| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
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| 6. |
- Bousquet, J., et al.
(author)
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Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
- 2016
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In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
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Research review (peer-reviewed)abstract
- Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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| 7. |
- Reifarth, R., et al.
(author)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Conference paper (peer-reviewed)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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| 8. |
- Bousquet, J., et al.
(author)
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MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation
- 2015
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY-BLACKWELL. - 0105-4538 .- 1398-9995. ; 70:11, s. 1372-1392
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Journal article (peer-reviewed)abstract
- Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
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| 9. |
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| 10. |
- Altstadt, S.G., et al.
(author)
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B-13,B-14(n,gamma) via Coulomb Dissociation for Nucleosynthesis towards the r-Process
- 2014
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In: Nuclear Data Sheets. - : Elsevier BV. - 1095-9904 .- 0090-3752. ; 120, s. 197-200
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Conference paper (peer-reviewed)abstract
- Radioactive beams of 14,15B produced by fragmentation of a primary 40Ar beam were directed onto a Pb target to investigate the neutron breakup within the Coulomb field. The experiment was performed at the LAND/R3B setup. Preliminary results for the Coulomb dissociation cross sections as well as for the astrophysically interesting inverse reactions, 13,14B(n,γ), are presented.
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| 11. |
- Blain, H., et al.
(author)
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A comprehensive fracture prevention strategy in older adults : the European union geriatric medicine society (EUGMS) statement
- 2016
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In: European Geriatric Medicine. - : Elsevier. - 1878-7649 .- 1878-7657. ; 7:6, s. 519-525
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Journal article (peer-reviewed)abstract
- Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest group on falls and fracture prevention of the European union geriatric medicine society (EUGMS), in collaboration with the International association of gerontology and geriatrics for the European region (IAGG-ER), the European union of medical specialists (EUMS), the Fragility fracture network (FFN), the International osteoporosis foundation (IOF) - European society for clinical and economic aspects of osteoporosis and osteoarthritis (ECCEO), outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.
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| 12. |
- Caesar, C., et al.
(author)
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Beyond the neutron drip line: The unbound oxygen isotopes O-25 and O-26
- 2013
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 88:3
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Journal article (peer-reviewed)abstract
- The very neutron-rich oxygen isotopes O-25 and O-26 are investigated experimentally and theoretically. The unbound states are populated in an experiment performed at the R3B-LAND setup at GSI via proton-knockout reactions from F-26 and F-27 at relativistic energies around 442 and 414 MeV/nucleon, respectively. From the kinematically complete measurement of the decay into O-24 plus one or two neutrons, the O-25 ground-state energy and width are determined, and upper limits for the O-26 ground-state energy and lifetime are extracted. In addition, the results provide indications for an excited state in O-26 at around 4 MeV. The experimental findings are compared to theoretical shell-model calculations based on chiral two- and three-nucleon (3N) forces, including for the first time residual 3N forces, which are shown to be amplified as valence neutrons are added.
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| 13. |
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| 14. |
- Heine, M., et al.
(author)
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Determination of the neutron-capture rate of C-17 for r-process nucleosynthesis
- 2017
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In: Physical Review C. - 2469-9985 .- 2469-9993. ; 95:1, s. Article no 014613 -
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Journal article (peer-reviewed)abstract
- With the (RB)-B-3-LAND setup at GSI we have measured exclusive relative-energy spectra of the Coulomb dissociation of C-18 at a projectile energy around 425A MeV on a lead target, which are needed to determine the radiative neutron-capture cross sections of C-17 into the ground state of C-18. Those data have been used to constrain theoretical calculations for transitions populating excited states in C-18. This allowed to derive the astrophysical cross section sigma(n gamma)*. accounting for the thermal population of C-17 target states in astrophysical scenarios. The experimentally verified capture rate is significantly lower than those of previously obtained Hauser-Feshbach estimations at temperatures T-9
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| 15. |
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| 16. |
- Röder, M., et al.
(author)
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Coulomb dissociation of 20,21 N
- 2016
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 93:6
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Journal article (peer-reviewed)abstract
- Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at T
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| 17. |
- Thies, Ronja, 1987, et al.
(author)
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Systematic investigation of projectile fragmentation using beams of unstable B and C isotopes
- 2016
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 93:5
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Journal article (peer-reviewed)abstract
- Models describing nuclear fragmentation and fragmentation fission deliver important input for planning nuclear physics experiments and future radioactive ion beam facilities. These models are usually benchmarked against data from stable beam experiments. In the future, two-step fragmentation reactions with exotic nuclei as stepping stones are a promising tool for reaching the most neutron-rich nuclei, creating a need for models to describe also these reactions. Purpose: We want to extend the presently available data on fragmentation reactions towards the light exotic region on the nuclear chart. Furthermore, we want to improve the understanding of projectile fragmentation especially for unstable isotopes. Method: We have measured projectile fragments from C10,12-18 and B10-15 isotopes colliding with a carbon target. These measurements were all performed within one experiment, which gives rise to a very consistent data set. We compare our data to model calculations. Results: One-proton removal cross sections with different final neutron numbers (1pxn) for relativistic C10,12-18 and B10-15 isotopes impinging on a carbon target. Comparing model calculations to the data, we find that the epax code is not able to describe the data satisfactorily. Using abrabla07 on the other hand, we find that the average excitation energy per abraded nucleon needs to be decreased from 27 MeV to 8.1 MeV. With that decrease abrabla07 describes the data surprisingly well. Conclusions: Extending the available data towards light unstable nuclei with a consistent set of new data has allowed a systematic investigation of the role of the excitation energy induced in projectile fragmentation. Most striking is the apparent mass dependence of the average excitation energy per abraded nucleon. Nevertheless, this parameter, which has been related to final-state interactions, requires further study.
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| 18. |
- Antonov, A. N., et al.
(author)
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The electron-ion scattering experiment ELISe at the International Facility for Antiproton and Ion Research (FAIR)-A conceptual design study
- 2011
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087. ; 637:1, s. 60-76
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Journal article (peer-reviewed)abstract
- The electron-ion scattering experiment ELISe is part of the installations envisaged at the new experimental storage ring at the International Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany. It offers an unique opportunity to use electrons as probe in investigations of the structure of exotic nuclei. The conceptual design and the scientific challenges of ELISe are presented. (C) 2011 Elsevier B.V. All rights reserved.
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| 19. |
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| 20. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 21. |
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| 22. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 23. |
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| 24. |
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| 25. |
- Chotiyarnwong, P., et al.
(author)
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Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group
- 2022
-
In: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Journal article (peer-reviewed)abstract
- A Summary The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. Introduction The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. Methods The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. Results and Conclusion The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.
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| 26. |
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| 27. |
- Pasquier, J. T., et al.
(author)
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The Ny-Ålesund Aerosol Cloud Experiment (NASCENT) : Overview and First Results
- 2022
-
In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 103:11, s. e2533-E2558
-
Journal article (peer-reviewed)abstract
- The Arctic is warming at more than twice the rate of the global average. This warming is influenced by clouds, which modulate the solar and terrestrial radiative fluxes and, thus, determine the surface energy budget. However, the interactions among clouds, aerosols, and radiative fluxes in the Arctic are still poorly understood. To address these uncertainties, the Ny-Ålesund Aerosol Cloud Experiment (NASCENT) study was conducted from September 2019 to August 2020 in Ny-Ålesund, Svalbard. The campaign’s primary goal was to elucidate the life cycle of aerosols in the Arctic and to determine how they modulate cloud properties throughout the year. In situ and remote sensing observations were taken on the ground at sea level, at a mountaintop station, and with a tethered balloon system. An overview of the meteorological and the main aerosol seasonality encountered during the NASCENT year is introduced, followed by a presentation of first scientific highlights. In particular, we present new findings on aerosol physicochemical and molecular properties. Further, the role of cloud droplet activation and ice crystal nucleation in the formation and persistence of mixed-phase clouds, and the occurrence of secondary ice processes, are discussed and compared to the representation of cloud processes within the regional Weather Research and Forecasting Model. The paper concludes with research questions that are to be addressed in upcoming NASCENT publications.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Kramer, K. P., et al.
(author)
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Band structure of overdoped cuprate superconductors: Density functional theory matching experiments
- 2019
-
In: Physical Review B. - 2469-9969 .- 2469-9950. ; 99:22
-
Journal article (peer-reviewed)abstract
- A comprehensive angle-resolved photoemission spectroscopy study of the band structure in singlelayer cuprates is presented with the aim of uncovering universal trends across different materials. Five different hole-and electron-overdoped cuprate superconductors (La1.59Eu0.2Sr0.21CuO4, La1.77Sr0.23CuO4, Bi1.74Pb0.38Sr1.88CuO6+delta, Tl2Ba2CuO6+delta, and Pr1.15La0.7Ce0.15CuO4) have been studied with special focus on the bands with a predominately d-orbital character. Using a light polarization analysis, the e(g) and t(2g) bands are identified across these materials. A clear correlation between the d(3z2-r2) band energy and the apical oxygen distance d(A) is demonstrated. Moreover, the compound dependence of the d(x2-y2) band bottom and the t(2g) band top is revealed. A direct comparison to density functional theory (DFT) calculations employing hybrid exchange-correlation functionals demonstrates excellent agreement. We thus conclude that the DFT methodology can be used to describe the global band structure of overdoped single-layer cuprates on both the hole-and electron-doped side.
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| 32. |
- Modi, A., et al.
(author)
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Association of gastrointestinal events with quality of life and treatment satisfaction in osteoporosis patients: results from the Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS)
- 2017
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:10, s. 2867-2876
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Journal article (peer-reviewed)abstract
- The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. Introduction The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. Methods MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. Results Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P <= 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. Conclusions The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.
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| 33. |
- Modi, A, et al.
(author)
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Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study.
- 2016
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 27:3, s. 1227-1238
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Journal article (peer-reviewed)abstract
- The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms.
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| 34. |
- Modi, A., et al.
(author)
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Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for Osteoporosis in Europe and Canada
- 2015
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In: Clinical and Experimental Rheumatology. - 0392-856X. ; 33:4, s. 537-544
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Journal article (peer-reviewed)abstract
- Objective The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women >= 50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.
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| 35. |
- Modi, A., et al.
(author)
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The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study
- 2018
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:2, s. 329-337
-
Journal article (peer-reviewed)abstract
- The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score >= 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score >= 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.
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| 36. |
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| 37. |
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| 38. |
- Horio, M., et al.
(author)
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Oxide Fermi liquid universality revealed by electron spectroscopy
- 2020
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 102:24
-
Journal article (peer-reviewed)abstract
- We present a combined soft x-ray and high-resolution vacuum-ultraviolet angle-resolved photoemission spectroscopy study of the electron-overdoped cuprate Pr1.3-xLa0.7CexCuO4 (PLCCO). Demonstration of its highly two-dimensional band structure enabled precise determination of the in-plane self-energy dominated by electron-electron scattering. Through analysis of this self-energy and the Fermi liquid cut-off energy scale, we find-in contrast to hole-doped cuprates-a momentum isotropic and comparatively weak electron correlation in PLCCO. Yet, the self-energies extracted from multiple oxide systems combine to demonstrate a logarithmic divergent relation between the quasiparticle scattering rate and mass. This constitutes a spectroscopic version of the Kadowaki-Woods relation with an important merit-the demonstration of Fermi liquid quasiparticle lifetime and mass being set by a single energy scale.
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| 41. |
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| 43. |
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| 44. |
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| 45. |
- Rodarte, Elsa M, et al.
(author)
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Munc13 proteins control regulated exocytosis in mast cells.
- 2018
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 293:1, s. 345-358
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Journal article (peer-reviewed)abstract
- Mast cells (MCs) are involved in host defenses against pathogens and inflammation. Stimulated MCs release substances stored in their granules via regulated exocytosis. In other cell types, Munc13 (mammalian homolog of Caenorhabditis elegans uncoordinated gene 13) proteins play essential roles in regulated exocytosis. Here, we found that MCs express Munc13-2 and -4, and we studied their roles using global and conditional knock-out (KO) mice. In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and MC-specific Munc13-4 KO mice developed less hypothermia. This protection correlated with lower plasma histamine levels and with histological evidence of defective MC degranulation but not with changes in MC development, distribution, numbers, or morphology. In vitro assays revealed that the defective response in Munc13-4-deficient MCs was limited to regulated exocytosis, leaving other MC secretory effector responses intact. Single cell capacitance measurements in MCs from mouse mutants differing in Munc13-4 expression levels in their MCs revealed that as levels of Munc13-4 decrease, the rate of exocytosis declines first, and then the total amount of exocytosis decreases. A requirement for Munc13-2 in MC exocytosis was revealed only in the absence of Munc13-4. Electrophysiology and EM studies uncovered that the number of multigranular compound events (i.e. granule-to-granule homotypic fusion) was severely reduced in the absence of Munc13-4. We conclude that although Munc13-2 plays a minor role, Munc13-4 is essential for regulated exocytosis in MCs, and that this MC effector response is required for a full anaphylactic response.
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| 46. |
- Sandahl, Julie Damgaard, et al.
(author)
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t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia : an international study of 62 patients
- 2014
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 99:5, s. 865-872
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia with t(6; 9)(p22; q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6; 9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6; 9)/DEKNUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6; 9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6; 9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.
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| 47. |
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| 48. |
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| 49. |
- Simutis, Gediminas, et al.
(author)
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In situ uniaxial pressure cell for x-ray and neutron scattering experiments
- 2023
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In: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 94:1
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Journal article (peer-reviewed)abstract
- We present an in situ uniaxial pressure device optimized for small angle x-ray and neutron scattering experiments at low-temperatures and high magnetic fields. A stepper motor generates force, which is transmitted to the sample via a rod with an integrated transducer that continuously monitors the force. The device has been designed to generate forces up to 200 N in both compressive and tensile configurations, and a feedback control allows operating the system in a continuous-pressure mode as the temperature is changed. The uniaxial pressure device can be used for various instruments and multiple cryostats through simple and exchangeable adapters. It is compatible with multiple sample holders, which can be easily changed depending on the sample properties and the desired experiment and allow rapid sample changes.
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