bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental tests on shallow foundations of onshore wind turbine towers
Authors: Lago Bruno Dal , Flessati Luca , Marveggio Pietro , Martinelli Paolo , Fraraccio Giancarlo , di Prisco Claudio , di Prisco Marco 
Published: February 2022

AbstractThe current effort towards the progressive switch from carbon‐based to renewable energy production is leading to a relevant spreading of both on‐ and off‐shore wind turbine towers. Regarding reinforced concrete shallow foundations of onshore wind turbine steel towers, possible reductions of reinforcement may increase their sustainability, speed of erection, and competitiveness. The article presents the results of an experimental program carried out at Politecnico di Milano concerning both cyclic and monotonic loading, simulating extreme wind conditions on 1:15 scaled models of wind turbine steel towers connected by stud bolt adapters to reinforced concrete shallow foundations embedded in a sandy soil. Three couples of foundation specimens were tested with different reinforcement layouts: (a) similar to current praxis, (b) without shear reinforcement, and (c) without shear reinforcement and with 50% of ordinary steel rebars replaced by steel fibers. Additional vertical loads were added to the small‐scale models in order to ensure similarity in terms of stresses. The test results allowed to (i) characterize the mechanical behavior of the foundation element considering soil‐structure interaction under both service and ultimate load conditions, (ii) assess the foundation failure mode, (iii) highlight the role of each typology of reinforcing bars forming the cage, and (iv) provide hints for the optimization of these latter.
Involvement of the NF‐κB and PI3K/Akt/mTOR pathways in cell death triggered by stypoldione, an o‐quinone isolated from the brown algae Stypopodium zonale
Authors: Walter Laura O. , Maioral Mariana F. , Silva Lisandra O. , Speer Douglas B. , Campbell Sanjay C. , Gallimore Winklet , Falkenberg Miriam B. , Santos‐Silva Maria Cláudia 
Published: February 2022

AbstractMultiple myeloma (MM) is a clonal plasma cell malignancy that remains incurable to date. Thus, the aims of this study were to evaluate the involvement of the NF‐κB and PI3K/Akt/mTOR pathways in the cytotoxicity of stypoldione, an o‐quinone isolated from the brown algae Stypopodium zonale, in MM cells (MM1.S). The cytotoxic effect was evaluated in MM1.S cells and peripheral blood mononuclear cells (PBMCs) by MTT assay. The stypoldione reduced the cell viability of MM1.S cells in a concentration and time‐dependent manner (IC50 in MM.1S from 2.55 to 5.38 μM). However, it was also cytotoxic to PBMCs, but at a lower range. Additionally, no significant hemolysis was observed even at concentration up to 10 times the IC50. Apoptotic cell death was confirmed by cell morphology and Annexin V‐FITC assay. Stypoldione induced intrinsic and extrinsic apoptosis by increasing FasR expression and reactive oxygen species (ROS) production, inverting the Bax/Bcl‐2 ratio, and inducing ΔΨm loss, which resulted in AIF release and caspase‐3 activation. It also increased Ki‐67 and survivin expression and inhibited the NF‐κB and PI3K/Akt/mTOR pathways. These results suggest that stypoldione is a good candidate for the development of new drugs for MM treatment.
Waste plastic oil to fuel: An experimental study in thermal barrier coated CI engine with exhaust gas recirculation
Authors: Sudeshkumar Moranahalli Ponnusamy , Francis Xavier Joseph Raj , Balu Pandian , Jayaseelan Veerasundaram , Sudhakar Kumarasamy 
Published: February 2022

AbstractThe disposal of waste plastic has intensified into a massive environmental crisis. A sound disposal technology may be extremely expensive or complex in operation. As a result, experts are investigating alternative methods of recycling waste plastic. Waste plastic oils (WPO) are gaining interest as a replacement for petroleum‐based fuels since they can deliver substantial performance while having a low environmental impact. The goal of this research is to look into the use of WPO in a retarded timing (RT) engine with a partially stabilized zirconium combustion chamber surface (PSZ). In addition, Exhaust Gas Recirculation (EGR) augmentation was used to realize WPO performance fully. With 20% EGR, the engine's thermal efficiency increased by 6.33%, along with the significant reduction of NOx. However, CO, HC, and smoke particle emissions increased by 4.56%, 5.76%, and 3.54%. More research on the sustainability aspects of the WPO is required before considering it as a fuel for the transportation sector.
Accuracy and impact of prenatal diagnosis of common arterial trunk
Authors: Laux D. , Derridj N. , Stirnemann J. , Lucron H. , Stos B. , Levy M. , Houyel L. , Bonnet D. 
Published: February 2022

AbstractObjectivesOutcome of common arterial trunk (CAT) depends mainly on truncal valve function, presence of coronary artery abnormalities and presence of interrupted aortic arch. The main objective of this study was to evaluate the accuracy of prenatal diagnosis of CAT by analyzing prenatal vs postnatal assessment of: (1) anatomic subtypes and (2) truncal valve function. The secondary objective was to assess the potential impact of prenatal diagnosis of CAT on postnatal mortality and morbidity by comparing prenatally vs postnatally diagnosed patients.MethodsThis was a retrospective analysis of all CAT patients diagnosed either prenatally, with postnatal or fetopsy confirmation, or postnatally, from 2011 to 2019 in a single tertiary center. Cohen's kappa statistic was used to evaluate agreement between pre‐ and postnatal assessment of anatomic subtypes according to Van Praagh and of truncal valve function. Mortality and morbidity variables were compared between prenatally vs postnatally diagnosed CAT patients.ResultsA total of 84 patients (62 liveborn with prenatal diagnosis, 16 liveborn with postnatal diagnosis and six terminations of pregnancy with fetopsy) met the inclusion criteria. The accuracy of prenatal diagnosis of CAT anatomic subtype was 80.3%, and prenatal and postnatal concordance for subtype diagnosis was only moderate (κ = 0.43), with no patient with CAT Type A3 (0/4) and only half of patients with CAT Type A4 (8/17) being diagnosed prenatally. Fetal evaluation of truncal valve function underestimated the presence (no agreement; κ = 0.09) and severity (slight agreement; κ = 0.19) of insufficiency. However, four of five cases of postnatally confirmed significant truncal valve stenosis were diagnosed prenatally, with fair agreement for both presence and severity of stenosis (κ = 0.38 and 0.24, respectively). Mortality was comparable in patients with and those without prenatal diagnosis (log‐rank P = 0.87). CAT patients with fetal diagnosis underwent earlier intervention (P < 0.001), had shorter intubation time (P = 0.047) and shorter global hospital stay (P = 0.01).ConclusionsThe accuracy of prenatal diagnosis of CAT is insufficient to tailor neonatal management and to predict outcome. Fetal assessment of truncal valve dysfunction appears unreliable due to perinatal transition. Improvement is necessary in the fetal diagnosis of anatomic subtypes of CAT requiring postnatal prostaglandin infusion. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Eliciting Information for Developing a Circular Economy in the Amsterdam Metropolitan Area
Authors: Arciniegas Gustavo , Wandl Alexander , Mazur Marcin , Mazurek Damian 
Published: February 2022

AbstractAdvancing circularity in metropolitan areas involves planning, co-designing and implementing spatially explicit interventions with a multitude of stakeholders who are required to work with waste and resource management information. For the stakeholders, understanding information on these flows of resources and materials, and the spatial implications of these flows across the territory, is crucial when proposing new interventions and assessing the effects of these interventions. Spatial decision support systems constitute potential tools for supporting groups of stakeholders involved in the collaborative process of shaping the future of urban areas while achieving sustainability and increased circularity. This chapter focuses on the digital representation and portrayal, and the use of different types of information in a digital spatial decision support tool aimed at helping decision-makers through stages of the collaborative process that starts at problem identification and status quo understanding, and finishes at the proposed circular economy strategies for a metropolitan area. The way in which information is modeled and presented in the tool is largely based on the geodesign methodology, and is specific to individual stages of the planning process. The tool presents information relevant to a peri-urban area through different mediums: web maps and charts to describe the study area, Sankey diagrams linked with dynamic flow maps to portray its resource flow streams, and the integration of the above to portray and assess the scenarios developed jointly by the stakeholders. The tool was implemented in an interactive web application and applied to the collaborative process of developing spatial strategies for advancing circularity in the Amsterdam Metropolitan Area. A series of interconnected workshops were held with stakeholders, who used the tool to guide them through the stages of the co-development of the strategies. Stakeholders were presented with spatial information about the study area’s current resource and waste management situation in the form of web maps and the spatial distribution and dynamics of resource flows. This chapter describes how all this information was portrayed, presented, and used within the interactive web application at the collaborative workshops.
Urban Regeneration: An “Incremental Circularity” Perspective
Authors: Cottino Paolo , Domante Dario , Franchina Alice 
Published: February 2022

AbstractUrban Regeneration (UR) is an approach to urban development contrasting soil consumption by catalyzing social energies to reuse urban existing heritage (brownfields and dismissed buildings). The authors of this chapter are professionals within KCity Ltd., a bespoke consultancy specialized in UR design strategies adopting an interdisciplinary approach, derived in particular from policy analysis and urban planning. The aim of this chapter is investigating the potential of UR practices to give a contribution to the scientific debate about Circular Economy and its application into urban development.
From Wastescapes Towards Regenerative Territories. A Structural Approach for Achieving Circularity
Authors: Amenta Libera , van Timmeren Arjan 
Published: February 2022

AbstractIn this chapter, the understanding of circularity goes beyond material resource management, deepening the spatial implications of a more circular management and use of wastescapes, investigated at the urban and metropolitan scale.Besides the health (care) related challenges presented by the current outbreak of the COVID-19 pandemic, additional ones related to our living environment have been—and will continue to be—an urgent call for academic researchers, designers and policymakers to find (eco)innovative solutions and strategies for enhancing the quality of life of all and the availability of more and more safe public (open) spaces and facilities to sustain this. In this situation, the spaces most at risk of urban and peri-urban areas could be found in the unresolved places which are defined as wastescapes, since they are in general still poorly used and valued. Building on the European H2020 research project REPAiR, the definition of wastescapes, provided in this study, builds upon work for two main cases: the metropolitan areas of Amsterdam (The Netherlands) and Naples (Italy). Wastescapes are discarded territories, however, they can also be understood as opportunities to realize regenerative concepts and support strategies related to environmental, spatial and social challenges of the territories and their surroundings. Core is then to improve the socio-ecological values of such territories. Wastescapes are different case by case, being affected by site-specific challenges and characterized by high complexity. The research presented in this chapter shows that the route towards a Circular Economy requires the consideration of wastescapes as ‘spatial resources’ important to be included in strategies of transition. It represents a fundamental step to overcome problems related to both resource (and land) scarcity, land use in general and spatial fragmentation, while providing opportunities to include through eco-innovative services other values than just the monetary ones to society. The spatial regeneration of wastescapes in the built environment involves a re-thinking of the structure of these areas in a larger (metropolitan) context. Within such metropolitan settings, in particular peri-urban territories, also referred to as the areas in-between urban and rural landscapes, are most affected and characterized by this problem of wastescapes.
Outsourcing in Theory and Practice: Insights from Nuclear Risk Governance
Authors: Eydieux Jérémy 
Published: February 2022

AbstractThis chapter examines two cases of risk governance in which actors interpret outsourcing as a possible source of operational vulnerability while using it to strengthen safety governance. We propose to study this discrepancy through the lens of organisational hypocrisy, suggesting a pragmatist approach as a means of analysing hypocrisy in day-to-day managerial situations.
Contracting and Safety: Lessons from Observing an Outsourcing Process “in the Making”
Authors: Tillement Stéphanie , Leuridan Geoffrey 
Published: February 2022

AbstractDrawing from an inductive study at a nuclear plant, this chapter provides insights about an outsourcing situation that is barely studied in the literature, i.e. an outsourcing process (1) “in the making” of (2) a production activity. We highlight how practical, professional and contractual arrangements are elaborated throughout the progressive transfer of the activity. We discuss, from a situated perspective, the positive and negative effects of outsourcing in the short term and draw attention to key lessons for ensuring safe industrial performance in the long term.
Workload Planning Management of Maintenance Activities in Nuclear Power Plants: Compensation Mechanisms at the Contractor Interface
Authors: Dechy Nicolas , Largier Alexandre 
Published: February 2022

AbstractBy reviewing data from a normal operations safety assessment conducted by IRSN on nuclear safety management, we study some factors that impact the management of maintenance activities. We focus on practices, their benefits and limits, especially in the case of drifts that lead to compensation mechanisms observed at the contractor interface when dealing with workload planning.
Engaged Scholarship for Exploring Applicability of Relational Contracting to Nuclear Industry Projects
Authors: Gotcheva Nadezhda , Aaltonen Kirsi , Lahdenperä Pertti , Nysten-Haarala Soili 
Published: February 2022

AbstractWe employed engaged scholarship as a research strategy for exploring the applicability of relational contracting in nuclear power projects. Insights from a series of workshops with nuclear industry practitioners in Finland indicated that although project alliancing is not a familiar contractual approach in the nuclear industry, the benefits of its implementation are increasingly recognised.
Managing Workplace Safety in the Temporary Organisation—Theoretical and Practical Challenges Associated with Large Construction Projects
Authors: Griegel Heidi Helledal , Gould Kenneth Pettersen 
Published: February 2022

AbstractCompared to permanent organisations, temporary organising causes different challenges for safety and learning at the workplace. We discuss how these challenges faced by project organisations are not sufficiently acknowledged or managed, either within theories of workplace safety or current safety management approaches in the construction industry. In addition, the chapter’s insights contribute to an action-based approach to workplace safety.
Chronic Lymphocytic Leukaemia
Authors: Tournilhac Olivier , Dreger Peter 
Published: February 2022

AbstractAlthough chronic lymphocytic leukaemia (CLL) was one of the first two entities in which CAR-T cells were evaluated, it has not yet arrived in the clinical routine. Since the landmark study by Porter et al. (2011), only six CLL-specific clinical trials have been published, altogether comprising no more than 155 patients (Porter et al. 2015; Gill et al. 2018; Turtle et al. 2017; Gauthier et al. 2020; Siddiqi et al. 2020; Wierda et al. 2020; Frey et al. 2020). All six of these studies investigated CD19-directed CAR-T constructs in heavily pretreated patients, mostly having failed BTKi+/− venetoclax therapy. Despite overall response rates of 60–95%, including MRD clearance in a large proportion of patients, the CR rates appear to be relatively low, and only a few durable responses have been reported in patients achieving a CR (Porter et al. 2015; Frey et al. 2020; Cappell et al. 2020). While toxicity includes 5–20% grade 3 cytokine release syndrome and 5–25% grade 3 neurotoxicity and appears manageable, long-term efficacy remains an unresolved issue. CLL-specific efficacy barriers for CD19 CAR-T cells could include a reduced capacity for sustained T cell expansion in extensively pretreated elderly CLL patients (Lemal and Tournilhac 2019), along with impaired T cell motility, impaired T cell mitochondrial fitness, and T cell exhaustion (Bair and Porter 2019). Concurrent use of ibrutinib might reduce the CRS rate and severity (Gauthier et al. 2020; Gill et al. 2018; Wierda et al. 2020) without impairing CAR-T cell expansion.
Lymphodepleting Conditioning Regimens
Authors: Mohty Mohamad , Minnema Monique C. 
Published: February 2022

AbstractLymphodepleting conditioning regimens are essential for the success of CAR-T cell treatment. Their importance in the proliferation and persistence of CAR-T cells has become clearer in the recent years. The suggested mechanisms are described in Table 25.1 and include the effects on immune cells and cytokines, creating an environment for optimal functioning and increasing the peak of expansion of the infused CAR-T cells (Neelapu 2019).
Management of Other Toxicities
Authors: Einsele Hermann , Yakoub-Agha Ibrahim 
Published: February 2022

AbstractSecondary haemophagocytic lymphohistiocytosis (sHLH) or macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur in patients with severe infections, e.g., COVID-19 infection, malignancy or autoimmune diseases. It is also a rare complication of allogeneic haematopoietic cell transplantation (allo-HCT), independent of the underlying trigger mechanism or underlying disorders associated with high mortality. There have been increasing reports of sHLH/MAS occurrence following CAR-T cell therapy, but its differentiation from cytokine release syndrome (CRS) is often difficult (Sandler et al. 2020).
Post-CAR-T Cell Therapy (Consolidation and Relapse): Acute Lymphoblastic Leukaemia
Authors: Gauthier Jordan 
Published: February 2022

AbstractRole of consolidative allogeneic haematopoietic cell transplantation (allo-HCT) for B-cell acute lymphoblastic leukaemia (B-ALL) patients in minimal residual disease-negative (MRD) complete remission (CR) after CD19 CAR-T cell therapy.
Post-CAR-T Cell Therapy (Consolidation and Relapse): Multiple Myeloma
Authors: Rodríguez-Otero Paula , San Miguel Jesús F. 
Published: February 2022

AbstractAdoptive cell therapy with BCMA-directed autologous CAR-T cells has shown very encouraging results in end-stage relapse and refractory multiple myeloma (MM), with overall response rates ranging between 73% and 96.9%, complete response (CR) rates between 33% and 67.9%, and MRD negativity in 50–74% of patients in the two largest phase 2 studies of ide-cel (idecabtagene autoleucel, KarMMa) and cilta-cel (ciltacabtagene autoleucel, CARTITUDE 1) reported thus far (Madduri et al. 2020; Munshi et al. 2021). Unfortunately, responses are usually not maintained, and no plateau has yet been seen in the survival curves. The median progression-free survival (PFS) in the KarMMa study of ide-cel was 8.8 months (95% CI, 5.6–11.6) among all 128 patients infused, increased to 12.1 months (95% CI, 8.8–12.3) among patients receiving the highest dose (450 × 106 CAR + T cells) and increased to 20.2 months (95% CI, 12.3–NE) among those achieving a CR. In the CARTITUDE-1 study, with a median follow-up of 12.4 months, the median PFS has not yet been reached, and the 12-month PFS rate was 76.6% (95% CI; 66.0–84.3). The absence of a clear plateau in PFS differs from what has been observed in DLBCL or B-ALL with currently approved CD-19-directed CAR-T cells, where (albeit with a shorter PFS and lower rates of CR) patients remaining free from relapse beyond 6 months are likely to enjoy prolonged disease control or even be cured.
Long-Term Follow-Up and Late Effects
Authors: Hayden Patrick , Gagelmann Nico , Snowden John 
Published: February 2022

AbstractLittle is known about the long-term effects of CAR-T cell therapy. Although medium-term complications, such as cytopenia and hypogammaglobulinaemia, may persist and require ongoing treatment, there do not appear to be other durable toxicities specific to this new immunotherapeutic class (Fried et al. 2019; Cordeiro et al. 2020; Cappell et al. 2020). However, to date, CAR-T therapy has been evaluated in patients with multiple relapsed diseases following several lines of treatment, including allogeneic stem cell transplantation, making it difficult to identify which effects may be directly attributable to this novel treatment. Nonetheless, as the use of CAR-T cell therapy increases, structured models for survivorship care will need to be established. The factors that will affect care requirements include the primary malignancy, prior treatment, the specific CAR-T therapy and patient age and frailty.
Treatment Coverage and Reimbursement
Authors: Haag Cornelie 
Published: February 2022

AbstractThe conditions for reimbursement for CAR-T cell therapy are not uniform in Europe. Most European countries use a DRG system for billing hospital services, but the details vary. Nonetheless, the similarity is that expensive therapies, such as CAR-T cell therapy, are initially not included in the DRG system. Most countries possess instruments to ensure the financing of such expensive therapies outside the DRG system as separate payments. These reimbursement instruments of DRG systems are used in most countries both for short-term financing for innovative and new therapies and as long-term additional fees within the respective DRG system. Individual countries maintain different regulations, and therefore, hospitals have the responsibility to determine the specific requirements of their country before establishing CAR-T cell therapy.
Providing the Starting Material to the Manufacturer of an Approved and Commercially Available Autologous CAR-T Cell Treatment
Authors: Bonig Halvard , Chabannon Christian , Lozano Miquel 
Published: February 2022

AbstractCAR-T cell manufacturing starts from a collection of mononuclear cells (MNCs, although specifically only T lymphocytes will be used for the preparation) from the patient using apheresis. Although several initiatives are working on the development of allogeneic CAR-T cells, currently only CAR-T therapies of autologous origin are approved in the European Union. The present chapter only discusses already or soon-to-be marketed autologous CAR-T cells and excludes investigational CAR-T cells or rare CAR-T cells approved in the context of hospital exemption, such as the ARI-001 product (Ortiz-Maldonado et al. 2021); on this topic, please refer to Chapter 3c.