Western oceanus procellarum as seen by c1xs on chandrayaan-1

We present the analysis of an X-ray fluorescence (XRF) observation of the western part of Oceanus Procellarum on the Moon’s nearside made by the Chandrayaan-1 X-ray Spectrometer on 10th February 2009. Through forward modelling of the X-ray spectra, we provide estimates of the MgO/SiO2 and Al2O3/SiO2 ratios for seven regions along the flare’s ground track. These results are combined with FeO and TiO2 contents derived from Clementine multispectral reflectance data in order to investigate the compositional diversity of this region of the Moon. The ground track observed consists mainly of low-Ti basaltic units, and the XRF data are largely consistent with this expectation. However, we obtain higher Al2O3/SiO2 ratios for these units than for most basalts in the Apollo sample collection. The widest compositional variation between the different lava flows is in wt% FeO content. A footprint that occurs in a predominantly highland region, immediately to the north of Oceanus Procellarum, has a composition that is consistent with mixing between low-Ti mare basaltic and more feldspathic regoliths. In contrast to some previous studies, we find no evidence for systematic differences in surface composition, as determined through X-ray and gamma-ray spectroscopy techniques

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival

Maternal nutritional state determines the sensitivity of Daphnia magna offspring to Fenvalerate pulse exposure.

Abstract Daphnia populations in the field suffer periodic natural stress conditions such as low food levels. It is known that at low nutritional supply, Daphnia produces fewer but larger offspring, which are acutely less sensitive to chemical stress. We hypothesized that the change in the reproductive strategy may also alter the chronic sensitivity of offspring to pesticides, which usually occur in the field in a pulsed manner. We therefore investigated the influence of maternal food quantity of Daphnia magna on (1) offspring size and successive performance and (2) sensitivity to a 24-h exposure to the pyrethroid insecticide Fenvalerate. Daphnia cultures were maintained at a high and low food level. Produced offspring were subsequently used in life-table response experiments, which were performed under low food conditions. Results showed that low maternal food conditions (compared to high) increased the offspring size at time of birth, reduced age at first reproduction and increased reproductive output, which jointly enhanced offspring fitness as estimated by the population growth rate (r). Fenvalerate exposure in combination with low maternal food levels caused (compared to high) a strong decrease in acute sensitivity of neonates, which was generally also observed for chronic endpoints. Hence, reduction in population growth rate resulting from short-term pesticide exposure appeared to be less strong when compared to daphnids originating from high fed mothers. Our findings illustrate the importance of considering more environmentally relevant conditions (i.e. low maternal food level, short-term exposure) when linking effects observed in laboratory tests to potential risks in the field. Keywords: Short-term Fenvalerate exposure; Daphnia magna; Food quantity; Maternal effects; Sensitivity; Extrapolatio

Population developmental stage determines the recovery potential of Daphnia magna populations after fenvalerate application.

Abstract: This study investigated the responses of Daphnia magna populations to pulsed exposures of the pyrethroid insecticide Fenvalerate applied during an early and a late stage of population development, and analyzed the dynamics of the subsequent recovery. A novel digital observation technique was used to describe the size and numbers of animals. High Fenvalerate concentrations caused high mortality rates during exponential population growth as well as during the food-limited stationary phase. However, recovery of populations took considerably longer in the stationary phase than in populations growing exponentially. The poor nutritional and reproductive state of food-deprived adults was indicated as the main cause of the slow recovery of populations. It is argued that populations operating at the carrying capacity of their environment are vulnerable to toxicant-induced disturbances to an extent not predictable from observations on exponentially growing populations such as are commonly used in ecotoxicology