| 1. |
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| 2. |
- Tran, K. B., et al.
(författare)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 3. |
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| 4. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 5. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 6. |
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| 7. |
- Pijl, M. K. J., et al.
(författare)
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Parent-child interaction during the first year of life in infants at elevated likelihood of autism spectrum disorder
- 2021
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Ingår i: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453 .- 1934-8800. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) likely emerges from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the environment. The interaction with parents forms a key aspect of an infant’s social environment, but few prospective studies of infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) have examined parent-child interactions in the first year of life. As part of a European multisite network, parent-child dyads of free play were observed at 5 months (62 EL infants, 47 infants at typical likelihood (TL)) and 10 months (101 EL siblings, 77 TL siblings). The newly-developed Parent-Infant/Toddler Coding of Interaction (PInTCI) scheme was used, focusing on global characteristics of infant and parent behaviors. Coders were blind to participant information. Linear mixed model analyses showed no significant group differences in infant or parent behaviors at 5 or 10 months of age (all ps≥0.09, d≤0.36), controlling for infant’s sex and age, and parental educational level. However, without adjustments, EL infants showed fewer and less clear initiations at 10 months than TL infants (p = 0.02, d = 0.44), but statistical significance was lost after controlling for parental education (p = 0.09, d = 0.36), which tended to be lower in the EL group. Consistent with previous literature focusing on parent-infant dyads, our findings suggest that differences between EL and TL dyads may only be subtle during the first year of life. We discuss possible explanations and implications for future developmental studies.
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| 8. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
- 2014
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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| 9. |
- Fish, Laurel A., et al.
(författare)
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Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis
- 2021
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Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 62:11, s. 1308-1319
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype.Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants.Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (? = ?.16, 95% CI = ?0.31, ?0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ?catch-up?) between 14 and 24 months relative to those with other outcomes (typical: ? = .54, 95% CI = 0.08, 0.99; other: ? = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .05, 95% CI = 0.004, 0.11) traits.Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
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| 10. |
- Islar, Mine, et al.
(författare)
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Diverse values of nature for sustainability
- 2022
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620, s. 813-823
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature’s diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature’s values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a ‘values crisis’ underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature’s diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.
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| 11. |
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| 12. |
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| 13. |
- Begum, Noorjahan, et al.
(författare)
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Chelate and bridge diphosphine isomerization: triosmium and triruthenium clusters containing 1,1-bis(diphenylphosphino)ferrocene (dppf)
- 2007
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Ingår i: Organometallics. - : American Chemical Society (ACS). - 1520-6041 .- 0276-7333. ; 26:25, s. 6462-6472
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Tidskriftsartikel (refereegranskat)abstract
- The coordination mode of dppf {dppf = 1,1'-bis(diphenylphosphino)ferrocene} at triosmium and triruthenium carbonyl clusters has been studied. Heating [Os3(CO)12] with dppf in the presence of Me3NO in benzene at 60 C furnishes three triosmium compounds, [Os3(CO)11(1-dppf)] (1), [Os3(CO)10(2-dppf)] (2), and [Os3(CO)10(-dppf)] (3) in 10, 20, and 30% yields, respectively. Reaction of the labile cluster [Os3(CO)10(MeCN)2] with dppf at room temperature also gives 1, 2, and 3 (5, 10, and 35% yields). Treatment of 1, which contains a pendant diphosphine, with Me3NO at room temperature affords 2 via a ring closure reaction, whereas heating 2, in which the dppf ligand is chelating, at 110 C affords the thermodynamically stable bridging isomer 3, in which phosphorus atoms are bound at equatorial positions. Reaction of the unsaturated cluster [Os3(CO)10(-H)2] (4) with dppf in refluxing THF affords the bridging complex [Os3(CO)8(-dppf)(-H)2] (6) in high yield as the sole product. Hydrogenation of 3 with H2 at 110 C at 1 atm also yields 6. Reactions of both the saturated [Os3(CO)10(-dppm)] (7) and electron-deficient [Os3(CO)8{3-Ph2PCH2P(Ph)C6H4}(-H)] (8) with dppf at 110 C and at room temperature respectively yield [Os3(CO)9(-dppm)(1-dppf)] (9) and [Os3(CO)8(-dppm)(2-dppf)] (10). Compound 9 converts to 10 at 110 C via CO loss and phosphorus coordination. Reaction of [Ru3(CO)12] with dppf in the presence of Me3NO affords the dihydroxy-bridged complex, [Ru3(CO)8(-dppf)(-OH)2] (13), together with the previously reported compounds [Ru3(CO)10(-dppf)] (11) and [Ru3(CO)8(-dppf)2] (12).
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| 14. |
- Begum, Shamim A., et al.
(författare)
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Adsorption isotherm and kinetic studies of As(V) removal from aqueous solution using cattle bone char
- 2016
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Ingår i: Journal of Water Supply. - : IWA Publishing. - 0003-7214 .- 1365-2087. ; 65:3, s. 244-252
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Tidskriftsartikel (refereegranskat)abstract
- The As(V) adsorption onto bone char was investigated as a function of bone char dosage, pH and contact time in batch tests. The initial As(V) concentrations were varied from 0.1 to 1 mg/L to evaluate the adsorption kinetics and isotherm. The As(V) concentrations were analyzed using a graphite furnace atomic absorption spectrophotometer. The highest As(V) removal was found to be 62% after 3 d using 3 g bone char at a pH level of 4.0 for 0.5 mg/L As(V) concentration. The maximum adsorption capacity was 0.13 for 1 mg/L As(V) concentration. A Langmuir isotherm and second order adsorption kinetics were observed for As(V) adsorption.
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| 15. |
- Begum, Y. A., et al.
(författare)
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In situ Analyses Directly in Diarrheal Stool Reveal Large Variations in Bacterial Load and Active Toxin Expression o Enterotoxigenic Escherichia coli and Vibrio cholerae
- 2018
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Ingår i: Msphere. - 2379-5042. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial pathogens enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae are major causes of diarrhea. ETEC causes diarrhea by production of the heat-labile toxin (LT) and heat-stable toxins (STh and STp), while V. cholerae produces cholera toxin (CT). In this study, we determined the occurrence and bacterial doses of the two pathogens and their respective toxin expression levels directly in liquid diarrheal stools of patients in Dhaka, Bangladesh. By quantitative culture and real-time quantitative PCR (qPCR) detection of the toxin genes, the two pathogens were found to coexist in several of the patients, at concentrations between 10(2) and 10(8) bacterial gene copies per ml. Even in culture-negative samples, gene copy numbers of 10(2) to 10(4) of either ETEC or V. cholerae toxin genes were detected by qPCR. RNA was extracted directly from stool, and gene expression levels, quantified by reverse transcriptase qPCR (RT-qPCR), of the genes encoding CT, LT, STh, and STp showed expression of toxin genes. Toxin enzyme-linked immunosorbent assay (ELISA) confirmed active toxin secretion directly in the liquid diarrhea. Analysis of ETEC isolates by multiplex PCR, dot blot analysis, and genome sequencing suggested that there are genetic ETEC profiles that are more commonly found as dominating single pathogens and others that are coinfectants with lower bacterial loads. The ETEC genomes, including assembled genomes of dominating ETEC isolates expressing LT/STh/CS5/CS6 and LT/CS7, are provided. In addition, this study highlights an emerging important ETEC strain expressing LT/STp and the novel colonization factor CS27b. These findings have implications for investigations of pathogenesis as well as for vaccine development.& para;& para;IMPORTANCE The cause of diarrhea! disease is usually determined by screening for several microorganisms by various methods, and sole detection is used to assign the agent as the cause of disease. However, it has become increasingly clear that many infections are caused by coinfections with several pathogens and that the dose of the infecting pathogen is important. We quantified the absolute numbers of enterotoxigenic E. coil (ETEC) and Vibrio cholerae directly in diarrheal fluid. We noted several events where both pathogens were found but also a large dose dependency. In three samples, we found ETEC as the only pathogen sought for. These isolates belonged to globally distributed ETEC clones and were the dominating species in stool with active toxin expression. This suggests that certain superior virulent ETEC lineages are able to outcompete the gut microbiota and be the sole cause of disease and hence need to be specifically monitored.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Dwivedi, Garima, et al.
(författare)
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Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system
- 2022
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease. Methods: Osteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin’s grade 0–2, 23–83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile. Results: Immediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified. Conclusion: CBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression.
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| 21. |
- Farooqi, Zahoor H., et al.
(författare)
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Microfluidic Fabrication and Applications of Microgels and Hybrid Microgels
- 2023
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Ingår i: Critical reviews in analytical chemistry. - : Informa UK Limited. - 1040-8347 .- 1547-6510.
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Forskningsöversikt (refereegranskat)abstract
- Smart microgels have gained much attention because of their wide range of applications in the field of biomedical, environmental, nanotechnological and catalysis sciences. Most of the applications of microgels are strongly affected by their morphology, size and size distribution. Various methodologies have been adopted to obtain polymer microgel particles. Droplet microfluidic techniques have been widely reported for the fabrication of highly monodisperse microgel particles to be used for various applications. Monodisperse microgel particles of required size and morphology can be achieved via droplet microfluidic techniques by simple polymerization of monomers in the presence of suitable crosslinker or by gelation of high molecular weight polymers. This report gives recent research progress in fabrication, characterization, properties and applications of microgel particles synthesized by microfluidic methods.
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| 22. |
- Good, James A. D., 1985-, et al.
(författare)
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Attenuating Listeria monocytogenes virulence by targeting the regulatory protein PrfA
- 2016
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Ingår i: Cell chemical biology. - : Elsevier BV. - 2451-9448 .- 2451-9456. ; 23:3, s. 404-414
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Tidskriftsartikel (refereegranskat)abstract
- The transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring-fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes infectivity by reducing the expression of virulence genes, without compromising bacterial growth. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds within a hydrophobic pocket, located between the C- and N-terminal domains of PrfA, and interacts with residues important for PrfA activation. This indicates that these inhibitors maintain the DNA-binding helix-turn-helix motif of PrfA in a disordered state, thereby preventing a PrfA:DNA interaction. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes.
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| 23. |
- Hall, Michael, et al.
(författare)
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Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:51, s. 14733-14738
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Tidskriftsartikel (refereegranskat)abstract
- Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell. The crystal structure of PrfAWT in complex only with DNA confirms that PrfAWT can adopt a DNA binding-compatible structure without binding the GSH activator molecule. By binding to PrfA in the cytosol of the host cell, GSH induces the correct fold of the HTH motifs, thus priming the PrfA protein for DNA interaction.
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| 24. |
- Hendry, Alexandra, et al.
(författare)
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Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
- 2020
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Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
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Tidskriftsartikel (refereegranskat)abstract
- Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
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| 25. |
- Hyder, A. H. M. Golam, et al.
(författare)
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Adsorption isotherm and kinetic studies of hexavalent chromium removal from aqueous solution onto bone char
- 2015
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Ingår i: Journal of Environmental Chemical Engineering. - : Elsevier. - 2213-3437. ; 3:2, s. 1329-1336
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of hexavalent chromium [Cr(VI)] onto bone char was optimized as a function of pH, initial Cr(VI) concentration, and bone char dosage using aqueous solution in batch tests. The initial Cr(VI) concentrations were varied between 5 and 800 mg/L to investigate equilibrium, kinetics, and the adsorption isotherms. About 100% of Cr(VI) was removed at initial pH of 1.0 with initial Cr(VI) concentration of 10 mg/L, using 2 g of bone char after 2 h. The maximum adsorption capacity of the bone char was 4.8 mg/g for an initial Cr(VI) concentration of 800 mg/L. The adsorption kinetics of Cr(VI) onto bone char followed a second order kinetic model. The adsorption isotherm followed the Langmuir model for Cr(VI) adsorption. In general, bone char demonstrated promising results as an effective adsorbent for removal of Cr(VI) from the aqueous solution. The results from this study could be useful in designing a filtration unit with bone char as the adsorbent in a full-scale water and wastewater treatment plant for the removal of Cr(VI) from contaminated water.
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| 26. |
- Hyder, A. H. M. Golam, et al.
(författare)
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Sorption studies of Cr(VI) from aqueous solution using bio-char as an adsorbent
- 2014
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 69:11, s. 2265-2271
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Tidskriftsartikel (refereegranskat)abstract
- The characteristics of sorption of hexavalent chromium (Cr(VI)) onto bio-char derived from wood chips (spruce, pine, and fir) were evaluated as a function of pH, initial Cr(VI) concentration and bio-char dosage using synthetic wastewater in batch tests. The initial Cr(VI) concentrations were varied between 10 and 500 mg/L to investigate equilibrium, kinetics, and isotherms of the sorption process. About 100% of Cr(VI) was removed at pH 2 with initial Cr(VI) concentration of 10 mg/L using 4 g of bio-char after 5 hours of sorption reaction. The maximum sorption capacity of the bio-char was 1.717 mg/g for an initial Cr(VI) concentration of 500 mg/L after 5 hours. The sorption kinetics of total Cr onto bio-char followed the second-order kinetic model. The Langmuir isotherm model provided the best fit for total Cr sorption onto bio-char. The bio-char used is a co-product of a down draft gasifier that uses the derived syngas to produce electricity. Bio-char as a low cost adsorbent demonstrated promising results for removal of Cr(VI) from aqueous solution. The findings of this study would be useful in designing a filtration unit with bio-char in a full-scale water and wastewater treatment plant for the Cr(VI) removal from contaminated waters.
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| 27. |
- Johnson, David C, et al.
(författare)
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Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma.
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22-1.48, P=4.69 × 10(-9)). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors.
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| 28. |
- Kulén, Martina, et al.
(författare)
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Structure-based design of inhibitors targeting PrfA, the master virulence regulator of Listeria monocytogenes
- 2018
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:9, s. 4165-4175
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Tidskriftsartikel (refereegranskat)abstract
- Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intraprotein "tunnel" as the main inhibitor binding site (A1), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix−turn−helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-A1 selective PrfA inhibitors with potent antivirulence properties.
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| 29. |
- Nelson, Greg L., et al.
(författare)
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Differentiated Assessments for Advanced Courses that Reveal Issues with Prerequisite Skills : A Design Investigation
- 2020
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Ingår i: ITICSE-WGR'20. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450382939 ; , s. 75-129
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Konferensbidrag (refereegranskat)abstract
- Computing learners may not master basic concepts, or forget them between courses or from infrequent use. Learners also often struggle with advanced computing courses, perhaps from weakness with prerequisite concepts. One underlying challenge for researchers and instructors is determining the reason why a learner gets an advanced question wrong. Was the wrong answer because the learner lacked prerequisite skills, has not mastered the advanced skill, or some combination of the two? We contribute a design investigation into how to create differentiated questions which diagnose prerequisite and advanced skills at the same time. We focused on tracing and related skills as prerequisites, and on advanced object-oriented programming, concurrency, algorithm and data structures as the advanced skills. We conducted an inductive qualitative analysis of existing assessment questions from instructors and from a concept inventory with a validity argument (the Basic Data Structures Inventory). We found dependencies on a variety of prerequisite knowledge and mixed potential for diagnosing difficulties with prerequisites. Inspired by this analysis, we developed examples of differentiated assessments and reflected on design principles for creating/modifying assessments to better assess both advanced and prerequisite skills. Our example differentiated assessment questions and methods help enable research into how prerequisites skills affect learning of advanced concepts. They also may help instructors better understand and help learners with varying prerequisite knowledge, which may improve equity of learning outcomes. Our work also raises theoretical questions about what assessments really assess and how separate advanced topics and prerequisite skills are.
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| 30. |
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| 31. |
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| 33. |
- Visser, Gerard H A, et al.
(författare)
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FIGO opinion paper: Drivers and solutions to the cesarean delivery epidemic with emphasis on the increasing rates in Africa and Southeastern Europe.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - 1879-3479. ; 163:Suppl 2, s. 5-9
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Tidskriftsartikel (refereegranskat)abstract
- Cesarean delivery rates are rapidly increasing in Southeastern Europe (to more than 60%), North Africa (with a rate as high as 72% in Egypt), and in urban areas in Southern Africa (a rate of over 50% in Lagos, Nigeria). Data on the background to these increases are scarce, but likely to include poor birthing facilities in general hospitals, convenience for the doctor, private medicine, fear of litigation, socioeconomic status, shortage of midwives and nurses, and disappearance of vaginal instrumental deliveries. Options to reverse cesarean delivery trends are discussed. In this context there is a need to be better informed about how women are being counseled regarding vaginal or cesarean delivery. The long-term consequences in subsequent pregnancies for mothers and children may well be largely ignored, while these risks are highest in LMICs where higher birth numbers are desired. FIGO has begun discussions with obstetric and gynecologic societies, healthcare bodies, and governments in several countries discussed in this article, to find ways to lower the cesarean delivery rate. The requests came from the countries themselves, which may prove beneficial in helping advance progress.
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| 34. |
- Waeijen-Smit, Kiki, et al.
(författare)
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Global mortality and readmission rates following COPD exacerbation-related hospitalisation : a meta-analysis of 65 945 individual patients
- 2024
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations < 12 months prior to the index event. Conclusions This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.
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