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Abstract Children learn about art by actively engaging with their surroundings. This makes museums potentially rich environments for learning and development. Yet, the descriptions of paintings on show are usually written for adults rather than younger visitors. This study uses mobile eye tracking to examine how painting descriptions tailored for children influence their eye movements when viewing paintings at the Rijksmuseum - the national museum of The Netherlands. Our findings underscore the importance of adapting information specifically for children, rather than simply providing them with adult-oriented museum materials. Children who received information tailored to their developmental level showed increased glance durations to areas highlighted in the descriptions. Strikingly, the behavior of children provided with painting descriptions intended for adults was no different from their behavior when they received no information at all.

Abstract Successful implementation of remote monitoring of vital signs outside of the hospital setting hinges on addressing three crucial unmet needs: longer-term wear, skin comfort and signal quality. Earlier, we developed a Health Patch research platform that uses self-adhesive dry electrodes to measure vital digital biomarkers. Here, we report on the analytical validation for heart rate, heart rate variability and respiration rate. Study design included n = 25 adult participants with data acquisition during a 30-minute exercise protocol involving rest, squats, slow, and fast cycling. The Shimmer3 ECG Unit and Cosmed K5, were reference devices. Data analysis showed good agreement in heart rate and marginal agreement in respiratory rate, with lower agreement towards higher respiratory rates. The Lin’s concordance coefficient was 0.98 for heart rate and 0.56 for respiratory rate. Heart rate variability (RMSSD) had a coefficient of 0.85. Participants generally expressed a positive experience with the technology, with some minor irritation from the medical adhesive. The results highlighted potential of this technology for short-to-medium term clinical use for cardiorespiratory health, due to its reliability, accuracy, and compact design. Such technology could become instrumental for remote monitoring providing healthcare professionals with continuous data, remote assessment and enhancing patient outcomes in cardiorespiratory health management.

Claims of AI outperforming medical practitioners are under scrutiny, as the evidence supporting many of these claims is not convincing or transparently reported. These claims often lack specificity, contextualization, and empirical grounding. In this comment, we offer constructive ethical guidance that can benefit authors, journal editors, and peer reviewers when reporting and evaluating findings in studies comparing AI to physician performance. The guidance provided here forms an essential addition to current reporting guidelines for healthcare studies using machine learning.

NanoBioAccumulate is a free-to-use web-based tool hosted on the Enalos DIAGONAL Cloud Platform (https://www.enaloscloud.novamechanics.com/diagonal/pbpk/) that provides users with the capability to model and predict the uptake and bioaccumulation of nanomaterials (NMs) by soil and aquatic invertebrates using two common first-order one-compartment biokinetic models. NanoBioAccumulate offers an approach for comprehensively analyzing the kinetics of different forms of NMs via a nonlinear fitting feature, integrating them with environmental fate models, and considering important physiological processes. NanoBioAccumulate overcomes the constraint of requiring prior knowledge of kinetic rate constants associated with the biokinetic models and eliminates the need for external statistical analysis software as it quantifies the kinetic rate constants and other constants through the application of nonlinear regression, using user-provided experimental data. Furthermore, NanoBioAccumulate incorporates statistical analysis measures like the adjusted R-squared and the bias-corrected Akaike information criterion, allowing for assessment of the goodness-of-fit of the two different biokinetic models, assisting in the identification of the best-performing model for a specific nanoform and its uptake kinetics by a specific invertebrate. The tool also includes model scenarios, retrieved from literature, which involve examining the exposure of soil and aquatic invertebrates to various types of NMs such as TiO2, SiO2, C60, graphene, graphene oxide (GO), Au, Ag and its ionic control AgNO3. These model scenarios aim to enhance understanding of the uptake and elimination rates exhibited by different NM-species. NanoBioAccumulate features advanced integration capabilities, enabled by an extensive Application Programming Interface (API). This functionality promotes efficient data exchange and interoperability with other software and web applications, significantly expanding its utility in research, regulatory risk assessment and environmental surveillance and monitoring contexts. The inclusion of a user-friendly Graphical User Interface (GUI) in NanoBioAccumulate greatly improves the overall user experience by simplifying complex tasks and eliminating the need for programming proficiency, thereby expanding the tool's applicability to a diverse range of users across various fields such as environmental research, monitoring, and regulation.

Abstract Although chromium trihalides are widely regarded as a promising class of two-dimensional magnets for next-generation devices, an accurate description of their electronic structure and magnetic interactions has proven challenging to achieve. Here, we quantify electronic excitations and spin interactions in CrX 3 (X = Cl, Br, I) using embedded many-body wavefunction calculations and fully generalized spin Hamiltonians. We find that the three trihalides feature comparable d-shell excitations, consisting of a high-spin 4 A 2 $$({t}_{2g}^{3}{e}_{g}^{0})$$ ( t 2 g 3 e g 0 ) ground state lying 1.5–1.7 eV below the first excited state 4 T 2 ( $${t}_{2g}^{2}{e}_{g}^{1}$$ t 2 g 2 e g 1 ). CrCl3 exhibits a single-ion anisotropy A sia = − 0.02 meV, while the Cr spin-3/2 moments are ferromagnetically coupled through bilinear and biquadratic exchange interactions of J 1 = − 0.97 meV and J 2 = − 0.05 meV, respectively. The corresponding values for CrBr3 and CrI3 increase to A sia = −0.08 meV and A sia= − 0.12 meV for the single-ion anisotropy, J 1 = −1.21 meV, J 2 = −0.05 meV and J 1 = −1.38 meV, J 2 = −0.06 meV for the exchange couplings, respectively. We find that the overall magnetic anisotropy is defined by the interplay between A sia and A dip due to magnetic dipole–dipole interaction that favors in-plane orientation of magnetic moments in ferromagnetic monolayers and bulk layered magnets. The competition between the two contributions sets CrCl3 and CrI3 as the easy-plane (A sia + A dip >0) and easy-axis (A sia + A dip

Abstract Background People with dementia and severe challenging behavior in the Netherlands can be temporarily admitted to highly specialized units when their behavior is not manageable in regular dementia special care units (DSCUs). With scarce evidence available for the treatment of these patients, treatment in these units is in a pioneering phase. To gain more insight into these units, this study investigated organizational characteristics, i.e. admission and discharge characteristics, staffing, the physical environment, and the management of severe challenging behavior. Methods Three data collection methods were used: 1) a digital questionnaire to be completed by the unit manager, 2) an interview with the physician responsible for medical care and often another practitioner, and 3) an observation of the physical environment for which the OAZIS-dementia questionnaire was used. Descriptive analysis was used for quantitative data and thematic analysis for qualitative data, after which data was interpreted together. Thirteen units participated, with their sizes ranging from 10 to 28 places. Results Patients were mainly admitted from regular DSCUs, home or mental health care, and discharged to regular DSCUs. A multidisciplinary team comprising at least an elderly care physician or geriatrician, psychologist, and nursing staff member and other therapists as needed provided the treatment. Nursing staff hours per patient considerably differed among units. Nursing staff played a central role in the treatment. Competences such as reflectiveness on one’s own behavior, and being able to cope with stressful situations were described as relevant for nursing staff. Investing in a stable nursing staff team was described as important. The units varied in whether their work-up was more intuitive or methodological. In the diagnostic phase, observation together with an extensive analysis of the patient’s biography was essential. The units used a broad variety of interventions, and all paid attention to sensory stimuli. In the observation of the physical environment, the safety scored well and domesticity relatively low. Conclusion Highly specialized units show strong heterogeneity in organizational characteristics and management, which can be understood in the light of the pioneering phase. Despite this, similarities were found in nursing staff roles, frequent multidisciplinary evaluation, and attention to sensory stimuli.

Abstract Neltuma alba (Algarrobo blanco), Neltuma chilensis (Algarrobo Chileno) and Strombocarpa strombulifera (Fortuna) are some of the few drought resistant trees and shrubs found in small highly fragmented populations, throughout the Atacama Desert. We reconstructed their plastid genomes using de novo assembly of paired-end reads from total genomic DNA. We found that the complete plastid genomes of N. alba and N. chilensis are larger in size compared to species of the Strombocarpa genus. The Strombocarpa species presented slightly more GC content than the Neltuma species. Therefore, we assume that Strombocarpa species have been exposed to stronger natural selection than Neltuma species. We observed high variation values in the number of cpSSRs (chloroplast simple sequence repeats) and repeated elements among Neltuma and Strombocarpa species. The p-distance results showed a low evolutionary divergence within the genus Neltuma, whereas a high evolutionary divergence was observed between Strombocarpa species. The molecular divergence time found in Neltuma and Strombocarpa show that these genera diverged in the late Oligocene. With this study we provide valuable information about tree species that provide important ecosystem services in hostile environments which can be used to determine these species in the geographically isolated communities, and keep the highly fragmented populations genetically healthy.

Abstract Background Proton Pump Inhibitors (PPI) are frequently prescribed. Long-term use is associated with side-effects and patients often lack a valid indication. Inappropriate PPI prescribing thus needs to be addressed. This review aims to scope 1) what determinants are studied as reasons for PPI prescribing, 2) what strategies are used for changing PPI (de)prescribing, and 3) whether important determinants are addressed in these interventions. Methods We searched eight databases for papers on determinants of physician PPI prescribing. Studies were included if they were conducted in a Western country and focused on oral PPIs for an adult population. By following the Behaviour Change Wheel, we extracted information regarding PPI prescribing behavior, behavioral determinants and intervention strategies. Findings We included 74 papers. Most focused on the determinants knowledge and beliefs about consequences. The latter was consistently related to PPI prescribing. Results for knowledge were mixed. Most interventions used education or enablement (e.g., algorithms, quality check improvements, involvement of pharmacists) as strategies. Enablement consistently improved PPI prescribing, while results for education were mixed. Interpretation There is an overemphasis on reflective processes in studies on PPI prescribing. Future research should comprehensively identify behavioral determinants, focusing on reflective and impulsive processes, such that interventions can address the most important determinants.

Trace metal contamination is ubiquitous around the world and may affect the health of wildlife. Divalent trace metals, including ions of mercury (Hg) and lead (Pb), have been shown to be immunotoxic to avian species. However, little is known about the immunomodulatory effects of trace metal exposure on viral infections, especially in young birds, who may be more sensitive. Therefore, the objective of the current study is to provide more insights in the causality between trace metal exposure and the effects of exposure on the immune responses in young waterfowls. Pekin duckling was used as an animal model to investigate the effects of inorganic divalent Hg (II) and Pb (II) on avian immune responses upon a viral-like challenge with double-stranded RNA. Our results indicate that Hg (II) altered the immune gene expression 24 h post-challenge, as reflected by induction of pro-inflammatory genes IL-8, iNOS, TLR3 and TLR7, and a significant decrease of microRNA-155. Ducklings exposed to Pb (II) showed lower levels of natural antibodies, reduced white blood cell counts and lower heterophil proportions 24 h post-challenge. Although inorganic divalent Hg (II) and Pb (II) showed specific differential effects on the immune response of Pekin ducklings, the overall adverse immunomodulatory outcomes in both cases point to inflammation, impaired B-cell function, and weaker immunocompetence.

Background: Owing to increasing antibiotic resistance, the worldwide efficacy of Helicobacter pylori (HP) eradication treatment has decreased. Aim: To determine antimicrobial resistance of HP in primary care. Design & setting: Retrospective cohort study using real-world routine healthcare data from 80 general practices in the Netherlands. Method: Patients with International Classification of Primary Care (ICPC) codes for gastric symptoms or Anatomical Therapeutic Chemical (ATC) codes for acid inhibition in the period 2010–2020 were selected. Main outcomes were antimicrobial resistance of HP, defined as the prescription of a second eradication treatment within 12 months, and clinical remission of gastric symptoms, defined as no usage of acid inhibition 1 year following eradication therapy. Results: We identified 138 455 patients with gastric symptoms and/or acid inhibition use (mean age 57 years [standard deviation 18.2 years], 43% male). A total of 5224 (4%) patients received an HP eradication treatment. A second treatment was prescribed to 416 (8%) of those patients. From these, 380 patients received amoxicillin–clarithromycin, 16 amoxicillin–metronidazole, and 11 clarithromycin–metronidazole as first regimen and were considered antimicrobial resistant. We observed a 0.8% increment per year of patients requiring a second eradication treatment (P = 0.003, 95% confidence interval = 0.33 to 1.22). After successful eradication, 2329/4808 (48%) patients used acid inhibition compared with 355/416 (85%) patients following treatment failure (P

While the rhetorical battle over citizenship by investment has been won by the EU institutions, its legal success is still up for debate. Last week Advocate General Collins delivered his much-anticipated Opinion in Commission v Malta, proposing that the Court dismisses the Commission’s challenge in a concise, clear, and, as I will explain, convincing legal opinion.

To exploit the full industrial potential of additive manufacturing (AM) beyond prototyping, the resource-consuming identification of the optimal processing conditions needs to be minimized. This task becomes more challenging when multiple properties of the part shall be simultaneously optimized. We utilize machine learning (ML) methods in a case study on laser powder bed fusion (LPBF) of a Zr-based glass-forming alloy. Our experiments show that processing parameters affect density and amorphicity opposingly, demonstrating the efficacy of our ML-based approach. We employ multi-objective optimization using Gaussian Process Regression to model and predict target properties and their uncertainties of parts fabricated by LPBF – a widely used metal AM technology. With density and amorphicity as target parameters, we optimize models using the Pareto front facilitated by the Non-Dominated Sorting Genetic Algorithm II. Despite deviations in the amorphicity data, we demonstrate this method to identify the high-performance region of the process parameters and its ability to be iteratively enhanced with additional experimental data. This bi-objective optimization approach provides a robust toolset for navigating LPBF processing. It can be easily extended to a larger set of target properties and transferred to further AM technologies.

PurposeSustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma. The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We hypothesized that dietary factors affect the microbiome (abundance of butyrate-producing bacteria or stool butyrate concentration) and may be associated with multiple myeloma outcomes.Experimental designWe examined the relationship of dietary factors (via a food frequency questionnaire), stool metabolites (via gas chromatography-mass spectrometry), and the stool microbiome (via 16S sequencing - α-diversity and relative abundance of butyrate-producing bacteria) with sustained MRD negativity (via flow cytometry at two timepoints 1 year apart) in myeloma patients on lenalidomide maintenance. The Healthy Eating Index 2015 score and flavonoid nutrient values were calculated from the food frequency questionnaire. The Wilcoxon rank sum test was used to evaluate associations with two-sided P < 0.05 considered significant.ResultsAt 3 months, higher stool butyrate concentration (P = 0.037), butyrate producers (P = 0.025), and α-diversity (P = 0.0035) were associated with sustained MRD negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (P = 0.009) and sustained MRD negativity (P = 0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins P = 0.01, flavones P = 0.01, and flavanols P = 0.02).ConclusionsThis is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production, and sustained MRD negativity in multiple myeloma, providing rationale to evaluate a prospective dietary intervention.

Introduction Supervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of time-limited SIOT using injectable hydromorphone delivered in an existing Australian public opioid treatment programme, with secondary outcomes of safety, cost, changes in drug use and other health outcomes. If feasible, the goal is to scale up the intervention to be more widely available in Australia.Methods and analysis Between 20 and 30 participants will be offered two times per day hydromorphone to inject under direct observation, in addition to their current opioid agonist treatment (OAT), for up to 2 years. At the end of 2 years of supervised hydromorphone treatment, participants will be continued on standard OAT only. Informed consent will be obtained from all participants included in the study. This is a single-site, uncontrolled, open-label study where quantitative and qualitative interview data will be collected at baseline, 12 months and lastly at 3 months following their final hydromorphone dose. The main outcome measures are feasibility, as assessed by recruitment, retention and participation in treatment, and acceptability to participants, clinic staff and other stakeholders assessed by qualitative interviews. Secondary outcome measures of safety, as assessed by adverse events, and cost will also be assessed, as well as a range of other drug and health outcomes.Ethics and dissemination This study received ethical approval from the St Vincent’s Hospital Human Research Ethics Committee (2019/ETH00418). This will be the first study of time-limited SIOT in the Australian setting. All results will be submitted to peer-reviewed journals, scientific conferences and local practice meetings. A preliminary report on outcomes will also be presented to local health policy makers. A consumer and community forum will also be held to feedback results to a broader audience.Trial registration number ACTRN12621001729819.

Green macroalgae (Ulva sp.) and red macroalgae (Solieria sp.) were processed to produce eight different crude extracts enriched for marine sulphated polysaccharides (MSP). While all extracts showed direct anti-bacterial effects to some degree, two red algal extracts, in particular, showed high activity against several pathogenic fish bacteria in vitro. Stimulation of head kidney leukocytes (HKLs) in vitro with MSP-rich extracts showed fish species specific differences. In Nile tilapia, HKLs showed a dose dependent production of reactive oxygen species (ROS) following stimulation with Ulva-derived extracts, while stimulation with Solieria-derived extracts did not induce ROS production. In rainbow trout, HKLs showed relatively high reactive ROS potential and Solieria-derived extracts could induce significant ROS production, albeit without a clear dose dependent response. Gene expression of in vitro stimulated HKLs showed a clear induction of most cytokines measured (il1b, il10, tnfa, ifny, il12p40), with differences between species. Although cytokine gene expressions were more prominently induced in HKLs of Nile tilapia than in HKLs of rainbow trout, immunomodulatory effects of both, Ulva- and Solieria-derived extracts, always appeared evident. It is likely that HKLs have the ability to sense presence of MSP, via so far uncharacterized pattern recognition receptors which have known downstream signalling pathways. Expression of some genes associated with Toll-like Receptor (TLR) signalling, such as irak1 and especially the expression of genes associated with C-type Lectin Receptor (CLR) signalling, such as card9 and bcl10 were evident following stimulation with MSP-rich extracts. Possibly, immunomodulatory effects of MSP could be regulated by at least a CLR-mediated signalling, at least in Nile tilapia, for which most if not all red algae and green algae extracts induced changes in gene expression of card9 and bcl10. Overall, induction of ROS production and gene expression read-outs suggest immunomodulatory effects of MSP-rich extracts derived from green algae (Ulva sp.) and red algae (Solieria sp.), at least in vitro. The observed effects suggest clear fish species specific differences between the effects of MSP-rich extracts.