| 1. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Abu-Hayyeh, S., et al.
(författare)
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Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum
- 2016
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 63:4, s. 1287-1298
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Tidskriftsartikel (refereegranskat)abstract
- A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP.
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| 3. |
- Armstrong, R., et al.
(författare)
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Snow
- 2009
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Ingår i: Melting snow and ice – a call for action. - 9788276662641 ; , s. 24-31
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Benoit, D D, et al.
(författare)
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Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA.
- 2018
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Ingår i: Intensive care medicine. - 1432-1238. ; 44:7, s. 1039-1049
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Tidskriftsartikel (refereegranskat)abstract
- Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown.In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis.Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0-1.00) and 85.9% (75.4-92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20-2.92) or receiving a written TLD (HR 2.32, CI 1.11-4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former.Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.
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| 5. |
- DiJulio, D. D., et al.
(författare)
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A polyethylene-B4C based concrete for enhanced neutron shielding at neutron research facilities
- 2017
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 859, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- We present the development of a specialized concrete for neutron shielding at neutron research facilities, based on the addition of hydrogen atoms in the form of polyethylene and also B4C for enhancing the neutron capture properties of the concrete. We show information on the mechanical properties of the concrete and the neutronics, in particular its relevance to modern spallation neutron sources, such as the European Spallation Source (ESS), currently under construction in Lund, Sweden. The new concrete exhibits a 15% lower mass density, a compressible strength of 50% relative to a standard concrete and a significant increase in performance of shielding against MeV neutrons and lower energies. The concrete could find application at the ESS in for example common shielding components, individual beamline shielding and instrument caves. Initial neutronic tests of the concrete, carried out at Lund University, have also verified the performance in the MeV neutron energy range and the results are presented.
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| 6. |
- Dijulio, D. D., et al.
(författare)
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High-energy in-beam neutron measurements of metal-based shielding for accelerator-driven spallation neutron sources
- 2016
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Ingår i: Physical Review Accelerators and Beams. - 2469-9888. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Metal-based shielding plays an important role in the attenuation of harmful and unwanted radiation at an accelerator-driven spallation neutron source. At the European Spallation Source, currently under construction in Lund, Sweden, metal-based materials are planned to be used extensively as neutron guide substrates in addition to other shielding structures around neutron guides. The usage of metal-based materials in the vicinity of neutron guides however requires careful consideration in order to minimize potential background effects in a neutron instrument at the facility. Therefore, we have carried out a combined study involving high-energy neutron measurements and Monte Carlo simulations of metal-based shielding, both to validate the simulation methodology and also to investigate the benefits and drawbacks of different metal-based solutions. The measurements were carried out at The Svedberg Laboratory in Uppsala, Sweden, using a 174.1 MeV neutron beam and various thicknesses of aluminum-, iron-, and copper-based shielding blocks. The results were compared to Geant4 simulations and revealed excellent agreement. Our combined study highlights the particular situations where one type of metal-based solution may be preferred over another.
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| 7. |
- DiJulio, D. D., et al.
(författare)
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Measurements and Monte-Carlo simulations of the particle self-shielding effect of B4C grains in neutron shielding concrete
- 2018
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Ingår i: Radiation Physics and Chemistry. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0969-806X .- 1879-0895. ; 147, s. 40-44
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Tidskriftsartikel (refereegranskat)abstract
- A combined measurement and Monte-Carlo simulation study was carried out in order to characterize the particle self-shielding effect of B4C grains in neutron shielding concrete. Several batches of a specialized neutron shielding concrete, with varying B4C grain sizes, were exposed to a 2 angstrom neutron beam at the R2D2 test beamline at the Institute for Energy Technology located in Kjeller, Norway. The direct and scattered neutrons were detected with a neutron detector placed behind the concrete blocks and the results were compared to Geant4 simulations. The particle self-shielding effect was included in the Geant4 simulations by calculating effective neutron cross-sections during the Monte-Carlo simulation process. It is shown that this method well reproduces the measured results. Our results show that shielding calculations for low-energy neutrons using such materials would lead to an underestimate of the shielding required for a certain design scenario if the particle self shielding effect is not included in the calculations.
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| 8. |
- Messi, F., et al.
(författare)
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The neutron-tagging facility at Lund University
- 2020
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Ingår i: Modern Neutron Detection : Proceedings of a Technical Meeting - Proceedings of a Technical Meeting. - 1011-4289. - 9789201265203 - 9789201266200 ; :1935, s. 287-297
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Over the last decades, the field of thermal neutron detection has overwhelmingly employed He-3-based technologies. The He-3 crisis together with the forthcoming establishment of the European Spallation Source have necessitated the development of new technologies for neutron detection. Today, several promising He-3-free candidates are under detailed study and need to be validated. This validation process is in general long and expensive. The study of detector prototypes using neutron-emitting radioactive sources is a cost-effective solution, especially for preliminary investigations. That said, neutron-emitting sources have the general disadvantage of broad, structured, emitted-neutron energy ranges. Further, the emitted neutrons often compete with unwanted backgrounds of gamma-rays, alpha-particles, and fission-fragments. By blending experimental infrastructure such as shielding to provide particle beams with neutron-detection techniques such as tagging, disadvantages may be converted into advantages. In particular, a technique known as tagging involves exploiting the mixed-field generally associated with a neutron-emitting source to determine neutron time-of-flight and thus energy on an event-by-event basis. This allows for the definition of low-cost, precision neutron beams. The Source-Testing Facility, located at Lund University in Sweden and operated by the SONNIG Group of the Division of Nuclear Physics, was developed for just such low-cost studies. Precision tagged-neutron beams derived from radioactive sources are available around-the-clock for advanced detector diagnostic studies. Neutron measurements performed at the Source Testing Facility are thus cost-effective and have a very low barrier for entry. In this paper, we present an overview of the project.
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| 9. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 10. |
- Tanskanen, T., et al.
(författare)
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
- 2018
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Ingår i: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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