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IntroductionDisagreements between people on different sides of popular issues in STEM are often rooted in differences in “mental models,” which include both rational and emotional cognitive associations about the issue; especially given these issues are systemic in nature.MethodsIn the research described here, we employ the fuzzy cognitive mapping software MentalModeler (developed by one of the authors)1 as a tool for articulating implicit and explicit assumptions about one’s knowledge of both the environmental and social science and values underpinning complex system related issues. More specifically, we test the assumption that this pedagogical approach will foster certain aspects of perspective taking that can be traced with cognitive development and systems thinking as students not only articulate their own understanding of an issue, but also articulate the view of others.Results and discussionResults are discussed with respect to systems thinking that is developed through this type of modeling.

Systems Thinking (ST) can be defined as a mental construct that recognises patterns and connections in a particular complex system to make the “best decision” possible. In the field of sustainable agriculture and climate change, higher degrees of ST are assumed to be associated with more successful adaptation strategies under changing conditions, and “better” environmental decision making in a number of environmental and cultural settings. Future climate change scenarios highlight the negative effects on agricultural productivity worldwide, particularly in low-income countries (LICs) situated in the Global South. Alongside this, current measures of ST are limited by their reliance on recall, and are prone to possible measurement errors. Using Climate-Smart Agriculture (CSA), as an example case study, in this article we explore: (i) ST from a social science perspective; (ii) cognitive neuroscience tools that could be used to explore ST abilities in the context of LICs; (iii) an exploration of the possible correlates of systems thinking: observational learning, prospective thinking/memory and the theory of planned behaviour and (iv) a proposed theory of change highlighting the integration of social science frameworks and a cognitive neuroscience perspective. We find, recent advancements in the field of cognitive neuroscience such as Near-Infrared Spectroscopy (NIRS) provide exciting potential to explore previously hidden forms of cognition, especially in a low-income country/field setting; improving our understanding of environmental decision-making and the ability to more accurately test more complex hypotheses where access to laboratory studies is severely limited. We highlight that ST may correlate with other key aspects involved in environmental decision-making and posit motivating farmers via specific brain networks would: (a) enhance understanding of CSA practices (e.g., via the frontoparietal network extending from the dorsolateral prefrontal cortex (DLPFC) to the parietal cortex (PC) a control hub involved in ST and observational learning) such as tailoring training towards developing improved ST abilities among farmers and involving observational learning more explicitly and (b) motivate farmers to use such practices [e.g., via the network between the DLPFC and nucleus accumbens (NAc)] which mediates reward processing and motivation by focussing on a reward/emotion to engage farmers. Finally, our proposed interdisciplinary theory of change can be used as a starting point to encourage discussion and guide future research in this space.

OBJECTIVES/GOALS: SLC6A1-Related Neurodevelopmental Disorder (SLC6A1-NDD) is a leading genetic cause of epilepsy and autism. Haploinsufficiency of SLC6A1 leads to reduced uptake of GABA from the synaptic cleft, and increased extracellular GABA in mice. It is a candidate for gene transfer therapy, but translational read outs are needed. EEG is a promising biomarker. METHODS/STUDY POPULATION: The SLC6A1-NDD program includes a specialty clinic and prospective cohort study run in parallel with pre-clinical gene therapy development. Characterization and pre-clinical testing of a homozygous knock-out, heterozygous knock-out, and two humanized knock-in models are on-going, including EEG analyses before and after treatment. Patients with a confirmed diagnosis of SLC6A1-NDD are seen annually in a specialty clinic and a subset participate in the cohort study which collects standardized questionnaires, EEGs, and MR Spectroscopy to measure glutamate and GABA. Gene Therapy Program investigators meet weekly to discuss progress on pre-clinical and clinical trial readiness on SLC6A1-NDD and to align efforts on translational read outs, including EEG, in both humans and the pre-clinical models. RESULTS/ANTICIPATED RESULTS: We have enrolled the full cohort of 20 participants in the prospective SLC6A1-NDD cohort study. Preliminary results have shown that all but 1 individual has a history of developmental delay, and 8 of the 24 individuals in our clinical cohort had at least one episode of developmental regression. Over 90% have epilepsy, and 17/20 in the cohort study have intermittent rhythmic delta activity on EEG. The full knock out mice have behavioral and learning deficits and abnormal electrical brain activity on telemetry, including bursts of spike trains, analogous to epileptiform activity seen in humans. Next steps include quantitative analysis of both mouse and human EEG to develop a translational brain-based biomarker. We plan to assess delta power and investigate genotype-phenotype correlations in mice and humans. DISCUSSION/SIGNIFICANCE: With targeted therapies in development for SLC6A1-NDD, translational biomarkers that demonstrate engagement with the brain are critical. With clinical heterogeneity in SLC6A1-NDD, biomarkers can objectively capture change. Collaborative translational projects may improve efficiency in rare disease research to facilitate early phase trials.

Abstract The concept of social–ecological knowledge diversity (SEKD) provides a novel way of examining coupled human–environment interactions—it acknowledges differences in knowledge, values, and beliefs of stakeholder groups within social–ecological systems (SES). Thus, understanding and measuring SEKD is an essential component of sustainable management with implications for conflict resolution, collective action and policymaking. However, methods to efficiently define and model knowledge diversity are still underdeveloped. Using a semiquantitative cognitive mapping approach, we collected and analyzed stakeholder‐specific knowledge and perceptions of the Western Baltic cod fishery to model SEKD. Results demonstrate substantial variation in perceptions across different individuals and social groups. SEKD was evident in (a) distinctive meanings attached to social factors relative to ecological factors, (b) causal relationships underlying the understanding of SES dynamics, and (c) social impacts of ecological changes on ecosystems (and vice versa). By identifying and representing knowledge‐specific disparities in SES frameworks, our model explicitly improves the understanding of human–environment interactions with implications that could help reduce conflicts and legitimize management plans.

**Background**: Traditional socket-based prostheses are an important rehabilitation tool in lower limb amputation, however, patients often experience skin-related problems, pain, stump volume fluctuations and poor suspension. Osseointegration offers a suitable alternative by providing direct skeletal attachment for limb prosthesis. This study aims to review the complications following osseointegration for lower limb amputation, with attention to mechanical abutment failure. **Method**: A retrospective chart review was undertaken of all patients who underwent transfemoral osseointegration between January 2000 and June 2019 through the osseointegration and targeted muscle reinnervation surgical and rehabilitation program at The Alfred in Victoria, Australia. Ethics approval was obtained through The Alfred’s ethics committee (414/16). In 2016 this program was redesigned and in 2017 the osseointegration implant system was modified. Patients underwent a two-stage surgical procedure followed by a rehabilitation protocol that gradually increased their activity. **Results**: A total of 19 limbs were osseointegrated in 18 patients during the study period. Two patients had their implant removed due to failure of osseointegration. The most common complication was a mechanical abutment failure, occurring 46 times in 11 patients. Patients who suffered an abutment failure reported higher levels of postoperative activity. Soft-tissue infections occurred in five patients: three superficial skin infections and two collections. There were no mechanical abutment failures noted in the updated program. **Conclusion**: Osseointegration is a good option for patients who may have difficulties with traditional socket prosthesis. However, complications such as abutment fracture can occur, and appropriate patient selection and counselling are required.

Groups with higher cognitive diversity, i.e. variations in how people think and solve problems, are thought to contribute to improved performance in complex problem-solving. However, embracing or even engineering adequate cognitive diversity is not straightforward and may even jeopardize social inclusion. In response, those that want to promote cognitive diversity might make a simplified assumption that there exists a link between identity diversity, i.e. range of social characteristics, and variations in how people perceive and solve problems. If this assumption holds true, incorporating diverse identities may concurrently achieve cognitive diversity to the extent essential for complex problem-solving, while social inclusion is explicitly acknowledged. However, currently there is a lack of empirical evidence to support this hypothesis in the context of complex social-ecological systems—a system wherein human and environmental dimensions are interdependent, where common-pool resources are used or managed by multiple types of stakeholders. Using a fisheries example, we examine the relationship between resource stakeholders’ identities and their cognitive diversity. We used cognitive mapping techniques in conjunction with network analysis to measure cognitive distances within and between stakeholders of various social types (i.e., identities). Our results empirically show that groups with higher identity diversity also demonstrate more cognitive diversity, evidenced by disparate characteristics of their cognitive maps that represent their understanding of fishery dynamics. These findings have important implications for sustainable management of common-pool resources, where the inclusion of diverse stakeholders is routine, while our study shows it may also achieve higher cognitive coverage that can potentially lead to more complete, accurate, and innovative understanding of complex resource dynamics.

Introduction: Prostate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy. Methods: Tissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups – Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared. Results: Pathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066). Conclusion: In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.

Background: Early data showed that FOXP3 could induce epithelial-mesenchymal transition by stimulating the Wnt/β-catenin signaling pathway in non-small cell lung cancer (NSCLC). However, how the expression of FOXP3 is regulated in NSCLC remains unknown. We thus explored the impacts of the long noncoding RNA EGFR antisense RNA 1 (EGFR-AS1) and hypoxia-inducible factor-2A (HIF2A) on FOXP3 expression and the cancer stemness of NSCLC. Methods: Lung tissues samples from 87 patients with NSCLC and two NSCLC cell lines were used in this study. The regulation of FOXP3 and lung cancer cell stemness by EGFR-AS1 and HIF2A was determined at molecular levels in NSCLC tissue samples and cultured cells in the presence/absence of the smoking carcinogen, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (also known as nicotine-derived nitrosamine ketone). The results were confirmed in tumor xenograft models. Results: We found that NNK decreased the expression of EGFR-AS1 in the long term, but increased the expression of HIF2A and FOXP3 to stimulate lung cancer cell stemness. EGFR-AS1 significantly inhibited FOXP3 expression and NSCLC cell stemness, whereas HIF2A obviously promoted both. The enhancement of lung cancer stemness by FOXP3 was, at least partially, via stimulating Notch1, as the inhibition of Notch1 could markedly diminish the effect of FOXP3. Conclusions: FOXP3, the expression of which is under the fine control of EGFR-AS1, is a critical molecule that promotes NSCLC cancer cell stemness through stimulating the Notch1 pathway.

Participatory Modeling (PM) is becoming increasingly common in environmental planning and conservation, due in part to advances in cyberinfrastructure as well as to greater recognition of the importance of engaging a diverse array of stakeholders in decision making. We provide lessons learned, based on over 200 years of the authors’ cumulative and diverse experience, about PM processes. These include successful and, perhaps more importantly, not-so-successful trials. Our collective interdisciplinary background has supported the development, testing, and evaluation of a rich range of collaborative modeling approaches. We share here what we have learned as a community of participatory modelers, within three categories of reflection: a) lessons learned about participatory modelers; b) lessons learned about the context of collaboration; and c) lessons learned about the PM process. First, successful PM teams encompass a variety of skills beyond modeling expertise. Skills include: effective relationship-building, openness to learn from local experts, awareness of personal motivations and biases, and ability to translate discussions into models and to assess success. Second, the context for collaboration necessitates a culturally appropriate process for knowledge generation and use, for involvement of community co-leads, and for understanding group power dynamics that might influence how people from different backgrounds interact. Finally, knowing when to use PM and when not to, managing expectations, and effectively and equitably addressing conflicts is essential. Managing the participation process in PM is as important as managing the model building process. We recommend that PM teams consider what skills are present within a team, while ensuring inclusive creative space for collaborative exploration and learning supported by simple yet relevant models. With a realistic view of what it entails, PM can be a powerful approach that builds collective knowledge and social capital, thus helping communities to take charge of their future and address complex social and environmental problems.

This study explores the motivations and barriers for participation and persistence in an innovative citizen science pilot project with Virginia Master Naturalist volunteers. The project combines self-guided online training, in-person meetings, and collaboration through social networking and “mental modeling” to support on-the-ground development and execution of citizen science projects developed by participants. Results suggest that the two strongest motivators for volunteers to participate in the project were an interest in the environment and an interest in protecting a local natural resource. Our findings indicate that volunteers with more prior experience participating in citizen science projects and those with higher gross incomes were more likely to persist in the project. Our data also suggest that decisions to persist or drop out of the project were influenced by volunteers’ time commitment, their ability to use the online tools, the perceived relevance of the resources, and the saliency of the project. Projects that arose from pre-existing environmental issues seemed to be more salient and may have enhanced volunteer persistence. We discuss the influence of our findings and the implications for the development of future citizen science projects.

Nearshore aquaculture siting requires the integration of a range of physical, environmental, and social factors. As a result, the information demand often presents coastal managers with a range of complex issues regarding where specific types of aquaculture should be ideally located that reduce environmental and social impacts. Here we provide a framework and tool for managers faced with these issues that incorporate physical and biological parameters along with geospatial infrastructure. In addition, the development of the tool and underlying data included was undertaken with careful input and consideration of local population concerns and cultural practices. Using Hawaiʻi as a model system, we discuss the various considerations that were integrated into an end-user tool for aquaculture siting.

A primary goal of instruction is to prepare learners to transfer their knowledge and skills to new contexts, but how far this transfer goes is an open question. In the research reported here, we seek to explain a case of transfer through examining the processes by which a conceptual representation used to reason about complex systems was transferred from one natural system (an aquarium ecosystem) to another natural system (human cells and body systems). In this case study, a teacher was motivated to generalize her understanding of the Structure, Behaviour, and Function (SBF) conceptual representation to modify her classroom instruction and teaching materials for another system. This case of transfer was unexpected and required that we trace back through the video and artefacts collected over several years of this teacher enacting a technology-rich classroom unit organized around this conceptual representation. We provide evidence of transfer using three data sources: (1) artefacts that the teacher created (2) in-depth semi-structured interview data with the teacher about how her understanding of the representation changed over time and (3) video data over multiple years, covering units on the aquatic ecosystem and the new system that the teacher applied the SBF representation to, the cell and body. Borrowing from interactive ethnography, we traced backward from where the teacher showed transfer to understand how she got there. The use of the actor-oriented transfer and preparation for future learning perspectives provided lenses for understanding transfer. Results of this study suggest that identifying similarities under the lens of SBF and using it as a conceptual tool are some primary factors that may have supported transfer.