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1.
  • Glasbey, JC, et al. (author)
  • 2021
  • swepub:Mat__t
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  • Khatri, C, et al. (author)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Journal article (peer-reviewed)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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8.
  • De Angelis, A., et al. (author)
  • Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
  • 2018
  • In: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
  • Journal article (peer-reviewed)abstract
    • e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
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  • Santoro, V., et al. (author)
  • The HighNESS Project at the European Spallation Source : Current Status and Future Perspectives
  • 2024
  • In: Nuclear science and engineering. - 0029-5639 .- 1943-748X. ; 198:1, s. 31-63
  • Journal article (peer-reviewed)abstract
    • The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that, once completed at full specifications, will operate the world's most powerful pulsed neutron source. Supported by a 3 M Euro Research and Innovation Action within the European Union Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source located below the spallation target. Compared to the first source, which is located above the spallation target and designed for high cold and thermal brightness, the new source is being optimized to deliver higher intensity and a shift to longer wavelengths in the spectral regions of cold neutrons (CNs) (2 to 20 & Aring;), very cold neutrons (VCNs) (10 to 120 & Aring;), and ultracold neutrons (UCNs) (> 500 & Aring;). The second source consists of a large liquid deuterium moderator to deliver CNs and serve secondary VCN and UCN sources, for which different options are under study. These new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. The HighNESS project is now entering its last year, and we are working toward the Conceptual Design Report of the ESS upgrade. In this paper, results obtained in the first 2 years, ongoing developments, and future perspectives are described.
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  • Santoro, V., et al. (author)
  • DEVELOPMENT OF A HIGH INTENSITY NEUTRON SOURCE AT THE EUROPEAN SPALLATION SOURCE : THE HIGHNESS PROJECT
  • 2022
  • In: Proceedings of the 14th International Topical Meeting on Nuclear Applications of Accelerators, AccApp 2021, Embedded with the 2021 ANS Winter Meeting. - 9780894487842 ; , s. 11-20
  • Conference paper (peer-reviewed)abstract
    • The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that will operate the world’s most powerful pulsed neutron source. Supported by a 3M Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source below the spallation target. Compared to the first source, located above the spallation target and designed for high cold and thermal brightness, the new source will provide higher intensity, and a shift to longer wavelengths in the spectral regions of cold (2-20 Å), very cold (VCN, 10-120 Å), and ultra cold (UCN, > 500 Å) neutrons. The core of the second source will consist of a large liquid deuterium moderator to deliver a high flux of cold neutrons and to serve secondary VCN and UCN sources, for which different options are under study. The features of these new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. Part of the HighNESS project is also dedicated to the development of future instruments that will make use of the new source and will complement the initial suite of instruments in construction at ESS. The HighNESS project started in October 2020. In this paper, the ongoing developments and the results obtained in the first year are described.
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13.
  • Santoro, V., et al. (author)
  • HighNESS conceptual design report: Volume I
  • 2024
  • In: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 85-314
  • Journal article (peer-reviewed)abstract
    • The European Spallation Source, currently under construction in Lund, Sweden, is a multidisciplinary international laboratory. Once completed to full specifications, it will operate the world’s most powerful pulsed neutron source. Supported by a 3 million Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) has been completed to develop a second neutron source located below the spallation target. Compared to the first source, designed for high cold and thermal brightness, the new source has been optimized to deliver higher intensity, and a shift to longer wavelengths in the spectral regions of cold (CN, 2–20 Å), very cold (VCN, 10–120 Å), and ultracold (UCN, >500 Å) neutrons. The second source comprises a large liquid deuterium moderator designed to produce CN and support secondary VCN and UCN sources. Various options have been explored in the proposed designs, aiming for world-leading performance in neutronics. These designs will enable the development of several new instrument concepts and facilitate the implementation of a high-sensitivity neutron-antineutron oscillation experiment (NNBAR). This document serves as the Conceptual Design Report for the HighNESS project, representing its final deliverable.
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14.
  • Santoro, V., et al. (author)
  • HighNESS conceptual design report: Volume II. the NNBAR experiment.
  • 2024
  • In: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 315-406
  • Journal article (peer-reviewed)abstract
    • A key aim of the HighNESS project for the European Spallation Source is to enable cutting-edge particle physics experiments. This volume presents a conceptual design report for the NNBAR experiment. NNBAR would exploit a new cold lower moderator to make the first search in over thirty years for free neutrons converting to anti-neutrons. The observation of such a baryon-number-violating signature would be of fundamental significance and tackle open questions in modern physics, including the origin of the matter-antimatter asymmetry. This report shows the design of the beamline, supermirror focusing system, magnetic and radiation shielding, and anti-neutron detector necessary for the experiment. A range of simulation programs are employed to quantify the performance of the experiment and show how background can be suppressed. For a search with full background suppression, a sensitivity improvement of three orders of magnitude is expected, as compared with the previous search. Civil engineering studies for the NNBAR beamline are also shown, as is a costing model for the experiment.
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  • Bernasconi, G, et al. (author)
  • Evolutionary ecology of the prezygotic stage
  • 2004
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 303:5660, s. 971-975
  • Research review (peer-reviewed)abstract
    • The life cycles of sexually reproducing animals and flowering plants begin with male and female gametes and their fusion to form a zygote. Selection at this earliest stage is crucial for offspring quality and raises similar evolutionary issues, yet zoology and botany use dissimilar approaches. There are striking parallels in the role of prezygotic competition for sexual selection on males, cryptic female choice, sexual conflict, and against selfish genetic elements and genetic incompatibility. In both groups, understanding the evolution of sex-specific and reproductive traits will require an appreciation of the effects of prezygotic competition on fitness.
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  • Kreins, AY, et al. (author)
  • Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome
  • 2015
  • In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:10, s. 1641-1662
  • Journal article (peer-reviewed)abstract
    • Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
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  • Opheim, G., et al. (author)
  • 7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice
  • 2021
  • In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 96:7, s. 327-341
  • Journal article (peer-reviewed)abstract
    • Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.
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  • Van Hoovels, L., et al. (author)
  • Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results
  • 2022
  • In: RMD Open. - : BMJ. - 2056-5933. ; 8:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays. MATERIALS AND METHODS: Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls. RESULTS: Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA. CONCLUSION: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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21.
  • Wiedemeier, Daniel B., et al. (author)
  • Characterization, Quantification and Compound-specific Isotopic Analysis of Pyrogenic Carbon Using Benzene Polycarboxylic Acids (BPCA)
  • 2016
  • In: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :111
  • Journal article (peer-reviewed)abstract
    • Fire-derived, pyrogenic carbon (PyC), sometimes called black carbon (BC), is the carbonaceous solid residue of biomass and fossil fuel combustion, such as char and soot. PyC is ubiquitous in the environment due to its long persistence, and its abundance might even increase with the projected increase in global wildfire activity and the continued burning of fossil fuel. PyC is also increasingly produced from the industrial pyrolysis of organic wastes, which yields charred soil amendments (biochar). Moreover, the emergence of nanotechnology may also result in the release of PyC-like compounds to the environment. It is thus a high priority to reliably detect, characterize and quantify these charred materials in order to investigate their environmental properties and to understand their role in the carbon cycle. Here, we present the benzene polycarboxylic acid (BPCA) method, which allows the simultaneous assessment of PyC's characteristics, quantity and isotopic composition (C-13 and C-14) on a molecular level. The method is applicable to a very wide range of environmental sample materials and detects PyC over a broad range of the combustion continuum, i.e., it is sensitive to slightly charred biomass as well as high temperature chars and soot. The BPCA protocol presented here is simple to employ, highly reproducible, as well as easily extendable and modifiable to specific requirements. It thus provides a versatile tool for the investigation of PyC in various disciplines, ranging from archeology and environmental forensics to biochar and carbon cycling research.
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  • Bernasconi, Valentina, 1989, et al. (author)
  • Porous Nanoparticles With Self-Adjuvanting M2e-Fusion Protein and Recombinant Hemagglutinin Provide Strong and Broadly Protective Immunity Against Influenza Virus Infections
  • 2018
  • In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
  • Journal article (peer-reviewed)abstract
    • Due to the high risk of an outbreak of pandemic influenza, the development of a broadly protective universal influenza vaccine is highly warranted. The design of such a vaccine has attracted attention and much focus has been given to nanoparticle-based influenza vaccines which can be administered intranasally. This is particularly interesting since, contrary to injectable vaccines, mucosal vaccines elicit local IgA and lung resident T cell immunity, which have been found to correlate with stronger protection in experimental models of influenza virus infections. Also, studies in human volunteers have indicated that pre-existing CD4(+) T cells correlate well to increased resistance against infection. We have previously developed a fusion protein with 3 copies of the ectodomain of matrix protein 2 (M2e), which is one of the most explored conserved influenza A virus antigens for a broadly protective vaccine known today. To improve the protective ability of the self-adjuvanting fusion protein, CTA1-3M2e-DD, we incorporated it into porous maltodextrin nanoparticles (NPLs). This proof-of-principle study demonstrates that the combined vaccine vector given intranasally enhanced immune protection against a live challenge infection and reduced the risk of virus transmission between immunized and unimmunized individuals. Most importantly, immune responses to NPLs that also contained recombinant hemagglutinin (HA) were strongly enhanced in a CTA1-enzyme dependentmanner and we achieved broadly protective immunity against a lethal infection with heterosubtypic influenza virus. Immune protection wasmediated by enhanced levels of lung resident CD4(+) T cells as well as anti-HA and -M2e serum IgG and local IgA antibodies.
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  • Bouamar, R., et al. (author)
  • Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
  • 2013
  • In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 13:5, s. 1253-1261
  • Journal article (peer-reviewed)abstract
    • Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac.
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  • Covey, Kristofer, et al. (author)
  • Carbon and Beyond : The Biogeochemistry of Climate in a Rapidly Changing Amazon
  • 2021
  • In: Frontiers in Forests and Gobal Change. - : Frontiers Media S.A.. - 2624-893X. ; 4
  • Research review (peer-reviewed)abstract
    • The Amazon Basin is at the center of an intensifying discourse about deforestation, land-use, and global change. To date, climate research in the Basin has overwhelmingly focused on the cycling and storage of carbon (C) and its implications for global climate. Missing, however, is a more comprehensive consideration of other significant biophysical climate feedbacks [i.e., CH4, N2O, black carbon, biogenic volatile organic compounds (BV0Cs), aerosols, evapotranspiration, and albedo] and their dynamic responses to both localized (fire, land-use change, infrastructure development, and storms) and global (warming, drying, and some related to El Nino or to warming in the tropical Atlantic) changes. Here, we synthesize the current understanding of (1) sources and fluxes of all major forcing agents, (2) the demonstrated or expected impact of global and local changes on each agent, and (3) the nature, extent, and drivers of anthropogenic change in the Basin. We highlight the large uncertainty in flux magnitude and responses, and their corresponding direct and indirect effects on the regional and global climate system. Despite uncertainty in their responses to change, we conclude that current warming from non-CO2 agents (especially CH4 and N2O) in the Amazon Basin largely offsets- and most likely exceeds-the climate service provided by atmospheric CO2 uptake. We also find that the majority of anthropogenic impacts act to increase the radiative forcing potential of the Basin. Given the large contribution of less-recognized agents (e.g., Amazonian trees alone emit similar to 3.5% of all global CH4), a continuing focus on a single metric (i.e., C uptake and storage) is incompatible with genuine efforts to understand and manage the biogeochemistry of climate in a rapidly changing Amazon Basin.
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25.
  • Gierga, Merle, et al. (author)
  • Purification of fire derived markers for mu g scale isotope analysis (delta C-13, Delta C-14) using high performance liquid chromatography (HPLC)
  • 2014
  • In: Organic Geochemistry. - : Elsevier BV. - 0146-6380 .- 1873-5290. ; 70, s. 1-9
  • Journal article (peer-reviewed)abstract
    • Black carbon (BC) is the residue of incomplete biomass combustion. It is ubiquitous in nature and, due to its relative persistence, is an important factor in Earth's slow-cycling carbon pool. This resistant nature makes pure BC one of the most used materials for C-14 dating to elucidate its formation date or residence time in the environment. However, most BC samples cannot be physically separated from their matrices, precluding accurate C-14 values. Here we present a method for radiocarbon dating of the oxidation products of BC, benzene polycarboxylic acids, thereby circumventing interference from extraneous carbon. Individual compounds were isolated using high performance liquid chromatography (HPLC) and converted to CO2 via wet chemical oxidation for C-13 and C-14 isotope analysis. A detailed assessment was performed to identify and quantify sources of extraneous carbon contamination using two process standards with distinct isotopic signatures. The average blank was 1.6 +/- 0.7 mu g C and had an average radiocarbon content of 0.90 +/- 0.50 (FC)-C-14. We successfully analyzed the C-14 content of individual benzene polycarboxylic acids with a sample size as small as 20-30 mu g C after correcting for the presence of the average blank. The combination of delta C-13 and (FC)-C-14 analysis helps interpret the results and enables monitoring of extraneous carbon contribution in a fast and cost efficient way. Such a molecular approach to radiocarbon dating of BC residues enables the expansion of isotopic BC studies to samples that have either been too small or strongly affected by non-fire derived carbon.
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