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The purpose of this study was to analyze the effectiveness of scripted biology curriculum as a means of providing students with the information required to increase content knowledge, while comparing curriculum developed by the teacher that utilizesthe Understanding by Design (UbD) framework (Wiggins & McTighe, 2005). The study used a mixed method, concurrent triangulation design which revealed that there was a significant difference between student growth from the pretest to the posttest. The teacher reflection logs and student focus groups identified two themes regarding science content knowledge: instructional/learning style and using discussion within the instructional cycle for both curricula. It was evident that the increase in content knowledge was associated with the utilization of discussion during the learning cycle. The teacher reflection logs and student focus groups also identified two themes when looking at the perception of the learning environment: the effect of teacher relationship on instruction and the effect of time on the learning environment. According to the instrument used, both groups of students showed growth, however, there was a larger gain among the students receiving the Understanding by Design curriculum. A major contributing factor for the growth among all students was the relationship the teacher had with them to meet their individual academic needs.

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.

Acute intoxication with organophosphate (OP) cholinesterase inhibitors poses a significant public health risk. While currently approved medical countermeasures can improve survival rates, they often fail to prevent chronic neurological damage. Therefore, there is need to develop effective therapies and quantitative metrics for assessing OP-induced brain injury and its rescue by these therapies. In this study we used a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP), to test the hypothesis that T2 measures obtained from brain magnetic resonance imaging (MRI) scans provide quantitative metrics of brain injury and therapeutic efficacy. Adult male Sprague Dawley rats were imaged on a 7T MRI scanner at 3, 7 and 28 days post-exposure to DFP or vehicle (VEH) with or without treatment with the standard of care antiseizure drug, midazolam (MDZ); a novel antiseizure medication, allopregnanolone (ALLO); or combination therapy with MDZ and ALLO (DUO). Our results show that mean T2 values in DFP-exposed animals were: (1) higher than VEH in all volumes of interest (VOIs) at day 3; (2) decreased with time; and (3) decreased in the thalamus at day 28. Treatment with ALLO or DUO, but not MDZ alone, significantly decreased mean T2 values relative to untreated DFP animals in the piriform cortex at day 3. On day 28, the DUO group showed the most favorable T2 characteristics. This study supports the utility of T2 mapping for longitudinally monitoring brain injury and highlights the therapeutic potential of ALLO as an adjunct therapy to mitigate chronic morbidity associated with acute OP intoxication.

Recent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by acute organophosphate (OP) intoxication. However, there are concerns that combined midazolam and allopregnanolone increases risk of adverse cardiovascular events. To address this, we used telemetry devices to record cardiovascular responses in adult male Sprague-Dawley rats acutely intoxicated with diisopropylfluorophosphate (DFP). Animals were administered DFP (4 mg/kg, sc), followed immediately by atropine (2 mg/kg, i.m.) and 2-PAM (25 mg/kg, i.m.). At 40 min post-exposure, a subset of animals received midazolam (0.65 mg/kg, im); at 50 min, these rats received a second dose of midazolam or allopregnanolone (12 mg/kg, im). DFP significantly increased blood pressure by ~ 80 mmHg and pulse pressure by ~ 34 mmHg that peaked within 12 min. DFP also increased core temperature by ~ 3.5 °C and heart rate by ~ 250 bpm that peaked at ~ 2 h. Heart rate variability (HRV), an index of autonomic function, was reduced by ~ 80%. All acute (within 15 min of exposure) and two-thirds of delayed (hours after exposure) mortalities were associated with non-ventricular cardiac events within 10 min of cardiovascular collapse, suggesting that non-ventricular events should be closely monitored in OP-poisoned patients. Compared to rats that survived DFP intoxication without treatment, midazolam significantly improved recovery of cardiovascular parameters and HRV, an effect enhanced by allopregnanolone. These data demonstrate that midazolam improved recovery of cardiovascular and autonomic function and that the combination of midazolam and allopregnanolone may be a better therapeutic strategy than midazolam alone.

Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4 mg/kg, s.c.). Control animals were administered an equal volume (300 µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6 months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100β, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated β-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.

Recent studies have suggested that injection of solid particles such as alumina and calcite particles for stratospheric aerosol injection (SAI) instead of sulfur-based injections could reduce some of the adverse side effects of SAI such as ozone depletion and stratospheric heating. Here, we present a version of the global aerosol–chemistry–climate model SOCOL-AERv2 and the Earth system model (ESM) SOCOLv4 which incorporate a solid-particle microphysics scheme for assessment of SAI of solid particles. Microphysical interactions of the solid particle with the stratospheric sulfur cycle were interactively coupled to the heterogeneous chemistry scheme and the radiative transfer code (RTC) for the first time within an ESM. Therefore, the model allows simulation of heterogeneous chemistry at the particle surface as well as feedbacks between microphysics, chemistry, radiation and climate. We show that sulfur-based SAI results in a doubling of the stratospheric aerosol burden compared to the same mass injection rate of calcite and alumina particles with a radius of 240 nm. Most of the sulfuric acid aerosol mass resulting from SO2 injection does not need to be lifted to the stratosphere but is formed after in situ oxidation and subsequent water uptake in the stratosphere. Therefore, to achieve the same radiative forcing, larger injection rates are needed for calcite and alumina particle injection than for sulfur-based SAI. The stratospheric sulfur cycle would be significantly perturbed, with a reduction in stratospheric sulfuric acid burden by 53 %, when injecting 5 Mt yr−1 (megatons per year) of alumina or calcite particles of 240 nm radius. We show that alumina particles will acquire a sulfuric acid coating equivalent to about 10 nm thickness if the sulfuric acid is equally distributed over the whole available particle surface area in the lower stratosphere. However, due to the steep contact angle of sulfuric acid on alumina particles, the sulfuric acid coating would likely not cover the entire alumina surface, which would result in available surface for heterogeneous reactions other than the ones on sulfuric acid. When applying realistic uptake coefficients of 1.0, 10−5 and 10−4 for H2SO4, HCl and HNO3, respectively, the same scenario with injections of calcite particles results in 94 % of the particle mass remaining in the form of CaCO3. This likely keeps the optical properties of the calcite particles intact but could significantly alter the heterogeneous reactions occurring on the particle surfaces. The major process uncertainties of solid-particle SAI are (1) the solid-particle microphysics in the injection plume and degree of agglomeration of solid particles on the sub-ESM grid scale, (2) the scattering properties of the resulting agglomerates, (3) heterogeneous chemistry on the particle surface, and (4) aerosol–cloud interactions. These uncertainties can only be addressed with extensive, coordinated experimental and modelling research efforts. The model presented in this work offers a useful tool for sensitivity studies and incorporating new experimental results on SAI of solid particles.

Abstract Bracken ferns (genus Pteridium) are among the most prevalent plants worldwide, with their distribution expanding due to their invasive nature. The environmental implications of their proliferation in areas affected by human activity, natural disasters, or land-use changes are concerning, primarily because of the carcinogenic illudane glycosides they produce. These compounds cause domestic and wildlife animal poisoning, as well as contamination of dairy products and drinking water. Several illudane glycosides are known, but usually only ptaquiloside (PTA) is monitored. This study investigates the spatial and temporal variations in illudane glycosides PTA, caudatoside (CAU) and ptesculentoside (PTE) across two phenotypes of Pteridium aquilinum (vars. aquilinum and latiusculum) over a broad geographic range spanning Denmark, Sweden, and Finland, encompassing 66 locations. We analysed different parts of the fern fronds (the tips and the lowest pinnae) using LC–MS and statistically explored the influence of phenotype, frond part, geographic location, sunlight exposure, and the surrounding ecosystem on glycoside content. Our findings reveal that PTA accounts for approximately two-thirds of the total illudane glycoside content, followed by CAU at nearly one-third, and a minor contribution from PTE. Glycoside levels were not influenced by phenotypic varieties or the studied environmental factors, but were significantly affected by geographic location. Specifically, CAU levels increased progressively towards the northeast, while PTA concentrations were highest in Denmark and markedly decreased in northeastern countries by over threefold, presumably due to climatic gradient. It has been further supported by temporal analysis in selected PTA-dominant regions indicating a reduction in PTA towards the end of the growing season, aligning its levels with those of CAU. Our study highlights that CAU concentrations in bracken ferns may equal or surpass PTA, contesting the prevailing view that PTA is the only notable illudane glycoside in Bracken. To provide unbiased assessment of the potential risks posed by P. aquilinum in the region, environmental and toxicological research should include measurements of not only PTA, but also CAU and, if possible, PTE.

Summary: Background & aims: Accurate fat mass (FM) and muscle mass (MM) assessment is an informative marker of an individual's health. However, the optimal method for assessing body composition in transgender men remains to be determined. Here, we aim to compare body composition estimates in transgender men by bioimpedance analysis (BIA) using the reference settings for “males” and “females” and by dual x-ray absorptiometry (DXA) scans. Methods: We conducted a cross-sectional pilot study investigating the body composition of 10 transgender men undergoing hormonal therapy using BIA and DXA scans. Results: BIA yielded significantly different estimates of body composition depending on the use of either “female” or “male” settings (P

Abstract Background Cognitive impairment is prevalent across neuropsychiatric disorders but there is a lack of treatment strategies with robust, enduring effects. Emerging evidence indicates that altitude-like hypoxia cognition training may induce long-lasting neuroplasticity and improve cognition. We will investigate whether repeated cognition training under normobaric hypoxia can improve cognitive functions in healthy individuals and patients with affective disorders and the neurobiological underpinnings of such effects. Methods In sub-study 1, 120 healthy participants are randomized to one of four treatment arms in a double-blind manner, allowing for examination of separate and combined effects of three-week repeated moderate hypoxia and cognitive training, respectively. In sub-study 2, 60 remitted patients with major depressive disorder or bipolar disorder are randomized to hypoxia with cognition training or treatment as usual. Assessments of cognition, psychosocial functioning, and quality of life are performed at baseline, end-of-treatment, and at 1-month follow-up. Functional magnetic resonance imaging (fMRI) scans are conducted at baseline and 1-month follow-up, and [11C]UCB-J positron emission tomography (PET) scans are performed at end-of-treatment to quantify the synaptic vesicle glycoprotein 2A (SV2A). The primary outcome is a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference with minimum n = 26 per treatment arm. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data is analyzed with the FMRIB Software Library, while PET data is quantified using the simplified reference tissue model (SRTM) with centrum semiovale as reference region. Discussion The results will provide novel insights into whether repeated hypoxia cognition training increases cognition and brain plasticity, which can aid future treatment development strategies. Trial registration ClinicalTrials.gov, NCT06121206 . Registered on 31 October 2023.

Abstract Background Glioblastoma is a highly malignant disease with limited treatment options. Ibrutinib, a covalent Bruton tyrosine kinase inhibitor, is an oral agent with manageable side effects used for hematological diseases including Waldenström macroglobulinemia. We present the case of a 69-year-old Caucasian male patient treated with ibrutinib for suspected Bing–Neel syndrome (BNS), which following a biopsy, was reclassified as glioblastoma. Case presentation In December 2018, a 69-year-old Caucasian male patient was diagnosed with Waldenström macroglobulinemia. As the patient was asymptomatic, without bone marrow failure or high M-component count, watchful waiting was initiated. Due to increasing neurological symptoms, the patient, based on magnetic resonance imaging, was diagnosed with Bing–Neel syndrome in May 2019. The patient received different treatments before starting ibrutinib monotherapy in August 2019 due to disease progression, both on magnetic resonance imaging and clinically. The patient remained clinically stable for 7 months. In March 2020, the patient developed headaches, and both magnetic resonance imaging and a biopsy revealed glioblastoma IDH-wildtype. Treatment was changed in line with the new diagnosis, but the patient died at the end of 2020. Conclusion We present a case in which a patient with glioblastoma IDH-wildtype remained clinically stable for 7 months when treated with ibrutinib monotherapy, which is similar to what would be expected for the standard treatment for glioblastoma. To our knowledge, this is the first patient receiving ibrutinib for a glioblastoma IDH-wildtype with a meaningful clinical outcome. Our case may therefore support previous nonclinical findings, indicating a therapeutic value of ibrutinib in patients with glioblastoma and support for further investigation of ibrutinib as a possible treatment for glioblastoma.

Abstract Background Polypharmacy and inappropriate drug use are associated with adverse health outcomes in older people. Collaborative interventions between geriatricians and general practitioners have demonstrated effectiveness in improving clinical outcomes for complex medication regimens in home-dwelling patients. Since 2012, Norwegian municipalities have established municipal in-patient acute care (MipAC) units, designed to contribute towards reducing the number of hospital admissions. These units predominantly serve older people who typically benefit from multidisciplinary approaches. The primary objective of this study is to evaluate the effect of cooperative medication reviews conducted by MipAC physicians, supervised by geriatricians, and in collaboration with general practitioners, on health-related quality of life and clinical outcomes in MipAC patients ≥ 70 years with polypharmacy. Additionally, the study aims to assess the carbon footprint of the intervention. Methods This is a randomized, single-blind, controlled superiority trial with 16 weeks follow-up. Participants will be randomly assigned to either the control group, receiving usual care at the MipAC unit, or to the intervention group which in addition receive clinical medication reviews that go beyond what is considered usual care. The medication reviews will evaluate medication appropriateness using a structured but individualized framework, and the physicians will receive supervision from geriatricians. Following the clinical medication reviews, the MipAC physicians will arrange telephone meetings with the participants’ general practitioners to combine their assessments in a joint medication review. The primary outcome is health-related quality of life as measured by the 15D instrument. Secondary outcomes include physical and cognitive functioning, oral health, falls, admissions to healthcare facilities, and mortality. Discussion This study aims to identify potential clinical benefits of collaborative, clinical medication reviews within community-level MipAC units for older patients with polypharmacy. The results may offer valuable insights into optimizing patient care in comparable municipal healthcare settings. Trial registration The study was registered prospectively on ClinicalTrials.gov 30.08.2023 with identifier NCT06020391.

Introduction: Several evaluations of lifestyle interventions for childhood obesity exist; however, follow-up beyond 2 years is necessary to validate the effect. The aim of the present study was to investigate long-term weight development following children participating in one of two pragmatic family-centered lifestyle interventions treating childhood obesity. Methods: This real-life observational study included Danish children 4–17 years of age classified as having obesity. Data from 2010 to 2020, from two community-based family-centered lifestyle interventions (designated hereafter as the Aarhus- and the Randers-intervention) were merged with national registers and routine health check-ups, including height and weight. Adjusted mixed effect models were used to model changes in body mass index (BMI) z score. We performed exploratory analyses of the development in BMI z-score within stratified subgroups of children treated in the interventions before investigating potential effect modifications induced by sex, age, family structure, socioeconomic, or immigration status. Results: With a median follow-up of 2.8 years (interquartile range: 1.3; 4.8), 703 children participated in an intervention (445 the Aarhus-intervention; 258 the Randers-intervention) and 2,337 children were not invited to participate (no-intervention). Children in both interventions experienced a comparable reduction in BMI z-scores during the first 6 months compared to the no-intervention group (Aarhus-intervention: −0.12 SD/year and Randers-intervention: −0.25 SD/year). Only children in the Randers-intervention reduced their BMI z-score throughout follow-up (Aarhus-intervention vs. no-intervention: 0.01 SD/year; confidence interval [CI]: −0.01; 0.04; Randers-intervention vs. no-intervention: −0.05 SD/year; CI: −0.08; −0.02). In subgroup comparisons, combining the two interventions, family income below the median (−0.05 SD/year, CI: −0.02; −0.09), immigrant background (0.04 SD/year, CI: 0.00; 0.07), or receiving intervention less than 1 year (0.04 SD/year, CI: 0.00; 0.08) were associated with a yearly increase in BMI z score. In addition, effect modification analyses did not observe any interaction by sex, age, family structure, socioeconomic, or immigration. Conclusions: Although the more dynamic intervention with longer duration obtained and sustained a minor reduction in BMI z score, the clinical impact may only be modest and still not effective enough to induce a long-term beneficial development in BMI in children with obesity.

In recent years, research on normatively positive social tipping dynamics in response to the climate crisis has produced invaluable insights. In contrast, relatively little attention has been given to the potentially negative social tipping processes that might unfold due to an increasingly destabilized Earth system and to how they might in turn reinforce social and ecological destabilization dynamics and/or impede positive social change. In this paper, we discuss selected potential negative social tipping processes (anomie, radicalization and polarization, displacement, conflict, and financial destabilization) linked to Earth system destabilization. We draw on related research to understand the drivers and likelihood of these negative tipping dynamics, their potential effects on human societies and the Earth system, and the potential for cascading interactions (e.g. food insecurity and displacement) contributing to systemic risks. This first attempt to provide an explorative conceptualization and empirical account of potential negative social tipping dynamics linked to Earth system destabilization is intended to motivate further research into an under-studied area that is nonetheless crucial for our ability to respond to the climate crisis and for ensuring that positive social tipping dynamics are not averted by negative ones.

Abstract Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, consequently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice.

Disagreement exists about how to best spark young children's motivation to learn natural science. Both curiosity and wonder are considered important motivational factors for learning during early childhood (0-8 years). This systematic literature review explores research about scientific curiosity and wonder in early childhood education and care published from 2010-2020. The review outlines the population of interest (participants in the study, age of children, study location), methodological trends, and how curiosity and/or wonder are included in the research. The search yielded 300 peer-reviewed articles, of which 33 were included for analysis based on eligibility criteria. The main results showed that: (a) the term "curiosity" was more commonly used than the term "wonder," (b) few studies elaborated on their understanding of the two terms beyond them being naturally present in children, and (c) curiosity and/or wonder were emphasized as means to learn natural science or considered as stimulated by it, although few studies discussed how children's curiosity and wonder can be observed and nurtured. With a better understanding of what defines the terms curiosity and wonder and how to foster these qualities in early childhood education and care, we can learn to better support children's intrinsic motivation for science learning.

Social semiotic discussions about the role played by representations in effective teaching and learning in areas such as physics have led to theoretical proposals that have a strong common thread: in order to acquire an appropriate understanding of a particular object of learning, access to the disciplinary relevance aspects in the representations used calls for the attainment of representational competence across a particular "critical constellation of systematically used semiotic resources (which are referred to as" modes, "see more on this later)." However, an affirming empirical investigation into the relationship between a particular object of learning and different representational formulations, particularly with large numbers of students, is missing in the literature, especially in the context of university-level physics education. To start to address, this research shortfall the positioning for this article is that such studies need to embrace the complexities of student thinking and application of knowledge. To achieve this, both factor and network analyses were used. Even though both approaches are grounded in different frameworks, for the task at hand, both approaches are useful for analyzing clustering dynamics within the responses of a large number of participants. Both also facilitate an exploration of how such clusters may relate to the semiotic resource formulation of a representation. The data were obtained from a questionnaire given to 1,368 students drawn from 12 universities across 7 countries. The questionnaire deals with the refraction of light in introductory-level physics and involves asking students to give their best prediction of the relative visual positioning of images and objects in different semiotically constituted situations. The results of both approaches revealed no one-to-one relationship between a particular representational formulation and a particular cluster of student responses. The factor analysis used correct answer responses to reveal clusters that brought to the fore three different complexity levels in relation to representation formulation. The network analysis used all responses (correct and incorrect) to reveal three structural patterns. What is evident from the results of both analyses is that they confirm two broad conclusions that have emerged from social semiotic explorations dealing with representations in relation to attempting to optimize teaching and learning. The first, which is linked to a facilitating-awareness perspective, is that any given disciplinary visual representation can be expected to evoke a dispersed set of knowledge structures, which is referred to as their "relevance structure." Thus, the network analysis results can be seen as presenting a unique starting point for studies aiming to identify such "relevance structure." The second broad conclusion is that disciplinary visual representation can and often does contain more "disciplinary-relevant aspects" than what may be directly visible in a given representation. These are referred to as the "appresent" aspects that need to become part of the total awareness needed by someone to constitute an intended meaning. The results of the factor analysis can then also be seen to be a way of capturing "all" the disciplinary-relevant aspects (both present and appresent). Educational implications are discussed.