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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

In this work we investigate the effect of spheroidicity on complexity in self-gravitating, static systems. Utilizing the anisotropic generalisation of the Vaidya–Tikekar superdense stellar model, we employ the complexity factor to connect the spheroidal parameter to the pressure anisotropy and density inhomogeneity. Our findings indicate that deviation from spherical symmetry lead to a higher degree of complexity within the stellar body. We further show the equation of state of parameter is inherently linked to the complexity factor thus demonstrating that the nature of matter in self-gravitating bounded systems plays an important role in the effect of pressure anisotropy and density inhomogeneities.

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.

Technology acceptance has spawned considerable research in technology adoption, technology use, and technology switching. However, technology choice—i.e., an individual’s selection of a technology from a set of technologies that support similar tasks—has received limited attention in information systems research. This research was aimed at identifying the drivers of technology choice through a series of activities in two universities, in which students chose an information technology tool from various alternatives to complete the given tasks. A thematic analysis was conducted on the reasons for technology choice reported by 249 students, which yielded 18 technology, user, and environmental drivers that influenced individuals’ technology choice. This study provides insights into the drivers generally applicable for technology choice and drivers applicable in specific contexts. Implications for research and practice are discussed.

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...

Although the literature frequently examines achieving an integrated supply chain and participating in information sharing with supply chain partners, there is little guidance given to firms on how to progress to a state where these goals can become reality. This paper examines the struggles of one firm in moving toward information sharing with its suppliers and its hopes of achieving an integrated supply chain. This paper reveals lessons learned from the difficulties the firm encountered during the integration process. Despite putting an information system in place, the company discovered that people issues matter as much, if not more, than technology issues.

The purpose of this investigation was to examine the effect of auditory stimuli (AS) and visual stimuli (VS) on response time, speed, and distance in male and female college athletes. Thirty-five healthy National Collegiate Athletic Association Division I men's soccer and women's lacrosse athletes (mean age 20.7 +/- 2.3 years) participated in the study. This experiment was conducted in a laboratory environment, using a Cybex "Reactor" a 14-sensor force plate device used to detect response times, speed, and distance. Subjects stood on the "start" sensor and were instructed at the prompt (auditory: a prerecorded "go" command, visual: an illuminated circle on a television monitor) to run through the "end" sensor without braking. Three trials of each condition were performed by each subject. Movement time, speed, and distance were recorded for each trial. General linear model repeated measure analyses and post hoc 1-way analysis of variance were conducted on all dependent variables (p < or = 0.05). Movement time was significantly faster in men compared with women under AS (p = 0.008) and VS (p < 0.05) conditions. A trend toward a faster transit time was noted in men in the AS condition (p = 0.072), but transit time was faster in men in the VS condition (p < 0.001). Transit speed (distance covered) was faster in men in response to AS (p < 0.05) and VS (p < 0.001). Male athletes respond faster as compared with female athletes, and cover greater distance when presented with VSs as compared to ASs. Data suggest that performance in male athletes related to response times, speed, and distance may be enhanced with the use of visual cueing or VSs.

Information technology implementations continue to be significant endeavors for both research and practice. Although prior studies have extensively examined user training and user support, a consensus is lacking on their conceptualizations. Prior research has argued for direct, as well as indirect, effects of user training and user support on perceived benefits while appealing to different theoretical perspectives. This study clarifies the roles of user training and user support in information technology implementations using data on 302 software implementations. Using a Bayesian model comparison strategy, the authors found that the effects of user training and user support on perceived benefits are mediated by individuals’ perceptions regarding the characteristics of the information technologies. These findings suggest that user training and user support should be treated as enablers in process of implementing information technologies.

Doxorubicin-induced cardiotoxicity (CTX) occurs in 10 to 15% of patients. As such, there is an important need to improve our understanding of the relevance of cardiac mechanics in predicting CTX. The overall objective of our study was to use machine learning algorithms to identify new patterns in

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rifampicin is an antibiotic that is used to treat pulmonary tuberculosis. It induces several cytochrome P450 (CYP) enzymes and some drug transporter proteins; its greatest effect is as an inducer of CYP3A4 in the liver and in the small intestine. • Mechanistic drug–drug interaction studies with prototypic CYP3A4 inducers provide essential information for clinical drug development of new chemical entities that are metabolized by the involved CYP450 enzymes. • Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor being developed for the treatment of chronic obstructive pulmonary disease. • The pharmacological effect is based on the total PDE4 inhibitory activity, which represents the combined PDE4 inhibitory activity of roflumilast and its major active metabolite, roflumilast N-oxide. • In patients with chronic obstructive pulmonary disease, pulmonary tuberculosis can be an accompanying disease. Thus, the drug–drug interaction between rifampicin and roflumilast is of clinical relevance. WHAT THIS STUDY ADDS • The pharmacokinetics of roflumilast and of its major pharmacologically active metabolite roflumilast N-oxide is affected by co-administration of rifampicin. • The potent induction of CYP3A4 and other CYP450 enzymes (such as CYP2C19 and extrahepatic CYP1A1) by rifampicin has led to a 58% decrease in the total PDE4 inhibitory activity of roflumilast. • Co-administration of rifampicin with roflumilast may reduce the therapeutic efficacy of roflumilast. AIMS To evaluate the effect of co-administration of rifampicin, an inducer of cytochrome P450 (CYP)3A4, on the pharmacokinetics of roflumilast and roflumilast N-oxide. Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor, being developed for the treatment of chronic obstructive pulmonary disease. Roflumilast is metabolized by CYP3A4 and CYP1A2, with further involvement of CYP2C19 and extrahepatic CYP1A1. In vivo, roflumilast N-oxide contributes >90% to the total PDE4 inhibitory activity. METHODS Sixteen healthy male subjects were enrolled in an open-label, three-period, fixed-sequence study. They received a single oral dose of roflumilast 500 µg on days 1 and 12 and repeated oral doses of rifampicin 600 mg once daily on days 5–15. Plasma concentrations of roflumilast and roflumilast N-oxide were measured for up to 96 h. Test/Reference ratios and 90% confidence intervals (CIs) of geometric means for AUC and Cmax of roflumilast and roflumilast N-oxide and for oral apparent clearance (CL/F) of roflumilast were estimated. RESULTS During the steady-state of rifampicin, the AUC0–∞ of roflumilast decreased by 80% (point estimate 0.21; 90% CI 0.16, 0.27); Cmax by 68% (0.32; CI 0.26, 0.39); for roflumilast N-oxide, the AUC0–∞ decreased by 56% (0.44; CI 0.36, 0.55); Cmax increased by 30% (1.30; 1.15, 1.48); total PDE4 inhibitory activity decreased by 58% (0.42; 0.38, 0.48). CONCLUSIONS Co-administration of rifampicin and roflumilast led to a reduction in total PDE4 inhibitory activity of roflumilast by about 58%. The use of potent cytochrome P450 inducers may reduce the therapeutic effect of roflumilast.

This article describes the implementation of an enterprise resource planning (ERP) implemented by British Petroleum (BP) Worldwide, from the perspective of one of its subsidiary organizations, BP Singapore. The ERP solution, an internally developed system, was implemented globally by BP worldwide quite successfully from a global perspective, though not without challenges at the local level. This study examines the process of implementing a global ERP solution at the local subsidiaries, and the unique problems that may be encountered in force-fitting a global solution at the local level. Among the issues and problems experienced by the subsidiary are higher-than-anticipated costs, longer development times, lack of technical expertise, and compromises in business processes. The findings of the study could be helpful in formulating coping mechanisms in implementing global ERP solutions.

Acute myocardial infarction and its sequelae are the leading cause of death in the United States. Diagnostic imaging of myocardial infarction in both acute and chronic settings provides valuable prognostic information for clinical decision making. Cardiovascular MRI is unique in its ability to offer several different methods for predicting prognosis with regard to viability and future cardiovascular events. These MRI methods, which include dobutamine MRI, perfusion imaging, and delayed contrast-enhanced MRI, can assess contractile function and reserve, microvascular obstruction, and scar characterization, respectively. Future work will further characterize how cardiovascular MRI can assess prognosis as these emerging technologies become incorporated in routine clinical practice.

Although supply chain management and supply chain integration have become topics found within today’s organization as well as topics for researchers from various disciplines, little research has been completed concerning the linkage between business strategy, supply chain strategy, and the resulting decision which an organization makes to enter into an integration initiative. This paper discusses the experience of one organization in formulating a supply chain strategy consistent with its business strategy. The paper concludes with key elements driving the supply chain which emerge from this linkage, a framework for determining the importance of the supply chain to the organization, and a discussion of the benefits gained from creating a tangible incarnation, an enactment, of the firm’s strategy

BACKGROUND: Safe Male Circumcision (SMC) is a proven approach for partial protection of men from acquisition of HIV infection. Several sub-Saharan African countries have a target to circumcise 80% of males aged 15 to 49. The use of devices such as PrePex would aid scaling up of SMC. Since most health workers would have no prior experience with use of devices, skills training is needed. This paper explores a skills transfer model at an urban site in Uganda. OBJECTIVE: To assess the practicability and feasibility of rapid short duration training for safe PrePex device use. METHODS: A prospective study, conducted over 8 weeks (August-October 2012) at International Hospital Kampala, an urban Kampala hospital, examining the performance of various health worker cadres after training in the use of a non-surgical device (PrePex). The prospective study obtained approval from the Makerere School of Medicine Research and Ethics Committee and the Uganda National Council of Science and Technology. If eligible, and after the subject signed the informed consent form, they were enrolled into the study. RESULTS: Ten health workers were successfully trained in use of PrePex during a 3 day non-residential on-the-job training course. After the first three days of training, the trained health workers performed 561 placements and 529 device removals successfully. Over all adverse events (AE) rates were below ≤ 2%; however, there were some differences in AE rates across the cadres trained but not significant (p>0.25 for moderate AEs). CONCLUSION: Rapid training for safe use of the PrePex device is feasible for the range of health workers available for SMC in resource limited settings, but among those with past SMC experience.

Psychologists have identified several limitations to, and biases in, human decision-making processes. One such bias is the anchoring and adjustment effect, which has been demonstrated to be robust both inside and outside the experimental laboratory. Some decision support systems (DSS) have been designed to lessen the effects of decision-making limitations with promising results. This study tested a DSS designed to mitigate the effects of the anchoring and adjustment bias. The results show that anchoring and adjustment remains robust within the context of automated decision support. Implications that follow these results are offered.

Despite an overall increase in technology research in recent years, the focus on perceptions of technological issues across diverse cultures has received little attention. Moreover, the transfer of technology from industrialized nations to developing countries has essentially been overlooked by scholars. The purpose of this study is to measure differences in perceptions of technology between managers from Ecuador and the United States. The typology of motivators and inhibitors of technological growth developed by Cragg and King (1993) is used as the basis for this empirical inquiry. Results suggest that improving planning and control is a key motivator in Ecuador while stimulating managerial enthusiasm is important to U.S. managers. Excessive cost was found to be a powerful inhibitor in both nations. These findings have vast implications for both the public and private sectors as the business environment continues to change in Latin America.