Effect of soil organic matter content and pH on the toxicity of ZnO nanoparticles to Folsomia candida

Organic matter (OM) and pH may influence nanoparticle fate and effects in soil. This study investigated the influence of soil organic matter content and pH on the toxicity of ZnO–NP and ZnCl2 to Folsomia candida in four natural soils, having between 2.37% and 14.7% OM and pHCaCl2pHCaCl2 levels between 5.0 and 6.8. Porewater Zn concentrations were much lower in ZnO–NP than in ZnCl2 spiked soils, resulting in higher Freundlich sorption constants for ZnO–NP. For ZnCl2 the porewater Zn concentrations were significantly higher in less organic soils, while for ZnO–NP the highest soluble Zn level (23 mg Zn/l) was measured in the most organic soil, which had the lowest pH. Free Zn2+ ion concentrations were higher for ZnCl2 than for ZnO–NP and were greatly dependent on pH (pHpw) and dissolved organic carbon content of the pore water. The 28-d EC50 values for the effect of ZnCl2 on the reproduction of F. candida increased with increasing OM content from 356 to 1592 mg Zn/kg d.w. For ZnO–NP no correlation between EC50 values and OM content was found and EC50 values ranged from 1695 in the most organic soil to 4446 mg Zn/kg d.w. in the higher pH soil. When based on porewater and free Zn2+ concentrations, EC50 values were higher for ZnCl2 than for ZnO–NP, and consistently decreased with increasing pHpw. This study shows that ZnO–NP toxicity is dependent on soil properties, but is mainly driven by soil pH

Developmental Toxicity of Endocrine Disrupters Bisphenol A and Vinclozolin in a Terrestrial Isopod

Studies of the effects of endocrine-disrupting compounds (EDCs) on invertebrates are still largely underrepresented. This work aims to fill this gap by assessing the effects of bisphenol A (BPA) and vinclozolin (Vz) on the terrestrial isopod Porcellio scaber (common rough woodlouse). Male adult and sexually undifferentiated juvenile woodlice were exposed to the toxicants. Effects on molting regime and growth were investigated independently for males and female woodlice after sexual differentiation. Both chemicals elicited developmental toxicity to P. scaber by causing overall decreased growth. Nevertheless, BPA induced molting, whereas Vz delayed it. Although the LC50 values for juvenile and adult survival were fairly similar, juvenile woodlice showed an increased chronic sensitivity to both chemicals, and female woodlice were most the sensitive to BPA. We recommend the use of adults, juveniles, female, and male woodlice, as well as a large range of toxicant concentrations, to provide valuable information regarding differential dose responses, effects, and threshold values for EDCs

An ADER discontinuous Galerkin method on moving meshes for Liouville's equation of geometrical optics

Liouville's equation describes light propagation through an optical system. It governs the evolution of an energy distribution on phase space. This energy distribution is discontinuous across optical interfaces. Curved optical interfaces manifest themselves as moving boundaries on phase space. In this paper, an ADER discontinuous Galerkin (DG) method on a moving mesh is applied to solve Liouville's equation. In the ADER approach a temporal Taylor series is computed by replacing temporal derivatives with spatial derivatives using the Cauchy-Kovalewski procedure. The result is a fully discrete explicit scheme of arbitrary high order of accuracy. A moving mesh is not sufficient to be able to solve Liouville's equation numerically for the optical systems considered in this article. To that end, we combine the scheme with a new method we refer to as sub-cell interface method. When dealing with optical interfaces in phase space, non-local boundary conditions arise. These are incorporated in the DG method in an energy-preserving manner. Numerical experiments validate energy-preservation up to machine precision and show the high order of accuracy. Furthermore, the DG method is compared to quasi-Monte Carlo ray tracing for two examples showing that the DG method yields better accuracy in the same amount of computational time.</p

Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions

How does nudging the COVID-19 vaccine play out in people who are in doubt about vaccination?

In spite of the growing availability of COVID-19 vaccines, a substantial number of people is reluctant or uncertain about getting the vaccine. Nudges may improve vaccine uptake but it is unclear how this plays out with the experience of autonomous choice, decision competence, decision satisfaction, and being pressured to make a choice. In an online experiment among a representative sample (N = 884), we examined whether a social norm nudge or a default nudge (either or not transparent) was effective in steering the desired choice of making a hypothetical early vaccination appointment as compared to making a later appointment or no appointment. We also examined how both nudges affected autonomy and related downstream consequences. None of the nudges proved effective in making the desired choice of early vaccination and neither did they impact on downstream consequences. Rather, our results indicate that participants who were certain about their choice (i.e., opted for the earliest available vaccination opportunity or not getting vaccinated at all) reported higher levels of autonomy, competence and satisfaction than participants who did not know yet about vaccination or who postponed the moment of getting their vaccination. We conclude that the experience of autonomy and related downstream consequences is determined by having made up one's mind about vaccination, and is not affected by attempts to nudge the individual. Public Health and primary carePrevention, Population and Disease management (PrePoD

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

The use of gene expression to unravel the single and mixture toxicity of abamectin and difenoconazole on survival and reproduction of the springtail Folsomia candida

Pesticides risk assessments have traditionally focused on the effects on standard parameters, such as mortality, reproduction and development. However, one of the first signs of adverse effects that occur in organisms exposed to stress conditions is an alteration in their genomic expression, which is specific to the type of stress, sensitive to very low contaminant concentrations and responsive in a few hours. The aim of the present study was to evaluate the single and binary mixture toxicity of commercial products of abamectin (Kraft® 36 EC) and difenoconazole (Score® 250 EC) to Folsomia candida. Laboratory toxicity tests were conducted to access the effects of these pesticides on springtail survival, reproduction and gene expression. The reproduction assays gave EC50 and EC10 values, respectively, of 6.3 and 1.4 mg a.s./kg dry soil for abamectin; 1.0 and 0.12 mg a.s./kg dry soil for Kraft® 36 EC; and 54 and 23 mg a.s./kg dry soil for Score® 250 EC. Technical difenoconazole did not have any effect at the concentrations tested. No significant differences in gene expression were found between the abamectin concentrations tested (EC10 and EC50) and the solvent control. Exposure to Kraft® 36 EC, however, significantly induced Cyp6 expression at the EC50 level, while VgR was significantly downregulated at both the EC10 and EC50. Exposure to the simple pesticide mixture of Kraft® 36 EC + Score® 250 EC caused significant up regulation of ABC transporter, and significant down regulation of VgR relative to the controls. GABA receptor also showed significant down-regulation between the EC10 and EC50 mixture treatments. Results of the present study demonstrate that pesticide-induced gene expression effects precede and occur at lower concentrations than organism-level responses. Integrating "omic" endpoints in traditional bioassays may thus be a promising way forward in pesticide toxicity evaluations

Changes in disease characteristics and response rates among patients in the United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid arthritis between 2001 and 2008

Objectives. Anti-TNF therapy has significantly improved outcomes for patients with severe RA. In the UK, changing financial restrictions and increasing experience with their use may have resulted in changes to the way physicians use anti-TNF therapies. The aim of this analysis was to examine changes in disease characteristics and response rates among patients starting anti-TNF therapy for RA over an 8-year period

Model-Based Selection for Proton Therapy in Breast Cancer:Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences

Aims: Proton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences. Materials and methods: A national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy. Results: The model of Darby et al. (N Engl J Med 2013; 368:987–82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021. Conclusion: The NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands

Measurement of the Neutron Lifetime by Counting Trapped Protons in a Cold Neutron Beam

A measurement of the neutron lifetime $\tau_{n}$ performed by the absolute counting of in-beam neutrons and their decay protons has been completed. Protons confined in a quasi-Penning trap were accelerated onto a silicon detector held at a high potential and counted with nearly unit efficiency. The neutrons were counted by a device with an efficiency inversely proportional to neutron velocity, which cancels the dwell time of the neutron beam in the trap. The result is $\tau_{n} = (886.6\pm1.2{\rm [stat]}\pm3.2{\rm [sys]})$ s, which is the most precise measurement of the lifetime using an in-beam method. The systematic uncertainty is dominated by neutron counting, in particular the mass of the deposit and the $^{6}$Li({\it{n,t}}) cross section. The measurement technique and apparatus, data analysis, and investigation of systematic uncertainties are discussed in detail.Comment: 71 pages, 20 figures, 9 tables; submitted to PR