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2.
  • Prusti, T., et al. (författare)
  • The Gaia mission
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
  • Tidskriftsartikel (refereegranskat)abstract
    • Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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3.
  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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5.
  • Djoussé, L, et al. (författare)
  • Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.
  • 2003
  • Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 119A:3, s. 279-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
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6.
  • Lønborg, C., et al. (författare)
  • A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
  • 2024
  • Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters. 
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7.
  • Wortman, J. R., et al. (författare)
  • The 2008 update of the Aspergillus nidulans genome annotation: A community effort
  • 2009
  • Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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8.
  • Aamodt, A. H., et al. (författare)
  • Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
  • 2021
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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9.
  • Giblin, S. R., et al. (författare)
  • Pauling Entropy, Metastability, and Equilibrium in Dy2Ti2O7 Spin Ice
  • 2018
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Determining the fate of the Pauling entropy in the classical spin ice material Dy2Ti2O7 with respect to the third law of thermodynamics has become an important test case for understanding the existence and stability of ice-rule states in general. The standard model of spin ice-the dipolar spin ice model-predicts an ordering transition at T approximate to 0.15 K, but recent experiments by Pomaranski et al. suggest an entropy recovery over long timescales at temperatures as high as 0.5 K, much too high to be compatible with the theory. Using neutron scattering and specific heat measurements at low temperatures and with long timescales ( 0.35 K/10(6) s and 0.5 K/10(5) s, respectively) on several isotopically enriched samples, we find no evidence of a reduction of ice-rule correlations or spin entropy. High-resolution simulations of the neutron structure factor show that the spin correlations remain well described by the dipolar spin ice model at all temperatures. Furthermore, by careful consideration of hyperfine contributions, we conclude that the original entropy measurements of Ramirez et al. are, after all, essentially correct: The short-time relaxation method used in that study gives a reasonably accurate estimate of the equilibrium spin ice entropy due to a cancellation of contributions.
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10.
  • He, Min, et al. (författare)
  • Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion
  • 2016
  • Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 57:14, s. 6134-6146
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. METHODS. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. RESULTS. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 +/- 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHCMPC while 84.7 +/- 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 +/- 3.17% of cells were CK7-positive compared to PET where 67.10 +/- 12.08% of cells were CK7-positive cells. CONCLUSIONS. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.
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  • Uter, W., et al. (författare)
  • The epidemic of methylisothiazolinone contact allergy in Europe : follow-up on changing exposures
  • 2020
  • Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 34:2, s. 333-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Methylisothiazolinone (MI) has caused an unprecedented epidemic of contact allergy in Europe and elsewhere. Subsequently, regulatory action has been taken, at least in Europe, aiming at reducing risk of MI sensitization. Objective: To follow-up on the prevalence of contact allergy to MI in consecutively patch tested patients and assess the spectrum of products containing MI or methylchloroisothiazolinone (MCI)/MI in patients positive to MI which elicited current allergic contact dermatitis. Methods: A cross-sectional survey was performed in 2016 and 2017, including all adult patients patch tested with the baseline series (including MI 0.2% aq.) between 1 May and 31 October at 14 centres in 11 European countries. Patients with positive reactions (+ to +++) to MI were further examined regarding history, clinical characteristics and eliciting products, which were categorized into 34 types and 4 classes (leave-on, rinse-off, household, occupational). The results were compared with the reference year 2015. Results: A total of 317 patients, n = 202 of 4278 tested in 2016 (4.72%) and n = 115 of 3879 tested in 2017 (2.96%), had positive reactions to MI; the previous result from 2015 was 5.97% (P < 0.0001). The share of currently relevant contact allergy among all positive reactions declined significantly as well (P = 0.0032). Concerning product classes, a relative decline of leave-on and a relative increase of rinse-off and household products was noted. Conclusion: The prevalence of MI contact allergy decreased by 50% from 2015 to 2017. As a consequence of regulation, the share of cosmetics products (leave-on in particular) eliciting allergic contact dermatitis is decreasing. The chosen method of analysing causative products in sensitized patients has proven useful to monitor effects of intervention.
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14.
  • Beck, R., et al. (författare)
  • GPSDTN : Predictive velocity-enabled delay-tolerant networks for arctic research and sustainability
  • 2007
  • Ingår i: Second International Conference on Internet Monitoring and Protection (ICIMP 2007). - Los Alamitos, Calif : IEEE Computer Society Press. - 9780769529110
  • Konferensbidrag (refereegranskat)abstract
    • A Delay-Tolerant Network (DTN) is a necessity for communication nodes that may need to wait for long periods to form networks. The IETF Delay Tolerant Network Research Group is developing protocols to enable such networks for a broad variety of Earth and interplanetary applications. The Arctic would benefit from a predictive velocity-enabled version of DTN that would facilitate communications between sparse, ephemeral, often mobile and extremely power-limited nodes. We propose to augment DTN with power-aware, buffer-aware location- and time-based predictive routing for ad-hoc meshes to create networks that are inherently location and time (velocity) aware at the network level to support climate research, emergency services and rural education in the Arctic. On Earth, the primary source of location and universal time information for networks is the Global Positioning System (GPS). We refer to this Arctic velocity-enabled Delay-Tolerant Network protocol as "GPSDTN" accordingly. This paper describes our requirements analysis and general implementation strategy for GPSDTN to support Arctic research and sustainability efforts
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16.
  • Djoussé, Luc, et al. (författare)
  • Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
  • 2004
  • Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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17.
  • Drakenberg, Olof, 1964, et al. (författare)
  • Greening Development Planning: A review of country case studies for making the economic case for improved management of environment and natural resources : OECD Environment Working Papers, No. 5
  • 2009
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Different approaches to making the economic case for improved management of natural capital in national planning are reviewed in this report. In many low-income countries natural resources sectors (agriculture, mining, forestry, fishery, nature-based tourism) are identified as the engines of economic growth. However, a majority of the ecosystems on which human well-being depends are being degraded. The difficulties in providing economic and policy-relevant information about sustainable economic management of natural capital are often seen as an important reason for inadequate integration of the environment in macroeconomic and sector polices. The report concludes that the analysed country studies (Lao People's Democratic Republic, Mozambique, Peru, Tajikistan and Uganda) mainly relied on existing domestic or international analytical work, used relatively basic calculations/data (such as the market value of fisheries, the value of timber sold etc.) and often formed part of a broader analytical effort. Examples of findings in the country reports include prospects for increasing fiscal revenues from natural resources with more than 150 % (Mozambique) and estimates of costs associated with poor environmental management to be equivalent to 3.9 % of GDP (Peru). By involving policy makers in the process of making the country reports, and focusing on environmental and natural resources issues in function of their links with prioritised objectives like economic growth, poverty reduction and public health, the chances to influence policy making have been enhanced. Drawing from the review of these country case studies as well as literature on public policy, this report provides recommendations for governments wishing to undertake an economic analysis of the environment and natural resources management for planning purposes, and for OECD members interested in supporting the process.
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18.
  • Eekers, Danielle B. P., et al. (författare)
  • The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology
  • 2018
  • Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 128:1, s. 37-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (Cr) and magnetic resonance (MR) imaging. Methods: CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. Results: The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). Conclusion: In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at w.cancerdata.c and will be updated whenever required.
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19.
  • Gjestvang, D., et al. (författare)
  • Examination of how properties of a fissioning system impact isomeric yield ratios of the fragments
  • 2023
  • Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 108:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The population of isomeric states in the prompt decay of fission fragments-so-called isomeric yield ratios (IYRs)-is known to be sensitive to the angular momentum J that the fragment emerged with, and may therefore contain valuable information on the mechanism behind the fission process. In this work, we investigate how changes in the fissioning system impact the measured IYRs of fission fragments to learn more about what parameters affect angular momentum generation. To enable this, a new technique for measuring IYRs is first demonstrated. It is based on the time of arrival of discrete gamma rays, and has the advantage that it enables the study of the IYR as a function of properties of the partner nucleus. This technique is used to extract the IYR of 134Te, strongly populated in actinide fission, from the three different fissioning systems: 232Th(n, f), 238U(n, f), at two different neutron energies, as well as 252Cf(sf). The impacts of changing the fissioning system, the compound nuclear excitation energy, the minimum J of the binary partner, and the number of neutrons emitted on the IYR of 134Te are determined. The decay code TALYS is used in combination with the fission simulation code FREYA to calculate the primary fragment angular momentum from the IYR. We find that the IYR of 134Te has a slope of 0.004 +/- 0.002 with increase in compound nucleus (CN) mass. When investigating the impact on the IYR of increased CN excitation energy, we find no change with an energy increase similar to the difference between thermal and fast fission. By varying the mass of the partner fragment emerging with 134Te, it is revealed that the IYR of 134Te is independent of the total amount of prompt neutrons emitted from the fragment pair. This indicates that neutrons carry minimal angular momentum away from the fission fragments. Comparisons with the FREYA+TALYS simulations reveal that the average angular momentum in 134Te following 238U(n, f) is 6.0 h over bar . This is not consistent with the value deduced from recent CGMF calculations. Finally, the IYR sensitivity to the angular momentum of the primary fragment is discussed. These results are not only important to help understanding the underlying mechanism in nuclear fission, but can also be used to constrain and benchmark fission models, and are relevant to the gamma -ray heating problem of reactors.
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20.
  • Gonçalo, Margarida, et al. (författare)
  • Allergic contact dermatitis caused by nail acrylates in Europe. An EECDRG study
  • 2018
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 78:4, s. 254-260
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic contact dermatitis (ACD) caused by nail acrylates, also including methacrylates and cyanoacrylates here, is being increasingly reported. Methods: A retrospective study in 11 European Environmental Contact Dermatitis Research Group (EECDRG) clinics collected information on cases of ACD caused by nail acrylates diagnosed by aimed testing between 2013 and 2015. Results: Among 18 228 studied patients, 136 had ACD caused by nail acrylates (0.75%; 95%CI: 0.60–0.90), representing 67.3% (95%CI: 60.4–73.7) of ACD cases caused by acrylates. There were 135 females and 1 male, with a mean age ± standard deviation of 36.7 ± 12.2 years; 59 (43.4%) were exposed as consumers, and 77 (56.6%) were occupationally exposed. Occupational cases were more frequent in southern Europe (83.7%), and were younger (mean age of 33.4 ± 8.9 years); most developed ACD during the first year at work (65.0%), and at least 11.7% had to leave their jobs. Skin lesions involved the hands in 121 patients (88.9%) and the face in 50 (36.8%), with the face being the only affected site in 14 (10.3%). Most patients reacted to two or more acrylates on patch testing, mainly to 2-hydroxyethyl methacrylate (HEMA) (92.5%), 2-hydroxypropyl methacrylate (88.6%), ethylene glycol dimethacrylate (69.2%), and ethyl cyanoacrylate (9.9%). Conclusions: Nail cosmetics were responsible for the majority of ACD cases caused by acrylates, affecting nail beauticians and consumers, and therefore calling for stricter regulation and preventive measures. As HEMA detects most cases, and isolated facial lesions may be overlooked, inclusion of this allergen in the baseline series may be warranted.
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21.
  • Henjum, K., et al. (författare)
  • CSF sTREM2 in deliriumrelation to Alzheimer's disease CSF biomarkers A42, t-tau and p-tau
  • 2018
  • Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDelirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer's disease.MethodsWe analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n=120), and some of the patients developed delirium (n=65). A medical delirium cohort (n=26) was also examined. ELISA was used to determine the level of sTREM2 in CSF.ResultsDelirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p=0.046, n=15, n=44), particularly among patients developing delirium after CSF sampling (p=0.02, n=7, n=44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (r(S)=0.39, p=0.002, n=60) and correlated well with the CSF Alzheimer's disease biomarkers, A42, and t-tau/p-tau (r(S)=0.40, p=0.002, r(S)=0.46, p<0.001/ r(S)=0.49, p<0.001, n=60). Among patients with dementia, the level of A38 and A40 also correlated positively with sTREM2 in CSF (A38(MSD)r(S)=0.44, p=0.001; A40(MSD)r(S)=0.48, p<0.001; A42(MSD)r(S)=0.43, p<0.001, n=60).ConclusionThe findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk.
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23.
  • Knudtzen, F. C., et al. (författare)
  • Lyme neuroborreliosis with encephalitis; a systematic literature review and a Scandinavian cohort study
  • 2022
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X. ; 28:5, s. 649-656
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. Objectives: To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. Data sources: Medline, Embase, Scopus, Cochrane library. Study eligibility criteria: There was no discrimination on study type, time of publication or language. Participants: Review: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990–2019 were screened for patients with encephalitis. Methods: Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. Results: Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2–90 days). Of 38 patients with available follow-up after median 12 months (IQR 5–13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48–76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2–4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7–34), with further 7 days (IQR 3–34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113–389), 65.6% had residual symptoms. None had died. Conclusions: This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered. © 2021 The Author(s)
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24.
  • Landsverk, Ole J. B., et al. (författare)
  • Antibody-secreting plasma cells persist for decades in human intestine
  • 2017
  • Ingår i: Journal of Experimental Medicine. - NewYork, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:2, s. 309-317
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45(-) PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19(-) PC subsets support selection and maintenance of protective PCs for life in human intestine.
  •  
25.
  • Langbehn, D, et al. (författare)
  • A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.
  • 2004
  • Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 65:4, s. 267-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.
  •  
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