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Sökning: WFRF:(Kovacs Katalin)

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1.
  • Major, Balázs, et al. (författare)
  • Effect of plasma-core-induced self-guiding on phase matching of high-order harmonic generation in gases
  • 2019
  • Ingår i: Journal of the Optical Society of America B: Optical Physics. - 0740-3224. ; 36:6, s. 1594-1601
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, we numerically study a self-guiding process in which ionization plays a dominant role and analyze its effect on high-order harmonic generation (HHG) in gases. Although this type of self-guiding-termed "plasmacore- induced self-guiding" in previous works-limits the achievable cutoff by regulating the intensity of the laser beam, it provides favorable conditions for phase matching, which is indispensable for high-flux-gas highharmonic sources. To underline the role of self-guiding in efficient HHG, we investigate the time-dependent phase-matching conditions in the guided beam and show how the spatiotemporally constant fundamental intensity contributes to the constructive buildup of the harmonic field in a broad photon energy range up to the provided cutoff.
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2.
  • Patterson, Nick, et al. (författare)
  • Large-scale migration into Britain during the Middle to Late Bronze Age
  • 2022
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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3.
  • Rivas, Daniel, et al. (författare)
  • Propagation-enhanced generation of intense high-harmonic continua in the 100-eV spectral region
  • 2018
  • Ingår i: Optica. - 2334-2536. ; 5:10, s. 1283-1289
  • Tidskriftsartikel (refereegranskat)abstract
    • The study of core electron dynamics through nonlinear spectroscopy requires intense isolated attosecond extremeultraviolet or even X-ray pulses. A robust way to produce these pulses is high-harmonic generation (HHG) in agas medium. However, the energy upscaling of the process depends on a very demanding next-generation laser technologythat provides multi-terawatt (TW) laser pulses with few-optical-cycle duration and controlled electric field.Here, we revisit the HHG process driven by 16-TW sub-two-cycle laser pulses to reach high intensity in the 100-eVspectral region and beyond. We show that the combination of above barrier-suppression intensity with a long generationmedium significantly enhances the isolation of attosecond pulses compared to lower intensities and/or shortermedia and this way reduces the pulse duration as well as field-stability requirements on the laser driver. This novelregime facilitates the real-time observation of electron dynamics at the attosecond timescale in atoms, molecules, andsolids.
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4.
  • Barta, Zsolt, et al. (författare)
  • Process design and economics of on-site cellulase production on various carbon sources in a softwood-based ethanol plant.
  • 2010
  • Ingår i: Enzyme Research. - : Hindawi Limited. - 2090-0414.
  • Tidskriftsartikel (refereegranskat)abstract
    • On-site cellulase enzyme fermentation in a softwood-to-ethanol process, based on S -catalysed steam pretreatment followed by simultaneous saccharification and fermentation, was investigated from a techno-economic aspect using Aspen Plus and Aspen Icarus Process Evaluator softwares. The effect of varying the carbon source of enzyme fermentation, at constant protein and mycelium yields, was monitored through the whole process. Enzyme production step decreased the overall ethanol yield (270 L/dry tonne of raw material in the case of purchased enzymes) by 5–16 L/tonne. Capital cost was found to be the main cost contributor to enzyme fermentation, constituting to 60–78% of the enzyme production cost, which was in the range of 0.42–0.53 SEK/L ethanol. The lowest minimum ethanol selling prices (4.71 and 4.82 SEK/L) were obtained in those scenarios, where pretreated liquid fraction supplemented with molasses was used as carbon source. In some scenarios, on-site enzyme fermentation was found to be a feasible alternative.
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5.
  • Di Girolamo, Chiara, et al. (författare)
  • Progress in reducing inequalities in cardiovascular disease mortality in Europe
  • 2020
  • Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 106, s. 40-49
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess whether recent declines in cardiovascular mortality have benefited all socioeconomic groups equally and whether these declines have narrowed or widened inequalities in cardiovascular mortality in Europe.METHODS: In this prospective registry-based study, we determined changes in cardiovascular mortality between the 1990s and the early 2010s in 12 European populations by gender, educational level and occupational class. In order to quantify changes in the magnitude of differences in mortality, we calculated both ratio measures of relative inequalities and difference measures of absolute inequalities.RESULTS: Cardiovascular mortality has declined rapidly among lower and higher socioeconomic groups. Relative declines (%) were faster among higher socioeconomic groups; absolute declines (deaths per 100 000 person-years) were almost uniformly larger among lower socioeconomic groups. Therefore, although relative inequalities increased over time, absolute inequalities often declined substantially on all measures used. Similar trends were seen for ischaemic heart disease and cerebrovascular disease mortality separately. Best performer was England and Wales, which combined large declines in cardiovascular mortality with large reductions in absolute inequalities and stability in relative inequalities in both genders. In the early 2010s, inequalities in cardiovascular mortality were smallest in Southern Europe, of intermediate magnitude in Northern and Western Europe and largest in Central-Eastern European and Baltic countries.CONCLUSIONS: Lower socioeconomic groups have experienced remarkable declines in cardiovascular mortality rates over the last 25 years, and trends in inequalities can be qualified as favourable overall. Nevertheless, further reducing inequalities remains an important challenge for European health systems and policies.
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6.
  • Hegedus, Csaba, et al. (författare)
  • Redox control of cancer cell destruction
  • 2018
  • Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 16, s. 59-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Redox regulation has been proposed to control various aspects of carcinogenesis, cancer cell growth, metabolism, migration, invasion, metastasis and cancer vascularization. As cancer has many faces, the role of redox control in different cancers and in the numerous cancer-related processes often point in different directions. In this review, we focus on the redox control mechanisms of tumor cell destruction. The review covers the tumor intrinsic role of oxidants derived from the reduction of oxygen and nitrogen in the control of tumor cell proliferation as well as the roles of oxidants and antioxidant systems in cancer cell death caused by traditional anticancer weapons (chemotherapeutic agents, radiotherapy, photodynamic therapy). Emphasis is also put on the role of oxidants and redox status in the outcome following interactions between cancer cells, cytotoxic lymphocytes and tumor infiltrating macrophages.
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7.
  • Kovacs, Gabor G., et al. (författare)
  • Heroin abuse exaggerates age-related deposition of hyperphosphorylated tau and p62-positive inclusions
  • 2015
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 36:11, s. 3100-3107
  • Tidskriftsartikel (refereegranskat)abstract
    • The observation of increased hyperphosphorylated tau levels correlating with microglial activation in opiate abusers has been interpreted as predisposition to accelerated Alzheimer diseaseerelated changes. The present study focused on evaluating additional neurodegeneration-related proteins, including a-synuclein and TDP-43, and p62-positive deposits. We performed a systematic mapping of protein deposits in the brains of 27 individuals with documented heroin addiction (age: 19-40 years) and compared with 11 controls (age: 15-40 years). We confirm previous findings that heroin addiction associates with tau hyperphosphorylation in predilection brain areas for aging and Alzheimer disease. Furthermore, we show that this occurs also in areas implicated in the molecular disturbances and in vivo neuronal networks related to heroin abuse. There was, however, no presence of amyloid-beta deposits. We extend previous findings by showing the lack of TDP-43 or alpha-synuclein pathology and emphasize the independent effect of the duration of drug use on the appearance of age-related p62-positive neuritic profiles. These observations provide unique insights about neuropathological alterations in the brains of young heroin addicts and have implications about brain aging and the influences of environmental and toxic factors.
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8.
  • Kovacs, Gabor G, et al. (författare)
  • Neuropathology of the hippocampus in FTLD-Tau with Pick bodies : A study of the BrainNet Europe Consortium
  • 2013
  • Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 39:2, s. 166-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is characterized by the presence of tau immunoreactive spherical structures in the cytoplasm of neurons. In view of confusion about the molecular pathology of Pick's disease, we aimed to evaluate the spectrum of tau pathology and concomitant neurodegeneration-associated protein depositions in the characteristically affected hippocampus. Methods: We evaluated immunoreactivity for tau (AT8, 3R, 4R), α-synuclein, TDP43, p62, and ubiquitin in the hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed neuropathologically as Pick's disease. Results: Mean age at death was 68.2 years (range 49 to 96). Fifty-two (79%) brains showed 3R immunoreactive spherical inclusions in the granule cells of the dentate gyrus. These typical cases presented mainly with the behavioural variant of FTD, followed by progressive aphasia, mixed syndromes or early memory disturbance. α-Synuclein immunoreactivity was seen only in occasional spherical tau-positive inclusions, TDP-43 IR was absent, and 4R IR was present only as neurofibrillary tangles in pyramidal neurons. Aβ immunoreactivity was observed in 16 cases; however, the overall level of Alzheimer's disease-related alterations was mainly low or intermediate (n = 3). Furthermore, we identified six cases with unclassifiable tauopathy. Conclusions: 1) Pick's disease may occur also in elderly patients and is characterized by a relatively uniform pathology with 3R tau inclusions particularly in the granule cells of dentate gyrus; 2) even minor deviation from these morphological criteria suggests a different disorder; and 3) immunohistological revision of archival cases expands the spectrum of tauopathies that require further classification.
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9.
  • Kovacs, Katalin T., et al. (författare)
  • Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus : A preliminary study
  • 2016
  • Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 22:9, s. 1192-1201
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. Objective: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute. Methods: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission. Results: AQP4-IgG1 was present 1-2-5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p
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10.
  • Leinsalu, Mall, et al. (författare)
  • Educational inequalities in mortality in four Eastern European countries : divergence in trends during the post-communist transition from 1990 to 2000
  • 2009
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 38, s. 512-525
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Post-communist transition has had a huge impact on mortality in Eastern Europe. We examined how educational inequalities in mortality changed between 1990 and 2000 in Estonia, Lithuania, Poland and Hungary.METHODS:Cross-sectional data for the years around 1990 and 2000 were used. Age-standardized mortality rates and mortality rate ratios (for total mortality only) were calculated for men and women aged 35-64 in three educational categories, for five broad cause-of-death groups and for five (seven among women) specific causes of death.RESULTS:Educational inequalities in mortality increased in all four countries but in two completely different ways. In Poland and Hungary, mortality rates decreased or remained the same in all educational groups. In Estonia and Lithuania, mortality rates decreased among the highly educated, but increased among those of low education. In Estonia and Lithuania, for men and women combined, external causes and circulatory diseases contributed most to the increasing educational gap in total mortality.CONCLUSIONS:Different trends were observed between the two former Soviet republics and the two Central Eastern European countries. This divergence can be related to differences in socioeconomic development during the 1990s and in particular, to the spread of poverty, deprivation and marginalization. Alcohol and psychosocial stress may also have been important mediating factors.
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11.
  • Long, Di, et al. (författare)
  • Smoking and inequalities in mortality in 11 European countries : a birth cohort analysis
  • 2021
  • Ingår i: Population Health Metrics. - : BioMed Central (BMC). - 1478-7954. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To study the trends of smoking-attributable mortality among the low and high educated in consecutive birth cohorts in 11 European countries.METHODS: Register-based mortality data were collected among adults aged 30 to 79 years in 11 European countries between 1971 and 2012. Smoking-attributable deaths were estimated indirectly from lung cancer mortality rates using the Preston-Glei-Wilmoth method. Rate ratios and rate differences among the low and high-educated were estimated and used to estimate the contribution of inequality in smoking-attributable mortality to inequality in total mortality.RESULTS: In most countries, smoking-attributable mortality decreased in consecutive birth cohorts born between 1906 and 1961 among low- and high-educated men and high-educated women, but not among low-educated women among whom it increased. Relative educational inequalities in smoking-attributable mortality increased among both men and women with no signs of turning points. Absolute inequalities were stable among men but slightly increased among women. The contribution of inequality in smoking-attributable mortality to inequality in total mortality decreased in consecutive generations among men but increased among women.CONCLUSIONS: Smoking might become less important as a driver of inequalities in total mortality among men in the future. However, among women, smoking threatens to further widen inequalities in total mortality.
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12.
  • Lorant, Vincent, et al. (författare)
  • Socioeconomic inequalities in suicide in Europe : the widening gap
  • 2018
  • Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatry. - 0007-1250 .- 1472-1465. ; 212:6, s. 356-361
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide has been decreasing over the past decade. However, we do not know whether socioeconomic inequality in suicide has been decreasing as well.AimsWe assessed recent trends in socioeconomic inequalities in suicide in 15 European populations.METHOD: The DEMETRIQ study collected and harmonised register-based data on suicide mortality follow-up of population censuses, from 1991 and 2001, in European populations aged 35-79. Absolute and relative inequalities of suicide according to education were computed on more than 300 million person-years.RESULTS: In the 1990s, people in the lowest educational group had 1.82 times more suicides than those in the highest group. In the 2000s, this ratio increased to 2.12. Among men, absolute and relative inequalities were substantial in both periods and generally did not decrease over time, whereas among women inequalities were absent in the first period and emerged in the second.CONCLUSIONS: The World Health Organization (WHO) plan for 'Fair opportunity of mental wellbeing' is not likely to be met.Declaration of interestNone.
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13.
  • Mackenbach, Johan P., et al. (författare)
  • Determinants of inequalities in life expectancy : an international comparative study of eight risk factors
  • 2019
  • Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 4:10, s. E529-E537
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Socioeconomic inequalities in longevity have been found in all European countries. We aimed to assess which determinants make the largest contribution to these inequalities. Methods We did an international comparative study of inequalities in risk factors for shorter life expectancy in Europe. We collected register-based mortality data and survey-based risk factor data from 15 European countries. We calculated partial life expectancies between the ages of 35 years and 80 years by education and gender and determined the effect on mortality of changing the prevalence of eight risk factors-father with a manual occupation, low income, few social contacts, smoking, high alcohol consumption, high bodyweight, low physical exercise, and low fruit and vegetable consumption-among people with a low level of education to that among people with a high level of education (upward levelling scenario), using population attributable fractions. Findings In all countries, a substantial gap existed in partial life expectancy between people with low and high levels of education, of 2.3-8.2 years among men and 0.6-4.5 years among women. The risk factors contributing most to the gap in life expectancy were smoking (19.8% among men and 18.9% among women), low income (9.7% and 13.4%), and high bodyweight (7.7% and 11.7%), but large differences existed between countries in the contribution of risk factors. Sensitivity analyses using the prevalence of risk factors in the most favourable country (best practice scenario) showed that the potential for reducing the gap might be considerably smaller. The results were also sensitive to varying assumptions about the mortality risks associated with each risk factor. Interpretation Smoking, low income, and high bodyweight are quantitatively important entry points for policies to reduce educational inequalities in life expectancy in most European countries, but priorities differ between countries. A substantial reduction of inequalities in life expectancy requires policy actions on a broad range of health determinants.
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14.
  • Mackenbach, Johan P., et al. (författare)
  • Determinants of the magnitude of socioeconomic inequalities in mortality : A study of 17 European countries
  • 2017
  • Ingår i: Health and Place. - : Elsevier. - 1353-8292 .- 1873-2054. ; 47, s. 44-53
  • Tidskriftsartikel (refereegranskat)abstract
    • The magnitude of socioeconomic inequalities in mortality differs importantly between countries, but these variations have not been satisfactorily explained. We explored the role of behavioral and structural determinants of these variations, by using a dataset covering 17 European countries in the period 1970–2010, and by conducting multilevel multivariate regression analyses. Our results suggest that between-country variations in inequalities in current mortality can partly be understood from variations in inequalities in smoking, excessive alcohol consumption, and poverty. Also, countries with higher national income, higher quality of government, higher social transfers, higher health care expenditure and more self-expression values have smaller inequalities in mortality. Finally, trends in behavioral risk factors, particularly smoking and excessive alcohol consumption, appear to partly explain variations in inequalities in mortality trends. This study shows that analyses of variations in health inequalities between countries can help to identify entry-points for policy.
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15.
  • Mackenbach, Johan P, et al. (författare)
  • Inequalities in Alcohol-Related Mortality in 17 European Countries : A Retrospective Analysis of Mortality Registers.
  • 2015
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Socioeconomic inequalities in alcohol-related mortality have been documented in several European countries, but it is unknown whether the magnitude of these inequalities differs between countries and whether these inequalities increase or decrease over time.METHODS AND FINDINGS: We collected and harmonized data on mortality from four alcohol-related causes (alcoholic psychosis, dependence, and abuse; alcoholic cardiomyopathy; alcoholic liver cirrhosis; and accidental poisoning by alcohol) by age, sex, education level, and occupational class in 20 European populations from 17 different countries, both for a recent period and for previous points in time, using data from mortality registers. Mortality was age-standardized using the European Standard Population, and measures for both relative and absolute inequality between low and high socioeconomic groups (as measured by educational level and occupational class) were calculated. Rates of alcohol-related mortality are higher in lower educational and occupational groups in all countries. Both relative and absolute inequalities are largest in Eastern Europe, and Finland and Denmark also have very large absolute inequalities in alcohol-related mortality. For example, for educational inequality among Finnish men, the relative index of inequality is 3.6 (95% CI 3.3-4.0) and the slope index of inequality is 112.5 (95% CI 106.2-118.8) deaths per 100,000 person-years. Over time, the relative inequality in alcohol-related mortality has increased in many countries, but the main change is a strong rise of absolute inequality in several countries in Eastern Europe (Hungary, Lithuania, Estonia) and Northern Europe (Finland, Denmark) because of a rapid rise in alcohol-related mortality in lower socioeconomic groups. In some of these countries, alcohol-related causes now account for 10% or more of the socioeconomic inequality in total mortality. Because our study relies on routinely collected underlying causes of death, it is likely that our results underestimate the true extent of the problem.CONCLUSIONS: Alcohol-related conditions play an important role in generating inequalities in total mortality in many European countries. Countering increases in alcohol-related mortality in lower socioeconomic groups is essential for reducing inequalities in mortality. Studies of why such increases have not occurred in countries like France, Switzerland, Spain, and Italy can help in developing evidence-based policies in other European countries.
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16.
  • Mackenbach, Johan P, et al. (författare)
  • Trends in health inequalities in 27 European countries
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:25, s. 6440-6445
  • Tidskriftsartikel (refereegranskat)abstract
    • Unfavorable health trends among the lowly educated have recently been reported from the United States. We analyzed health trends by education in European countries, paying particular attention to the possibility of recent trend interruptions, including interruptions related to the impact of the 2008 financial crisis. We collected and harmonized data on mortality from ca 1980 to ca 2014 for 17 countries covering 9.8 million deaths and data on self-reported morbidity from ca 2002 to ca 2014 for 27 countries covering 350,000 survey respondents. We used interrupted time-series analyses to study changes over time and country-fixed effects analyses to study the impact of crisis-related economic conditions on health outcomes. Recent trends were more favorable than in previous decades, particularly in Eastern Europe, where mortality started to decline among lowly educated men and where the decline in less-than-good self-assessed health accelerated, resulting in some narrowing of health inequalities. In Western Europe, mortality has continued to decline among the lowly and highly educated, and although the decline of less-than-good self-assessed health slowed in countries severely hit by the financial crisis, this affected lowly and highly educated equally. Crisis-related economic conditions were not associated with widening health inequalities. Our results show that the unfavorable trends observed in the United States are not found in Europe. There has also been no discernible short-term impact of the crisis on health inequalities at the population level. Both findings suggest that European countries have been successful in avoiding an aggravation of health inequalities.
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17.
  • Mackenbach, Johan P, et al. (författare)
  • Trends in inequalities in premature mortality : a study of 3.2 million deaths in 13 European countries.
  • 2015
  • Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 69, s. 207-217
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Over the last decades of the 20th century, a widening of the gap in death rates between upper and lower socioeconomic groups has been reported for many European countries. For most countries, it is unknown whether this widening has continued into the first decade of the 21st century.METHODS: We collected and harmonised data on mortality by educational level among men and women aged 30-74 years in all countries with available data: Finland, Sweden, Norway, Denmark, England and Wales, Belgium, France, Switzerland, Spain, Italy, Hungary, Lithuania and Estonia.RESULTS: Relative inequalities in premature mortality increased in most populations in the North, West and East of Europe, but not in the South. This was mostly due to smaller proportional reductions in mortality among the lower than the higher educated, but in the case of Lithuania and Estonia, mortality rose among the lower and declined among the higher educated. Mortality among the lower educated rose in many countries for conditions linked to smoking (lung cancer, women only) and excessive alcohol consumption (liver cirrhosis and external causes). In absolute terms, however, reductions in premature mortality were larger among the lower educated in many countries, mainly due to larger absolute reductions in mortality from cardiovascular disease and cancer (men only). Despite rising levels of education, population-attributable fractions of lower education for mortality rose in many countries.CONCLUSIONS: Relative inequalities in premature mortality have continued to rise in most European countries, and since the 1990s, the contrast between the South (with smaller inequalities) and the East (with larger inequalities) has become stronger. While the population impact of these inequalities has further increased, there are also some encouraging signs of larger absolute reductions in mortality among the lower educated in many countries. Reducing inequalities in mortality critically depends upon speeding up mortality declines among the lower educated, and countering mortality increases from conditions linked to smoking and excessive alcohol consumption such as lung cancer, liver cirrhosis and external causes.
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18.
  • Merlo, Domenico Franco, et al. (författare)
  • Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression : The NewGeneris Cohort
  • 2014
  • Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:2, s. 193-200
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.
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19.
  • Nusselder, Wilma J, et al. (författare)
  • Determinants of inequalities in years with disability : an international-comparative study
  • 2021
  • Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 31:3, s. 527-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Persons with a lower socioeconomic position spend more years with disability, despite their shorter life expectancy, but it is unknown what the important determinants are. This study aimed to quantify the contribution to educational inequalities in years with disability of eight risk factors: father’s manual occupation, low income, few social contacts, smoking, high alcohol consumption, high body-weight, low physical exercise and low fruit and vegetable consumption. Methods: We collected register-based mortality and survey-based disability and risk factor data from 15 European countries covering the period 2010–14 for most countries. We calculated years with disability between the ages of 35 and 80 by education and gender using the Sullivan method, and determined the hypothetical effect of changing the prevalence of each risk factor to the prevalence observed among high educated (‘upward levelling scenario’), using Population Attributable Fractions. Results: Years with disability among low educated were higher than among high educated, with a difference of 4.9 years among men and 5.5 years among women for all countries combined. Most risk factors were more prevalent among low educated. We found the largest contributions to inequalities in years with disability for low income (men: 1.0 year; women: 1.4 year), high body-weight (men: 0.6 year; women: 1.2 year) and father’s manual occupation (men: 0.7 year; women: 0.9 year), but contributions differed by country. The contribution of smoking was relatively small. Conclusions: Disadvantages in material circumstances (low income), circumstances during childhood (father’s manual occupation) and high body-weight contribute to inequalities in years with disability.
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20.
  • Pattaro, Cristian, et al. (författare)
  • Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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21.
  • Pedersen, Marie, et al. (författare)
  • Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother-Child Study (NewGeneris)
  • 2013
  • Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:10, s. 1200-1206
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic-hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from -biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006-2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of -129 g (95% CI: -233, -25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (-248 g; 95% CI: -405, -92 g) compared with those with high intake (-58 g; 95% CI: -206, 90 g). Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.
  •  
22.
  • Stickley, Andrew, et al. (författare)
  • Socioeconomic inequalities in homicide mortality : a population-based comparative study of 12 European countries
  • 2012
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 27:11, s. 877-884
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent research has suggested that violent mortality may be socially patterned and a potentially important source of health inequalities within and between countries. Against this background the current study assessed socioeconomic inequalities in homicide mortality across Europe. To do this, longitudinal and cross-sectional data were obtained from mortality registers and population censuses in 12 European countries. Educational level was used to indicate socioeconomic position. Age-standardized mortality rates were calculated for post, upper and lower secondary or less educational groups. The magnitude of inequalities was assessed using the relative and slope index of inequality. The analysis focused on the 35-64 age group. Educational inequalities in homicide mortality were present in all countries. Absolute inequalities in homicide mortality were larger in the eastern part of Europe and in Finland, consistent with their higher overall homicide rates. They contributed 2.5 % at most (in Estonia) to the inequalities in total mortality. Relative inequalities were high in the northern and eastern part of Europe, but were low in Belgium, Switzerland and Slovenia. Patterns were less consistent among women. Socioeconomic inequalities in homicide are thus a universal phenomenon in Europe. Wide-ranging social and inter-sectoral health policies are now needed to address the risk of violent victimization that target both potential offenders and victims.
  •  
23.
  • Toth, Tunde N., et al. (författare)
  • Fingerprinting the macro-organisation of pigment-protein complexes in plant thylakoid membranes in vivo by circular-dichroism spectroscopy
  • 2016
  • Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1857:9, s. 1479-1489
  • Tidskriftsartikel (refereegranskat)abstract
    • Macro-organisation of the protein complexes in plant thylakoid membranes plays important roles in the regulation and fine-tuning of photosynthetic activity. These delicate structures might, however, undergo substantial changes during isolating the thylakoid membranes or during sample preparations, e.g., for electron microscopy. Circular-dichroism (CD) spectroscopy is a non-invasive technique which can thus be used on intact samples. Via excitonic and psi-type CD bands, respectively, it carries information on short-range excitonic pigment-pigment interactions and the macro-organisation (chiral macrodomains) of pigment-protein complexes (psi, polymer or salt-induced). In order to obtain more specific information on the origin of the major psi-type CD bands, at around (+)506, (-)674 and (+)690 nm, we fingerprinted detached leaves and isolated thylakoid membranes of wild-type and mutant plants and also tested the effects of different environmental conditions in vivo. We show that (i) the chiral macrodomains disassemble upon mild detergent treatments, but not after crosslinking the protein complexes; (ii) in different wild-type leaves of dicotyledonous and monocotyledonous angiosperms the CD features are quite robust, displaying very similar excitonic and psi-type bands, suggesting similar protein composition and (macro-) organisation of photosystem II (PSII) supercomplexes in the grana; (iii) the main positive psi-type bands depend on light-harvesting protein II contents of the membranes; (iv) the (+)506 nm band appears only in the presence of PSII-LHCII supercomplexes and does not depend on the xanthophyll composition of the membranes. Hence, CD spectroscopy can be used to detect different macro-domains in the thylakoid membranes with different outer antenna compositions in vivo. 
  •  
24.
  • Wuttke, Matthias, et al. (författare)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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