Interdependent human and biophysical systems are highly complex and behave in unpredictable and uncontrollable ways. Social and ecological challenges that emerge from this complexity often defy ...straightforward solutions, and efforts to address these problems will require not only scientific and technological capabilities but also learning and adaptation.
Scenarios are a useful tool for grappling with the uncertainty and complexity of social-ecological challenges because they enable participants to build adaptive capacity through the contemplation of multiple future possibilities. Furthermore, scenarios provide a platform for social learning, which is critical to acting in the face of uncertain, complex, and conflict-laden problems. We studied the Minnesota 2050 project, a collaborative project through which citizens collectively imagined future scenarios and contemplated the implications of these possibilities for the adaptability of their social and environmental communities.
Survey and interview data indicate that these participatory scenario workshops built and strengthened relationships, enhanced participants’ understanding of other perspectives, and triggered systemic thinking, all of which is relevant to collective efforts to respond to social-ecological challenges through sustainable development activities. Our analysis shows that participatory scenarios can stimulate social learning by enabling participants to engage and to discuss options for coping with uncertainty through collaborative actions. Such learning can be of value to participants and to the organizations and decisions in which they are engaged, and scenario processes can be effective tools for supporting collaborative sustainable development efforts.
Abstract
A common way to model an epidemic — restricted to contagion aspects only — is a modification of the Kermack-McKendrick SIR Epidemic model (SIR model) with differential equations. ...(Mis-)Information about epidemics may influence the behavior of the people and thus the course of epidemics as well. We have thus coupled an extended SIR model of the COVID-19 pandemic with a compartment model of the (mis-)information-based attitude of the population towards epidemic countermeasures. The resulting combined model is checked concerning basic plausibility properties like positivity and boundedness. It is calibrated using COVID-19 data from RKI and attitude data provided by the COVID-19 Snapshot Monitoring (COSMO) study. The values of parameters without corresponding observation data have been determined using an
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-fit under mild additional assumptions. The predictions of the calibrated model are essentially in accordance with observations. An uncertainty analysis of the model shows, that our results are in principle stable under measurement errors. We also assessed the scale, at which specific parameters can influence the evolution of epidemics. Another result of the paper is that in a multi-domain epidemic model, the notion of controlled reproduction number has to be redefined when being used as an indicator of the future evolution of epidemics.
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In children, the 2 major RMS subtypes are alveolar and embryonal RMS. Aberrant Hedgehog/Patched1 (Hh/Ptch) signaling is a ...hallmark of embryonal RMS. We demonstrate that mice carrying a Ptch mutation in mesodermal Delta1-expressing cells develop embryonal-like RMS at a similar rate as mice harboring a Ptch mutation in the germline or the brachury-expressing mesoderm. The tumor incidence decreases dramatically when Ptch is mutated in Myf5- or Pax3-expressing cells. No RMS develop from Myogenin/Mef2c-expressing cells. This suggests that Hh/Ptch-associated RMS are derived from Delta1-positive, Myf5-negative, Myogenin-negative and Pax3-negative mesodermal progenitors that can undergo myogenic differentiation but lack stable lineage commitment. Additional preliminary genetic data and data on mesodermal progenitors further imply an interplay of Hh/Ptch and Delta/Notch signaling activity during RMS initiation. In contrast, Wnt signals supposedly suppress RMS formation because RMS multiplicity decreases after inactivation of the Wnt-inhibitor Wif1. Finally, our results strongly suggest that the tumor-initiating event determines the lineage of RMS origin.
Background: Immune therapy has gained significant importance in managing urothelial cancer. The value of PD-L1 remains a matter of controversy, thus requiring an in-depth analysis of its biological ...and clinical relevance. Methods: A total of 193 tumors of muscle-invasive bladder cancer patients (MIBC) were assessed with four PD-L1 assays. PD-L1 scoring results were correlated with data from a comprehensive digital-spatial immune-profiling panel using descriptive statistics, hierarchical clustering and uni-/multivariable survival analyses. Results: PD-L1 scoring algorithms are heterogeneous (agreements from 63.1% to 87.7%), and stems from different constellations of immune and tumor cells (IC/TC). While Ventana IC5% algorithm identifies tumors with high inflammation and favorable baseline prognosis, CPS10 and the TCarea25%/ICarea25% algorithm identify tumors with TC and IC expression. Spatially organized immune phenotypes, which correlate either with high PD-L1 IC expression and favorable prognosis or constitutive PD-L1 TC expression and poor baseline prognosis, cannot be resolved properly by PD-L1 algorithms. PD-L1 negative tumors with relevant immune infiltration can be detected by sTILs scoring on HE slides and digital CD8+ scoring. Conclusions: Contemporary PD-L1 scoring algorithms are not sufficient to resolve spatially distributed MIBC immune phenotypes and their clinical implications. A more comprehensive view of immune phenotypes along with the integration of spatial PD-L1 expression on IC and TC is necessary in order to stratify patients for ICI.
Both scenario visioning and participatory system dynamics modeling emphasize the dynamic and uncontrollable nature of complex socio-ecological systems, and the significance of multiple feedback ...mechanisms. These two methodologies complement one another, but are rarely used together. We partnered with regional organizations in Minnesota to design a future visioning process that incorporated both scenarios and participatory system dynamics modeling. The three purposes of this exercise were: first, to assist regional leaders in making strategic decisions that would make their communities sustainable; second, to identify research gaps that could impede the ability of regional and state groups to plan for the future; and finally, to introduce more systems thinking into planning and policy-making around environmental issues. We found that scenarios and modeling complemented one another, and that both techniques allowed regional groups to focus on the sustainability of fundamental support systems (energy, food, and water supply). The process introduced some creative tensions between imaginative scenario visioning and quantitative system dynamics modeling, and between creating desired futures (a strong cultural norm) and inhabiting the future (a premise of the Minnesota 2050 exercise). We suggest that these tensions can stimulate more agile, strategic thinking about the future.
Grocery workers were essential to the workforce and exempt from lockdown requirements as per Minnesota Executive Order 20-20. The risk of COVID-19 transmission in grocery settings is not well ...documented. This study aimed to determine which factors influenced seropositivity among grocery workers. We conducted a cross-sectional study of Minnesota grocery workers aged 18 and older using a convenience sample. Participants were recruited using a flyer disseminated electronically via e-mail, social media, and newspaper advertising. Participants were directed to an electronic survey and were asked to self-collect capillary blood for IgG antibody testing. Data were analyzed using logistic regression and adjusted for urbanicity, which confounded the relationship between number of job responsibilities in a store and seropositivity. Of 861 Minnesota grocery workers surveyed, 706 (82%) were tested as part of this study, of which 56 (7.9%) tested positive for IgG antibodies. Participants aged 65-74 years had the highest percent positivity. Having multiple job responsibilities in a store was significantly associated with seropositivity in our adjusted model (OR: 1.14 95% CI: 1.01-1.27). Workplace factors influenced seropositivity among Minnesota grocery workers. Future research will examine other potential factors (e.g., in-store preventive measures and access to PPE) that may contribute to increased seropositivity.
•Scoring of stromal tumor infiltrating lymphocytes (sTILs) is feasible on hematoxylin and eosin stained tumor tissue slides of transurethral resections or radical cystectomies.•sTILs scoring values ...are highly correlated with objectively estimated infiltration of cytotoxic immune cell populations, thus reflecting the immunological microenvironment status of muscle-invasive urothelial cancer.•sTILs scoring is a valid, clinically applicable tool for risk and survival stratification of patients with muscle-invasive urothelial cancer undergoing radical cystectomy.
Multi-omics analyses of muscle-invasive bladder cancer (MIBC) demonstrated that specific patterns of tumor infiltrating lymphocytes (TILs) associates with improved outcomes in patients treated with radical cystectomy. However, methodologies for simple and robust quantification of TILs, especially for daily practice purposes, are lacking. Thus, we investigated the feasibility of stromal TIL scoring on hematoxylin/eosin stained (HE) slides in MIBC.
sTILs were scored on HE whole slides of 241 MIBC patients treated with radical cystectomy and adjuvant chemotherapy. Median infiltration of 10% was used as objective cut-off. Additionally, immunohistochemistry was performed on spatially organized tissue microarrays to quantify key immune cell populations objectively for correlational analyses with sTIL scoring results (CD3+/Pan-T-cells, CD8+/cytotoxic T-Cells, CD56+/NK-cells, CD68+/macrophages). sTILs amounts were correlated with clinicopathological features, recurrence-free (RFS), disease-specific (DSS), and overall survival (OS).
sTIL amounts correlated moderately to strongly with quantitatively estimated amounts of pan-T-cells (r = 0.73, P <0.0001), cytotoxic T-cells (r = 0.73, P <0.0001), NK-cells (r = 0.68, P <0.0001), macrophages (r = 0.55, P <0.0001) and with pan-cytotoxic immune infiltration (r = 0.78, P <0.0001), thus reflecting overall infiltration with key immune cell populations. sTIL infiltration ≥10% was associated with significantly higher 5-year OS (45.5% vs. 19.8%), DSS (56.6% vs. 25.6%) and RFS (56.2% vs. 18.9%; P <0.0001 for all three comparisons) rates, and lower pT-stage (P = 0.015), lower pN-stage (P = 0.028), lower rates of lymphovascular invasion (P = 0.0003) and blood vessel invasion (P = 0.01) when compared to sTIL infiltration of <10%. Multivariable regressions models confirmed sTILs as strongest independent predictor for improved outcomes following radical cystectomy.
HE based sTIL scoring is a reliable tool to assess MIBC inflammation status and to stratify the survival of MIBC patients undergoing radical cystectomy. sTIL amount is an independent predictor for improved survival, and might be an useful, routinely applicable tool to identify patients benefiting from perioperative platinum-based chemotherapy and checkpoint inhibitor therapy. However, external validation of our data is required.
The current study determined the extracellular content of glutamate, 10 additional amino acids, lactate, glucose and some antioxidants in a rodent model of malignant glioma, its peritumoral space and ...the adjacent cortex. RG2 tumors were induced in the right frontal cortex of Fischer-344 rats (n = 10) by a standardized procedure to obtain a maximum sagittal tumor width of 3-4 mm diameter. After confirmation of tumor growth and localization by contrast enhanced MRI three microdialysis probes were implanted simultaneously in the cortex: at the tumor implantation site (tumor), 2 mm caudally, brain around tumor (BAT) and 4 mm caudally (cortex) to the site of implantation. Dialysate concentrations of glutamate were increased 3.9-fold in tumor and 2-fold in BAT compared with cortex. Glycine was elevated 11.4-fold in tumor and 2.6-fold in BAT. Lactate was increased 1.7-fold in tumor, 1.2-fold in BAT. Levels of glucose, ascorbic acid and uric acid were not significantly different in tumor, BAT and cortex. The increased dialysate levels of glutamate and glycine in the peritumoral space may contribute to impaired neuronal function and epileptiform activity associated with this tumor type in humans.
The close connection between safety and security has led to a growing interest in a combined handling of these two areas of research. The paper presents a roadmap for realizing such a combined ...handling. The conditions enabling a combined safety and security analysis are identified and used as starting point of the elaboration. Utilizing these properties, a theoretical framework unifying key aspects of both safety and security is developed, whereby a model-based approach is chosen using the DEVS (Discrete Event System Specification) paradigm. A drafted generalized notion of risk extends the framework. The validity and utility of the considerations are shown by discussing power grids as use case in the context of this framework. Opportunities for further research indicate options for continuing the roadmap.
Ceramic/ceramic joining can transform surface channels on a ceramic subcomponent into an interior channel. Interior channels have a number of potential uses in advanced ceramic applications, ...including application as conduits of a variety of fluids, such as fuel, medicine, or cooling fluids. For cooling fluids in particular, the surface texture and shape of the channel can greatly affect its heat transfer and fluid flow characteristics. This paper explores means of “engineering” the surface textures and shapes of such channels, including the fabrication of channels with circular and non-circular cross-sections as well as channels with smooth or textured walls (and channels with a combination of smooth and textured regions). The microstructure of the channels is analyzed using laser scanning confocal microscopy (LSCM). Although LSCM has been used extensively in biological studies, this study is one of the first studies to apply LSCM as a tool to characterize three-dimensional shapes and textures in ceramic materials.
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