1. |
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2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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4. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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5. |
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6. |
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7. |
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8. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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9. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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10. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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11. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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12. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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13. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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14. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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15. |
- Petroff, E., et al.
(författare)
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A polarized fast radio burst at low Galactic latitude
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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16. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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17. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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18. |
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19. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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20. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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21. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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22. |
- Agrawal, K., et al.
(författare)
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Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 150:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Objective: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Methods: Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ–induced epithelial cell signature and a tissue resident memory T-cell signature. Results: Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ–induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell–associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. Conclusions: The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations.
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23. |
- Dewaraja, Yuni K., et al.
(författare)
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Improved quantitative 90Y bremsstrahlung SPECT/CT reconstruction with Monte Carlo scatter modeling
- 2017
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Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 44:12, s. 6364-6376
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In 90Y microsphere radioembolization (RE), accurate post-therapy imaging-based dosimetry is important for establishing absorbed dose versus outcome relationships for developing future treatment planning strategies. Additionally, accurately assessing microsphere distributions is important because of concerns for unexpected activity deposition outside the liver. Quantitative 90Y imaging by either SPECT or PET is challenging. In 90Y SPECT model based methods are necessary for scatter correction because energy window-based methods are not feasible with the continuous bremsstrahlung energy spectrum. The objective of this work was to implement and evaluate a scatter estimation method for accurate 90Y bremsstrahlung SPECT/CT imaging. Methods: Since a fully Monte Carlo (MC) approach to 90Y SPECT reconstruction is computationally very demanding, in the present study the scatter estimate generated by a MC simulator was combined with an analytical projector in the 3D OS-EM reconstruction model. A single window (105 to 195-keV) was used for both the acquisition and the projector modeling. A liver/lung torso phantom with intrahepatic lesions and low-uptake extrahepatic objects was imaged to evaluate SPECT/CT reconstruction without and with scatter correction. Clinical application was demonstrated by applying the reconstruction approach to five patients treated with RE to determine lesion and normal liver activity concentrations using a (liver) relative calibration. Results: There was convergence of the scatter estimate after just two updates, greatly reducing computational requirements. In the phantom study, compared with reconstruction without scatter correction, with MC scatter modeling there was substantial improvement in activity recovery in intrahepatic lesions (from > 55% to > 86%), normal liver (from 113% to 104%), and lungs (from 227% to 104%) with only a small degradation in noise (13% vs. 17%). Similarly, with scatter modeling contrast improved substantially both visually and in terms of a detectability index, which was especially relevant for the low uptake extrahepatic objects. The trends observed for the phantom were also seen in the patient studies where lesion activity concentrations and lesion-to-liver concentration ratios were lower for SPECT without scatter correction compared with reconstruction with just two MC scatter updates: in eleven lesions the mean uptake was 4.9 vs. 7.1 MBq/mL (P = 0.0547), the mean normal liver uptake was 1.6 vs. 1.5 MBq/mL (P = 0.056) and the mean lesion-to-liver uptake ratio was 2.7 vs. 4.3 (P = 0.0402) for reconstruction without and with scatter correction respectively. Conclusions: Quantitative accuracy of 90Y bremsstrahlung imaging can be substantially improved with MC scatter modeling without significant degradation in image noise or intensive computational requirements.
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24. |
- Griswold, Max G., et al.
(författare)
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Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2018
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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25. |
- Le Breton, Michael, 1986, et al.
(författare)
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Online gas- and particle-phase measurements of organosulfates, organosulfonates and nitrooxy organosulfates in Beijing utilizing a FIGAERO ToF-CIMS
- 2018
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:14, s. 10355-10371
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Tidskriftsartikel (refereegranskat)abstract
- A time-of-flight chemical ionization mass spectrometer (CIMS) utilizing the Filter Inlet for Gas and Aerosol (FIGAERO) was deployed at a regional site 40 km north-west of Beijing and successfully identified and measured 17 sulfur-containing organics (SCOs are organo/nitrooxy organosulfates and sulfonates) with biogenic and anthropogenic precursors. The SCOs were quantified using laboratory-synthesized standards of lactic acid sulfate and nitrophenol organosulfate (NP OS). The variation in field observations was confirmed by comparison to offline measurement techniques (orbitrap and high-performance liquid chromatography, HPLC) using daily averages. The mean total (of the 17 identified by CIMS) SCO particle mass concentration was 210 +/- 110 ng m(-3) and had a maximum of 540 ng m(-3), although it contributed to only 2 +/- 1% of the organic aerosol (OA). The CIMS identified a persistent gas-phase presence of SCOs in the ambient air, which was further supported by separate vapour-pressure measurements of NP OS by a Knudsen Effusion Mass Spectrometer (KEMS). An increase in relative humidity (RH) promoted partitioning of SCO to the particle phase, whereas higher temperatures favoured higher gas-phase concentrations. Biogenic emissions contributed to only 19% of total SCOs measured in this study. Here, C10H16NSO7, a monoterpene-derived SCO, represented the highest fraction (10 %) followed by an isoprene-derived SCO. The anthropogenic SCOs with polycyclic aromatic hydrocarbon (PAH) and aromatic precursors dominated the SCO mass loading (51 %) with C11H11SO7, derived from methyl naphthalene oxidation, contributing to 40 ng m(-3) and 0.3% of the OA mass. Anthropogenic-related SCOs correlated well with benzene, although their abundance depended highly on the photochemical age of the air mass, tracked using the ratio between pinonic acid and its oxidation product, acting as a qualitative photochemical clock. In addition to typical anthropogenic and biogenic precursors the biomass-burning precursor nitrophenol (NP) provided a significant level of NP OS. It must be noted that the contribution analysis here is only representative of the detected SCOs. There are likely to be many more SCOs present which the CIMS has not identified. Gas- and particle-phase measurements of glycolic acid suggest that partitioning towards the particle phase promotes glycolic acid sulfate production, contrary to the current formation mechanism suggested in the literature. Furthermore, the HSO4 center dot H2SO4- cluster measured by the CIMS was utilized as a qualitative marker for acidity and indicates that the production of total SCOs is efficient in highly acidic aerosols with high SO42- and organic content. This dependency becomes more complex when observing individual SCOs due to variability of specific VOC precursors.
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26. |
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27. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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28. |
- Pecunia, Vincenzo, et al.
(författare)
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Roadmap on energy harvesting materials
- 2023
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Ingår i: Journal of Physics. - : IOP Publishing. - 2515-7639. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.
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29. |
- Qiao, K., et al.
(författare)
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Size-resolved effective density of submicron particles during summertime in the rural atmosphere of Beijing, China
- 2018
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Ingår i: Journal of Environmental Sciences. - : Elsevier BV. - 1001-0742. ; 73, s. 69-77
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Tidskriftsartikel (refereegranskat)abstract
- Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical aging processes of aerosols particles. In the present study, a centrifugal particle mass analyzer (CPMA) combined with a differential mobility analyzer (DMA) was deployed to determine the size-resolved effective density of 50 to 350 nm particles at a rural site of Beijing during summer 2016. The measured particle effective densities decreased with increasing particle sizes and ranged from 1.43 to 1.55 g/cm(3), on average. The effective particle density distributions were dominated by a mode peaked at around 1.5 g/cm(3) for 50 to 350 nm particles. Extra modes with peaks at 1.0, 0.8, and 0.6 g/cm(3) for 150, 240, and 350 nm particles, which might be freshly emitted soot particles, were observed during intensive primary emissions episodes. The particle effective densities showed a diurnal variation pattern, with higher values during daytime. A case study showed that the effective density of Aitken mode particles during the new particle formation (NPF) event decreased considerably, indicating the significant contribution of organics to new particle growth. (C) 2018 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.
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30. |
- Soam, Shveta, 1987-, et al.
(författare)
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Life cycle assessment of rice straw utilization practices in India
- 2017
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 228, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to find potential utilization practice of rice straw in India from an environmental perspective. Life cycle assessment (LCA) is conducted for four most realistic utilization practices of straw including: (1) incorporation into the field as fertilizer (2) animal fodder (3) electricity (4) biogas. The results show that processing of 1 ton straw to electricity and biogas resulted in net reduction of 1471 and 1023 kg CO2 eq., 15.0 and 3.4 kg SO2 eq. and 6.7 and 7.1 kg C2H6 eq. emissions in global warming, acidification and photochemical oxidation creation potential respectively. Electricity production from straw replaces the coal based electricity and resulted in benefits in most of the environmental impacts whereas use as an animal fodder resulted in eutrophication benefits. The burning of straw is a harmful practice of managing straw in India which can be avoided by utilizing straw for bioenergy.
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31. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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32. |
- Bauer, Michael, et al.
(författare)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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33. |
- Fauchez, Thomas J. J., et al.
(författare)
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TRAPPIST Habitable Atmosphere Intercomparison (THAI) Workshop Report
- 2021
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Ingår i: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- The era of atmospheric characterization of terrestrial exoplanets is just around the corner. Modeling prior to observations is crucial in order to predict the observational challenges and to prepare for the data interpretation. This paper presents the report of the TRAPPIST Habitable Atmosphere Intercomparison workshop (2020 September 14-16). A review of the climate models and parameterizations of the atmospheric processes on terrestrial exoplanets, model advancements, and limitations, as well as direction for future model development, was discussed. We hope that this report will be used as a roadmap for future numerical simulations of exoplanet atmospheres and maintaining strong connections to the astronomical community.
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34. |
- Hallquist, Mattias, 1969, et al.
(författare)
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Photochemical smog in China: scientific challenges and implications for air-quality policies
- 2016
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Ingår i: National Science Review. - : Oxford University Press (OUP). - 2095-5138 .- 2053-714X. ; 3:4, s. 401-403
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Tidskriftsartikel (refereegranskat)abstract
- In large areas of China severe air pollution events pose a significant threat to human health, ecosystems and climate. Current reduction of primary emissions will also affect secondary pollutants such as ozone (O3) and particulate matter (PM), but the magnitude of the effects is uncertain. Major scientific challenges are related to the formation of O3 and secondary particulate matter including Secondary Organic Aerosols (SOA). Large uncertainties also remain regarding the interactions of soot, SOA and O3 under the influence of different SO2, NOX and VOC concentrations. To improve the understanding of these secondary atmospheric interactions in China, scientific areas of central importance for photochemically induced air pollutants have been identified. In addition to the scientific challenges, results from research need to be synthesized across several disciplines and communicated to stakeholders affected by air pollution and to policy makers responsible for developing abatement strategies. Development of these science-policy interactions can benefit from experience gained under the UN ECE Convention on Long Range Transboundary Air Pollution (LRTAP)
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35. |
- Hoffmann, Thomas J, et al.
(författare)
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Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.
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36. |
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37. |
- Lazaryan, Aleksandr, et al.
(författare)
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Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
- 2020
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 105:5, s. 1329-1338
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
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38. |
- Le Breton, Michael, 1986, et al.
(författare)
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Chlorine oxidation of VOCs at a semi-rural site in Beijing: significant chlorine liberation from ClNO2 and subsequent gas- and particle-phase Cl-VOC production
- 2018
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:17, s. 13013-13030:18, s. 13013-13030
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Tidskriftsartikel (refereegranskat)abstract
- Nitryl chloride (ClNO2) accumulation at night acts as a significant reservoir for active chlorine and impacts the following day's photochemistry when the chlorine atom is liberated at sunrise. Here, we report simultaneous measurements of N2O5 and a suite of inorganic halogens including ClNO2 and reactions of chloride with volatile organic compounds (Cl-VOCs) in the gas and particle phases utilising the Filter Inlet for Gas and AEROsols time-of-flight chemical ionisation mass spectrometer (FIGAERO-ToF-CIMS) during an intensive measurement campaign 40 km northwest of Beijing in May and June 2016. A maximum mixing ratio of 2900 ppt of ClNO2 was observed with a mean campaign nighttime mixing ratio of 487 ppt, appearing to have an anthropogenic source supported by correlation with SO2, CO and benzene, which often persisted at high levels after sunrise until midday. This was attributed to such high mixing ratios persisting after numerous e-folding times of the photolytic lifetime enabling the chlorine atom production to reach 2.3 x 10(5) molecules cm(-3) from ClNO2 alone, peaking at 09:30 LT and up to 8.4 x 10(5) molecules cm(-3) when including the supporting inorganic halogen measurements. Cl-VOCs were observed in the particle and gas phases for the first time at high time resolution and illustrate how the iodide ToF-CIMS can detect unique markers of chlorine atom chemistry in ambient air from both biogenic and anthropogenic sources. Their presence and abundance can be explained via time series of their measured and steady-state calculated precursors, enabling the assessment of competing OH and chlorine atom oxidation via measurements of products from both of these mechanisms and their relative contribution to secondary organic aerosol (SOA) formation.
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39. |
- Liu, Qianyun, et al.
(författare)
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Roadside assessment of a modern city bus fleet: Gaseous and particle emissions
- 2019
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Ingår i: Atmospheric Environment: X. - : Elsevier BV. - 2590-1621. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Authors In many cities worldwide, modern fleets have been introduced to reduce gaseous and particle emissions from city buses. To date, most emission studies are limited to a few vehicles, making a statistically significant assessment of control options difficult, especially under real-world driving conditions. Exhaust emissions of 234 individual city buses were measured under real-world stop-and-go traffic conditions at a bus stop in Gothenburg, Sweden. The buses comprised models fulfilling Euro III-VI and EEV (Enhanced Environmentally Friendly Vehicle) standards with different engine technologies, fuels, and exhaust after-treatment systems, and also included hybrid-electric buses (HEV). Both gaseous (NOx, CO, HC, and SO2) and size-resolved particle number (PN) and mass (PM) emission factors (EF) were calculated for vehicles using compressed natural gas (CNG), diesel (DSL), Rapeseed Methyl Ester (RME) and Hydro-treated Vegetable Oil (HVO) equipped with various after-treatment technologies, e.g., diesel particulate filter (DPF), selective catalytic reduction (SCR) and exhaust gas recirculation (EGR) systems. The highest median EFPN was obtained from Euro VHEV-HVO-SCR buses (MdEFPN = 18×1014 # kg-1) when their combustion engines were used though 53% of their accelerations were below detection limits indicating the use of their electrical engine. The highest MdEFPM was obtained from the Euro V-DSL-SCR buses (MdEFPM = 150 mg kg-1) and the lowest from EEV-CNG buses (below detection threshold) and Euro VIHEV-HVO- SCR+EGR+DPF buses (MdEFPM = 19 mg kg-1). The highest MdEFNOx was obtained from the Euro V-RME-SCR (MdEFNOx = 30 g kg-1) and Euro VHEV-HVO-SCR buses (MdEFNOx = 24 g kg-1), and the lowest from CNG buses (MdEFNOx = 4.8 g kg-1) and Euro VIHEV-HVO-SCR+EGR+DPF buses (MdEFNOx = 7.4 g kg-1). Hybrid buses can give higher PN emissions compared to traditional diesel engines, likely due to downsized combustion engines. Replacing diesel by biodiesel fuel reduced MdEFPM significantly but increased MdEFNOx which may be due to the higher combustion temperature and oxygen contents of the fuel (for RME). Overall, the EEV-CNG buses performed the best regarding both the MdEF and low contribution to the high emitters. It was also found that a small (5%) proportion of the buses contributed significantly (14-30%) to the total emissions. Identification and monitoring the maintenance of the high emitters in the fleets should be considered for the improvement of air quality.
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40. |
- Lof, Sanne, et al.
(författare)
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Learning Curves of Minimally Invasive Distal Pancreatectomy in Experienced Pancreatic Centers
- 2023
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 158:9, s. 927-933
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data. OBJECTIVE To evaluate the length of pooled learning curves of MIDP in experienced centers. DESIGN, SETTING, AND PARTICIPANTS This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022. EXPOSURES The learning curve for MIDP was estimated by pooling data from all centers. MAIN OUTCOMES AND MEASURES The learning curvewas assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix-expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C. RESULTS From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean [SD] patient age, 58 [15.3] years; among 2040 with reported sex, 1249 were female [61.2%] and 791 male [38.8%]). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at 70%. The learning-associated loss of TBO rate was estimated at 3.3%. For conversion, a break point was estimated at 40 procedures (95% CI, 11-68 procedures); for operation time, at 56 procedures (95% CI, 35-77 procedures); and for intraoperative blood loss, at 71 procedures (95% CI, 28-114 procedures). For postoperative pancreatic fistula, no break point could be estimated. CONCLUSION AND RELEVANCE In experienced international centers, the learning curve length of MIDP for TBO was considerable with 85 procedures. These findings suggest that although learning curves for conversion, operation time, and intraoperative blood loss are completed earlier, extensive experience may be needed to master the learning curve of MIDP.
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41. |
- Nichols, Emma, et al.
(författare)
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Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:1, s. 88-106
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Tidskriftsartikel (refereegranskat)abstract
- Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.Methods: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugarsweetened beverages).Findings: In 2016, the global number of individuals who lived with dementia was 43.8 million (95% uncertainty interval [UI] 3 7. 8-51.0), increased from 20.2 million (17. 4-23 5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1.7% (1.0-2.4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27.0 million, 95% UI 23 .3-31. 4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2.4 million (95% UI 2.1-2.8) deaths. Overall, 28.8 million (95% UI 24. 5-34. 0) DALYs were attributed to dementia; 6.4 million (95% UI 3 .4-10. 5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.Interpretation: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.
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42. |
- Ramakrishna, Sarayu, et al.
(författare)
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APOE4 affects basal and NMDAR mediated protein synthesis in neurons by perturbing calcium homeostasis
- 2021
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 41:42, s. 8686-8709
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (APOE), one of the primary lipoproteins in the brain has three isoforms in humans - APOE2, APOE3, and APOE4. APOE4 is the most well-established risk factor increasing the pre-disposition for Alzheimer's disease. The presence of the APOE4 allele alone is shown to cause synaptic defects in neurons and recent studies have identified multiple pathways directly influenced by APOE4. However, the mechanisms underlying APOE4 induced synaptic dysfunction remain elusive. Here, we report that the acute exposure of primary cortical neurons or synaptoneurosomes to APOE4 leads to a significant decrease in global protein synthesis. Primary cortical neurons were derived from male and female embryos of Sprague-Dawley rats or C57BL/6J mice. Synaptoneurosomes were prepared from P30 male Sprague-Dawley rats. APOE4 treatment also abrogates the NMDA mediated translation response indicating an alteration of synaptic signaling. Importantly, we demonstrate that both APOE3 and APOE4 generate a distinct translation response which is closely linked to their respective calcium signature. Acute exposure of neurons to APOE3 causes a short burst of calcium through NMDARs leading to an initial decrease in protein synthesis which quickly recovers. Contrarily, APOE4 leads to a sustained increase in calcium levels by activating both NMDARs and L-VGCCs, thereby causing sustained translation inhibition through eEF2 phosphorylation, which in turn disrupts the NMDAR response. Thus, we show that APOE4 affects basal and activity mediated protein synthesis responses in neurons by affecting calcium homeostasis.SIGNIFICANCE STATEMENTDefective protein synthesis has been shown as an early defect in familial Alzheimer's disease. However, this has not been studied in the context of sporadic Alzheimer's disease, which constitutes the majority of cases. In our study, we show that APOE4, the predominant risk factor for Alzheimer's disease, inhibits global protein synthesis in neurons. APOE4 also affects NMDA activity mediated protein synthesis response, thus inhibiting synaptic translation. We also show that the defective protein synthesis mediated by APOE4 is closely linked to the perturbation of calcium homeostasis caused by APOE4 in neurons. Thus, we propose the dysregulation of protein synthesis as one of the possible molecular mechanisms to explain APOE4 mediated synaptic and cognitive defects. Hence, the study not only suggests an explanation for the APOE4 mediated pre-disposition to Alzheimer's disease, it also bridges the gap in understanding APOE4 mediated pathology.
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43. |
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44. |
- Soam, Shveta, 1987-, et al.
(författare)
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Life cycle assessment of fuel ethanol from sugarcane molasses in northern and western India and its impact on Indian biofuel programme
- 2015
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Ingår i: Energy Journal. - : Elsevier BV. - 0195-6574 .- 1944-9089. ; 83, s. 307-315
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Tidskriftsartikel (refereegranskat)abstract
- India's biofuel programme relies on the ethanol from molasses for blending into gasoline. Therefore, quantification of GHG (green house gas) emissions and the energy consumed during the process of ethanol production is desirable to help policy makers to take meaningful decisions. In order to establish the environmental impact of the biofuels, LCA (life cycle assessment) is conducted for 1 ton of fuel grade ethanol in the NR (northern region) and WR (western region) of India. Four different allocation approaches, WA (without any allocation), MA (mass allocation), EA (energy allocation) and MPA (market price allocation) are used to distribute emissions and energy consumption between the product and the co-products. Total GHG emissions are from 543.3 (−75.9%) to 8219.8 kg CO2-eq. (262.7%) in NR and 552.0 (−75.8%) to 7382.4 kg CO2-eq. (225.6%) with respect to gasoline. Similarly, the NER (net energy ratio) also varies with different allocation approaches and ranged from 0.38 to 3.39 in the NR and 0.48 to 4.23 in WR. Using MA approach, maximum GHG emissions reduction are, −75.9 and −75.8% and NER, 3.39 and 4.23 in NR and WR respectively indicates the environment and net energy benefits of fuel ethanol. It is observed that MA and EA approaches give more acceptable and real life results.
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45. |
- Srivastava, Rajesh K., et al.
(författare)
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Spatial and temporal distribution of Large Igneous Provinces in the Indian Shield - Highlights of recent investigations
- 2020
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Ingår i: Proceedings of the Indian National Science Academy. - : Indian National Science Academy. - 0370-0046. ; 86:1, s. 313-330
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Forskningsöversikt (refereegranskat)abstract
- This report highlights investigations since 2016 on the Large Igneous Provinces (LIPs), particularly based on their mafic dyke swarms (MDSs) and continental flood basalts (CFBs), from the Indian Shield. Recent research, particularly geochemistry, geochronology and paleomagnetism, allow identification and characterization of distinct generations of LIPs in space and time in the Indian Shield. This could be the basis for critical new tests of paleogeographic reconstructions of supercontinents and paleocontinents of the Earth's history and the position of India in different ancient supercontinent/supercratons. The high-quality data generated in recent years also helped significantly to understand the nature, composition and evolution of the sub-continental lithospheric mantle beneath the Indian Shield, which aims at resolving important geological aspects, such as the role of plume tectonics, ancient subduction events, extent of the LIPs paleo-supercontinent reconstructions, etc., and has received considerable national and international attention.
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46. |
- Stacchiotti, S., et al.
(författare)
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Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
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Forskningsöversikt (refereegranskat)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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47. |
- Tanner, Lloyd, et al.
(författare)
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Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation
- 2021
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1873-5010 .- 1569-1993. ; 20:2, s. 346-355
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cystic fibrosis (CF), involves excessive airway accumulation of neutrophils, often in parallel with severe infection caused by Pseudomonas aeruginosa. Free histones are known to possess bactericidal properties, but the degree of antibacterial activity exerted on specific lung-based pathogens is largely unknown. Neutrophils have a high content of peptidyl deiminase 4 (PADI4), which citrullinate cationic peptidyl-arginines. In histone H3.1, several positions in the NH2-terminal tail are subject to citrullination.METHODS: Full-length and segmented histone subunit H3.1 was investigated for bactericidal activity towards P. aeruginosa (strain PAO1). PADI4-induced citrullination of histone H3.1 was assessed for antibacterial activity towards P. aeruginosa. Next, the effect of neutrophil elastase (NE)-mediated proteolysis of histone H3.1 was investigated. Finally, PADI4, H3.1, and citrullinated H3.1 were examined in healthy control and CF patient lung tissues.RESULTS: Full-length histone H3.1 and sections of the histone H3.1 tail, displayed bactericidal activity towards P. aeruginosa. These antibacterial effects were reduced following citrullination by PADI4 or proteolysis by NE. Interestingly, citrullination of histone H3.1 exacerbated NE-mediated degradation. In CF lung tissue, citrullinated histone H3.1 and PADI4 immunoreactivity was abundant. Degraded histone H3.1 was detected in the sputum of CF patients but was absent in the sputum of healthy controls.CONCLUSIONS: Citrullination impairs the antibacterial activity of histone H3.1 and exacerbates its proteolytic degradation by NE. Citrullination is likely to play an important role during resolution of acute inflammation. However, in chronic inflammation akin to CF, citrullination may dampen host defense and promote pathogen survival, as exemplified by P. aeruginosa.
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48. |
- Tiwari, Atul, et al.
(författare)
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Biopolymers : An Indispensable Tool for Biotechnology
- 2012
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Ingår i: Biotechnology in Biopolymers. - United Kingdom : Smithers Rapra. - 9781847355423 ; , s. 1-16
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This comprehensive book provides up-to-date information on the developments in the field of biopolymers. Close attention has been paid to include all the important aspects that are necessary to understand the field. The book introduces the reader with the progress in the field, followed by outlining its applications in different areas. Different methods and techniques of synthesis and characterization are detailed as individual chapters. Various mode and mechanism of degradation of materials will be discussed. There is a dedicated chapter on industrially available biopolymers and their applications and well as a chapter detailing the ongoing research, current trends and future challenges.
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49. |
- Wang, X. F., et al.
(författare)
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Size distributions of aerosol sulfates and nitrates in Beijing during the 2008 Olympic Games: Impacts of pollution control measures and regional transport
- 2013
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Ingår i: Advances in Atmospheric Sciences. - : Springer Science and Business Media LLC. - 0256-1530 .- 1861-9533. ; 30:2, s. 341-353
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Tidskriftsartikel (refereegranskat)abstract
- For the 2008 Olympic Games, drastic control measures were implemented on industrial and urban emissions of sulfur dioxide (SO2), nitrogen oxides (NO (x) ) and other pollutants to address the issues of poor air quality in Beijing. To investigate the effects of SO2 and NO (x) reductions on the particulate sulfate and nitrate concentrations as well as their size distributions, size-segregated aerosol samples were collected using micro-orifice uniform deposit impactors (MOUDIs) at urban and downwind rural sites in Beijing before and after full-scale controls. During the sampling period, the mass concentrations of fine particles (PM1.8) at the urban and rural sites were 94.0 and 85.9 mu g m(-3), respectively. More than 90% of the sulfates and similar to 60% of nitrates formed as fine particles. Benefiting from the advantageous meteorological conditions and the source controls, sulfates were observed in rather low concentrations and primarily in condensation mode during the Olympics. The effects of the control measures were separately analyzed for the northerly and the southerly air-mass-dominated days to account for any bias. After the control measures were implemented, PM, sulfates, and nitrates were significantly reduced when the northerly air masses prevailed, with a higher percentage of reduction in larger particles. The droplet mode particles, which dominated the sulfates and nitrates before the controls were implemented, were remarkably reduced in mass concentration after the control measures were implemented. Nevertheless, when the polluted southerly air masses prevailed, the local source control measures in Beijing did not effectively reduce the ambient sulfate concentration due to the enormous regional contribution from the North China Plain.
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50. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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