| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
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| 5. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 6. |
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| 7. |
- Rheinbay, E, et al.
(author)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Journal article (peer-reviewed)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 8. |
- Carlevaro-Fita, J, et al.
(author)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Journal article (peer-reviewed)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 9. |
- Soininen, E.M., et al.
(author)
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Location of studies and evidence of effects of herbivory on Arctic vegetation: a systematic map
- 2021
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In: Environmental Evidence. - : BioMed Central (BMC). - 2047-2382. ; 10:1
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Journal article (peer-reviewed)abstract
- Background: Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims to identify the ecological contexts in which herbivore impacts on vegetation have been studied in the Arctic. Specifically, the primary question of the systematic map was: “What evidence exists on the effects of herbivores on Arctic vegetation?”.Methods: We used a published systematic map protocol to identify studies addressing the effects of herbivores on Arctic vegetation. We conducted searches for relevant literature in online databases, search engines and specialist websites. Literature was screened to identify eligible studies, defined as reporting primary data on herbivore impacts on Arctic plants and plant communities. We extracted information on variables that describe the ecological context of the studies, from the studies themselves and from geospatial data. We synthesized the findings narratively and created a Shiny App where the coded data are searchable and variables can be visually explored.Review findings: We identified 309 relevant articles with 662 studies (representing different ecological contexts or datasets within the same article). These studies addressed vertebrate herbivory seven times more often than invertebrate herbivory. Geographically, the largest cluster of studies was in Northern Fennoscandia. Warmer and wetter parts of the Arctic had the largest representation, as did coastal areas and areas where the increase in temperature has been moderate. In contrast, studies spanned the full range of ecological context variables describing Arctic vertebrate herbivore diversity and human population density and impact.Conclusions: The current evidence base might not be sufficient to understand the effects of herbivores on Arctic vegetation throughout the region, as we identified clear biases in the distribution of herbivore studies in the Arctic and a limited evidence base on invertebrate herbivory. In particular, the overrepresentation of studies in areas with moderate increases in temperature prevents robust generalizations about the effects of herbivores under different climatic scenarios.
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| 10. |
- Perez-Nadales, Elena, et al.
(author)
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Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
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In: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
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Journal article (peer-reviewed)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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| 11. |
- Coll, M., et al.
(author)
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Towards Oxide Electronics: a Roadmap
- 2019
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In: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 482, s. 1-93
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Journal article (peer-reviewed)abstract
- At the end of a rush lasting over half a century, in which CMOS technology has been experiencing a constant and breathtaking increase of device speed and density, Moore’s law is approaching the insurmountable barrier given by the ultimate atomic nature of matter. A major challenge for 21st century scientists is finding novel strategies, concepts and materials for replacing silicon-based CMOS semiconductor technologies and guaranteeing a continued and steady technological progress in next decades. Among the materials classes candidate to contribute to this momentous challenge, oxide films and heterostructures are a particularly appealing hunting ground. The vastity, intended in pure chemical terms, of this class of compounds, the complexity of their correlated behaviour, and the wealth of functional properties they display, has already made these systems the subject of choice, worldwide, of a strongly networked, dynamic and interdisciplinary research community. Oxide science and technology has been the target of a wide four-year project, named Towards Oxide-Based Electronics (TO-BE), that has been recently running in Europe and has involved as participants several hundred scientists from 29 EU countries. In this review and perspective paper, published as a final deliverable of the TO-BE Action, the opportunities of oxides as future electronic materials for Information and Communication Technologies ICT and Energy are discussed. The paper is organized as a set of contributions, all selected and ordered as individual building blocks of a wider general scheme. After a brief preface by the editors and an introductory contribution, two sections follow. The first is mainly devoted to providing a perspective on the latest theoretical and experimental methods that are employed to investigate oxides and to produce oxide-based films, heterostructures and devices. In the second, all contributions are dedicated to different specific fields of applications of oxide thin films and heterostructures, in sectors as data storage and computing, optics and plasmonics, magnonics, energy conversion and harvesting, and power electronics.
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| 12. |
- Aranha, M. R., et al.
(author)
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Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome
- 2023
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In: Alzheimers & Dementia. - 1552-5260. ; 19:11, s. 4817-4827
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Journal article (peer-reviewed)abstract
- BackgroundBasal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. MethodsWe included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. ResultsIn DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DiscussionBF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.
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| 13. |
- Iulita, M. F., et al.
(author)
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Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome
- 2023
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In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2
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Journal article (peer-reviewed)abstract
- The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-beta 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein.4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein.4, female.4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein.4 and biomarkers showed that female.4 carriers tended to exhibit lower CSF amyloid-beta 42/amyloid-beta 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein.4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.
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| 14. |
- ODonnell, Michael, et al.
(author)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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In: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Journal article (peer-reviewed)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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| 15. |
- Varea, A., et al.
(author)
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Tuneable magnetic patterning of paramagnetic Fe60Al40 (at. %) by consecutive ion irradiation through pre-lithographed shadow masks
- 2011
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 109:9, s. 093918-
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Journal article (peer-reviewed)abstract
- Arrays of ferromagnetic circular dots (with diameters ranging from 225 to 420 nm) have been prepared at the surface of atomically ordered paramagnetic Fe60Al40 (at. %) sheets by means of ion irradiation through prelithographed poly(methyl methacrylate) (PMMA) masks. The cumulative effects of consecutive ion irradiation (using Ar+ ions at 1.2 x 10(14) ions/cm(2) with 10, 13, 16, 19 and 22 keV incident energies) on the properties of the patterned dots have been investigated. A progressive increase in the overall magneto-optical Kerr signal is observed for increasingly larger irradiation energies, an effect which is ascribed to accumulation of atomic disorder. Conversely, the coercivity, H-C, shows a maximum after irradiating at 16-19 keV and it decreases for larger irradiation energies. Such a decrease in H-C is ascribed to the formation of vortex states during magnetization reversal, in agreement with results obtained from micromagnetic simulations. At the same time, the PMMA layer, with an initial thickness of 90 nm, becomes progressively thinned during the successive irradiation processes. After irradiation at 22 keV, the remaining PMMA layer is too thin to stop the incoming ions and, consequently, ferromagnetism starts to be generated underneath the nominally masked areas. These experimental results are in agreement with calculations using the Monte-Carlo simulation Stopping Range of Ions in Matter software, which show that for exceedingly thin PMMA layers Ar+ ions can reach the Fe60Al40 layer despite the presence of the mask.
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| 16. |
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| 17. |
- Astuto, Lisa M., et al.
(author)
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Genetic heterogeneity of Usher syndrome : analysis of 151 families with Usher type 1
- 2000
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 67:6, s. 1569-1574
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Journal article (peer-reviewed)abstract
- Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.
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| 18. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 19. |
- Kimberling, William J., et al.
(author)
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Gene mapping of Usher syndrome type IIa : localization of the gene to a 2.1-cM segment on chromosome 1q41
- 1995
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In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 56:1, s. 216-223
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Journal article (peer-reviewed)abstract
- Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor β2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.
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| 20. |
- Pedersen, Marie, et al.
(author)
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Is There an Association Between Ambient Air Pollution and Bladder Cancer Incidence? Analysis of 15 European Cohorts
- 2018
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In: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 4:1, s. 113-120
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Journal article (peer-reviewed)abstract
- Background: Ambient air pollution contains low concentrations of carcinogens implicated in the etiology of urinary bladder cancer (BC). Little is known about whether exposure to air pollution influences BC in the general population. Objective: To evaluate the association between long-term exposure to ambient air pollution and BC incidence. Design, setting and participants: We obtained data from 15 population-based cohorts enrolled between 1985 and 2005 in eight European countries (N = 303 431; mean follow-up 14.1 yr). We estimated exposure to nitrogen oxides (NO2 and NOx), particulate matter (PM) with diameter <10 mu m (PM10), <2.5 mu m (PM2.5). between 2.5 and 10 mu m (PM2.5-10). PM2.5 absorbance (soot), elemental constituents of PM, organic carbon, and traffic density at baseline home addresses using standardized land-use regression models from the European Study of Cohorts for Air Pollution Effects project. Outcome measurements and statistical analysis: We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and meta-analyses to estimate summary hazard ratios (HRS) for BC incidence. Results and limitations: During follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of the exposures were associated with BC risk. The summary HRs associated with a 10-mu g/m(3) increase in NO2 and 51-mu g/m(3) increase in PM2.5 were 0.98 (95% confidence interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations include the lack of information about lifetime exposure. Conclusions: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC. Patient summary: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study population to date and extensive assessment of exposure and comprehensive data on personal risk factors such as smoking. We found no association between the levels of outdoor air pollution at place of residence and bladder cancer risk.
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| 21. |
- Raaschou-Nielsen, Ole, et al.
(author)
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Air pollution and lung cancer incidence in 17 European cohorts : prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2013
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 14:9, s. 813-822
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Journal article (peer-reviewed)abstract
- BACKGROUND: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations.METHODS: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses.FINDINGS: The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day).INTERPRETATION: Particulate matter air pollution contributes to lung cancer incidence in Europe.FUNDING: European Community's Seventh Framework Programme.
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| 22. |
- Silva-Tamayo, Juan Carlos, et al.
(author)
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Global perturbation of the marine calcium cycle during the Permian-Triassic transition
- 2018
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In: Geological Society of America Bulletin. - 0016-7606. ; 130:7-8, s. 1323-1338
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Journal article (peer-reviewed)abstract
- A negative shift in the calcium isotopiccomposition of marine carbonate rocksspanning the end-Permian extinction horizonin South China has been used to arguefor an ocean acidification event coincidentwith mass extinction. This interpretationhas proven controversial, both because theexcursion has not been demonstrated acrossmultiple, widely separated localities, and becausemodeling results of coupled carbon andcalcium isotope records illustrate that calciumcycle imbalances alone cannot accountfor the full magnitude of the isotope excursion.Here, we further test potential controlson the Permian-Triassic calcium isotoperecord by measuring calcium isotope ratiosfrom shallow-marine carbonate successionsspanning the Permian-Triassic boundary inTurkey, Italy, and Oman. All measured sectionsdisplay negative shifts in δ44/40Ca of upto 0.6‰. Consistency in the direction, magnitude,and timing of the calcium isotope excursionacross these widely separated localitiesimplies a primary and global δ44/40Ca signature.Based on the results of a coupled boxmodel of the geological carbon and calciumcycles, we interpret the excursion to reflect aseries of consequences arising from volcanicCO2 release, including a temporary decreasein seawater δ44/40Ca due to short-lived oceanacidification and a more protracted increasein calcium isotope fractionation associatedwith a shift toward more primary aragonitein the sediment and, potentially, subsequentlyelevated carbonate saturation statescaused by the persistence of elevated CO2delivery from volcanism. Locally, changingbalances between aragonite and calcite productionare sufficient to account for the calciumisotope excursions, but this effect alonedoes not explain the globally observed negativeexcursion in the δ13C values of carbonatesediments and organic matter as well. Onlya carbon release event and related geochemicalconsequences are consistent both withcalcium and carbon isotope data. The carbonrelease scenario can also account for oxygenisotope evidence for dramatic and protractedglobal warming as well as paleontologicalevidencefor the preferential extinction ofmarine animals most susceptible to acidification,warming, and anoxia.
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| 23. |
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| 24. |
- Andersen, Zorana J., et al.
(author)
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Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
- 2017
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In: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
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| 25. |
- Béquignon, Olivier J. M., et al.
(author)
-
Collaborative SAR Modeling and Prospective In Vitro Validation of Oxidative Stress Activation in Human HepG2 Cells
- 2023
-
In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 63:17, s. 5433-5445
-
Journal article (peer-reviewed)abstract
- Oxidative stress is the consequence of an abnormal increase of reactive oxygen species (ROS). ROS are generated mainly during the metabolism in both normal and pathological conditions as well as from exposure to xenobiotics. Xenobiotics can, on the one hand, disrupt molecular machinery involved in redox processes and, on the other hand, reduce the effectiveness of the antioxidant activity. Such dysregulation may lead to oxidative damage when combined with oxidative stress overpassing the cell capacity to detoxify ROS. In this work, a green fluorescent protein (GFP)-tagged nuclear factor erythroid 2-related factor 2 (NRF2)-regulated sulfiredoxin reporter (Srxn1-GFP) was used to measure the antioxidant response of HepG2 cells to a large series of drug and drug-like compounds (2230 compounds). These compounds were then classified as positive or negative depending on cellular response and distributed among different modeling groups to establish structure-activity relationship (SAR) models. A selection of models was used to prospectively predict oxidative stress induced by a new set of compounds subsequently experimentally tested to validate the model predictions. Altogether, this exercise exemplifies the different challenges of developing SAR models of a phenotypic cellular readout, model combination, chemical space selection, and results interpretation.
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| 26. |
- Cordoba Gallego, Jose Manuel, et al.
(author)
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Morphology influence of the oxidation kinetics of carbon nanofibers
- 2009
-
In: CORROSION SCIENCE. - : Elsevier BV. - 0010-938X. ; 51:4, s. 926-930
-
Journal article (peer-reviewed)abstract
- This paper reports the stability and oxidation rate of five types of carbon nanofiber (CNF) with distinctly different orientation of their graphite sheets based on conversion to CO2 when heated in the presence of oxygen. A non-isothermal technique was used to determine the oxidation kinetic parameters including the activation energy (E-a) Graphite shows a similar activation energy (E-a = 158 kJ/mol(-1)) to CNF with longitudinal alignment (E-a = 156kJ/mol(-1)). CNF type herringbone (E-a = 126kJ/mol(-1)) and platelet (E-a = 145 kJ/mol(-1)) show the lowest oxidation resistance which improved dramatically after a heat treatment at 3023 K of the herringbone (E-a = 216 kJ/mol(-1)) and platelet (E-a = 174 kJ/mol(-1)) structures.
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| 27. |
- Eudy, James D., et al.
(author)
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Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa
- 1998
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 280:5370, s. 1753-1757
-
Journal article (peer-reviewed)abstract
- Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.
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| 28. |
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| 29. |
- Nagel, Gabriele, et al.
(author)
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Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2018
-
In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:7, s. 1632-1643
-
Journal article (peer-reviewed)abstract
- Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancersof the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient airpollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-useregression models for particulate matter (PM) below 10mm (PM10), below 2.5mm (PM2.5), between 2.5 and 10mm (PMcoarse),PM2.5absorbance and nitrogen oxides (NO2and NOX) as well as approximated by traffic indicators. Cox regression modelswith adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined withrandom effects meta-analyses. During average follow-up of 14.1 years of 305,551 individuals, 744 incident cases of gastriccancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5mg/m3of PM2.5was 1.38 (95% CI 0.99; 1.92)for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures consid-ered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influencemarkedly the effect estimate for PM2.5and gastric cancer. Higher estimated risks of gastric cancer associated with PM2.5wasfound in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study showsan association between long-term exposure to PM2.5and gastric cancer, but not UADT cancers, suggesting that air pollutionmay contribute to gastric cancer risk.
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| 30. |
- Ocampo, R. A., et al.
(author)
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Formation of highly ordered TiO2 nanotubes on Ti6Al4V alloys manufactured by electron beam powder bed fusion (E-PBF)
- 2023
-
In: The International Journal of Advanced Manufacturing Technology. - : Springer Science+Business Media B.V.. - 0268-3768 .- 1433-3015. ; 128:1-2, s. 257-266
-
Journal article (peer-reviewed)abstract
- Highly ordered TiO2 nanotubes were obtained by anodization on Ti6Al4V substrates manufactured by electron beam powder bed fusion (E-PBF). Effects of anodization parameters such as anodizing time, stirring, fluoride concentration, and water content were analyzed in an organic electrolyte (ethylene glycol) that contains ammonium fluoride. The ordering of the nanotubes was measured by regularity ratio calculations based on fast Fourier transform (FFT) from SEM images. It was found that for the processed specimens, the highest ordering of the TiO2 nanotubes was reached at 30 V for 5000 s with a concentration of 9 vol% H2O and 0.4 wt.% NH4F, exhibiting nanotubes free of delamination, cracks, and coral-like structures with a regularity ratio (RR) of 1.91. This work offers a simple method for creating homogeneous and organized TiO2 nanotubes on Ti6Al4V substrates manufactured by E-PBF which potentially improves its functionality in diverse industrial applications such as nanosensors, controlled-release substances, solar cells, water splitting, electrochromic devices, and Li-ion battery anodes. Graphical Abstract: [Figure not available: see fulltext.].
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| 31. |
- Perez-Escobar, Oscar A., et al.
(author)
-
The origin and speciation of orchids
- 2024
-
In: NEW PHYTOLOGIST. - 0028-646X .- 1469-8137.
-
Journal article (peer-reviewed)abstract
- Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.
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| 32. |
- Raaschou-Nielsen, Ole, et al.
(author)
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Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts
- 2017
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:7, s. 1528-1537
-
Journal article (peer-reviewed)abstract
- Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air pollution at the residence and the incidence of kidney parenchyma cancer in the general population. We used data from 14 European cohorts from the ESCAPE study. We geocoded and assessed air pollution concentrations at baseline addresses by land-use regression models for particulate matter (PM10 , PM2.5 , PMcoarse , PM2.5 absorbance (soot)) and nitrogen oxides (NO2 , NOx ), and collected data on traffic. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses to calculate summary hazard ratios (HRs). The 289,002 cohort members contributed 4,111,908 person-years at risk. During follow-up (mean 14.2 years) 697 incident cancers of the kidney parenchyma were diagnosed. The meta-analyses showed higher HRs in association with higher PM concentration, e.g. HR=1.57 (95%CI: 0.81-3.01) per 5μg/m(3) PM2.5 and HR=1.36 (95%CI: 0.84-2.19) per 10(-5) m(-1) PM2.5 absorbance, albeit never statistically significant. The HRs in association with nitrogen oxides and traffic density on the nearest street were slightly above one. Sensitivity analyses among participants who did not change residence during follow-up showed stronger associations, but none were statistically significant. This study provides suggestive evidence that exposure to outdoor PM at the residence may be associated with higher risk for kidney parenchyma cancer; the results should be interpreted cautiously as associations may be due to chance.
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| 33. |
- Tamayo-Ariztondo, J., et al.
(author)
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Effect of heat treatment of carbon nanofibres on electroless copper deposition
- 2010
-
In: Composites Science And Technology. - : Elsevier BV. - 0266-3538 .- 1879-1050. ; 70:16, s. 2269-2275
-
Journal article (peer-reviewed)abstract
- Cu is a well known heat sink material due to its high thermal conductivity. However, its coefficient of thermal expansion (CTE) is high. One of the most promising solutions for reducing it is to reinforce copper with carbon nanofibres (CNF) because of their low CTE. To exploit the properties of the CNFs a good dispersion of the reinforcement within the matrix must be achieved. One of the processing methods used to obtain a homogeneous CNF distribution is coating the CNF with Cu using electrochemical deposition. In this paper, the effect of the carbon structure on electroless deposition technique is studied. Different CNF have been compared: herringbone (HB), platelet (PL) and longitudinally aligned (previously heat treated) (LAHT). Herringbone and Platelet CNF were heat treated at 2750 °C for 30′ which resulted in a structure resembling graphite with loops at the fibre surface. These loops are responsible for an enhancement of the copper coating. It is shown that the Cu coverage in electroless deposition is high for the graphene plane and poor at the edges of the plane.
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| 34. |
- Thielke, M. W., et al.
(author)
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Full Lignin-Derived Electrospun Carbon Materials as Electrodes for Supercapacitors
- 2022
-
In: Frontiers in Materials. - : Frontiers Media S.A.. - 2296-8016. ; 9
-
Journal article (peer-reviewed)abstract
- In the search for more sustainable energy storage devices, biomass-derived materials have been widely researched as carbon source for electrode applications. Here we present the processing of high molecular lignin, an abundant carbon rich biopolymer and byproduct of the pulp and paper industry, into freestanding nonwoven carbon fiber (CNFs) electrodes by using electrospinning. It is worth mentioning that no petrol-derived polymers that are usually included in the electrospinning of lignin, were employed in this work, making these electrodes more sustainable than common lignin-derived carbon electrodes. The effect of the carbonization temperature and oxygen plasma treatment in the electrochemical performance of the CNFs as electrodes for supercapacitors was studied. The upscaling of the processing of lignin into carbon electrodes was also explored by comparing a standard electrospinning set up with a needleless electrospinning equipment that enabled faster and higher throughput. The electrochemical performance of the CNFs increased after plasma treatment of the surface and the electrodes prepared using the standard set up exhibited the highest activity, achieving specific capacitances of up to 103.6 F g−1. Copyright © 2022 Thielke, Lopez Guzman, Victoria Tafoya, García Tamayo, Castro Herazo, Hosseinaei and Sobrido.
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| 35. |
- van der Stel, Wanda, et al.
(author)
-
New Approach Methods (NAMs) Supporting Read-Across : Two Neurotoxicity AOP-based IATA Case Studies
- 2021
-
In: Altex. - : ALTEX Edition. - 1868-596X .- 1868-8551. ; 38:4, s. 615-635
-
Journal article (peer-reviewed)abstract
- Read-across approaches are considered key in moving away from in vivo animal testing towards addressing data-gaps using new approach methods (NAMs). Ample successful examples are still required to substantiate this strategy. Here we present and discuss the learnings from two OECD IATA endorsed read-across case studies. They involve two classes of pesticides - rotenoids and strobilurins - each having a defined mode-of-action that is assessed for its neurological hazard by means of an AOP-based testing strategy coupled to toxicokinetic simulations of human tissue concentrations. The endpoint in question is potential mitochondrial respiratory chain mediated neurotoxicity, specifically through inhibition of complex I or III. An AOP linking inhibition of mitochondrial respiratory chain complex I to the degeneration of dopaminergic neurons formed the basis for both cases but was deployed in two different regulatory contexts. The two cases also exemplify several different read-across concepts: analogue versus category approach, consolidated versus putative AOP, positive versus negative prediction (i.e., neurotoxicity versus low potential for neurotoxicity), and structural versus biological similarity. We applied a range of NAMs to explore the toxicodynamic properties of the compounds, e.g., in silico docking as well as in vitro assays and readouts - including transcriptomics - in various cell systems, all anchored to the relevant AOPs. Interestingly, although some of the data addressing certain elements of the read-across were associated with high uncertainty, their impact on the overall read-across conclusion remained limited. Coupled to the elaborate regulatory review that the two cases underwent, we propose some generic learnings of AOP-based testing strategies supporting read-across.
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| 36. |
- Vargas, C. A., et al.
(author)
-
Morphological analysis of plasma electrolytic oxidation coatings formed on Ti6Al4V alloys manufactured by electron beam powder bed fusion
- 2023
-
In: Heliyon. - : Elsevier BV. - 2405-8440. ; 9:9
-
Journal article (peer-reviewed)abstract
- This study investigates and compares plasma electrolytic oxidation (PEO) coatings produced on wrought Ti6Al4V alloy substrates with those resulting from electron beam powder bed fusion (PBF-EB). For a duration of 1000 s, a phosphate/silicate electrolyte with a current density of 50 A/cm2 was employed to fabricate the coatings. Surface and polished cross-sections of the coated specimens underwent SEM and X-ray diffraction (XRD) analyses. The obtained coatings exhibit differences of up to approximately 18% in thickness and formation, as well as in their anatase phase. The anatase phase is present at a level of 54.09% in the substrates processed by PBF-EB and 38.54% in wrought substrates. After 1000 s of PEO, the coatings formed on the wrought substrates exhibited higher porosity and larger pores (>1 μm) compared to those produced on the PBF-EB specimens. The PBF-EB coatings had lower porosity because they contained fewer pores larger than 1 μm. The findings imply that the unique microstructural arrangement of PBF-EB-produced additively made Ti6Al4V materials plays a significant impact in the development and morphological properties of PEO oxide coatings.
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| 37. |
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| 38. |
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| 39. |
- Beal, Jacob, et al.
(author)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 40. |
- Cascan, Edgar Tamayo, et al.
(author)
-
Multi-Objective Calibration of Microscopic Traffic Simulation for Highway Traffic Safety
- 2019
-
In: Proceedings of the 2019 IEEE Intelligent Transportation Systems Conference (ITSC). ; , s. 4548-4555
-
Conference paper (peer-reviewed)abstract
- Microscopic traffic simulation has become an important tool to investigate traffic efficiency and road safety. In order to produce meaningful results, driver behaviour models need to be carefully calibrated to represent real world conditions. If this type of simulations are to be used to evaluate safety features of traffic, on top of macroscopic relationships such as the speed-density diagram, they should also adequately represent the average risk of accidents occurring on the road. In this paper, we present a two-stage computationally feasible multi-objective calibration process. The first stage performs a parameter sensitivity analysis to select only parameters with considerable effect on the respective objective functions. The second stage employs a multi-objective genetic algorithm utilizing only few influential parameters that produces a front of Pareto optimal solutions with respect to the conflicting objective functions. Compared to traditional methods which focus on only one objective while sacrificing the accuracy of the other, our method achieves a high degree of realism for both traffic flow and average risk.
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| 41. |
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| 42. |
- McRae, Nia, et al.
(author)
-
Blood manganese levels during pregnancy and postpartum depression : A cohort study among women in Mexico
- 2020
-
In: Neurotoxicology. - : Elsevier. - 0161-813X .- 1872-9711. ; 76, s. 183-190
-
Journal article (peer-reviewed)abstract
- Background: Occupational studies have shown an association between elevated Mn exposure and depressive symptoms. Blood Mn (BMn) naturally rises during pregnancy due to mobilization from tissues, suggesting it could contribute to pregnancy and postpartum depressive symptoms. Objectives: To assess the association between BMn levels during pregnancy and postpartum depression (PPD), creating opportunities for possible future interventions. Methods: We studied 561 women from the reproductive longitudinal Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort in Mexico City. BMn was measured at the 2nd and 3rd trimesters, as well as delivery. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD symptoms at 12-months postpartum. We used a generalized linear model assuming a Poisson distribution to assess the association between BMn levels and PPD, with adjustments for age, stress and depressive symptoms during pregnancy, education, socioeconomic status, and contemporaneous blood lead levels. Results: The mean +/- standard deviation (SD) EPDS score at 12-months postpartum was 6.51 +/- 5.65, and 17.11% of women met the criteria for possible PPD (score >= 13). In adjusted models, BMn during the 3rd trimester (beta: 0.13, 95% CI: 0.04-0.21) and BMn levels averaged at the 2nd and 3rd trimester (beta: 0.14, 95% CI: 0.02-0.26) had a positive association with EPDS scores at 12 months postpartum. BMn at the 2nd trimester (beta: 0.07, 95% CI: -0.09-0.22) and delivery (beta: 0.03, 95% CI: -0.04-0.10) had a non-significant positive association with EPDS scores at 12-months postpartum. Stress and depressive symptoms during pregnancy was associated with higher EPDS scores at 12-months postpartum in all of the adjusted models but were only significant when either BMn during 3rd trimester or BMn averaged across 2nd and 3rd trimester was assessed as the exposure. Discussion: Our results demonstrate that elevated BMn levels during pregnancy predict PPD symptoms and could be a potential pathway for intervention and prevention of PPD.
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| 43. |
- Mgaieth, Farah, et al.
(author)
-
Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome.
- 2023
-
In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 19:11, s. 5129-37
-
Journal article (peer-reviewed)abstract
- Adults with Down syndrome (DS) are at ultra-high risk of developing Alzheimer's disease (AD), characterized by poor episodic memory and semantic fluency in the preclinical phase in the general population. We explored semantic fluency performance in DS and its relationship to age, AD, and blood biomarkers.A total of 302 adults with DS at baseline and 87 at follow-up from the London Down Syndrome Consortium cohort completed neuropsychological assessments. Blood biomarkers were measured with the single molecule array technique in a subset of 94 participants.Poorer verbal fluency performance was observed as age increases. Number of correct words declined in those with AD compared to those without over 2 years and was negatively correlated with neurofilament light (r=-0.37, P=.001) and glial fibrillary acidic protein (r=-0.31, P=.012).Semantic fluency may be useful as an early indicator of cognitive decline and provide additional information on AD-related change, showing associations with biomarkers in DS.
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| 44. |
- Mootha, VK, et al.
(author)
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PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
- 2003
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 34:3, s. 267-273
-
Journal article (peer-reviewed)abstract
- DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.
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| 45. |
- Padilla, P., et al.
(author)
-
Glide Symmetry to Prevent the Lowest Stopband of Printed Corrugated Transmission Lines
- 2018
-
In: IEEE Microwave and Wireless Components Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 1531-1309 .- 1558-1764. ; 28:9, s. 750-752
-
Journal article (peer-reviewed)abstract
- In this letter, we demonstrate that the dispersion properties of printed double-sided parallel-strip lines can be controlled by using glide symmetry. Glide symmetry is introduced in with corrugations in both strips of a double-sided line. We demonstrate that glide symmetry eliminates the stopband between first and second propagating modes and yields to a higher propagation constant, preserving its linearity, and the broadband nature of the underlying guiding technology. Thus, the glide-symmetric double-sided line can be designed to possess a high equivalent refractive index in an ultrawide range of frequencies. These exceptional properties have been numerically and experimentally validated. Finally, we demonstrate the possibilities of this technology with a specific design, a glide-symmetric double-sided parallel-strip line with filtering properties. Potential applications are low-dispersive leaky-wave antennas and electromechanical tunable phase shifters and filters.
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| 46. |
- Prusakov, Pavel, et al.
(author)
-
A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
- 2021
-
In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
-
Journal article (peer-reviewed)abstract
- Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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| 47. |
- Reyna, Matthew A, et al.
(author)
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Pathway and network analysis of more than 2500 whole cancer genomes
- 2020
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
-
Journal article (peer-reviewed)abstract
- The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
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| 48. |
- Rosa, M. J., et al.
(author)
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Identifying critical windows of prenatal particulate matter (PM2.5) exposure and early childhood blood pressure
- 2020
-
In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 182
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Journal article (peer-reviewed)abstract
- Background: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Some evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 μm in diameter (PM2.5) exposure and children's BP at ages 4–6 years. Methods: Participants included 537 mother-child dyads enrolled in the Programming Research in Obesity, GRowth Environment, and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used distributed lag models (DLMs) to examine associations between daily PM2.5 exposure and systolic and diastolic BP (SBP and DBP), adjusting for child's age, sex and BMI, as well as maternal education, preeclampsia and indoor smoking report during the second and third trimester, seasonality and average postnatal year 1 PM2.5 exposure. Results: We found that PM2.5 exposure between weeks 11–32 of gestation (days 80–226) was significantly associated with children's increased SBP. Similarly, PM2.5 exposure between weeks 9–25 of gestation (days 63–176) was significantly associated with increased DBP. To place this into context, a constant 10 μg/m3 increase in PM2.5 sustained throughout this critical window would predict a cumulative increase of 2.6 mmHg (CI: 0.5, 4.6) in SBP and 0.88 mmHg (CI: 0.1, 1.6) in DBP at ages 4–6 years. In a stratified analysis by sex, this association persisted in boys but not in girls. Conclusions: Second and third trimester PM2.5 exposure may increase children's BP in early life. Further work investigating PM2.5 exposure with BP trajectories later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations, including pregnant women.
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| 49. |
- Tamayo-Dominguez, A., et al.
(author)
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High Scanning Rate Leaky Wave Antenna Based on Glide Symmetry for 77 GHz Automotive Radar
- 2020
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In: 2020 14TH EUROPEAN CONFERENCE ON ANTENNAS AND PROPAGATION (EUCAP 2020). - : Institute of Electrical and Electronics Engineers (IEEE).
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Conference paper (peer-reviewed)abstract
- This work presents a leaky wave antenna at W band with glide-symmetric protrusions that enhance the scanning ratio of previous works. Also, a conventional leaky wave antenna is designed for comparing the results in terms of required bandwidth and steering range. Both prototypes are based on gap waveguide technology to prevent the leakage due to air gaps between layers. In order to reduce the manufacturing cost, the designs are aimed to 3D-printing. A Taylor amplitude modulation is conducted in the two cases to reduce side lobe levels. The glide-symmetric leaky wave antenna provides a variation of the steering angle from 12.14 degrees to 50.84 degrees in a band from 74.2 GHz to 79.8 GHz. The scanning ratio compared with the simple leaky wave antenna is enhanced by a factor of 6.41. This rapid variation of the steering angle in a narrow band (7%) is of interest for automotive radars.
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| 50. |
- Tamayo-Dominguez, A., et al.
(author)
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One-Plane Glide-Symmetric Structures Over Dielectric Substrate
- 2019
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In: 13th European Conference on Antennas and Propagation, EuCAP 2019. - : Institute of Electrical and Electronics Engineers (IEEE). - 9788890701887
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Conference paper (peer-reviewed)abstract
- This work presents a new configuration to create glide-symmetric structures in a single plane, which can be printed on the metallic face of a dielectric substrate. This type of glide symmetry facilitates the fabrication and avoids alignment problems in the assembly process when compared to traditional glide-symmetric structures based on several planes. This article also includes a study based on dispersion diagrams on the appearance of stop-bands by breaking the symmetry. Finally, we present the simulated S parameters of structures with 10x10 unit cells to illustrate the attenuation in these stop-bands.
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