| 1. |
- Abend, Sven, et al.
(författare)
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Terrestrial very-long-baseline atom interferometry : Workshop summary
- 2024
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Ingår i: AVS Quantum Science. - : American Institute of Physics (AIP). - 2639-0213. ; 6:2
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Forskningsöversikt (refereegranskat)abstract
- This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more kilometer--scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions.
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| 2. |
- Barthel, Roland, 1967, et al.
(författare)
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Hydrogeology – A Consistent Basin-Wide Representation of the Major Aquifers in the Upper Danube Basin
- 2016
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Ingår i: Regional Assessment of Global Change Impacts. - New York : Springer International Publishing. - 9783319167503 ; , s. 125-131
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Modelling the changes of groundwater resources under conditions of global change is a crucial task in the UDC, where groundwater forms the main source of drinking water. The first step in the development of a numerical modelling of groundwater flow and storage changes is to develop a conceptual hydrogeological model that adequately represents the relevant geological and hydrological features of the model area. The large area of the UDC and the coarse resolution of the common DANUBIA model thereby demand strict simplification of the actual hydrogeological conditions. A central decision in this conceptualisation process is the definition of the major regional hydrogeological units to be considered by the model. This chapter describes the process of data collection, data homogenisation and aggregation into ten main hydrogeological units, called “base classes”. The properties and the relevance of these base classes for the numerical model are explained. The most important simplifications made are briefly discussed.
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| 3. |
- de Jager, Vincent D., et al.
(författare)
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Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 38
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Forskningsöversikt (refereegranskat)abstract
- In the past two decades, the treatment of metastatic non-small cell lung cancer (NSCLC), has undergone significant changes due to the introduction of targeted therapies and immunotherapy. These advancements have led to the need for predictive molecular tests to identify patients eligible for targeted therapy. This review provides an overview of the development and current application of targeted therapies and predictive biomarker testing in European patients with advanced stage NSCLC. Using data from eleven European countries, we conclude that recommendations for predictive testing are incorporated in national guidelines across Europe, although there are differences in their comprehensiveness. Moreover, the availability of recently EMA-approved targeted therapies varies between European countries. Unfortunately, routine assessment of national/regional molecular testing rates is limited. As a result, it remains uncertain which proportion of patients with metastatic NSCLC in Europe receive adequate predictive biomarker testing. Lastly, Molecular Tumor Boards (MTBs) for discussion of molecular test results are widely implemented, but national guidelines for their composition and functioning are lacking. The establishment of MTB guidelines can provide a framework for interpreting rare or complex mutations, facilitating appropriate treatment decision-making, and ensuring quality control.
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| 4. |
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| 5. |
- Feuerbacher, Michael, et al.
(författare)
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The Samson phase, β-Mg2Al3, revisited
- 2007
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Ingår i: Zeitschrift fur Kristallographie. - : Walter de Gruyter GmbH. - 0044-2968. ; 222:6, s. 259-288
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Forskningsöversikt (refereegranskat)abstract
- The Al-Mg phase diagram has been reinvestigated in the vicinity of the stability range of the Samson phase, β-Mg2Al3 (cF1168). For the composition Mg38.5Al61.5, this cubic phase, space group Fd3̄m (no 227), a = 28.242(1) Å, V = 22526(2) Å3, undergoes at 214°C a first-order phase transition to rhombohedral β′-Mg2Al3, (hR293), a = 19.968(1) Å, c = 48.9114(8) Å, V = 16889(2) Å3, (i.e. 22519 Å3 for the equivalent cubic unit cell) space group R3m (no 160), a subgroup of index four of Fd3̄m. The structure of the β-phase has been redetermined at ambient temperature as well as in situ at 400°C. It essentially agrees with Samson's model, even in most of the many partially occupied and split positions. The structure of β′-Mg 2Al3 is closely related to that of the β-phase. Its atomic sites can be derived from those of the β-phase by group-theoretical considerations. The main difference between the two structures is that all atomic sites are fully occupied in case of the β′-phase. The reciprocal space, Bragg as well as diffuse scattering, has been explored as function of temperature and the β- to β′-phase transition was studied in detail. The microstructures of both phases have been analyzed by electron microscopy and X-ray topography showing them highly defective. Finally, the thermal expansion coefficients and elastic parameters have been determined. Their values are somewhere in between those of Al and Mg.
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| 6. |
- Huntington-Klein, Nick, et al.
(författare)
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Subjective evidence evaluation survey for many-analysts studies
- 2024
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Ingår i: Royal Society Open Science. - : The Royal Society. - 2054-5703 .- 2054-5703. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Many-analysts studies explore how well an empirical claim withstands plausible alternative analyses of the same dataset by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g. effect size) provided by each analysis team. Although informative about the range of plausible effects in a dataset, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item subjective evidence evaluation survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous many-analysts study.
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| 7. |
- Kerr, Keith M., et al.
(författare)
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The evolving landscape of biomarker testing for non-small cell lung cancer in Europe
- 2021
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Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 154, s. 161-175
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Forskningsöversikt (refereegranskat)abstract
- The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by small molecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment.& nbsp; Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for single driver mutations have been implemented. Improvements in DNA-and RNA-based next-generation sequencing & nbsp;technologies enable analysis of a group of genes in one assay; however, turnaround times remain relatively long. Consequently, rapid screening technologies are being implemented alongside next-generation sequencing.& nbsp; Further challenges in the evolving landscape of biomarker testing in NSCLC are actionable primary and secondary resistance mechanisms to targeted therapies. Therefore, comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumour DNA may provide important information to guide second-or third-line therapies. Furthermore, longitudinal biomarker testing can provide insights into tumour evolution and heterogeneity during the course of the disease. We summarise best practice strategies for Europe in the changing landscape of biomarker testing at diagnosis and during treatment.
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| 8. |
- Northcott, Paul A, et al.
(författare)
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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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| 9. |
- Poutanen, Markku, et al.
(författare)
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DynaQlim – Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas
- 2010
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Ingår i: New Frontiers in Integrated Solid Earth Sciences. - Dordrecht : Springer. - 9789048127368 - 9789048127375 ; , s. 349-372
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The isostatic adjustment of the solid Earth to the glacial loading (GIA, Glacial Isostatic Adjustment) with its temporal signature offers a great opportunity to retrieve information of Earth’s upper mantle to the changing mass of glaciers and ice sheets, which in turn is driven by variations in Quaternary climate. DynaQlim (Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas) has its focus to study the relations between upper mantle dynamics, its composition and physical properties, temperature, rheology, and Quaternary climate. Its regional focus lies on the cratonic areas of northern Canada and Scandinavia.Geodetic methods like repeated precise levelling, tide gauges, high-resolution observations of recent movements, gravity change and monitoring of postglacial faults have given information on the GIA process for more than 100 years. They are accompanied by more recent techniques like GPS observations and the GRACE and GOCE satellite missions which provide additional global and regional constraints on the gravity field. Combining geodetic observations with seismological investigations, studies of the postglacial faults and continuum mechanical modelling of GIA, DynaQlim offers new insights into properties of the lithosphere. Another step toward a better understanding of GIA has been the joint inversion of different types of observational data – preferentially connected with geological relative sea-level evidence of the Earth’s rebound during the last 10,000 years.Due to the changes in the lithospheric stress state large faults ruptured violently at the end of the last glaciation in large earthquakes, up to the magnitudes MW = 7–8. Whether the rebound stress is still able to trigger a significant fraction of intraplate seismic events in these regions is not completely understood due to the complexity and spatial heterogeneity of the regional stress field. Understanding of this mechanism is of societal importance.Glacial ice sheet dynamics are constrained by the coupled process of the deformation of the viscoelastic solid Earth, the ocean and climate variability. Exactly how the climate and oceans reorganize to sustain growth of ice sheets that ground to continents and shallow continental shelves is poorly understood. Incorporation of nonlinear feedback in modelling both ocean heat transport systems and atmospheric CO2 is a major challenge. Climate-related loading cycles and episodes are expected to be important, hence also more short-term features of palaeoclimate should be explicitly treated.Within this Chapter View ChapterIntroductionObservational BasisCurrent Models and Problems to be SolvedClimateChallenges with DynaQlimReferencesReferencesOther actionsExport citationsAbout this BookReprints and Permissions
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| 10. |
- Schnitzbauer, Andreas A., et al.
(författare)
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mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors
- 2020
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Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 272:5, s. 855-862
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). Summary and Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov:NCT00355862), the effect of sirolimus on the recurrence of HCC after LTwas investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. Patients and Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. Results: Sirolimus use for >= 3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) >= 10 ng/mL and having used sirolimus for >= 3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49- 0.59, P = 0.0079- 0.0245). Conclusions: mTOR-inhibitor treatment with sirolimus for >= 3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. Clinical Trial Registration: EudraCT: 2005-005362-36 Clinicaltrials.gov: NCT00355862.
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