| 1. |
- Pulit, S. L., et al.
(författare)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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| 2. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 3. |
- Marini, S., et al.
(författare)
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Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
- 2019
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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| 4. |
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| 5. |
- Foldager, C. B., et al.
(författare)
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Aarhus Regenerative Orthopaedics Symposium (AROS): Regeneration in the ageing population
- 2016
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 87, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- The combination of modern interventional and preventive medicine has led to an epidemic of ageing. While this phenomenon is a positive consequence of an improved lifestyle and achievements in a society, the longer life expectancy is often accompanied by decline in quality of life due to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem.
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| 6. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 7. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 8. |
- Jansen, Joachim, 1989-, et al.
(författare)
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Monitoring of carbon-water fluxes at Eurasian meteorological stations using random forest and remote sensing
- 2023
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Simulating the carbon-water fluxes at more widely distributed meteorological stations based on the sparsely and unevenly distributed eddy covariance flux stations is needed to accurately understand the carbon-water cycle of terrestrial ecosystems. We established a new framework consisting of machine learning, determination coefficient (R2), Euclidean distance, and remote sensing (RS), to simulate the daily net ecosystem carbon dioxide exchange (NEE) and water flux (WF) of the Eurasian meteorological stations using a random forest model or/and RS. The daily NEE and WF datasets with RS-based information (NEE-RS and WF-RS) for 3774 and 4427 meteorological stations during 2002-2020 were produced, respectively. And the daily NEE and WF datasets without RS-based information (NEE-WRS and WF-WRS) for 4667 and 6763 meteorological stations during 1983-2018 were generated, respectively. For each meteorological station, the carbon-water fluxes meet accuracy requirements and have quasi-observational properties. These four carbon-water flux datasets have great potential to improve the assessments of the ecosystem carbon-water dynamics.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Rees, R. M., et al.
(författare)
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Nitrous oxide emissions from European agriculture; an analysis of variability and drivers of emissions from field experiments
- 2012
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Ingår i: Biogeosciences Discussions. - : Copernicus GmbH. - 1810-6277. ; 9:7, s. 9259-9288
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Tidskriftsartikel (refereegranskat)abstract
- Nitrous oxide emissions from a network of agricultural experiments in Europe and Zimbabwe were used to explore the relative importance of site and management controls of emissions. At each site, a selection of management interventions were compared 5 within replicated experimental designs in plot based experiments. Arable experiments were conducted at Beano in Italy, El Encin in Spain, Foulum in Denmark, Logården in Sweden, Maulde in Belgium, Paulinenaue in Germany, Harare in Zimbabwe and Tulloch in the UK. Grassland experiments were conducted at Crichton, Nafferton and Peaknaze in the UK, Gödöllö in Hungary, Rzecin in Poland, Zarnekow in Germany and 10 Theix in France. Nitrous oxide emissions were measured at each site over a period of at least two years using static chambers. Emissions varied widely between sites and as a result of manipulation treatments. Average site emissions (throughout the study period) varied between 0.04 and 21.21 kg N2O-N ha−1 yr−1, with the largest fluxes and variability associated with the grassland sites. Total nitrogen addition was found to be 15 the single most important determinant of emissions, accounting for 15% of the variance (using linear regression) in the data from the arable sites (p < 0.0001), and 77% in the grassland sites. The annual emissions from arable sites were significantly greater than those that would be predicted by IPCC default emission factors. Variability in N2O within sites that occurred as a result of manipulation treatments was greater than that 20 resulting from site to site and year to year variation, highlighting the importance of management interventions in contributing to greenhouse gas mitigation.
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| 13. |
- Rees, R. M., et al.
(författare)
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Nitrous oxide emissions from European agriculture - an analysis of variability and drivers of emissions from field experiments
- 2013
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 10:4, s. 2671-2682
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Tidskriftsartikel (refereegranskat)abstract
- Nitrous oxide emissions from a network of agricultural experiments in Europe and Zimbabwe were used to explore the relative importance of site and management controls of emissions. At each site, a selection of management interventions were compared within replicated experimental designs in plot based experiments. Arable experiments were conducted at Beano in Italy, El Encin in Spain, Foulum in Denmark, Logården in Sweden, Maulde in Belgium, Paulinenaue in Germany, Harare in Zimbabwe and Tulloch in the UK. Grassland experiments were conducted at Crichton, Nafferton and Peaknaze in the UK, Gödöllö in Hungary, Rzecin in Poland, Zarnekow in Germany and Theix in France. Nitrous oxide emissions were measured at each site over a period of at least two years using static chambers. Emissions varied widely between sites and as a result of manipulation treatments. Average site emissions (throughout the study period) varied between 0.04 and 21.21 kg N2O-N ha−1 yr−1, with the largest fluxes and variability associated with the grassland sites. Total nitrogen addition was found to be the single most important determinant of emissions, accounting for 15% of the variance (using linear regression) in the data from the arable sites (p < 0.0001), and 77% in the grassland sites. The annual emissions from arable sites were significantly greater than those that would be predicted by IPCC default emission factors. Variability in N2O within sites that occurred as a result of manipulation treatments was greater than that resulting from site to site and year to year variation, highlighting the importance of management interventions in contributing to greenhouse gas mitigation.
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| 14. |
- Gordin, D., et al.
(författare)
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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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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 26:5, s. 294-302
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Tidskriftsartikel (refereegranskat)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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| 15. |
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| 16. |
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| 17. |
- Petersen, S. O., et al.
(författare)
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In-vitro method and model to estimate methane emissions from liquid manure management on pig and dairy farms in four countries
- 2024
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Ingår i: Journal of Environmental Management. - : Academic Press. - 0301-4797 .- 1095-8630. ; 353
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Tidskriftsartikel (refereegranskat)abstract
- Methane (CH4) emissions from manure management on livestock farms are a key source of greenhouse gas emissions in some regions and for some production systems, and the opportunities for mitigation may be significant if emissions can be adequately documented. We investigated a method for estimating CH4 emissions from liquid manure (slurry) that is based on anaerobic incubation of slurry collected from commercial farms. Methane production rates were used to derive a parameter of the Arrhenius temperature response function, lnA', representing the CH4 production potential of the slurry at the time of sampling. Results were used for parameterization of an empirical model to estimate annual emissions with daily time steps, where CH4 emissions from individual sources (barns, outside storage tanks) can be calculated separately. A monitoring program was conducted in four countries, i.e., Denmark, Sweden, Germany and the Netherlands, during a 12-month period where slurry was sampled to represent barn and outside storage on finishing pig and dairy farms. Across the four countries, lnA' was higher in pig slurry compared to cattle slurry (p < 0.01), and higher in slurry from barns compared to outside storage (p < 0.01). In a separate evaluation of the incubation method, in-vitro CH4 production rates were comparable with in-situ emissions. The results indicate that lnA' in barns increases with slurry age, probably due to growth or adaptation of the methanogenic microbial community. Using lnA' values determined experimentally, empirical models with daily time steps were constructed for finishing pig and dairy farms and used for scenario analyses. Annual emissions from pig slurry were predicted to be 2.5 times higher than those from cattle slurry. Changing the frequency of slurry export from the barn on the model pig farm from 40 to 7 d intervals reduced total annual CH4 emissions by 46 %; this effect would be much less on cattle farms with natural ventilation. In a scenario with cattle slurry, the empirical model was compared with the current IPCC methodology. The seasonal dynamics were less pronounced, and annual CH4 emissions were lower than with the current methodology, which calls for further investigations. Country-specific models for individual animal categories and point sources could be a tool for assessing CH4 emissions and mitigation potentials at farm level.
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| 18. |
- Seifert, Mariam B., et al.
(författare)
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Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation
- 2019
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Ingår i: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X .- 1542-474X. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Abnormal P-wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P-wave abnormalities. Methods: Four SNPs were studied in 176 unrelated individuals with early-onset lone AF (age at onset <50 years), median age 38 years (19–63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1—positive in leads X and Y and negative in lead Z, Type 2—positive in leads X and Y and biphasic (−/+) in lead Z, Type 3—positive in lead X and biphasic in lead Y (+/−), and the remaining as atypical. Results: Two SNPs were found to be significantly associated with altered P-wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non-Type 1 P-wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3–10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1–20.5, p = 0.04). No association was observed for rs2200733 and rs13376333. Conclusion: In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P-wave morphology distribution in patients with early-onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.
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| 19. |
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| 20. |
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| 21. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 22. |
- Andlin-Sobocki, P, et al.
(författare)
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Cost of disorders of the brain in Europe
- 2005
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Ingår i: European journal of neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 1212 Suppl 1, s. 1-
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Tidskriftsartikel (refereegranskat)
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| 23. |
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| 24. |
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| 25. |
- Boström, C., et al.
(författare)
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Distribution, structure and function of Nordic eelgrass (Zostera marina) ecosystems: Implications for coastal management and conservation
- 2014
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Ingår i: Aquatic conservation. - : Wiley. - 1052-7613. ; 24:3, s. 410-434
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Forskningsöversikt (refereegranskat)abstract
- This paper focuses on the marine foundation eelgrass species, Zostera marina, along a gradient from the northern Baltic Sea to the north-east Atlantic. This vast region supports a minimum of 1480km2 eelgrass (maximum >2100km2), which corresponds to more than four times the previously quantified area of eelgrass in Western Europe. Eelgrass meadows in the low salinity Baltic Sea support the highest diversity (4-6 spp.) of angiosperms overall, but eelgrass productivity is low (<2g dw m-2 d-1) and meadows are isolated and genetically impoverished. Higher salinity areas support monospecific meadows, with higher productivity (3-10g dw m-2 d-1) and greater genetic connectivity. The salinity gradient further imposes functional differences in biodiversity and food webs, in particular a decline in number, but increase in biomass of mesograzers in the Baltic. Significant declines in eelgrass depth limits and areal cover are documented, particularly in regions experiencing high human pressure. The failure of eelgrass to re-establish itself in affected areas, despite nutrient reductions and improved water quality, signals complex recovery trajectories and calls for much greater conservation effort to protect existing meadows. The knowledge base for Nordic eelgrass meadows is broad and sufficient to establish monitoring objectives across nine national borders. Nevertheless, ensuring awareness of their vulnerability remains challenging. Given the areal extent of Nordic eelgrass systems and the ecosystem services they provide, it is crucial to further develop incentives for protecting them. © 2014 The Authors.
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| 26. |
- Brond, J. C., et al.
(författare)
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Simple Method for the Objective Activity Type Assessment with Preschoolers, Children and Adolescents
- 2020
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Ingår i: Children. - : MDPI AG. - 2227-9067. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- Background:The objective and accurate assessment of children's sedentary and physical behavior is important for investigating their relation to health. The purpose of this study is to validate a simple and robust method for the identification of sitting, standing, walking, running and biking performed by preschool children, children and adolescents in the age from 3 to 16 years from a single thigh-worn accelerometer.Method:A total of 96 children were included in the study and all subjects followed a structured activity protocol performed in the subject's normal kindergarten or school environment. Thigh acceleration was measured using the Axivity AX3 (Axivity, Newcastle, UK) device. Method development and accuracy was evaluated by equally dividing the subjects into a development and test group.Results:The sensitivity and specificity for identifying sitting and standing was above 99.3% and for walking and running above 82.6% for all age groups. The sensitivity and specificity for identifying biking was above 85.8% for children and adolescents and above 64.8% for the preschool group using running bikes.Conclusion:The accurate assessment of sitting, standing, walking, running and biking from thigh acceleration and with children in the age range of 3 to 16 is valid, although not with preschool children using running bikes.
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| 27. |
- Chiesa, Giacomo, et al.
(författare)
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Remove sensible heat from indoor environments
- 2023
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Ingår i: International Energy Agency - Resilient Cooling of Buildings - State of the Art Review. - Vienna : Institute of Building Research & Innovation. ; , s. 130-189
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The world is facing a rapid increase of air conditioning of buildings. It is the motivation of Annex 80 to develop, assess and communicate solutions of resilient cooling and overheating protection. Resilient Cooling is used to denote low energy and low carbon cooling solutions that strengthen the ability of individuals and our community to withstand, and prevent, thermal and other impacts of changes in global and local climates. It encompasses the assessment and Research & Development of both active and passive cooling technologies of the following four groups:Reduce heat loads to people and indoor environments.Remove sensible heat from indoor environments.Enhance personal comfort apart from space cooling.Remove latent heat from indoor environments.The present review sums up the state of the art in cooling solutions which may be regarded as resilient. Its main objective is to systematically describe the available cooling solutions, their physical basis, their benefits and limitations, their technology readiness level, their practical availability, and applicability. Doing so, the State-of-the-Art Review forms the basis for the work of Annex 80.
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| 28. |
- Cirtwill, Alyssa, et al.
(författare)
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Between-year changes in community composition shape species' roles in an Arctic plant-pollinator network
- 2018
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Ingår i: Oikos. - : WILEY. - 0030-1299 .- 1600-0706. ; 127:8, s. 1163-1176
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Tidskriftsartikel (refereegranskat)abstract
- Inter-annual turnover in community composition can affect the richness and functioning of ecological communities. If incoming and outgoing species do not interact with the same partners, ecological functions such as pollination may be disrupted. Here, we explore the extent to which turnover affects species' roles - as defined based on their participation in different motifs positions - in a series of temporally replicated plant-pollinator networks from high-Arctic Zackenberg, Greenland. We observed substantial turnover in the plant and pollinator assemblages, combined with significant variation in species' roles between networks. Variation in the roles of plants and pollinators tended to increase with the amount of community turnover, although a negative interaction between turnover in the plant and pollinator assemblages complicated this trend for the roles of pollinators. This suggests that increasing turnover in the future will result in changes to the roles of plants and likely those of pollinators. These changing roles may in turn affect the functioning or stability of this pollination network.
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| 29. |
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| 30. |
- Damber, Jan-Erik, 1949, et al.
(författare)
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The Effect of Baseline Testosterone on the Efficacy of Degarelix and Leuprolide: Further Insights From A 12-Month, Comparative, Phase III Study in Prostate Cancer Patients
- 2012
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Ingår i: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 80:1, s. 174-180
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen (PSA) suppression using data from a phase III trial (CS21) comparing degarelix and leuprolide in prostate cancer. METHODS In CS21, patients with histologically confirmed prostate cancer (all stages) were randomized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg, or leuprolide 7.5 mg/month. Patients receiving leuprolide could receive antiandrogens for flare protection. Treatment effects on testosterone and PSA reduction, testosterone surge, and microsurges were investigated in 3 baseline testosterone subgroups: <3.5, 3.5-5.0, and >5.0 ng/mL. Data are presented for the groups receiving degarelix 240/80 mg (the approved dose) and leuprolide 7.5 mg. RESULTS Higher baseline testosterone delayed castration with both treatments. However, castrate testosterone levels and PSA suppression occurred more rapidly with degarelix irrespective of baseline testosterone. With leuprolide, the magnitude of testosterone surge and microsurges increased with increasing baseline testosterone. There was no overall correlation between baseline testosterone and initial PSA decrease in either treatment group, although PSA suppression tended to be slowest with leuprolide and fastest with degarelix in the high baseline testosterone subgroup. CONCLUSION Patients with high baseline testosterone may have greater risk of tumor stimulation (clinical flare) and mini-flares during gonadotrophin-releasing hormone agonist treatment and so the need for flare protection with antiandrogens in these patients is obvious, especially in metastatic disease. Although higher baseline testosterone delays castration, castrate testosterone and PSA suppression occur more rapidly with degarelix, irrespective of baseline testosterone, without the need for flare protection. UROLOGY 80: 174-181, 2012. (c) 2012 Elsevier Inc.
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| 31. |
- Domazet, Sidsel L., et al.
(författare)
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Low-grade inflammation in persons with recently diagnosed type 2 diabetes : The role of abdominal adiposity and putative mediators
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Ingår i: Diabetes, Obesity and Metabolism. - 1462-8902.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. Materials and Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. Results: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%). Conclusions: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.
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| 32. |
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| 33. |
- Ehlers, B. K., et al.
(författare)
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Floral morphology and reproductive success in the orchid Epipactis helleborine : regional and local across-habitat variation
- 2002
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Ingår i: Plant Systematics and Evolution. - : Springer Science and Business Media LLC. - 0378-2697 .- 1615-6110. ; 236:1-2, s. 19-32
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Tidskriftsartikel (refereegranskat)abstract
- The terrestrial orchid Epipactis helleborine is a morphologically variable species with a wide distribution in Europe. It is pollinated by social wasps, and most populations show the morphological characteristics of outcrossing species. However, local predominantly selfing subspecies and varieties have been documented from drier habitats. To document geographic variation in floral morphology, ability to produce seeds through autogamy, and reproductive success in E. helleborine, we sampled 13 populations from three geographic regions along a latitudinal gradient of c. 1000 km from northern to southern Sweden. In the southernmost region, populations in dry and mesic habitats were compared. Supplemental hand-pollination was conducted to determine whether among-population variation in fruit set could be explained by differences in the natural level of pollination, and whether any relationship between floral morphology and fruit production could be explained by interactions with pollinators. Bagging experiments showed no evidence of autogamy in any of the study populations. Number of flowers, pollinia removal and fruit set varied significantly among populations but did not differ among regions. Pollinia removal was positively correlated with population size and both pollinia removal and fruit set were lower in dry than in mesic habitats. At the level of the individual plant, the number of pollinia removed increased more rapidly with flower number than did number of fruits produced. The hand-pollination experiment indicated that the positive relationship between number of flowers and fruit production was due to a higher degree of pollen limitation in plants with few flowers than in plants with many flowers. The experiment also showed that variation in the level of pollen limitation could only partly explain variation in fruit set among populations.
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| 34. |
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| 35. |
- Frokjaer, J. B., et al.
(författare)
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Integrity of central nervous function in diabetes mellitus assessed by resting state EEG frequency analysis and source localization
- 2017
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Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727. ; 31:2, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) is associated with structural and functional changes of the central nervous system. We used electroencephalography (EEG) to assess resting state cortical activity and explored associations to relevant clinical features. Multichannel resting state EEG was recorded in 27 healthy controls and 24 patients with longstanding DM and signs of autonomic dysfunction. The power distribution based on wavelet analysis was summarized into frequency bands with corresponding topographic mapping. Source localization analysis was applied to explore the electrical cortical sources underlying the EEG. Compared to controls, DM patients had an overall decreased EEG power in the delta (1-4 Hz) and gamma (30-45 Hz) bands. Topographic analysis revealed that these changes were confined to the frontal region for the delta band and to central cortical areas for the gamma band. Source localization analysis identified sources with reduced activity in the left postcentral gyrus for the gamma band and in right superior parietal lobule for the alpha 1 (8-10 Hz) band. DM patients with clinical signs of autonomic dysfunction and gastrointestinal symptoms had evidence of altered resting state cortical processing. This may reflect metabolic, vascular or neuronal changes associated with diabetes.
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| 36. |
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| 37. |
- Hautakangas, H, et al.
(författare)
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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:2, s. 152-
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Tidskriftsartikel (refereegranskat)abstract
- Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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| 38. |
- Karlsson, Roger, 1975, et al.
(författare)
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Strain-level typing and identification of bacteria using mass spectrometry-based proteomics.
- 2012
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Ingår i: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 11:5, s. 2710-20
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Tidskriftsartikel (refereegranskat)abstract
- Because of the alarming expansion in the diversity and occurrence of bacteria displaying virulence and resistance to antimicrobial agents, it is increasingly important to be able to detect these microorganisms and to differentiate and identify closely related species, as well as different strains of a given species. In this study, a mass spectrometry proteomics approach is applied, exploiting lipid-based protein immobilization (LPI), wherein intact bacterial cells are bound, via membrane-gold interactions, within a FlowCell. The bound cells are subjected to enzymatic digestion for the generation of peptides, which are subsequently identified, using LC-MS. Following database matching, strain-specific peptides are used for subspecies-level discrimination. The method is shown to enable a reliable typing and identification of closely related strains of the same bacterial species, herein illustrated for Helicobacter pylori .
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| 39. |
- Komen, J. J., et al.
(författare)
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Heterogeneity after harmonisation : A retrospective cohort study of bleeding and stroke risk after the introduction of direct oral anticoagulants in four Western European countries
- 2023
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:11, s. 1223-1232
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison.Methods: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar-based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1-year cohort window were included. DOAC, vitamin K antagonist and aspirin treat-ment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual-level baseline characteristics.Results: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017.Conclusions: Stroke prevention therapy improved from 2012 to 2017 with a corre-sponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database.
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| 40. |
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| 41. |
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| 42. |
- Nielsen, Jonas B., et al.
(författare)
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Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 102:1, s. 103-115
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.
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| 43. |
- Nourozi, Behrouz, 1986-, et al.
(författare)
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Heating energy implications of utilizing gas-phase air cleaners in buildings’ centralized air handling units
- 2022
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Ingår i: Results in Engineering (RINENG). - : Elsevier B.V.. - 2590-1230. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Ventilation systems are a vital component of buildings in order to ensure a healthy and comfortable environment for the occupants. In cold climate regions, ventilation systems are responsible for approximately 30% of building heat losses. In addition to outdoor pollutants (particulate matters, NOX, etc.), indoor emissions from materials in the form of gas pollutants and emissions from occupants are the principal indoor air quality metrics for securing an acceptable indoor concentration level. Therefore, it is of great interest to study the use of gas-phase air cleaning technologies in low-energy centralized air handling units. This study focused on reducing buildings' heating requirements by recirculating indoor air while maintaining an acceptable indoor air quality level. The heating performance of a typical residential and office building in the central Swedish climate was studied by dynamic building simulations. Indoor air recirculation rates and air changes per hour were the key parameters considered during the simulation of the building's heating demand and indoor gaseous air pollution concentration. We found that introducing indoor air recirculation reduces buildings' heating demand depending on the air change rates per hour. The results show that it is possible to reduce the energy use for heating by less than approximaytely 10% and 20% for residential and office buildings, respectively and maintain acceptable indoor air quality by using gas-phase air cleaning.
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| 44. |
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| 45. |
- Olesen, J, et al.
(författare)
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Cost of disorders of the brain in Denmark
- 2008
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Ingår i: Nordic journal of psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 62:2, s. 114-120
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Tidskriftsartikel (refereegranskat)
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| 46. |
- Olesen, J, et al.
(författare)
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Funding of headache research in Europe
- 2007
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Ingår i: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 27:9, s. 995-999
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Tidskriftsartikel (refereegranskat)abstract
- Migraine costs European Society ¬27 billion per year. Other headaches may account for a similar amount. Given this enormous impact, the question arises as to whether the funding of research efforts in this field are sufficient. A recent European study called the Resource Allocation to Brain Research in Europe (RABRE) examined funding of brain research. Identified charities and Government agencies in Europe filled out a questionnaire regarding their funding of brain diseases. Industry spending was evaluated by three different previously validated methods. In the present report, detailed results are presented for migraine and other headaches. In 2004, migraine research was funded by nearly €315 million. Of this, €308 million was invested by the pharmaceutical industry, whereas public funding was estimated at €7 million. No funding was identified for non-migraine headache disorders. Of the public spending, €714 000 came from private foundations. There was a very large difference between different European countries in the funding of headache research. When public funding was compared with the cost of different brain disorders, migraine funding was in the middle range. This was due to relatively large industry funding. Compared with societal costs, migraine received the least public funds amongst all brain disorders, i.e. 0.025%. We conclude that migraine attracts reasonable interest from the pharmaceutical industry, but Governmental and charity funding is extremely low and no funding was identified for non-migraine headache disorders. Considering the huge economic impact of these disorders, public funding of research into migraine and other headaches should be greatly increased in the future.
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| 47. |
- Olesen, J, et al.
(författare)
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The economic cost of brain disorders in Europe
- 2012
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Ingår i: European Journal of Neurology. - : Wiley-Blackwell. - 1351-5101 .- 1468-1331. ; 19:1, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries.METHODS: One-year prevalence and annual cost per person of 19 major groups of disorders are based on 'best estimates' derived from systematic literature reviews by panels of experts in epidemiology and health economics. Our cost estimation model was populated with national statistics from Eurostat to adjust to 2010 values, converting all local currencies to Euros (€), imputing cost for countries where no data were available, and aggregating country estimates to purchasing power parity-adjusted estimates of the total cost of brain disorders in Europe in 2010.RESULTS: Total European 2010 cost of brain disorders was €798 billion, of which direct health care cost 37%, direct non-medical cost 23%, and indirect cost 40%. Average cost per inhabitant was €5.550. The European average cost per person with a disorder of the brain ranged between €285 for headache and €30 000 for neuromuscular disorders. Total annual cost per disorder (in billion € 2010) was as follows: addiction 65.7; anxiety disorders 74.4; brain tumor 5.2; child/adolescent disorders 21.3; dementia 105.2; eating disorders 0.8; epilepsy 13.8; headache 43.5; mental retardation 43.3; mood disorders 113.4; multiple sclerosis 14.6; neuromuscular disorders 7.7; Parkinson's disease 13.9; personality disorders 27.3; psychotic disorders 93.9; sleep disorders 35.4; somatoform disorder 21.2; stroke 64.1; and traumatic brain injury 33.0.CONCLUSION: Our cost model revealed that brain disorders overall are much more costly than previously estimated constituting a major health economic challenge for Europe. Our estimate should be regarded as conservative because many disorders or cost items could not be included because of lack of data.
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| 48. |
- Olesen, M. V., et al.
(författare)
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Y5 neuropeptide Y receptor overexpression in mice neither affects anxiety- and depression-like behaviours nor seizures but confers moderate hyperactivity
- 2012
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Ingår i: Neuropeptides. - : Elsevier BV. - 1532-2785 .- 0143-4179. ; 46:2, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) has been implicated in anxiolytic- and antidepressant-like behaviour as well as seizure-suppressant effects in rodents. Although these effects appear to be predominantly mediated via other NPY receptors (Y1 and/or Y2), several studies have also indicated a role for Y5 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY, Y1 or Y2 receptors in the hippocampus or amygdala has previously been shown to modulate emotional behaviour and seizures in rodents. The present study explored the potential effects of gene therapy with the Y5 receptor, by testing effects of recombinant adeno-associated viral vector (rAAV) encoding Y5 (rAAV-Y5) in anxiety- and depression-like behaviour as well as in kainate-induced seizures in adult mice. The rAAV-Y5 vector injected into the hippocampus and amygdala induced a pronounced and sustained increase in Y5 receptor mRNA expression and functional Y5 receptor binding, but no significant effects were found with regard to anxiety- and depression-like behaviours or seizure susceptibility. Instead, rAAV-mediated Y5 receptor transgene overexpression resulted in moderate hyperactivity in the open field test. These results do not support a potential role for single transgene overexpression of Y5 receptors for modulating anxiety-/depression-like behaviours or seizures in adult mice. Whether the induction of hyperactivity by rAAV-Y5 could be relevant for other conditions remains to be studied. (C) 2012 Elsevier Ltd. All rights reserved.
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