| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Clark, DW, et al.
(author)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Journal article (peer-reviewed)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 4. |
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| 5. |
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| 6. |
- Limpens, J., et al.
(author)
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Climatic modifiers of the response to nitrogen deposition in peat-forming Sphagnum mosses : a meta-analysis
- 2011
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 191:2, s. 496-507
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Journal article (peer-reviewed)abstract
- Peatlands in the northern hemisphere have accumulated more atmospheric carbon (C) during the Holocene than any other terrestrial ecosystem, making peatlands long-term C sinks of global importance. Projected increases in nitrogen (N) deposition and temperature make future accumulation rates uncertain. Here, we assessed the impact of N deposition on peatland C sequestration potential by investigating the effects of experimental N addition on Sphagnum moss. We employed meta-regressions to the results of 107 field experiments, accounting for sampling dependence in the data. We found that high N loading (comprising N application rate, experiment duration, background N deposition) depressed Sphagnum production relative to untreated controls. The interactive effects of presence of competitive vascular plants and high tissue N concentrations indicated intensified biotic interactions and altered nutrient stochiometry as mechanisms underlying the detrimental N effects. Importantly, a higher summer temperature (mean for July) and increased annual precipitation intensified the negative effects of N. The temperature effect was comparable to an experimental application of almost 4 g N m(-2) yr(-1) for each 1 degrees C increase. Our results indicate that current rates of N deposition in a warmer environment will strongly inhibit C sequestration by Sphagnum-dominated vegetation.
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| 7. |
- Limpens, J., et al.
(author)
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Glasshouse vs field experiments : do they yield ecologically similar results for assessing N impacts on peat mosses?
- 2012
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 195:2, s. 408-418
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Journal article (peer-reviewed)abstract
- Peat bogs have accumulated more atmospheric carbon (C) than any other terrestrial ecosystem today. Most of this C is associated with peat moss (Sphagnum) litter. Atmospheric nitrogen (N) deposition can decrease Sphagnum production, compromising the C sequestration capacity of peat bogs. The mechanisms underlying the reduced production are uncertain, necessitating multifactorial experiments. We investigated whether glasshouse experiments are reliable proxies for field experiments for assessing interactions between N deposition and environment as controls on Sphagnum N concentration and production. We performed a meta-analysis over 115 glasshouse experiments and 107 field experiments. We found that glasshouse and field experiments gave similar qualitative and quantitative estimates of changes in Sphagnum N concentration in response to N application. However, glasshouse-based estimates of changes in production even qualitative assessments diverged from field experiments owing to a stronger N effect on production response in absence of vascular plants in the glasshouse, and a weaker N effect on production response in presence of vascular plants compared to field experiments. Thus, although we need glasshouse experiments to study how interacting environmental factors affect the response of Sphagnum to increased N deposition, we need field experiments to properly quantify these effects.
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| 8. |
- Gronwall, C, et al.
(author)
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THE RELATIONSHIP BETWEEN DIFFERENT IGG AND IGA ANTI-MODIFIED PROTEIN AUTOANTIBODIES IN RHEUMATOID ARTHRITIS
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 206-207
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Conference paper (other academic/artistic)abstract
- Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared
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| 9. |
- Tai, F, et al.
(author)
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Abdominal Wall Miscellaneous
- 2015
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In: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S5-S12
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Journal article (peer-reviewed)
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| 10. |
- Langefeld, Carl D., et al.
(author)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 11. |
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| 12. |
- Smith, Jennifer A, et al.
(author)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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In: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Journal article (peer-reviewed)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 13. |
- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 14. |
- Leeksma, AC, et al.
(author)
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Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study
- 2021
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:1, s. 87-97
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Journal article (peer-reviewed)abstract
- Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as ≥5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.
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| 15. |
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| 16. |
- Michalsen, B. O., et al.
(author)
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Regional and national antimicrobial stewardship activities: a survey from the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN)
- 2023
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In: Jac-Antimicrobial Resistance. - 2632-1823. ; 5:2
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Journal article (peer-reviewed)abstract
- Background Antibiotic overuse and misuse in primary care are common, highlighting the importance of antimicrobial stewardship (AMS) efforts in this setting. Audit and feedback (A&F) interventions can improve professional practice and performance in some settings. Objectives and methods To leverage the expertise from international members of the Joint Programming Initiative on Antimicrobial Resistance - Primary care Antibiotic Audit and feedback Network (JPIAMR-PAAN). Network members all have experience of designing and delivering A&F interventions to reduce inappropriate antibiotic prescribing in primary care settings. We aim to introduce the network and explore ongoing A&F activities in member regions. An online survey was administered to all network members to collect regional information. Results Fifteen respondents from 11 countries provided information on A&F activities in their country, and national/regional antibiotic stewardship programmes or policies. Most countries use electronic medical records as the primary data source, antibiotic appropriateness as the main outcome of feedback, and target GPs as the prescribers of interest. Funding sources varied across countries, which could influence the frequency and quality of A&F interventions. Nine out of 11 countries reported having a national antibiotic stewardship programme or policy, which aim to provide systematic support to ongoing AMS efforts and aid sustainability. Conclusions The survey identified gaps and opportunities for AMS efforts that include A&F across member countries in Europe, Canada and Australia. JPIAMR-PAAN will continue to leverage its members to produce best practice resources and toolkits for antibiotic A&F interventions in primary care settings and identify research priorities.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Ademuyiwa, Adesoji O., et al.
(author)
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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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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)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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| 22. |
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| 23. |
- Arias-Andrés, M., et al.
(author)
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Lower tier toxicity risk assessment of agriculture pesticides detected on the Rio Madre de Dios watershed, Costa Rica
- 2018
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In: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 25:14, s. 13312-13321
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Journal article (peer-reviewed)abstract
- Costa Rica is a tropical country with one of the highest biodiversity on Earth. It also has an intensive agriculture, and pesticide runoff from banana and pineapple plantations may cause a high toxicity risk to non-target species in rivers downstream the plantations. We performed a first tier risk assessment of the maximum measured concentrations of 32 pesticides detected over 4 years in the River Madre de Dios (RMD) and its coastal lagoon on the Caribbean coast of Costa Rica. Species sensitivity distributions (SSDs) were plotted in order to derive HC5 values for each pesticide, i.e., hazard concentrations for 5 % of the species, often used as environmental criteria values in other countries. We also carried out toxicity tests for selected pesticides with native Costa Rican species in order to calculate risk coefficients according to national guidelines in Costa Rica. The concentrations of herbicides diuron and ametryn and insecticides carbofuran, diazinon, and ethoprophos exceeded either the HC5 value or the lower limit of its 90 % confidence interval suggesting toxic risks above accepted levels. Risk coefficients of diuron and carbofuran derived using local guidelines indicate toxicity risks as well. The assessed fungicides did not present acute toxic risks according to our analysis. Overall, these results show a possible toxicity of detected pesticides to aquatic organisms and provide a comparison of Costa Rican national guidelines with more refined methods for risk assessment based on SSDs. Further higher tier risk assessments of pesticides in this watershed are also necessary in order to consider pesticide water concentrations over time, toxicity from pesticide mixtures, and eventual effects on ecosystem functions.
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| 24. |
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| 25. |
- Bremer, Johan, 1991, et al.
(author)
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Electric-Based Thermal Characterization of GaN Technologies Affected by Trapping Effects
- 2020
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In: IEEE Transactions on Electron Devices. - 1557-9646 .- 0018-9383. ; 67:5, s. 1952-1958
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Journal article (peer-reviewed)abstract
- This article presents an electric-based methodology for thermal characterization of semiconductor technologies. It is shown that for technologies such as gallium nitride (GaN) high electron mobility transistors, which exhibit several field induced electron trapping effects, the thermal characterization has to be performed under specific conditions. The electric field is limited to low levels to avoid activation of trap states. At the same time, the dissipated power needs to be high enough to change the operating temperature of the device. The method is demonstrated on a test structure implemented as a GaN resistor with large contact separation. It is used to evaluate the thermal properties of samples with different silicon carbide suppliers and buffer thickness.
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| 26. |
- Cederbrant, Karin, et al.
(author)
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In vitro Lymphoproliferative Assays with HgCl2 Cannot Identify Patients with Systemic Symptoms Attributed to Dental Amalgam
- 1999
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In: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 78:8, s. 1450-1458
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Journal article (peer-reviewed)abstract
- Dental amalgam is suspected, by some exposed individuals, to cause various systemic psychological, sensory, and neurological symptoms. Since not all amalgam-bearers experience such reactions, an individual characteristic—for example, a susceptible immune system—might explain these conditions. In vitro lymphocyte proliferation is a valuable tool in the diagnosis of allergy. With HgCl2 as the antigen, however, the test is hampered, because Hg2+ can cause unspecific lymphocyte proliferation, optimal at 1.4 to 9.5 μg HgCl2/mL. Recently, the use of suboptimal HgCl2 concentrations (≤ 0.5 μg/mL) has been suggested to circumvent these problems. The main aim of this study was to investigate whether patients with systemic symptoms alleged to result from the presence of dental amalgam differ from healthy controls, with reference to in vitro lymphoproliferative responses to HgCl2 ≤ 0.5 μg/mL. Three different test protocols—lymphocyte transformation test (LTT) in micro- and macro-cultures, and the memory lymphocyte immunostimulation assay (MELISA®)—were used. Other immune parameters—such as a standard patch test for dental materials, the number of T- and B-lymphocytes, monocytes, granulocytes, and NK cells in peripheral blood, allergic symptoms, and predisposition-were also investigated. Twenty-three amalgam patients, 30 healthy blood donors with amalgam, ten healthy subjects without amalgam, and nine patients with oral lichen planus (OLP) adjacent to dental amalgam and a positive patch test to Hg0 were tested. None of the investigated immune parameters revealed any significant differences between amalgam patients and controls. The sensitivity of in vitro lymphocyte proliferation ranged from 33 to 67%, with the OLP patients as a positive control group, and the specificity from 0 to 70% for healthy controls with a negative patch test to Hg°. Thus, despite the use of HgCl2 ≤ 0.5 μg/mL, a high frequency of positive results was obtained among healthy subjects with or without dental amalgam. Consequently, in vitro lymphocyte proliferation with HgCl2 cannot be used as an objective marker for mercury allergy in dental amalgam-bearers.
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| 27. |
- DAWODY, JAZAER, 1959, et al.
(author)
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E4-Mistra, a research program for the development of an energy efficient low emission exhaust aftertreatment system for heavy duty vehicles
- 2012
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In: World Renewable Energy Forum, WREF 2012, Including World Renewable Energy Congress XII and Colorado Renewable Energy Society (CRES) Annual Conference. - : American Solar Energy Society. - 9781622760923 ; , s. 4530-4536
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Conference paper (peer-reviewed)abstract
- This paper presents a unique system approach applied in a joint academic - industrial research program, E4 Mistra, to reach the goals of energy efficiency and low emissions exhaust aftertreatment system for heavy duty vehicles. The high energy efficiency is achieved by heat recuperation, on-board hydrogen production for use in both an auxiliary power unit and for NOx reduction and by finding new solutions for making the after-treatment system active at low exhaust temperatures. To reach low particulate emissions a mechanical filter using a sintered metal filter is developed. Low NOx emissions are achieved by an efficient NOx reduction catalyst. The system is based on four technological advances: Thermoelectric material s for heat recuperation, catalytic reduction of NOx over innovative catalyst substrates using hydrocarbons from the fuel and H2 from a high efficiency fuel reformer, and particulate filtration over a porous metal filter.
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| 28. |
- de la Vega, Maria Pagnon, et al.
(author)
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The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation
- 2021
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:606
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Journal article (peer-reviewed)abstract
- Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.
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| 29. |
- Ekelund, L, et al.
(author)
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Imaging of Four-Corner Fusion (SLAC Arthrodesis) of the Wrist with 64-Slice Computed Tomography.
- 2007
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In: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 48:1, s. 76-79
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Journal article (peer-reviewed)abstract
- Purpose: To find out whether it is possible to evaluate the healing of wrist arthrodesis, carried out with a metallic spider plate, by means of 64-slice computed tomography (CT). Material and Methods: 18 CT examinations were performed in 12 patients 2 weeks to 37 months following scapholunate advanced collapse (SLAC) arthrodesis fixed with a metallic plate. Ten patients also had plain films of the wrist. Radiation doses were estimated. Results: Plain films were difficult to evaluate due to overprojection of the spider plate. With 64-slice CT, however, it was possible to evaluate the healing process in all patients in spite of metallic artifacts. Radiation doses were low. Conclusion: The healing of SLAC arthrodesis of the wrist is difficult to evaluate with conventional radiography due to the metallic plate. By means of 64-slice CT, however, it was possible to “see under” the plate in all 12 patients.
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| 30. |
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| 31. |
- Gilbert, F., et al.
(author)
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Sediment reworking by the burrowing polychaete Hediste diversicolor modulated by environmental and biological factors across the temperate North Atlantic. A tribute to Gaston Desrosiers
- 2021
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In: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 541
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Journal article (peer-reviewed)abstract
- Particle mixing and irrigation of the seabed by benthic fauna (bioturbation) have major impacts on ecosystem functions such as remineralization of organic matter and sediment-water exchange. As a tribute to Prof. Gaston Desrosiers by the Nereis Park association, eighteen laboratories carried out a collaborative experiment to acquire a global snapshot of particle reworking by the polychaete Hediste diversicolor at 16 sites surrounding the Northern Atlantic. Organisms and soft sediments were collected during May - July at different geographical locations and, using a common laboratory protocol, particulate fluorescent tracers (`luminophores') were used to quantify particle transport over a 10-day period. Particle mixing was quantified using the maximum penetration depth of tracers (MPD), particle diffusive coefficients (D-b), and non-local transport coefficients (r). Non-local coefficients (reflecting centimeter scale transport steps) ranged from 0.4 to 15 yr(-1), and were not correlated across sites with any measured biological (biomass, biovolume) or environmental parameters (temperature, grain size, organic matter). Maximum penetration depths (MPD) averaged similar to 10.7 cm (6.5-14.5 cm), and were similar to the global average bioturbation depth inferred from short-lived radiochemical tracers. MPD was also not correlated with measures of size (individual biomass), but increased with grain size and decreased with temperature. Bio-diffusion (D-b) correlated inversely with individual biomass (size) and directly with temperature over the environmental range (Q(10) similar to 1.7; 5-21 degrees C). The transport data were comparable in magnitude to rates reported for localized H. diversicolor populations of similar size, and confirmed some but not all correlations between sediment reworking and biological and environmental variables found in previous studies. The results imply that measures of particle reworking activities of a species from a single location can be generally extrapolated to different populations at similar conditions.
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| 32. |
- Golding, Michael A., et al.
(author)
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The burden of food allergy on children and teens : A systematic review
- 2022
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In: Pediatric Allergy and Immunology. - : John Wiley & Sons. - 0905-6157 .- 1399-3038. ; 33:3
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Research review (peer-reviewed)abstract
- Background Over the last two decades, researchers have placed increasing attention on understanding how food allergy affects the health-related quality of life (HRQL) and psychosocial well-being of children and teens. In response, a number of reviews have been published that aim at synthesizing the literature. However, many of these papers focus narrowly on HRQL or suffer from methodological limitations.Method The current review aims to fill this gap by providing a comprehensive overview of the burden of pediatric food allergy by synthesizing the quantitative and qualitative literature.Results Findings from the present review provide evidence of reduced HRQL among children and teens with food allergy, particularly older children and those with more severe manifestations of the condition. In comparison to HRQL, the link between food allergy and psychosocial functioning is less clear; however, some evidence can be cited linking food allergy to greater levels of psychological distress. Qualitative evidence suggests that the burden of pediatric food allergy largely stems from worries surrounding exposures outside of the home and the social consequences of the condition. The current review also highlights several gaps in the literature, including a paucity of longitudinal research, research focused on predictors of psychological distress among children and teens with food allergy as well as a dearth of studies comparing rates of bullying in food-allergic and non-food-allergic samples.Conclusion More emphasis should be placed on not only alleviating the social and psychological consequences of food allergy, but also on identifying and assisting those most acutely burdened by the condition.
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| 33. |
- Gómez, M., et al.
(author)
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From agroindustries to integrated biomass logistics centres. Agroinlog project : Summary of final results
- 2020
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In: European Biomass Conference and Exhibition Proceedings. - : ETA-Florence Renewable Energies. ; , s. 941-952
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Conference paper (peer-reviewed)abstract
- AGROinLOG project has tested the integrated biomass logistics centres (IBLC) concept in three real agro-industries in Europe. The relevance of the IBLC strategy relies on the fact that it allows agro-industries to create a new activity with lower investment, increasing incomes, stabilizing their annual activity (avoiding idle periods) and maintaining or creating new jobs. The demos’ studies were performed in Spain at a fodder industry, in Greece at an olive oil industry, and in Sweden inside a cereal processing industry. AGROinLOG validated these demos´ business models from a holistic perspective, also studying the replicability of the IBLC business model in other agro-industries from different sectors (vegetable oil extraction, olive oil chain, feed & fodder, wine, grain chain and sugar industry). Sectorial analysis was carried out as well, allowing the identification of opportunities among the targeted sector to replicate the IBLC concept, drawing barriers to overcome in each case. Thus, technical, economic and environmental feasibility of integrated biomass logistics centers (IBLCs) for food and non-food products have been assessed in detail.
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| 34. |
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| 35. |
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| 36. |
- Gunnarsson, L., et al.
(author)
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Pharmacology beyond the patient - The environmental risks of human drugs
- 2019
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 129, s. 320-332
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Journal article (peer-reviewed)abstract
- Background: The presence of pharmaceuticals in the environment is a growing global concern and although environmental risk assessment is required for approval of new drugs in Europe and the USA, the adequacy of the current triggers and the effects-based assessments has been questioned. Objective: To provide a comprehensive analysis of all regulatory compliant aquatic ecotoxicity data and evaluate the current triggers and effects-based environmental assessments to facilitate the development of more efficient approaches for pharmaceuticals toxicity testing. Methods: Publicly-available regulatory compliant ecotoxicity data for drugs targeting human proteins was compiled together with pharmacological information including drug targets, Cmax and lipophilicity. Possible links between these factors and the ecotoxicity data for effects on, growth, mortality and/or reproduction, were evaluated. The environmental risks were then assessed based on a combined analysis of drug toxicity and predicted environmental concentrations based on European patient consumption data. Results: For most (88%) of the of 975 approved small molecule drugs targeting human proteins a complete set of regulatory compliant ecotoxicity data in the public domain was lacking, highlighting the need for both intelligent approaches to prioritize legacy human drugs for a tailored environmental risk assessment and a transparent database that captures environmental data. We show that presence/absence of drug-target orthologues are predictive of susceptible species for the more potent drugs. Drugs that target the endocrine system represent the highest potency and greatest risk. However, for most drugs ( > 80%) with a full set of ecotoxicity data, risk quotients assuming worst-case exposure assessments were below one in all European countries indicating low environmental risks for the endpoints assessed. Conclusion: We believe that the presented analysis can guide improvements to current testing procedures, and provide valuable approaches for prioritising legacy drugs (i.e. those registered before 2006) for further ecotoxicity testing. For drugs where effects of possible concern (e.g. behaviour) are not captured in regulatory tests, additional mechanistic testing may be required to provide the highest confidence for avoiding environmental impacts.
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| 37. |
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| 38. |
- Gunnarsson, Mikael, et al.
(author)
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No radiation protection reasons for restrictions on C-14 urea breath tests in children.
- 2002
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In: British Journal of Radiology. - : British Institute of Radiology. - 1748-880X .- 0007-1285. ; 75:900, s. 982-986
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Journal article (peer-reviewed)abstract
- Traditional 14C urea breath tests are normally not used for younger children because the radiation exposure is unknown. High sensitivity accelerator mass spectrometry and an ultra-low amount (440 Bq) of 14C urea were therefore used both to diagnose Helicobacter pylori (HP) infection in seven children, aged 3–6 years, and to make radiation dose estimates. The activity used was 125 times lower than the amount normally used for older children and 250 times lower than that used for adults. Results were compared with previously reported biokinetic and dosimetric data for adults and older children aged 7–14 years. 14C activity concentrations in urine and exhaled air per unit administered activity for younger children (3–6 years) correspond well with those for older children (7–14 years). For a child aged 3–6 years who is HP negative, the urinary bladder wall receives the highest absorbed dose, 0.3 mGy MBq-1. The effective dose is 0.1 mSv MBq-1 for the 3-year-old child and 0.07 mSv MBq-1 for the 6-year-old child. For two children, the 10 min and 20 min post-14C administration samples of exhaled air showed a significantly higher amount of 14C activity than for the rest of the children, that is 6% and 19% of administered activity exhaled per hour compared with 0.3–0.9% (mean 0.5%) of administered activity exhaled per hour indicating that these two children that is were HP positive. For a 3-year-old HP positive child, absorbed dose to the urinary bladder wall was 0.3 mGy MBq-1 and effective dose per unit of administered activity was 0.4 mSv MBq-1. Using 55 kBq, which is a normal amount for older children when liquid scintillation counters are used for measurement, the effective dose will be approximately 6 µSv to a 3-year-old HP negative child and 20 µSv to a HP positive child. Thus there is no reason for restrictions on performing a normal 14C urea breath test, even on young children.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Khoonsari, P. E., et al.
(author)
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Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers
- 2019
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 67:2, s. 639-651
-
Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: A beta(42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. Objective: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. Methods: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4-9 years and 21 of these converted to AD, whereas 53 remained stable. Results: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCl/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. Conclusions: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.
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| 44. |
- Koitzsch, A., et al.
(author)
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Core-hole screening response in two-dimensional cuprates : A high-resolution x-ray photoemission study
- 2002
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In: Physical Review B Condensed Matter. - : American Physical Society. - 0163-1829 .- 1095-3795. ; 66:2
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Journal article (peer-reviewed)abstract
- We have studied the core level photoemission spectra of the two-dimensional cuprates Sr2CuO2Cl2, Sr2CuO2Br2, Ca2CuO2Cl2, Bi2Sr2CaCu2O8+δ, and Nd2CuO4, with particular focus on the screening response to core-hole creation in the Cu−2p3/2 level. The influence of the apex positions on the shape of the so-called main line is investigated, and found to be weak. Additionally, an Anderson impurity model was used to fit the shape of the main lines, obtaining good agreement with the data from Nd2CuO4. For the other compounds, while the energy spread of the two screening channels (local and nonlocal) is well reproduced, the theory underestimates the width of the nonlocally screened feature. The shapes of the main lines are discussed in detail.
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| 45. |
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| 46. |
- Lundtoft, Christian, et al.
(author)
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Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
- 2022
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:11, s. 1842-1850
-
Journal article (peer-reviewed)abstract
- Objective Complete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjogren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS. Methods The presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients. Results Heterozygous C2 deficiency-when present in combination with a low C4A copy number-substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5-37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5-48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 x 10(-9)) and impaired function of the classical complement pathway (P = 0.03) were detected in SLE patients with heterozygous C2 deficiency. Finally, in a primary SS patient homozygous for C2 deficiency, we observed low levels of anti-Scl-70, which suggests a risk of developing systemic sclerosis or potential overlap between primary SS and other systemic autoimmune diseases. Conclusion We demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary SS. Our results emphasize the central role of the complement system in the pathogenesis of both SLE and primary SS.
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| 47. |
- Lyons, PA, et al.
(author)
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Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5120-
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Journal article (peer-reviewed)abstract
- Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
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| 48. |
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| 49. |
- Neuen, B. L., et al.
(author)
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Factors Associated with Patency Following Angioplasty of Hemodialysis Fistulae
- 2014
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In: Journal of Vascular and Interventional Radiology. - : Elsevier BV. - 1051-0443. ; 25:9, s. 1419-1426
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Journal article (peer-reviewed)abstract
- Purpose: Patency after percutaneous transluminal angioplasty of native hemodialysis arteriovenous fistulae (AVFs) is highly variable. This study aimed to identify predictors of patency following angioplasty in native AVFs. Materials and Methods: All endovascular procedures performed in native AVFs between 2005 and 2013 at two institutions were retrospectively reviewed. Clinical, anatomic, biochemical, and medication variables Were subjected to univariate and multivariate Cox regression analysis to identify predictors of postintervention primary and secondary patency. Results: During the study period, 207 patients underwent first angioplasty of their AVF. Follow-up ranged from 14 days to 8 years, during which another 247 endovascular interventions were performed to maintain patency. Postintervention primary patency rates at 6, 12, and 24 months were 66%, 49%, and 29%, respectively. Postintervention secondary patency rates at 6, 12, and 24 months were 94%, 84%, and 79%, respectively. On multivariate adjusted Cox regression analysis, upper-arm AVFs (P = .00072), AVFs less than 6 months of age (P = .0014), presence of multiple stenoses (P = .019), and degree of initial stenosis (P = .016) were significantly associated with shorter postintervention primary patency. A previously failed AVF was the only significant predictor of postintervention secondary patency loss (P = .0053). Conclusions: Anatomic factors related to the AVF location, AVF age, and the extent of the lesion are important predictors of restenosis after balloon angioplasty. Traditional cardiovascular risk factors, metabolic and inflammatory markers, and medications were not associated with postintervention potency.
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| 50. |
- Neuen, B. L., et al.
(author)
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Neutrophil-lymphocyte ratio predicts cardiovascular and all-cause mortality in hemodialysis patients
- 2016
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In: Renal Failure. - : Informa UK Limited. - 0886-022X .- 1525-6049. ; 38:1, s. 70-76
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Journal article (peer-reviewed)abstract
- Neutrophil-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been shown to predict mortality in patients with malignancies, ischemic heart disease and peripheral vascular disease. Its prognostic value in hemodialysis patients is unclear. The aims of this study were to: (i) explore the relationship between NLR and other biochemical parameters and (ii) to examine the value of NLR as a predictor of cardiovascular and all-cause mortality in hemodialysis patients. The study included all the incident hemodialysis patients from a single center between 2007 and 2012. NLR was calculated using samples obtained 3 months after commencing hemodialysis. One hundred seventy hemodialysis patients were included with a median follow-up of 37 months. There were 54 deaths (32%). NLR was positively correlated with C-reactive protein (r=0.24, p=0.0023) and negatively correlated with hemoglobin (r=-0.27, p=0.00048), albumin (r=-0.23, p=0.0034) and total cholesterol (r=-0.17, p=0.049) levels. In multivariate Cox regression, NLR was independently associated with both all-cause mortality (adjusted hazard ratio [HR] 1.4; 95% confidence interval [CI], 1.2-1.6; p0.0001) and cardiovascular death (HR 1.3, 95% CI 1.1-1.6, p=0.0032). Other predictors of all-cause mortality were age (HR 1.6 per decade; 95% CI, 1.2-2.1; p=0.0017), body mass index (HR 0.93; 95% CI, 0.88-0.98; p=0.0047), albumin (HR 0.91; 95% CI, 0.86-0.97; p=0.0035) and peripheral vascular disease (HR 2.7; 95% CI, 1.4-5.1; p=0.0023). NLR is a practical, cost-efficient and easy to use predictor of cardiovascular and all-cause mortality in incident hemodialysis patients.
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