Search results for: seismically designed buildings

Authors: Anne E. Goodenough

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One of the most important roles of higher education professionals is to ensure that graduates have excellent employment prospects. This means providing students with the skills necessary to be immediately effective in the workplace. Increasingly, universities are seeking to achieve this by moving from lecture-based and campus-delivered curricula to more varied delivery, which takes students out of their academic comfort zone and allows them to engage with, and be challenged by, real world issues. One popular approach is integration of problem-based learning (PBL) projects into curricula. However, although the potential benefits of PBL are considerable, it can be difficult to devise projects that are meaningful, such that they can be regarded as mere ‘hoop jumping’ exercises. This study examines three-way partnerships between academics, students, and external link organizations. It studied the experiences of all partners involved in different collaborative projects to identify how benefits can be maximized and challenges overcome. Focal collaborations included: (1) development of real-world modules with novel assessment whereby the organization became the ‘client’ for student consultancy work; (2) frameworks where students collected/analyzed data for link organizations in research methods modules; (3) placement-based internships and dissertations; (4) immersive fieldwork projects in novel locations; and (5) students working as partners on staff-led research with link organizations. Focus groups, questionnaires and semi-structured interviews were used to identify opportunities and barriers, while quantitative analysis of students’ grades was used to determine academic effectiveness. Common challenges identified by academics were finding suitable link organizations and devising projects that simultaneously provided education opportunities and tangible benefits. There was no ‘one size fits all’ formula for success, but careful planning and ensuring clarity of roles/responsibilities were vital. Students were very positive about collaboration projects. They identified benefits to confidence, time-keeping and communication, as well as conveying their enthusiasm when their work was of benefit to the wider community. They frequently highlighted employability opportunities that collaborative projects opened up and analysis of grades demonstrated the potential for such projects to increase attainment. Organizations generally recognized the value of project outputs, but often required considerable assistance to put the right scaffolding in place to ensure projects worked. Benefits were maximized by ensuring projects were well-designed, innovative, and challenging. Co-publication of projects in peer-reviewed journals sometimes gave additional benefits for all involved, being especially beneficial for student curriculum vitae. PBL and student projects are by no means new pedagogic approaches: the novelty here came from creating meaningful three-way partnerships between academics, students, and link organizations at all undergraduate levels. Such collaborations can allow students to make a genuine contribution to knowledge, answer real questions, solve actual problems, all while providing tangible benefits to organizations. Because projects are actually needed, students tend to engage with learning at a deep level. This enhances student experience, increases attainment, encourages development of subject-specific and transferable skills, and promotes networking opportunities. Such projects frequently rely upon students and staff working collaboratively, thereby also acting to break down the traditional teacher/learner division that is typically unhelpful in developing students as advanced learners.

Keywords: higher education, employability, link organizations, innovative teaching and learning methods, interactions between enterprise and education, student experience

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Authors: Hilary Modir, Kyle Dutton, Michelle Swab, Shabnam Asghari

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Since its emergence, the cutaneous manifestations of COVID-19 have been documented in the literature. However, the majority are case reports with significant limitations in appraisal quality, thus leaving the role of dermatological manifestations of COVID-19 erroneously underexplored. The primary aim of this review was to systematically examine clinical patterns of dermatological manifestations as reported in the literature. This study was designed as a systematic review of case reports. The inclusion criteria consisted of all published reports and articles regarding COVID-19 in English, from September 1st, 2019, until June 22nd, 2020. The population consisted of confirmed cases of COVID-19 with associated cutaneous signs and symptoms. Exclusion criteria included research in planning stages, protocols, book reviews, news articles, review studies, and policy analyses. With the collaboration of a librarian, a search strategy was created consisting of a mixture of keyword terms and controlled vocabulary. Electronic databases searched were MEDLINE via PubMed, EMBASE, CINAHL, Web of Science, LILACS, PsycINFO, WHO Global Literature on Coronavirus Disease, Cochrane Library, Campbell Collaboration, Prospero, WHO International Clinical Trials Registry Platform, Australian and New Zealand Clinical Trials Registry, U.S. Institutes of Health Ongoing Trials Register, AAD Registry, OSF preprints, SSRN, MedRxiV and BioRxiV. The study selection featured an initial pre-screening of titles and abstracts by one independent reviewer. Results were verified by re-examining a random sample of 1% of excluded articles. Eligible studies progressed for full-text review by two calibrated independent reviewers. Covidence was used to store and extract data, such as citation information and findings pertaining to COVID-19 and cutaneous signs and symptoms. Data analysis and summarization methodology reflect the framework proposed by PRISMA and recommendations set out by Cochrane and Joanna Brigg’s Institute for conducting systematic reviews. The Oxford Centre for Evidence-Based Medicine’s level of evidence was used to appraise the quality of individual studies. The literature search revealed a total of 1221 articles. After the abstract and full-text screening, only 95 studies met the eligibility criteria, proceeding to data extraction. Studies were divided into 58% case reports and 42% series. A total of 833 manifestations were reported in 723 confirmed COVID-19 cases. The most frequent lesions were 23% maculopapular, 15% urticarial and 13% pseudo-chilblains, with 46% of lesions reporting pruritus, 16% erythema, 14% pain, 12% burning sensation, and 4% edema. The most common lesion locations were 20% trunk, 19.5% lower limbs, and 17.7% upper limbs. The time to resolution of lesions was between one and twenty-one days. In conclusion, over half of the reported cutaneous presentations in COVID-19 positive patients were maculopapular, urticarial and pseudo-chilblains, with the majority of lesions distributed to the extremities and trunk. As this review’s sample size only contained COVID-19 confirmed cases with skin presentations, it becomes difficult to deduce the direct relationship between skin findings and COVID-19. However, it can be correlated that acute onset of skin lesions, such as chilblains-like, may be associated with or may warrant consideration of COVID-19 as part of the differential diagnosis.

Keywords: COVID-19, cutaneous manifestations, cutaneous signs, general dermatology, medical dermatology, Sars-Cov-2, skin and infectious disease, skin findings, skin manifestations

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Authors: Michael Radwan Omary

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Context: This scientific innovation demonstrate organic catalysis engineered media effective desalination of surface and groundwater. The author has developed a technology called “Storm-Water Ions Filtration Treatment” (SWIFTTM) cold reactor modules designed to retrofit typical urban street storm drains or catch basins. SWIFT triggers biochemical redox reactions with water stream-embedded toxic total dissolved solids (TDS) and electrical conductivity (EC). SWIFTTM Catalysts media unlock the sub-molecular bond energy, break down toxic chemical bonds, and neutralize toxic molecules, bacteria and pathogens. Research Aim: This research aims to develop and design lower O&M cost, zero-brine discharge, energy input-free, chemical-free water desalination and disinfection systems. The objective is to provide an effective resilient and sustainable solution to urban storm-water and groundwater decontamination and disinfection. Methodology: We focused on the development of organic, non-chemical, no-plugs, no pumping, non-polymer and non-allergenic approaches for water and waste water desalination and disinfection. SWIFT modules operate by directing the water stream to flow freely through the electrically charged media cold reactor, generating weak interactions with a water-dissolved electrically conductive molecule, resulting in the neutralization of toxic molecules. The system is powered by harvesting sub-molecular bonds embedded in energy. Findings: The SWIFTTM Technology case studies at CSU-CI and CSU-Fresno Water Institute, demonstrated consistently high reduction of all 40 detected waste-water pollutants including pathogens to levels below a state of California Department of Water Resources “Drinking Water Maximum Contaminants Levels”. The technology has proved effective in reducing pollutants such as arsenic, beryllium, mercury, selenium, glyphosate, benzene, and E. coli bacteria. The technology has also been successfully applied to the decontamination of dissolved chemicals, water pathogens, organic compounds and radiological agents. Theoretical Importance: SWIFT technology development, design, engineering, and manufacturing, offer cutting-edge advancement in achieving clean-energy source bio-catalysis media solution, an energy input free water and waste water desalination and disinfection. A significant contribution to institutions and municipalities achieving sustainable, lower cost, zero-brine and zero CO2 discharges clean energy water desalination. Data Collection and Analysis Procedures: The researchers collected data on the performance of the SWIFTTM technology in reducing the levels of various pollutants in water. The data was analyzed by comparing the reduction achieved by the SWIFTTM technology to the Drinking Water Maximum Contaminants Levels set by the state of California. The researchers also conducted live oral presentations to showcase the applications of SWIFTTM technology in storm water capture and decontamination as well as providing clean drinking water during emergencies. Conclusion: The SWIFTTM Technology has demonstrated its capability to effectively reduce pollutants in water and waste water to levels below regulatory standards. The Technology offers a sustainable solution to groundwater and storm-water treatments. Further development and implementation of the SWIFTTM Technology have the potential to treat storm water to be reused as a new source of drinking water and an ambient source of clean and healthy local water for recharge of ground water.

Keywords: catalysis, bio electro interactions, water desalination, weak-interactions

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Authors: Robert E. Kenney, Efrain Antunez, Samuel Nodal, Ameer Malik, Richard B. Aguilar

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Physician burnout has gained much attention during the COVID pandemic. After-hours workload, HCC coding, HEDIS metrics, and clinical documentation negatively impact career satisfaction. These and other influences have increased the rate of physicians leaving the workforce. In addition, roughly 1% of the entire physician workforce will be retiring earlier than expected based on pre-pandemic trends. The two Medical Specialties with the highest rates of burnout are Family Medicine and Primary Care. With a predicted shortage of primary care physicians looming, the need to address physician burnout is crucial. Commonly reported issues leading to clinician burnout are clerical documentation requirements, increased time working on Electronic Health Records (EHR) after hours, and a decrease in work-life balance. Clinicians experiencing burnout with physical and emotional exhaustion are at an increased likelihood of providing lower quality and less efficient patient care. This may include a lack of suitable clinical documentation, medication reconciliation, clinical assessment, and treatment plans. While the annual baseline turnover rates of physicians hover around 6-7%, the COVID pandemic profoundly disrupted the delivery of healthcare. A report found that 43% of physicians switched jobs during the initial two years of the COVID pandemic (2020 and 2021), tripling the expected average annual rate to 21.5 %/yr. During this same time, an average of 4% and 1.5% of physicians retired or left the workforce for a non-clinical career, respectively. The report notes that 35.2% made career changes for a better work-life balance and another 35% reported the reason as being unhappy with their administration’s response to the pandemic. A physician-led primary care-focused health organization, Cano Health (CH), based out of Florida, sought to preemptively address this problem by implementing several supportive measures. Working with >120 clinics and >280 PCPs from Miami to Tampa and Orlando, managing nearly 120,000 Medicare Advantage lives, CH implemented a number of changes to assist with the clinician’s workload. Supportive services such as after hour and home visits by APRNs, in-clinic care managers, and patient educators were implemented. In 2021, assistive Artificial Intelligence Software (AIS) was integrated into the EHR platform. This AIS converts free text within PDF files into a usable (copy-paste) format facilitating documentation. The software also systematically and chronologically organizes clinical data, including labs, medical records, consultations, diagnostic images, medications, etc., into an easy-to-use organ system or chronic disease state format. This reduced the excess time and documentation burden required to meet payor and CMS guidelines. A clinician Documentation Support team was employed to improve the billing/coding performance. The effects of these newly designed workflow interventions were measured via analysis of clinician turnover from CH’s hiring and termination reporting software. CH’s annualized average clinician turnover rate in 2020 and 2021 were 17.7% and 12.6%, respectively. This represents a 30% relative reduction in turnover rate compared to the reported national average of 21.5%. Retirement rates during both years were 0.1%, demonstrating a relative reduction of >95% compared to the national average (4%). This model successfully promoted the retention of clinicians in a Value-Based Care setting.

Keywords: clinician burnout, COVID-19, value-based care, burnout, clinician retirement

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Authors: Zdravko Trivic, John Chye Fung, Ruzica Bozovic-Stamenovic

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Within the context of rapidly ageing population in Singapore and the pressing demands on both caregivers and care providers, an integrated approach to ageing-friendly and ability-sensitive enabling environment becomes an imperative. This particularly applies to nursing home environments and their immediate surroundings, as they are becoming one of the main available options of long-term care for many senior adults who are unable to age at home. Yet, despite the considerable efforts to break the still predominant clinical approach to eldercare and to introduce more home-like design and person-centric care model, nursing homes keep being stigmatised and perceived as not so desirable environments to grow old in. The challenges are further emphasised by the associated physical, sensorial, psychological and cognitive declines that are the common consequences of ageing. Such declines have an immense impact on almost all aspects of older adults’ daily functioning, including problems with mobility and spatial orientation, difficulties in communication, withdrawal from social interaction, higher level of depression and decreased sense of independence and autonomy. However, typical nursing home designs tend to neglect the full capacities of balanced and carefully integrated multisensory stimuli as active component of care and ability building. This paper outlines part of a larger multi-disciplinary study of six nursing homes in Singapore, with overarching objectives to create new models of supportive nursing home environments that go beyond the clinical care model and encourage community integration with the nursing home settings. The paper focuses on the largely neglected aspects of sensorial comfort and multi-sensorial properties of nursing homes, including both indoor and immediate outdoor spaces (boundaries). The objective was to investigate the sensory rhythms and explore their role in nursing home users’ daily routine and therapeutic capacities. Socio-sensory rhythms were captured and analysed through a combination of on-site sensory recordings of “objective” quantitative sensory data (air temperature and humidity, sound level and luminance) using multi-function environment meter, perceived experienced data, spatial mapping, first-person observations of nursing home users’ activity patterns, and interviews. This was done in addition to employment of available assessment tools, such as Wisconsin Person Directed Care assessment tool, Dementia Quality of Life [DQoL] instrument, and Resident Environment Impact Scale [REIS], as these tools address the issues of sensorial experience insufficiently and selectively. Key findings indicate varied levels of sensory comfort, as well as diversity, intensity, and customisation of multi-sensory conditions within different nursing home spaces. Sensory stimulation is typically concentrated in communal living areas of the nursing homes or in the areas that often provide controlled or limited access, including specifically designed sensory rooms and outdoor green spaces (gardens and terraces). Opportunities for sensory stimulation are particularly limited for bed-bound senior residents and within more functional areas, such as corridors. This suggests that the capacities of nursing home designs to provide more diverse and better integrated pleasant sensory conditions as integrated “therapeutic devices” to build nursing home residents’ physical and mental abilities, encourage activity and improve wellbeing are far from exhausted.

Keywords: ageing-supportive environment, enabling design, multi-sensory assessment, nursing home environment

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Authors: Sofia Horjales, Florencia Palma

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Our society is currently experiencing a profound transformation, demanding a proactive response from governmental bodies and higher education institutions to empower the next generation as catalysts for change. Environmental sustainability is rooted in the critical need to maintain the equilibrium and integrity of natural ecosystems, ensuring the preservation of precious natural resources and biodiversity for the benefit of both present and future generations. It is an essential cornerstone of sustainable development, complementing social and economic sustainability. In this evolving landscape, active methodologies take a central role, aligning perfectly with the principles of the 2030 Agenda for Sustainable Development and emerging as a pivotal element of teacher education. The emphasis on active learning methods has been driven by the urgent need to nurture sustainability and instill social responsibility in our future leaders. The Universidad Tecnológica of Uruguay (UTEC) is a public, technologically-oriented institution established in 2012. UTEC is dedicated to decentralization, expanding access to higher education throughout Uruguay, and promoting inclusive social development. Operating through Regional Technological Institutes (ITRs) and associated centers spread across the country, UTEC faces the challenge of remote student populations. To address this, UTEC utilizes e-learning for equal opportunities, self-regulated learning, and digital skills development, enhancing communication among students, teachers, and peers through virtual classrooms. The Interdisciplinary Continuing Education Program is part of the Innovation and Entrepreneurship Department of UTEC. The main goal is to strengthen innovation skills through a transversal and multidisciplinary approach. Within this Program, we have developed a Case of Study and Project-Based Learning Virtual Course designed for university students and open to the broader UTEC community. The primary aim of this course is to establish a strong foundation for comprehending and addressing environmental sustainability issues from an interdisciplinary perspective. Upon completing the course, we expect students not only to understand the intricate interactions between social and ecosystem environments but also to utilize their knowledge and innovation skills to develop projects that offer enhancements or solutions to real-world challenges. Our course design centers on innovative learning experiences, rooted in active methodologies. We explore the intersection of these methods with sustainability and social responsibility in the education of university students. A paramount focus lies in gathering student feedback, empowering them to autonomously generate ideas with guidance from instructors, and even defining their own project topics. This approach underscores that when students are genuinely engaged in subjects of their choice, they not only acquire the necessary knowledge and skills but also develop essential attributes like effective communication, critical thinking, and problem-solving abilities. These qualities will benefit them throughout their lifelong learning journey. We are convinced that education serves as the conduit to merge knowledge and cultivate interdisciplinary collaboration, igniting awareness and instigating action for environmental sustainability. While systemic changes are undoubtedly essential for society and the economy, we are making significant progress by shaping perspectives and sparking small, everyday actions within the UTEC community. This approach empowers our students to become engaged global citizens, actively contributing to the creation of a more sustainable future.

Keywords: active learning, environmental education, project-based learning, soft skills development

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Authors: Zbigniew Czyz, Ksenia Siadkowska, Krzysztof Skiba, Karol Scislowski

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Today’s progress in the rotorcraft is mostly associated with an optimization of aircraft performance achieved by active and passive modifications of main rotor assemblies and a tail propeller. The key task is to improve their performance, improve the hover quality factor for rotors but not change in specific fuel consumption. One of the tasks to improve the helicopter is an active optimization of the main rotor providing for flight stages, i.e., an ascend, flight, a descend. An active interference with the airflow around the rotor blade section can significantly change characteristics of the aerodynamic airfoil. The efficiency of actuator systems modifying aerodynamic coefficients in the current solutions is relatively high and significantly affects the increase in strength. The solution to actively change aerodynamic characteristics assumes a periodic change of geometric features of blades depending on flight stages. Changing geometric parameters of blade warping enables an optimization of main rotor performance depending on helicopter flight stages. Structurally, an adaptation of shape memory alloys does not significantly affect rotor blade fatigue strength, which contributes to reduce costs associated with an adaptation of the system to the existing blades, and gains from a better performance can easily amortize such a modification and improve profitability of such a structure. In order to obtain quantitative and qualitative data to solve this research problem, a number of numerical analyses have been necessary. The main problem is a selection of design parameters of the main rotor and a preliminary optimization of its performance to improve the hover quality factor for rotors. This design concept assumes a three-bladed main rotor with a chord of 0.07 m and radius R = 1 m. The value of rotor speed is a calculated parameter of an optimization function. To specify the initial distribution of geometric warping, a special software has been created that uses a numerical method of a blade element which respects dynamic design features such as fluctuations of a blade in its joints. A number of performance analyses as a function of rotor speed, forward speed, and altitude have been performed. The calculations were carried out for the full model assembly. This approach makes it possible to observe the behavior of components and their mutual interaction resulting from the forces. The key element of each rotor is the shaft, hub and pins holding the joints and blade yokes. These components are exposed to the highest loads. As a result of the analysis, the safety factor was determined at the level of k > 1.5, which gives grounds to obtain certification for the strength of the structure. The construction of the joint rotor has numerous moving elements in its structure. Despite the high safety factor, the places with the highest stresses, where the signs of wear and tear may appear, have been indicated. The numerical analysis carried out showed that the most loaded element is the pin connecting the modular bearing of the blade yoke with the element of the horizontal oscillation joint. The stresses in this element result in a safety factor of k=1.7. The other analysed rotor components have a safety factor of more than 2 and in the case of the shaft, this factor is more than 3. However, it must be remembered that the structure is as strong as the weakest cell is. Designed rotor for unmanned aerial vehicles adapted to work with blades with intelligent materials in its structure meets the requirements for certification testing. Acknowledgement: This work has been financed by the Polish National Centre for Research and Development under the LIDER program, Grant Agreement No. LIDER/45/0177/L-9/17/NCBR/2018.

Keywords: main rotor, rotorcraft aerodynamics, shape memory alloy, materials, unmanned helicopter

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Authors: Savvas Rogotis, Nikolaos Kalatzis, Stergios Dimou-Sakellariou, Nikolaos Marianos

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As precision holds the key for the introduction of distinct benefits in agriculture (e.g., energy savings, reduced labor costs, optimal application of inputs, improved products, and yields), it steadily becomes evident that new initiatives should focus on rendering Precision Agriculture (PA) more accessible to the average farmer. PA leverages on technologies such as the Internet of Things (IoT), earth observation, robotics and positioning systems (e.g., the Global Navigation Satellite System – GNSS - as well as individual positioning systems like GPS, Glonass, Galileo) that allow: from simple data georeferencing to optimal navigation of agricultural machinery to even more complex tasks like Variable Rate Applications. An identified customer pain point is that, from one hand, typical triangulation-based positioning systems are not accurate enough (with errors up to several meters), while on the other hand, high precision positioning systems reaching centimeter-level accuracy, are very costly (up to thousands of euros). Within this paper, a Ground-Based Augmentation System (GBAS) is introduced, that can be adapted to any existing IoT field-sensing station infrastructure. The latter should cover a minimum set of requirements, and in particular, each station should operate as a fixed, obstruction-free towards the sky, energy supplying unit. Station augmentation will allow them to function in pairs with GNSS rovers following the differential GNSS base-rover paradigm. This constitutes a key innovation element for the proposed solution that encompasses differential GNSS capabilities into an IoT field-sensing infrastructure. Integrating this kind of information supports the provision of several additional PA beneficial services such as spatial mapping, route planning, and automatic field navigation of unmanned vehicles (UVs). Right at the heart of the designed system, there is a high-end GNSS toolkit with base-rover variants and Real-Time Kinematic (RTK) capabilities. The GNSS toolkit had to tackle all availability, performance, interfacing, and energy-related challenges that are faced for a real-time, low-power, and reliable in the field operation. Specifically, in terms of performance, preliminary findings exhibit a high rover positioning precision that can even reach less than 10-centimeters. As this precision is propagated to the full dataset collection, it enables tractors, UVs, Android-powered devices, and measuring units to deal with challenging real-world scenarios. The system is validated with the help of Gaiatrons, a mature network of agro-climatic telemetry stations with presence all over Greece and beyond ( > 60.000ha of agricultural land covered) that constitutes part of “gaiasense” (www.gaiasense.gr) smart farming (SF) solution. Gaiatrons constantly monitor atmospheric and soil parameters, thus, providing exact fit to operational requirements asked from modern SF infrastructures. Gaiatrons are ultra-low-cost, compact, and energy-autonomous stations with a modular design that enables the integration of advanced GNSS base station capabilities on top of them. A set of demanding pilot demonstrations has been initiated in Stimagka, Greece, an area with a diverse geomorphological landscape where grape cultivation is particularly popular. Pilot demonstrations are in the course of validating the preliminary system findings in its intended environment, tackle all technical challenges, and effectively highlight the added-value offered by the system in action.

Keywords: GNSS, GBAS, precision agriculture, RTK, smart farming

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Authors: Gulce Kanturer Yasar, Hayriye Esbah Tuncay

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Cultivated food production systems have coexisted harmoniously with nature for thousands of years through ancient techniques. Based on this experience, experimentation, and discovery, these culturally embedded methods have evolved to sustain food production, restore ecosystems, and harmoniously adapt to nature. In this era, as we seek solutions to food security challenges, enhancing and repairing our food production systems is crucial, making them more resilient to future disasters without harming the ecosystem. Instead of unsustainable conventional systems with ongoing destructive effects, we must investigate innovative and restorative production systems that integrate ancient wisdom and technology. Whether we consider agricultural fields, pastures, forests, coastal wetland ecosystems, or lagoons, it is crucial to harness the potential of these natural resources in addressing future global challenges, fostering both socio-economic resilience and ecological sustainability through strategic organization for food production. When thoughtfully designed and managed, marine-based food production has the potential to function as a living infrastructure system that addresses social and environmental challenges despite its known adverse impacts on the environment and local economies. These areas are also stages of daily life, vibrant hubs where local culture is produced and shared, contributing to the distinctive rural character of coastal settlements and exhibiting numerous spatial expressions of public nature. When we consider the history of humanity, indigenous communities have engaged in these sustainable production practices that provide goods for food, trade, culture, and the environment for many ages. Ecosystem restoration and socio-economic resilience can be achieved by combining production techniques based on ecological knowledge developed by indigenous societies with modern technologies. Coastal lagoons are highly productive coastal features that provide various natural services and societal values. They are especially vulnerable to severe physical, ecological, and social impacts of changing, challenging global conditions because of their placement within the coastal landscape. Coastal lagoons are crucial in sustaining fisheries productivity, providing storm protection, supporting tourism, and offering other natural services that hold significant value for society. Although there is considerable literature on the physical and ecological dimensions of lagoons, much less literature focuses on their economic and social values. This study will discuss the possibilities of coastal lagoons to achieve both ecologically sustainable and socio-economically resilient while maintaining their productivity by combining local techniques and modern technologies. The case study will present Turkey’s traditional aquaculture method, "Dalyans," predominantly operated by small-scale farmers in coastal lagoons. Due to human, ecological, and economic factors, dalyans are losing their landscape characteristics and efficiency. These 1000-year-old ancient techniques, rooted in centuries of traditional and agroecological knowledge, are under threat of tourism, urbanization, and unsustainable agricultural practices. Thus, Dalyans have diminished from 29 to approximately 4-5 active Dalyans. To deal with the adverse socio-economic and ecological consequences on Turkey's coastal areas, conserving Dalyans by protecting their indigenous practices while incorporating contemporary methods is essential. This study seeks to generate scenarios that envision the potential ways protection and development can manifest within case study areas.

Keywords: coastal foodscape, lagoon aquaculture, regenerative food systems, watershed food networks

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Authors: Shari S. C. Shang, Lynn S. L. Chiu

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In the digital payment market, some consumers use only one payment wallet while many others play multi-homing with a variety of payment services. With the diffusion of new payment systems, we examined the determinants of the adoption of multi-homing behavior. This study aims to understand how a digital payment provider dynamically expands business touch points with cross-business strategies to enrich the digital ecosystem and avoid the trap of multi-homing in customers. By synthesizing platform ecosystem literature, we constructed a two-dimensional research framework with one determinant of user digital behavior from offline to online intentions and the other determinant of digital payment touch points from convenient accessibility to cross-business platforms. To explore on a broader scale, we selected 12 digital payments from 5 countries of UK, US, Japan, Korea, and Taiwan. With the interplays of user digital behaviors and payment touch points, we group the study cases into four types: (1) Channel Initiated: users originated from retailers with high access to in-store shopping with face-to-face guidance for payment adoption. Providers offer rewards for customer loyalty and secure the retailer’s efficient cash flow management. (2) Social Media Dependent: users usually are digital natives with high access to social media or the internet who shop and pay digitally. Providers might not own physical or online shops but are licensed to aggregate money flows through virtual ecosystems. (3) Early Life Engagement: digital banks race to capture the next generation from popularity to profitability. This type of payment aimed to give children a taste of financial freedom while letting parents track their spending. Providers are to capitalize on the digital payment and e-commerce boom and hold on to new customers into adulthood. (4) Traditional Banking: plastic credit cards are purposely designed as a control group to track the evolvement of business strategies in digital payments. Traditional credit card users may follow the bank’s digital strategy to land on different types of digital wallets or mostly keep using plastic credit cards. This research analyzed business growth models and inter-firms’ coopetition strategies of the selected cases. Results of the multiple case analysis reveal that channel initiated payments bundled rewards with retailer’s business discount for recurring purchases. They also extended other financial services, such as insurance, to fulfill customers’ new demands. Contrastively, social media dependent payments developed new usages and new value creation, such as P2P money transfer through network effects among the virtual social ties, while early life engagements offer virtual banking products to children who are digital natives but overlooked by incumbents. It has disrupted the banking business domains in preparation for the metaverse economy. Lastly, the control group of traditional plastic credit cards has gradually converted to a BaaS (banking as a service) model depending on customers’ preferences. The multi-homing behavior is not avoidable in digital payment competitions. Payment providers may encounter multiple waves of a multi-homing threat after a short period of success. A dynamic cross-business collaboration strategy should be explored to continuously evolve the digital ecosystems and allow users for a broader shopping experience and continual usage.

Keywords: digital payment, digital ecosystems, multihoming users, cross business strategy, user digital behavior intentions

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Authors: Ghidey Ghebreyohanes, Eltahir Awad Gasim Khalil, Zemenfes Tsighe, Faiza Ali

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Background: reproductive health (RH) is a state of physical, mental and social well-being in all matters relating to the reproductive system at all stages of life. In East Africa including Eritrea, adolescents comprise more than a quarter of the population. The region holds the highest rates of sexually transmitted diseases, HIV, unwanted pregnancy and unsafe abortion with its complications. Young girls carry the highest burden of reproductive health problems due to their risk taking behavior, lack of knowledge, peer pressure, physiologic immaturity and low socioeconomic status. Design: this was a Community-based, randomized, case-controlled and pre-test-post-test intervention study. Setting: Zoba Debub was randomly selected out of the six zobas in Eritrea. The four high schools out of the 26 in Zoba Debub were randomly selected as study target schools. Over three quarter of the people live on farming. The target population was female students attending grade nine with majority of these girls live in the distant villages and walk to school. The study participants were randomly selected (n=165) from each school. Furthermore, the 1 intervention and 3 controls for the study arms were assigned randomly. Objectives: this study aimed to assess the effectiveness of peer reproductive health education in improving knowledge, attitude, and health service use of high school adolescent girls in Eritrea Methods: the protocol was reviewed and approved by the Scientific and Ethics Committees of Faculty of Nursing Sciences, University of Khartoum. Data was collected using pre-designed and pretested questionnaire emphasizing on reproductive health knowledge, attitude and practice. Sample size was calculated using proportion formula (α 0.01; power of 95%). Measures used were scores and proportions. Descriptive and inferential statistics, t-test and chi square at (α .01), 99% confidence interval were used to compare changes of pre and post-intervention scores using SPSS soft ware. Seventeen students were selected for peer educators by the school principals and other teachers based on inclusion criteria that include: good academic performance and acceptable behavior. One peer educator educated one group composed of 8-10 students for two months. One faculty member was selected to supervise peer educators. The principal investigator conducted the training of trainers and provided supervision and discussion to peer educators every two weeks until the end of intervention. Results: following informed consent, 627 students [164 in intervention and 463 in the control group] with a ratio of 1 to 3, were enrolled in the study. The mean age for the total study population was 15.4±1.0 years. The intervention group mean age was 15.3±1.0 year; while the control group had a mean age of 15.4±1.0. The mean ages for the study arms were similar (p= 0.4). The majority (96 %) of the study participants are from Tigrigna ethnic group. Reproductive knowledge scores which was calculated out of a total 61 grade points: intervention group (pretest 6.7 %, post-test 33.6 %; p= 0.0001); control group (pretest 7.3 %, posttest 7.3 %, p= 0.92). Proportion difference in attitude calculated out of 100%: intervention group (pretest 42.3 % post test 54.7% p= 0.001); controls group (pretest 45%, post test 44.8 p= 0.7). Proportion difference in Practice calculated out of 100 %: intervention group (pretest 15.4%, post test 80.4 % p= 0.0001); control group (pretest 16.8%, posttest 16.9 % p= 0.8). Mothers were quoted as major (> 90 %) source of reproductive health information. All focus group discussants and most of survey participants agreed on the urgent need of reproductive health information and services for adolescent girls. Conclusion: reproductive health knowledge and use of facilities is poor among adolescent girls in sub-urban Eretria. School-based peer reproductive health education is effective and is the best strategy to improve reproductive health knowledge and attitudes.

Keywords: reproductive health, adolescent girls, eretria, health education

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Authors: Sireetorn Kuharat, Anwar Beg

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Motivation- Solar energy constitutes the most promising renewable energy source on earth. Nanofluids are a very successful family of engineered fluids, which contain well-dispersed nanoparticles suspended in a stable base fluid. The presence of metallic nanoparticles (e.g. gold, silver, copper, aluminum etc) significantly improves the thermo-physical properties of the host fluid and generally results in a considerable boost in thermal conductivity, density, and viscosity of nanofluid compared with the original base (host) fluid. This modification in fundamental thermal properties has profound implications in influencing the convective heat transfer process in solar collectors. The potential for improving solar collector direct absorber efficiency is immense and to gain a deeper insight into the impact of different metallic nanoparticles on efficiency and temperature enhancement, in the present work, we describe recent computational fluid dynamics simulations of an annular solar collector system. The present work studies several different metallic nano-particles and compares their performance. Methodologies- A numerical study of convective heat transfer in an annular pipe solar collector system is conducted. The inner tube contains pure water and the annular region contains nanofluid. Three-dimensional steady-state incompressible laminar flow comprising water- (and other) based nanofluid containing a variety of metallic nanoparticles (copper oxide, aluminum oxide, and titanium oxide nanoparticles) is examined. The Tiwari-Das model is deployed for which thermal conductivity, specific heat capacity and viscosity of the nanofluid suspensions is evaluated as a function of solid nano-particle volume fraction. Radiative heat transfer is also incorporated using the ANSYS solar flux and Rosseland radiative models. The ANSYS FLUENT finite volume code (version 18.1) is employed to simulate the thermo-fluid characteristics via the SIMPLE algorithm. Mesh-independence tests are conducted. Validation of the simulations is also performed with a computational Harlow-Welch MAC (Marker and Cell) finite difference method and excellent correlation achieved. The influence of volume fraction on temperature, velocity, pressure contours is computed and visualized. Main findings- The best overall performance is achieved with copper oxide nanoparticles. Thermal enhancement is generally maximized when water is utilized as the base fluid, although in certain cases ethylene glycol also performs very efficiently. Increasing nanoparticle solid volume fraction elevates temperatures although the effects are less prominent in aluminum and titanium oxide nanofluids. Significant improvement in temperature distributions is achieved with copper oxide nanofluid and this is attributed to the superior thermal conductivity of copper compared to other metallic nano-particles studied. Important fluid dynamic characteristics are also visualized including circulation and temperature shoots near the upper region of the annulus. Radiative flux is observed to enhance temperatures significantly via energization of the nanofluid although again the best elevation in performance is attained consistently with copper oxide. Conclusions-The current study generalizes previous investigations by considering multiple metallic nano-particles and furthermore provides a good benchmark against which to calibrate experimental tests on a new solar collector configuration currently being designed at Salford University. Important insights into the thermal conductivity and viscosity with metallic nano-particles is also provided in detail. The analysis is also extendable to other metallic nano-particles including gold and zinc.

Keywords: heat transfer, annular nanofluid solar collector, ANSYS FLUENT, metallic nanoparticles

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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

Procedia PDF Downloads 118

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 132

Authors: Nazym Zhumabayeva, Aleksandr Mezin, Alexandra Knysheva

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Women's underrepresentation in STEM is critical, worsened by ineffective engagement in educational practices. UNICEF Kazakhstan and GameLab KBTU's collaborative initiatives aim to enhance female STEM participation by fostering an inclusive environment. Learning from LEVEL UP's 2023 program, which featured a hackathon, the 2024 strategy pivots towards non-competitive gamification. Although the data from last year's project showed higher than average student engagement, observations and in-depth interviews with participants showed that the format was stressful for the girls, making them focus on points rather than on other values. This study presents a gamified educational system, DPG Lab, aimed at incentivizing young women's participation in STEM through the development of digital public goods (DPGs). By prioritizing collaborative gamification elements, the project seeks to create an inclusive learning environment that increases engagement and interest in STEM among young women. The DPG Lab aims to find a solution to minimize competition and support collaboration. The project is designed to motivate female participants towards the development of digital solutions through an introduction to the concept of DPGs. It consists of a short online course, a simulation videogame, and a real-time online quest with an offline finale at the KBTU campus. The online course offers short video lectures on open-source development and DPG standards. The game facilitates the practical application of theoretical knowledge, enriching the learning experience. Learners can also participate in a quest that encourages participants to develop DPG ideas in teams by choosing missions throughout the quest path. At the offline quest finale, the participants will meet in person to exchange experiences and accomplishments without engaging in comparative assessments: the quest ensures that each team’s trajectory is distinct by design. This marks a shift from competitive hackathons to a collaborative format, recognizing the unique contributions and achievements of each participant. The pilot batch of students is scheduled to commence in April 2024, with the finale anticipated in June. It is projected that this group will comprise 50 female high-school students from various regions across Kazakhstan. Expected outcomes include increased engagement and interest in STEM fields among young female participants, positive emotional and psychological impact through an emphasis on collaborative learning environments, and improved understanding and skills in DPG development. GameLab KBTU intends to undertake a hypothesis evaluation, employing a methodology similar to that utilized in the preceding LEVEL UP project. This approach will encompass the compilation of quantitative metrics (conversion funnels, test results, and surveys) and qualitative data from in-depth interviews and observational studies. For comparative analysis, a select group of participants from the previous year's project will be recruited to engage in the DPG Lab. By developing and implementing a gamified framework that emphasizes inclusion, engagement, and collaboration, the study seeks to provide practical knowledge about effective gamification strategies for promoting gender diversity in STEM. The expected outcomes of this initiative can contribute to the broader discussion on gamification in education and gender equality in STEM by offering a replicable and scalable model for similar interventions around the world.

Keywords: collaborative learning, competitive learning, digital public goods, educational gamification, emerging regions, STEM, underprivileged groups

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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 139

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: Fatima Saeed, Abdullah Mudassar

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Introduction: Patient safety remains a global priority in the ever-evolving healthcare landscape. At the forefront of this endeavor are the International Patient Safety Goals (IPSGs), a standardized framework designed to mitigate risks and elevate the quality of care. Doctors, positioned as primary caregivers, wield a pivotal role in upholding and adhering to IPSGs, underscoring the critical significance of their knowledge and understanding of these goals. This research embarks on a comprehensive exploration into the depth of Doctors ' comprehension of IPSGs, aiming to unearth potential gaps and provide insights for targeted educational interventions. Established by influential healthcare bodies, including the World Health Organization (WHO), IPSGs represent a universally applicable set of objectives spanning crucial domains such as medication safety, infection control, surgical site safety, and patient identification. Adherence to these goals has exhibited substantial reductions in adverse events, fostering an overall enhancement in the quality of care. This study operates on the fundamental premise that an informed Doctors workforce is indispensable for effectively implementing IPSGs. A nuanced understanding of these goals empowers Doctors to identify potential risks, advocate for necessary changes, and actively contribute to a safety-centric culture within healthcare institutions. Despite the acknowledged importance of IPSGs, there is a growing concern that nurses may need more knowledge to integrate these goals into their practice seamlessly. Methodology: A Comprehensive research methodology covering study design, setting, duration, sample size determination, sampling technique, and data analysis. It introduces the philosophical framework guiding the research and details material, methods, and the analysis framework. The descriptive quantitative cross-sectional study in teaching care hospitals utilized convenient sampling over six months. Data collection involved written informed consent and questionnaires, analyzed with SPSS version 23, presenting results graphically and descriptively. The chapter ensures a clear understanding of the study's design, execution, and analytical processes. Result: The survey results reveal a substantial distribution across hospitals, with 34.52% in MTIKTH and 65.48% in HMC MTI. There is a notable prevalence of patient safety incidents, emphasizing the significance of adherence to IPSGs. Positive trends are observed, including 77.0% affirming the "time-out" procedure, 81.6% acknowledging effective healthcare provider communication, and high recognition (82.7%) of the purpose of IPSGs to improve patient safety. While the survey reflects a good understanding of IPSGs, areas for improvement are identified, suggesting opportunities for targeted interventions. Discussion: The study underscores the need for tailored care approaches and highlights the bio-socio-cultural context of 'contagion,' suggesting areas for further research amid antimicrobial resistance. Shifting the focus to patient safety practices, the survey chapter provides a detailed overview of results, emphasizing workplace distribution, patient safety incidents, and positive reflections on IPSGs. The findings indicate a positive trend in patient safety practices with areas for improvement, emphasizing the ongoing need for reinforcing safety protocols and cultivating a safety-centric culture in healthcare. Conclusion: In summary, the survey indicates a positive trend in patient safety practices with a good understanding of IPSGs among participants. However, identifying areas for potential improvement suggests opportunities for targeted interventions to enhance patient safety further. Ongoing efforts to reinforce adherence to safety protocols, address identified gaps, and foster a safety culture will contribute to continuous improvements in patient care and outcomes.

Keywords: infection control, international patient safety, patient safety practices, proper medication

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Authors: Veenapani Rajeev Verma

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Context: Assessing facility readiness is paramount as it can indicate capacity of facilities to provide essential care for resilience to health challenges. In the context of decentralization, estimation of supply side readiness indices at sub national level is imperative for effective evidence based policy but remains a colossal challenge due to lack of dependable and representative data sources. Setting: District Poonch of Jammu and Kashmir was selected for this study. It is remote, rural district with unprecedented topographical barriers and is identified as high priority by government. It is also a fragile area as is bounded by Line of Control with Pakistan bearing the brunt of cease fire violations, military skirmishes and sporadic militant attacks. Hilly geographical terrain, rudimentary/absence of road network and impoverishment are quintessential to this area. Objectives: Objective of the study is to a) Evaluate the service readiness of health facilities and create a concise index subsuming plethora of discrete indicators and b) Ascertain supply side barriers in service provisioning via stakeholder’s analysis. Study also strives to expand analytical domain unravelling context and area specific intricacies associated with service delivery. Methodology: Mixed method approach was employed to triangulate quantitative analysis with qualitative nuances. Facility survey encompassing 90 Subcentres, 44 Primary health centres, 3 Community health centres and 1 District hospital was conducted to gauge general service availability and service specific availability (depth of coverage). Compendium of checklist was designed using Indian Public Health Standards (IPHS) in form of standard core questionnaire and scorecard generated for each facility. Information was collected across dimensions of amenities, equipment, medicines, laboratory and infection control protocols as proposed in WHO’s Service Availability and Readiness Assesment (SARA). Two stage polychoric principal component analysis employed to generate a parsimonious index by coalescing an array of tracer indicators. OLS regression method used to determine factors explaining composite index generated from PCA. Stakeholder analysis was conducted to discern qualitative information. Myriad of techniques like observations, key informant interviews and focus group discussions using semi structured questionnaires on both leaders and laggards were administered for critical stakeholder’s analysis. Results: General readiness score of health facilities was found to be 0.48. Results indicated poorest readiness for subcentres and PHC’s (first point of contact) with composite score of 0.47 and 0.41 respectively. For primary care facilities; principal component was characterized by basic newborn care as well as preparedness for delivery. Results revealed availability of equipment and surgical preparedness having lowest score (0.46 and 0.47) for facilities providing secondary care. Presence of contractual staff, more than 1 hr walk to facility, facilities in zone A (most vulnerable) to cross border shelling and facilities inaccessible due to snowfall and thick jungles was negatively associated with readiness index. Nonchalant staff attitude, unavailability of staff quarters, leakages and constraint in supply chain of drugs and consumables were other impediments identified. Conclusions/Policy Implications: It is pertinent to first strengthen primary care facilities in this setting. Complex dimensions such as geographic barriers, user and provider behavior is not under precinct of this methodology.

Keywords: effective coverage, principal component analysis, readiness index, universal health coverage

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Authors: Z. 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. 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 socket, 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. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-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 fresh 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 (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-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 proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and 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 thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

Procedia PDF Downloads 86

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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Authors: Stephen Verderber

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The World Health Organization (WHO) calls for research and development on ecologically sustainable, resilient structures capable of effectively responding to disaster events globally, in response to climate change, politically based diasporas, earthquakes, and other adverse events upending the rhythms of everyday life globally. By 2050, nearly 80% of the world’s population will reside in coastal zones, and this, coupled with the increasingly dire impacts of climate change, constitute a recipe for further chaos and disruption, and in light of these events, architects have yet to rise up to meet the challenge. In the arena of healthcare, rapidly deployable clinics and field hospitals can provide immediate assistance in medically underserved disaster strike zones. Transportable facilities offer multiple advantages over conventional, fixed-site hospitals, as lightweight, comparatively unencumbered alternatives. These attributes have been proven repeatedly in 20th century vehicular and tent-based structures deployed in frontline combat theaters and in prior natural disasters. Prefab transportable clinics and trauma centers recently responded adroitly to medical emergencies in the aftermath of the Haitian (2010) and Ecuadorian (2016) earthquakes, and in North American post-hurricane relief efforts (2017) while architects continue to be castigated by their engineer colleagues as chronically poor first responders. Architecturally based portable structures for healthcare currently include Redeployable Health Centers (RHCs), Redeployable Trauma Centers (RTCs), and Permanent Modular Installations (PMIs). Five tectonic variants within this typology have recently been operationalized in the field: 1. Vehicular-based Nomadics: Prefab modules installed on a truck chassis with interior compartments dropped in prior to final assembly. Alternately, a two-component apparatus is preferred, with a truck cab pulling a modular medical unit, with independent transiting component; 2. Tent and Pneumatic Systems: Tent/yurt precursors and inflatable systems lightweight and responsive to topographically challenging terrain and diverse climates; 3. Containerized Systems: The standard modular intermodal-shipping container affords structural strength, resiliency in difficult transiting conditions, and can be densely close-packed and these can be custom-built or hold flat-pack systems; 4. Flat-Packs and Pop-Up Systems: These kit-of-part assemblies are shipped in standardized or specially-designed ISO containers; and 5. Hybrid Systems: These consist of composite facilities representing a synthesis of mobile vehicular components and/or tent or shipping containers, fused with conventional or pneumatically activated tent systems. Hybrids are advantageous in many installation contexts from an aesthetic, fabrication, and transiting perspective. Advantages/disadvantages of various modular systems are comparatively examined, followed by presentation of a compendium of 80 evidence (research)-based planning and design considerations addressing site/context, transiting and commissioning, triage, decontamination/intake, diagnostic and treatment, facility tectonics, and administration/total environment. The benefits of offsite pre-manufactured fabrication are examined, as is anticipated growth in international demand for transportable healthcare facilities to meet the challenges posed by accelerating global climate change and global conflicts. This investigation into rapid response facilities for pre and post-disaster zones is drawn from a recent book by the author, the first on architecture on this topic (Innovations in Transportable Healthcare Architecture).

Keywords: disaster mitigation, rapid response healthcare architecture, offsite prefabrication

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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

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

Procedia PDF Downloads 163

Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

Abstract:

Background The Delivering Innovations in Selfcare (DISC) project promotes universal access to quality selfcare services beginning with subcutaneous depot medroxy progesterone acetate (DMPA-SC) contraceptive self-injection (SI) option. Self-inject (SI) offers women a highly effective and convenient option that saves them frequent trips to providers. Its increased use has the potential to improve the efficiency of an overstretched healthcare system by reducing provider workloads. State Social and Behavioral Change Communications (SBCC) Officers lead project demand creation and service delivery innovations that have resulted in significant increases in SI uptake among women who opt for injectables. Strategies Service Delivery Innovations The implementation of the "Moment of Truth (MoT)" innovation helped providers overcome biases and address client fear and reluctance to self-inject. Bi-annual program audits and supportive mentoring visits helped providers retain their competence and motivation. Proper documentation, tracking, and replenishment of commodities were ensured through effective engagement with State Logistics Units. The project supported existing state monitoring and evaluation structures to effectively record and report subcutaneous depot medroxy progesterone acetate (DMPA-SC) service utilization. Demand creation Innovations SBCC Officers provide oversight, routinely evaluate performance, trains, and provides feedback for the demand creation activities implemented by community mobilizers (CMs). The scope and intensity of training given to CMs affect the outcome of their work. The project operates a demand creation model that uses a schedule to inform the conduct of interpersonal and group events. Health education sessions are specifically designed to counter misinformation, address questions and concerns, and educate target audience in an informed choice context. The project mapped facilities and their catchment areas and enlisted the support of identified influencers and gatekeepers to enlist their buy-in prior to entry. Each mobilization event began with pre-mobilization sensitization activities, particularly targeting male groups. Context-specific interventions were informed by the religious, traditional, and cultural peculiarities of target communities. Mobilizers also support clients to engage with and navigate online digital Family Planning (FP) online portals such as DiscoverYourPower website, Facebook page, digital companion (chat bot), interactive voice response (IVR), radio and television (TV) messaging. This improves compliance and provides linkages to nearby facilities. Results The project recorded 136,950 self-injection (SI) visits and a self-injection (SI) proportion rate that increased from 13 percent before the implementation of interventions in 2021 to 62 percent currently. The project cost-effectively demonstrated catalytic impact by leveraging state and partner resources, institutional platforms, and geographic scope to scale up interventions. The project also cost effectively demonstrated catalytic impact by leveraging on the state and partner resources, institutional platforms, and geographic scope to sustainably scale-up these strategies. Conclusion Using evidence-informed iterations of service delivery and demand creation models have been useful to significantly drive self-injection (SI) uptake. It will be useful to consider this implementation model during program design. Contemplation should also be given to systematic and strategic execution of strategies to optimize impact.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, innovation, service delivery, demand creation.

Procedia PDF Downloads 45

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 52

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 60