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Sökning: WFRF:(Krämer B.)

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1.
  • Coda, S., et al. (författare)
  • Overview of the TCV tokamak program : Scientific progress and facility upgrades
  • 2017
  • Ingår i: Nuclear Fusion. - Institute of Physics Publishing. - 0029-5515 .- 1741-4326. ; 57:10
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The TCV tokamak is augmenting its unique historical capabilities (strong shaping, strong electron heating) with ion heating, additional electron heating compatible with high densities, and variable divertor geometry, in a multifaceted upgrade program designed to broaden its operational range without sacrificing its fundamental flexibility. The TCV program is rooted in a three-pronged approach aimed at ITER support, explorations towards DEMO, and fundamental research. A 1 MW, tangential neutral beam injector (NBI) was recently installed and promptly extended the TCV parameter range, with record ion temperatures and toroidal rotation velocities and measurable neutral-beam current drive. ITER-relevant scenario development has received particular attention, with strategies aimed at maximizing performance through optimized discharge trajectories to avoid MHD instabilities, such as peeling-ballooning and neoclassical tearing modes. Experiments on exhaust physics have focused particularly on detachment, a necessary step to a DEMO reactor, in a comprehensive set of conventional and advanced divertor concepts. The specific theoretical prediction of an enhanced radiation region between the two X-points in the low-field-side snowflake-minus configuration was experimentally confirmed. Fundamental investigations of the power decay length in the scrape-off layer (SOL) are progressing rapidly, again in widely varying configurations and in both D and He plasmas; in particular, the double decay length in L-mode limited plasmas was found to be replaced by a single length at high SOL resistivity. Experiments on disruption mitigation by massive gas injection and electron-cyclotron resonance heating (ECRH) have begun in earnest, in parallel with studies of runaway electron generation and control, in both stable and disruptive conditions; a quiescent runaway beam carrying the entire electrical current appears to develop in some cases. Developments in plasma control have benefited from progress in individual controller design and have evolved steadily towards controller integration, mostly within an environment supervised by a tokamak profile control simulator. TCV has demonstrated effective wall conditioning with ECRH in He in support of the preparations for JT-60SA operation.</p>
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2.
  • Hibar, D. P., et al. (författare)
  • Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
  • 2018
  • Ingår i: Molecular Psychiatry. - 1359-4184. ; 23:4, s. 932-942
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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3.
  • Teumer, Alexander, et al. (författare)
  • Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
  • 2019
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
4.
  • Dimakopoulou, Konstantina, et al. (författare)
  • Air pollution and nonmalignant respiratory mortality in 16 cohorts within the ESCAPE project
  • 2014
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - Am Thoracic Soc. - 1073-449X. ; 189:6, s. 684-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. Objectives: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Methods: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Measurements and Main Results: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. Conclusions: In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratorymortality.
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5.
  • Hibar, D. P., et al. (författare)
  • Subcortical volumetric abnormalities in bipolar disorder
  • 2016
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
  • Tidskriftsartikel (refereegranskat)abstract
    • Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7) and thalamus (d=-0.148; P=4.27 × 10 -3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. © 2016 Macmillan Publishers Limited, part of Springer Nature.
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6.
  • Beelen, Rob, et al. (författare)
  • Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project
  • 2014
  • Ingår i: Lancet (London, England). - 1474-547X. ; 383:9919, s. 785-795
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. Methods We used data from 22 European cohort studies, which created a total study population of 367 251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM 10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx) with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects metaanalysis. Findings The total study population consisted of 367 251 participants who contributed 5 118 039 person-years at risk (average follow-up 13.9 years), of whom 29 076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m3 was recorded. No heterogeneity was noted between individual cohort effect estimates (I2 p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m3 (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m3 (1.07, 1.01-1.13). Interpretation Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value.
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7.
  • Beelen, Rob, et al. (författare)
  • Long-term exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts
  • 2014
  • Ingår i: Epidemiology (Cambridge, Mass.). - 1531-5487. ; 25:3, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and 10 μm to 2.5 μm (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM 2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 μg/m and for PM10, 1.22 (0.91-1.63) per 10 μg/m. Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
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8.
  • Han, LKM, et al. (författare)
  • Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
  • 2020
  • Ingår i: Molecular Psychiatry. - 1359-4184.
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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9.
  • Accomando, E., et al. (författare)
  • Physics with e + e - linear colliders
  • 1998
  • Ingår i: Physics Report. - Elsevier. - 0370-1573. ; 299:1, s. 1-78
  • Tidskriftsartikel (refereegranskat)abstract
    • The physics potential of e + e - linear colliders is summarized in this report. These machines are planned to operate in the first phase at a center-of-mass energy of 500 GeV, before being scaled up to about 1 TeV. In the second phase of the operation, a final energy of about 2 TeV is expected. The machines will allow us to perform precision tests of the heavy particles in the Standard Model, the top quark and the electroweak bosons. They are ideal facilities for exploring the properties of Higgs particles, in particular in the intermediate mass range. New vector bosons and novel matter particles in extended gauge theories can be searched for and studied thoroughly. The machines provide unique opportunities for the discovery of particles in supersymmetric extensions of the Standard Model, the spectrum of Higgs particles, the supersymmetric partners of the electroweak gauge and Higgs bosons, and of the matter particles. High precision analyses of their properties and interactions will allow for extrapolations to energy scales close to the Planck scale where gravity becomes significant. In alternative scenarios, i.e. compositeness models, novel matter particles and interactions can be discovered and investigated in the energy range above the existing colliders up to the TeV scale. Whatever scenario is realized in Nature, the discovery potential of e + e - linear colliders and the high precision with which the properties of particles and their interactions can be analyzed, define an exciting physics program complementary to hadron machines.
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10.
  • Hastan, D, et al. (författare)
  • Chronic rhinosinusitis in Europe : an underestimated disease. A GA²LEN study
  • 2011
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - Copenhagen : Munksgaard. - 0105-4538 .- 1398-9995. ; 66:9, s. 1216-1223
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background:  Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA<sup>2</sup>LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP<sup>3</sup>OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe.</p> <p>Method:  A postal questionnaire was sent to a random sample of adults aged 15–75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP<sup>3</sup>OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for &gt;12 weeks in the past year – with at least one symptom being nasal blockage or discharge.</p> <p>Results:  Information was obtained from 57 128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP<sup>3</sup>OS criteria was 10.9% (range 6.9–27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6–1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP<sup>3</sup>OS-diagnosed CRS.</p> <p>Conclusion:  This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe.</p>
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