Mortality inequalities by occupational class among men in Japan, South Korea and eight European countries : a national register-based study, 1990-2015

Background We compared mortality inequalities by occupational class in Japan and South Korea with those in European countries, in order to determine whether patterns are similar. Methods National register-based data from Japan, South Korea and eight European countries (Finland, Denmark, England/Wales, France, Switzerland, Italy (Turin), Estonia, Lithuania) covering the period between 1990 and 2015 were collected and harmonised. We calculated age-standardised all-cause and cause-specific mortality among men aged 35-64 by occupational class and measured the magnitude of inequality with rate differences, rate ratios and the average inter-group difference. Results Clear gradients in mortality were found in all European countries throughout the study period: manual workers had 1.6-2.5 times higher mortality than upper non-manual workers. However, in the most recent time-period, upper non-manual workers had higher mortality than manual workers in Japan and South Korea. This pattern emerged as a result of a rise in mortality among the upper non-manual group in Japan during the late 1990s, and in South Korea during the late 2000s, due to rising mortality from cancer and external causes (including suicide), in addition to strong mortality declines among lower non-manual and manual workers. Conclusion Patterns of mortality by occupational class are remarkably different between European countries and Japan and South Korea. The recently observed patterns in the latter two countries may be related to a larger impact on the higher occupational classes of the economic crisis of the late 1990s and the late 2000s, respectively, and show that a high socioeconomic position does not guarantee better health.Peer reviewe

Determinants of inequalities in life expectancy : an international comparative study of eight risk factors

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. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.Peer reviewe

Smoking and inequalities in mortality in 11 European countries : a birth cohort analysis

Altres ajuts: Netspar (Network for Studies on Pensions, Aging and Retirement).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

Determinants of inequalities in years with disability : an international-comparative study

Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association.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.Peer reviewe

Trends in health inequalities in 27 European countries

Inequalities in mortality and morbidity among socioeconomic groups are a highly persistent phenomenon despite having been the focus of public health policy in many countries. The United States has recently witnessed a widening of health inequalities due to rising mortality and morbidity among the lowly educated. Our study shows that, despite the financial crisis, most European countries have experienced an improvement in the health of the lowly educated in recent years. In Eastern Europe, this even represents a reversal as compared with previous decades. The 2008 financial crisis has had mixed effects without widening health inequalities. Our results suggest that European countries have been successful in avoiding an aggravation of health inequalities.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.Peer reviewe

Mortality inequalities by occupational class among men in Japan, South Korea and eight European countries: a national register-based study, 1990-2015

BACKGROUND We compared mortality inequalities by occupational class in Japan and South Korea with those in European countries, in order to determine whether patterns are similar. METHODS National register-based data from Japan, South Korea and eight European countries (Finland, Denmark, England/Wales, France, Switzerland, Italy (Turin), Estonia, Lithuania) covering the period between 1990 and 2015 were collected and harmonised. We calculated age-standardised all-cause and cause-specific mortality among men aged 35-64 by occupational class and measured the magnitude of inequality with rate differences, rate ratios and the average inter-group difference. RESULTS Clear gradients in mortality were found in all European countries throughout the study period: manual workers had 1.6-2.5 times higher mortality than upper non-manual workers. However, in the most recent time-period, upper non-manual workers had higher mortality than manual workers in Japan and South Korea. This pattern emerged as a result of a rise in mortality among the upper non-manual group in Japan during the late 1990s, and in South Korea during the late 2000s, due to rising mortality from cancer and external causes (including suicide), in addition to strong mortality declines among lower non-manual and manual workers. CONCLUSION Patterns of mortality by occupational class are remarkably different between European countries and Japan and South Korea. The recently observed patterns in the latter two countries may be related to a larger impact on the higher occupational classes of the economic crisis of the late 1990s and the late 2000s, respectively, and show that a high socioeconomic position does not guarantee better health

Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

The present study reports the discovery of a small-molecule negative allosteric modulator for the β2-adrenergic receptor (β2AR) via in vitro affinity-based iterative selection of highly diverse DNA-encoded small-molecule libraries. Characterization of the compound demonstrates its selectivity for the β2AR and that it negatively modulates a wide range of receptor functions. More importantly, our findings establish a generally applicable, proof-of-concept strategy for screening DNA-encoded small-molecule libraries against purified G-protein–coupled receptors (GPCRs), which holds great potential for discovering therapeutic molecules

Characterization of sills associated with the U reflection on the Newfoundland margin : evidence for widespread early post-rift magmatism on a magma-poor rifted margin

Author Posting. © The Authors, 2010. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 182 (2010): 113-136, doi:10.1111/j.1365-246X.2010.04635.x.Drilling during ODP Leg 210 penetrated two post-rift sills (dated as ∼105.3 and ∼97.8 Ma) in the deep sediments overlying basement of the continent–ocean transition zone on the magma-poor Newfoundland margin. The sill emplacement post-dated the onset of seafloor spreading by at least 7–15 Myr. The shallower of the two sills coincides with the high-amplitude U reflection observed throughout the deep Newfoundland Basin, and strong reflectivity in the sub-U sequence suggests that a number of other sills are present there. In this paper, we use multichannel seismic reflection data and synthetic seismograms to investigate the nature, magnitude and extent of this post-rift magmatism in the deep basin. Features observed in seismic profiles that we attribute to sill injection include high-amplitude reflections with geometries characteristic of intrusions such as step-like aspect; abrupt endings, disruptions and junctions of reflections; finger-like forms; differential compaction around possible loci of magma injection and disruption of overlying sediments by apparent fluid venting. Interpreted sills occur only over transitional basement that probably consists of a mixture of serpentinized peridotite and highly thinned continental crust, and they cover an area of ∼80 000 km2. From analysis of synthetic seismograms, we estimate that sill intrusions may comprise ∼26 per cent of the sub-U high-reflectivity sequence, which yields a crude estimate of ∼5800 km3 for the total volume of sills emplaced by post-rift magmatism. This is significant for a margin usually described as 'non-volcanic'. We discuss competing hypotheses about the source of the magmatism, which is still uncertain.G. Peron-Pinvidic's post-doctoral research at the University of Strasbourg and Woods Hole Oceanographic Institution was supported by TOTAL. B. Tucholke's research was supported by NSF grant OCE0647035. Multichannel seismic field programs that provided much of the data used for this research were supported by NSF grants OCE839085, OCE830823 and OCE9819053

Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma

AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision

Incomplete Inhibition of Sphingosine 1-Phosphate Lyase Modulates Immune System Function yet Prevents Early Lethality and Non-Lymphoid Lesions

BACKGROUND: S1PL is an aldehyde-lyase that irreversibly cleaves sphingosine 1-phosphate (S1P) in the terminal step of sphingolipid catabolism. Because S1P modulates a wide range of physiological processes, its concentration must be tightly regulated within both intracellular and extracellular environments. METHODOLOGY: In order to better understand the function of S1PL in this regulatory pathway, we assessed the in vivo effects of different levels of S1PL activity using knockout (KO) and humanized mouse models. PRINCIPAL FINDINGS: Our analysis showed that all S1PL-deficient genetic models in this study displayed lymphopenia, with sequestration of mature T cells in the thymus and lymph nodes. In addition to the lymphoid phenotypes, S1PL KO mice (S1PL(-/-)) also developed myeloid cell hyperplasia and significant lesions in the lung, heart, urinary tract, and bone, and had a markedly reduced life span. The humanized knock-in mice harboring one allele (S1PL(H/-)) or two alleles (S1PL(H/H)) of human S1PL expressed less than 10 and 20% of normal S1PL activity, respectively. This partial restoration of S1PL activity was sufficient to fully protect both humanized mouse lines from the lethal non-lymphoid lesions that developed in S1PL(-/-) mice, but failed to restore normal T-cell development and trafficking. Detailed analysis of T-cell compartments indicated that complete absence of S1PL affected both maturation/development and egress of mature T cells from the thymus, whereas low level S1PL activity affected T-cell egress more than differentiation. SIGNIFICANCE: These findings demonstrate that lymphocyte trafficking is particularly sensitive to variations in S1PL activity and suggest that there is a window in which partial inhibition of S1PL could produce therapeutic levels of immunosuppression without causing clinically significant S1P-related lesions in non-lymphoid target organs