A simulational study of the indirect geometry neutron spectrometer, BIFROST at the European Spallation Source, from neutron source position to detector position

The European Spallation Source (ESS) is intended to become the most powerful spallation neutron source in the world and the flagship of neutron science in the upcoming decades. The exceptionally high neutron flux will provide unique opportunities for scientific experiments, but also set high requirements for the detectors. One of the most challenging aspects is the rate capability and in particular the peak instantaneous rate capability, i.e. the number of neutrons hitting the detector per channel or cm$^2$ at the peak of the neutron pulse. The primary purpose of this paper is to estimate the incident rates that are anticipated for the BIFROST instrument planned for ESS, and also to demonstrate the use of powerful simulation tools for the correct interpretation of neutron transport in crystalline materials. A full simulation model of the instrument from source to detector position, implemented with the use of multiple simulation software packages is presented. For a single detector tube instantaneous incident rates with a maximum of 1.7 GHz for a Bragg peak from a single crystal, and 0.3 MHz for a vanadium sample are found. This paper also includes the first application of a new pyrolytic graphite model, and a comparison of different simulation tools to highlight their strengths and weaknesses.Comment: 45 pages, 20 figure

Hospital managers' need for information in decision-making--An interview study in nine European countries.

Assessments of new health technologies in Europe are often made at the hospital level. However, the guidelines for health technology assessment (HTA), e.g. the EUnetHTA Core Model, are produced by national HTA organizations and focus on decision-making at the national level. This paper describes the results of an interview study with European hospital managers about their need for information when deciding about investments in new treatments. The study is part of the AdHopHTA project. Face-to-face, structured interviews were conducted with 53 hospital managers from nine European countries. The hospital managers identified the clinical, economic, safety and organizational aspects of new treatments as being the most relevant for decision-making. With regard to economic aspects, the hospital managers typically had a narrower focus on budget impact and reimbursement. In addition to the information included in traditional HTAs, hospital managers sometimes needed information on the political and strategic aspects of new treatments, in particular the relationship between the treatment and the strategic goals of the hospital. If further studies are able to verify our results, guidelines for hospital-based HTA should be altered to reflect the information needs of hospital managers when deciding about investments in new treatments

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.

BackgroundLong non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients.ResultsWe use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy.ConclusionsThese studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy

The instrument suite of the European Spallation Source

An overview is provided of the 15 neutron beam instruments making up the initial instrument suite of the European Spallation Source (ESS), and being made available to the neutron user community. The ESS neutron source consists of a high-power accelerator and target station, providing a unique long-pulse time structure of slow neutrons. The design considerations behind the time structure, moderator geometry and instrument layout are presented. The 15-instrument suite consists of two small-angle instruments, two reflectometers, an imaging beamline, two single-crystal diffractometers; one for macromolecular crystallography and one for magnetism, two powder diffractometers, and an engineering diffractometer, as well as an array of five inelastic instruments comprising two chopper spectrometers, an inverse-geometry single-crystal excitations spectrometer, an instrument for vibrational spectroscopy and a high-resolution backscattering spectrometer. The conceptual design, performance and scientific drivers of each of these instruments are described. All of the instruments are designed to provide breakthrough new scientific capability, not currently available at existing facilities, building on the inherent strengths of the ESS long-pulse neutron source of high flux, flexible resolution and large bandwidth. Each of them is predicted to provide world-leading performance at an accelerator power of 2 MW. This technical capability translates into a very broad range of scientific capabilities. The composition of the instrument suite has been chosen to maximise the breadth and depth of the scientific impact o