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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Dornelas, M., et al. (författare)
  • BioTIME: A database of biodiversity time series for the Anthropocene
  • 2018
  • Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:7, s. 760-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)). Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
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4.
  • Fomalont, E. B., et al. (författare)
  • THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
  • 2015
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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7.
  • Bosson, J. K., et al. (författare)
  • Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations
  • 2021
  • Ingår i: Journal of Cross-Cultural Psychology. - : SAGE Publications. - 0022-0221 .- 1552-5422. ; 52:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB's distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role.
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8.
  • Shimwell, T. W., et al. (författare)
  • The LOFAR Two-metre Sky Survey: II. First data release
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
  • Forskningsöversikt (refereegranskat)abstract
    • The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120-168 MHz survey of the entire northern sky for which observations are now 20% complete. We present our first full-quality public data release. For this data release 424 square degrees, or 2% of the eventual coverage, in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00′00″ to 57°00′00″) were mapped using a fully automated direction-dependent calibration and imaging pipeline that we developed. A total of 325 694 sources are detected with a signal of at least five times the noise, and the source density is a factor of ∼10 higher than the most sensitive existing very wide-area radio-continuum surveys. The median sensitivity is S144 MHz = 71 μJy beam -1 and the point-source completeness is 90% at an integrated flux density of 0.45 mJy. The resolution of the images is 6″ and the positional accuracy is within 0.2″. This data release consists of a catalogue containing location, flux, and shape estimates together with 58 mosaic images that cover the catalogued area. In this paper we provide an overview of the data release with a focus on the processing of the LOFAR data and the characteristics of the resulting images. In two accompanying papers we provide the radio source associations and deblending and, where possible, the optical identifications of the radio sources together with the photometric redshifts and properties of the host galaxies. These data release papers are published together with a further ∼20 articles that highlight the scientific potential of LoTSS.
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9.
  • Shimwell, T. W., et al. (författare)
  • The LOFAR Two-metre Sky Survey: V. Second data release
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
  • Tidskriftsartikel (refereegranskat)abstract
    • In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120a 168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44 30a and 1h00m +28 00a and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6a resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beama 1; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2a; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beama 1. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > a ±a 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20a resolution 120a168 MHz continuum images have a median rms sensitivity of 95 μJy beama 1, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480a A a 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beama 1 at 4a and 2.2 mJy beama 1 at 20a; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data to facilitate the thorough scientific exploitation of this unique dataset.
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10.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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13.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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16.
  • Prokopishyn, Nicole L., et al. (författare)
  • The Concentration of Total Nucleated Cells in Harvested Bone Marrow for Transplantation Has Decreased over Time
  • 2019
  • Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 25:7, s. 1325-1330
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact the quality of BM harvests. In this study, we examined >15,000 BM donations collected at National Marrow Donor Program centers between 1994 and 2016 and found a significant decline in the quality of BM products, as defined by the concentration of total nucleated cells (TNCs). The mean TNC concentration in BM donations dropped from 21.8 x 10(6) cells/mL in the earliest era (1994 to 1996) to 18.7 x 10(6) cells/mL in the most recent era (2012 to 2016) (means ratio,.83; P < .001). This decline in BM quality was seen despite the selection of more donors perceived to be optimal (eg, younger and male). Multivariate regression analysis showed that higher volume centers (performing >30 collections per era) had better-quality harvests with higher concentrations of TNCs collected. In conclusion, we have identified a significant decrease in the quality of BM collections over time, and lower-volume collection centers had poorer-quality harvests. In this analysis, we could not elucidate the direct cause for this finding, suggesting the need for further studies to investigate the key factors responsible and to explore the impact on transplant recipients. (C) 2019 American Society for Blood and Marrow Transplantation.
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17.
  • Hale, S. E., et al. (författare)
  • Evaluating Nature-Based Solutions for Water Management in Peri-Urban Areas
  • 2023
  • Ingår i: Water. - : MDPI. - 2073-4441. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The term nature-based solutions (NBS) has gained traction in recent years and has been applied in many settings. There are few comprehensive assessment frameworks available that can guide NBS planning and implementation while at the same time capturing the short- and long-term impacts and benefits of the NBS. Here a recently presented framework, which builds on the theory of change and was developed to assess NBS at different phases of the project cycle, was applied to seven diverse case studies. The case studies addressed water quality and quantity issues in peri-urban areas across the global north and south. Framework indicators covering the sustainability dimensions (environmental, social and economic) were assessed at three stages of the framework: context, process and results. The work sought to investigate the following research objectives: (1) Can this framework be robust and yet flexible enough to be applied across a diverse selection of NBS projects that are at different phases of the project cycle and address different kinds of water challenges within varied ecological, social and economic contexts? (2) Is it possible to draw generalisations from a comparative analysis of the application of the framework to the case studies? Results showed that the framework was able to be applied to the case studies; however, their diversity showed that NBS projects designed in one context, for a specific purpose in a specific location, can not necessarily be transferred easily to another location. There were several process-based indicators that were universally significant for the case studies, including expertise, skills and knowledge of the involved actors, roles and responsibilities of involved actors and political support. The result-based indicators were case study-specific when environmental indicators were case study-specific, and important social indicators were environmental identity and recreational values. Overall, the use of the framework benefits the recognition of the implementation’s advances, such as the change in context, the processes in place and the results obtained.
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18.
  • Hsu, Jack W., et al. (författare)
  • Collection of Peripheral Blood Progenitor Cells in 1 Day Is Associated with Decreased Donor Toxicity Compared to 2 Days in Unrelated Donors
  • 2020
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:6, s. 1210-1217
  • Tidskriftsartikel (refereegranskat)abstract
    • Peripheral blood stem cells (PBSCs) have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells. Current National Marrow Donor Program policy recommends 5 days of daily filgrastim, followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers between 2006 and 2016. Of these 22,348 donors, 20,004 (89.5%) had collection on 1 day, and the other 2344 (9.5%) had collection over 2 days. Information on why donors underwent apheresis in 1 day or 2 days was not available. Donors who underwent apheresis in 1 day were more likely to be male (67% versus 46%; P < .001), younger (age <30 years, 48% versus 36%; P < .001), and have a higher body weight (83.0 kg versus 75.9 kg; P< .001) and body mass index (BMI; >30, 30% versus 22%; P < .001). Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of 1-day collections and in 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34' cells/I, in the product was higher on the second day of apheresis compared with the first day (23.8 x 10(6) CD34(+)/L. on day 1 versus 28.7 x 10(6) CD34(+)/L. on day 2; P< .001). Donors who underwent collection in 1 day were less likely to experience citrate toxicity (36% versus 52%; P< .001), hospitalization (1% versus 6%; P< .001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% versus 26%; P < .001). Female sex, older age, collection via central lines, and higher BMI were factors associated with greater likelihood for the development of toxicity, whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in 1 day or 2 days, 1-day apheresis procedures were associated with less overall toxicity, and thus we recommend single-day collections, especially if the requested number of cells have been collected in 1 day.
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19.
  • Mohammed Taha, Hiba, et al. (författare)
  • The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry
  • 2022
  • Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
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20.
  • Radivoyevitch, Tomas, et al. (författare)
  • Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma
  • 2018
  • Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 130-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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21.
  • Jencson, Jacob E., et al. (författare)
  • Discovery of an Intermediate-luminosity Red Transient in M51 and Its Likely Dust-obscured, Infrared-variable Progenitor
  • 2019
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 880:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the discovery of an optical transient (OT) in Messier. 51, designated M51 OT2019-1 (also ZTF 19aadyppr, AT 2019abn, ATLAS19bz1), by the Zwicky Transient Facility (ZTF). The OT rose over 15. days to an observed luminosity of M-r = -13 (nu L-nu = 9 x 10(6) L-circle dot), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of approximate to 400 km s(-1), Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called SN impostors and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a 4.5 mu m luminosity of M-[4.5] approximate to -12.2 mag and a [3.6]-[4.5] color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [ 4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of E(B - V) approximate to 0.7 mag and higher intrinsic luminosity of M-r approximate to -14.9 mag (nu L-nu = 5.3 x 10(7) L-circle dot) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51. OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.
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22.
  • Stroncek, David F, et al. (författare)
  • Donor Experiences of Second Marrow or Peripheral Blood Stem Cell Collection Mirror the First, but CD34+ Yields Are Less
  • 2018
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:1, s. 175-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about the experiences of individuals donating peripheral blood stem cells (PBSCs) or marrow for a second time. To study this, unrelated donors making a second donation through the National Marrow Donor Program between 2004 and 2013 were evaluated. Experiences of second-time donors giving marrow (n = 118: first donation was PBSC in 76 and marrow in 42) were compared with those making only 1 marrow donation (n = 5829). Experiences of second-time donors giving PBSCs (n = 602) (first donation was PBSCs in 362; marrow in 240) were compared to first-time PBSC donors (n = 16,095). For donors giving a second PBSC or marrow donation there were no significant differences in maximum skeletal pain, maximum symptoms measured by an established modified toxicity criteria, and recovery time compared with those who donated only once. Notably, the yield of marrow nucleated cells and PBSC CD34+ cells with second donations was less. As previously noted with single first-time donations, female (PBSCs and marrow) and obese donors (PBSCs) had higher skeletal pain and/or toxicity with a second donation. PBSC donors who experienced high levels of pain or toxicity with the first donation also experienced high levels of these symptoms with their second donation and slower recovery times. In conclusion, for most donors second donation experiences were similar to first donation experiences, but CD34+ yields were less. Knowledge of the donor's first experience and stem cell yields may help centers decide whether second donations are appropriate and institute measures to improve donor experiences.
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23.
  • Ayas, Mouhab, et al. (författare)
  • Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia.
  • 2013
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 31:13, s. 1669-76
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. PATIENTS AND METHODS We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. CONCLUSION Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.
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24.
  • De, Kishalay, et al. (författare)
  • The Zwicky Transient Facility Census of the Local Universe. I. Systematic Search for Calcium-rich Gap Transients Reveals Three Related Spectroscopic Subclasses
  • 2020
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the Zwicky Transient Facility alert stream, we are conducting a large spectroscopic campaign to construct a complete, volume-limited sample of transients brighter than 20 mag, and coincident within 100 '' of galaxies in the Census of the Local Universe catalog. We describe the experiment design and spectroscopic completeness from the first 16 months of operations, which have classified 754 supernovae. We present results from a systematic search for calcium-rich gap transients in the sample of 22 low-luminosity (peak absolute magnitude M > -17), hydrogen-poor events found in the experiment. We report the detection of eight new events, and constrain their volumetric rate to greater than or similar to 15% +/- 5% of the SN Ia rate. Combining this sample with 10 previously known events, we find a likely continuum of spectroscopic properties ranging from events with SN Ia-like features (Ca-Ia objects) to those with SN Ib/c-like features (Ca-Ib/c objects) at peak light. Within the Ca-Ib/c events, we find two populations distinguished by their red (g - r approximate to 1.5 mag) or green (g - r approximate to 0.5 mag) colors at the r-band peak, wherein redder events show strong line blanketing features and slower light curves (similar to Ca-Ia objects), weaker He lines, and lower [Ca II]/[O I] in the nebular phase. We find that all together the spectroscopic continuum, volumetric rates, and striking old environments are consistent with the explosive burning of He shells on low-mass white dwarfs. We suggest that Ca-Ia and red Ca-Ib/c objects arise from the double detonation of He shells, while green Ca-Ib/c objects are consistent with low-efficiency burning scenarios like detonations in low-density shells or deflagrations.
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25.
  • Graham, Melissa L., et al. (författare)
  • Supernova siblings and their parent galaxies in the Zwicky Transient Facility Bright Transient Survey
  • 2022
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 511:1, s. 241-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Supernova (SN) siblings - two or more SNe in the same parent galaxy - are useful tools for exploring progenitor stellar populations as well as properties of the host galaxies such as distance, star-formation rate, dust extinction, and metallicity. Since the average SN rate for a Milky Way-type galaxy is just one per century, a large imaging survey is required to discover an appreciable sample of SN siblings. From the wide-field Zwicky Transient Facility (ZTF) Bright Transient Survey (which aims for spectroscopic completeness for all transients which peak brighter than r < 18.5 mag) we present 10 SN siblings in five parent galaxies. For each of these families, we analyse the SN's location within the host and its underlying stellar population, finding agreement with expectations that SNe from more massive progenitors are found nearer to their host core and in regions of more active star formation. We also present an analysis of the relative rates of core collapse and thermonuclear SN siblings, finding a significantly lower ratio than past SN sibling samples due to the unbiased nature of the ZTF.
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26.
  • Ho, Anna Y. Q., et al. (författare)
  • Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova : Pre-explosion Emission and a Rapidly Rising Luminous Transient
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 887:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 +/- 0.1 mag hr(-1)) and luminous (M-g,M- peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (L-bol greater than or similar to 3 x 10(44) erg s(-1)), the short rise time (t(rise) = 3 days in g band), and the blue colors at peak (g-r similar to -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T-eff greater than or similar to 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M-g similar to M-r approximate to -14 mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E-gamma,E- iso < 4.9 x 10(48) erg, a limit on X-ray emission L-X < 10(40) erg s(-1), and a limit on radio emission nu L-v less than or similar to 10(37) erg s(-1). Taken together, we find that the early (< 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M-circle dot) at large radii (3 x 10(14) cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (> 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56.
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27.
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28.
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29.
  • Kanzler, Kathryn E, et al. (författare)
  • Mitigating the Effect of Pain Severity on Activity and Disability in Patients with Chronic Pain : The Crucial Context of Acceptance.
  • 2018
  • Ingår i: Pain medicine (Malden, Mass.). - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The purpose of this study was to examine the effect of pain severity on activity levels and physical disability in the context of high pain acceptance. We hypothesized that pain acceptance moderates the effect of pain severity on general activity and physical disability, such that at higher levels of acceptance, the deleterious effect of pain is mitigated.Methods: Two hundred seven patients with chronic pain were recruited from three clinics in a large southwestern military treatment facility. Participants completed an anonymous self-report battery of standardized measures, including the Chronic Pain Acceptance Questionnaire, modified Oswestry Disability Index, and Pain Severity and General Activity subscales of the West Haven-Yale Multidimensional Pain Inventory.Results: Chronic pain acceptance was found to significantly moderate relations between pain severity and general activity (b  =  0.0061, t(198) = 2.75, P = 0.007, 95% confidence interval [CI] = 0.002 to 0.011) and pain severity and disability (b  =  0.036, t(193) = -2.564, P = 0.011, 95% CI = -0.063 to -0.008). In the context of higher acceptance, the negative effect of pain on activity and disability appeared reduced. Conversely, in the context of low acceptance, the effect of pain on disability appeared accentuated at all levels of pain severity.Conclusions: Higher acceptance mitigated both activity level and disability in a military-affiliated clinical sample of patients with chronic pain. Results further establish the role of acceptance in relation to functioning in a unique sample of people with chronic pain. These findings have implications for understanding and enhancing functioning in chronic pain populations.
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30.
  • Marina, Neyssa M., et al. (författare)
  • Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1) : an open-label, international, randomised controlled trial
  • 2016
  • Ingår i: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.
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31.
  • McPhearson, Timon, et al. (författare)
  • A social-ecological-technological systems framework for urban ecosystem services
  • 2022
  • Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:5, s. 505-518
  • Tidskriftsartikel (refereegranskat)abstract
    • As rates of urbanization and climatic change soar, decision-makers are increasingly challenged to provide innovative solutions that simultaneously address climate change impacts and risks and inclusively ensure quality of life for urban residents. Cities have turned to nature-based solutions to help address these challenges. Nature-based solutions, through the provision of ecosystem services, can yield numerous benefits for people and address multiple challenges simultaneously. Yet, efforts to mainstream nature-based solutions are impaired by the complexity of the interacting social, ecological, and technological dimensions of urban systems. This complexity must be understood and managed to ensure ecosystem-service provisioning is effective, equitable, and resilient. Here, we provide a social-ecological-technological system (SETS) framework that builds on decades of urban ecosystem services research to better understand four core challenges associated with urban nature-based solutions: multi-functionality, systemic valuation, scale mismatch of ecosystem services, and inequity and injustice. The framework illustrates the importance of coordinating natural, technological, and socio-economic systems when designing, planning, and managing urban nature-based solutions to enable optimal social-ecological outcomes.
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32.
  • Welsh, Gavin I, et al. (författare)
  • Insulin signaling to the glomerular podocyte is critical for normal kidney function
  • 2010
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 12:4, s. 329-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetic nephropathy (DN) is the leading cause of renal failure in the world. It is characterized by albuminuria and abnormal glomerular function and is considered a hyperglycemic "microvascular" complication of diabetes, implying a primary defect in the endothelium. However, we have previously shown that human podocytes have robust responses to insulin. To determine whether insulin signaling in podocytes affects glomerular function in vivo, we generated mice with specific deletion of the insulin receptor from their podocytes. These animals develop significant albuminuria together with histological features that recapitulate DN, but in a normoglycemic environment. Examination of "normal" insulin-responsive podocytes in vivo and in vitro demonstrates that insulin signals through the MAPK and PI3K pathways via the insulin receptor and directly remodels the actin cytoskeleton of this cell. Collectively, this work reveals the critical importance of podocyte insulin sensitivity for kidney function.
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33.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)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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34.
  • Dandoy, Christopher E., et al. (författare)
  • Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant
  • 2020
  • Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    •  Importance: Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other).Objective: To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.Design, Setting, and Participants: A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018.Main Outcomes and Measures: Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups.Results: Of the 16875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]).Conclusions and Relevance: In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population. This cohort study examines the incidence, timing, risk factors, and outcomes of patients who develop mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI) in the first 100 days after hematopoietic stem cell transplant (HSCT).
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35.
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36.
  • Hale, Madeline R, et al. (författare)
  • Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment.
  • 2024
  • Ingår i: Neurobiology of aging. - 1558-1497. ; 133, s. 87-98
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropsychological measures sensitive to decline in the preclinical phase of Alzheimer's diseaseare needed. We previously demonstrated that higher amyloid-beta (Aβ) assessed by positron emission tomography in adults without cognitive impairment was associated with recall of fewer proper names in Logical Memory story recall. The current study investigated the association between proper names and cerebrospinal fluidbiomarkers (Aβ42/40, phosphorylated tau181 [pTau181], neurofilament light) in 223 participants from the Wisconsin Registry for Alzheimer's Prevention. We assessed associations between biomarkers and delayed Logical Memory total score and proper names using binary logistic regressions. Sensitivity analyses used multinomial logistic regression and stratified biomarker groups. Lower Logical Memory total score and proper names scores from themost recent visit were associated with biomarker positivity. Relatedly, there was a 27% decreased risk of being classified Aβ42/40+/pTau181+for each additional proper name recalled. A linear mixed effects model found that longitudinal change in proper names recall was predicted by biomarker status. These results demonstrate a novel relationship between proper names and Alzheimer's disease-cerebrospinal fluid pathology.
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37.
  • Liu, Chang, et al. (författare)
  • SN 2020jgb : A Peculiar Type Ia Supernova Triggered by a Helium-shell Detonation in a Star-forming Galaxy
  • 2023
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 946:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The detonation of a thin (less than or similar to 0.03 M (circle dot)) helium shell (He-shell) atop a similar to 1 M (circle dot) white dwarf (WD) is a promising mechanism to explain normal Type Ia supernovae (SNe Ia), while thicker He-shells and less massive WDs may explain some recently observed peculiar SNe Ia. We present observations of SN 2020jgb, a peculiar SN Ia discovered by the Zwicky Transient Facility (ZTF). Near maximum brightness, SN 2020jgb is slightly subluminous (ZTF g-band absolute magnitude -18.7 mag less than or similar to M ( g ) less than or similar to -18.2 mag depending on the amount of host-galaxy extinction) and shows an unusually red color (0.2 mag less than or similar to g (ZTF) - r (ZTF) less than or similar to 0.4 mag) due to strong line-blanketing blueward of similar to 5000 angstrom. These properties resemble those of SN 2018byg, a peculiar SN Ia consistent with an He-shell double detonation (DDet) SN. Using detailed radiative transfer models, we show that the optical spectroscopic and photometric evolution of SN 2020jgb is broadly consistent with a similar to 0.95-1.00 M (circle dot) (C/O core + He-shell) progenitor ignited by a greater than or similar to 0.1 M (circle dot) He-shell. However, one-dimensional radiative transfer models without non-local-thermodynamic-equilibrium treatment cannot accurately characterize the line-blanketing features, making the actual shell mass uncertain. We detect a prominent absorption feature at similar to 1 mu m in the near-infrared (NIR) spectrum of SN 2020jgb, which might originate from unburnt helium in the outermost ejecta. While the sample size is limited, we find similar 1 mu m features in all the peculiar He-shell DDet candidates with NIR spectra obtained to date. SN 2020jgb is also the first peculiar He-shell DDet SN discovered in a star-forming dwarf galaxy, indisputably showing that He-shell DDet SNe occur in both star-forming and passive galaxies, consistent with the normal SN Ia population.
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38.
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39.
  • Pasquini, Ricardo, et al. (författare)
  • HLA-matched sibling hematopoietic stem cell transplantation for fanconi anemia: comparison of irradiation and nonirradiation containing conditioning regimens.
  • 2008
  • Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 14:10, s. 1141-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Related to the underlying DNA repair defect that is the hallmark of Fanconi anemia (FA), preparatory regimen-related toxicities have been obstacles to hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and severity of regimen-related toxicities, nonirradiation regimens have been explored. The aim of this study is to compare outcomes after irradiation and nonirradiation regimens in 148 FA patients and identify risk factors impacting upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host disease (aGVHD, GVHD), and mortality were similar after irradiation and nonirradiation regimens. In both groups of recipients aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. With median follow-ups >5 years, the 5-year probability of overall survival, adjusted for factors impacting overall mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61. In view of the high risk of cancer and other radiation-related effects on growth and development, these results support the use of nonirradiation preparatory regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years, longer follow-up is required before definitive statements can be made regarding the impact of nonirradiation regimens on cancer risk.
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40.
  • Rohwedder, A., et al. (författare)
  • Cloudbuster: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples
  • 2022
  • Ingår i: Interface Focus. - : ROYAL SOC. - 2042-8898 .- 2042-8901. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Three-dimensional (3D) spheroid cultures are generating increasing interest in cancer research, e.g. for the evaluation of pharmacological effects of novel small molecule inhibitors. This is mainly due to the fact that such 3D structures reflect physiological characteristics of tumours and the cellular microenvironments they reside in more faithfully than two-dimensional (2D) cell cultures; in addition, they allow the reduction of animal experiments while providing significantly relevant human-based models. Quantification of such organoid structures as well as the mainly slice-based acquisition and thus forced 2D representation of 3D spheroids provide a challenge for the interpretation of the associated generated data. Here, we provide a novel open-source workflow to reconstruct a 3D entity from slice-recorded microscopical images with or without treatment with anti-migratory small molecule inhibitors. This reconstruction produces distinct point clouds as basis for subsequent comparison of basic readout parameters using average computer processor, memory and graphics resources within an acceptable time frame. We were able to validate the usefulness of this workflow using 3D data generated by various imaging techniques, including z-stacks from confocal microscopy and histochemically labelled spheroid sectioning, and demonstrate the possibility to accurately characterize inhibitor effects in great detail.
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41.
  • Yeung, A T Y, et al. (författare)
  • Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function
  • 2015
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • The ability to differentiate genetically modified mouse embryonic stem (ES) cells into functional macrophages provides a potentially attractive resource to study host-pathogen interactions without the need for animal experimentation. This is particularly useful in instances where the gene of interest is essential and a knockout mouse is not available. Here we differentiated mouse ES cells into macrophages in vitro and showed, through a combination of flow cytometry, microscopic imaging and RNA-Seq, that ES cell-derived macrophages responded to S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages. We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is known to play a role in tumour necrosis factor-α signalling but has not been studied for its role in infections or response to Toll-like receptor agonists. Interestingly, traf2-deficient macrophages produced reduced levels of inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin stimulation and exhibited increased susceptibility to S. Typhimurium infection.
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42.
  • Arp, Hans Peter H., et al. (författare)
  • The presence, emission and partitioning behavior of polychlorinated biphenyls in waste, leachate and aerosols from Norwegian waste-handling facilities
  • 2020
  • Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 715, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Even though production and open use of polychlorinated biphenyls (PCBs) have been phased out in Western industrialised countries since the 1980s, PCBs were still present in waste collected from different waste handling facilities in Norway in 2013. Sums of seven indicator-PCBs (I-PCB7:PCB-28, -52, -101, -118, -138, -153 and -180) were highest in plastic waste (3700 +/- 1800 mu g/kg, n=15), waste electrical and electronic equipment (WEEE) (1300 +/- 400 mu g/kg, n=12) and fine vehicle fluff (1800 = 1400 mu g/kg, n=4) and lowest in glass waste, combustibles, bottom ash and fly ash (0.3 to 65 mu g/kg). Concentrations in leachate water varied from 1.7 to 2900 ng/L, with higher concentrations found at vehicle and WEEE handling facilities. Particles in leachate water exhibited similar PCB sorption properties as solid waste collected on site, with waste-water partitioning coefficients ranging from 10(5)to 10(7) .I-PCB7 in air samples collected at the sites were mostly in the gas phase (100-24000 pg/m(3)), compared to those associated with particles (9-1900 pg/m(3)). In contrast, brominated flame retardants (BFRs) in the same samples were predominantly found associated with particles (e.g. sum of 10 brominated diethyl ethers, Sigma BDE10, associated with particles 77-194,000 pg/m(3)) compared to the gas phase (Sigma DE10 6-473 pg/m(3)). Measured gas-phase I-PCB7 concentrations are less than predicted, assuming waste-air partitioning in equilibrium with predominant waste on site. However, the gas-particle partitioning behavior of PCBs and BFRs could be predicted using an established partitioning model for ambient aerosols. PCB emissions from Norwegian waste handling facilities occurred primarily in the form of atmospheric vapor or leachate particles.
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43.
  • Hale, G, et al. (författare)
  • Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration
  • 2004
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:4, s. 948-955
  • Tidskriftsartikel (refereegranskat)abstract
    • Alemtuzumab is a humanized anti-CD52 antibody licensed for refractory B-cell chronic lymphocytic leukemia (B-CLL), when given intravenously at 30 mg thrice weekly. However, the intravenous route is associated with infusion-related reactions and is inconvenient. We measured blood concentrations in 30 relapsed patients treated with intravenous alemtuzumab and in 20 patients from a previously untreated group who received similar doses subcutaneously. Highest trough samples in the intravenous group were less than 0.5 μg/mL to 18.3 μg/mL (mean 5.4 μg/mL). The cumulative dose required to reach 1.0 μg/mL was 13 mg to 316 mg (mean 90 mg). Higher blood concentrations correlated with the achievement of better clinical responses and minimal residual disease. The highest measured concentrations in the subcutaneous group were similar (0.6 μg/mL to 24.8 μg/mL, mean 5.4 μg/mL). However, the cumulative dose to reach 1.0 μg/mL was higher: 146 mg to 1106 mg (mean 551 mg). No antiglobulin responses were detected in 30 patients given intravenous alemtuzumab whereas 2 of 32 patients given subcutaneous alemtuzumab made substantial anti-idiotype responses. Thus, subcutaneous alemtuzumab achieved concentrations similar to those for intravenous alemtuzumab, although with slightly higher cumulative doses. Subcutaneous alemtuzumab is more convenient and better tolerated but may be associated with some patients forming anti–alemtuzumab antibodies, particularly those patients who were previously untreated.
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44.
  • Kupryianchyk, Darya, et al. (författare)
  • Positioning Activated Carbon Amendment Technologies in a Novel Framework for Sediment Management
  • 2015
  • Ingår i: Integrated Environmental Assessment and Management. - : Wiley. - 1551-3777 .- 1551-3793. ; 11:2, s. 221-234
  • Forskningsöversikt (refereegranskat)abstract
    • Contaminated sediments can pose serious threats to human health and the environment by acting as a source of toxic chemicals. The amendment of contaminated sediments with strong sorbents like activated C (AC) is a rapidly developing strategy to manage contaminated sediments. To date, a great deal of attention has been paid to the technical and ecological features and implications of sediment remediation with AC, although science in this field still is rapidly evolving. This article aims to provide an update on the recent literature on these features, and for the first time provides a comparison of sediment remediation with AC to other sediment management options, emphasizing their full-scale application. First, a qualitative overview of advantages and disadvantages of current alternatives to remediate contaminated sediments is presented. Subsequently, AC treatment technology is critically reviewed, including current understanding of the effectiveness and ecological safety for the use of AC in natural systems. Finally, this information is used to provide a novel framework for supporting decisions concerning sediment remediation and beneficial reuse.
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45.
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46.
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47.
  • Martinsen, V., et al. (författare)
  • pH effects of the addition of three biochars to acidic Indonesian mineral soils
  • 2015
  • Ingår i: Soil science and plant nutrition (Tokyo). - : Informa UK Limited. - 0038-0768 .- 1747-0765. ; 61:5, s. 821-834
  • Tidskriftsartikel (refereegranskat)abstract
    • Soil acidity may severely reduce crop production. Biochar (BC) may increase soil pH and cation exchange capacity (CEC) but reported effects differ substantially. In a systematic approach, using a standardized protocol on a uniquely large number set of 31 acidic soils, we quantified the effect of increasing amounts (0-30%; weight:weight) of three types of field-produced BCs (from cacao (Theobroma cacao. L.) shell, oil palm (Elaeis guineensis. Jacq.) shell and rice (Oryza sativa. L.) husk) on soil pH and CEC. Soils were sampled from croplands at Java, Sumatra and Kalimantan, Indonesia. All BCs caused a significant increase in mean soil pH with a stronger response and a greater maximum increase for the cacao shell BC addition, due to a greater acid neutralizing capacity (ANC) and larger amounts of extractable base cations. At 1% BC addition, corresponding to about 30tonsha(-1), the estimated increase in soil pH from the initial mean pH of 4.7 was about 0.5 units for the cacao shell BC, whereas this was only 0.05 and 0.04 units for the oil palm shell and rice husk BC, respectively. Besides depending on BC type, the increase in soil pH upon the addition of each of the three BCs was mainly dependent on soil CEC (low CEC resulting in stronger pH increase), and to a lesser extent on initial soil pH (higher initial pH resulting in stronger pH increase). Addition of BC also increased the amount of exchangeable base cations (cacao shell >> oil palm and rice husk) and CEC. Through this systematic screening of the effect of BC on pH and CEC of acidic soils, we show that a small addition of BC, in particular if made of cacao shell, to acidic agricultural soils increases soil pH and CEC. However, the response is highly dependent on the type, quality and amount of the added BC as well as on intrinsic soil properties, mainly CEC.
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48.
  • Morin, Nicolas A. O., et al. (författare)
  • The presence and partitioning behavior of flame retardants in waste, leachate, and air particles from Norwegian waste-handling facilities
  • 2017
  • Ingår i: Journal of Environmental Sciences(China). - : Science Press. - 1001-0742 .- 1878-7320. ; 62, s. 115-132
  • Tidskriftsartikel (refereegranskat)abstract
    • Flame retardants in commercial products eventually make their way into the waste stream. Herein the presence of flame retardants in Norwegian landfills, incineration facilities and recycling sorting/defragmenting facilities is investigated. These facilities handled waste electrical and electronic equipment (WEEE), vehicles, digestate, glass, combustibles, bottom ash and fly ash. The flame retardants considered included polybrominated diphenyl ethers (∑ BDE-10) as well as dechlorane plus, polybrominated biphenyls, hexabromobenzene, pentabromotoluene and pentabromoethylbenzene (collectively referred to as ∑ FR-7). Plastic, WEEE and vehicles contained the largest amount of flame retardants (∑ BDE-10: 45,000–210,000 μg/kg; ∑ FR-7: 300–13,000 μg/kg). It was hypothesized leachate and air concentrations from facilities that sort/defragment WEEE and vehicles would be the highest. This was supported for total air phase concentrations (∑ BDE-10: 9000–195,000 pg/m3 WEEE/vehicle facilities, 80–900 pg/m3 in incineration/sorting and landfill sites), but not for water leachate concentrations (e.g., ∑ BDE-10: 15–3500 ng/L in WEEE/Vehicle facilities and 1–250 ng/L in landfill sites). Landfill leachate exhibited similar concentrations as WEEE/vehicle sorting and defragmenting facility leachate. To better account for concentrations in leachates at the different facilities, waste-water partitioning coefficients, Kwaste were measured (for the first time to our knowledge for flame retardants). WEEE and plastic waste had elevated Kwaste compared to other wastes, likely because flame retardants are directly added to these materials. The results of this study have implications for the development of strategies to reduce exposure and environmental emissions of flame retardants in waste and recycled products through improved waste management practices.
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49.
  • Okkenhaug, G, et al. (författare)
  • The presence and leachability of antimony in different wastes and waste handling facilities in Norway
  • 2015
  • Ingår i: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 17:11, s. 1880-1891
  • Tidskriftsartikel (refereegranskat)abstract
    • The environmental behaviour of antimony (Sb) is gathering attention due to its increasingly extensive use in various products, particularly in plastics. Because of this it may be expected that plastic waste is an emission source for Sb in the environment. This study presents a comprehensive field investigation of Sb concentrations in diverse types of waste from waste handling facilities in Norway. The wastes included waste electrical and electronic equipment (WEEE), glass, vehicle fluff, combustibles, bottom ash, fly ash and digested sludge. The highest solid Sb concentrations were found in WEEE and vehicle plastic (from 1238 to 1715 mg kg−1) and vehicle fluff (from 34 to 4565 mg kg−1). The type of acid used to digest the diverse solid waste materials was also tested. It was found that HNO3:HCl extraction gave substantially lower, non-quantitative yields compared to HNO3:HF. The highest water-leachable concentration for wastes when mixed with water at a 1:10 ratio were observed for plastic (from 0.6 to 2.0 mg kg−1) and bottom ash (from 0.4 to 0.8 mg kg−1). For all of the considered waste fractions, Sb(V) was the dominant species in the leachates, even though Sb(III) as Sb2O3 is mainly used in plastics and other products, indicating rapid oxidation in water. This study also presents for the first time a comparison of Sb concentrations in leachate at waste handling facilities using both active grab samples and DGT passive samples. Grab samples target the total suspended Sb, whereas DGT targets the sum of free- and other chemically labile species. The grab sample concentrations (from 0.5 to 50 μg L−1) were lower than the predicted no-effect concentration (PNEC) of 113 μg L−1. The DGT concentrations were substantially lower (from 0.05 to 9.93 μg L−1) than the grab samples, indicating much of the Sb is present in a non-available colloidal form. In addition, air samples were taken from the chimney and areas within combustible waste incinerators, as well as from the vent of WEEE sorting facility. The WEEE vent had the highest Sb concentration (from <100 to 2200 ng m−3), which were orders of magnitude higher than the air surrounding the combustible shredder (from 25 to 217 ng m−3), and the incinerator chimney (from <30 to 100 ng m−3). From these results, it seems evident that Sb from waste is not an environmental concern in Norway, and that Sb is mostly readily recovered from plastic and bottom ash.
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50.
  • Olsson, Richard T., et al. (författare)
  • Acceleration of the cationic polymerization of an epoxy with hexanediol
  • 2004
  • Ingår i: Journal of thermal analysis and calorimetry (Print). - 1388-6150 .- 1588-2926. ; 76:2, s. 367-377
  • Tidskriftsartikel (refereegranskat)abstract
    • Thin films of 3,4-epoxycyclohexyhnethyl 3',4'-epoxycyclohexane carboxylate were UV irradiated (1.1 J cm(-2)) under isothermal conditions ranging from 0 to 50degreesC. Under these conditions the polymerization advanced quickly but only to a conversion level of less than 10% before the reaction rate slowed by more than an order of magnitude. This drop off in rate was not caused by the glass transition temperature, T-g, reaching or exceeding the reaction temperature, T-rxn, since the epoxide's T-g remained at least 40degreesC below T-rxn. Raising the sample temperature above 60degreesC caused a sharp increase in the conversion level. At 100degreesC conversion exceeds 80% and the ultimate T-g approaches 190degreesC. The addition of 10 mass% 1,6-hexanediol, HD, to the epoxy caused the conversion at room temperature to quintuple over the level obtained without the alcohol present. The heat liberated from this alcohol epoxy blend during cure on a UV conveyor belt system caused the sample's temperature to increase by about 100degreesC above ambient whereas the epoxy alone under these conditions only experienced a modest temperature rise of about 26degreesC. If the amount of HD in the blend is increased above 10% the heat of reaction at 23degreesC decreases due to HD being trapped in a nonreactive crystalline phase. Boosting reaction temperatures above 50degreesC melts the HD crystals and yields significantly improved conversion ratios. As the level of alcohol blended with the epoxy is raised its ultimate T-g is lowered and when the concentration of alcohol in the blend nears 30 mass% T-g drops below room temperature.
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