ABSTRACT
This report provides an extensive review of the experimental programme of direct detection searches of particle dark matter. It focuses mostly on European efforts, both current and planned, but does it within a broader context of a worldwide activity in the field. It aims at identifying the virtues, opportunities and challenges associated with the different experimental approaches and search techniques. It presents scientific and technological synergies, both existing and emerging, with some other areas of particle physics, notably collider and neutrino programmes, and beyond. It addresses the issue of infrastructure in light of the growing needs and challenges of the different experimental searches. Finally, the report makes a number of recommendations from the perspective of a long-term future of the field. They are introduced, along with some justification, in the opening overview and recommendations section and are next summarised at the end of the report. Overall, we recommend that the direct search for dark matter particle interactions with a detector target should be given top priority in astroparticle physics, and in all particle physics, and beyond, as a positive measurement will provide the most unambiguous confirmation of the particle nature of dark matter in the Universe.
ABSTRACT
Background Accurate assessment of kidney function is needed for a variety of clinical indications and for research. The measurement of the serum clearance of iohexol has emerged as a feasible method to reach this objective. We report the analytical validation and clinical application of a new high-performance liquid chromatography (HPLC) - tandem mass spectrometry (MS/MS) assay to quantify iohexol in human serum. Specificity was enhanced due to the use of method specific acceptance limits for relative ion (RI) intensities. Methods The internal standard ioversol was added to 50 µL serum prior to protein precipitation with methanol. Linear gradient elution was performed on a Waters Oasis® HLB column. Three transitions for both iohexol and ioversol were monitored allowing calculation of RIs. Measurements acquired during method validation were used as a training set to establish stricter acceptance criteria for RIs which were then tested retrospectively on clinical routine measurements (86 measurements) and on mathematically simulated interferences. Results The method was linear between 5.0 µg/mL (lower limit of quantification [LLOQ]) and 100.3 µg/mL iohexol. Intraday and interday imprecision were ≤2.6% and ≤3.2%, respectively. Bias was -1.6% to 1.5%. All validation criteria were met, including selectivity, recovery, extraction efficiency and matrix effects. Retrospectively acceptance limits for RIs could be narrowed to ±4 relative standard deviations of the corresponding RIs in the training set. The new limits resulted in an enhanced sensitivity for the simulated interferences. Conclusions Criteria for validation were met and the assay is now used in our clinical routine diagnostics and in research.
