Search results for: chemical alternative assessment
Commenced in January 2007
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Search results for: chemical alternative assessment

22 Interference of Polymers Addition in Wastewaters Microbial Survey: Case Study of Viral Retention in Sludges

Authors: Doriane Delafosse, Dominique Fontvieille

Abstract:

Background: Wastewater treatment plants (WWTPs) generally display significant efficacy in virus retention yet, are sometimes highly variable, partly in relation to large fluctuating loads at the head of the plant and partly because of episodic dysfunctions in some treatment processes. The problem is especially sensitive when human enteric viruses, such as human Noroviruses Genogroup I or Adenoviruses, are in concern: their release downstream WWTP, in environments often interconnected to recreational areas, may be very harmful to human communities even at low concentrations. It points out the importance of WWTP permanent monitoring from which their internal treatment processes could be adjusted. One way to adjust primary treatments is to add coagulants and flocculants to sewage ahead settling tanks to improve decantation. In this work, sludge produced by three coagulants (two organics, one mineral), four flocculants (three cationic, one anionic), and their combinations were studied for their efficacy in human enteric virus retention. Sewage samples were coming from a WWTP in the vicinity of the laboratory. All experiments were performed three times and in triplicates in laboratory pilots, using Murine Norovirus (MNV-1), a surrogate of human Norovirus, as an internal control (spiking). Viruses were quantified by (RT-)qPCR after nucleic acid extraction from both treated water and sediment. Results: Low values of sludge virus retention (from 4 to 8% of the initial sewage concentration) were observed with each cationic organic flocculant added to wastewater and no coagulant. The largest part of the virus load was detected in the treated water (48 to 90%). However, it was not counterbalancing the amount of the introduced virus (MNV-1). The results pertained to two types of cationic flocculants, branched and linear, and in the last case, to two percentages of cations. Results were quite similar to the association of a linear cationic organic coagulant and an anionic flocculant, though suggesting that differences between water and sludges would sometimes be related to virus size or virus origins (autochthonous/allochthonous). FeCl₃, as a mineral coagulant associated with an anionic flocculant, significantly increased both auto- and allochthonous virus retention in the sediments (15 to 34%). Accordingly, virus load in treated water was lower (14 to 48%) but with a total that still does not reach the amount of the introduced virus (MNV-1). It also appeared that the virus retrieval in a bare 0.1M NaCl suspension varied rather strongly according to the FeCl₃ concentration, suggesting an inhibiting effect on the molecular analysis used to detect the virus. Finally, no viruses were detected in both phases (sediment and water) with the combination branched cationic coagulant-linear anionic flocculant, which was later demonstrated as an effect, here also, of polymers on the virus detection-molecular analysis. Conclusions: The combination of FeCl₃-anionic flocculant gave its highest performance to the decantation-based virus removal process. However, large unbalanced values in spiking experiments were observed, suggesting that polymers cast additional obstacles to both elution buffer and lysis buffer on their way to reach the virus. The situation was probably even worse with autochthonous viruses already embedded into sewage's particulate matter. Polymers and FeCl₃ also appeared to interfere in some steps of molecular analyses. More attention should be paid to such impediments wherever chemical additives are considered to be used to enhance WWTP processes. Acknowledgments: This research was supported by the ABIOLAB laboratory (Montbonnot Saint-Martin, France) and by the ASPOSAN association. Field experiments were possible thanks to the Grand Chambéry WWTP authorities (Chambéry, France).

Keywords: flocculants-coagulants, polymers, enteric viruses, wastewater sedimentation treatment plant

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21 Optimum Irrigation System Management for Climate Resilient and Improved Productivity of Flood-based Livelihood Systems

Authors: Mara Getachew Zenebe, Luuk Fleskens, Abdu Obieda Ahmed

Abstract:

This paper seeks to advance our scientific understanding of optimizing flood utilization in regions impacted by climate change, with a focus on enhancing agricultural productivity through effective irrigation management. The study was conducted as part of a three-year (2021 to 2023) USAID-supported initiative aimed at promoting Economic Growth and Peace in the Gash Agricultural Scheme (GAS), situated in Sudan's water-stressed Eastern region. GAS is the country's largest flood-irrigated scheme, covering 100,800 hectares of cultivable land, with a potential to provide the food security needs of over a quarter of a million agro-pastoral community members. GAS relies on the Gash River, which sources its water from high-intensity rainfall events in the highlands of Ethiopia and Eritrea. However, climate change and variations in these highlands have led to increased variability in the Gash River's flow. The study conducted water balance analyses based on a ten-year dataset of the annual Gash River flow, irrigated area; as well as the evapotranspiration demand of the major sorghum crop. Data collection methods included field measurements, surveys, remote sensing, and CropWat modelling. The water balance assessment revealed that the existing three-year rotation-based irrigation system management, capping cultivated land at 33,000 hectares annually, is excessively risk-averse. While this system reduced conflicts among the agro-pastoral communities by consistently delivering on the land promised to be annually cultivated, it also increased GAS's vulnerability to flood damage due to several reasons. The irrigation efficiency over the past decade was approximately 30%, leaving significant unharnessed floodwater that caused damage to infrastructure and agricultural land. The three-year rotation resulted in inadequate infrastructural maintenance, given the destructive nature of floods. Additionally, it led to infrequent land tillage, allowing the encroachment of mesquite trees hindering major sorghum crop growth. Remote sensing data confirmed that mesquite trees have overtaken 70,000 hectares in the past two decades, rendering them unavailable for agriculture. The water balance analyses suggest shifting to a two-year rotation, covering approximately 50,000 hectares annually while maintaining risk aversion. This shift could boost GAS's annual sorghum production by two-thirds, exceeding 850,000 tons. The scheme's efficiency can be further enhanced through low-cost on-farm interventions. Currently, large irrigation plots that range from 420 to 756 hectares are irrigated with limited water distribution guidance, leading to uneven irrigation. As demonstrated through field trials, implementing internal longitudinal bunds and horizontal deflector bunds can increase adequately irrigated parts of the irrigation plots from 50% to 80% and thus nearly double the sorghum yield to 2 tons per hectare while reducing the irrigation duration from 30 days to a maximum of 17 days. Flow measurements in 2021 and 2022 confirmed that these changes sufficiently meet the sorghum crop's water requirements, even with a conservative 60% field application efficiency assumption. These insights and lessons from the GAS on enhancing agricultural resilience and sustainability in the face of climate change are relevant to flood-based livelihood systems globally.

Keywords: climate change, irrigation management and productivity, variable flood flows, water balance analysis

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20 “SockGEL/PLUG” Injectable Smart/Intelligent and Bio-Inspired Sol-Gel Nanomaterials for Simple and Complex Oro-Dental and Cranio-Maxillo-Facial Interventional Applications

Authors: Ziyad S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

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19 Assessing Diagnostic and Evaluation Tools for Use in Urban Immunisation Programming: A Critical Narrative Review and Proposed Framework

Authors: Tim Crocker-Buque, Sandra Mounier-Jack, Natasha Howard

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Background: Due to both the increasing scale and speed of urbanisation, urban areas in low and middle-income countries (LMICs) host increasingly large populations of under-immunized children, with the additional associated risks of rapid disease transmission in high-density living environments. Multiple interdependent factors are associated with these coverage disparities in urban areas and most evidence comes from relatively few countries, e.g., predominantly India, Kenya, Nigeria, and some from Pakistan, Iran, and Brazil. This study aimed to identify, describe, and assess the main tools used to measure or improve coverage of immunisation services in poor urban areas. Methods: Authors used a qualitative review design, including academic and non-academic literature, to identify tools used to improve coverage of public health interventions in urban areas. Authors selected and extracted sources that provided good examples of specific tools, or categories of tools, used in a context relevant to urban immunization. Diagnostic (e.g., for data collection, analysis, and insight generation) and programme tools (e.g., for investigating or improving ongoing programmes) and interventions (e.g., multi-component or stand-alone with evidence) were selected for inclusion to provide a range of type and availability of relevant tools. These were then prioritised using a decision-analysis framework and a tool selection guide for programme managers developed. Results: Authors reviewed tools used in urban immunisation contexts and tools designed for (i) non-immunization and/or non-health interventions in urban areas, and (ii) immunisation in rural contexts that had relevance for urban areas (e.g., Reaching every District/Child/ Zone). Many approaches combined several tools and methods, which authors categorised as diagnostic, programme, and intervention. The most common diagnostic tools were cross-sectional surveys, key informant interviews, focus group discussions, secondary analysis of routine data, and geographical mapping of outcomes, resources, and services. Programme tools involved multiple stages of data collection, analysis, insight generation, and intervention planning and included guidance documents from WHO (World Health Organisation), UNICEF (United Nations Children's Fund), USAID (United States Agency for International Development), and governments, and articles reporting on diagnostics, interventions, and/or evaluations to improve urban immunisation. Interventions involved service improvement, education, reminder/recall, incentives, outreach, mass-media, or were multi-component. The main gaps in existing tools were an assessment of macro/policy-level factors, exploration of effective immunization communication channels, and measuring in/out-migration. The proposed framework uses a problem tree approach to suggest tools to address five common challenges (i.e. identifying populations, understanding communities, issues with service access and use, improving services, improving coverage) based on context and available data. Conclusion: This study identified many tools relevant to evaluating urban LMIC immunisation programmes, including significant crossover between tools. This was encouraging in terms of supporting the identification of common areas, but problematic as data volumes, instructions, and activities could overwhelm managers and tools are not always suitably applied to suitable contexts. Further research is needed on how best to combine tools and methods to suit local contexts. Authors’ initial framework can be tested and developed further.

Keywords: health equity, immunisation, low and middle-income countries, poverty, urban health

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18 Teacher Collaboration Impact on Bilingual Students’ Oral Communication Skills in Inclusive Contexts

Authors: Diana González, Marta Gràcia, Ana Luisa Adam-Alcocer

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Incorporating digital tools into educational practices represents a valuable approach for enriching the quality of teachers' educational practices in oral competence and fostering improvements in student learning outcomes. This study aims to promote a collaborative and culturally sensitive approach to professional development between teachers and a speech therapist to enhance their self-awareness and reflection on high-quality educational practices that integrate school components to strengthen children’s oral communication and pragmatic skills. The study involved five bilingual teachers fluent in both English and Spanish, with three specializing in special education and two in general education. It focused on Spanish-English bilingual students, aged 3-6, who were experiencing speech delays or disorders in a New York City public school, with the collaboration of a speech therapist. Using EVALOE-DSS (Assessment Scale of Oral Language Teaching in the School Context - Decision Support System), teachers conducted self-assessments of their teaching practices, reflect and make-decisions throughout six classes from March to June, focusing on students' communicative competence across various activities. Concurrently, the speech therapist observed and evaluated six classes per teacher using EVALOE-DSS during the same period. Additionally, professional development meetings were held monthly between the speech therapist and teachers, centering on discussing classroom interactions, instructional strategies, and the progress of both teachers and students in their classes. Findings highlight the digital tool EVALOE-DSS's value in analyzing communication patterns and trends among bilingual children in inclusive settings. It helps in identifying improvement areas through teacher and speech therapist collaboration. After self-reflection meetings, teachers demonstrated increased awareness of student needs in oral language and pragmatic skills. They also exhibited enhanced utilization of strategies outlined in EVALOE-DSS, such as actively guiding and orienting students during oral language activities, promoting student-initiated communicative interactions, teaching students how to seek and provide information, and managing turn-taking to ensure inclusive participation. Teachers participating in the professional development program have shown positive progress in assessing their classes across all dimensions of the training tool, including instructional design, teacher conversation management, pupil conversation management, communicative functions, teacher strategies, and pupil communication functions. This includes aspects related to both teacher actions and child actions, particularly in child language development. This progress underscores the effectiveness of individual reflection (conducted weekly or biweekly using EVALOE-DSS) as well as collaborative reflection among teachers and the speech therapist during meetings. The EVALOE-SSD has proven effective in supporting teachers' self-reflection, decision-making, and classroom changes, leading to improved development of students' oral language and pragmatic skills. It has facilitated culturally sensitive evaluations of communication among bilingual children, cultivating collaboration between teachers and speech therapist to identify areas of growth. Participants in the professional development program demonstrated substantial progress across all dimensions assessed by EVALOE-DSS. This included improved management of pupil communication functions, implementation of effective teaching strategies, and better classroom dynamics. Regular reflection sessions using EVALOE-SSD supported continuous improvement in instructional practices, highlighting its role in fostering reflective teaching and enriching student learning experiences. Overall, EVALOE-DSS has proven invaluable for enhancing teaching effectiveness and promoting meaningful student interactions in diverse educational settings.

Keywords: bilingual students, collaboration, culturally sensitive, oral communication skills, self-reflection

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17 Hydrocarbon Source Rocks of the Maragh Low

Authors: Elhadi Nasr, Ibrahim Ramadan

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Biostratigraphical analyses of well sections from the Maragh Low in the Eastern Sirt Basin has allowed high resolution correlations to be undertaken. Full integration of this data with available palaeoenvironmental, lithological, gravity, seismic, aeromagnetic, igneous, radiometric and wireline log information and a geochemical analysis of source rock quality and distribution has led to a more detailed understanding of the geological and the structural history of this area. Pre Sirt Unconformity two superimposed rifting cycles have been identified. The oldest is represented by the Amal Group of sediments and is of Late Carboniferous, Kasimovian / Gzelian to Middle Triassic, Anisian age. Unconformably overlying is a younger rift cycle which is represented the Sarir Group of sediments and is of Early Cretaceous, late Neocomian to Aptian in age. Overlying the Sirt Unconformity is the marine Late Cretaceous section. An assessment of pyrolysis results and a palynofacies analysis has allowed hydrocarbon source facies and quality to be determined. There are a number of hydrocarbon source rock horizons in the Maragh Low, these are sometimes vertically stacked and they are of fair to excellent quality. The oldest identified source rock is the Triassic Shale, this unit is unconformably overlain by sandstones belonging to the Sarir Group and conformably overlies a Triassic Siltstone unit. Palynological dating of the Triassic Shale unit indicates a Middle Triassic, Anisian age. The Triassic Shale is interpreted to have been deposited in a lacustrine palaeoenvironment. This particularly is evidenced by the dark, fine grained, organic rich nature of the sediment and is supported by palynofacies analysis and by the recovery of fish fossils. Geochemical analysis of the Triassic Shale indicates total organic carbon varying between 1.37 and 3.53. S2 pyrolysate yields vary between 2.15 mg/g and 6.61 mg/g and hydrogen indices vary between 156.91 and 278.91. The source quality of the Triassic Shale varies from being of fair to very good / rich. Linked to thermal maturity it is now a very good source for light oil and gas. It was once a very good to rich oil source. The Early Barremian Shale was also deposited in a lacustrine palaeoenvironment. Recovered palynomorphs indicate an Early Cretaceous, late Neocomian to early Barremian age. The Early Barremian Shale is conformably underlain and overlain by sandstone units belonging to the Sarir Group of sediments which are also of Early Cretaceous age. Geochemical analysis of the Early Barremian Shale indicates that it is a good oil source and was originally very good. Total organic carbon varies between 3.59% and 7%. S2 varies between 6.30 mg/g and 10.39 mg/g and the hydrogen indices vary between 148.4 and 175.5. A Late Barremian Shale unit of this age has also been identified in the central Maragh Low. Geochemical analyses indicate that total organic carbon varies between 1.05 and 2.38%, S2 pyrolysate between 1.6 and 5.34 mg/g and the hydrogen index between 152.4 and 224.4. It is a good oil source rock which is now mature. In addition to the non marine hydrocarbon source rocks pre Sirt Unconformity, three formations in the overlying Late Cretaceous section also provide hydrocarbon quality source rocks. Interbedded shales within the Rachmat Formation of Late Cretaceous, early Campanian age have total organic carbon ranging between, 0.7 and 1.47%, S2 pyrolysate varying between 1.37 and 4.00 mg/g and hydrogen indices varying between 195.7 and 272.1. The indication is that this unit would provide a fair gas source to a good oil source. Geochemical analyses of the overlying Tagrifet Limestone indicate that total organic carbon varies between 0.26% and 1.01%. S2 pyrolysate varies between 1.21 and 2.16 mg/g and hydrogen indices vary between 195.7 and 465.4. For the overlying Sirt Shale Formation of Late Cretaceous, late Campanian age, total organic carbon varies between 1.04% and 1.51%, S2 pyrolysate varies between 4.65 mg/g and 6.99 mg/g and the hydrogen indices vary between 151 and 462.9. The study has proven that both the Sirt Shale Formation and the Tagrifet Limestone are good to very good and rich sources for oil in the Maragh Low. High resolution biostratigraphical interpretations have been integrated and calibrated with thermal maturity determinations (Vitrinite Reflectance (%Ro), Spore Colour Index (SCI) and Tmax (ºC) and the determined present day geothermal gradient of 25ºC / Km for the Maragh Low. Interpretation of generated basin modelling profiles allows a detailed prediction of timing of maturation development of these source horizons and leads to a determination of amounts of missing section at major unconformities. From the results the top of the oil window (0.72% Ro) is picked as high as 10,700’ and the base of the oil window (1.35% Ro) assuming a linear trend and by projection is picked as low as 18,000’ in the Maragh Low. For the Triassic Shale the early phase of oil generation was in the Late Palaeocene / Early to Middle Eocene and the main phase of oil generation was in the Middle to Late Eocene. The Early Barremian Shale reached the main phase of oil generation in the Early Oligocene with late generation being reached in the Middle Miocene. For the Rakb Group section (Rachmat Formation, Tagrifet Limestone and Sirt Shale Formation) the early phase of oil generation started in the Late Eocene with the main phase of generation being between the Early Oligocene and the Early Miocene. From studying maturity profiles and from regional considerations it can be predicted that up to 500’ of sediment may have been deposited and eroded by the Sirt Unconformity in the central Maragh Low while up to 2000’ of sediment may have been deposited and then eroded to the south of the trough.

Keywords: Geochemical analysis of the source rocks from wells in Eastern Sirt Basin.

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16 From Linear to Circular Model: An Artificial Intelligence-Powered Approach in Fosso Imperatore

Authors: Carlotta D’Alessandro, Giuseppe Ioppolo, Katarzyna Szopik-Depczyńska

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— The growing scarcity of resources and the mounting pressures of climate change, water pollution, and chemical contamination have prompted societies, governments, and businesses to seek ways to minimize their environmental impact. To combat climate change, and foster sustainability, Industrial Symbiosis (IS) offers a powerful approach, facilitating the shift toward a circular economic model. IS has gained prominence in the European Union's policy framework as crucial enabler of resource efficiency and circular economy practices. The essence of IS lies in the collaborative sharing of resources such as energy, material by-products, waste, and water, thanks to geographic proximity. It can be exemplified by eco-industrial parks (EIPs), which are natural environments for boosting cooperation and resource sharing between businesses. EIPs are characterized by group of businesses situated in proximity, connected by a network of both cooperative and competitive interactions. They represent a sustainable industrial model aimed at reducing resource use, waste, and environmental impact while fostering economic and social wellbeing. IS, combined with Artificial Intelligence (AI)-driven technologies, can further optimize resource sharing and efficiency within EIPs. This research, supported by the “CE_IPs” project, aims to analyze the potential for IS and AI, in advancing circularity and sustainability at Fosso Imperatore. The Fosso Imperatore Industrial Park in Nocera Inferiore, Italy, specializes in agriculture and the industrial transformation of agricultural products, particularly tomatoes, tobacco, and textile fibers. This unique industrial cluster, centered around tomato cultivation and processing, also includes mechanical engineering enterprises and agricultural packaging firms. To stimulate the shift from a traditional to a circular economic model, an AI-powered Local Development Plan (LDP) is developed for Fosso Imperatore. It can leverage data analytics, predictive modeling, and stakeholder engagement to optimize resource utilization, reduce waste, and promote sustainable industrial practices. A comprehensive SWOT analysis of the AI-powered LDP revealed several key factors influencing its potential success and challenges. Among the notable strengths and opportunities arising from AI implementation are reduced processing times, fewer human errors, and increased revenue generation. Furthermore, predictive analytics minimize downtime, bolster productivity, and elevate quality while mitigating workplace hazards. However, the integration of AI also presents potential weaknesses and threats, including significant financial investment, since implementing and maintaining AI systems can be costly. The widespread adoption of AI could lead to job losses in certain sectors. Lastly, AI systems are susceptible to cyberattacks, posing risks to data security and operational continuity. Moreover, an Analytic Hierarchy Process (AHP) analysis was employed to yield a prioritized ranking of the outlined AI-driven LDP practices based on the stakeholder input, ensuring a more comprehensive and representative understanding of their relative significance for achieving sustainability in Fosso Imperatore Industrial Park. While this study provides valuable insights into the potential of AIpowered LDP at the Fosso Imperatore, it is important to note that the findings may not be directly applicable to all industrial parks, particularly those with different sizes, geographic locations, or industry compositions. Additional study is necessary to scrutinize the generalizability of these results and to identify best practices for implementing AI-driven LDP in diverse contexts.

Keywords: artificial intelligence, climate change, Fosso Imperatore, industrial park, industrial symbiosis

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15 Unleashing Potential in Pedagogical Innovation for STEM Education: Applying Knowledge Transfer Technology to Guide a Co-Creation Learning Mechanism for the Lingering Effects Amid COVID-19

Authors: Lan Cheng, Harry Qin, Yang Wang

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Background: COVID-19 has induced the largest digital learning experiment in history. There is also emerging research evidence that students have paid a high cost of learning loss from virtual learning. University-wide survey results demonstrate that digital learning remains difficult for students who struggle with learning challenges, isolation, or a lack of resources. Large-scale efforts are therefore increasingly utilized for digital education. To better prepare students in higher education for this grand scientific and technological transformation, STEM education has been prioritized and promoted as a strategic imperative in the ongoing curriculum reform essential for unfinished learning needs and whole-person development. Building upon five key elements identified in the STEM education literature: Problem-based Learning, Community and Belonging, Technology Skills, Personalization of Learning, Connection to the External Community, this case study explores the potential of pedagogical innovation that integrates computational and experimental methodologies to support, enrich, and navigate STEM education. Objectives: The goal of this case study is to create a high-fidelity prototype design for STEM education with knowledge transfer technology that contains a Cooperative Multi-Agent System (CMAS), which has the objectives of (1) conduct assessment to reveal a virtual learning mechanism and establish strategies to facilitate scientific learning engagement, accessibility, and connection within and beyond university setting, (2) explore and validate an interactional co-creation approach embedded in project-based learning activities under the STEM learning context, which is being transformed by both digital technology and student behavior change,(3) formulate and implement the STEM-oriented campaign to guide learning network mapping, mitigate the loss of learning, enhance the learning experience, scale-up inclusive participation. Methods: This study applied a case study strategy and a methodology informed by Social Network Analysis Theory within a cross-disciplinary communication paradigm (students, peers, educators). Knowledge transfer technology is introduced to address learning challenges and to increase the efficiency of Reinforcement Learning (RL) algorithms. A co-creation learning framework was identified and investigated in a context-specific way with a learning analytic tool designed in this study. Findings: The result shows that (1) CMAS-empowered learning support reduced students’ confusion, difficulties, and gaps during problem-solving scenarios while increasing learner capacity empowerment, (2) The co-creation learning phenomenon have examined through the lens of the campaign and reveals that an interactive virtual learning environment fosters students to navigate scientific challenge independently and collaboratively, (3) The deliverables brought from the STEM educational campaign provide a methodological framework both within the context of the curriculum design and external community engagement application. Conclusion: This study brings a holistic and coherent pedagogy to cultivates students’ interest in STEM and develop them a knowledge base to integrate and apply knowledge across different STEM disciplines. Through the co-designing and cross-disciplinary educational content and campaign promotion, findings suggest factors to empower evidence-based learning practice while also piloting and tracking the impact of the scholastic value of co-creation under the dynamic learning environment. The data nested under the knowledge transfer technology situates learners’ scientific journey and could pave the way for theoretical advancement and broader scientific enervators within larger datasets, projects, and communities.

Keywords: co-creation, cross-disciplinary, knowledge transfer, STEM education, social network analysis

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14 General Evaluation of a Three-Year Holistic Physical Activity Interventions Program in Qatar Campuses: Step into Health (SIH) in Campuses 2013- 2016

Authors: Daniela Salih Khidir, Mohamed G. Al Kuwari, Mercia V. Walt, Izzeldin J. Ibrahim

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Background: University-based physical activity interventions aim to establish durable social patterns during the transition to adulthood. This study is a comprehensive evaluation of a 3-year intervention-based program to increase the culture of physical activity (PA) routine in Qatar campuses community, using a holistic approach. Methodology: General assessment methods: formative evaluation-SIH Campuses logic model design, stakeholders’ identification; process evaluation-members’ step counts analyze and qualitative Appreciative Inquiry session (4-D model); daily steps categorized as: ≤5,000, inactive; 5,000-7,499 low active; ≥7,500, physically active; outcome evaluation - records 3 years interventions. Holistic PA interventions methods: walking interventions - pedometers distributions and walking competitions for students and staff; educational interventions - in campuses implementation of bilingual educational materials, lectures, video related to PA in prevention of non-communicable diseases (NCD); articles published online; monthly emails and sms notifications for pedometer use; mass media campaign - radio advertising, yearly pre/post press releases; community stakeholders interventions-biyearly planning/reporting/achievements rewarding/ qualitative meetings; continuous follow-up communication, biweekly steps reports. Findings: Results formative evaluation - SIH in Campuses logic model identified the need of PA awareness and education within universities, resources, activities, health benefits, program continuity. Results process evaluation: walking interventions: Phase 1: 5 universities recruited, 2352 members, 3 months competition; Phase 2: 6 new universities recruited, 1328 members in addition, 4 months competition; Phase 3: 4 new universities recruited in addition, 1210 members, 6 months competition. Results phase 1 and 2: 1,299 members eligible for analyzes: 800 females (62%), 499 males (38%); 86% non-Qataris, 14% Qatari nationals, daily step count 5,681 steps, age groups 18–24 (n=841; 68%) students, 25–64; (n=458; 35.3%) staff; 38% - low active, 37% physically active and 25% inactive. The AI main themes engaging stakeholders: awareness/education - 5 points (100%); competition, multi levels of involvement in SIH, community-based program/motivation - 4 points each (80%). The AI points represent themes’ repetition within stakeholders’ discussions. Results education interventions: 2 videos implementation, 35 000 educational materials, 3 online articles, 11 walking benefits lectures, 40 emails and sms notifications. Results community stakeholders’ interventions: 6 stakeholders meetings, 3 rewarding gatherings, 1 focus meeting, 40 individual reports, 18 overall reports. Results mass media campaign: 1 radio campaign, 7 press releases, 52 campuses newsletters. Results outcome evaluation: overall 2013-2016, the study used: 1 logic model, 3 PA holistic interventions, partnerships 15 universities, registered 4890 students and staff (aged 18-64 years), engaged 30 campuses stakeholders and 14 internal stakeholders; Total registered population: 61.5% female (2999), 38.5% male (1891), 20.2% (988) Qatari nationals, 79.8% (3902) non-Qataris, 55.5% (2710) students aged 18 – 25 years, 44.5% (2180) staff aged 26 - 64 years. Overall campaign 1,558 members eligible for analyzes: daily step count 7,923; 37% - low active, 43% physically active and 20% inactive. Conclusion: The study outcomes confirm program effectiveness and engagement of young campuses community, specifically female, in PA. The authors recommend implementations of 'holistic PA intervention program approach in Qatar' aiming to impact the community at national level for PA guidelines achievement in support of NCD prevention.

Keywords: campuses, evaluation, Qatar, step-count

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13 Characterization of Aluminosilicates and Verification of Their Impact on Quality of Ceramic Proppants Intended for Shale Gas Output

Authors: Joanna Szymanska, Paulina Wawulska-Marek, Jaroslaw Mizera

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Nowadays, the rapid growth of global energy consumption and uncontrolled depletion of natural resources become a serious problem. Shale rocks are the largest and potential global basins containing hydrocarbons, trapped in closed pores of the shale matrix. Regardless of the shales origin, mining conditions are extremely unfavourable due to high reservoir pressure, great depths, increased clay minerals content and limited permeability (nanoDarcy) of the rocks. Taking into consideration such geomechanical barriers, effective extraction of natural gas from shales with plastic zones demands effective operations. Actually, hydraulic fracturing is the most developed technique based on the injection of pressurized fluid into a wellbore, to initiate fractures propagation. However, a rapid drop of pressure after fluid suction to the ground induces a fracture closure and conductivity reduction. In order to minimize this risk, proppants should be applied. They are solid granules transported with hydraulic fluids to locate inside the rock. Proppants act as a prop for the closing fracture, thus gas migration to a borehole is effective. Quartz sands are commonly applied proppants only at shallow deposits (USA). Whereas, ceramic proppants are designed to meet rigorous downhole conditions to intensify output. Ceramic granules predominate with higher mechanical strength, stability in strong acidic environment, spherical shape and homogeneity as well. Quality of ceramic proppants is conditioned by raw materials selection. Aim of this study was to obtain the proppants from aluminosilicates (the kaolinite subgroup) and mix of minerals with a high alumina content. These loamy minerals contain a tubular and platy morphology that improves mechanical properties and reduces their specific weight. Moreover, they are distinguished by well-developed surface area, high porosity, fine particle size, superb dispersion and nontoxic properties - very crucial for particles consolidation into spherical and crush-resistant granules in mechanical granulation process. The aluminosilicates were mixed with water and natural organic binder to improve liquid-bridges and pores formation between particles. Afterward, the green proppants were subjected to sintering at high temperatures. Evaluation of the minerals utility was based on their particle size distribution (laser diffraction study) and thermal stability (thermogravimetry). Scanning Electron Microscopy was useful for morphology and shape identification combined with specific surface area measurement (BET). Chemical composition was verified by Energy Dispersive Spectroscopy and X-ray Fluorescence. Moreover, bulk density and specific weight were measured. Such comprehensive characterization of loamy materials confirmed their favourable impact on the proppants granulation. The sintered granules were analyzed by SEM to verify the surface topography and phase transitions after sintering. Pores distribution was identified by X-Ray Tomography. This method enabled also the simulation of proppants settlement in a fracture, while measurement of bulk density was essential to predict their amount to fill a well. Roundness coefficient was also evaluated, whereas impact on mining environment was identified by turbidity and solubility in acid - to indicate risk of the material decay in a well. The obtained outcomes confirmed a positive influence of the loamy minerals on ceramic proppants properties with respect to the strict norms. This research is perspective for higher quality proppants production with costs reduction.

Keywords: aluminosilicates, ceramic proppants, mechanical granulation, shale gas

Procedia PDF Downloads 163
12 Blue Economy and Marine Mining

Authors: Fani Sakellariadou

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The Blue Economy includes all marine-based and marine-related activities. They correspond to established, emerging as well as unborn ocean-based industries. Seabed mining is an emerging marine-based activity; its operations depend particularly on cutting-edge science and technology. The 21st century will face a crisis in resources as a consequence of the world’s population growth and the rising standard of living. The natural capital stored in the global ocean is decisive for it to provide a wide range of sustainable ecosystem services. Seabed mineral deposits were identified as having a high potential for critical elements and base metals. They have a crucial role in the fast evolution of green technologies. The major categories of marine mineral deposits are deep-sea deposits, including cobalt-rich ferromanganese crusts, polymetallic nodules, phosphorites, and deep-sea muds, as well as shallow-water deposits including marine placers. Seabed mining operations may take place within continental shelf areas of nation-states. In international waters, the International Seabed Authority (ISA) has entered into 15-year contracts for deep-seabed exploration with 21 contractors. These contracts are for polymetallic nodules (18 contracts), polymetallic sulfides (7 contracts), and cobalt-rich ferromanganese crusts (5 contracts). Exploration areas are located in the Clarion-Clipperton Zone, the Indian Ocean, the Mid Atlantic Ridge, the South Atlantic Ocean, and the Pacific Ocean. Potential environmental impacts of deep-sea mining include habitat alteration, sediment disturbance, plume discharge, toxic compounds release, light and noise generation, and air emissions. They could cause burial and smothering of benthic species, health problems for marine species, biodiversity loss, reduced photosynthetic mechanism, behavior change and masking acoustic communication for mammals and fish, heavy metals bioaccumulation up the food web, decrease of the content of dissolved oxygen, and climate change. An important concern related to deep-sea mining is our knowledge gap regarding deep-sea bio-communities. The ecological consequences that will be caused in the remote, unique, fragile, and little-understood deep-sea ecosystems and inhabitants are still largely unknown. The blue economy conceptualizes oceans as developing spaces supplying socio-economic benefits for current and future generations but also protecting, supporting, and restoring biodiversity and ecological productivity. In that sense, people should apply holistic management and make an assessment of marine mining impacts on ecosystem services, including the categories of provisioning, regulating, supporting, and cultural services. The variety in environmental parameters, the range in sea depth, the diversity in the characteristics of marine species, and the possible proximity to other existing maritime industries cause a span of marine mining impact the ability of ecosystems to support people and nature. In conclusion, the use of the untapped potential of the global ocean demands a liable and sustainable attitude. Moreover, there is a need to change our lifestyle and move beyond the philosophy of single-use. Living in a throw-away society based on a linear approach to resource consumption, humans are putting too much pressure on the natural environment. Applying modern, sustainable and eco-friendly approaches according to the principle of circular economy, a substantial amount of natural resource savings will be achieved. Acknowledgement: This work is part of the MAREE project, financially supported by the Division VI of IUPAC. This work has been partly supported by the University of Piraeus Research Center.

Keywords: blue economy, deep-sea mining, ecosystem services, environmental impacts

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11 Femicide: The Political and Social Blind Spot in the Legal and Welfare State of Germany

Authors: Kristina F. Wolff

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Background: In the Federal Republic of Germany, violence against women is deeply embedded in society. Germany is, as of March 2020, the most populous member state of the European Union with 83.2 million inhabitants and, although more than half of its inhabitants are women, gender equality was not certified in the Basic Law until 1957. Women have only been allowed to enter paid employment without their husband's consent since 1977 and have marital rape prosecuted only since 1997. While the lack of equality between men and women is named in the preamble of the Istanbul Convention as the cause of gender-specific, structural, traditional violence against women, Germany continues to sink on the latest Gender Equality Index. According to Police Crime Statistics (PCS), women are significantly more often victims of lethal violence, emanating from men than vice versa. The PCS, which, since 2015, also collects gender-specific data on violent crimes, is kept by the Federal Criminal Police Office, but without taking into account the relevant criteria for targeted prevention, such as the history of violence of the perpetrator/killer, weapon, motivation, etc.. Institutions such as EIGE or the World Health Organization have been asking Germany for years in vain for comparable data on violence against women in order to gain an overview or to develop cross-border synergies. The PCS are the only official data collection on violence against women. All players involved are depend on this data set, which is published only in November of the following year and is thus already completely outdated at the time of publication. In order to combat German femicides causally, purposefully and efficiently, evidence-based data was urgently needed. Methodology: Beginning in January 2019, a database was set up that now tracks more than 600 German femicides, broken down by more than 100 crime-related individual criteria, which in turn go far beyond the official PCS. These data are evaluated on the one hand by daily media research, and on the other hand by case-specific inquiries at the respective public prosecutor's offices and courts nationwide. This quantitative long-term study covers domestic violence as well as a variety of different types of gender-specific, lethal violence, including, for example, femicides committed by German citizens abroad. Additionallyalcohol/ narcotic and/or drug abuse, infanticides and the gender aspect in the judiciary are also considered. Results: Since November 2020, evidence-based data from a scientific survey have been available for the first time in Germany, supplementing the rudimentary picture of reality provided by PCS with a number of relevant parameters. The most important goal of the study is to identify "red flags" that enable general preventive awareness, that serve increasingly precise hazard assessment in acute hazard situations, and from which concrete instructions for action can be identified. Already at a very early stage of the study it could be proven that in more than half of all femicides with a sexual perpetrator/victim constellation there was an age difference of five years or more. Summary: Without reliable data and an understanding of the nature and extent, cause and effect, it is impossible to sustainably curb violence against girls and women, which increasingly often culminates in femicide. In Germany, valid data from a scientific survey has been available for the first time since November 2020, supplementing the rudimentary reality picture of the official and, to date, sole crime statistics with several relevant parameters. The basic research provides insights into geo-concentration, monthly peaks and the modus operandi of male violent excesses. A significant increase of child homicides in the course of femicides and/or child homicides as an instrument of violence against the mother could be proven as well as a danger of affected persons due to an age difference of five years and more. In view of the steadily increasing wave of violence against women, these study results are an eminent contribution to the preventive containment of German femicides.

Keywords: femicide, violence against women, gender specific data, rule Of law, Istanbul convention, gender equality, gender based violence

Procedia PDF Downloads 91
10 Revolutionizing Financial Forecasts: Enhancing Predictions with Graph Convolutional Networks (GCN) - Long Short-Term Memory (LSTM) Fusion

Authors: Ali Kazemi

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Those within the volatile and interconnected international economic markets, appropriately predicting market trends, hold substantial fees for traders and financial establishments. Traditional device mastering strategies have made full-size strides in forecasting marketplace movements; however, monetary data's complicated and networked nature calls for extra sophisticated processes. This observation offers a groundbreaking method for monetary marketplace prediction that leverages the synergistic capability of Graph Convolutional Networks (GCNs) and Long Short-Term Memory (LSTM) networks. Our suggested algorithm is meticulously designed to forecast the traits of inventory market indices and cryptocurrency costs, utilizing a comprehensive dataset spanning from January 1, 2015, to December 31, 2023. This era, marked by sizable volatility and transformation in financial markets, affords a solid basis for schooling and checking out our predictive version. Our algorithm integrates diverse facts to construct a dynamic economic graph that correctly reflects market intricacies. We meticulously collect opening, closing, and high and low costs daily for key inventory marketplace indices (e.g., S&P 500, NASDAQ) and widespread cryptocurrencies (e.g., Bitcoin, Ethereum), ensuring a holistic view of marketplace traits. Daily trading volumes are also incorporated to seize marketplace pastime and liquidity, providing critical insights into the market's shopping for and selling dynamics. Furthermore, recognizing the profound influence of the monetary surroundings on financial markets, we integrate critical macroeconomic signs with hobby fees, inflation rates, GDP increase, and unemployment costs into our model. Our GCN algorithm is adept at learning the relational patterns amongst specific financial devices represented as nodes in a comprehensive market graph. Edges in this graph encapsulate the relationships based totally on co-movement styles and sentiment correlations, enabling our version to grasp the complicated community of influences governing marketplace moves. Complementing this, our LSTM algorithm is trained on sequences of the spatial-temporal illustration discovered through the GCN, enriched with historic fee and extent records. This lets the LSTM seize and expect temporal marketplace developments accurately. Inside the complete assessment of our GCN-LSTM algorithm across the inventory marketplace and cryptocurrency datasets, the version confirmed advanced predictive accuracy and profitability compared to conventional and opportunity machine learning to know benchmarks. Specifically, the model performed a Mean Absolute Error (MAE) of 0.85%, indicating high precision in predicting day-by-day charge movements. The RMSE was recorded at 1.2%, underscoring the model's effectiveness in minimizing tremendous prediction mistakes, which is vital in volatile markets. Furthermore, when assessing the model's predictive performance on directional market movements, it achieved an accuracy rate of 78%, significantly outperforming the benchmark models, averaging an accuracy of 65%. This high degree of accuracy is instrumental for techniques that predict the course of price moves. This study showcases the efficacy of mixing graph-based totally and sequential deep learning knowledge in economic marketplace prediction and highlights the fee of a comprehensive, records-pushed evaluation framework. Our findings promise to revolutionize investment techniques and hazard management practices, offering investors and economic analysts a powerful device to navigate the complexities of cutting-edge economic markets.

Keywords: financial market prediction, graph convolutional networks (GCNs), long short-term memory (LSTM), cryptocurrency forecasting

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9 Light Sensitive Plasmonic Nanostructures for Photonic Applications

Authors: Istvan Csarnovics, Attila Bonyar, Miklos Veres, Laszlo Himics, Attila Csik, Judit Kaman, Julia Burunkova, Geza Szanto, Laszlo Balazs, Sandor Kokenyesi

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In this work, the performance of gold nanoparticles were investigated for stimulation of photosensitive materials for photonic applications. It was widely used for surface plasmon resonance experiments, not in the last place because of the manifestation of optical resonances in the visible spectral region. The localized surface plasmon resonance is rather easily observed in nanometer-sized metallic structures and widely used for measurements, sensing, in semiconductor devices and even in optical data storage. Firstly, gold nanoparticles on silica glass substrate satisfy the conditions for surface plasmon resonance in the green-red spectral range, where the chalcogenide glasses have the highest sensitivity. The gold nanostructures influence and enhance the optical, structural and volume changes and promote the exciton generation in gold nanoparticles/chalcogenide layer structure. The experimental results support the importance of localized electric fields in the photo-induced transformation of chalcogenide glasses as well as suggest new approaches to improve the performance of these optical recording media. Results may be utilized for direct, micrometre- or submicron size geometrical and optical pattern formation and used also for further development of the explanations of these effects in chalcogenide glasses. Besides of that, gold nanoparticles could be added to the organic light-sensitive material. The acrylate-based materials are frequently used for optical, holographic recording of optoelectronic elements due to photo-stimulated structural transformations. The holographic recording process and photo-polymerization effect could be enhanced by the localized plasmon field of the created gold nanostructures. Finally, gold nanoparticles widely used for electrochemical and optical sensor applications. Although these NPs can be synthesized in several ways, perhaps one of the simplest methods is the thermal annealing of pre-deposited thin films on glass or silicon surfaces. With this method, the parameters of the annealing process (time, temperature) and the pre-deposited thin film thickness influence and define the resulting size and distribution of the NPs on the surface. Localized surface plasmon resonance (LSPR) is a very sensitive optical phenomenon and can be utilized for a large variety of sensing purposes (chemical sensors, gas sensors, biosensors, etc.). Surface-enhanced Raman spectroscopy (SERS) is an analytical method which can significantly increase the yield of Raman scattering of target molecules adsorbed on the surface of metallic nanoparticles. The sensitivity of LSPR and SERS based devices is strongly depending on the used material and also on the size and geometry of the metallic nanoparticles. By controlling these parameters the plasmon absorption band can be tuned and the sensitivity can be optimized. The technological parameters of the generated gold nanoparticles were investigated and influence on the SERS and on the LSPR sensitivity was established. The LSPR sensitivity were simulated for gold nanocubes and nanospheres with MNPBEM Matlab toolbox. It was found that the enhancement factor (which characterize the increase in the peak shift for multi-particle arrangements compared to single-particle models) depends on the size of the nanoparticles and on the distance between the particles. This work was supported by GINOP- 2.3.2-15-2016-00041 project, which is co-financed by the European Union and European Social Fund. Istvan Csarnovics is grateful for the support through the New National Excellence Program of the Ministry of Human Capacities, supported by the ÚNKP-17-4 Attila Bonyár and Miklós Veres are grateful for the support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Keywords: light sensitive nanocomposites, metallic nanoparticles, photonic application, plasmonic nanostructures

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8 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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7 A Comprehensive Study of Spread Models of Wildland Fires

Authors: Manavjit Singh Dhindsa, Ursula Das, Kshirasagar Naik, Marzia Zaman, Richard Purcell, Srinivas Sampalli, Abdul Mutakabbir, Chung-Horng Lung, Thambirajah Ravichandran

Abstract:

These days, wildland fires, also known as forest fires, are more prevalent than ever. Wildfires have major repercussions that affect ecosystems, communities, and the environment in several ways. Wildfires lead to habitat destruction and biodiversity loss, affecting ecosystems and causing soil erosion. They also contribute to poor air quality by releasing smoke and pollutants that pose health risks, especially for individuals with respiratory conditions. Wildfires can damage infrastructure, disrupt communities, and cause economic losses. The economic impact of firefighting efforts, combined with their direct effects on forestry and agriculture, causes significant financial difficulties for the areas impacted. This research explores different forest fire spread models and presents a comprehensive review of various techniques and methodologies used in the field. A forest fire spread model is a computational or mathematical representation that is used to simulate and predict the behavior of a forest fire. By applying scientific concepts and data from empirical studies, these models attempt to capture the intricate dynamics of how a fire spreads, taking into consideration a variety of factors like weather patterns, topography, fuel types, and environmental conditions. These models assist authorities in understanding and forecasting the potential trajectory and intensity of a wildfire. Emphasizing the need for a comprehensive understanding of wildfire dynamics, this research explores the approaches, assumptions, and findings derived from various models. By using a comparison approach, a critical analysis is provided by identifying patterns, strengths, and weaknesses among these models. The purpose of the survey is to further wildfire research and management techniques. Decision-makers, researchers, and practitioners can benefit from the useful insights that are provided by synthesizing established information. Fire spread models provide insights into potential fire behavior, facilitating authorities to make informed decisions about evacuation activities, allocating resources for fire-fighting efforts, and planning for preventive actions. Wildfire spread models are also useful in post-wildfire mitigation strategies as they help in assessing the fire's severity, determining high-risk regions for post-fire dangers, and forecasting soil erosion trends. The analysis highlights the importance of customized modeling approaches for various circumstances and promotes our understanding of the way forest fires spread. Some of the known models in this field are Rothermel’s wildland fuel model, FARSITE, WRF-SFIRE, FIRETEC, FlamMap, FSPro, cellular automata model, and others. The key characteristics that these models consider include weather (includes factors such as wind speed and direction), topography (includes factors like landscape elevation), and fuel availability (includes factors like types of vegetation) among other factors. The models discussed are physics-based, data-driven, or hybrid models, also utilizing ML techniques like attention-based neural networks to enhance the performance of the model. In order to lessen the destructive effects of forest fires, this initiative aims to promote the development of more precise prediction tools and effective management techniques. The survey expands its scope to address the practical needs of numerous stakeholders. Access to enhanced early warning systems enables decision-makers to take prompt action. Emergency responders benefit from improved resource allocation strategies, strengthening the efficacy of firefighting efforts.

Keywords: artificial intelligence, deep learning, forest fire management, fire risk assessment, fire simulation, machine learning, remote sensing, wildfire modeling

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6 Surface Acoustic Wave (SAW)-Induced Mixing Enhances Biomolecules Kinetics in a Novel Phase-Interrogation Surface Plasmon Resonance (SPR) Microfluidic Biosensor

Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini

Abstract:

Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.

Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance

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5 Improvement in the Photocatalytic Activity of Nanostructured Manganese Ferrite – Type of Materials by Mechanochemical Activation

Authors: Katerina Zaharieva, Katya Milenova, Zara Cherkezova-Zheleva, Alexander Eliyas, Boris Kunev, Ivan Mitov

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The synthesized nanosized manganese ferrite-type of samples have been tested as photocatalysts in the reaction of oxidative degradation of model contaminant Reactive Black 5 (RB5) dye in aqueous solutions under UV irradiation. As it is known this azo dye is applied in the textile-coloring industry and it is discharged into the waterways causing pollution. The co-precipitation procedure has been used for the synthesis of manganese ferrite-type of materials: Sample 1 - Mn0.25Fe2.75O4, Sample 2 - Mn0.5Fe2.5O4 and Sample 3 - MnFe2O4 from 0.03M aqueous solutions of MnCl2•4H2O, FeCl2•4H2O and/or FeCl3•6H2O and 0.3M NaOH in appropriate amounts. The mechanochemical activation of co-precipitated ferrite-type of samples has been performed in argon (Samples 1 and 2) or in air atmosphere (Sample 3) for 2 hours at a milling speed of 500 rpm. The mechano-chemical treatment has been carried out in a high energy planetary ball mill type PM 100, Retsch, Germany. The mass ratio between balls and powder was 30:1. As a result mechanochemically activated Sample 4 - Mn0.25Fe2.75O4, Sample 5 - Mn0.5Fe2.5O4 and Sample 6 - MnFe2O4 have been obtained. The synthesized manganese ferrite-type photocatalysts have been characterized by X-ray diffraction method and Moessbauer spectroscopy. The registered X-ray diffraction patterns and Moessbauer spectra of co-precipitated ferrite-type of materials show the presence of manganese ferrite and additional akaganeite phase. The presence of manganese ferrite and small amounts of iron phases is established in the mechanochemically treated samples. The calculated average crystallite size of manganese ferrites varies within the range 7 – 13 nm. This result is confirmed by Moessbauer study. The registered spectra show superparamagnetic behavior of the prepared materials at room temperature. The photocatalytic investigations have been made using polychromatic UV-A light lamp (Sylvania BLB, 18 W) illumination with wavelength maximum at 365 nm. The intensity of light irradiation upon the manganese ferrite-type photocatalysts was 0.66 mW.cm-2. The photocatalytic reaction of oxidative degradation of RB5 dye was carried out in a semi-batch slurry photocatalytic reactor with 0.15 g of ferrite-type powder, 150 ml of 20 ppm dye aqueous solution under magnetic stirring at rate 400 rpm and continuously feeding air flow. The samples achieved adsorption-desorption equilibrium in the dark period for 30 min and then the UV-light was turned on. After regular time intervals aliquot parts from the suspension were taken out and centrifuged to separate the powder from solution. The residual concentrations of dye were established by a UV-Vis absorbance single beam spectrophotometer CamSpec M501 (UK) measuring in the wavelength region from 190 to 800 nm. The photocatalytic measurements determined that the apparent pseudo-first-order rate constants calculated by linear slopes approximating to first order kinetic equation, increase in following order: Sample 3 (1.1х10-3 min-1) < Sample 1 (2.2х10-3 min-1) < Sample 2 (3.3 х10-3 min-1) < Sample 4 (3.8х10-3 min-1) < Sample 6 (11х10-3 min-1) < Sample 5 (15.2х10-3 min-1). The mechanochemically activated manganese ferrite-type of photocatalyst samples show significantly higher degree of oxidative degradation of RB5 dye after 120 minutes of UV light illumination in comparison with co-precipitated ferrite-type samples: Sample 5 (92%) > Sample 6 (91%) > Sample 4 (63%) > Sample 2 (53%) > Sample 1 (42%) > Sample 3 (15%). Summarizing the obtained results we conclude that the mechanochemical activation leads to a significant enhancement of the degree of oxidative degradation of the RB5 dye and photocatalytic activity of tested manganese ferrite-type of catalyst samples under our experimental conditions. The mechanochemically activated Mn0.5Fe2.5O4 ferrite-type of material displays the highest photocatalytic activity (15.2х10-3 min-1) and degree of oxidative degradation of the RB5 dye (92%) compared to the other synthesized samples. Especially a significant improvement in the degree of oxidative degradation of RB5 dye (91%) has been determined for mechanochemically treated MnFe2O4 ferrite-type of sample with the highest extent of substitution of iron ions by manganese ions than in the case of the co-precipitated MnFe2O4 sample (15%). The mechanochemically activated manganese ferrite-type of samples show good photocatalytic properties in the reaction of oxidative degradation of RB5 azo dye in aqueous solutions and it could find potential application for dye removal from wastewaters originating from textile industry.

Keywords: nanostructured manganese ferrite-type materials, photocatalytic activity, Reactive Black 5, water treatment

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4 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

Abstract:

The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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3 Reducing the Risk of Alcohol Relapse after Liver-Transplantation

Authors: Rebeca V. Tholen, Elaine Bundy

Abstract:

Background: Liver transplantation (LT) is considered the only curative treatment for end-stage liver disease Background: Liver transplantation (LT) is considered the only curative treatment for end-stage liver disease (ESLD). The effects of alcoholism can cause irreversible liver damage, cirrhosis and subsequent liver failure. Alcohol relapse after transplant occurs in 20-50% of patients and increases the risk for recurrent cirrhosis, organ rejection, and graft failure. Alcohol relapse after transplant has been identified as a problem among liver transplant recipients at a large urban academic transplant center in the United States. Transplantation will reverse the complications of ESLD, but it does not treat underlying alcoholism or reduce the risk of relapse after transplant. The purpose of this quality improvement project is to implement and evaluate the effectiveness of a High-Risk Alcoholism Relapse (HRAR) Scale to screen and identify patients at high-risk for alcohol relapse after receiving an LT. Methods: The HRAR Scale is a predictive tool designed to determine the severity of alcoholism and risk of relapse after transplant. The scale consists of three variables identified as having the highest predictive power for early relapse including, daily number of drinks, history of previous inpatient treatment for alcoholism, and the number of years of heavy drinking. All adult liver transplant recipients at a large urban transplant center were screened with the HRAR Scale prior to hospital discharge. A zero to two ordinal score is ranked for each variable, and the total score ranges from zero to six. High-risk scores are between three to six. Results: Descriptive statistics revealed 25 patients were newly transplanted and discharged from the hospital during an 8-week period. 40% of patients (n=10) were identified as being high-risk for relapse and 60% low-risk (n=15). The daily number of drinks were determined by alcohol content (1 drink = 15g of ethanol) and number of drinks per day. 60% of patients reported drinking 9-17 drinks per day, and 40% reported ≤ 9 drinks. 50% of high-risk patients reported drinking ≥ 25 years, 40% for 11-25 years, and 10% ≤ 11 years. For number of inpatient treatments for alcoholism, 50% received inpatient treatment one time, 20% ≥ 1, and 30% reported never receiving inpatient treatment. Findings reveal the importance and value of a validated screening tool as a more efficient method than other screening methods alone. Integration of a structured clinical tool will help guide the drinking history portion of the psychosocial assessment. Targeted interventions can be implemented for all high-risk patients. Conclusions: Our findings validate the effectiveness of utilizing the HRAR scale to screen and identify patients who are a high-risk for alcohol relapse post-LT. Recommendations to help maintain post-transplant sobriety include starting a transplant support group within the organization for all high-risk patients. (ESLD). The effects of alcoholism can cause irreversible liver damage, cirrhosis and subsequent liver failure. Alcohol relapse after transplant occurs in 20-50% of patients, and increases the risk for recurrent cirrhosis, organ rejection, and graft failure. Alcohol relapse after transplant has been identified as a problem among liver transplant recipients at a large urban academic transplant center in the United States. Transplantation will reverse the complications of ESLD, but it does not treat underlying alcoholism or reduce the risk of relapse after transplant. The purpose of this quality improvement project is to implement and evaluate the effectiveness of a High-Risk Alcoholism Relapse (HRAR) Scale to screen and identify patients at high-risk for alcohol relapse after receiving a LT. Methods: The HRAR Scale is a predictive tool designed to determine severity of alcoholism and risk of relapse after transplant. The scale consists of three variables identified as having the highest predictive power for early relapse including, daily number of drinks, history of previous inpatient treatment for alcoholism, and the number of years of heavy drinking. All adult liver transplant recipients at a large urban transplant center were screened with the HRAR Scale prior to hospital discharge. A zero to two ordinal score is ranked for each variable, and the total score ranges from zero to six. High-risk scores are between three to six. Results: Descriptive statistics revealed 25 patients were newly transplanted and discharged from the hospital during an 8-week period. 40% of patients (n=10) were identified as being high-risk for relapse and 60% low-risk (n=15). The daily number of drinks were determined by alcohol content (1 drink = 15g of ethanol) and number of drinks per day. 60% of patients reported drinking 9-17 drinks per day, and 40% reported ≤ 9 drinks. 50% of high-risk patients reported drinking ≥ 25 years, 40% for 11-25 years, and 10% ≤ 11 years. For number of inpatient treatments for alcoholism, 50% received inpatient treatment one time, 20% ≥ 1, and 30% reported never receiving inpatient treatment. Findings reveal the importance and value of a validated screening tool as a more efficient method than other screening methods alone. Integration of a structured clinical tool will help guide the drinking history portion of the psychosocial assessment. Targeted interventions can be implemented for all high-risk patients. Conclusions: Our findings validate the effectiveness of utilizing the HRAR scale to screen and identify patients who are a high-risk for alcohol relapse post-LT. Recommendations to help maintain post-transplant sobriety include starting a transplant support group within the organization for all high-risk patients.

Keywords: alcoholism, liver transplant, quality improvement, substance abuse

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2 The Impact of the Macro-Level: Organizational Communication in Undergraduate Medical Education

Authors: Julie M. Novak, Simone K. Brennan, Lacey Brim

Abstract:

Undergraduate medical education (UME) curriculum notably addresses micro-level communications (e.g., patient-provider, intercultural, inter-professional), yet frequently under-examines the role and impact of organizational communication, a more macro-level. Organizational communication, however, functions as foundation and through systemic structures of an organization and thereby serves as hidden curriculum and influences learning experiences and outcomes. Yet, little available research exists fully examining how students experience organizational communication while in medical school. Extant literature and best practices provide insufficient guidance for UME programs, in particular. The purpose of this study was to map and examine current organizational communication systems and processes in a UME program. Employing a phenomenology-grounded and participatory approach, this study sought to understand the organizational communication system from medical students' perspective. The research team consisted of a core team and 13 medical student co-investigators. This research employed multiple methods, including focus groups, individual interviews, and two surveys (one reflective of focus group questions, the other requesting students to submit ‘examples’ of communications). To provide context for student responses, nonstudent participants (faculty, administrators, and staff) were sampled, as they too express concerns about communication. Over 400 students across all cohorts and 17 nonstudents participated. Data were iteratively analyzed and checked for triangulation. Findings reveal the complex nature of organizational communication and student-oriented communications. They reveal program-impactful strengths, weaknesses, gaps, and tensions and speak to the role of organizational communication practices influencing both climate and culture. With regard to communications, students receive multiple, simultaneous communications from multiple sources/channels, both formal (e.g., official email) and informal (e.g., social media). Students identified organizational strengths including the desire to improve student voice, and message frequency. They also identified weaknesses related to over-reliance on emails, numerous platforms with inconsistent utilization, incorrect information, insufficient transparency, assessment/input fatigue, tacit expectations, scheduling/deadlines, responsiveness, and mental health confidentiality concerns. Moreover, they noted gaps related to lack of coordination/organization, ambiguous point-persons, student ‘voice-only’, open communication loops, lack of core centralization and consistency, and mental health bridges. Findings also revealed organizational identity and cultural characteristics as impactful on the medical school experience. Cultural characteristics included program size, diversity, urban setting, student organizations, community-engagement, crisis framing, learning for exams, inefficient bureaucracy, and professionalism. Moreover, they identified system structures that do not always leverage cultural strengths or reduce cultural problematics. Based on the results, opportunities for productive change are identified. These include leadership visibly supporting and enacting overall organizational narratives, making greater efforts in consistently ‘closing the loop’, regularly sharing how student input effects change, employing strategies of crisis communication more often, strengthening communication infrastructure, ensuring structures facilitate effective operations and change efforts, and highlighting change efforts in informational communication. Organizational communication and communications are not soft-skills, or of secondary concern within organizations, rather they are foundational in nature and serve to educate/inform all stakeholders. As primary stakeholders, students and their success directly affect the accomplishment of organizational goals. This study demonstrates how inquiries about how students navigate their educational experience extends research-based knowledge and provides actionable knowledge for the improvement of organizational operations in UME.

Keywords: medical education programs, organizational communication, participatory research, qualitative mixed methods

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1 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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