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This deliverable 4.4 Risk Management is published under WP4Control and real-time simulation of the construction of the ASHVIN project. Abstract In order to develop comprehensive digital-twin supported site risk management regime it is important to collect data on productivity from well-documented previous construction activities. One of the highest risk activities in construction relates to unknown or unanticipated soil conditions. Soils are naturally occurring, variable materials whose properties depend on stress and strain level and vary temporally. Current design methods deal with uncertainty by assuming conservative estimates of soil properties and calculating the response of the geotechnical structure to some unlikely set of extreme loads. In certain analyses involving soil-structure interaction problems (e.g. soil retaining structures) the loads experienced by structural elements (such as piles, anchors, walls etc.) are directly related to the displacements (strains) experienced. Therefore, only a model that uses the most-likely soil and structure properties at any given point in the life-cycle of a structure to accurately predict the displacement can allow the real safety level (resistance to additional loading) of a structure to be determined. This deliverable uses monitoring data collected from the construction of a deep sea quay wall to determine the real safety level of the wall throughout the construction programme. An advanced finite element model is implemented that can capture the real response. By comparing the measured and predicted response of the wall, a number of updates are initiated that incorporate the knowledge gathered and allow for reduction of uncertainty in a logical and consistent manner. The development of Ports is driven by ever increasing vessel sizes. To replace an existing quay wall to allow for larger vessels means an investment of several 100 million euros and a significant environmental cost in terms of CO2 emissions from new construction. In this report the digital twin developed demonstrated the safety level of the existing wall to several metres of additional dredging.

Lassa fever is a deadly viral illness that is endemic in some parts of West Africa, including Nigeria. A deterministic model in the form of a non-linear system of differential equations is developed to analyse the dynamics and possible control of the disease. The model is tested by fitting it to data from Nigeria’s Lassa fever outbreak using a least-squares fitting routine and the model is shown to provide a reasonable fit to the data. Parameters representing various control measures in the model are estimated using the model fitting. Important epidemiological features of the model such as the basic reproduction number (R0), the disease-free equilibrium, and the endemic equilibrium are determined and analysed. The disease-free equilibrium is shown to be asymptotically stable when R0

Relapse following CD19-directed chimeric antigen receptor T-cells (CAR-T) for relapsed/refractory large B-cell lymphoma (r/r LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multi-antigen targeting and PD-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in r/r LBCL as inpatient or outpatient therapy (NCT03289455, https://clinicaltrials.gov/ct2/show/NCT03289455). Endpoints include toxicity (primary) and response rates (secondary). AUTO3 was manufactured for 62 patients using autologous leukapheresis, modified with a bicistronic transgene. 52 patients received AUTO3 (7/52,50x106; 45/52,150-450x106) and 48/52 received pembrolizumab. Median age was 59 years (range,27-83) and 46/52 had stage III/IV disease. Median follow-up was 21.6 months (range,15.1-51.3) at last data cut (Feb 28, 2022). AUTO3 was safe: grade 1-2 and grade 3 CRS affected 18/52 (34.6%) and 1/52 (1.9%) patients, neurotoxicity arose in 4 patients (2/4, grade 3-4), HLH affected 2 patients, and no Pembrolizumab-associated autoimmune sequalae were observed. On this basis, outpatient administration was tested in 20 patients, saving a median of 14 hospital days/patient. AUTO3 was effective: overall response rates were 66% (48.9%, CR; 17%, PR). For patients with CR, median DOR was not reached, with 54.4% (CI: 32.8, 71.7) projected to remain progression-free beyond 12 months after onset of remission. DOR for all responding patients was 8.3 months (95% CI: 3.0, NE) with 42.6% projected to remain progression-free beyond 12 months after onset of remission. Overall, AUTO3 +/- pembrolizumab for r/r LBCL was safe, lending itself to outpatient administration, and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion/persistence in vivo, and selection of CAR binders active at low antigen densities.

Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear. We conducted a phase 1 trial in pediatric and young adult patients with relapsed or refractory B-ALL (n = 15) to test AUTO3, autologous transduced T cells expressing both anti-CD19 and anti-CD22 CARs (AMELIA trial, EUDRA CT 2016-004680-39). The primary endpoints were the incidence of grade 3–5 toxicity in the dose-limiting toxicity period and the frequency of dose-limiting toxicities. Secondary endpoints included the rate of morphological remission (complete response or complete response with incomplete bone marrow recovery) with minimal residual disease-negative response, as well as the frequency and severity of adverse events, expansion and persistence of AUTO3, duration of B cell aplasia, and overall and event-free survival. The study endpoints were met. AUTO3 showed a favorable safety profile, with no dose-limiting toxicities or cases of AUTO3-related severe cytokine release syndrome or neurotoxicity reported. At 1 month after treatment the remission rate (that is, complete response or complete response with incomplete bone marrow recovery) was 86% (13 of 15 patients). The 1 year overall and event-free survival rates were 60% and 32%, respectively. Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL., Bicistronic CAR T cells targeting CD19 and CD22 exhibit clinical activity and low toxicity in pediatric and young adult patients with B cell acute lymphoblastic leukemia, with relapses associated with limited CAR T cell persistence.

The ASHVIN Work Package (WP3) “Data fusion for real-time construction monitoring” establishes novel algorithms for extracting the required features to be mapped from the real world to the simulated reality. Deliverable 3.2 entitled “ Digital Twin-based Geo-Monitoring” is one of the public technical deliverables of this WP. It is linked to task 3.3 Geo-Monitoring led by NGEO.&nbsp

News media serve as a repository of location data, whether embedded in datelines or news feature content. This study explores how to leverage these data to visualize the regional distribution of risk and benefit news themes associated with reporting on marine aquaculture, a growing domestic industry with complex social and ecological impacts. We extracted geographic content (place names) from news articles about aquaculture risk and/or benefit using natural language processing, geocoded articles by their focal location, and qualitatively validated theme-location associations for geospatial analysis. We present emergent results from this analysis and provide recommendations for applying or integrating this methodology in interdisciplinary team science.

Environmental journalists, as gatekeepers, often become arbiters of risk and benefit information. This study explores how their routine news value judgments may influence reporting on marine aquaculture, a growing domestic industry with complex social and ecological impacts. We interviewed New England newspaper journalists using Q methodology, a qualitative dominant mixed-method approach to study shared subjectivity in small samples. Results revealed four distinct reporting perspectives—“state structuralist,” “neighborhood preservationist,” “industrial futurist,” and “local proceduralist”—stemming from the news value and objectivity routines journalists used in news selection. Findings suggest implications for public understanding of, and positionality toward, natural resource use and development.

This study examines how cone penetration test (CPT) parameters, such as cone tip resistance and friction sleeve resistance, can be used to assess the compressibility of fine-grained soils across the Netherlands based on a database of 286 paired CPTs and oedometer tests from across the country. This is done with the aim of refining and simplifying the parameterisation of the Koppejan consolidation coefficients, a procedure which can yield significant error and is prone to misinterpretation. It was found that there is significant potential in using gradient boosting methods to obtain a relationship between the CPT parameters and the Koppejan parameters, with further investigation required into the noise within the dataset and the acquisition of additional high-quality samples. The use of such methods will offer a means of reducing the influence of human error or misinterpretation on the prediction of settlement and provide further confidence in the use of machine learning methods in engineering practice.

Despite having been practiced in U.S. waters for many decades, marine aquaculture (cultivating seafood in salt or brackish water) is less familiar to many Americans than land-based farming. As aqua...

The birth of the modern environmental movement in the 1970s sparked more extended and in-depth news coverage of ecological issues and awakened interest among journalism educators and prospective jo...

Educators continue to utilize add-ons, extensions, or replacements to traditional Learning Management Systems (LMSs) to supplement capabilities and improve the classroom experience. This work resul...

Cardiovascular magnetic resonance imaging has been the noninvasive method of choice for the evaluation of regional myocardial movement since myocardial tagging was invented almost 30 years ago. A number of developments and improvements on the technique have taken place to improve image resolution, quality, three-dimensional image acquisition, and scan duration. These techniques have also been applied in a variety of heart diseases spanning ischemic heart disease, hypertrophic cardiomyopathy, and other forms of nonischemic cardiomyopathy, pericardial diseases, valvular heart disease, right heart diseases, and congenital heart diseases. In recent years, feature tracking on cine images allowed generation of much greater amount of data on regional function of cardiac diseases. The clinical decision-making with integration of regional myocardial motion analyses is on the horizon.

Capsule Using game birds as surrogate carcasses for raptors could significantly bias calibration searches for wind turbine collision fatalities.

The ranging behaviour and habitat occupancy by three elephant groups (cow herd, bulls, and an orphan group) were studied over a two-year period in a small, fenced reserve. No summer dispersal was observed. Distinct seasonal home ranges were exhibited for all groups, with the summer (wet season) ranges being smaller than the winter (dry season) ranges. Home range size was much smaller than in other locations. The dam and surrounding high density of patches of vegetation of high nutritional quality are thought to be the reasons. Habitat selection was strongly evident with all of the elephant groups selecting River Line habitats in the dry season. In the wet season the cow herd and orphans selected the more open Acacia habitats and the bulls exhibited no significant habitat preference.Keywords: elephant, seasonal range, habitat selection, range use

ONO-2952, a novel antagonist of translocator protein 18 kDa (TSPO), binds with high affinity to TSPO in rat brain and human tumor cell line membrane preparations. This study used the TSPO-specific PET radioligand [

Aquaculture has been responsible for an impressive growth in the global supply of seafood. As of 2016, more than half of all global seafood production comes from aquaculture. To meet future global seafood demands, there is need and opportunity to expand marine aquaculture production in ways that are both socially and ecologically sustainable. This requires integrating biophysical, social, and engineering sciences. Such interdisciplinary research is difficult due to the complexity and multi-scale aspects of marine aquaculture and inherent challenges researchers face working across disciplines. To this end, we developed a framework based on Elinor Ostrom&rsquo, s social&ndash, ecological system framework (SESF) to guide interdisciplinary research on marine aquaculture. We first present the framework and the social&ndash, ecological system variables relevant to research on marine aquaculture and then illustrate one application of this framework to interdisciplinary research underway in Maine, the largest producer of marine aquaculture products in the United States. We use the framework to compare oyster aquaculture in two study regions, with a focus on factors influencing the social and biophysical carrying capacity. We conclude that the flexibility provided by the SESF is well suited to inform interdisciplinary research on marine aquaculture, especially comparative, cross-case analysis.

This article is a critique of the claim made by Gerard O’Hanlon that von Balthasar has pioneered a new way of combining metaphorical and literal discourse, and that this enables him to predicate change, suffering, and surprise of God, while maintaining classical positions on divine transcendence. Some such positions on divine nature and on the notions of univocity, analogy, and metaphor are explored. It is argued—using in particular the contemporary Thomism of Herbert McCabe and some recent studies on the philosophy of metaphor—that von Balthasar, as interpreted by O’Hanlon, tries to give literal expression to what in metaphors is non-propositional. The article concludes that there is no novel advance in combining analogy and metaphor that could enable von Balthasar to avoid self-contradiction in a classical framework.

Despite the persistent belief that Asians are the "model minority" there is accumulating evidence of health concerns within Asian subgroups. In this study, we implemented a cross-sectional participatory community health assessment in an urban city in Massachusetts, to understand differences and similarities in demographics, health and healthcare access in Chinese and Vietnamese adults. We gathered qualitative data from community stakeholders to inform the development of a community health assessment tool. The tool elicited information on healthcare access, health status, behavioral health and chronic disease history and treatment. Healthcare access issues and poor health status, particularly among Chinese participants and mental health symptomotology in both groups were areas of concern. These findings revealed important health concerns in two Asian ethnic groups. Studies are needed to better understand these concerns and inform programs and policies to improve health outcomes in these Asian ethnic groups.

This study presents an assessment of the changes in the telecommunications industry and their impact on market returns. Events were identified from a sample of global telecom companies and assessed...