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Numrering	Referens	Omslagsbild	Hitta
1.	2017 swepub:Mat__t
2.	Niemi, MEK, et al. (författare) 2021 swepub:Mat__t
3.	Thomas, HS, et al. (författare) 2019 swepub:Mat__t
4.	Kanai, M, et al. (författare) 2023 swepub:Mat__t
5.	Bhangu, A, et al. (författare) Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study 2018 Ingår i: The Lancet. Infectious diseases. - : Elsevier. - 1474-4457 .- 1473-3099. ; 18:5, s. 516-525 Tidskriftsartikel (refereegranskat)
6.	Bhangu, A, et al. (författare) Mortality of emergency abdominal surgery in high-, middle- and low-income countries 2016 Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 103:8, s. 971-988 Tidskriftsartikel (refereegranskat)
7.	Abbafati, Cristiana, et al. (författare) 2020 Tidskriftsartikel (refereegranskat)
8.	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.
9.	Murray, Christopher J. L., et al. (författare) Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051 Tidskriftsartikel (refereegranskat)abstract Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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.	Micah, Angela E., et al. (författare) Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050 2021 Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343 Forskningsöversikt (refereegranskat)abstract Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
12.	Ademuyiwa, Adesoji O., et al. (författare) Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries 2016 Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4 Tidskriftsartikel (refereegranskat)abstract Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
13.	Khetan, A. K., et al. (författare) Variations in the financial impact of the COVID-19 pandemic across 5 continents: A cross-sectional, individual level analysis 2022 Ingår i: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 44 Tidskriftsartikel (refereegranskat)abstract Background: COVID-19 has caused profound socio-economic changes worldwide. However, internationally comparative data regarding the financial impact on individuals is sparse. Therefore, we conducted a survey of the financial impact of the pandemic on individuals, using an international cohort that has been well-characterized prior to the pandemic. Methods: Between August 2020 and September 2021, we surveyed 24,506 community-dwelling participants from the Prospective Urban-Rural Epidemiology (PURE) study across high (HIC), upper middle (UMIC)-and lower middle (LMIC)-income countries. We collected information regarding the impact of the pandemic on their self-reported personal finances and sources of income. Findings: Overall, 32.4% of participants had suffered an adverse financial impact, defined as job loss, inability to meet financial obligations or essential needs, or using savings to meet financial obligations. 8.4% of participants had lost a job (temporarily or permanently); 14.6% of participants were unable to meet financial obligations or essential needs at the time of the survey and 16.3% were using their savings to meet financial obligations. Participants with a post-secondary education were least likely to be adversely impacted (19.6%), compared with 33.4% of those with secondary education and 33.5% of those with pre-secondary education. Similarly, those in the highest wealth tertile were least likely to be financially impacted (26.7%), compared with 32.5% in the middle tertile and 30.4% in the bottom tertile participants. Compared with HICs, financial impact was greater in UMIC [odds ratio of 2.09 (1.88–2.33)] and greatest in LMIC [odds ratio of 16.88 (14.69–19.39)]. HIC participants with the lowest educational attainment suffered less financial impact (15.1% of participants affected) than those with the highest education in UMIC (22.0% of participants affected). Similarly, participants with the lowest education in UMIC experienced less financial impact (28.3%) than those with the highest education in LMIC (45.9%). A similar gradient was seen across country income categories when compared by pre-pandemic wealth status. Interpretation: The financial impact of the pandemic differs more between HIC, UMIC, and LMIC than between socio-economic categories within a country income level. The most disadvantaged socio-economic subgroups in HIC had a lower financial impact from the pandemic than the most advantaged subgroup in UMIC, with a similar disparity seen between UMIC and LMIC. Continued high levels of infection will exacerbate financial inequity between countries and hinder progress towards the sustainable development goals, emphasising the importance of effective measures to control COVID-19 and, especially, ensuring high vaccine coverage in all countries. Funding: Funding for this study was provided by the Canadian Institutes of Health Research and the International Development Research Centre. © 2022 The Author(s)
14.	Boakye, K., et al. (författare) Perceived built environment characteristics associated with walking and cycling across 355 communities in 21 countries 2023 Ingår i: Cities. - : Elsevier BV. - 0264-2751. ; 132 Tidskriftsartikel (refereegranskat)abstract Research examining built environment (BE) characteristics and walking/cycling behaviors has been conducted primarily in high-income countries and conclusions cannot be applied directly to low- and middle-income countries. We evaluated perceived BE characteristics and walking/cycling behaviors across 355 urban communities in 21 low-, middle-, and high- income countries using individual data for 39,908 adults in the Prospective Urban and Rural Epidemiology study. The 1-week long-form International Physical Activity Questionnaire was used to measure walking/cycling behaviors. Perceived BE characteristics were measured using the Neighborhood Environment Walkability Scale. Mixed effects logistic regression models examined associations between BE measures and walking for transport (≥150 min/wk), walking for leisure (≥150 min/wk), and any cycling for transport, controlling for individual, household, and community factors. Land-use mix diversity, land-use mix access, and street connectivity were associated with higher odds of walking for transport. Land-use mix diversity, land-use mix access, safety from traffic and safety from crime were associated with higher odds of walking for leisure. Land-use mix diversity, land-use mix access, and aesthetics were associated with higher odds of cycling. Differences in associations were observed by country-income status. Our findings can help guide policy makers globally to implement BE design to encourage walking and cycling behaviors.
15.	Mente, A., et al. (författare) Diet, cardiovascular disease, and mortality in 80 countries 2023 Ingår i: European Heart Journal. - 0195-668X. ; 44:28, s. 2560-2579 Tidskriftsartikel (refereegranskat)abstract Aims To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. Methods and results A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of & LE;1 points, a diet score of & GE;5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). Conclusion A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.
16.	Mente, A., et al. (författare) Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study 2017 Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 5:10, s. 774-787 Tidskriftsartikel (refereegranskat)abstract Background The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries. Methods We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk markerbased estimates with directly observed associations of saturated fatty acids with cardiovascular disease events. Findings Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all p(trend) < 0.0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all p(trend) < 0.0001, apart from ApoB [p(trend) = 0.0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol. Interpretation Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.
17.	Atiomo, William, et al. (författare) Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome 2017 Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 87:5, s. 557-565 Tidskriftsartikel (refereegranskat)abstract Objective: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). Aim: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). Conclusions: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.
18.	Fakhar-E-Alam, M., et al. (författare) Anticancer effects of nanometallic oxides and their ligands with photosensitizers in osteosarcoma cells 2015 Ingår i: Journal of Optoelectronics and Advanced Materials. - : NATL INST OPTOELECTRONICS. - 1454-4164 .- 1841-7132. ; 17:11-12, s. 1808-1815 Tidskriftsartikel (refereegranskat)abstract We studied the cytotoxic effects in Osteosarcoma (U2OS) cells to different nanosized metallic oxides e.g. zinc oxide nanowires (ZnO-NRs), manganese di-oxide nanowires (MnO2 NWs), ferric oxide nanoparticles (Fe2O3 NPs) individually and their connplexed forms with photosensitizers photofrin (R), 5-Aminolevulinic acid (5-ALA), and protoporphyrin IX (Pp IX). Cellular toxicity was assayed by cellular morphology, reactive oxygen species (ROS) detection, MTT assay under ultraviolet (UV), visible light and laser exposed conditions. Prominent cell death with above cited nanomaterials in their complexed forms with Photosensitizer was observed in labeled U2OS cells. This cell death might be due to their synergetic effect via the release of singlet oxygen species in Osteosarcoma cells showing their anticancer-cell effects.
19.	Keck, Michaela Kristina, et al. (författare) Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification 2023 Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69 Tidskriftsartikel (refereegranskat)abstract Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
20.	Khan, M. Ajmal, et al. (författare) Effect of titania concentration on the grain boundary conductivity of calcium-doped ceria electrolyte 2014 Ingår i: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 40:7, s. 9775-9781 Tidskriftsartikel (refereegranskat)abstract A solid-state technique was used to synthesize ceria-based (CDC-xT, in which x=0-1 mol%) solid electrolyte ceramics. The effects of doping the ceramic solid electrolyte (CDC) with titanium oxide were studied with regard to densification, crystal structure, morphology, electro-impedance spectroscopy and fuel cell performance. TiO2 doping afforded materials a 95% relative density at 940 degrees C, approximately 200 degrees C lower than the temperature required without titanium oxide. The addition of titanium oxide (TiO2) reduced the CDC sintering temperature and significantly improved the grain boundary conduction. The minimum grain boundary resistivity was obtained at 0.8 mol% TiO2. X-ray diffraction (XRD) results showed that the lattice parameters enhanced with increased titanium oxide concentrations up to 0.8 mol%, revealing the solubility limit for Caria's fluorite structure. The optimum doping level (0.8 mol%) is provided maximum conductivity. Conductivities were measured using EIS (Electrochemical Impedance Spectroscopy) with a two-probe method, and the activation energies were calculated using the Arrhenius plots. The maximum power density (660 mW/cm(2)) was achieved with CDC 0.8T electrolyte at 650 degrees C using LiCuZnNi oxide electrodes.
21.	Lubcke, M., et al. (författare) Twisted plasma column 2002 Ingår i: Phys. Lett.. ; B534, s. 195-200 Tidskriftsartikel (refereegranskat)abstract We inspect a particular gauge field theory model that describes the properties of a variety of physical systems, including a charge neutral two-component plasma, a Gross-Pitaevskii functional of two charged Cooper pair condensates, and a limiting case of the bosonic sector in the Salam-Weinberg model. It has been argued that this field theory model also admits stable knot-like solitons. Here we produce numerical evidence in support for the existence of these solitons, by considering stable axis-symmetric solutions that can be thought of as straight twisted vortex lines clamped at the two ends. We compute the energy of these solutions as a function of the amount of twist per unit length. The result can be described in terms of a energy spectral function. We find that this spectral function acquires a minimum which corresponds to a nontrivial twist per unit length, strongly suggesting that the model indeed supports stable toroidal solitons.
22.	Majid, Farzana, et al. (författare) Exploration of magnesium based MgX2O4 (X = Rh, Bi) spinels for thermoelectric applications using density functional theory (DFT) 2020 Ingår i: Journal of Materials Research and Technology. - : Elsevier. - 2238-7854 .- 2214-0697. ; 9:3, s. 6135-6142 Tidskriftsartikel (refereegranskat)abstract By using WIEN2k code, we investigated the mechanical and thermoelectric properties of magnesium based MgX2O4 (X = Rh and Bi) spinels. To compute the mechanical behavior of MgX2O4 (X = Rh and Bi), the Perdew-Bruke-Ernzerhof (PBEsol) flavor of generalized gradient approximation is used. From structural optimization, ground state lattice constant (a0) show a comparable with the previously evaluated theoretical and experimental values. The Born stability criterion represents that the investigated spinels are stable in the cubic phase and their ductile behaviors are observed by calculating Pugh’s ratio as well as Poisson ratio. Besides, thermodynamic behavior is concluded in terms of the Debye temperature. To investigate the electronic and thermoelectric behavior, the modified Becke and Johnson (mBJ) potential is employed. Finally, we investigated the thermoelectric behavior to represent the importance of studied spinels in thermoelectric appliances by calculating the figure of merit (ZT). High values of the See-beck coefficient and ZT at room temperature explores the potential of the studied spinels in thermoelectric devices.
23.	Maller, Ori, et al. (författare) Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression 2020 Ingår i: Nature Materials. - : Springer Science and Business Media LLC. - 1476-1122 .- 1476-4660. Tidskriftsartikel (refereegranskat)abstract Stromal stiffening accompanies malignancy, compromises treatment and promotes tumour aggression. Clarifying the molecular nature and the factors that regulate stromal stiffening in tumours should identify biomarkers to stratify patients for therapy and interventions to improve outcome. We profiled lysyl hydroxylase-mediated and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in aggressive human breast cancer subtypes with the stiffest stroma. These tissues harbour the highest number of tumour-associated macrophages, whose therapeutic ablation in experimental models reduced metastasis, and decreased collagen crosslinks and stromal stiffening. Epithelial-targeted expression of the crosslinking enzyme, lysyl oxidase, had no impact on collagen crosslinking in PyMT mammary tumours, whereas stromal cell targeting did. Stromal cells in microdissected human tumours expressed the highest level of collagen crosslinking enzymes. Immunohistochemical analysis of biopsies from a cohort of patients with breast cancer revealed that stromal expression of lysyl hydroxylase 2, an enzyme that induces hydroxylysine aldehyde-derived collagen crosslinks and stromal stiffening, correlated significantly with disease specific mortality. The findings link tissue inflammation, stromal cell-mediated collagen crosslinking and stiffening to tumour aggression and identify lysyl hydroxylase 2 as a stromal biomarker.
24.	Mariatti, M., et al. (författare) Effect of hole drilling techniques on tensile properties of continuous fiber impregnated thermoplastic (COFIT) plain weave composites 2004 Ingår i: Journal of reinforced plastics and composites (Print). - : SAGE Publications. - 0731-6844 .- 1530-7964. ; 23:11, s. 1173-1186 Tidskriftsartikel (refereegranskat)abstract The effect of hole drilling technique on tensile properties of COFIT plain weave composite using circular hole was investigated. As expected, the tensile properties of COFIT woven system decrease with increasing hole sizes. The laminate, which was drilled by orbital technique, seems to impart higher tensile properties and better damage resistance compared to those of conventional drilling technique. In order to predict the laminate strength with the presence of open hole, the Point Stress Criterion was used. Results indicate that good agreement was obtained between experimental and estimation tensile strengths.
25.	Masood, KI, et al. (författare) Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome 2021 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 22958- Tidskriftsartikel (refereegranskat)abstract Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.
26.	Nasir, M. Anis U., et al. (författare) The power of both choices : Practical load balancing for distributed stream processing engines 2015 Ingår i: Proceedings - International Conference on Data Engineering. - : IEEE conference proceedings. - 9781479979639 ; , s. 137-148 Konferensbidrag (refereegranskat)abstract We study the problem of load balancing in distributed stream processing engines, which is exacerbated in the presence of skew. We introduce Partial Key Grouping (PKG), a new stream partitioning scheme that adapts the classical 'power of two choices' to a distributed streaming setting by leveraging two novel techniques: key splitting and local load estimation. In so doing, it achieves better load balancing than key grouping while being more scalable than shuffle grouping. We test PKG on several large datasets, both real-world and synthetic. Compared to standard hashing, PKG reduces the load imbalance by up to several orders of magnitude, and often achieves nearly-perfect load balance. This result translates into an improvement of up to 60% in throughput and up to 45% in latency when deployed on a real Storm cluster.
27.	Smith, Stuart W., et al. (författare) Tree species that 'live slow, die older' enhance tropical peat swamp restoration : Evidence from a systematic review 2022 Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 59:8, s. 1950-1966 Forskningsöversikt (refereegranskat)abstract 1. Degraded tropical peatlands lack tree cover and are often subject to seasonal flooding and repeated burning. These harsh environments for tree seedlings to survive and grow are therefore challenging to revegetate. Knowledge on species performance from previous plantings represents an important evidence base to help guide future tropical peat swamp forest (TPSF) restoration efforts.2. We conducted a systematic review of the survival and growth of tree species planted in degraded peatlands across Southeast Asia to examine (1) species differences, (2) the impact of seedling and site treatments on survival and growth and (3) the potential use of plant functional traits to predict seedling survival and growth rates.3. Planted seedling monitoring data were compiled through a systematic review of journal articles, conference proceedings, reports, theses and unpublished datasets. In total, 94 study-sites were included, spanning three decades from 1988 to 2019, and including 141 indigenous peatland tree and palm species. Accounting for variable planting numbers and monitoring durations, we analysed three measures of survival and growth: (1) final survival weighted by the number of seedlings planted, (2) half-life, that is, duration until 50% mortality and (3) relative growth rates (RGR) corrected for initial planting height of seedlings.4. Average final survival was 62% and half-life was 33 months across all species, sites and treatments. Species differed significantly in survival and half-life. Seedling and site treatments had small effects with the strongest being higher survival of mycorrhizal fungi inoculated seedlings; lower survival, half-life and RGR when shading seedlings; and lower RGR and higher survival when fertilising seedlings. Leaf nutrient and wood density traits predicted TPSF species survival, but not half-life and RGR. RGR and half-life were negatively correlated, meaning that slower growing species survived for longer.5. Synthesis and applications. To advance tropical peat swamp reforestation requires expanding the number and replication of species planted and testing treatments by adopting control vs. treatment experimental designs. Species selection should involve slower growing species (e.g. Lophopetalum rigidum, Alstonia spatulata, Madhuca motleyana) that survive for longer and explore screening species based on functional traits associated with nutrient acquisition, flooding tolerance and recovery from fire.
28.	Tedersoo, Leho, et al. (författare) Global patterns in endemicity and vulnerability of soil fungi. 2022 Ingår i: Global change biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 28:22, s. 6696-6710 Tidskriftsartikel (refereegranskat)abstract Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms.
29.	Aslay, Cigdem, et al. (författare) Mining Frequent Patterns in Evolving Graphs Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Given a labeled graph, the frequent-subgraph mining (FSM) problem asks to find all the k-vertex subgraphs that appear with frequency greater than a given threshold. FSM has numerous appli- cations ranging from biology to network science, as it provides a compact summary of the characteristics of the graph. However, the task is challenging, even more so for evolving graphs due to the streaming nature of the input and the exponential time complexity of the problem. In this paper, we initiate the study of approximate FSM problem in both incremental and fully-dynamic streaming settings, where arbitrary edges can be added or removed from the graph. For each streaming setting, we propose algorithms that can extract a high-quality approximation of the frequent k-vertex subgraphs for a given threshold, at any given time instance, with high probability. In contrast to the existing state-of-the-art solutions that require iterating over the entire set of subgraphs for any update, our algorithms operate by maintaining a uniform sample of k-vertex subgraphs with optimized neighborhood-exploration procedures local to the updates. We provide theoretical analysis of the proposed algorithms and emprically demonstrate that the proposed algorithms generate high-quality results compared to baselines.
30.	Assarsson, A., et al. (författare) Kinetic and thermodynamic study of the interactions between human carbonic anhydrase variants and polystyrene nanoparticles of different size 2016 Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 6:42, s. 35868-35874 Tidskriftsartikel (refereegranskat)abstract The activity and adsorption of three variants of human carbonic anhydrase (HCA) with similar topology but variation in charge and stability were studied in the presence of carboxyl-modified polystyrene nanoparticles of different sizes ranging from 25 nm to 114 nm. The balance of forces driving the adsorption of carbonic anhydrase variants is affected by the physicochemical properties of the protein and the nanoparticle size. All enzymes are totally inhibited upon adsorption due to the transition towards a molten globule like state that lacks enzymatic activity. The size of the particle affects the adsorption of human carbonic anhydrase I and N-terminal truncated human carbonic anhydrase II. Investigations on pH effects indicate that the size of the particle modulates the lateral interactions at the protein layer for these particular variants whose adsorption is mainly driven by electrostatic forces. A third variant, human carbonic anhydrase II, instead shows no strong influence of nanoparticle size which supports an adsorption process mainly driven by the hydrophobic effect.
31.	Duong, MyLinh, et al. (författare) Differences and agreement between two portable hand-held spirometers across diverse community-based populations in the Prospective Urban Rural Epidemiology (PURE) study. 2022 Ingår i: PLOS global public health. - : Public Library of Science (PLoS). - 2767-3375. ; 2:2 Tidskriftsartikel (refereegranskat)abstract Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics.From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method.Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation.In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.
32.	Kamat, Nasir, et al. (författare) Chemotherapy induced microsatellite instability and loss of heterozygosity in chromosomes 2, 5, 10, and 17 in solid tumor patients 2014 Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 14, s. 118- Tidskriftsartikel (refereegranskat)abstract Background: The inevitable side effects of the currently used chemotherapy are associated with serious syndromes. Genotoxic effects and consequent genetic instability may play an important role in these syndromes. The aim of the study was to evaluate chemotherapy-related microsatellite instability (MSI), loss of heterozygosity (LOH), and loss of mismatch repair (MMR) expression in solid tumor patients. Methods: Samples were collected from 117 de novo patients with solid tumors of different origins. Specimens, taken pre- and post-treatment, were screened for MSI and LOH in 10 microsatellite sequences in blood, and expression of five MMR proteins were analyzed in cancer tissues using immunohistochemistry. Statistical analysis included the use of; Fisher's exact test, Chi Square, and an inter-rater reliability test using Cohen's kappa coefficient. Results: Microsatellite analysis showed that 66.7% of the patients had MSI, including 23.1% high-positive MSI and 43.6% low-positive MSI. A large portion (41%) of the patients exhibited LOH in addition to MSI. MSI and LOH were detected in seven loci in which incidence rates ranged from 3.8% positive for Bat-26 to 34.6% positive for Tp53-Alu. Immunohistochemistry revealed that human mutL homolog 1 (hMLH1) expression was deficient in 29.1% of the patients, whereas 18.8%, 23.9%, 13.4%, and 9.7% were deficient for human mutS homolog 2 (hMSH2), P53, human mutS homolog 6 (hMSH6) and human post-meiotic segregation increased 2 (hPMS2), respectively. There was a significant correlation between MSI and LOH incidence in Tp53-Alu, Mfd41, and APC with low or deficient expression of hMLH1, hMSH2, and P53. A significant association between MSI and LOH, and incidence of secondary tumors was also evident. Conclusions: The negative correlation between MMR expression, MSI, and LOH and increased resistance to anti-cancer drugs and development of secondary cancers demonstrates a useful aid in early detection of potential chemotherapy-related side-effects. The diagnostic value demonstrated in our earlier study on breast cancer patients was confirmed for other solid tumors.
33.	Kamat, Nasir, et al. (författare) High incidence of microsatellite instability and loss of heterozygosity in three loci in breast cancer patients receiving chemotherapy : a prospective study 2012 Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 373- Tidskriftsartikel (refereegranskat)abstract Background: The aim of the study was to evaluate potential chemotherapy-induced microsatellite instability, loss of heterozygosity, loss of expression in mismatch repair proteins and associations with clinical findings in breast cancer patients, especially resistance to chemotherapy and/or development of other tumors in the four years following chemotherapy treatment. Methods: A comprehensive study of chemotherapy-related effects with a follow-up period of 48 months post treatment was conducted. A total of 369 peripheral blood samples were collected from 123 de novo breast cancer patients. Microsatellite instability and loss of heterozygosity in five commonly used marker loci (including Tp53-Alu of the tumor suppressor gene TP53) were analyzed in blood samples. Sampling was conducted on three occasions; 4-5 weeks prior to the first chemotherapy session (pre-treatment), to serve as a baseline, followed by two consecutive draws at 12 weeks intervals from the first collection. Mismatch repair protein expression was evaluated in cancer tissues using immunohistochemistry for three mismatch-repair related proteins. Results: A total of 70.7% of the patients showed microsatellite instability for at least one locus, including 18.6% marked as high-positive and 52.1% as low-positive; 35.8% showed loss of heterozygosity in addition to microsatellite instability, while 29.3% exhibited microsatellite stability. The following incidence rates for microsatellite instability and loss of heterozygosity were detected: 39.1% positive for Tp53-Alu, 31.1% for locus Mfd41, and 25.3% for locus Mfd28. A higher occurrence of loss of heterozygosity was noted with alleles 399 and 404 of Tp53-Alu. The mismatch repair protein expression analysis showed that the chemotherapy caused a loss of 29.3% in hMLH1 expression, and 18.7% and 25.2% loss in hMSH2 and P53 expression, respectively. A strong correlation between low or deficient hMSH2 protein expression and occurrence of mismatch repair/loss of heterozygosity events in Mfd41, Tp53-Alu, and Mfd28 was evident. A significant association between mismatch repair/loss of heterozygosity and incidence of secondary tumors was also established. Conclusion: Our results suggest that microsatellite instability, loss of heterozygosity, and deficiency in mismatch repair may serve as early prognostic factors for potential chemotherapy-related side effects in breast cancer patients.
34.	Kamat, Nasir, et al. (författare) Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer : A retrospective study 2013 Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 6:5, s. 1413-1420 Tidskriftsartikel (refereegranskat)abstract Microsatellite instability (MSI) is a mutator phenotype that results from a defective mismatch repair (MMR) pathway. The present study examined the incidence of MSI and loss of heterozygosity (LOH) according to five markers from the panel of the National Cancer Institute (NCI) in 38 colorectal cancer (CRC) patients from the United Arab Emirates (UAE). MSI and LOH were analyzed using fragment analyses in a multiplex PCR setting on a capillary array electrophoresis platform. The expression of the MMR proteins, hMLH1 and hMSH2, was analyzed using immunohistochemistry. The cohort consisted of 17 females (44.7%) and 21 males (55.3%) with mean ages of 59.9 and 63.3 years, respectively. The overall MSI incidence was 31.3% (95% CI, 16.1-50.0), and included three patients with high MSI (MSI-H; 9.4%; 95% CI, 2.0-25.0) and seven patients with low MSI (MSI-L; 21.9%; 95% CI, 10.7-39). LOH was detected in three patients, while the remaining 25 patients (65.8%) showed no instability and were therefore classified as microsatellite stable (MSS). MSI was detected in the following screened markers: Bat25 in seven patients, Bat26 in three patients, adenomatous polyposis coli (APC; D5S346) in five patients, AFM093xh3 (D2S123) in two patients and Mfd15 (D17S250) in three patients. Of the five MSI-positive patients, four (80%) were evidently younger, aged 38, 48, 49 and 59 years, respectively. The MSI-H incidence (9.4%) was lower compared with that of other ethnic groups. In terms of the MMR proteins, hMLH1 expression was deficient in seven patients, of whom three were MSI-H patients, and hMSH2 was deficient in three patients. Fisher's exact test showed significant associations between hMLH1 and MSI when classified as MSS, MSI-L or MSI-H (P=0.0003). No such association was observed with abnormal MMR protein expression, age, cancer stage or gender.
35.	Lim, WK, et al. (författare) Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma 2014 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:8, s. 877-880 Tidskriftsartikel (refereegranskat)
36.	Lübcke, Martin, et al. (författare) Twisted Vortices in a Gauge Field Theory 2002 Ingår i: Physics Letters B. ; 534:1-4, s. 195-200 Tidskriftsartikel (refereegranskat)
37.	Mikryukov, Vladimir, et al. (författare) Connecting the multiple dimensions of global soil fungal diversity 2023 Ingår i: Science advances. - 2375-2548. ; 9:48 Tidskriftsartikel (refereegranskat)abstract How the multiple facets of soil fungal diversity vary worldwide remains virtually unknown, hindering the management of this essential species-rich group. By sequencing high-resolution DNA markers in over 4000 topsoil samples from natural and human-altered ecosystems across all continents, we illustrate the distributions and drivers of different levels of taxonomic and phylogenetic diversity of fungi and their ecological groups. We show the impact of precipitation and temperature interactions on local fungal species richness (alpha diversity) across different climates. Our findings reveal how temperature drives fungal compositional turnover (beta diversity) and phylogenetic diversity, linking them with regional species richness (gamma diversity). We integrate fungi into the principles of global biodiversity distribution and present detailed maps for biodiversity conservation and modeling of global ecological processes.
38.	Nasir, Jamal M. (författare) Pavement maintenance budget allocation policy analysis and design : the Swedish National Road Administration case 1999 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)
39.	Nasir, M. Anis U., et al. (författare) Gossip-based partitioning and replication for Online Social Networks 2014 Ingår i: ASONAM 2014 - Proceedings of the 2014 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining. - : Institute of Electrical and Electronics Engineers Inc.. - 9781479958771 ; , s. 33-42 Konferensbidrag (refereegranskat)abstract Online Social Networks (OSNs) have been gaining tremendous growth and popularity in the last decade, as they have been attracting billions of users from all over the world. Such networks generate petabytes of data from the social interactions among their users and create many management and scalability challenges. OSN users share common interests and exhibit strong community structures, which create complex dependability patterns within OSN data, thus, make it difficult to partition and distribute in a data center environment. Existing solutions, such as, distributed databases, key-value stores and auto scaling services use random partitioning to distribute the data across a cluster, which breaks existing dependencies of the OSN data and may generate huge inter-server traffic. Therefore, there is a need for intelligent data allocation strategy that can reduce the network cost for various OSN operations. In this paper, we present a gossip-based partitioning and replication scheme that efficiently splits OSN data and distributes the data across a cluster. We achieve fault tolerance and data locality, for one-hop neighbors, through replication. Our main contribution is a social graph placement strategy that divides the social graph into predefined size partitions and periodically updates the partitions to place socially connected users together. To evaluate our algorithm, we compare it with random partitioning and a state-of-the-art solution SPAR. Results show that our algorithm generates up to four times less replication overhead compared to random partitioning and half the replication overhead compared to SPAR.
40.	Nasir, M. Anis U., et al. (författare) Mining Frequent Patterns in Evolving Graphs Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Given a labeled graph, the frequent-subgraph mining (FSM) problem asks to find all the k-vertex subgraphs that appear with frequency greater than a given threshold. FSM has numerous appli- cations ranging from biology to network science, as it provides a compact summary of the characteristics of the graph. However, the task is challenging, even more so for evolving graphs due to the streaming nature of the input and the exponential time complexity of the problem. In this paper, we initiate the study of approximate FSM problem in both incremental and fully-dynamic streaming settings, where arbitrary edges can be added or removed from the graph. For each streaming setting, we propose algorithms that can extract a high-quality approximation of the frequent k-vertex subgraphs for a given threshold, at any given time instance, with high probability. In contrast to the existing state-of-the-art solutions that require iterating over the entire set of subgraphs for any update, our algorithms operate by maintaining a uniform sample of k-vertex subgraphs with optimized neighborhood-exploration procedures local to the updates. We provide theoretical analysis of the proposed algorithms and emprically demonstrate that the proposed algorithms generate high-quality results compared to baselines.
41.	Nasir, Waqas, et al. (författare) Histo-Blood Group Antigen Presentation Is Critical for Binding of Norovirus VLP to Glycosphingolipids in Model Membranes 2017 Ingår i: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 12:5, s. 1288-1296 Tidskriftsartikel (refereegranskat)abstract Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane associated glycans is more restricted than that of glycans in solution, particularly because of orientational constraints imposed on the glycolipid through its lateral interactions with other membrane lipids and proteins. We have developed and employed a total internal reflection fluorescence microscopy-based binding assay and. a scheme for molecular dynamics (MD) membrane simulations to investigate the consequences of various glycan presentation effects. The system studied was histo-blood group antigen (HBGA) epitopes of membrane-bound glycosphingolipids (GSLs) derived from small intestinal epithelium of humans (type 1 chain) and dogs (type 2 chain) interacting with GII.4 norovirus-like particles. Our experimental results showed strong binding to all lipid-linked type 1 chain HBGAs but no or only weak binding to the corresponding type 2 chain HBGAs. This is in contrast to results derived from STD experiments with free HBGAs in solution where binding was observed for Lewis x. The MD data suggest that the strong binding to type 1 chain glycolipids was due to the well-exposed (1,2)-linked alpha-L-Fucp and (1,4)- linked alpha-L-Fucp residues, while the weaker binding or lack of binding to type 2 chain HBGAs was due to the very restricted accessibility of the (1,3) -linked alpha-L-Fucp residue when the glycolipid is embedded in a phospholipid membrane. Our results not only contribute to a general understanding of protein carbohydrate interactions on model membrane surfaces, particularly in the context of virus binding, but also suggest a possible role of human intestinal GSLs as potential receptors for norovirus uptake.
42.	Nasir, W., et al. (författare) Histo-blood group antigen presentation is critical for norovirus VLP binding to glycosphingolipids in membranes 2016 Ingår i: Glycobiology. - 1460-2423 .- 0959-6658. ; 26:12, s. 1409-1409 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
43.	Nasir, Waqas, et al. (författare) Lewis histo-blood group alpha1,3/alpha1,4 fucose residues may both mediate binding to GII.4 noroviruses 2012 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 22:9, s. 1163-72 Tidskriftsartikel (refereegranskat)abstract Human noroviruses cause recurrent epidemics of gastroenteritis known to be dominated by the clinically important GII.4 genotype which recognizes human Secretor gene-dependent ABH histo-blood group antigens (HBGAs) as attachment factors. There is increasing evidence that GII.4 noroviruses have undergone evolutionary changes to recognize Lewis antigens and non-Secretor saliva. In this study, we have investigated the possibilities of the Lewis alpha1,3/alpha1,4 fucoses as mediators of binding of GII.4 noroviruses to Lewis antigens. The study was carried out using molecular dynamics simulations of Lewis type-1 and type-2 chain HBGAs in complex with VA387 P domain dimers in explicit water. Based on the computer simulations, we suggest the possibility of two receptor binding modes for Lewis HBGAs: the "Secretor pose" with the Secretor Fucalpha1,2 in the binding site and the "Lewis pose" with the Lewis Fucalpha1,3/alpha1,4 residues in the binding site. This was further supported by an extensive GlyVicinity analysis of the Protein Data Bank with respect to the occurrence of the Lewis and Secretor poses in complexes of Lewis antigens with lectins and antibodies as well as GII norovirus strains. The Lewis pose can also explain the interactions of GII.4 norovirus strains with Le(x) and SLe(x) structures. Moreover, the present model suggests binding of complex branched polysaccharides, with the Lewis antigens at the nonreducing end, to P domain dimers of GII.4 strains. Our results are relevant for understanding the evolution of norovirus binding specificities and for in silico design of future antiviral therapeutics.
44.	Nasir, Waqas, et al. (författare) SweetNET: A Bioinformatics Workflow for Glycopeptide MS/MS Spectral Analysis 2016 Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 15:8, s. 2826-2840 Tidskriftsartikel (refereegranskat)abstract Glycoproteomics has rapidly become an independent analytical platform bridging the fields of glycomics and proteomics to address site-specific protein glycosylation and its impact in biology. Current glycopeptide characterization relies on time-consuming manual interpretations and demands high levels of personal expertise. Efficient data interpretation constitutes one of the major challenges to be overcome before true high throughput glycopeptide analysis can be achieved. The development of new glyco-related bioinformatics tools is thus of crucial importance to fulfill this goal. Here we present SweetNET: a data-oriented bioinformatics workflow for efficient analysis of hundreds of thousands of glycopeptide MS/MS-spectra. We have analyzed MS data sets from two separate glycopeptide enrichment protocols targeting sialylated glycopeptides and chondroitin sulfate linkage region glycopeptides, respectively. Molecular networking was performed to organize the glycopeptide MS/MS data based on spectral similarities. The combination of spectral clustering, oxonium ion intensity profiles, and precursor ion m/z shift distributions provided typical signatures for the initial assignment of different N-, O- and CS-glycopeptide classes and their respective glycoforms. These signatures were further used to guide database searches leading to the identification and validation of a large number of glycopeptide variants including novel deoxyhexose (fucose) modifications in the linkage region of chondroitin sulfate proteoglycans.
45.	Parwal, Arvind, et al. (författare) Wave Energy Research at Uppsala University and The Lysekil Research Site, Sweden : A Status Update 2015 Konferensbidrag (refereegranskat)abstract This paper provides a summarized status update ofthe Lysekil wave power project. The Lysekil project is coordinatedby the Div. of Electricity, Uppsala University since 2002, with theobjective to develop full-scale wave power converters (WEC). Theconcept is based on a linear synchronous generator (anchored tothe seabed) driven by a heaving point absorber. This WEC has nogearbox or other mechanical or hydraulic conversion systems,resulting in a simpler and robust power plant. Since 2006, 12 suchWECs have been build and tested at the research site located atthe west coast of Sweden. The last update includes a new andextended project permit, deployment of a new marine substation,tests of several concepts of heaving buoys, grid connection,improved measuring station, improved modelling of wave powerfarms, implementation of remote operated vehicles forunderwater cable connection, and comprehensive environmentalmonitoring studies.
46.	Pett, C., et al. (författare) Effective Assignment of alpha 2,3/alpha 2,6-Sialic Acid Isomers by LC-MS/MS-Based Glycoproteomics 2018 Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 57:30, s. 9320-9324 Tidskriftsartikel (refereegranskat)abstract Distinct structural changes of the alpha 2,3/alpha 2,6-sialic acid glycosidic linkages on glycoproteins are of importance in cancer biology, inflammatory diseases, and virus tropism. Current glycoproteomic methodologies are, however, not amenable toward high-throughput characterization of sialic acid isomers. To enable such assignments, a mass spectrometry method utilizing synthetic model glycopeptides for the analysis of oxonium ion intensity ratios was developed. This method was successfully applied in large-scale glycoproteomics, thus allowing the site-specific structural characterization of sialic acid isomers.
47.	Tan, J, et al. (författare) Genomic landscapes of breast fibroepithelial tumors 2015 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:11, s. 1341- Tidskriftsartikel (refereegranskat)
48.	Tronnier, Volker M., et al. (författare) The appropriate management of persisting pain after spine surgery : a European panel study with recommendations based on the RAND/UCLA method 2019 Ingår i: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 28:1, s. 31-45 Tidskriftsartikel (refereegranskat)abstract Purpose: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS.Methods: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9).Results: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability.Conclusions: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care.
49.	Zajitschek, Susanne, et al. (författare) Paternal personality and social status influence offspring activity in zebrafish 2017 Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 17 Tidskriftsartikel (refereegranskat)abstract Background: Evidence for the transmission of non-genetic information from father to offspring is rapidly accumulating. While the impact of chemical and physical factors such as toxins or diet on the fitness of the parents and their offspring have been studied extensively, the importance of behavioural and social circumstances has only recently been recognised. Behavioural traits such as personality characteristics can be relatively stable, and partly comprise a genetic component but we know little about the non-genetic transmission of plastic behavioural traits from parents to offspring. We investigated the relative effect of personality and of social dominance as indicators at the opposite ends of the plasticity range on offspring behaviour in the zebrafish (Danio rerio). We assessed male boldness, a behavioural trait that has previously been shown previously to possess genetic underpinnings, and experimentally manipulated male social status to assess the association between the two types of behaviour and their correlation with offspring activity. Results: We found a clear interaction between the relatively stable and putative genetic effects based on inherited differences in personality and the experimentally induced epigenetic effects from changes in the social status of the father on offspring activity. Conclusions: Our study shows that offspring behaviour is determined by a combination of paternal personality traits and on-genetic effects derived from the social status of the father.

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