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  • 2021
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  • Thomas, HS, et al. (författare)
  • 2019
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  • Alvarez, E. M., et al. (författare)
  • The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 23:1, s. 27-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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  • Kocarnik, J. M., et al. (författare)
  • Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019 A Systematic Analysis for the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Jama Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 8:3, s. 420-488
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3%(95% UI, 20.3%-32.3%) increase in new cases, a 20.9%(95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4%(1.1%-1.8%) in the low SDI quintile to 5.7%(4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and YDALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
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  • Cousin, E., et al. (författare)
  • Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 10:3, s. 177-192
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990-2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73.7% (68.3 to 77.4) were classified as due to type 1 diabetes. The age-standardised death rate was 0.50 (0.44 to 0.58) per 100 000 population, and 15 900 (97.5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0.13 (0.12 to 0.14) per 100 000 population in the high SDI quintile, 0.60 (0.51 to 0.70) per 100 000 population in the low-middle SDI quintile, and 0.71 (0.60 to 0.86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r(2)=0.62). From 1990 to 2019, age-standardised death rates decreased globally by 17.0% (-28.4 to -2.9) for all diabetes, and by 21.0% (-33.0 to -5.9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (-13.6% [-28.4 to 3.4]) and for type 1 diabetes (-13.6% [-29.3 to 8.9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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  • Sheena, B. S., et al. (författare)
  • Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:9, s. 796-829
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-ofsample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4 center dot 1% (95% uncertainty interval [UI] 3 center dot 7 to 4 center dot 5), corresponding to 316 million (284 to 351) infected people. There was a 31 center dot 3% (29 center dot 0 to 33 center dot 9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76 center dot 8% (76 center dot 2 to 77 center dot 5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5 center dot 9% [-5 center dot 6 to 19 center dot 2]) and between 2015 and 2019 (by 2 center dot 9% [-5 center dot 9 to 11 center dot 3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination.
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  • Drake, TM, et al. (författare)
  • Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
  • 2020
  • Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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  • Sharma, R., et al. (författare)
  • Global, regional, and national burden of colorectal cancer and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:7, s. 627-647
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990-2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408-868 574) to 2.17 million (2.00-2.34), and deaths increased from 518 126 (493 682-537 877) to 1.09 million (1.02-1.15). The global age-standardised incidence rate increased from 22.2 (95% UI 21.3-23.0) per 100 000 to 26.7 (24.6-28.9) per 100 000, whereas the age-standardised mortality rate decreased from 14.3 (13.5-14.9) per 100 000 to 13.7 (12.6-14.5) per 100 000 and the age-standardised DALY rate decreased from 308.5 (294.7-320.7) per 100 000 to 295.5 (275.2-313.0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62.0 [48.9-80.0] per 100 000), Monaco (60.7 [48.5-73.6] per 100 000), and Andorra (56.6 [42.8-71.9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31.4 [26.0-37.1] per 100 000), Brunei (30.3 [26.6-34.1] per 100 000), and Hungary (28.6 [23.6-34.0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age <50 years), particularly in high Socio-demographic Index (SDI) countries. Globally, a diet low in milk (15.6%), smoking (13.3%), a diet low in calcium (12.9%), and alcohol use (9.9%) were the main contributors to colorectal cancer DALYs in 2019. Interpretation The increase in incidence rates in people younger than 50 years requires vigilance from researchers, clinicians, and policy makers and a possible reconsideration of screening guidelines. The fast-rising burden in low SDI and middle SDI countries in Asia and Africa calls for colorectal cancer prevention approaches, greater awareness, and cost-effective screening and therapeutic options in these regions. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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  • Solmi, M, et al. (författare)
  • 2022
  • Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)
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  • Snodgrass, C., et al. (författare)
  • The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission
  • 2017
  • Ingår i: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2097
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/ Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies. This article is part of the themed issue 'Cometary science after Rosetta'.
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25.
  • Depledge, D. P., et al. (författare)
  • High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid from Cases of Varicella Zoster Virus Encephalitis
  • 2018
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:10, s. 1592-1601
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods. Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results. Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions. Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.
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  • Hawlader, M. D. H., et al. (författare)
  • Quality of life of COVID-19 recovered patients : a 1-year follow-up study from Bangladesh
  • 2023
  • Ingår i: Infectious Diseases of Poverty. - : Springer Nature. - 2095-5162. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The COVID-19 pandemic posed a danger to global public health because of the unprecedented physical, mental, social, and environmental impact affecting quality of life (QoL). The study aimed to find the changes in QoL among COVID-19 recovered individuals and explore the determinants of change more than 1 year after recovery in low-resource settings. Methods: COVID-19 patients from all eight divisions of Bangladesh who were confirmed positive by reverse transcription-polymerase chain reaction from June 2020 to November 2020 and who subsequently recovered were followed up twice, once immediately after recovery and again 1 year after the first follow-up. The follow-up study was conducted from November 2021 to January 2022 among 2438 individuals using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). After excluding 48 deaths, 95 were rejected to participate, 618 were inaccessible, and there were 45 cases of incomplete data. Descriptive statistics, paired-sample analyses, generalized estimating equation (GEE) analysis, and multivariable logistic regression analyses were performed to test the mean difference in participants’ QoL scores between the two interviews. Results: Most participants (n = 1710, 70.1%) were male, and one-fourth (24.4%) were older than 46. The average physical domain score decreased significantly from baseline to follow-up, and the average scores in psychological, social, and environmental domains increased significantly at follow-up (P < 0.05). By the GEE equation approach, after adjusting for other factors, we found that older age groups (P < 0.001), being female (P < 0.001), having hospital admission during COVID-19 illness (P < 0.001), and having three or more chronic diseases (P < 0.001), were significantly associated with lower physical and psychological QoL scores. Higher age and female sex [adjusted odd ratio (aOR) = 1.3, 95% confidence interval (CI) 1.0–1.6] were associated with reduced social domain scores on multivariable logistic regression analysis. Urban or semi-urban people were 49% less likely (aOR = 0.5, 95% CI 0.4–0.7) and 32% less likely (aOR = 0.7, 95% CI 0.5–0.9) to have a reduced QoL score in the psychological domain and the social domain respectively, than rural people. Higher-income people were more likely to experience a decrease in QoL scores in physical, psychological, social, and environmental domains. Married people were 1.8 times more likely (aOR = 1.8, 95% CI 1.3–2.4) to have a decreased social QoL score. In the second interview, people admitted to hospitals during their COVID-19 infection showed a 1.3 times higher chance (aOR = 1.3, 95% CI 1.1–1.6) of a decreased environmental QoL score. Almost 13% of participants developed one or more chronic diseases between the first and second interviews. Moreover, 7.9% suffered from reinfection by COVID-19 during this 1-year time. Conclusions: The present study found that the QoL of COVID-19 recovered people improved 1 year after recovery, particularly in psychological, social, and environmental domains. However, age, sex, the severity of COVID-19, smoking habits, and comorbidities were significantly negatively associated with QoL. Events of reinfection and the emergence of chronic disease were independent determinants of the decline in QoL scores in psychological, social, and physical domains, respectively. Strong policies to prevent and minimize smoking must be implemented in Bangladesh, and we must monitor and manage chronic diseases in people who have recovered from COVID-19. Graphical Abstract: [Figure not available: see fulltext.] 
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  • Lönnberg, Tapio, et al. (författare)
  • Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria
  • 2017
  • Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 2:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiation of naïve CD4(+) T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates.
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  • Villforth, C., et al. (författare)
  • Variability and stability in blazar jets on time-scales of years : optical polarization monitoring of OJ 287 in 2005-2009
  • 2010
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:3, s. 2087-2111
  • Tidskriftsartikel (refereegranskat)abstract
    • OJ 287 is a BL Lac object at redshift z = 0.306 that has shown double-peaked bursts at regular intervals of similar to 12 yr during the last similar to 40 yr. We analyse optical photopolarimetric monitoring data from 2005 to 2009, during which the latest double-peaked outburst occurred. The aim of this study is twofold: firstly, we aim to analyse variability patterns and statistical properties of the optical polarization light curve. We find a strong preferred position angle in optical polarization. The preferred position angle can be explained by separating the jet emission into two components: an optical polarization core and chaotic jet emission. The optical polarization core is stable on time-scales of years and can be explained as emission from an underlying quiescent jet component. The chaotic jet emission sometimes exhibits a circular movement in the Stokes plane. We find six such events, all on the time-scales of 10-20 d. We interpret these events as a shock front moving forwards and backwards in the jet, swiping through a helical magnetic field. Secondly, we use our data to assess different binary black hole models proposed to explain the regularly appearing double-peaked bursts in OJ 287. We compose a list of requirements a model has to fulfil to explain the mysterious behaviour observed in OJ 287. The list includes not only characteristics of the light curve but also other properties of OJ 287, such as the black hole mass and restrictions on accretion flow properties. We rate all existing models using this list and conclude that none of the models is able to explain all observations. We discuss possible new explanations and propose a new approach to understanding OJ 287. We suggest that both the double-peaked bursts and the evolution of the optical polarization position angle could be explained as a sign of resonant accretion of magnetic field lines, a 'magnetic breathing' of the disc.
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  • Khan, M. A. S., et al. (författare)
  • The impact of comorbidity on the quality of life of people who recovered from COVID-19 in Bangladesh
  • 2024
  • Ingår i: IJID Regions. - : Elsevier BV. - 2772-7076. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: COVID-19 affects the quality of life (QoL) in a reverse way after recovery, which might be multiplied by the comorbid non-communicable diseases. This study explored the relationship between comorbidities and the QoL of people who recovered from COVID-19 in Bangladesh. Methods: The cross-sectional study was conducted among 3244 participants between June 2020 and November 2020 using a pre-tested questionnaire through over-the-phone interviews. The WHOQOL-BREF was used to explore the QoL among the study participants. A multivariable linear regression model was conducted to identify the effects of the number of comorbidities on QoL scores of all four domains. Results: Of 3244 patients who recovered from COVID-19, over one-third (39.4%) had one or more chronic diseases, such as hypertension, diabetes mellitus, ischemic heart disease, bronchial asthma/chronic obstructive pulmonary disease, chronic kidney disease, and cancer. Around 46.85% of the participants aged above 40 years presented with one to two chronic diseases, and 16.33% had three or more chronic diseases. Among all comorbidities, the participants with cancer and chronic kidney disease were found to have relatively lower scores in all four domains than other comorbidities. The lowest QoL scores were observed in the psychological domain. Those with three or more simultaneous chronic comorbidities had the lowest QoL score in all four domains: physical, psychological, social relationship, and environmental. Conclusions: Persons who recovered from COVID-19 with comorbidities undergo a lower QoL. Therefore, special attention is required to these vulnerable groups to ensure their smooth recuperation. 
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35.
  • Kumar, Manish, 1982, et al. (författare)
  • Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling
  • 2018
  • Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 49, s. 128-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Malnutrition is a severe non-communicable disease, which is prevalent in children from low-income countries. Recently, a number of metagenomics studies have illustrated associations between the altered gut microbiota and child malnutrition. However, these studies did not examine metabolic functions and interactions between individual species in the gut microbiota during health and malnutrition. Here, we applied genome-scale metabolic modeling to model the gut microbial species, which were selected from healthy and malnourished children from three countries. Our analysis showed reduced metabolite production capabilities in children from two lowincome countries compared with a high-income country. Additionally, the models were also used to predict the community-level metabolic potentials of gut microbes and the patterns of pairwise interactions among species. Hereby we found that due to bacterial interactions there may be reduced production of certain amino acids in malnourished children compared with healthy children from the same communities. To gain insight into alterations in the metabolism of malnourished (stunted) children, we also performed targeted plasma metabolic profiling in the first 2 years of life of 25 healthy and 25 stunted children. Plasma metabolic profiling further revealed that stunted children had reduced plasma levels of essential amino acids compared to healthy controls. Our analyses provide a framework for future efforts towards further characterization of gut microbial metabolic capabilities and their contribution to malnutrition.
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36.
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37.
  • Lindblad, Rebecka, et al. (författare)
  • Energy level alignment in TiO2/metal sulfide/polymer interfaces for solar cell applications.
  • 2014
  • Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 16:32, s. 17099-107
  • Tidskriftsartikel (refereegranskat)abstract
    • Semiconductor sensitized solar cell interfaces have been studied with photoelectron spectroscopy to understand the interfacial electronic structures. In particular, the experimental energy level alignment has been determined for complete TiO2/metal sulfide/polymer interfaces. For the metal sulfides CdS, Sb2S3 and Bi2S3 deposited from single source metal xanthate precursors, it was shown that both driving forces for electron injection into TiO2 and hole transfer to the polymer decrease for narrower bandgaps. The energy level alignment results were used in the discussion of the function of solar cells with the same metal sulfides as light absorbers. For example Sb2S3 showed the most favourable energy level alignment with 0.3 eV driving force for electron injection and 0.4 eV driving force for hole transfer and also the most efficient solar cells due to high photocurrent generation. The energy level alignment of the TiO2/Bi2S3 interface on the other hand showed no driving force for electron injection to TiO2, and the performance of the corresponding solar cell was very low.
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38.
  • Norberg, Peter, 1974, et al. (författare)
  • Recombination of Globally Circulating Varicella-Zoster Virus
  • 2015
  • Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 89:14, s. 7133-7146
  • Tidskriftsartikel (refereegranskat)abstract
    • Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.
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39.
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40.
  • O'Mahony, Flannan T. F., et al. (författare)
  • Low-temperature solution processing of mesoporous metal-sulfide semiconductors as light-harvesting photoanodes.
  • 2013
  • Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 52:46, s. 12047-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Structured absorbers: Mesoporous films of highly crystalline Sb 2S3 are prepared from a doctor-bladed precursor paste that is thermally annealed. This facile and versatile processing route allows for control of the pore size through variation of the annealing temperature. The resulting high surface area allows for efficient charge transfer to a polymeric hole acceptor; hence, such films could form the basis of a novel hybrid organic-inorganic photovoltaic device.
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41.
  • Rajwa, Pawel, et al. (författare)
  • Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer : big data analytics using the PIONEER platform
  • 2024
  • Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 63, s. 81-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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42.
  • Sartelli, Massimo, et al. (författare)
  • Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
  • 2023
  • Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
  • Forskningsöversikt (refereegranskat)abstract
    • Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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43.
  • Shamba, Donat, et al. (författare)
  • Barriers and enablers to routine register data collection for newborns and mothers: EN-BIRTH multi-country validation study.
  • 2021
  • Ingår i: BMC pregnancy and childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 21:Suppl 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Policymakers need regular high-quality coverage data on care around the time of birth to accelerate progress for ending preventable maternal and newborn deaths and stillbirths. With increasing facility births, routine Health Management Information System (HMIS) data have potential to track coverage. Identifying barriers and enablers faced by frontline health workers recording HMIS source data in registers is important to improve data for use.The EN-BIRTH study was a mixed-methods observational study in five hospitals in Bangladesh, Nepal and Tanzania to assess measurement validity for selected Every Newborn coverage indicators. We described data elements required in labour ward registers to track these indicators. To evaluate barriers and enablers for correct recording of data in registers, we designed three interview tools: a) semi-structured in-depth interview (IDI) guide b) semi-structured focus group discussion (FGD) guide, and c) checklist assessing care-to-documentation. We interviewed two groups of respondents (January 2018-March 2019): hospital nurse-midwives and doctors who fill ward registers after birth (n = 40 IDI and n = 5 FGD); and data collectors (n = 65). Qualitative data were analysed thematically by categorising pre-identified codes. Common emerging themes of barriers or enablers across all five hospitals were identified relating to three conceptual framework categories.Similar themes emerged as both barriers and enablers. First, register design was recognised as crucial, yet perceived as complex, and not always standardised for necessary data elements. Second, register filling was performed by over-stretched nurse-midwives with variable training, limited supervision, and availability of logistical resources. Documentation complexity across parallel documents was time-consuming and delayed because of low staff numbers. Complete data were valued more than correct data. Third, use of register data included clinical handover and monthly reporting, but little feedback was given from data users.Health workers invest major time recording register data for maternal and newborn core health indicators. Improving data quality requires standardised register designs streamlined to capture only necessary data elements. Consistent implementation processes are also needed. Two-way feedback between HMIS levels is critical to improve performance and accurately track progress towards agreed health goals.
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44.
  • Su, H., et al. (författare)
  • Long-term hypercaloric diet exacerbates metabolic liver disease in PNPLA3 I148M animals
  • 2023
  • Ingår i: Liver International. - 1478-3223. ; 43:8, s. 1699-1713
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & AimsNonalcoholic fatty liver disease (NAFLD) is a major health burden associated with the metabolic syndrome leading to liver fibrosis, cirrhosis and ultimately liver cancer. In humans, the PNPLA3 I148M polymorphism of the phospholipase patatin-like phospholipid domain containing protein 3 (PNPLA3) has a well-documented impact on metabolic liver disease. In this study, we used a mouse model mimicking the human PNPLA3 I148M polymorphism in a long-term high fat diet (HFD) experiment to better define its role for NAFLD progression. MethodsMale mice bearing wild-type Pnpla3 (Pnpla3(WT)), or the human polymorphism PNPLA3 I148M (Pnpla3(148M/M)) were subjected to HFD feeding for 24 and 52 weeks. Further analysis concerning basic phenotype, inflammation, proliferation and cell death, fibrosis and microbiota were performed in each time point. ResultsAfter 52 weeks HFD Pnpla3(148M/M) animals had more liver fibrosis, enhanced numbers of inflammatory cells as well as increased Kupffer cell activity. Increased hepatocyte cell turnover and ductular proliferation were evident in HFD Pnpla3(148M/M) livers. Microbiome diversity was decreased after HFD feeding, changes were influenced by HFD feeding (36%) and the PNPLA3 I148M genotype (12%). Pnpla3(148M/M) mice had more faecal bile acids. RNA-sequencing of liver tissue defined an HFD-associated signature, and a Pnpla3(148M/M) specific pattern, which suggests Kupffer cell and monocytes-derived macrophages as significant drivers of liver disease progression in Pnpla3(148M/M) animals. ConclusionWith long-term HFD feeding, mice with the PNPLA3 I148M genotype show exacerbated NAFLD. This finding is linked to PNPLA3 I148M-specific changes in microbiota composition and liver gene expression showing a stronger inflammatory response leading to enhanced liver fibrosis progression.
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45.
  • Vyas, Agin, 1992, et al. (författare)
  • Investigation of palladium current collectors for vertical graphene-based microsupercapacitors
  • 2019
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1319:1
  • Konferensbidrag (refereegranskat)abstract
    • As microsystems are reduced in size and become integrated in the Internet of Things (IoT), they require an adequate power supply which can be integrated at the same size scale. Microsupercapacitors (MSCs), if coupled with on-chip harvesters, can offer solutions for a self-sustaining, on-chip power supply. However, the implementation of reliable MSC wafer-scale production compatible with CMOS technology remains a challenge. Palladium (Pd) is known as a CMOS compatible metal and, in this paper, we investigate the use of Pd as a contact material for vertical graphene (VG) electrodes in wafer-scale MSC fabrication. We show that a Ti diffusion barrier is required to prevent short-circuiting for the successful employment of Pd contacts. The fabricated MSCs demonstrate a capacitance of 1.3 μF/cm2 with an energy density of 0.42 μJ/cm2. Thus, utilization of a Ti diffusion barrier with a CMOS compatible Pd metal electrode is a step towards integrating MSCs in semiconductor microsystems.
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46.
  • Zimerman, Andre, et al. (författare)
  • Pooled analysis of adverse event collection from 4 acute coronary syndrome trials
  • 2016
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 174, s. 60-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied.Methods: Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting. Events were classified as serious (SAE) or nonserious (AE) from hospital discharge to 1 year; study end points were excluded.Results: In total, 84,901 events were reported. Of those, 12,266 (14.4%) were SAEs and 72,635 (85.6%) were AEs. Of all participants, 7,823 (16.3%) had SAEs, 18,124 (37.7%) had only AEs, and 22,171 (46.1%) had neither. Nonserious adverse events were distributed across system organ classes: general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), cardiovascular (8.4%), and other (35%). Serious adverse events had a higher proportion of cardiovascular causes (14.0%). Event reporting was highest after hospital discharge, decreasing rapidly during the following 3 months. In a Cox proportional hazards model, chronic obstructive pulmonary disease (hazard ratio 1.58, 95% CI 1.44-1.74), heart failure (1.55, 1.40-1.70), older age, and female sex were independent predictors of more SAEs, whereas enrollment in Eastern Europe (0.63, 0.58-0.69) or Asia (0.84, 0.75-0.94) were independent predictors of fewer SAEs.Conclusions: Half of all participants reported adverse events in the year after acute coronary syndrome; most were AEs and occurred within 3 months. The high volume of events, as well as the variation in SAE reporting by characteristics and enrollment region, indicates that efforts to refine event collection in large trials are warranted.
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