Involving research participants in a pan-European research initiative: the EPAD participant panel experience

Abstract: Background: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. Methods: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. Results: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. Conclusions: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations

Postcolonial healing landscapes and mental health in a remote Indigenous community in subarctic Ontario, Canada

The concept of therapeutic landscape is concerned with a holistic, socio-ecological model of health, but most studies have attempted to explore land-health links from a Western perspective. On an Indigenous reserve in Northern Ontario, part of the Canadian subarctic, we explore the importance of spaces and places in creating postcolonial therapeutic landscapes to treat the wounds inflicted by colonialism. The aim of this research is to gain insight from views and experiences of First Nations residents living on reservations that are undergoing a process of regaining traditional spiritual beliefs and teachings to construct therapeutic spaces to face mental health problems caused by legal opioid analgesic abuse. This qualitative study used semi-structured interviews with Cree and Ojibwe participants to understand how they are reconnecting with earth, spirituality and traditional animist beliefs on their way to recovery. We find that practices such as taking part in ceremonies and ritual spaces, and seeking knowledge and advice from Elders assist with personal healing and enable Indigenous people to be physically and mentally healthy. Our research findings provide important insights into the relationship between space, healing and culture as determinants of health and well-being and document some key factors that contribute to substance abuse recovery.This work was supported by the Ministry of Education and Science (Spain) [I + D+i SEJ2005-09344/SOCI]; Social Sciences and Humanities Research Council (Canada) [I + D+i CURA/NORTHERN]

Pharmacokinetic-Pharmacodynamic Modeling of the D2 and 5-HT2A Receptor Occupancy of Risperidone and Paliperidone in Rats

A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of brain concentration and dopamine D-2 and serotonin 5-HT2A receptor occupancy (RO) of the atypical antipsychotic drugs risperidone and paliperidone in rats. A population approach was utilized to describe the PK-PD of risperidone and paliperidone using plasma and brain concentrations and D-2 and 5-HT2A RO data. A previously published physiology- and mechanism-based (PBPKPD) model describing brain concentrations and D-2 receptor binding in the striatum was expanded to include metabolite kinetics, active efflux from brain, and binding to 5-HT2A receptors in the frontal cortex. A two-compartment model best fit to the plasma PK profile of risperidone and paliperidone. The expanded PBPKPD model described brain concentrations and D-2 and 5-HT2A RO well. Inclusion of binding to 5-HT2A receptors was necessary to describe observed brain-to-plasma ratios accurately. Simulations showed that receptor affinity strongly influences brain-to-plasma ratio pattern. Binding to both D-2 and 5-HT2A receptors influences brain distribution of risperidone and paliperidone. This may stem from their high affinity for D-2 and 5-HT2A receptors. Receptor affinities and brain-to-plasma ratios may need to be considered before choosing the best PK-PD model for centrally active drugs

80Se(n,?) cross-section measurement at CERN n TOF

Radiative neutron capture cross section measurements are of fundamental importance for the study of the slow neutron capture (s-) process of nucleosynthesis. This mechanism is responsible for the formation of most elements heavier than iron in the Universe. Particularly relevant are branching nuclei along the s-process path, which are sensitive to the physical conditions of the stellar environment. One such example is the branching at $^{79}$Se (3.27 × 10$^{5}$ y), which shows a thermally dependent β-decay rate. However, an astrophysically consistent interpretation requires also the knowledge of the closest neighbour isotopes involved. In particular, the $^{80}$Se(n,γ) cross section directly affects the stellar yield of the "cold" branch leading to the formation of the s-only $^{82}$Kr. Experimentally, there exists only one previous measurement on $^{80}$Se using the time of flight (TOF) technique. However, the latter suffers from some limitations that are described in this presentation. These drawbacks have been significantly improved in a recent measurement at CERN n TOF. This contribution presents a summary of the latter measurement and the status of the data analysis

Review and new concepts for neutron-capture measurements of astrophysical interest

The idea of slow-neutron capture nucleosynthesis formulated in 1957 triggered a tremendous experimental effort in different laboratories worldwide to measure the relevant nuclear physics input quantities, namely (n, γ) cross sections over the stellar temperature range (from few eV up to several hundred keV) for most of the isotopes involved from Fe up to Bi. A brief historical review focused on total energy detectors will be presented to illustrate how advances in instrumentation have led to the assessment of new aspects of s-process nucleosynthesis and to the progressive refinement of stellar models. A summary will be presented on current efforts to develop new detection concepts, such as the Total-Energy Detector with γ-ray imaging capability (i-TED). The latter is based on the simultaneous combination of Compton imaging with neutron time-of-flight (TOF) techniques, in order to achieve a superior level of sensitivity and selectivity in the measurement of stellar neutron capture rates.European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Consolidator Grant project HYMNS) 681740Instituto de Salud Carlos III Spanish Government FPA2014-52823-C2-1-P FPA2017-83946-C2-1-PConsejo Superior de Investigaciones Cientificas (CSIC) PIE-201750I26Program Severo Ochoa SEV-2014-039

First results of the Th-230(n,f) cross section measurements at the CERN n_TOF facility

The study of neutron-induced reactions on actinides is of considerable importance for the design of advanced nuclear systems and alternative fuel cycles. Specifically, Th-230 is produced from the alpha-decay of U-234 as a byproduct of the Th-232/U-233 fuel cycle, thus the accurate knowledge of its fission cross section is strongly required. However, few experimental datasets exist in literature with large deviations among them, covering the energy range between 0.2 to 25 MeV. In addition, the study of the Th-230(n,f) cross-section is of great interest in the research on the fission process related to the structure of the fission barriers. Previous measurements have revealed a large resonance at E-n=715 keV and additional fine structures, but with high discrepancies among the cross-section values of these measurements. This contribution presents preliminary results of the Th-230(n,f) cross-section measurements at the CERN n_TOF facility. The high purity targets of the natural, but very rare isotope Th-230, were produced at JRC-Geel in Belgium. The measurements were performed at both experimental areas (EAR-1 and EAR-2) of the n_TOF facility, covering a very broad energy range from thermal up to at least 100 MeV. The experimental setup was based on Micromegas detectors with the U-235(n,f) and U-238(n,f) reaction cross-sections used as reference

First results of the Am-241(n,f) cross section measurement at the Experimental Area 2 of the n_TOF facility at CERN

This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme Human Resources Development, Education and Lifelong Learning in the context of the project "Strengthening Human Resources Research Potential via Doctorate Research" (MIS-5000432), implemented by the State Scholarships Foundation (IKY). Also, the authors would like to acknowledge the support of the European Commission under the CHANDA project (7th Framework Programme).Feasibility, design and sensitivity studies on innovative nuclear reactors that could address the issue of nuclear waste transmutation using fuels enriched in minor actinides, require high accuracy cross section data for a variety of neutron-induced reactions from thermal energies to several tens of MeV. The isotope Am-241 (T-1/2= 433 years) is present in high-level nuclear waste (HLW), representing about 1.8 % of the actinide mass in spent PWR UOx fuel. Its importance increases with cooling time due to additional production from the beta-decay of Pu-241 with a half-life of 14.3 years. The production rate of 241Am in conventional reactors, including its further accumulation through the decay of Pu-241 and its destruction through transmutation/incineration are very important parameters for the design of any recycling solution. In the present work, the Am-241(n,f) reaction cross-section was measured using Micromegas detectors at the Experimental Area 2 of the n_TOF facility at CERN. For the measurement, the U-235(n,f) and U-238(n,f) reference reactions were used for the determination of the neutron flux. In the present work an overview of the experimental setup and the adopted data analysis techniques is given along with preliminary results.European Union (European Social Fund-ESF) through the Operational Programme Human Resources Development, Education and Lifelong Learning MIS-5000432European Commission under the CHANDA project (7th Framework Programme

Monte Carlo simulations and n-p differential scattering data measured with Proton Recoil Telescopes

The authors wish to thank the National Center of the INFN for Research and Development in Information and Communication Technologies (CNAF) for their computational support.The neutron-induced fission cross section of U-235, a standard at thermal energy and between 0.15 MeV and 200 MeV, plays a crucial role in nuclear technology applications. The long-standing need of improving cross section data above 20 MeV and the lack of experimental data above 200 MeV motivated a new experimental campaign at the n_TOF facility at CERN. The measurement has been performed in 2018 at the experimental area 1 (EAR1), located at 185 m from the neutron-producing target (the experiment is presented by A. Manna et al. in a contribution to this conference). The U-235(n,f) cross section from 20 MeV up to about 1 GeV has been measured relative to the H-1(n,n)H-1 reaction, which is considered the primary reference in this energy region. The neutron flux impinging on the U-235 sample (a key quantity for determining the fission events) has been obtained by detecting recoil protons originating from n-p scattering in a C2H4 sample. Two Proton Recoil Telescopes (PRT), consisting of several layers of solid-state detectors and fast plastic scintillators, have been located at proton scattering angles of 25.07 degrees and 20.32 degrees, out of the neutron beam. The PRTs exploit the Delta E-E technique for particle identification, a basic requirement for the rejection of charged particles from neutron-induced reactions in carbon. Extensive Monte Carlo simulations were performed to characterize proton transport through the different slabs of silicon and scintillation detectors, to optimize the experimental set-up and to deduce the efficiency of the whole PRT detector. In this work we compare measured data collected with the PRTs with a full Monte Carlo simulation based on the Geant-4 toolkit

Neutron capture measurement at the n TOF facility of the 204Tl and 205Tl s-process branching points

Neutron capture cross sections are one of the fundamental nuclear data in the study of the s (slow) process of nucleosynthesis. More interestingly, the competition between the capture and the decay rates in some unstable nuclei determines the local isotopic abundance pattern. Since decay rates are often sensible to temperature and electron density, the study of the nuclear properties of these nuclei can provide valuable constraints to the physical magnitudes of the nucleosynthesis stellar environment. Here we report on the capture cross section measurement of two thallium isotopes, $^{204}$Tl and $^{205}$Tl performed by the time-of-flight technique at the n TOF facility at CERN. At some particular stellar s-process environments, the decay of both nuclei is strongly enhanced, and determines decisively the abundance of two s-only isotopes of lead, $^{204}$Pb and $^{205}$Pb. The latter, as a long-lived radioactive nucleus, has potential use as a chronometer of the last s-process events that contributed to final solar isotopic abundances

Setup for the measurement of the U-235(n,f) cross section relative to n-p scattering up to 1 GeV

The neutron induced fission of U-235 is extensively used as a reference for neutron fluence measurements in various applications, ranging from the investigation of the biological effectiveness of high energy neutrons, to the measurement of high energy neutron cross sections of relevance for accelerator driven nuclear systems. Despite its widespread use, no data exist on neutron induced fission of U-235 above 200 MeV. The neutron facility n_TOF offers the possibility to improve the situation. The measurement of U-235(n,f) relative to the differential n-p scattering cross-section, was carried out in September 2018 with the aim of providing accurate and precise cross section data in the energy range from 10 MeV up to 1 GeV. In such measurements, Recoil Proton Telescopes (RPTs) are used to measure the neutron flux while the fission events are detected and counted with dedicated detectors. In this paper the measurement campaign and the experimental set-up are illustrated