Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability

BACKGROUND: The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting. METHODS: Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry. RESULTS: A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older ( 6565 years) subjects (ROC area: 0.584; 95% CI: 0.399-0.769). Among the young, assays have different optimal thresholds (120 \u3bcg/g for ELISA, 50 \u3bcg/g for CLIA and 100 \u3bcg/g for turbidimetry). CONCLUSIONS: We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV

New Capabilities of the FLUKA Multi-Purpose Code

FLUKA is a general purpose Monte Carlo code able to describe the transport and interaction of any particle and nucleus type in complex geometries over an energy range extending from thermal neutrons to ultrarelativistic hadron collisions. It has many different applications in accelerator design, detector studies, dosimetry, radiation protection, medical physics, and space research. In 2019, CERN and INFN, as FLUKA copyright holders, together decided to end their formal collaboration framework, allowing them henceforth to pursue different pathways aimed at meeting the evolving requirements of the FLUKA user community, and at ensuring the long term sustainability of the code. To this end, CERN set up the FLUKA.CERN Collaboration1. This paper illustrates the physics processes that have been newly released or are currently implemented in the code distributed by the FLUKA.CERN Collaboration2 under new licensing conditions that are meant to further facilitate access to the code, as well as intercomparisons. The description of coherent effects experienced by high energy hadron beams in crystal devices, relevant to promising beam manipulation techniques, and the charged particle tracking in vacuum regions subject to an electric field, overcoming a former lack, have already been made available to the users. Other features, namely the different kinds of low energy deuteron interactions as well as the synchrotron radiation emission in the course of charged particle transport in vacuum regions subject to magnetic fields, are currently undergoing systematic testing and benchmarking prior to release. FLUKA is widely used to evaluate radiobiological effects, with the powerful support of the Flair graphical interface, whose new generation (Available at http://flair.cern) offers now additional capabilities, e.g., advanced 3D visualization with photorealistic rendering and support for industry-standard volume visualization of medical phantoms. FLUKA has also been playing an extensive role in the characterization of radiation environments in which electronics operate. In parallel, it has been used to evaluate the response of electronics to a variety of conditions not included in radiation testing guidelines and standards for space and accelerators, and not accessible through conventional ground level testing. Instructive results have been obtained from Single Event Effects (SEE) simulations and benchmarks, when possible, for various radiation types and energies. The code has reached a high level of maturity, from which the FLUKA.CERN Collaboration is planning a substantial evolution of its present architecture. Moving towards a modern programming language allows to overcome fundamental constraints that limited development options. Our long term goal, in addition to improving and extending its physics performances with even more rigorous scientific oversight, is to modernize its structure to integrate independent contributions more easily and to formalize quality assurance through state-of-the-art software deployment techniques. This includes a continuous integration pipeline to automatically validate the codebase as well as automatic processing and analysis of a tailored physics-case test suite. With regard to the aforementioned objectives, several paths are currently envisaged, like finding synergies with Geant4, both at the core structure and interface level, this way offering the user the possibility to run with the same input different Monte Carlo codes and crosscheck the results

Positive biodiversity-productivity relationship predominant in global forests

The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone - US$166 billion to 490 billion per year according to our estimation - is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities.Peer Reviewe

Benchmarking LHC background particle simulation with the CMS triple-GEM detector

In 2018, a system of large-size triple-GEM demonstrator chambers was installed in the CMS experiment at CERN\u27s Large Hadron Collider (LHC). The demonstrator\u27s design mimicks that of the final detector, installed for Run-3. A successful Monte Carlo (MC) simulation of the collision-induced background hit rate in this system in proton-proton collisions at 13 TeV is presented. The MC predictions are compared to CMS measurements recorded at an instantaneous luminosity of 1.5 ×10$^{34}$ cm$^{-2}$ s$^{-1}$. The simulation framework uses a combination of the FLUKA and GEANT4 packages. FLUKA simulates the radiation environment around the GE1/1 chambers. The particle flux by FLUKA covers energy spectra ranging from 10$^{-11}$ to 10$^{4}$ MeV for neutrons, 10$^{-3}$ to 10$^{4}$ MeV for γ\u27s, 10$^{-2}$ to 10$^{4}$ MeV for e$^{±}$, and 10$^{-1}$ to 10$^{4}$ MeV for charged hadrons. GEANT4 provides an estimate of the detector response (sensitivity) based on an accurate description of the detector geometry, the material composition, and the interaction of particles with the detector layers. The detector hit rate, as obtained from the simulation using FLUKA and GEANT4, is estimated as a function of the perpendicular distance from the beam line and agrees with data within the assigned uncertainties in the range 13.7-14.5%. This simulation framework can be used to obtain a reliable estimate of the background rates expected at the High Luminosity LHC

Modeling the triple-GEM detector response to background particles for the CMS Experiment

An estimate of environmental background hit rate on triple-GEM chambers is performed using Monte Carlo (MC) simulation and compared to data taken by test chambers installed in the CMS experiment (GE1/1) during Run-2 at the Large Hadron Collider (LHC). The hit rate is measured using data collected with proton-proton collisions at 13 TeV and a luminosity of 1.5$\times10^{34}$ cm$^{-2}$ s$^{-1}$. The simulation framework uses a combination of the FLUKA and Geant4 packages to obtain the hit rate. FLUKA provides the radiation environment around the GE1/1 chambers, which is comprised of the particle flux with momentum direction and energy spectra ranging from $10^{-11}$ to $10^{4}$ MeV for neutrons, $10^{-3}$ to $10^{4}$ MeV for $\gamma$'s, $10^{-2}$ to $10^{4}$ MeV for $e^{\pm}$, and $10^{-1}$ to $10^{4}$ MeV for charged hadrons. Geant4 provides an estimate of detector response (sensitivity) based on an accurate description of detector geometry, material composition and interaction of particles with the various detector layers. The MC simulated hit rate is estimated as a function of the perpendicular distance from the beam line and agrees with data within the assigned uncertainties of 10-14.5%. This simulation framework can be used to obtain a reliable estimate of background rates expected at the High Luminosity LHC.Comment: 16 pages, 9 figures, 6 table