Light profoundly impacts many aspects of human physiology and behaviour, including the synchronization of the circadian clock, the production of melatonin, and cognition. These effects of light, termed the non-visual effects of light, have been primarily investigated in laboratory settings, where light intensity, spectrum and timing can be carefully controlled to draw associations with physiological outcomes of interest. Recently, the increasing availability of wearable light loggers has opened the possibility of studying personal light exposure in free-living conditions where people engage in activities of daily living, yielding findings associating aspects of light exposure and health outcomes, supporting the importance of adequate light exposure at appropriate times for human health. However, comprehensive protocols capturing environmental (e.g., geographical location, season, climate, photoperiod) and individual factors (e.g., culture, personal habits, behaviour, commute type, profession) contributing to the measured light exposure are currently lacking. Here, we present a protocol that combines smartphone-based experience sampling (experience sampling implementing Karolinska Sleepiness Scale, KSS ratings) and high-quality light exposure data collection at three body sites (near-corneal plane between the two eyes mounted on spectacle, neck-worn pendant/badge, and wrist-worn watch-like design) to capture daily factors related to individuals’ light exposure. We will implement the protocol in an international multi-centre study to investigate the environmental and socio-cultural factors influencing light exposure patterns in Germany, Ghana, Netherlands, Spain, Sweden, and Turkey (minimum n = 15, target n = 30 per site, minimum n = 90, target n = 180 across all sites). With the resulting dataset, lifestyle and context-specific factors that contribute to healthy light exposure will be identified. This information is essential in designing effective public health interventions.
MULTIFILE
For almost fifteen years, the availability and regulatory acceptance of new approach methodologies (NAMs) to assess the absorption, distribution, metabolism and excretion (ADME/biokinetics) in chemical risk evaluations are a bottleneck. To enhance the field, a team of 24 experts from science, industry, and regulatory bodies, including new generation toxicologists, met at the Lorentz Centre in Leiden, The Netherlands. A range of possibilities for the use of NAMs for biokinetics in risk evaluations were formulated (for example to define species differences and human variation or to perform quantitative in vitro-in vivo extrapolations). To increase the regulatory use and acceptance of NAMs for biokinetics for these ADME considerations within risk evaluations, the development of test guidelines (protocols) and of overarching guidance documents is considered a critical step. To this end, a need for an expert group on biokinetics within the Organisation of Economic Cooperation and Development (OECD) to supervise this process was formulated. The workshop discussions revealed that method development is still required, particularly to adequately capture transporter mediated processes as well as to obtain cell models that reflect the physiology and kinetic characteristics of relevant organs. Developments in the fields of stem cells, organoids and organ-on-a-chip models provide promising tools to meet these research needs in the future.
MULTIFILE
In pre-treatment dose verification, low resolution detector systems are unable to identify shifts of individual leafs of high resolution multi leaf collimator (MLC) systems from detected changes in the dose deposition. The goal of this study was to introduce an alternative approach (the shutter technique) combined with a previous described iterative reconstruction method to accurately reconstruct high resolution MLC leaf positions based on low resolution measurements. For the shutter technique, two additional radiotherapy treatment plans (RT-plans) were generated in addition to the original RT-plan; one with even MLC leafs closed for reconstructing uneven leaf positions and one with uneven MLC leafs closed for reconstructing even leaf positions. Reconstructed leaf positions were then implemented in the original RT-plan for 3D dose reconstruction. The shutter technique was evaluated for a 6 MV Elekta SLi linac with 5 mm MLC leafs (Agility(™)) in combination with the MatriXX Evolution detector with detector spacing of 7.62 mm. Dose reconstruction was performed with the COMPASS system (v2.0). The measurement setup allowed one row of ionization chambers to be affected by two adjacent leaf pairs. Measurements were obtained for various field sizes with MLC leaf position errors ranging from 1.0 mm to 10.0 mm. Furthermore, one clinical head and neck IMRT treatment beam with MLC introduced leaf position errors of 5.0 mm was evaluated to illustrate the impact of the shutter technique on 3D dose reconstruction. Without the shutter technique, MLC leaf position reconstruction showed reconstruction errors up to 6.0 mm. Introduction of the shutter technique allowed MLC leaf position reconstruction for the majority of leafs with sub-millimeter accuracy resulting in a reduction of dose reconstruction errors. The shutter technique in combination with the iterative reconstruction method allows high resolution MLC leaf position reconstruction using low resolution measurements with sub-millimeter accuracy.
