| 1. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - : Societa Italiana di Fisica. - 1029-8479 .- 1126-6708. ; :8
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :8
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 6. |
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| 7. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 8. |
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| 9. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 10. |
- Chami, Nathalie, et al.
(författare)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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| 11. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 12. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 13. |
- Fajar, Jonny Karunia, et al.
(författare)
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Global Prevalence and Potential Influencing Factors of COVID-19 Vaccination Hesitancy : A Meta-Analysis
- 2022
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 10:8
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Forskningsöversikt (refereegranskat)abstract
- Countries worldwide have deployed mass COVID-19 vaccination drives, but there are people who are hesitant to receive the vaccine. Studies assessing the factors associated with COVID-19 vaccination hesitancy are inconclusive. This study aimed to assess the global prevalence of COVID-19 vaccination hesitancy and determine the potential factors associated with such hesitancy. We performed an organized search for relevant articles in PubMed, Scopus, and Web of Science. Extraction of the required information was performed for each study. A single-arm meta-analysis was performed to determine the global prevalence of COVID-19 vaccination hesitancy; the potential factors related to vaccine hesitancy were analyzed using a Z-test. A total of 56 articles were included in our analysis. We found that the global prevalence of COVID-19 vaccination hesitancy was 25%. Being a woman, being a 50-year-old or younger, being single, being unemployed, living in a household with five or more individuals, having an educational attainment lower than an undergraduate degree, having a non-healthcare-related job and considering COVID-19 vaccines to be unsafe were associated with a higher risk of vaccination hesitancy. In contrast, living with children at home, maintaining physical distancing norms, having ever tested for COVID-19, and having a history of influenza vaccination in the past few years were associated with a lower risk of hesitancy to COVID-19 vaccination. Our study provides valuable information on COVID-19 vaccination hesitancy, and we recommend special interventions in the sub-populations with increased risk to reduce COVID-19 vaccine hesitancy.
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| 14. |
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| 15. |
- Vangeti, Sindhu, 1989-, et al.
(författare)
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Serum Fc-Mediated Monocyte Phagocytosis Activity Is Stable for Several Months after SARS-CoV-2 Asymptomatic and Mildly Symptomatic Infection
- 2022
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the temporal profile of multiple components of the serological response after asymptomatic or mildly symptomatic SARS-CoV-2 infection, in a cohort of 67 previously SARS-CoV-2 naive young adults, up to 8.5 months after infection. We found a significant decrease of spike IgG and neutralization antibody titers from early (11 to 56 days) to late (4 to 8.5 months) time points postinfection. Over the study period, S1-specific IgG levels declined significantly faster than that of the S2-specific IgG. Further, serum antibodies from PCR-confirmed participants cross-recognized S2, but not S1, of the betacoronaviruses HKU1 and OC43, suggesting a greater degree of cross-reactivity of S2 among betacoronaviruses. Antibody-Dependent Natural Killer cell Activation (ADNKA) was detected at the early time point but significantly decreased at the late time point. Induction of serum Antibody-Dependent Monocyte Phagocytosis (ADMP) was detected in all the infected participants, and its levels remained stable over time. Additionally, a reduced percentage of participants had detectable neutralizing activity against the Beta (50%), Gamma (61 to 67%), and Delta (90 to 94%) variants, both early and late postinfection, compared to the ancestral strain (100%). Antibody binding to S1 and RBD of Beta, Gamma, Delta (1.7 to 2.3-fold decrease), and Omicron (10 to 16-fold decrease) variants was also significantly reduced compared to the ancestral SARS-CoV-2 strain. Overall, we found variable temporal profiles of specific components and functionality of the serological response to SARS-CoV-2 in young adults, which is characterized by lasting, but decreased, neutralizing activity and antibody binding to S1, stable ADMP activity, and relatively stable S2-specific IgG levels.
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| 16. |
- Zhukova, Nataliya, et al.
(författare)
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WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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| 17. |
- Alegiry, Mohamed H., et al.
(författare)
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Attitudes Toward Psychological Disorders and Alternative Medicine in Saudi Participants
- 2021
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study was designed to investigate Saudis' attitudes toward mental distress and psychotropic medication, attribution of causes, expected side effects, and to analyze participants' expectations toward alternative or complementary medicine using aromatic and medicinal plants, through a survey.Method: The study included 674 participants (citizens and residents in Saudi Arabia) who were randomly contacted via email and social media and gave their consent to complete a questionnaire dealing with 39 items that can be clustered in six parts. Descriptive statistics and Chi-square for cross-tabulation were generated using SPSS.Results: Among the 664 participants, 73.4% believed that there are some positive and negative outcomes of psychotropic medication. Participants (72.0%) think that the most important reason leading to psychological disorders is mainly due to the loss of a relative or beloved person, and 73.9% considered psychic session as one of the possible treatments of psychological disorders. Surprisingly, only 18.8% of the participants agreed that medicinal and aromatic plants could be a possible treatment of the psychological disorder. Participants (82%) consider that physicians are the most trustful and preferred source of information about alternative and complementary medicine.
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| 18. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 19. |
- Burney, Peter, et al.
(författare)
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Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study
- 2021
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 203:11, s. 1353-1365
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD).Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors.Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks.Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites.Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
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| 20. |
- Chambers, John C., et al.
(författare)
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Genetic loci influencing kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 373-375
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Tidskriftsartikel (refereegranskat)abstract
- Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
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| 21. |
- Eberhardt, Mirjam, et al.
(författare)
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H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway.
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5:Jul 15
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Tidskriftsartikel (refereegranskat)abstract
- Nitroxyl (HNO) is a redox sibling of nitric oxide (NO) that targets distinct signalling pathways with pharmacological endpoints of high significance in the treatment of heart failure. Beneficial HNO effects depend, in part, on its ability to release calcitonin gene-related peptide (CGRP) through an unidentified mechanism. Here we propose that HNO is generated as a result of the reaction of the two gasotransmitters NO and H2S. We show that H2S and NO production colocalizes with transient receptor potential channel A1 (TRPA1), and that HNO activates the sensory chemoreceptor channel TRPA1 via formation of amino-terminal disulphide bonds, which results in sustained calcium influx. As a consequence, CGRP is released, which induces local and systemic vasodilation. H2S-evoked vasodilatatory effects largely depend on NO production and activation of HNO-TRPA1-CGRP pathway. We propose that this neuroendocrine HNO-TRPA1-CGRP signalling pathway constitutes an essential element for the control of vascular tone throughout the cardiovascular system.
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| 22. |
- Hoffman, Lindsey M., et al.
(författare)
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Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG) : A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries
- 2018
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:19, s. 1963-1972
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Tidskriftsartikel (refereegranskat)abstract
- PurposeDiffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs).Materials and MethodsData abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia.ResultsAmong 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration (P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002).ConclusionWe report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.
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| 23. |
- Kliemann, Nathalie, et al.
(författare)
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Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition
- 2021
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.Methods: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.Results: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30–1.74), WC (OR1-sd 1.46, 95% CI 1.27–1.69), and WHR (OR1-sd 1.54, 95% CI 1.33–1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07–1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06–0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05–0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32–0.87, p = 0.01).Conclusions: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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| 24. |
- Perley, Daniel A., et al.
(författare)
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Real-time discovery of AT2020xnd : a fast, luminous ultraviolet transient with minimal radioactive ejecta
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 508:4, s. 5138-5147
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Tidskriftsartikel (refereegranskat)abstract
- The many unusual properties of the enigmatic AT2018cow suggested that at least some subset of the empirical class of fast blue optical transients (FBOTs) represents a genuinely new astrophysical phenomenon. Unfortunately, the intrinsic rarity and fleeting nature of these events have made it difficult to identify additional examples early enough to acquire the observations necessary to constrain theoretical models. We present here the Zwicky Transient Facility discovery of AT2020xnd (ZTF20acigmel, the 'Camel') at z = 0.243, the first unambiguous AT2018cow analogue to be found and confirmed in real time. AT2018cow and AT2020xnd share all key observational properties: a fast optical rise, sustained high photospheric temperature, absence of a second peak attributable to ejection of a radioactively heated stellar envelope, extremely luminous radio, millimetre, and X-ray emission, and a dwarf-galaxy host. This supports the argument that AT2018cow-like events represent a distinct phenomenon from slower-evolving radio-quiet supernovae, likely requiring a different progenitor or a different central engine. The sample properties of the four known members of this class to date disfavour tidal disruption models but are consistent with the alternative model of an accretion powered jet following the direct collapse of a massive star to a black hole. Contextual filtering of alert streams combined with rapid photometric verification using multiband imaging provides an efficient way to identify future members of this class, even at high redshift.
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| 25. |
- Stamps, R. L., et al.
(författare)
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The 2014 Magnetism Roadmap
- 2014
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Ingår i: Journal of Physics D-Applied Physics. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 47:33
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Tidskriftsartikel (refereegranskat)abstract
- Magnetism is a very fascinating and dynamic field. Especially in the last 30 years, there have been many major advances in a range of areas from novel fundamental phenomena to new products. Applications such as hard disc drives and magnetic sensors are part of our daily life and new applications, such as in non-volatile computer random access memory, are expected to surface shortly. Thus it is an opportune time for describing the current status and current and future challenges in the form of a roadmap article. The 2014 Magnetism Roadmap provides a view on several selected, presently very active innovative developments. It consists of twelve sections, each written by an expert in the field and addressing a specific subject, with a strong emphasis on future potential. This Roadmap cannot cover the entire field. Several highly relevant areas have been selected without attempting to provide a full review - a future update will aim to address further. The scope covers mostly nanomagnetic phenomena and applications, where surfaces and interfaces provide additional functionality. New developments in fundamental topics such as interacting nanoelements, novel magnon-based spintronics concepts, spin-orbit torques and spin-caloric phenomena are addressed. New materials such as organic magnetic materials and permanent magnets are covered. New applications are presented such as nanomagnetic logic, non-local and domain-wall based devices, heat-assisted magnetic recording, magnetic random access memory and applications in biotechnology. This Roadmap acts to serve as a guideline for future emerging research directions in modern magnetism.
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| 26. |
- Torchia, Jonathon, et al.
(författare)
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Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
- 2015
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
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Tidskriftsartikel (refereegranskat)abstract
- Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
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| 27. |
- van der Vlegel, Marjolein, et al.
(författare)
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Health care utilization and outcomes in older adults after Traumatic Brain Injury : a CENTER-TBI study
- 2022
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Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 53:8, s. 2774-2782
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI.METHODS: We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury.RESULTS: Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms.CONCLUSION: The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.
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| 28. |
- Voormolen, Daphne C., et al.
(författare)
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Post-Concussion Symptoms in Complicated vs. Uncomplicated Mild Traumatic Brain Injury Patients at Three and Six Months Post-Injury : Results from the CENTER-TBI Study
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the occurrence of post-concussion symptoms and post-concussion syndrome (PCS) in a large cohort of patients after complicated and uncomplicated mild traumatic brain injury (mTBI) at three and six months post-injury. Patients were included through the prospective cohort study: Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI). Patients enrolled with mTBI (Glasgow Coma Scale 13-15) were further differentiated into complicated and uncomplicated mTBI based on the presence or absence of computed tomography abnormalities, respectively. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) assessed post-concussion symptoms and PCS according to the mapped ICD-10 classification method. The occurrence of post-concussion symptoms and syndrome at both time points was calculated. Chi square tests were used to test for differences between and within groups. Logistic regression was performed to analyse the association between complicated versus uncomplicated mTBI and the prevalence of PCS. Patients after complicated mTBI reported slightly more post-concussion symptoms compared to those after uncomplicated mTBI. A higher percentage of patients after complicated mTBI were classified as having PCS at three (complicated: 46% vs. uncomplicated: 35%) and six months (complicated: 43% vs. uncomplicated 34%). After adjusting for baseline covariates, the effect of complicated versus uncomplicated mTBI at three months appeared minimal: odds ratio 1.25 (95% confidence interval: 0.95-1.66). Although patients after complicated mTBI report slightly more post-concussion symptoms and show higher PCS rates compared to those after uncomplicated mTBI at three and six months, complicated mTBI was only found a weak indicator for these problems.
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| 29. |
- Abdelrahim, Nada A., et al.
(författare)
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Human herpes virus type-6 is associated with central nervous system infections in children in Sudan
- 2022
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Ingår i: African Journal of Laboratory Medicine. - : AOSIS. - 2225-2002 .- 2225-2010. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30-44 × 103 copies/PCR run [12 × 103 - 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.
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| 30. |
- Al-Haddad, Benjamin J S, et al.
(författare)
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The fetal origins of mental illness.
- 2019
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 221:6, s. 549-562
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Forskningsöversikt (refereegranskat)abstract
- The impact of infections and inflammation during pregnancy on the developing fetal brain remains incompletely defined, with important clinical and research gaps. Although the classic infectious TORCH pathogens (ie, Toxoplasma gondii, rubella virus, cytomegalovirus [CMV], herpes simplex virus) are known to be directly teratogenic, emerging evidence suggests that these infections represent the most extreme end of a much larger spectrum of injury. We present the accumulating evidence that prenatal exposure to a wide variety of viral and bacterial infections-or simply inflammation-may subtly alter fetal brain development, leading to neuropsychiatric consequences for the child later in life. The link between influenza infections in pregnant women and an increased risk for development of schizophrenia in their children was first described more than 30 years ago. Since then, evidence suggests that a range of infections during pregnancy may also increase risk for autism spectrum disorder and depression in the child. Subsequent studies in animal models demonstrated that both pregnancy infections and inflammation can result in direct injury to neurons and neural progenitor cells or indirect injury through activation of microglia and astrocytes, which can trigger cytokine production and oxidative stress. Infectious exposures can also alter placental serotonin production, which can perturb neurotransmitter signaling in the developing brain. Clinically, detection of these subtle injuries to the fetal brain is difficult. As the neuropsychiatric impact of perinatal infections or inflammation may not be known for decades after birth, our construct for defining teratogenic infections in pregnancy (eg, TORCH) based on congenital anomalies is insufficient to capture the full adverse impact on the child. We discuss the clinical implications of this body of evidence and how we might place greater emphasis on prevention of prenatal infections. For example, increasing uptake of the seasonal influenza vaccine is a key strategy to reduce perinatal infections and the risk for fetal brain injury. An important research gap exists in understanding how antibiotic therapy during pregnancy affects the fetal inflammatory load and how to avoid inflammation-mediated injury to the fetal brain. In summary, we discuss the current evidence and mechanisms linking infections and inflammation with the increased lifelong risk of neuropsychiatric disorders in the child, and how we might improve prenatal care to protect the fetal brain.
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| 31. |
- Aleksandrova, Krasimira, et al.
(författare)
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Physical activity, mediating factors and risk of colon cancer : insights into adiposity and circulating biomarkers from the EPIC cohort
- 2017
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 46:6, s. 1823-1835
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Tidskriftsartikel (refereegranskat)abstract
- There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
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| 32. |
- Amroussia, Nada, et al.
(författare)
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Explaining mental health inequalities in Northern Sweden : a decomposition analysis
- 2017
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: There has been a substantial increase of income inequalities in Sweden over the last 20 years, which also could be reflected in health inequalities, including mental health inequalities. Despite the growing body of literature focusing on health inequalities in Sweden, income-related inequalities in mental health have received little attention. Particularly scarce are research from Northern Sweden and examinations of the social determinants of health inequalities.Objectives: The present study seeks to provide evidence regarding inequalities in mental health in Northern Sweden. The specific aims were to (1) quantify the income-related inequality in mental health in Northern Sweden, and (2) determine the contribution of social determinants to the inequality.Methods: The study population comprised 25,646 participants of the 2014 Health on Equal Terms survey in the four northernmost counties of Sweden, aged 16 to 84 years old. Income-related inequalities in mental health were quantified by the concentration index and further decomposed by applying Wagstaff-type decomposition analysis.Results: The overall concentration index of mental health in Northern Sweden was −0.15 (95% CI: −0.17 to −0.13), indicating income inequalities in mental health disfavoring the less affluent population. The decomposition analysis results revealed that socio-economic conditions, including employment status (31%), income (22.6%), and cash margin (14%), made the largest contribution to the pro-rich inequalities in mental health. The second-largest contribution came from demographic factors, mainly age (11.3%) and gender (6%). Psychosocial factors were of smaller importance, with perceived discrimination (8%) and emotional support (3.4%) making moderate contributions to the health inequalities. Conclusions: The present study demonstrates substantial income-related mental health inequalities in Northern Sweden, and provides insights into their underpinnings. These findings suggest that addressing the root causes is essential for promoting mental health equity in this region.
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| 33. |
- Bile, Ahmed Said, et al.
(författare)
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Assessing Vaccination Delivery Strategies for Zero-Dose and Under-Immunized Children in the Fragile Context of Somalia
- 2024
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Somalia is one of 20 countries in the world with the highest numbers of zero-dose children. This study aims to identify who and where zero-dose and under-vaccinated children are and what the existing vaccine delivery strategies to reach zero-dose children in Somalia are. This qualitative study was conducted in three geographically diverse regions of Somalia (rural/remote, nomadic/pastoralists, IDPs, and urban poor population), with government officials and NGO staff (n = 17), and with vaccinators and community members (n = 52). The data were analyzed using the GAVI Vaccine Alliance IRMMA framework. Nomadic populations, internally displaced persons, and populations living in remote and Al-shabaab-controlled areas are three vulnerable and neglected populations with a high proportion of zero-dose children. Despite the contextual heterogeneity of these population groups, the lack of targeted, population-specific strategies and meaningful engagement of local communities in the planning and implementation of immunization services is problematic in effectively reaching zero-dose children. This is, to our knowledge, the first study that examines vaccination strategies for zero-dose and under-vaccinated populations in the fragile context of Somalia. Evidence on populations at risk of vaccine-preventable diseases and barriers to vital vaccination services remain critical and urgent, especially in a country like Somalia with complex health system challenges.
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| 34. |
- Davison, Lucy J, et al.
(författare)
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Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 322-333
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Tidskriftsartikel (refereegranskat)abstract
- The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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| 35. |
- de Roos, Baukje, et al.
(författare)
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Targeting the delivery of dietary plant bioactives to those who would benefit most: from science to practical applications
- 2019
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 58:53 (suppl. 2), s. 65-73
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Forskningsöversikt (refereegranskat)abstract
- Background A healthy diet and optimal lifestyle choices are amongst the most important actions for the prevention of cardiometabolic diseases. Despite this, it appears difficult to convince consumers to select more nutritious foods. Furthermore, the development and production of healthier foods do not always lead to economic profits for the agro-food sector. Most dietary recommendations for the general population represent a "one-size-fits-all approach" which does not necessarily ensure that everyone has adequate exposure to health-promoting constituents of foods. Indeed, we now know that individuals show a high variability in responses when exposed to specific nutrients, foods, or diets. Purpose This review aims to highlight our current understanding of inter-individual variability in response to dietary bioactives, based on the integration of findings of the COST Action POSITIVe. We also evaluate opportunities for translation of scientific knowledge on inter-individual variability in response to dietary bioactives, once it becomes available, into practical applications for stakeholders, such as the agro-food industry. The potential impact from such applications will form an important impetus for the food industry to develop and market new high quality and healthy foods for specific groups of consumers in the future. This may contribute to a decrease in the burden of diet-related chronic diseases. Key messages Individual differences in ADME (Absorption, Digestion, Metabolism and Excretion) is believed to underpin much of the inter-individual variation in responses. Recent developments in the area of food metabolome databases and fast improvements in innovative metabotyping technologies hold great promise for improved profiling of dietary intake, exposure to individual ingredients, foods and dietary patterns, as well as our ability to identify individual responsiveness. The food industry needs well-defined population clusters or targets in order to be able to design "personalized products". There are indeed excellent industrial opportunities for foods that modulate gut microbiota, and thereby enable the delivery of food bioactive metabolites. It is currently not clear whether knowledge on individual nutrient needs, based on genetic or metagenomic data, would affect long-term dietary and health behaviours. Data to support the development of dietary recommendations may need to be generated by new n-of-1-based study designs in the future.
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| 36. |
- Dimitriadis, Georgios, et al.
(författare)
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SN 2021zny : an early flux excess combined with late-time oxygen emission suggests a double white dwarf merger event
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 521:1, s. 1162-1183
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Tidskriftsartikel (refereegranskat)abstract
- We present a photometric and spectroscopic analysis of the ultraluminous and slowly evolving 03fg-like Type Ia SN 2021zny. Our observational campaign starts from similar to 5.3 h after explosion (making SN 2021zny one of the earliest observed members of its class), with dense multiwavelength coverage from a variety of ground-and space-based telescopes, and is concluded with a nebular spectrum similar to 10 months after peak brightness. SN 2021zny displayed several characteristics of its class, such as the peak brightness (M-B = -19.95 mag), the slow decline (delta m(15)(B) = 0.62 mag), the blue early-time colours, the low ejecta velocities, and the presence of significant unburned material above the photosphere. However, a fluxexcess for the first similar to 1.5 d after explosion is observed in four photometric bands, making SN 2021zny the third 03fg-like event with this distinct behaviour, while its + 313 d spectrum shows prominent [OI] lines, a very unusual characteristic of thermonuclear SNe. The early flux excess can be explained as the outcome of the interaction of the ejecta with similar to 0 . 04 M-? of H/He-poor circumstellar material at a distance of similar to 10(12) cm, while the low ionization state of the late-time spectrum re veals lo w abundances of stable iron-peak elements. All our observations are in accordance with a progenitor system of two carbon/oxygen white dwarfs that undergo a merger event, with the disrupted white dwarf ejecting carbon-rich circumstellar material prior to the primary white dwarf detonation.
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| 37. |
- ElSayed, Doaa Ali, et al.
(författare)
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Validation and Cultural Adaptation of the Parent Attitudes about Childhood Vaccines (PACV) Questionnaire in Arabic Language Widely Spoken in a Region with a High Prevalence of COVID-19 Vaccine Hesitancy
- 2022
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Ingår i: Tropical Medicine and Infectious Disease. - : MDPI AG. - 2414-6366. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- The parents’ attitude toward vaccinating children and adolescents against coronavirus disease 2019 (COVID-19) remains inconsistent and needs further elucidation. The high rates of COVID-19 vaccine hesitancy in the Middle East and North Africa (MENA) region require intensive research to understand the determinants of this phenomenon. This study aimed to validate a version of the Parent Attitudes about Childhood Vaccines (PACV) tool in Arabic, the most widely spoken language in the MENA. The study objectives included the investigation of Arab-speaking parents’ views regarding COVID-19 vaccination of their children. Parents living in Egypt with at least one child aged 5–18 years were eligible to participate in the study that was conducted through an online survey with 15 PACV items. The PACV tool was translated into Arabic using forward and backward translation. To assess the psychometric properties of the Arabic version of PACV, Pearson’s correlation coefficient and exploratory and confirmatory factor analysis (EFA and CFA) were performed. A total of 223 parents participated in the study: 59.82% aged 30–39 years, 69.20% were females, 46.19% were university-educated, and 40.63% had one child. The overall Cronbach’s alpha for the Arabic version of PACV was 0.799. The EFA of the 15 items showed that three domains were most conceptually equivalent. All items had a positive significant correlation with the mean score of each subscale except for item 4 (r = 0.016, p = 0.811). Regression analyses results indicated that education, previous COVID-19 infection, vaccine status of parents, and PACV score were significantly associated with the intention of the parents to vaccinate their children against COVID-19. The CFA results showed that most of the factor loadings were statistically significant (p < 0.010) except for items 4 and 7. However, the root mean square error of approximation (RMSEA = 0.080) and the standardized root mean squared residual (SRMR = 0.080) indicated that the model had a reasonable fit, and the three factors were good in reproducing each correlation. Our study results indicated the validity and reliability of the PACV instrument in Arabic language. Consequently, the PACV can be used to assess COVID-19 vaccine hesitancy in a majority of MENA countries for better delineation of this highly prevalent phenomenon in the region.
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| 38. |
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| 39. |
- Koido, Kati, et al.
(författare)
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Lack of guidelines and translational knowledge is hindering the implementation of psychiatric genetic counseling and testing within Europe : A multi-professional survey study
- 2023
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Ingår i: European Journal of Medical Genetics. - : Elsevier. - 1769-7212 .- 1878-0849. ; 66:8
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Tidskriftsartikel (refereegranskat)abstract
- Genetic research has identified a large number of genetic variants, both rare and common, underlying neurodevelopmental disorders (NDD) and major psychiatric disorders. Currently, these findings are being translated into clinical practice. However, there is a lack of knowledge and guidelines for psychiatric genetic testing (PsychGT) and genetic counseling (PsychGC). The European Union-funded COST action EnGagE (CA17130) network was started to investigate the current implementation status of PsychGT and PsychGC across 35 participating European countries. Here, we present the results of a pan-European online survey in which we gathered the opinions, knowledge, and practices of a self-selected sample of professionals involved/interested in the field.We received answers from 181 respondents. The three main occupational categories were genetic counselor (21.0%), clinical geneticist (24.9%), and researcher (25.4%). Of all 181 respondents, 106 provide GC for any psychiatric disorder or NDD, corresponding to 58.6% of the whole group ranging from 43.2% in Central Eastern Europe to 66.1% in Western Europe. Overall, 65.2% of the respondents reported that genetic testing is offered to individuals with NDD, and 26.5% indicated the same for individuals with major psychiatric disorders. Only 22.1% of the respondents indicated that they have guidelines for PsychGT. Pharmacogenetic testing actionable for psychiatric disorders was offered by 15%. Interestingly, when genetic tests are fully covered by national health insurance, more genetic testing is provided for individuals with NDD but not those with major psychiatric disorders.Our qualitative analyses of responses highlight the lack of guidelines and knowledge on utilizing and using genetic tests and education and training as the major obstacles to implementation. Indeed, the existence of psychiatric genetic training courses was confirmed by only 11.6% of respondents. The question on the relevance of up-to-date education and training in psychiatric genetics on everyday related practice was highly relevant.We provide evidence that PsychGC and PsychGT are already in use across European countries, but there is a lack of guidelines and education. Harmonization of practice and development of guidelines for genetic counseling, testing, and training professionals would improve equality and access to quality care for individuals with psychiatric disorders within Europe.
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| 40. |
- Lindblom, Rickard P. F., et al.
(författare)
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Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response
- 2015
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking. Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2(-/-) mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures. Results: Expression of Cr2 in naive spinal cord was low but strongly up regulated at 5-7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA. Conclusions: These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.
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| 41. |
- Love-Gregory, Latisha, et al.
(författare)
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Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36
- 2016
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 57:12, s. 2176-2184
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Tidskriftsartikel (refereegranskat)abstract
- Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a approximate to 410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPAR, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce adipose and heart CD36 RNA expression to inter-individual variability of postprandial lipid metabolism and document changes in CD36 DNA methylation that influence both CD36 expression and lipids.
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| 42. |
- Lu, Y. L., et al.
(författare)
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Forty years of reform and opening up: China's progress toward a sustainable path
- 2019
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- After 40 years of reform and "opening up," China has made remarkable economic progress. Such economic prosperity, however, has been coupledwith environmental degradation. We analyze diverse long-termdata to determine whether China is experiencing a decoupling of economic growth and environmental impacts, and where China stands with respect to the Sustainable Development Goals (SDGs) in terms of reducing regional division, urban-rural gap, social inequality, and land-based impacts on oceans. The results highlight that China's desire to achieve " ecological civilization" has resulted in a decoupling trend for major pollutants since 2015, while strong coupling remainswith CO2 emissions. Progress has been made in health care provision, poverty reduction, and gender equity in education, while income disparity continues between regions and with rural-urban populations. There is a considerable way to go toward achieving delivery of the SDGs; however, China's progress toward economic prosperity and concomitant sustainability provides important insights for other countries.
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| 43. |
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| 44. |
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| 45. |
- Pirc, Katja, et al.
(författare)
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An oomycete NLP cytolysin forms transient small pores in lipid membranes
- 2022
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:10, s. eabj9406-
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Tidskriftsartikel (refereegranskat)abstract
- Microbial plant pathogens secrete a range of effector proteins that damage host plants and consequently constrain global food production. Necrosis and ethylene-inducing peptide 1-like proteins (NLPs) are produced by numerous phytopathogenic microbes that cause important crop diseases. Many NLPs are cytolytic, causing cell death and tissue necrosis by disrupting the plant plasma membrane. Here, we reveal the unique molecular mechanism underlying the membrane damage induced by the cytotoxic model NLP. This membrane disruption is a multistep process that includes electrostatic-driven, plant-specific lipid recognition, shallow membrane binding, protein aggregation, and transient pore formation. The NLP-induced damage is not caused by membrane reorganization or large-scale defects but by small membrane ruptures. This distinct mechanism of lipid membrane disruption is highly adapted to effectively damage plant cells.
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| 46. |
- Stepien, Magdalena, et al.
(författare)
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Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers : findings from a prospective cohort study
- 2016
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 138:2, s. 348-360
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Tidskriftsartikel (refereegranskat)abstract
- Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
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| 47. |
- Stromberg, E., et al.
(författare)
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Oral health-related quality-of-life in homebound elderly dependent on moderate and substantial supportive care for daily living
- 2013
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Ingår i: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 71:3-4, s. 771-777
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To describe the oral health-related quality-of-life in homebound elderly dependent on moderate and substantial supportive care for daily living. Materials and methods. A total of 302 selected persons in three counties in Sweden over 65 years of age and in need of daily support from society participated in the study. Half of the participants had moderate needs of support, defined as supportive care of 15-50 h per month and half had substantial needs of supportive care, i.e. 3-times a day with a night overview. An oral examination was performed and structured questions were asked about general health and living conditions, medication, oral care routines and quality-of-life, using the instrument GOHAI (Geriatric Oral Health Assessment Instrument). Results. Cardiovascular disease was common and an average of seven prescription drugs was used. More than half of the participants had dentures. The strongest correlation with GOHAI was the total number of teeth. There was a significant difference between individuals with moderate and substantial needs according to GOHAI, irrespective of gender. More elderly people with substantial needs of support had low GOHAI values. Decayed teeth, DT/T, root remnants and dry mouth were negatively correlated to GOHAI among individuals with substantial needs. Conclusions. This study found that elderly homebound individuals with substantial needs of supportive care had a lower quality-of-life than elderly homebound individuals with moderate needs of supportive care, although both medical and odontological variables were similar in the groups.
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| 48. |
- van Roekel, Eline H., et al.
(författare)
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Circulating metabolites associated with alcohol intake in the european prospective investigation into cancer and nutrition cohort
- 2018
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTMp180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption withmetabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.
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| 49. |
- Voormolen, Daphne C., et al.
(författare)
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Outcomes after Complicated and Uncomplicated Mild Traumatic Brain Injury at Three-and Six-Months Post-Injury : Results from the CENTER-TBI Study
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to provide a comprehensive examination of the relation of complicated and uncomplicated mild traumatic brain injury (mTBI) with multidimensional outcomes at three- and six-months after TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) research project. Patients after mTBI (Glasgow Coma scale (GCS) score of 13–15) enrolled in the study were differentiated into two groups based on computed tomography (CT) findings: complicated mTBI (presence of any traumatic intracranial injury on first CT) and uncomplicated mTBI (absence of any traumatic intracranial injury on first CT). Multidimensional outcomes were assessed using seven instruments measuring generic and disease-specific health-related quality of life (HRQoL) (SF-36 and QOLIBRI), functional outcome (GOSE), and psycho-social domains including symptoms of post-traumatic stress disorder (PTSD) (PCL-5), depression (PHQ-9), and anxiety (GAD-7). Data were analyzed using a multivariate repeated measures approach (MANOVA-RM), which inspected mTBI groups at three- and six-months post injury. Patients after complicated mTBI had significantly lower GOSE scores, reported lower physical and mental component summary scores based on the SF-36 version 2, and showed significantly lower HRQoL measured by QOLIBRI compared to those after uncomplicated mTBI. There was no difference between mTBI groups when looking at psychological outcomes, however, a slight improvement in PTSD symptoms and depression was observed for the entire sample from three to six months. Patients after complicated mTBI reported lower generic and disease specific HRQoL and worse functional outcome compared to individuals after uncomplicated mTBI at three and six months. Both groups showed a tendency to improve from three to six months after TBI. The complicated mTBI group included more patients with an impaired long-term outcome than the uncomplicated group. Nevertheless, patients, clinicians, researchers, and decisions-makers in health care should take account of the short and long-term impact on outcome for patients after both uncomplicated and complicated mTBI.
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| 50. |
- Wang, Qinan, et al.
(författare)
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Revealing the Progenitor of SN 2021zby through Analysis of the TESS Shock-cooling Light Curve
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 943:2
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Tidskriftsartikel (refereegranskat)abstract
- We present early observations and analysis of the double-peaked Type IIb supernova (SN IIb) SN 2021zby. TESS captured the prominent early shock-cooling peak of SN 2021zby within the first ∼10 days after explosion with a 30 minute cadence. We present optical and near-infrared spectral series of SN 2021zby, including three spectra during the shock-cooling phase. Using a multiband model fit, we find that the inferred properties of its progenitor are consistent with a red supergiant or yellow supergiant, with an envelope mass of ∼0.30–0.65 M⊙ and an envelope radius of ∼120–300 R⊙. These inferred progenitor properties are similar to those of other SNe IIb with a double-peaked feature, such as SNe 1993J, 2011dh, 2016gkg, and 2017jgh. This study further validates the importance of the high cadence and early coverage in resolving the shape of the shock-cooling light curve, while the multiband observations, particularly UV, are also necessary to fully constrain the progenitor properties.
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