Search results for: human auditory system model

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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Authors: Almas Rajguru

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The Oligocene succession of the Tapti- Daman area is one of the established petroleum plays in Tapti-Daman block of the Mumbai Offshore Basin. Despite good control and production history, the sand geometry and continuity of reservoir character of these sediments are less understood as most reservoirs are thin and fall below seismic resolution. The present work focuses on a detailed analysis of the Early Oligocene Mahuva Formation at the reservoir scale through laboratory studies (sedimentology and biostratigraphy) of core and sidewall cores in integration with electro logs for firming up facies’ distribution, micro-depositional environment and sequence stratigraphy, diagenesis and reservoir characterization from seventeen wells from North Tapti-C-37 area in Tapti Daman Block, WOB. The thick shale/claystone with thin interbeds of sandstone and siltstones of deeper marine in the lower part of Mahuva Fm represents deposition in a transgressive regime. The overlying interbedded sandstone, glauconitic-siltstone/fine-grained sandstone, and thin beds of packstone/grainstone within highly fissile shale were deposited in a prograding tide-dominated delta during late-rise normal regression. Nine litho facies (F1-F9) representing deposition in various microenvironments of the tide-dominated delta are identified based on their characteristic sediment texture, structure and microfacies. Massive, gritty sandstone (F1) with poorly sorted sands lithic fragments with calcareous and Fe-rich matrix represents channel fill sediments. High-angle cross-stratified sandstone (F2) deposited in rapidly shifting/migrating bars under strong tidal currents. F3 records the laterally accreted tidal-channel point bars. F3 (low-angle cross-stratified to parallel bedded sandstone) and F4 (Clean sandstone) are often associated with F2 in a tidal bar complex. F5 (interbedded thin sand and mud) and F6 (bioturbated sandstone) represent tidal flat deposits. High energy open marine carbonate shoals (F8) and fossiliferous sandstone in offshore bars (F7) represent deepening up facies. Shallow marine standstill conditions facilitated the deposition of thick shale (F9) beds. The reservoir facies (F1-F6) are commonly poorly to moderately sorted; bimodal, immature sandstone represented by quartz-wacke. The framework grains are sub-angular to sub-rounded, medium to coarse-grained (occasionally gritty) embedded within argillaceous (kaolinite/chlorite/chamosite) to highly Fe-rich matrix (sideritic). The facies F7 and F8, representing the sandy packstone and grainstone facies, respectively, exhibit poor reservoir characteristics due to sanitization, diagenetic compaction and matrix-filled intergranular spaces. The various diagenetic features such as the presence of authigenic clays (kaolinite/dickite/smectite); ferruginous minerals like siderite, pyrite, hematite and other iron oxides; bioturbations; glauconite; calcite and quartz cementation, precipitation of gypsum, pressure solution and other compaction effects are identified. These diagenetic features, wherever present, have reduced porosity and permeability thereby adversely affecting reservoir quality. Tidal bar sandstones possess good reservoir characteristics such as moderate to good sorting, fair to good porosity and geometry that facilitates efficient lateral extension and vertical thickness of reservoir. The sand bodies of F2, F3 and F4 facies of Well L, M and Q deposited in a tidal bar complex exhibit good reservoir quality represented by relatively cleaner, poorly burrowed, loose, friable sandstone with good porosity. Sandstone facies around these wells could prove a potential hydrocarbon reservoir and could be considered for further exploration.

Keywords: reservoir sedimentology, facies analysis, HST, tide dominated delta, tidal bars

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Authors: Mariza Kaskara, Stella Girtsou, Maria Prodromou, Alexia Tsouni, Christodoulos Mettas, Stavroula Alatza, Kyriaki Fotiou, Marios Tzouvaras, Charalampos Kontoes, Diofantos Hadjimitsis

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Natural hazard assessment and monitoring are crucial in managing the risks associated with fires, floods, and geohazards, particularly in regions prone to these natural disasters, such as Greece and Cyprus. Recent advancements in technology, developed by the BEYOND Center of Excellence of the National Observatory of Athens, have been successfully applied in Greece and are now set to be transferred to Cyprus. The implementation of these advanced technologies in Greece has significantly improved the country's ability to respond to these natural hazards. For wildfire risk assessment, a scalar wildfire occurrence risk index is created based on the predictions of machine learning models. Predicting fire danger is crucial for the sustainable management of forest fires as it provides essential information for designing effective prevention measures and facilitating response planning for potential fire incidents. A reliable forecast of fire danger is a key component of integrated forest fire management and is heavily influenced by various factors that affect fire ignition and spread. The fire risk model is validated by the sensitivity and specificity metric. For flood risk assessment, a multi-faceted approach is employed, including the application of remote sensing techniques, the collection and processing of data from the most recent population and building census, technical studies and field visits, as well as hydrological and hydraulic simulations. All input data are used to create precise flood hazard maps according to various flooding scenarios, detailed flood vulnerability and flood exposure maps, which will finally produce the flood risk map. Critical points are identified, and mitigation measures are proposed for the worst-case scenario, namely, refuge areas are defined, and escape routes are designed. Flood risk maps can assist in raising awareness and save lives. Validation is carried out through historical flood events using remote sensing data and records from the civil protection authorities. For geohazards monitoring (e.g., landslides, subsidence), Synthetic Aperture Radar (SAR) and optical satellite imagery are combined with geomorphological and meteorological data and other landslide/ground deformation contributing factors. To monitor critical infrastructures, including dams, advanced InSAR methodologies are used for identifying surface movements through time. Monitoring these hazards provides valuable information for understanding processes and could lead to early warning systems to protect people and infrastructure. Validation is carried out through both geotechnical expert evaluations and visual inspections. The success of these systems in Greece has paved the way for their transfer to Cyprus to enhance Cyprus's capabilities in natural hazard assessment and monitoring. This transfer is being made through capacity building activities, fostering continuous collaboration between Greek and Cypriot experts. Apart from the knowledge transfer, small demonstration actions are implemented to showcase the effectiveness of these technologies in real-world scenarios. In conclusion, the transfer of advanced natural hazard assessment technologies from Greece to Cyprus represents a significant step forward in enhancing the region's resilience to disasters. EXCELSIOR project funds knowledge exchange, demonstration actions and capacity-building activities and is committed to empower Cyprus with the tools and expertise to effectively manage and mitigate the risks associated with these natural hazards. Acknowledgement:Authors acknowledge the 'EXCELSIOR': ERATOSTHENES: Excellence Research Centre for Earth Surveillance and Space-Based Monitoring of the Environment H2020 Widespread Teaming project.

Keywords: earth observation, monitoring, natural hazards, remote sensing

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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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Authors: C.Ardil

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Open Science translates the understanding and application of various theories and practices in open science philosophy, systems, paradigms and epistemology. Open Science originates with the premise that universal scientific knowledge is a product of a collective scholarly and social collaboration involving all stakeholders and knowledge belongs to the global society. Scientific outputs generated by public research are a public good that should be available to all at no cost and without barriers or restrictions. Open Science has the potential to increase the quality, impact and benefits of science and to accelerate advancement of knowledge by making it more reliable, more efficient and accurate, better understandable by society and responsive to societal challenges, and has the potential to enable growth and innovation through reuse of scientific results by all stakeholders at all levels of society, and ultimately contribute to growth and competitiveness of global society. Open Science is a global movement to improve accessibility to and reusability of research practices and outputs. In its broadest definition, it encompasses open access to publications, open research data and methods, open source, open educational resources, open evaluation, and citizen science. The implementation of open science provides an excellent opportunity to renegotiate the social roles and responsibilities of publicly funded research and to rethink the science system as a whole. Open Science is the practice of science in such a way that others can collaborate and contribute, where research data, lab notes and other research processes are freely available, under terms that enable reuse, redistribution and reproduction of the research and its underlying data and methods. Open Science represents a novel systematic approach to the scientific process, shifting from the standard practices of publishing research results in scientific publications towards sharing and using all available knowledge at an earlier stage in the research process, based on cooperative work and diffusing scholarly knowledge with no barriers and restrictions. Open Science refers to efforts to make the primary outputs of publicly funded research results (publications and the research data) publicly accessible in digital format with no limitations. Open Science is about extending the principles of openness to the whole research cycle, fostering, sharing and collaboration as early as possible, thus entailing a systemic change to the way science and research is done. Open Science is the ongoing transition in how open research is carried out, disseminated, deployed, and transformed to make scholarly research more open, global, collaborative, creative and closer to society. Open Science involves various movements aiming to remove the barriers for sharing any kind of output, resources, methods or tools, at any stage of the research process. Open Science embraces open access to publications, research data, source software, collaboration, peer review, notebooks, educational resources, monographs, citizen science, or research crowdfunding. The recognition and adoption of open science practices, including open science policies that increase open access to scientific literature and encourage data and code sharing, is increasing in the open science philosophy. Revolutionary open science policies are motivated by ethical, moral or utilitarian arguments, such as the right to access digital research literature for open source research or science data accumulation, research indicators, transparency in the field of academic practice, and reproducibility. Open science philosophy is adopted primarily to demonstrate the benefits of open science practices. Researchers use open science applications for their own advantage in order to get more offers, increase citations, attract media attention, potential collaborators, career opportunities, donations and funding opportunities. In open science philosophy, open data findings are evidence that open science practices provide significant benefits to researchers in scientific research creation, collaboration, communication, and evaluation according to more traditional closed science practices. Open science considers concerns such as the rigor of peer review, common research facts such as financing and career development, and the sacrifice of author rights. Therefore, researchers are recommended to implement open science research within the framework of existing academic evaluation and incentives. As a result, open science research issues are addressed in the areas of publishing, financing, collaboration, resource management and sharing, career development, discussion of open science questions and conclusions.

Keywords: Open Science, Open Science Philosophy, Open Science Research, Open Science Data

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Authors: Chiu-Yin Leung

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This research investigates a complex assemblage among indigenous identities, socio-political organization and national apparatus in the border landscape of post-colonial Hong Kong. This former British colony had designated a transient mode of governance in its New Territories and particularly the northernmost borderland in 1951-2012. With a discriminated system of land provisions for the indigenous villagers, the place has been inherited with distinctive village-based culture, historic monuments and agrarian practices until its sovereignty return into the People’s Republic of China. In its latest development imperatives by the national strategic planning, the frontier area of Hong Kong has been identified as a strategy site for regional economic integration in South China, with cross-border projects of innovation and technology zones, mega-transport infrastructure and inter-jurisdictional arrangement. Contemporary literature theorizes borders as the material and discursive production of territoriality, which manifest in state apparatus and the daily lives of its citizens and condense in the contested articulations of power, security and citizenship. Drawing on the concept of assemblage, this paper attempts to tract how the border regime and infrastructure in Hong Kong as a city are deeply ingrained in the everyday lived spaces of the local communities but also the changing urban and regional strategies across different longitudinal moments. Through an intensive ethnographic fieldwork among the borderland villages since 2008 and the extensive analysis of colonial archives, new development plans and spatial planning frameworks, the author navigates the genealogy of the border landscape in Ta Kwu Ling frontier area and its implications as the milieu for new state space, covering heterogeneous fields particularly in indigenous rights, heritage preservation, rural sustainability and regional economy. Empirical evidence suggests an apparent bias towards indigenous power and colonial representation in classifying landscape values and conserving historical monuments. Squatter and farm tenants are often deprived of property rights, statutory participation and livelihood option in the planning process. The postcolonial bureaucracies have great difficulties in mobilizing resources to catch up with the swift, political-first approach of the mainland counterparts. Meanwhile, the cultural heritage, lineage network and memory landscape are not protected altogether with any holistic view or collaborative effort across the border. The enactment of land resumption and compensation scheme is furthermore disturbed by lineage-based customary law, technocratic bureaucracy, intra-community conflicts and multi-scalar political mobilization. As many traces of colonial misfortune and tyranny have been whitewashed without proper management, the author argues that postcolonial justice is yet reconciled in this fragmented border landscape. The assemblage of border in mainstream representation has tended to oversimplify local struggles as a collective mist and setup a wider production of schizophrenia experiences in the discussion of further economic integration among Hong Kong and other mainland cities in the Pearl River Delta Region. The research is expected to shed new light on the theorizing of border regions and postcolonialism beyond Eurocentric perspectives. In reassembling the borderland experiences with other arrays in state governance, village organization and indigenous identities, the author also suggests an alternative epistemology in reconciling socio-spatial differences and opening up imaginaries for positive interventions.

Keywords: heritage conservation, indigenous communities, post-colonial borderland, regional development, rural sustainability

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Authors: Murat Arıbaş, Uğur Özcan

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Due to the increasing number of universities and academics, the fund of the universities for research activities and grants/supports given by government institutions have increased number and quality of academic research projects. Although every academic research project has a specific purpose and importance, limited resources (money, time, manpower etc.) require choosing the best ones from all (Amiri, 2010). It is a pretty hard process to compare and determine which project is better such that the projects serve different purposes. In addition, the evaluation process has become complicated since there are more than one evaluator and multiple criteria for the evaluation (Dodangeh, Mojahed and Yusuff, 2009). Mehrez and Sinuany-Stern (1983) determined project selection problem as a Multi Criteria Decision Making (MCDM) problem. If a decision problem involves multiple criteria and objectives, it is called as a Multi Attribute Decision Making problem (Ömürbek & Kınay, 2013). There are many MCDM methods in the literature for the solution of such problems. These methods are AHP (Analytic Hierarchy Process), ANP (Analytic Network Process), TOPSIS (Technique for Order Preference by Similarity to Ideal Solution), PROMETHEE (Preference Ranking Organization Method for Enrichment Evaluation), UTADIS (Utilities Additives Discriminantes), ELECTRE (Elimination et Choix Traduisant la Realite), MAUT (Multiattribute Utility Theory), GRA (Grey Relational Analysis) etc. Teach method has some advantages compared with others (Ömürbek, Blacksmith & Akalın, 2013). Hence, to decide which MCDM method will be used for solution of the problem, factors like the nature of the problem, types of choices, measurement scales, type of uncertainty, dependency among the attributes, expectations of decision maker, and quantity and quality of the data should be considered (Tavana & Hatami-Marbini, 2011). By this study, it is aimed to develop a systematic decision process for the grant support applications that are expected to be evaluated according to their scientific adequacy by multiple evaluators under certain criteria. In this context, project evaluation process applied by The Scientific and Technological Research Council of Turkey (TÜBİTAK) the leading institutions in our country, was investigated. Firstly in the study, criteria that will be used on the project evaluation were decided. The main criteria were selected among TÜBİTAK evaluation criteria. These criteria were originality of project, methodology, project management/team and research opportunities and extensive impact of project. Moreover, for each main criteria, 2-4 sub criteria were defined, hence it was decided to evaluate projects over 13 sub-criterion in total. Due to superiority of determination criteria weights AHP method and provided opportunity ranking great number of alternatives TOPSIS method, they are used together. AHP method, developed by Saaty (1977), is based on selection by pairwise comparisons. Because of its simple structure and being easy to understand, AHP is the very popular method in the literature for determining criteria weights in MCDM problems. Besides, the TOPSIS method developed by Hwang and Yoon (1981) as a MCDM technique is an alternative to ELECTRE method and it is used in many areas. In the method, distance from each decision point to ideal and to negative ideal solution point was calculated by using Euclidian Distance Approach. In the study, main criteria and sub-criteria were compared on their own merits by using questionnaires that were developed based on an importance scale by four relative groups of people (i.e. TUBITAK specialists, TUBITAK managers, academics and individuals from business world ) After these pairwise comparisons, weight of the each main criteria and sub-criteria were calculated by using AHP method. Then these calculated criteria’ weights used as an input in TOPSİS method, a sample consisting 200 projects were ranked on their own merits. This new system supported to opportunity to get views of the people that take part of project process including preparation, evaluation and implementation on the evaluation of academic research projects. Moreover, instead of using four main criteria in equal weight to evaluate projects, by using weighted 13 sub-criteria and decision point’s distance from the ideal solution, systematic decision making process was developed. By this evaluation process, new approach was created to determine importance of academic research projects.

Keywords: Academic projects, Ahp method, Research projects evaluation, Topsis method.

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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

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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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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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