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Multiple-documents-based (inquiry) tasks are often used to examine historical thinking, as they require students to apply discipline-specific ways of reasoning and writing. Intervention studies using such tasks have often relied on principles from cognitive apprenticeship to make these discipline-specific heuristics explicit to students. While several studies have found positive results, they offer little insight into how and where exactly students' progress on historical thinking manifests itself, nor into the differential effects of the intervention. Building on essay data gathered during an intervention study on students' historical inquiry skills, this study explores differential effects of the intervention according to students' initial historical inquiry ability. To this end, a purposeful sample of students was selected for whom the intervention was particularly effective. The qualitative analysis of students' essay tasks (pretest and posttest) revealed remarkable differences between students with high and low pretest scores. Although both groups made progress on all aspects of the essay task, they differed in terms of where and how this progress manifested itself: at posttest, students with a high initial score outperformed others in evaluating sources and rebuttals. This study offers insight into patterns of progress in students' historical inquiry skills which can inform differentiation in instructional practices.

Abstract There is clearly a need for novel antifungal agents, not only concerning spectrum, but also oral bioavailability, tolerability, and drug-drug interactions. There is growing concern for antifungal resistance for current available antifungals, mainly driven by environmental fungicide use or long-term exposure to antifungals, in the setting of mould-active prophylaxis or for chronic antifungal infections, such as chronic pulmonary aspergillosis. Moreover, the incidence of breakthrough infections is increasing, because of the introduction of (mould-active) prophylaxis (1-4). There is emergence of difficult to treat invasive fungal infections, such as those caused by Lomentospora prolificans, cryptic species of Aspergillus, Scedosporium and Coccidioides. Olorofim (F901318) is the first-in class of the orotomides, a novel antifungal class targeting dihydroorotate dehydrogenase (DHODH), a key enzyme in the biosynthesis of pyrimidines. Olorofim shows good in vitro and in vivo activity against Aspergillus species, rare and difficult to treat moulds and endemic dimorphic fungi, including azole- and amphotericin-resistant isolates. It lacks activity against yeasts and the Mucorales species. It is only orally available and shows very promising results in ongoing clinical trials. In this review we will describe the mechanism of action of olorofim, the spectrum of activity in vitro and in vivo, pharmacokinetics, pharmacodynamics, drug-drug interactions, resistance, and clinical outcomes.

Aquatic ecosystems world-wide are being irreversibly altered, suggesting that new and innovative management strategies are necessary to improve ecosystem function and sustainability. In river ecosystems degraded by dams environmental flows and selective withdrawal (SWD) infrastructure have been used to improve habitat for native species. Yet, few studies have quantified nutrient and food web export subsidies from upstream reservoirs, despite their potential to subsidize downstream riverine food webs. We sampled nutrient, phytoplankton, and zooplankton concentrations in outflows from the Shasta-Keswick reservoir complex in Northern California over a 12-month period to understand how SWD operation and internal reservoir conditions interact to influence subsidies to the Sacramento River. We found that nutrients, phytoplankton, and zooplankton were continuously exported from Shasta Reservoir to the Sacramento River and that gate operations at Shasta Dam were important in controlling exports. Further, our results indicate that gate operations and water-export depth strongly correlated with zooplankton community exports, whereas internal reservoir conditions (mixing and residence time) controlled concentrations of exported zooplankton biomass and chlorophyll a. These results demonstrate that reservoirs can be an important source of nutrient and food web subsidies and that selective withdrawal infrastructure may provide a valuable management tool to control ecosystem-level productivity downstream of dams.

Exposure models are essential for a range of contexts involving exposure science. The Exposure Models Working Group, established under ISES Europe, identified that to improve model use, suitable training and education is required. However, there is currently no formal educational training programme for exposure modelling in Europe. We present results from an online survey disseminated to the European exposure science community to identify modelling training needs. The questionnaire had three sections: background information about the respondents and interests in exposure science, previous attendance of exposure modelling courses, interest in future training and education in exposure modelling and their coverage and format.A total of 88 survey recipients completed the survey. Most respondents were from governmental organizations (36 %), with 50 % of all respondents having less than 10 years of experience. About two-thirds of the respondents stated that they had previously attended exposure modelling courses. These were mostly focused on specific models, up to one day in duration and took place in-person. Two thirds of respondents expressed interest in attending future exposure modelling training modules, with the most important topics being interpretation of model results and use of models to meet regulatory standards/requirements. Preferred attendance of training courses was virtual or blended. Costs and certificates of attendance seemed less influential when selecting a training course. Our survey suggests that there is a demand for training in exposure modelling and provides insight to inform the development of training modules that are suitable to fulfil the training needs of exposure scientists and practitioners.

Maximal standard-of-care (SOC) management could not stop the life-threatening progression of a necrotizing fasciitis induced by Panton-Valentine Leukocidin-producing Methicillin-Resistant Staphylococcus aureus (MRSA) in a 12-year-old boy. Multi-route phage therapy was initiated along with antibiotics against Staphylococcus aureus, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, eventually leading to full recovery with no reported adverse events.

This paper introduces the technology Time of Arrival (TOA) based on chirp pulses (according to IEEE 802.15.4a) as a means to perform localization in Wireless Sensor Networks (WSN's) active at 2.4 GHz. Advantages and disadvantages of the technology are discussed and act as a guideline for improving localization accuracy. Tests concerning TOA are performed by means of the location engine of Nanotron. Adapting this engine leads to improved localization results. It is shown that TOA measurements are susceptible to reflections and dynamic environments.

Drivers of phytoplankton and zooplankton dynamics vary spatially and temporally in estuaries due to variation in hydrodynamic exchange and residence time, complicating efforts to understand controls on food web productivity. We conducted approximately monthly (2012–2019; n = 74) longitudinal sampling at 10 fixed stations along a freshwater tidal terminal channel in the San Francisco Estuary, California, characterized by seaward to landward gradients in water residence time, turbidity, nutrient concentrations, and plankton community composition. We used multivariate autoregressive state space (MARSS) models to quantify environmental (abiotic) and biotic controls on phytoplankton and mesozooplankton biomass. The importance of specific abiotic drivers (e.g., water temperature, turbidity, nutrients) and trophic interactions differed significantly among hydrodynamic exchange zones with different mean residence times. Abiotic drivers explained more variation in phytoplankton and zooplankton dynamics than a model including only trophic interactions, but individual phytoplankton–zooplankton interactions explained more variation than individual abiotic drivers. Interactions between zooplankton and phytoplankton were strongest in landward reaches with the longest residence times and the highest zooplankton biomass. Interactions between cryptophytes and both copepods and cladocerans were stronger than interactions between bacillariophytes (diatoms) and zooplankton taxa, despite contributing less biovolume in all but the most landward reaches. Our results demonstrate that trophic interactions and their relative strengths vary in a hydrodynamic context, contributing to food web heterogeneity within estuaries at spatial scales smaller than the freshwater to marine transition.

This paper presents our research on the influence of metal plates on a radio frequency identification (RFID) loop antenna operating at 13.56MHz. More specific we have tested different types of metal plates near a loop antenna in terms of resonance frequency. The performance of an RFID system strongly depends on the configuration of the antenna. The study shows that the resonance frequency will shift up in a metallic environment, resulting in a failing performance. A solution is presented to avoid the influence of a changing environment around a loop antenna. As an example a loop antenna is designed to prove the increase of stability.

Estuaries are among the most productive of aquatic ecosystems. Yet the collective understanding of patterns and drivers of primary production in estuaries is incomplete, in part due to complex hydrodynamics and multiple controlling factors that vary at a range of temporal and spatial scales. A whole-ecosystem experiment was conducted in a deep, pelagically dominated terminal channel of the Sacramento-San Joaquin Delta (California, USA) that seasonally appears to become nitrogen limited, to test whether adding calcium nitrate would stimulate primary productivity or increase phytoplankton density. Production did not respond consistently to fertilization, in part because nitrate and phytoplankton were dispersed away from the manipulated area within 1–3 days. Temporal and spatial patterns of gross primary production were more strongly related to stratification and light availability (i.e., turbidity) than nitrogen, highlighting the role of hydrodynamics in regulating system production. Similarly, chlorophyll was positively related not only to stratification but also to nitrogen—with a positive interaction—suggesting stratification may trigger nutrient limitation. The average rate of primary production (4.3 g O2 m−2 d−1), metabolic N demand (0.023 mg N L−1 d−1), and ambient dissolved inorganic nitrogen concentration (0.03 mg N L−1) indicate that nitrogen can become limiting in time and space, especially during episodic stratification events when phytoplankton are isolated within the photic zone, or farther upstream where water clarity increases, dispersive flux decreases, and stratification is stronger and more frequent. The role of hydrodynamics in organizing habitat connectivity and regulating physical and chemical processes at multiple temporal and spatial scales is critical for determining resource availability and evaluating biogeochemical processes in estuaries.

Background: Bisphenol A (BPA; or 4,4′-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. Objective: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18–73 years (n = 4,226) and its determinants. Methods: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. Results: Total BPA was quantified in 85–100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA’s BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. Conclusion: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

History museums offer a wide range of possibilities to engage students in learning about the past, as well as about history. When compared to scholarly research on other types of museums, their educational promises are underexposed. Within these promises, instructional practices and instructional agents such as museum educators and history teachers play an important role. In order to get a view on research methods and findings regarding instruction within history museums, we conducted a systematic literature review. Three scholarly databases were searched, yielding 45 peer-reviewed journal articles. Those have been fully screened, analysed and compared regarding their research design (in terms of research questions, participants involved, and theoretical and methodological approaches) and their research outcomes (in terms of what they revealed about the content, the nature and the approach of instruction in history museums). Review outcomes reveal four different types of research designs, ranging from describing instructional practices to studying beliefs or a combination thereof, or a focus on the relationship between instruction and students’ learning. Within each of these types, great variety was observed regarding the involved participants and the theoretical and methodological approaches. Besides, the review distinguished three areas of research outcomes, namely the goals of instruction, the instructional methods and the relationship between schools and museums before, during and after instruction. Findings within these areas reveal that certain tensions exist, for example between cognitive and emotional-affective learning goals, also related to disciplinary (historical) and civic educational goals. Other tensions were to be distinguished between student- and teacher-centred instructional methods and between beliefs and practices regarding collaborations between schools and museums. Taken together, these research outcomes yield important implications for instructional practices in history museums and for future scholarly research on them.

Abstract Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014–2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3–18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20–45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (β coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:β = − 9.1 µg/g creatinine, 95% CI − 15.8, − 2.4; GAMA: β = − 3.4 µg/g creatinine, 95% CI − 4.7, − 2.2), living in rural areas (AAMA:β = − 4.7 µg/g creatinine, 95% CI − 8.6, − 0.8; GAMA:β = − 1.1 µg/g creatinine, 95% CI − 1.9, − 0.4) and increasing age (AAMA:β = − 1.9 µg/g creatinine, 95% CI − 2.4, − 1.4; GAMA:β = − 0.7 µg/g creatinine, 95% CI − 0.8, − 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

Condition indices are key predictors of health and fitness in wild fish populations. Variation in body condition, therefore, can be used to identify stressful conditions that may impact endangered species, such as California’s endemic Delta Smelt (Hypomesus transpacificus McAllister, 1963). Here, we examined spatiotemporal variation in the condition indices of > 1600 Delta Smelt collected over nine years (2011–2019), a period characterized by tremendous variability in hydrodynamic and water quality conditions. The population exhibited low hepatosomatic index (HSI) and condition factor (CF) during September/October/November (fall), and both condition indices declined over the nine-year study during fall. HSI was positively correlated with indicators of pelagic productivity (e.g., Chlorophyll a, zooplankton biomass, and proximity to tidal wetlands), whereas CF was negatively correlated with temperature, peaking at a relatively cool 10–13 °C. In sum, seasonal and interannual variation in body condition corresponded most strongly with pelagic productivity and water temperature, with little correlation to freshwater outflow. Management actions that increase pelagic productivity, restore and freshen productive wetlands during late summer-fall, and reduce water temperatures overall are likely to benefit condition indices and, therefore, fitness of the Delta Smelt population.

Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has been postulated as a promising preventive intervention. However, previous attempts at such eradication using oral antibiotics or probiotics have led to discouraging results. Phage therapy, the therapeutic use of bacteriophage viruses, might represent a worthy alternative in this context. Taking inspiration from this clinical challenge, we built Gut-On-A-Chip (GOAC) models, which are tridimensional cell culture models mimicking a simplified gut section. These were used to better understand bacterial dynamics under phage pressure using two relevant species: Pseudomonas aeruginosa and Escherichia coli. Model mucus secretion was documented by ELISA assays. Bacterial dynamics assays were performed in GOAC triplicates monitored for 72 h under numerous conditions, such as pre-, per-, or post-bacterial timing of phage introduction, punctual versus continuous phage administration, and phage expression of mucus-binding properties. The potential genomic basis of bacterial phage resistance acquired in the model was investigated by variant sequencing. The bacterial “escape growth” rates under phage pressure were compared to static in vitro conditions. Our results suggest that there is specific bacterial prosperity in this model compared to other in vitro conditions. In E. coli assays, the introduction of a phage harboring unique mucus-binding properties could not shift this balance of power, contradicting previous findings in an in vivo mouse model and highlighting the key differences between these models. Genomic modifications were correlated with bacterial phage resistance acquisition in some but not all instances, suggesting that alternate ways are needed to evade phage predation, which warrants further investigation.

Ecosystem metabolism is a key ecological attribute and easy to describe, but quantifying metabolism in estuaries is challenging. Properly scaling measurements through time and space requires consideration of hydrodynamics and mixing water from heterogeneous sources, making any estimation uncertain. Here, we compared three methods for modeling ecosystem metabolism in a portion of the Sacramento-San Joaquin Delta. Metabolism estimates based on laboratory incubations, continuous in situ buoys, and an oxygen isotope approach all indicated the system was net heterotrophic, and calculated rates were comparable in magnitude when averaged over the 2-month study. Daily metabolic rates based on in situ buoys were the most variable, likely due to horizontal and vertical advection and poor portrayal of the dissolved oxygen budget. After temporally averaging in situ buoy estimates or smoothing the dissolved oxygen time series for tidal effects, rates were more comparable to the other methods, which may be necessary to account for tidal advection and unbalanced contributions from subhabitats within the metabolic footprint. Incubation-based rates represent the finest temporal and spatial scale and only account for pelagic processes, which may explain why incubation-based rates were lower than the other two methods. The oxygen isotope method provided temporally and spatially integrated rates that were bracketed by the other two methods and may be a valuable tool in systems matching the model requirements. Because uncertainty arises in each method from a number of assumptions and scaling calculations, the resolution of metabolic rates in estuaries is likely coarser and more variable than in other aquatic ecosystems.

Persistent pollutants, namely brominated flame retardants (BFRs) and heavy metals, are compounds that are added to a wide range of products and materials for preventing ignition, increasing the functionality of materials or improving their performance, e.g. electric conductivity. The exposure of children might consequently be inferred, through indoor dust and hand-to-mouth or toy-chewing behaviors. The current study is aimed at assessing the exposure of Moroccan children to BFRs and heavy metal elements, and evaluating their associations with global DNA methylation. First, parents responded to a questionnaire pertaining to children’s lifestyle, then blood and urine samples were collected from (n = 93) children aged between 5 and 11 years for biomonitoring and DNA methylation analysis. BFRs were detected in 54.84% of samples with a median concentration of 0.01 nmol/mL (range: 0.004–0.051 nmol/mL) while metal elements were detected in more than 90% of samples. BFRs showed no variations with global DNA methylation, unlike metal elements, which revealed significant associations with global DNA methylation markers, namely 5-mC, 5-hmC and N⁶-mA levels. Moroccan children may be exposed to flame retardants and heavy metals through several routes. Further research is required to assess the exposure and the health impacts of environmental pollutants and ultimately protect the Moroccan population by the prevention of adverse health effects.

In the Western United States, volcanic spring-fed rivers are anticipated to become increas-ingly more important for salmonids and other native fishes, as these rivers will retain coldwater habitats as the climate warms. Despite this, little is known about the hydro-biogeochemical interactions within these ecosystems. A review of existing literature on spring-fed rivers, coupled with a decade of research on volcanic spring-fed rivers of northern California, finds that these systems are exceptionally productive and exhibit stable environmental conditions. These unique conditions stem from hydrogeologic processes typical of young volcanic terrains. Aquatic macrophytes, com-mon to some nutrient-rich spring-fed systems, play a disproportionate role in hydrologic and geo-morphic processes by facilitating ecological interactions and velocity conditions that improve juvenile salmonid growth. We find that volcanic spring-fed rivers are also resilient to climate change, due not only to their ability to dampen water temperature changes through deep groundwater flow but also because of their nutrient-driven high ecosystem productivity, which may enable coldwater species to metabolically compensate for marginal increases in water temperature. Understanding the fundamental geomorphic and ecological differences between these rare ecosystems and their numerically dominant runoff rivers is essential for developing long-term conservation strategies for coldwater species under a rapidly changing climate.