1%, p<0.05) and prolonged isovolumic contraction time (IVCt) at LV lateral (12.8+/-4.3 vs 10.1+/-3.3%, p<0.05), septal (12.5+/-3.5 vs 8.9+/-1.9%, p<0.001) and RV free wall segments (12.0+/-3.6 vs 8.3+/-2.1%, p<0.001). Strain was reduced at LV lateral basal segment (-4.6+/-14.0 vs -20.2+9.1, p<0.001), RV free wall mid segment (-16.2+/-12.8 vs -29.4+/-15.2) as well as both septal segments (-4.1+/-11.7 vs -16.2+/-9.0%, p<0.001, -8.8+/-11.5 vs -19.4+/-8.4%, p<0.001 for septal basal and mid-segment). Even in the absence of septal hypertrophy the septal strain was reduced and the regional IVCt was prolonged. CONCLUSIONS: This is the first clinical study using TDI and strain in patients with FAP showing functional abnormalities before any morphological echocardiographic abnormalities were present. Both the left and right heart functions are involved and the disease should therefore be regarded as biventricular.
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| 41. |
- Lundin, Samuel B, 1970, et al.
(author)
-
The local and systemic T-cell response to Helicobacter pylori in gastric cancer patients is characterised by production of interleukin-10.
- 2007
-
In: Clinical immunology (Orlando, Fla.). - : Elsevier BV. - 1521-6616. ; 125:2, s. 205-13
-
Journal article (peer-reviewed)abstract
- Helicobacter pylori causes a life-long infection that may lead to development of gastric adenocarcinoma (GC) and thereby cause major worldwide health problems. The present study was designed to study whether those that develop GC have an altered immune response to H. pylori compared to individuals that remain asymptomatic. When stimulated with H. pylori antigens, T cells from both peripheral blood and gastric mucosa of H. pylori-infected GC patients produced high amounts of IL-10, while the IL-10 production from blood T cells of H. pylori-infected asymptomatic subjects was low. Furthermore, mRNA levels of IL-10 were increased in the gastric mucosa of GC patients. In addition, the frequency of activated CD8(+) T cells was markedly reduced in stomach mucosa of patients with GC compared to asymptomatic individuals. We propose that the increased production of the suppressive cytokine IL-10 in H. pylori-infected GC patients leads to a diminished cytotoxic anti-tumour T-cell response in the stomach, which may contribute to tumour progression in subjects suffering from GC.
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| 42. |
- McGuckian, Thomas B., et al.
(author)
-
Development of complex executive function over childhood : Longitudinal growth curve modeling of performance on the Groton Maze Learning Task
- 2023
-
In: Child Development. - : John Wiley & Sons. - 0009-3920 .- 1467-8624. ; 94:3, s. 648-658
-
Journal article (peer-reviewed)abstract
- This longitudinal study modeled children's complex executive function (EF) development using the Groton Maze Learning Task (GMLT). Using a cohort-sequential design, 147 children (61 males, 5.5–11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. Race/ethnicity data were not available. Children were assessed on the GMLT at 6-month intervals over 2-years between 2010 and 2012. Growth curve models describe age-related change from 5.5 to 12.5 years old. Results showed a quadratic growth trajectory on each measure of error—that is, those that reflect visuospatial memory, executive control (or the ability to apply rules for action), and complex EF. The ability to apply rules for action, while a rate-limiting factor in complex EF, develops rapidly over early-to-mid childhood.
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| 43. |
- Niu, Shuli, et al.
(author)
-
Thermal optimality of net ecosystem exchange of carbon dioxide and underlying mechanisms.
- 2012
-
In: New Phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 194:3, s. 775-783
-
Journal article (peer-reviewed)abstract
- • It is well established that individual organisms can acclimate and adapt to temperature to optimize their functioning. However, thermal optimization of ecosystems, as an assemblage of organisms, has not been examined at broad spatial and temporal scales. • Here, we compiled data from 169 globally distributed sites of eddy covariance and quantified the temperature response functions of net ecosystem exchange (NEE), an ecosystem-level property, to determine whether NEE shows thermal optimality and to explore the underlying mechanisms. • We found that the temperature response of NEE followed a peak curve, with the optimum temperature (corresponding to the maximum magnitude of NEE) being positively correlated with annual mean temperature over years and across sites. Shifts of the optimum temperature of NEE were mostly a result of temperature acclimation of gross primary productivity (upward shift of optimum temperature) rather than changes in the temperature sensitivity of ecosystem respiration. • Ecosystem-level thermal optimality is a newly revealed ecosystem property, presumably reflecting associated evolutionary adaptation of organisms within ecosystems, and has the potential to significantly regulate ecosystem-climate change feedbacks. The thermal optimality of NEE has implications for understanding fundamental properties of ecosystems in changing environments and benchmarking global models.
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| 44. |
- Nyström, Markus B. T., et al.
(author)
-
Shame and interpersonal sensitivity : Gender differences and the association between internalized shame coping strategies and interpersonal sensitivity
- 2018
-
In: Bulletin of the Menninger Clinic. - : Guilford Publications. - 0025-9284 .- 1943-2828. ; 82:2, s. 137-155
-
Journal article (peer-reviewed)abstract
- The present study investigated gender differences in interpersonal sensitivity and internalized shame coping strategies in 252 undergraduate students. To measure interpersonal sensitivity and shame coping strategies, the self-assessment forms Interpersonal Sensitivity Measure and Compass of Shame Scale were used. The analyses revealed that compared to men, women display interpersonal sensitivity to a higher degree, and they use internalized shame coping strategies to a greater extent. The results also showed that interpersonal sensitivity is highly correlated with shame coping strategies. However, in contrast to earlier research, no gender difference was found, and gender did not significantly mediate the association between interpersonal sensitivity and internalized shame coping. These results could aid clinicians and researchers in promoting, designing, delivering, and evaluating treatments for patients with, for example, depression, anxiety, and interpersonal and/or relational problems.
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| 45. |
- Oei, Ling, et al.
(author)
-
A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
-
In: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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| 46. |
- Quintela-Sabarís, Celestino, et al.
(author)
-
Assessing phytotoxicity of trace element-contaminated soils phytomanaged with gentle remediation options at ten European field trials
- 2017
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 599-600, s. 1388-1398
-
Journal article (peer-reviewed)abstract
- Gentle remediation options (GRO), i.e. in situ stabilisation, (aided) phytoextraction and (aided) phytostabilisation, were implemented at ten European sites contaminated with trace elements (TE) from various anthropogenic sources: mining, atmospheric fallout, landfill leachates, wood preservatives, dredged-sediments, and dumped wastes. To assess the performance of the GRO options, topsoil was collected from each field trial, potted, and cultivated with lettuce (Lactuca sativa L.) for 48 days. Shoot dry weight (DW) yield, photosynthesis efficiency and major element and TE concentrations in the soil pore water and lettuce shoots were measured.GRO implementation had a limited effect on TE concentrations in the soil pore water, although use of multivariate Co-inertia Analysis revealed a clear amelioration effect in phytomanaged soils. Phytomanagement increased shoot DW yield at all industrial and mine sites, whereas in agricultural soils improvements were produced in one out of five sites. Photosynthesis efficiency was less sensitive than changes in shoot biomass and did not discriminate changes in soil conditions.Based on lettuce shoot DW yield, compost amendment followed by phytoextraction yielded better results than phytostabilisation; moreover shoot ionome data proved that, depending on initial soil conditions, recurrent compost application may be required to maintain crop production with common shoot nutrient concentrations.
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| 47. |
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| 48. |
- Rotander, Anna, et al.
(author)
-
Metoxylated polybrominated diphenyl ethers (MeO-PBDEs) are major contributors to the persistent organobromine load in sub-Arctic and Arctic marine mammals, 1986-2009
-
Other publication (other academic/artistic)abstract
- A selection of MeO-PBDE and PBDE congeners were analyzed in pooled blubber samples of pilot whale (Globicephala melas), ringed seal (Phoca hispida), minke whale (Balaenoptera acutorostrata), fin whale (Balaenoptera physalus), harbour porpoise (Phocoena phocoena), hooded seal (Cystophora cristata), and Atlantic white-sided dolphin (Lagenorhynchus acutus), covering a time period of more than 20 years (1986-2009). The analytes were extracted and cleaned-up using open column extraction and multi-layer silica gel column chromatography. The analysis was performed using both low resolution and high resolution GC-MS. MeO-PBDE concentrations relative to total PBDE concentrations varied greatly between sampling periods and species. The highest MeO-PBDE levels were found in the toothed whale species pilot whale and white-sided dolphin, often exceeding the concentration of the most abundant PBDE, BDE-47. The lowest MeO-PBDE levels were found in fin whales and ringed seals. The main MeO-PBDE congeners were 6MBDE-47 and 2PMBDE-68. A weak correlation only between BDE-47 and its metoxylated analogue 6MBDE-47 was found and is indicative of a natural source for MeO-PBDEs.
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| 49. |
- Rotander, Anna, et al.
(author)
-
Polychlorinated naphtalenes (PCNs) in sub-Arctic and Arctic marine mammals, 1986-2009
-
Other publication (other academic/artistic)abstract
- A selection of PCN congeners was analyzed in pooled blubber samples of pilot whale (Globicephala melas), ringed seal (Phoca hispida), minke whale (Balaenoptera acutorostrata), fin whale (Balaenoptera physalus), harbour porpoise (Phocoena phocoena), hooded seal (Cystophora cristata) and Atlantic white-sided dolphin (Lagenorhynchus acutus), covering a time period of more than 20 years (1986-2009). The analytes were extracted and cleaned-up using open column extraction and multi-layer silica gel column chromatography. The analysis was performed using high resolution GC-MS. PCN congeners #48, #52, #53, #66 and #69 were found in the blubber samples between 0.03 and 5.9 ng/g lw. Also PCBs were analyzed in minke whales and fin whales from Iceland. The total PCN content accounted for less than 1% of the total coplanar PCB content. The lowest PCN concentrations were found in the samples from the latest sampling period (2006-2009). The results indicate a decline in the PCN load in marine mammals from the studied area in recent years.
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| 50. |
- Schaller, Matthieu, et al.
(author)
-
Swift : a modern highly parallel gravity and smoothed particle hydrodynamics solver for astrophysical and cosmological applications
- 2024
-
In: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 530:2, s. 2378-2419
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Journal article (peer-reviewed)abstract
- Numerical simulations have become one of the key tools used by theorists in all the fields of astrophysics and cosmology. The development of modern tools that target the largest existing computing systems and exploit state-of-the-art numerical methods and algorithms is thus crucial. In this paper, we introduce the fully open-source highly-parallel, versatile, and modular coupled hydrodynamics, gravity, cosmology, and galaxy-formation code SWIFT. The software package exploits hybrid shared- and distributed-memory task-based parallelism, asynchronous communications, and domain-decomposition algorithms based on balancing the workload, rather than the data, to efficiently exploit modern high-performance computing cluster architectures. Gravity is solved for using a fast-multipole-method, optionally coupled to a particle mesh solver in Fourier space to handle periodic volumes. For gas evolution, multiple modern flavours of Smoothed Particle Hydrodynamics are implemented. SWIFT also evolves neutrinos using a state-of-the-art particle-based method. Two complementary networks of sub-grid models for galaxy formation as well as extensions to simulate planetary physics are also released as part of the code. An extensive set of output options, including snapshots, light-cones, power spectra, and a coupling to structure finders are also included. We describe the overall code architecture, summarize the consistency and accuracy tests that were performed, and demonstrate the excellent weak-scaling performance of the code using a representative cosmological hydrodynamical problem with ≈300 billion particles. The code is released to the community alongside extensive documentation for both users and developers, a large selection of example test problems, and a suite of tools to aid in the analysis of large simulations run with SWIFT.
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