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Numrering	Referens	Omslagsbild	Hitta
1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
2.	2019 Tidskriftsartikel (refereegranskat)
3.	Fox, Z, et al. (författare) Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count>or=300 cells/microL who were assigned to 7.5 MIU interleukin-2 2007 Ingår i: HIV medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 8:2, s. 112-123 Tidskriftsartikel (refereegranskat)
4.	Wang, Haidong, et al. (författare) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
5.	Forouzanfar, Mohammad H, et al. (författare) 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 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323 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.
6.	Lozano, Rafael, et al. (författare) 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 Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138 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.
7.	Vos, Theo, et al. (författare) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 2015 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800 Tidskriftsartikel (refereegranskat)abstract Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
8.	Kassebaum, Nicholas J., et al. (författare) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658 Tidskriftsartikel (refereegranskat)abstract Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
9.	Naghavi, Mohsen, et al. (författare) 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 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171 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.
10.	Stanaway, Jeffrey D., et al. (författare) 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 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 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.
11.	Abbafati, Cristiana, et al. (författare) 2020 Tidskriftsartikel (refereegranskat)
12.	Blanton, Michael R., et al. (författare) Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe 2017 Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1 Tidskriftsartikel (refereegranskat)abstract We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
13.	Lim, Stephen S, et al. (författare) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. 2012 Ingår i: Lancet. - 1474-547X. ; 380:9859, s. 2224-60 Tidskriftsartikel (refereegranskat)abstract Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time.
14.	Kottyan, Leah C., et al. (författare) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. 2015 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596 Tidskriftsartikel (refereegranskat)abstract Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
15.	Boulougoura, A, et al. (författare) A phase 1, randomized, controlled clinical study of CC-11050 in people living with HIV with suppressed plasma viremia on antiretroviral therapy (APHRODITE) 2019 Ingår i: JOURNAL OF IMMUNOLOGY. - 0022-1767. ; 202:1 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
16.	Bood, Mattias, et al. (författare) Pentacyclic adenine: a versatile and exceptionally bright fluorescent DNA base analogue 2018 Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 9:14, s. 3494-3502 Tidskriftsartikel (refereegranskat)abstract Emissive base analogs are powerful tools for probing nucleic acids at the molecular level. Herein we describe the development and thorough characterization of pentacyclic adenine (pA), a versatile base analog with exceptional fluorescence properties. When incorporated into DNA, pA pairs selectively with thymine without perturbing the B-form structure and is among the brightest nucleobase analogs reported so far. Together with the recently established base analog acceptor qAnitro, pA allows accurate distance and orientation determination via Forster resonance energy transfer (FRET) measurements. The high brightness at emission wavelengths above 400 nm also makes it suitable for fluorescence microscopy, as demonstrated by imaging of single liposomal constructs coated with cholesterolanchored pA-dsDNA, using total internal reflection fluorescence microscopy. Finally, pA is also highly promising for two-photon excitation at 780 nm, with a brightness (5.3 GM) that is unprecedented for a base analog.
17.	Daly, Sarah B, et al. (författare) Mutations in HPSE2 cause urofacial syndrome. 2010 Ingår i: American journal of human genetics. - 1537-6605. ; 86:6, s. 963-9 Tidskriftsartikel (refereegranskat)abstract Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.
18.	Schmidt, Amand F., et al. (författare) Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9 2019 Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
19.	Unsalan, Ozan, et al. (författare) The Sariçiçek howardite fall in Turkey : Source crater of HED meteorites on Vesta and impact risk of Vestoids 2019 Ingår i: Meteoritics and Planetary Science. - Hoboken : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:5, s. 953-1008 Tidskriftsartikel (refereegranskat)abstract The Sariçiçek howardite meteorite shower consisting of 343 documented stones occurred on September 2, 2015 in Turkey and is the first documented howardite fall. Cosmogenic isotopes show that Sariçiçek experienced a complex cosmic‐ray exposure history, exposed during ~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid was launched by an impact 22 ± 2 Ma ago to Earth (as did one‐third of all HED meteorites). SIMS dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages for the basaltic magma clasts. The apatite U‐Pb age of 4525 ± 17 Ma, K‐Ar age of ~3.9 Ga, and the U,Th‐He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic and impact‐related resetting ages, respectively. Petrographic; geochemical; and O‐, Cr‐, and Ti‐isotopic studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic observations and analysis of organic material indicate a small portion of carbonaceous chondrite material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 km s−1 from NW; fragmentations at 37, 33, 31, and 27 km altitude; and provide a pre‐atmospheric orbit that is the first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data indicate the similarity of Sariçiçek with the Vesta asteroid family (V‐class) spectra, a group of asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ≤4 m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antionia impact crater on Vesta was formed on terrain of the same age as given by the 4He retention age of Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was formed ~22 Ma ago.
20.	Dodkins, Rupert H., et al. (författare) First principle simulator of a stochastically varying image plane for photon-counting high contrast applications 2020 Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 132:1016, s. 1-12 Tidskriftsartikel (refereegranskat)abstract Optical and near-infrared Microwave Kinetic Inductance Detectors, or MKIDs are low-temperature detectors with inherent spectral resolution that are able to instantly register individual photons with potentially no false counts or readout noise. These properties make MKIDs transformative for exoplanet direct imaging by enabling photon-statistics-based planet-discrimination techniques as well as performing conventional noise-subtraction techniques on shorter timescales. These detectors are in the process of rapid development, and as such, the full extent of their performance enhancing potential has not yet be quantified. MKID Exoplanet Direct Imaging Simulator, or MEDIS, is a general-purpose end-to-end numerical simulator for high-contrast observations with MKIDs. The simulator exploits current optical propagation libraries and augments them with a new MKIDs simulation module to provide a pragmatic model of many of the degradation effects present during the detection process. We use MEDIS to demonstrate how changes in various MKID properties affect the contrast-separation performance when conventional differential imaging techniques are applied to low-flux, short duration observations. We show that to improve performance at close separations will require increasing the maximum count rate or pixel sampling when there is high residual flux after the coronagraph. We predict that taking pixel yield from the value achieved by current instruments of 80% and increasing it to 100% would result in an improvement in contrast of a factor of ∼4 at 3λ/D and ∼8 at 6λ/D. Achieving better contrast performance in this low flux regime would then require exploiting the information encoded in the photon arrival time statistics.
21.	Glasner, J, et al. (författare) A small molecule alpha(4)beta(1) antagonist prevents development of murine Lyme arthritis without affecting protective immunity 2005 Ingår i: Journal of Immunology. - 1550-6606. ; 175:7, s. 4724-4734 Tidskriftsartikel (refereegranskat)abstract After infection with Borrelia burgdorferi, humans and mice under certain conditions develop arthritis. Initiation of inflammation is dependent on the migration of innate immune cells to the site of infection, controlled by interactions of a variety of adhesion molecules. In this study, we used the newly synthesized compound S18407, which is a prodrug of the active drug S16197, to analyze the functional importance of alpha(4)beta(1)-dependent cell adhesion for the development of arthritis and for the antibacterial immune response. S16197 is shown to interfere specifically with the binding of alpha(4)beta(1) integrin to its ligands VCAM-1 and fibronectin in vitro. Treatment of B. burgdorferi-infected C3H/Hej mice with the alpha(4)beta(1), antagonist significantly ameliorated the outcome of clinical arthritis and the influx of neutrophilic granulocytes into ankle joints. Furthermore, local mRNA up-regulation of the proinflammatory mediators IL-1, IL-6, and cyclooxygenase-2 was largely abolished. Neither the synthesis of spirochete-specific Igs nor the development of a Th1-dominated immune response was altered by the treatment. Importantly, the drug also did not interfere with Ab-mediated control of spirochete load in the tissues. These findings demonstrate that the pathogenesis, but not the protective immune response, in Lyme arthritis is dependent on the alpha(4)beta(1)-mediated influx of inflammatory cells. The onset of inflammation can be successfully targeted by treatment with S18407.
22.	Gould, Rebecca L., et al. (författare) Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND) : a multicentre, parallel, randomised controlled trial in the UK 2024 Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 403:10442, s. 2381-2394 Tidskriftsartikel (refereegranskat)abstract Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.Methods: We conducted a parallel, multicentre, two -arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory -supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web -based system, stratified by site. Participants were followed up at 6 months and 9 months post -randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire -Revised (MQOL-R) at 6 months post -randomisation. Primary analyses were multi -level modelling and modified intention to treat among participants with available data. This trial was pre -registered with the ISRCTN Registry (ISRCTN12655391).Findings: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63⋅1 years (SD 11⋅0). 155 (81%) participants had primary outcome data at 6 months post -randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0⋅66 [95% CI 0⋅22-1⋅10]; d=0⋅46 [0⋅16-0⋅77]; p=0⋅0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention.Interpretation: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services.
23.	Kakkos, Stavros K, et al. (författare) Editor's Choice - European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis 2021 Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 61:1, s. 9-82 Forskningsöversikt (refereegranskat)
24.	Metzler, Veronika M., et al. (författare) Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development 2017 Ingår i: Placenta. - : W B SAUNDERS CO LTD. - 0143-4004 .- 1532-3102. ; 56, s. 79-85 Tidskriftsartikel (refereegranskat)abstract The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.
25.	Scheeren, Thomas W. L., et al. (författare) Current use of inotropes in circulatory shock 2021 Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 11:1 Tidskriftsartikel (refereegranskat)abstract BackgroundTreatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.MethodsFrom November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions.ResultsA total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement).ConclusionInotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
26.	Anderegg, William R L, et al. (författare) A climate risk analysis of Earth's forests in the 21st century 2022 Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 377:6610, s. 1099-1103 Tidskriftsartikel (refereegranskat)abstract Earth's forests harbor extensive biodiversity and are currently a major carbon sink. Forest conservation and restoration can help mitigate climate change; however, climate change could fundamentally imperil forests in many regions and undermine their ability to provide such mitigation. The extent of climate risks facing forests has not been synthesized globally nor have different approaches to quantifying forest climate risks been systematically compared. We combine outputs from multiple mechanistic and empirical approaches to modeling carbon, biodiversity, and disturbance risks to conduct a synthetic climate risk analysis for Earth's forests in the 21st century. Despite large uncertainty in most regions we find that some forests are consistently at higher risk, including southern boreal forests and those in western North America and parts of the Amazon.
27.	Bauer, Thomas, et al. (författare) Cross-domain Modelling of Verification and Validation Workflows in the Large Scale European Research Project VALU3S 2021 Ingår i: Lecture Notes in Computer Science. - Cham : Springer. ; , s. 386-382 Konferensbidrag (refereegranskat)abstract The complexity of systems continues to increase rapidly, especially due to the multi-level integration of subsystems from different domains into cyber-physical systems. This results in special challenges for the efficient verification and validation (V&V) of these systems with regard to their requirements and properties. In order to tackle the new challenges and improve the quality assurance processes, the V&V workflows have to be documented and analyzed. In this paper, a novel approach for the workflow modelling of V&V activities is presented. The generic approach is tailorable to different industrial domains and their specific constraints, V&V methods, and toolchains. The outcomes comprise a dedicated modelling notation (VVML) and tool-support using the modelling framework Enterprise Architect for the efficient documentation and implementation of workflows in the use cases. The solution enables the design of re-usable workflow assets such as V&V activities and artifacts that are exchanged between workflows. This work is part of the large scale European research project VALU3S that deals with the improvement and evaluation of V&V processes in different technical domains, focusing on safety, cybersecurity, and privacy properties.
28.	Dahlqvist, Per, et al. (författare) Pseudoacromegaly : A Differential Diagnostic Problem for Acromegaly With a Genetic Solution 2017 Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 1:8, s. 1104-1109 Tidskriftsartikel (refereegranskat)abstract Acromegaly is usually not a difficult condition to diagnose once the possibility of this disease has been raised. However, a few conditions present with some aspects of acromegaly or gigantism but without growth hormone (GH) excess. Such cases are described as "pseudoacromegaly" or "acromegaloidism". Here we describe a female patient investigated for GH excess at 10 years of age for tall stature since infancy (height and weight > +3 standard deviations) and typical acromegalic features, including large hands/feet, large jaw, tongue, hoarse deep voice, and headache. Results of radiography of the sella turcica and GH response at an oral glucose tolerance test and insulin-arginine- thyrotrophin-luteinizing hormone-releasing hormone test were normal. Ethinylestradiol and medroxyprogesterone were given for 2 years; this successfully stopped further height increase. Although the patient's growth rate plateaued, coarsening of the facial features and acral enlargement also led to investigations for suspicion of acromegaly at 23 and 36 years of age, both with negative results. On referral at the age of 49 years, she had weight gain, sweating, sleep apnea, headaches, joint pain, and enlarged tongue. Endocrine assessment again showing normal GH axis was followed by genetic testing with a macrocephaly/overgrowth syndrome panel. A denovo mutation in the NSD1 gene (c.6605G>C; p.Cys2202Ser) was demonstrated. Mutations affecting the same cysteine residue have been identified in patients with Sotos syndrome. In summary, Sotos syndrome and other overgrowth syndromes can mimic the clinical manifestations of acromegaly or gigantism. Genetic assessment could be helpful in these cases.
29.	Gericke, Martin, et al. (författare) The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources 2024 Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 326 Tidskriftsartikel (refereegranskat)abstract Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.
30.	Gillies, Michael A., et al. (författare) Peri-operative goal-directed therapy A definitive answer remains elusive 2018 Ingår i: European Journal of Anaesthesiology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0265-0215 .- 1365-2346. ; 35:7, s. 467-468 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract n/a
31.	Giustina, Marissa, et al. (författare) A Significant-Loophole-Free Test of Bells Theorem with Entangled Photons 2017 Ingår i: QUANTUM INFORMATION SCIENCE AND TECHNOLOGY III. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510613492 - 9781510613485 Konferensbidrag (refereegranskat)abstract John Bells theorem of 1964 states that local elements of physical reality, existing independent of measurement, are inconsistent with the predictions of quantum mechanics (Bell, J. S. (1964), Physics (College. Park. Md). 1 (3), 195). Specifically, correlations between measurement results from distant entangled systems would be smaller than predicted by quantum physics. This is expressed in Bells inequalities. Employing modifications of Bells inequalities, many experiments have been performed that convincingly support the quantum predictions. Yet, all experiments rely on assumptions, which provide loopholes for a local realist explanation of the measurement. Here we report an experiment with polarization-entangled photons that simultaneously closes the most significant of these loopholes. We use a highly efficient source of entangled photons, distributed these over a distance of 58.5 meters, and implemented rapid random setting generation and high-efficiency detection to observe a violation of a Bell inequality with high statistical significance. The merely statistical probability of our results to occur under local realism is less than 3.74 . 10(-31), corresponding to an 11.5 standard deviation effect.
32.	Giustina, Marissa, et al. (författare) Significant-Loophole-Free Test of Bells Theorem with Entangled Photons 2015 Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 115:25, s. 250401- Tidskriftsartikel (refereegranskat)abstract Local realism is the worldview in which physical properties of objects exist independently of measurement and where physical influences cannot travel faster than the speed of light. Bells theorem states that this worldview is incompatible with the predictions of quantum mechanics, as is expressed in Bells inequalities. Previous experiments convincingly supported the quantum predictions. Yet, every experiment requires assumptions that provide loopholes for a local realist explanation. Here, we report a Bell test that closes the most significant of these loopholes simultaneously. Using a well-optimized source of entangled photons, rapid setting generation, and highly efficient superconducting detectors, we observe a violation of a Bell inequality with high statistical significance. The purely statistical probability of our results to occur under local realism does not exceed 3.74 x 10(-31), corresponding to an 11.5 standard deviation effect.
33.	Gould, Rebecca, et al. (författare) Acceptance and Commitment Therapy for people living with motor neuron disease : an uncontrolled feasibility study 2023 Ingår i: Pilot and Feasibility Studies. - : Springer Nature. - 2055-5784. ; 9 Tidskriftsartikel (refereegranskat)abstract Background: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND.Methods: PlwMND aged >= 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (>= 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (>= 70% completing >= 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months.Results: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended >= 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status.Conclusions: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway.
34.	Groot, Colin, et al. (författare) Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer's disease subgroups 2021 Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 30 Tidskriftsartikel (refereegranskat)abstract The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups of amyloid-β positive individuals clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 ± 5). All participants underwent neuropsychological assessment with tests covering memory, executive-functioning, language and visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment compared to the intra-individual average across domains, which yielded the following subgroups in our sample; AD-Memory (n = 41), AD-Executive (n = 117), AD-Language (n = 33), AD-Visuospatial (n = 171). We performed voxel-wise contrasts of GM volumes derived from 3Tesla structural MRI between subgroups and controls (n = 127, age 58 ± 9, 42% male, MMSE 29 ± 1), and observed that differences in regional GM volumes compared to controls closely matched the respective cognitive profiles. Specifically, we detected lower medial temporal lobe GM volumes in AD-Memory, lower fronto-parietal GM volumes in AD-Executive, asymmetric GM volumes in the temporal lobe (left < right) in AD-Language, and lower GM volumes in posterior areas in AD-Visuospatial. In order to examine possible biological drivers of these differences in regional GM volumes, we correlated subgroup-specific regional GM volumes to brain-wide gene expression profiles based on a stereotactic characterization of the transcriptional architecture of the human brain as provided by the Allen human brain atlas. Gene-set enrichment analyses revealed that variations in regional expression of genes involved in processes like mitochondrial respiration and metabolism of proteins were associated with patterns of regional GM volume across multiple subgroups. Other gene expression vs GM volume-associations were only detected in particular subgroups, e.g., genes involved in the cell cycle for AD-Memory, specific sets of genes related to protein metabolism in AD-Language, and genes associated with modification of gene expression in AD-Visuospatial. We conclude that cognitively-defined AD subgroups show neurobiological differences, and distinct biological pathways may be involved in the emergence of these differences.
35.	Haigh, Daisy B., et al. (författare) The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer 2022 Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:20 Tidskriftsartikel (refereegranskat)abstract Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing androgen biosynthesis or via AR signalling inhibition (ARSi) are common treatments. The N6-methyladenosine (m6A) RNA modification is involved in regulating mRNA expression, translation, and alternative splicing, and through these mechanisms has been implicated in cancer development and progression. RNA-m6A is dynamically regulated by the METTL3 RNA methyltransferase complex and the FTO and ALKBH5 demethylases. While there is evidence supporting a role for aberrant METTL3 in many cancer types, including localised PCa, the wider contribution of METTL3, and by inference m6A, in androgen signalling in PCa remains poorly understood. Therefore, the aim of this study was to investigate the expression of METTL3 in PCa patients and study the clinical and functional relevance of METTL3 in PCa. It was found that METTL3 is aberrantly expressed in PCa patient samples and that siRNA-mediated METTL3 knockdown or METTL3-pharmacological inhibition significantly alters the basal and androgen-regulated transcriptome in PCa, which supports targeting m6A as a novel approach to modulate androgen signalling in PCa.
36.	Joshi, Siddarth Koduru, et al. (författare) Space QUEST mission proposal : experimentally testing decoherence due to gravity 2018 Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 20 Tidskriftsartikel (refereegranskat)abstract Models of quantum systems on curved space-times lack sufficient experimental verification. Some speculative theories suggest that quantum correlations, such as entanglement, may exhibit different behavior to purely classical correlations in curved space. By measuring this effect or lack thereof, we can test the hypotheses behind several such models. For instance, as predicted by Ralph et al [5] and Ralph and Pienaar [1], a bipartite entangled system could decohere if each particle traversed through a different gravitational field gradient. We propose to study this effect in a ground to space uplink scenario. We extend the above theoretical predictions of Ralph and coworkers and discuss the scientific consequences of detecting/failing to detect the predicted gravitational decoherence. We present a detailed mission design of the European Space Agency's Space QUEST (Space-Quantum Entanglement Space Test) mission, and study the feasibility of the mission scheme.
37.	Kabosova, Andrea, et al. (författare) Compositional differences between infant and adult human corneal basement membranes 2007 Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 48:11, s. 4989-4999 Tidskriftsartikel (refereegranskat)abstract PURPOSE. Adult human corneal epithelial basement membrane ( EBM) and Descemet's membrane ( DM) components exhibit heterogeneous distribution. The purpose of the study was to identify changes of these components during postnatal corneal development. METHODS. Thirty healthy adult corneas and 10 corneas from 12-day- to 3-year-old children were studied by immunofluorescence with antibodies against BM components. RESULTS. Type IV collagen composition of infant corneal central EBM over Bowman's layer changed from alpha 1-alpha 2 to alpha 3-alpha 4 chains after 3 years of life; in the adult, alpha 1-alpha 2 chains were retained only in the limbal BM. Laminin alpha 2 and beta 2 chains were present in the adult limbal BM where epithelial stem cells are located. By 3 years of age, beta 2 chain appeared in the limbal BM. In all corneas, limbal BM contained laminin gamma 3 chain. In the infant DM, type IV collagen alpha 1-alpha 6 chains, perlecan, nidogen-1, nidogen-2, and netrin-4 were found on both faces, but they remained only on the endothelial face of the adult DM. The stromal face of the infant but not the adult DM was positive for tenascin-C, fibrillin-1, SPARC, and laminin-332. Type VIII collagen shifted from the endothelial face of infant DM to its stromal face in the adult. Matrilin-4 largely disappeared after the age of 3 years. CONCLUSIONS. The distribution of laminin gamma 3 chain, nidogen-2, netrin-4, matrilin-2, and matrilin-4 is described in the cornea for the first time. The observed differences between adult and infant corneal BMs may relate to changes in their mechanical strength, corneal cell adhesion and differentiation in the process of postnatal corneal maturation.
38.	Knudsen, Gitte M, et al. (författare) Guidelines for the content and format of PET brain data in publications and archives : A consensus paper 2020 Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 40:8, s. 1576-1585 Tidskriftsartikel (refereegranskat)abstract It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis.
39.	Meissner, A, et al. (författare) CC chemokine ligand 20 partially controls adhesion of naive B cells to activated endothelial cells under shear stress 2003 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 102:8, s. 2724-2727 Tidskriftsartikel (refereegranskat)abstract Chemokines are thought to control lymphocyte recruitment to the inflamed endothelium. To dissect chemokine-mediated adhesion, binding of ex vivo isolated splenocytes to tumor necrosis factor (TNF)-activated endothelial cells was analyzed under shear stress. We observed specific adhesion of naive follicular B cells, which could be blocked by pertussis toxin. This indicated a G protein-mediated binding and pointed at a contribution of chemokine receptors to B-cell adhesion. Analysis of chemokines expressed by TNF-activated endothelial cells showed that CC chemokine ligand 2 (CCL2), CCL17, and CCL20 were up-regulated. Only on follicular B cells was the cognate receptor for CCL20, CC chemokine receptor 6 (CCR6), expressed strongly, and a functional transmigration assay with CCR6-negative B cells demonstrated conclusively the sole signaling of CCL20 through CCR6. Desensitization of CCR6 on naive B cells with CCL20 resulted in receptor down-regulation and reduced B-cell adhesion. We conclude that CCL20 plays a vital role in B-cell adhesion to the inflamed endothelium. (C) 2003 by The American Society of Hematology.
40.	Nørgaard, Martin, et al. (författare) Cerebral serotonin transporter measurements with [11C]DASB : A review on acquisition and preprocessing across 21 PET centres 2019 Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X .- 1559-7016. ; 39:2, s. 210-222 Tidskriftsartikel (refereegranskat)abstract Positron Emission Tomography (PET) imaging has become a prominent tool to capture the spatiotemporal distribution of neurotransmitters and receptors in the brain. The outcome of a PET study can, however, potentially be obscured by suboptimal and/or inconsistent choices made in complex processing pipelines required to reach a quantitative estimate of radioligand binding. Variations in subject selection, experimental design, data acquisition, preprocessing, and statistical analysis may lead to different outcomes and neurobiological interpretations. We here review the approaches used in 105 original research articles published by 21 different PET centres, using the tracer [11C]DASB for quantification of cerebral serotonin transporter binding, as an exemplary case. We highlight and quantify the impact of the remarkable variety of ways in which researchers are currently conducting their studies, while implicitly expecting generalizable results across research groups. Our review provides evidence that the foundation for a given choice of a preprocessing pipeline seems to be an overlooked aspect in modern PET neuroscience. Furthermore, we believe that a thorough testing of pipeline performance is necessary to produce reproducible research outcomes, avoiding biased results and allowing for better understanding of human brain function.
41.	Ocko, Samuel A., et al. (författare) Solar-powered ventilation of African termite mounds 2017 Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 220:18, s. 3260-3269 Tidskriftsartikel (refereegranskat)abstract How termite mounds function to facilitate climate control is still only partially understood. Recent experimental evidence in the mounds of a single species, the south Asian termite Odontotermes obesus, suggests that the daily oscillations of radiant heating associated with diurnal insolation patterns drive convective flow within them. How general this mechanism is remains unknown. To probe this, we consider the mounds of the African termite Macrotermes michaelseni, which thrives in a very different environment. By directly measuring air velocities and temperatures within the mound, we see that the overall mechanisms and patterns involved are similar to that in the south Asian species. However, there are also some notable differences between the physiology of these mounds associated with the temporal variations in radiant heating patterns and CO2 dynamics. Because of the difference between direct radiant heating driven by the position of the sun in African conditions, and the more shaded south Asian environments, we see changes in the convective flows in the two types of mounds. Furthermore, we also see that the south Asian mounds showa significant overturning of stratified gases, once a day, while the African mounds have a relatively uniform concentration of CO2. Overall, our observations show that despite these differences, termite architectures can harness periodic solar heating to drive ventilation inside them in very different environments, functioning as an external lung, with clear implications for human engineering.
42.	Ostaszewski, Marek, et al. (författare) COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms 2021 Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10 Tidskriftsartikel (refereegranskat)abstract We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
43.	Palahi, Marc, et al. (författare) Concerns about reported harvests in European forests 2021 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 592:7856, s. E15-E17 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
44.	Prowle, John R., et al. (författare) Postoperative acute kidney injury in adult non-cardiac surgery : joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative 2021 Ingår i: Nature Reviews Nephrology. - : Springer Nature. - 1759-5061 .- 1759-507X. ; 17:9, s. 605-618 Forskningsöversikt (refereegranskat)abstract The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI. Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.
45.	Pugh, Thomas A.M., et al. (författare) The anthropogenic imprint on temperate and boreal forest demography and carbon turnover 2024 Ingår i: Global Ecology and Biogeography. - 1466-822X. ; 33:1, s. 100-115 Tidskriftsartikel (refereegranskat)abstract Aim: The sweeping transformation of the biosphere by humans over the last millennia leaves only limited windows into its natural state. Much of the forests that dominated temperate and southern boreal regions have been lost and those that remain typically bear a strong imprint of forestry activities and past land-use change, which have changed forest age structure and composition. Here, we ask how would the dynamics, structure and function of temperate and boreal forests differ in the absence of forestry and the legacies of land-use change?. Location: Global. Time Period: 2001–2014, integrating over the legacy of disturbance events from 1875 to 2014. Major Taxa Studied: Trees. Methods: We constructed an empirical model of natural disturbance probability as a function of community traits and climate, based on observed disturbance rate and form across 77 protected forest landscapes distributed across three continents. Coupling this within a dynamic vegetation model simulating forest composition and structure, we generated estimates of stand-replacing disturbance return intervals in the absence of forestry for northern hemisphere temperate and boreal forests. We then applied this model to calculate forest stand age structure and carbon turnover rates. Results: Comparison with observed disturbance rates revealed human activities to have almost halved the median return interval of stand-replacing disturbances across temperate forest, with more moderate changes in the boreal region. The resulting forests are typically much younger, especially in northern Europe and south-eastern North America, resulting in a 32% reduction in vegetation carbon turnover time across temperate forests and a 7% reduction for boreal forests. Conclusions: The current northern hemisphere temperate forest age structure is dramatically out of equilibrium with its natural disturbance regimes. Shifts towards more nature-based approaches to forest policy and management should more explicitly consider the current disturbance surplus, as it substantially impacts carbon dynamics and litter (including deadwood) stocks.
46.	Rupert, A. E., et al. (författare) Assessment of tissue viability following electroosmotic push-pull perfusion from organotypic hippocampal slice cultures 2013 Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 4:5, s. 849-857 Tidskriftsartikel (refereegranskat)abstract We have developed a novel sampling technique that allows both introduction and removal of fluid from the extracellular space of living tissue. This method is based on the fluidics of push-pull perfusion but flow is driven by electroosmosis. We have applied this method to organotypic hippocampal cultures. A source capillary is inserted into the tissue and a collection capillary is in contact with the tissue surface through a thin layer of fluid. A voltage is applied across the proximal ends of source and collection capillary. In the applied field, fluid will move from source, into the tissue, and then be collected. In this process, damage to cells may occur. To understand better what sampling conditions influence damage most, we tested various sampling geometries and applied voltages, quantifying damage 16-24 h later using propidium iodide as a cell death marker. We found that damage correlates with both voltage drop and power dissipated in the tissue, but that voltage drop is a better indicator of damage when comparing models in which capillary arrangement and length are different. © 2013 American Chemical Society.
47.	Rupert, A. E., et al. (författare) Electroosmotic Push-Pull Perfusion: Description and Application to Qualitative Analysis of the Hydrolysis of Exogenous Galanin in Organotypic Hippocampal Slice Cultures 2013 Ingår i: Acs Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 4:5, s. 838-848 Tidskriftsartikel (refereegranskat)abstract We demonstrate here a method that perfuses a small region of an organotypic hippocampal culture
48.	Saari, Ulla A., et al. (författare) Designing green marketing across industries : A conceptual framework and implications for consumers and transdisciplinary research 2018 Ingår i: Handbook of sustainability science and research. - Cham : Springer. - 9783319630069 - 9783319630076 ; , s. 581-596 Bokkapitel (refereegranskat)abstract Understanding what marketing messages trigger sustainable consumer behavior is one of the key issues for companies to be able to design effective green marketing. The goal of this paper is to present a conceptual framework for a green marketing approach that includes product, industry, production processes, and supply chain specific considerations to be utilized in the design of green product marketing for the mass markets. Based on a literature review, we have created a conceptual framework with industry-specific aspects on the basis of unique features in seven industrial sectors that are of relevance to the personal needs of consumers from an environmental perspective, but are focusing on the product-specific aspects of the marketed products. The originality of this study lies in the proposition that green marketing should use the actual product features as a starting point and not focus only on green consumers. The greenness of a product should be an additional dimension that adds to the competitiveness of the product when compared to conventional products. Theoretically, we propose that a transdisciplinary approach that integrates sustainable supply chain management perspectives to green marketing would benefit companies designing green marketing approaches and consumers making green product choices.
49.	Saari, Ulla A., et al. (författare) Eco-friendly brands to drive sustainable development : Replication and extension of the brand experience scale in a cross-national context 2017 Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 9:7 Tidskriftsartikel (refereegranskat)abstract The purpose of this study is to explore how consumers perceive eco-friendliness in their brand experiences and how this can be measured cross-nationally. This is a replication-extension study based on an existing brand experience scale. Data were collected in India and Finland from smartphone users (N = 1008). The fitness of the brand experience model is validated cross-nationally with structural equation modeling. The empirical data consisting of consumers' responses on the Apple, Samsung, and Nokia brands confirm that there is a unique dimension of eco-friendliness in the general brand experiences of consumers, and it is generalizable cross-nationally in India and Finland. The study presents a consumer-focused measure of sustainable development that could be used to track how consumers perceive the eco-friendliness of brands. The paper links consumer experiences that guide sustainable consumption behavior to the macro-level management of sustainable development. This paper extends previous research on brand experience measurement by testing cross-nationally a scale including a dimension for measuring eco-friendliness. The brand experience measurement scale could aid companies in tracking the success of their sustainable development initiatives on the brand level.
50.	Saari, Ulla A., et al. (författare) How consumers’ respect for nature and environmental self-assets influence their car brand experiences 2020 Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 261 Tidskriftsartikel (refereegranskat)abstract This paper provides a novel perspective on sustainability research by exploring how two pro-environmental characteristics of consumers – respect for nature and environmental self-assets – influence their brand experiences. The study uses survey data collected on a car brand that incorporated eco-friendly advances. The results show that respect for nature has an impact on how respondents experience the eco-friendliness of brands and that eco-friendly brand experiences in turn influence general brand experiences. The findings also suggest that the effects of the two pro-environmental characteristics depend on the education level of the consumer: eco-friendly brand experiences of highly educated consumers are affected by their respect for nature, whereas those of consumers with lower education levels are affected by environmental self-assets.

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