Search results for: vaccine administration

Authors: Antonella Falanga, Armando Cartenì

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"Big data" refers to extremely vast and complex sets of data, encompassing extraordinarily large and intricate datasets that require specific tools for meaningful analysis and processing. These datasets can stem from diverse origins like sensors, mobile devices, online transactions, social media platforms, and more. The utilization of big data is pivotal, offering the chance to leverage vast information for substantial advantages across diverse fields, thereby enhancing comprehension, decision-making, efficiency, and fostering innovation in various domains. Big data, distinguished by its remarkable attributes of enormous volume, high velocity, diverse variety, and significant value, represent a transformative force reshaping the industry worldwide. Their pervasive impact continues to unlock new possibilities, driving innovation and advancements in technology, decision-making processes, and societal progress in an increasingly data-centric world. The use of these technologies is becoming more widespread, facilitating and accelerating operations that were once much more complicated. In particular, big data impacts across multiple sectors such as business and commerce, healthcare and science, finance, education, geography, agriculture, media and entertainment and also mobility and logistics. Within the transportation sector, which is the focus of this study, big data applications encompass a wide variety, spanning across optimization in vehicle routing, real-time traffic management and monitoring, logistics efficiency, reduction of travel times and congestion, enhancement of the overall transportation systems, but also mitigation of pollutant emissions contributing to environmental sustainability. Meanwhile, in public administration and the development of smart cities, big data aids in improving public services, urban planning, and decision-making processes, leading to more efficient and sustainable urban environments. Access to vast data reservoirs enables deeper insights, revealing hidden patterns and facilitating more precise and timely decision-making. Additionally, advancements in cloud computing and artificial intelligence (AI) have further amplified the potential of big data, enabling more sophisticated and comprehensive analyses. Certainly, utilizing big data presents various advantages but also entails several challenges regarding data privacy and security, ensuring data quality, managing and storing large volumes of data effectively, integrating data from diverse sources, the need for specialized skills to interpret analysis results, ethical considerations in data use, and evaluating costs against benefits. Addressing these difficulties requires well-structured strategies and policies to balance the benefits of big data with privacy, security, and efficient data management concerns. Building upon these premises, the current research investigates the efficacy and influence of big data by conducting an overview of the primary and recent implementations of big data in transportation systems. Overall, this research allows us to conclude that big data better provide to enhance rational decision-making for mobility choices and is imperative for adeptly planning and allocating investments in transportation infrastructures and services.

Keywords: big data, public transport, sustainable mobility, transport demand, transportation planning

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Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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Authors: Keith Schofield, Garry R. Prentice

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The perceptions of the work an academic does, and the environment in which they do it, contributes to the professional identity of that academic. In turn, this has implications for the level of involvement they have in their job, their satisfaction, and their work product. This research explores academic identities in British and Irish institutions and considers the complex interplay between identity, practice, and participation. Theoretical assumptions made in this paper assert that meaningful work has positive effects on work pride, organisational commitment, organisational citizenship, and motivation; when employees participate enthusiastically they are likely to be more engaged, more successful, and more satisfied. Further examination is given to the context in which this participation happens; the nature of institutional process, management, and relationships with colleagues, team members, and students is considered. The present study follows a mixed-methods approach to explore work satisfaction constructs in a number of academic contexts in the UK and Ireland. The quantitative component of this research (Convenience Sample: 155 academics, and support/ administrative staff; 36.1% male, 63.9% female; 60.8% academic staff, 39.2% support/ administration staff; across a number of universities in the UK and Ireland) was based on an established emotional labour model and was tested across gender groups, job roles, and years of service. This was complimented by qualitative semi-structured interviews (Purposive Sample: 10 academics, and 5 support/ administrative staff across the same universities in the UK and Ireland) to examine various themes including values within academia, work conditions, professional development, and transmission of knowledge to students. Experiences from both academic and support perspectives were sought in order to gain a holistic view of academia and to provide an opportunity to explore the dynamic of the academic/administrator relationship within the broader institutional context. The quantitative emotional labour model, tested via a path analysis, provided a robust description of the relationships within the data. The significant relationships found within the quantitative emotional labour model included a link between non-expression of true feelings resulting in emotional labourious work and lower levels of intrinsic motivation and higher levels of extrinsic motivation. Higher levels of intrinsic motivation also linked positively to work pride. These findings were further explored in the qualitative elements of the research where themes emerged including the disconnection between faculty management and staff, personal fulfilment and the friction between the identities of teacher, researcher/ practitioner and administrator. The implications of the research findings from this study are combined and discussed in relation to possible identity-related and emotional labour management-related interventions. Further, suggestions are made to institutions concerning the application of these findings including the development of academic practices, with specific reference to the duality of identity required to service the combined teacher/ researcher role. Broader considerations of the paper include how individuals and institutions may engage with the changing nature of students-as-consumers as well as a recommendation to centralise personal fulfillment through the development of professional academic identities.

Keywords: academic work, emotional labour, identity friction, mixed methods

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Authors: Swati Bhomia, C. M. Kishtawal, Neeru Jaiswal

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Traditionally, monsoon forecasts have encountered many difficulties that stem from numerous issues such as lack of adequate upper air observations, mesoscale nature of convection, proper resolution, radiative interactions, planetary boundary layer physics, mesoscale air-sea fluxes, representation of orography, etc. Uncertainties in any of these areas lead to large systematic errors. Global circulation models (GCMs), which are developed independently at different institutes, each of which carries somewhat different representation of the above processes, can be combined to reduce the collective local biases in space, time, and for different variables from different models. This is the basic concept behind the multi-model superensemble and comprises of a training and a forecast phase. The training phase learns from the recent past performances of models and is used to determine statistical weights from a least square minimization via a simple multiple regression. These weights are then used in the forecast phase. The superensemble forecasts carry the highest skill compared to simple ensemble mean, bias corrected ensemble mean and the best model out of the participating member models. This approach is a powerful post-processing method for the estimation of weather forecast parameters reducing the direct model output errors. Although it can be applied successfully to the continuous parameters like temperature, humidity, wind speed, mean sea level pressure etc., in this paper, this approach is applied to rainfall, a parameter quite difficult to handle with standard post-processing methods, due to its high temporal and spatial variability. The present study aims at the development of advanced superensemble schemes comprising of 1-5 day daily precipitation forecasts from five state-of-the-art global circulation models (GCMs), i.e., European Centre for Medium Range Weather Forecasts (Europe), National Center for Environmental Prediction (USA), China Meteorological Administration (China), Canadian Meteorological Centre (Canada) and U.K. Meteorological Office (U.K.) obtained from THORPEX Interactive Grand Global Ensemble (TIGGE), which is one of the most complete data set available. The novel approaches include the dynamical model selection approach in which the selection of the superior models from the participating member models at each grid and for each forecast step in the training period is carried out. Multi-model superensemble based on the training using similar conditions is also discussed in the present study, which is based on the assumption that training with the similar type of conditions may provide the better forecasts in spite of the sequential training which is being used in the conventional multi-model ensemble (MME) approaches. Further, a variety of methods that incorporate a 'neighborhood' around each grid point which is available in literature to allow for spatial error or uncertainty, have also been experimented with the above mentioned approaches. The comparison of these schemes with respect to the observations verifies that the newly developed approaches provide more unified and skillful prediction of the summer monsoon (viz. June to September) rainfall compared to the conventional multi-model approach and the member models.

Keywords: multi-model superensemble, dynamical model selection, similarity criteria, neighborhood technique, rainfall prediction

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Authors: Laura Butabayeva, Svetlana Ismagulova, Gulbarshin Nogaibayeva, Maiya Temirbayeva, Aidana Zhussip

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Over the years of independence, Kazakhstan has not only ratified international documents regulating the rights of children to Inclusive education, but also developed its own inclusive educational policy. Along with this, the state pays particular attention to high school students' preparedness for professional self-determination. However, a number of problematic issues in this field have been revealed, such as the lack of systemic mechanisms coordinating stakeholders’ actions in preparing schoolchildren for a conscious choice of in-demand profession, meeting their individual capabilities and special educational needs (SEN). The analysis of the state’s current situation indicates school graduates’ adaptation to the labor market does not meet existing demands of the society. According to the Ministry of Labor and Social Protection of the Population of the Republic of Kazakhstan, about 70 % of Kazakhstani school graduates find themselves difficult to choose a profession, 87 % of schoolchildren make their career choice under the influence of parents and school teachers, 90 % of schoolchildren and their parents have no idea about the most popular professions on the market. The results of the study conducted by KorlanSyzdykova in 2016 indicated the urgent need of Kazakhstani school graduates in obtaining extensive information about in- demand professions and receiving professional assistance in choosing a profession in accordance with their individual skills, abilities, and preferences. The results of the survey, conducted by Information and Analytical Center among heads of colleges in 2020, showed that despite significant steps in creating conditions for students with SEN, they face challenges in studying because of poor career guidance provided to them in schools. The results of the study, conducted by the Center for Inclusive Education of the National Academy of Education named after Y. Altynsarin in the state’s general education schools in 2021, demonstrated the lack of career guidance, pedagogical and psychological support for children with SEN. To investigate these issues, the further study was conducted to examine the state of students’ career guidance and socialization, taking into account their SEN. The hypothesis of this study proposed that to prepare school graduates for a conscious career choice, school teachers and specialists need to develop their competencies in early identification of students' interests, inclinations, SEN and ensure necessary support for them. The state’s 5 regions were involved in the study according to the geographical location. The triangulation approach was utilized to ensure the credibility and validity of research findings, including both theoretical (analysis of existing statistical data, legal documents, results of previous research) and empirical (school survey for students, interviews with parents, teachers, representatives of school administration) methods. The data were analyzed independently and compared to each other. The survey included questions related to provision of pedagogical support for school students in making their career choice. Ethical principles were observed in the process of developing the methodology, collecting, analyzing the data and distributing the results. Based on the results, methodological recommendations on students’ career guidance for school teachers and specialists were developed, taking into account the former’s individual capabilities and SEN.

Keywords: career guidance, children with special educational needs, inclusive education, Kazakhstan

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Authors: Prem Kumar, Anuj Tyagi, Harsh Panwar, Vaneet Inder Kaur

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Though aquaculture started as an occupation for poor and weak farmers for livelihood, it has now acquired the shape of one of the biggest industry to grow live protein in the form of aquatic organisms. Industrialization of the aquaculture sector has led to intensification resulting in stress on aquatic organisms and frequent disease outbreaks leading to huge economic impacts. Indiscriminate use of antibiotics as growth promoter and prophylactic agent in aquaculture has resulted in rapid emergence and spread of antibiotic resistance in bacterial pathogens. Over the past few years, use of probiotics (as an alternative of antibiotics) in aquaculture has gained attention due to their immunostimulant and growth promoting properties. It has now well known that after administration, a probiotic bacterium has to compete and establish itself against native microbiota to show its eventual beneficial properties. Due to their non-fish origin, commercial probiotics sometimes may display poor probiotic functionalities and antagonistic effects. Thus, isolation and characterization of probiotic bacteria from same fish host is very much necessary. In this study, attempts were made to isolate potent probiotic lactic acid bacteria (LAB) from intestinal microflora of rohu fish. Twenty-five experimental rohu fishes (mean weight 400 ± 20gm, mean standard length 20 ± 3cm) were used in the study to collect fish gut after dissection in a sterile condition. A total of 150 tentative LAB isolates from selective agar media (de Man-Rogosa-Sharpe (MRS)) were screened for their antimicrobial activity against Aeromonas hydrophila and Microccocus leuteus. A total of 17 isolates, identified as Lactobacillus plantarum and Lactococcus lactis, identified by biochemical tests and PCR amplification and sequencing of 16S rRNA gene fragment, displayed promising antimicrobial activity against both the pathogens. Two isolates from each species (FLB1, FLB2 from L. plantarum; and FLC1, FLC2 from L. lactis) were subjected to downstream probiotic potential characterization. These isolates were compared in vitro for their hemolytic activity, acid and bile tolerance for growth kinetics, auto-aggregation, cell-surface hydrophobicity against xylene, and chloroform, tolerance to phenol, cell adhesion, and safety parameters (by intraperitoneal and intramuscular injections). None of the tested isolates showed any hemolytic activity indicating their potential safety. Moreover, these isolates were tolerant to 0.3% bile (75-82% survival), phenol stress (96-99% survival) with 100% viability at pH 3 over a period of 3 h. Antibiotic sensitivity test revealed that all the tested LAB isolates were resistant to vancomycin, gentamicin, streptomycin, and erythromycin and sensitive to Erythromycin, Chloramphenicol, Ampicillin, Trimethoprim, and Nitrofurantoin. Tetracycline resistance was found in L. plantarum (FLB1 and FLB2 isolates), whereas L. lactis were susceptible to it. Intramuscular and intraperitoneal challenges to fingerlings of rohu fish (5 ± 1gm weight) with FLB1 showed no pathogenicity and occurrence of disease symptoms in fishes over an observation period of 7 days. The results revealed FLB1 as a potential probiotic candidate for aquaculture application among other isolates.

Keywords: aquaculture, Lactobacillus plantarum, Lactococcus lactis, probiotics

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Salvatore Luongo, Carlo Luongo

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This paper discusses the implementation solutions to reduce the computational load for the Traffic Situational Awareness with Alerts (TSAA) application, based on Automatic Dependent Surveillance-Broadcast (ADS-B) technology. In 2008, there were 23 total mid-air collisions involving general aviation fixed-wing aircraft, 6 of which were fatal leading to 21 fatalities. These collisions occurred during visual meteorological conditions, indicating the limitations of the see-and-avoid concept for mid-air collision avoidance as defined in the Federal Aviation Administration’s (FAA). The commercial aviation aircraft are already equipped with collision avoidance system called TCAS, which is based on classic transponder technology. This system dramatically reduced the number of mid-air collisions involving air transport aircraft. In general aviation, the same reduction in mid-air collisions has not occurred, so this reduction is the main objective of the TSAA application. The major difference between the original conflict detection application and the TSAA application is that the conflict detection is focused on preventing loss of separation in en-route environments. Instead TSAA is devoted to reducing the probability of mid-air collision in all phases of flight. The TSAA application increases the flight crew traffic situation awareness providing alerts of traffic that are detected in conflict with ownship in support of the see-and-avoid responsibility. The relevant effort has been spent in the design process and the code generation in order to maximize the efficiency and performances in terms of computational load and memory consumption reduction. The TSAA architecture is divided into two high-level systems: the “Threats database” and the “Conflict detector”. The first one receives the traffic data from ADS-B device and provides the memorization of the target’s data history. Conflict detector module estimates ownship and targets trajectories in order to perform the detection of possible future loss of separation between ownship and each target. Finally, the alerts are verified by additional conflict verification logic, in order to prevent possible undesirable behaviors of the alert flag. In order to reduce the computational load, a pre-check evaluation module is used. This pre-check is only a computational optimization, so the performances of the conflict detector system are not modified in terms of number of alerts detected. The pre-check module uses analytical trajectories propagation for both target and ownship. This allows major accuracy and avoids the step-by-step propagation, which requests major computational load. Furthermore, the pre-check permits to exclude the target that is certainly not a threat, using an analytical and efficient geometrical approach, in order to decrease the computational load for the following modules. This software improvement is not suggested by FAA documents, and so it is the main innovation of this work. The efficiency and efficacy of this enhancement are verified using fast-time and real-time simulations and by the execution on a real device in several FAA scenarios. The final implementation also permits the FAA software certification in compliance with DO-178B standard. The computational load reduction allows the installation of TSAA application also on devices with multiple applications and/or low capacity in terms of available memory and computational capabilities

Keywords: traffic situation awareness, general aviation, aircraft conflict detection, computational load reduction, implementation solutions, software certification

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Authors: Amna Tariq Shah

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Amid the pandemic, the contemporary landscape has experienced accelerated growth in small business activities and an expanding digital marketplace, further exacerbating the issue of non-compliance among self-employed individuals through aggressive tax planning and evasion. This research seeks to address these challenges by developing strategic tax policies that promote voluntary compliance and improve taxpayer facilitation. The study employs the innovative MINDSPACE framework to examine three psychosocial factors—tax communication, tax literacy, and shaming—to optimize policy responses, address administrative shortcomings, and ensure adequate revenue collection for public goods and services. Preliminary findings suggest that incomprehensible communication from tax authorities drives individuals to seek alternative, potentially biased sources of tax information, thereby exacerbating non-compliance. Furthermore, the study reveals low tax literacy among Australian and Pakistani respondents, with many struggling to navigate complex tax processes and comprehend tax laws. Consequently, policy recommendations include simplifying tax return filing and enhancing pre-populated tax returns. In terms of shaming, the research indicates that Australians, being an individualistic society, may not respond well to shaming techniques due to privacy concerns. In contrast, Pakistanis, as a collectivistic society, may be more receptive to naming and shaming approaches. The study employs a mixed-method approach, utilizing interviews and surveys to analyze the issue in both jurisdictions. The use of mixed methods allows for a more comprehensive understanding of tax compliance behavior, combining the depth of qualitative insights with the generalizability of quantitative data, ultimately leading to more robust and well-informed policy recommendations. By examining evidence from opposite jurisdictions, namely a developed country (Australia) and a developing country (Pakistan), the study's applicability is enhanced, providing perspectives from two disparate contexts that offer insights from opposite ends of the economic, cultural, and social spectra. The non-comparative case study methodology offers valuable insights into human behavior, which can be applied to other jurisdictions as well. The application of the MINDSPACE framework in this research is particularly significant, as it introduces a novel approach to tax compliance behavior analysis. By integrating insights from behavioral economics, the framework enables a comprehensive understanding of the psychological and social factors influencing taxpayer decision-making, facilitating the development of targeted and effective policy interventions. This research carries substantial importance as it addresses critical challenges in tax compliance and administration, with far-reaching implications for revenue collection and the provision of public goods and services. By investigating the psychosocial factors that influence taxpayer behavior and utilizing the MINDSPACE framework, the study contributes invaluable insights to the field of tax policy. These insights can inform policymakers and tax administrators in developing more effective tax policies that enhance taxpayer facilitation, address administrative obstacles, promote a more equitable and efficient tax system, and foster voluntary compliance, ultimately strengthening the financial foundation of governments and communities.

Keywords: individual tax compliance behavior, psychosocial factors, tax non-compliance, tax policy

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Authors: Chenyi Ma

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Background: The second costliest hurricane in U.S. history, Sandy landed in southern New Jersey on October 29, 2012, and struck the entire state with high winds and torrential rains. The disaster killed more than 100 people, left more than 8.5 million households without power, and damaged or destroyed more than 200,000 homes across the state. Immediately after the disaster, public policy support was provided in nine coastal counties that constituted 98% of the major and severely damaged housing units in NJ overall. The programs include Individuals and Households Assistance Program, Small Business Loan Program, National Flood Insurance Program, and the Federal Emergency Management Administration (FEMA) Public Assistance Grant Program. In the most severely affected counties, additional funding was provided through Community Development Block Grant: Reconstruction, Rehabilitation, Elevation, and Mitigation Program, and Homeowner Resettlement Program. How these policies individually and as a whole impacted housing recovery across communities with different socioeconomic and demographic profiles has not yet been studied, particularly in relation to damage levels. The concept of community social vulnerability has been widely used to explain many aspects of natural disasters. Nevertheless, how communities are vulnerable has been less fully examined. Community resilience has been conceptualized as a protective factor against negative impacts from disasters, however, how community resilience buffers the effects of vulnerability is not yet known. Because housing recovery is a dynamic social and economic process that varies according to context, this study examined the path from community vulnerability and resilience to housing recovery looking at both community characteristics and policy interventions. Sample/Methods: This retrospective longitudinal case study compared a literature-identified set of pre-disaster community characteristics, the effects of multiple public policy programs, and a set of time-variant community resilience indicators to changes in housing stock (operationally defined by percent of building permits to total occupied housing units/households) between 2010 and 2014, two years before and after Hurricane Sandy. The sample consisted of 51 municipalities in the nine counties in which between 4% and 58% of housing units suffered either major or severe damage. Structural equation modeling (SEM) was used to determine the path from vulnerability to the housing recovery, via multiple public programs, separately and as a whole, and via the community resilience indicators. The spatial analytical tool ArcGIS 10.2 was used to show the spatial relations between housing recovery patterns and community vulnerability and resilience. Findings: Holding damage levels constant, communities with higher proportions of Hispanic households had significantly lower levels of housing recovery while communities with households with an adult >age 65 had significantly higher levels of the housing recovery. The contrast was partly due to the different levels of total public support the two types of the community received. Further, while the public policy programs individually mediated the negative associations between African American and female-headed households and housing recovery, communities with larger proportions of African American, female-headed and Hispanic households were “vulnerable” to lower levels of housing recovery because they lacked sufficient public program support. Even so, higher employment rates and incomes buffered vulnerability to lower housing recovery. Because housing is the "wobbly pillar" of the welfare state, the housing needs of these particular groups should be more fully addressed by disaster policy.

Keywords: community social vulnerability, community resilience, hurricane, public policy

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Authors: Peregrine James Dalziel, Philip Vu Tran

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Objective / Introduction: Demand for radiology services from Emergency Departments (ED) continues to increase with greater demands placed on radiology staff providing reports for the management of complex cases. Queuing theory indicates that wide variability of process time with the random nature of request arrival increases the probability of significant queues. This can lead to delays in the time-to-availability of radiology reports (TTA-RR) and potentially impaired ED patient flow. In addition, greater “cognitive workload” of greater volume may lead to reduced productivity and increased errors. We sought to quantify the potential ED flow improvements obtainable from increased radiology providers serving 3 public hospitals in Melbourne Australia. We sought to assess the potential productivity gains, quality improvement and the cost-effectiveness of increased labor inputs. Methods & Materials: The Western Health Medical Imaging Department moved from single resident coverage on weekend days 8:30 am-10:30 pm to a limited period of 2 resident coverage 1 pm-6 pm on both weekend days. The TTA-RR for weekend CT scans was calculated from the PACs database for the 8 month period symmetrically around the date of staffing change. A multivariate linear regression model was developed to isolate the improvement in TTA-RR, between the two 4-months periods. Daily and hourly scan volume at the time of each CT scan was calculated to assess the impact of varying department workload. To assess any improvement in report quality/errors a random sample of 200 studies was assessed to compare the average number of clinically significant over-read addendums to reports between the 2 periods. Cost-effectiveness was assessed by comparing the marginal cost of additional staffing against a conservative estimate of the economic benefit of improved ED patient throughput using the Australian national insurance rebate for private ED attendance as a revenue proxy. Results: The primary resident on call and the type of scan accounted for most of the explained variability in time to report availability (R2=0.29). Increasing daily volume and hourly volume was associated with increased TTA-RR (1.5m (p<0.01) and 4.8m (p<0.01) respectively per additional scan ordered within each time frame. Reports were available 25.9 minutes sooner on average in the 4 months post-implementation of double coverage (p<0.01) with additional 23.6 minutes improvement when 2 residents were on-site concomitantly (p<0.01). The aggregate average improvement in TTA-RR was 24.8 hours per weekend day This represents the increased decision-making time available to ED physicians and potential improvement in ED bed utilisation. 5% of reports from the intervention period contained clinically significant addendums vs 7% in the single resident period but this was not statistically significant (p=0.7). The marginal cost was less than the anticipated economic benefit based assuming a 50% capture of improved TTA-RR inpatient disposition and using the lowest available national insurance rebate as a proxy for economic benefit. Conclusion: TTA-RR improved significantly during the period of increased staff availability, both during the specific period of increased staffing and throughout the day. Increased labor utilisation is cost-effective compared with the potential improved productivity for ED cases requiring CT imaging.

Keywords: workflow, quality, administration, CT, staffing

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Elena Parmentier, Henrik Endeman

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Introduction: Large mediastinal masses often present with diagnostic and clinical challenges due to compression of the respiratory and hemodynamic system. We present a case of a mediastinal mass with symptomatic mechanical compression of the trachea, resulting in challenging airway management. Methods: We present a case of 66-year-old male, complaining of progressive dysphagia. Initial esophagogastroscopy revealed a stenosis secondary to external compression, biopsies were inconclusive. Additional CT scan showed a large mediastinal mass of unknown origin, situated between the vertebrae and esophagus. Symptoms progressed and patient developed dyspnea and stridor. A new CT showed quick growth of the mass with compression of the trachea, subglottic to just above the carina. A tracheal covered stent was successfully placed. Endobronchial ultrasound revealed a large irregular mass without tracheal invasion, biopsies were taken. 4 days after stent placement, the patients’ condition deteriorated with worsening of stridor, dyspnea and desaturation. Migration of the tracheal stent into the right main bronchus was seen on chest X ray, with obstruction of the left main bronchus and secondary atelectasis. Different methods have been described in the literature for tracheobronchial stent removal (surgical, endoscopic, fluoroscopyguided), our first choice in this case was flexible bronchoscopy. However, this revealed tracheal compression above the migrated stent and passage of the scope occurred impossible. Patient was admitted to the ICU, high-flow nasal oxygen therapy was started and the situation stabilized, giving time for extensive assessment and preparation of the airway management approach. Close cooperation between the intensivist, pulmonologist, anesthesiologist and otorhinolaryngologist was essential. Results: In case of sudden deterioration, a protocol for emergency situations was made. Given the increased risk of additional tracheal compression after administration of neuromuscular blocking agents, an approach with awake fiberoptic intubation maintaining spontaneous ventilation was proposed. However, intubation without retrieval of the tracheal stent was found undesirable due to expected massive shunting over the left atelectatic lung. As rescue option, assistance of extracorporeal circulation was considered and perfusionist was kept on standby. The patient stayed stable and was transferred to the operating theatre. High frequency jet ventilation under general anesthesia resulted in desaturations up to 50%, making rigid bronchoscopy impossible. Subsequently an endotracheal tube size 8 could be placed successfully and the stent could be retrieved via bronchoscopy over (and with) the tube, after which the patient was reintubated. Finally, a tracheostomy (Shiley™ Tracheostomy Tube With Cuff, size 8) was placed, fiberoptic control showed a patent airway. Patient was readmitted to the ICU and could be quickly weaned of the ventilator. Pathology was positive for rhabdomyosarcoma, without indication for systemic therapy. Extensive surgery (laryngectomy, esophagectomy) was suggested, but patient refused and palliative care was started. Conclusion: Due to meticulous planning in an interdisciplinary team, we showed a successful airway management approach in this complicated case of critical airway compression secondary to a rare rhabdomyosarcoma, complicated by tracheal stent migration. Besides presenting our thoughts and considerations, we support exploring other possible approaches of this specific clinical problem.

Keywords: airway management, rhabdomyosarcoma, stent displacement, tracheal stenosis

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Authors: Rahel Birhane Eshetu

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This research investigates the complex landscape of project management practices and operational challenges in conflict-affected areas, with a specific focus on Kewot Woreda in the North Shewa Zone of the Amhara region in Ethiopia. The study aims to identify essential project management methodologies, the significant operational hurdles faced, and the adaptive strategies employed by project managers in these challenging environments. Utilizing a mixed-methods approach, the research combines qualitative and quantitative data collection. Initially, a comprehensive literature review was conducted to establish a theoretical framework. This was followed by the administration of questionnaires to gather empirical data, which was then analyzed using statistical software. This sequential approach ensures a robust understanding of the context and challenges faced by project managers. The findings reveal that project managers in conflict zones encounter a range of escalating challenges. Initially, they must contend with immediate security threats and the presence of displaced populations, which significantly disrupt project initiation and execution. As projects progress, additional challenges arise, including limited access to essential resources and environmental disruptions such as natural disasters. These factors exacerbate the operational difficulties that project managers must navigate. In response to these challenges, the study highlights the necessity for project managers to implement formal project plans while simultaneously adopting adaptive strategies that evolve over time. Key adaptive strategies identified include flexible risk management frameworks, change management practices, and enhanced stakeholder engagement approaches. These strategies are crucial for maintaining project momentum and ensuring that objectives are met despite the unpredictable nature of conflict environments. The research emphasizes that structured scope management, clear documentation, and thorough requirements analysis are vital components for effectively navigating the complexities inherent in conflict-affected regions. However, the ongoing threats and logistical barriers necessitate a continuous adjustment to project management methodologies. This adaptability is not only essential for the immediate success of projects but also for fostering long-term resilience within the community. Concluding, the study offers actionable recommendations aimed at improving project management practices in conflict zones. These include the adoption of adaptive frameworks specifically tailored to the unique conditions of conflict environments and targeted training for project managers. Such training should focus on equipping managers with the skills to better address the dynamic challenges presented by conflict situations. The insights gained from this research contribute significantly to the broader field of project management, providing a practical guide for practitioners operating in high-risk areas. By emphasizing sustainable and resilient project outcomes, this study underscores the importance of adaptive management strategies in ensuring the success of projects in conflict-affected regions. The findings serve not only to enhance the understanding of project management practices in Kewot Woreda but also to inform future research and practice in similar contexts, ultimately aiming to promote stability and development in areas beset by conflict.

Keywords: project management practices, operational challenges, conflict zones, adaptive strategies

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Authors: Philip A. Szlosek, M. Susan Guyer, Mary G. Barnum, Elizabeth M. Mullin

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In the United States, athletic training is a healthcare profession that encompasses the prevention, examination, diagnosis, treatment, and rehabilitation of injuries and medical conditions. Athletic trainers work under the direction of or in collaboration with a physician and are recognized by the American Medical Association as allied healthcare professionals. Internationally, this profession is often known as athletic therapy. As healthcare professionals, athletic trainers must be prepared for autonomous practice immediately after graduation. However, new athletic trainers have been shown to have clinical areas of strength and weakness.To better assess professional readiness and improve the preparedness of new athletic trainers, the factors of athletic training professional readiness must be defined. Limited research exists defining the holistic aspects of professional readiness needed for athletic trainers. Confirming the factors of professional readiness in athletic training could enhance the professional preparation of athletic trainers and result in more highly prepared new professionals. The objective of this study was to further explore and confirm the factors of professional readiness in athletic training. Authors useda qualitative design based in grounded theory. Participants included athletic trainers with greater than 24 months of experience from a variety of work settings from each district of the National Athletic Trainer’s Association. Participants took the demographic questionnaire electronically using Qualtrics Survey Software (Provo UT). After completing the demographic questionnaire, 20 participants were selected to complete one-on-one interviews using GoToMeeting audiovisual web conferencing software. IBM Statistical Package for the Social Sciences (SPSS, v. 21.0) was used to calculate descriptive statistics for participant demographics. The first author transcribed all interviews verbatim and utilized a grounded theory approach during qualitative data analysis. Data were analyzed using a constant comparative analysis and open and axial coding. Trustworthiness was established using reflexivity, member checks, and peer reviews. Analysis revealed four overarching themes, including management, interpersonal relations, clinical decision-making, and confidence. Management was categorized as athletic training services not involving direct patient care and was divided into three subthemes, including administration skills, advocacy, and time management. Interpersonal Relations was categorized as the need and ability of the athletic trainer to properly interact with others. Interpersonal relations was divided into three subthemes, including personality traits, communication, and collaborative practice. Clinical decision-making was categorized as the skills and attributes required by the athletic trainer whenmaking clinical decisions related to patient care. Clinical decision-making was divided into three subthemes including clinical skills, continuing education, and reflective practice. The final theme was confidence. Participants discussed the importance of confidence regarding relationships building, clinical and administrative duties, and clinical decision-making. Overall, participants explained the value of a well-rounded athletic trainer and emphasized that athletic trainers need communication and organizational skills, the ability to collaborate, and must value self-reflection and continuing education in addition to having clinical expertise. Future research should finalize a comprehensive model of professional readiness for athletic training, develop a holistic assessment instrument for athletic training professional readiness, and explore the preparedness of new athletic trainers.

Keywords: autonomous practice, newly certified athletic trainer, preparedness for professional practice, transition to practice skills

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Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Hsing-Hua Stella Chang, Mong-Ching Lin, Cher-Min Fong

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There has recently been a notable rise in the number of emerging-market industrial small and medium-sized enterprises (SMEs) that have managed to upgrade their operations. Evolving from original equipment manufacturing (OEM) into value-added original or own brand manufacturing (OBM) in such firms represents a specific process of internationalization. The OEM-OBM upgrade requires development of a firm’s own brand. In this respect, the extant literature points out that emerging-market industrial marketers (latecomers) have developed some marketing capabilities, of which branding has been identified as one of the most important. In specific, an industrial non-brand marketer (OEM) marks the division of labor between manufacturing and branding (as part of marketing). In light of this discussion, this research argues that branding capability plays a critical role in supporting the evolution of manufacture upgrade. This is because a smooth transformation from OEM to OBM entails the establishment of strong brands through which branding capability is developed. Accordingly, branding capability can be exemplified as a series of processes and practices in relation to mobilizing branding resources and orchestrating branding activities, which will result in the establishment of business relationships, greater acceptance of business partners (channels, suppliers), and increased industrial brand equity in the firm as key resource advantages). For the study purpose, Taiwan was chosen as the research context, representing a typical case that exemplifies the industrial development path of more-established emerging markets, namely, transformation from OEM to OBM. This research adopted a two-phase research design comprising exploratory (a qualitative study) and confirmatory approaches (a survey study) The findings show that: Country-specific advantage is positively related to branding capability for internationalizing SMEs. Firm-specific advantage is positively related to branding capability for internationalizing SMEs. Hsing-Hua Stella Chang is Assistant Professor with National Taichung University of Education, International Master of Business Administration, (Yingcai Campus) No.227, Minsheng Rd., West Dist., Taichung City 40359, Taiwan, R.O.C. (phone: 886-22183612; e-mail: [email protected]). Mong-Ching Lin is PhD candidate with National Sun Yat-Sen University, Department of Business Management, 70 Lien-hai Rd., Kaohsiung 804, Taiwan, R.O.C. (e-mail: [email protected]). Cher-Min Fong is Full Professor with National Sun Yat-Sen University, Department of Business Management, 70 Lien-hai Rd., Kaohsiung 804, Taiwan, R.O.C. (e-mail: [email protected]). Branding capability is positively related to international performance for internationalizing SMEs. This study presents a pioneering effort to distinguish industrial brand marketers from non-brand marketers in exploring the role of branding capability in the internationalizing small and medium-sized industrial brand marketers from emerging markets. Specifically, when industrial non-brand marketers (OEMs) enter into a more advanced stage of internationalization (i.e., OBM), they must overcome disadvantages (liabilities of smallness, foreignness, outsidership) that do not apply in the case of incumbent developed-country MNEs with leading brands. Such critical differences mark the urgency and significance of distinguishing industrial brand marketers from non-brand marketers on issues relating to their value-adding branding and marketing practices in international markets. This research thus makes important contributions to the international marketing, industrial branding, and SME internationalization literature.

Keywords: brand marketers, branding capability, emerging markets, SME internationalization

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Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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Authors: Oleg Shovkovyy

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This research conducted in response to one of the most pressing questions on the agenda of many public administration offices around the world: “What could be done for better integration and assimilation of immigrants into hosting communities?” In author’s view, the answer could be suggested by immigrants themselves. They, often ‘bogged down in the past,’ snared by own idols and demons, perceive things differently, which, in turn, may result in their inability to integrate smoothly into hosting communities. Brief literature review suggests that perceptions of immigrants are completely neglected or something unsought in the current research on migrants, which, often, based on opinion polls by members of hosting communities themselves or superficial research data by various research organizations. Even those specimens that include voices of immigrants, unlikely to shed any additional light onto the problem simply because certain things are not made to speak out loud, especially to those in whose hands immigrants’ fate is (authorities). In this regard, this qualitative study, conducted by an insider to a few Russian-speaking communities, represents a unique opportunity for all stakeholders to look at the question of integration through the eyes of immigrants, from a different perspective and thus, makes research findings especially valuable for better understanding of the problem. Case study research employed ethnographic methods of gathering data where, approximately 200 Russian-speaking immigrants of first and second generations were closely observed by the Russian-speaking researcher in their usual setting, for eight months, and at different venues. The number of informal interviews with 27 key informants, with whom the researcher managed to establish a good rapport and who were keen enough to share their experiences voluntarily, were conducted. The field notes were taken at 14 locations (study sites) within the Brisbane region of Queensland, Australia. Moreover, all this time, researcher lived in dwelling of one of the immigrants and was an active participant in the social life (worship, picnics, dinners, weekend schools, concerts, cultural events, social gathering, etc.) of observed communities, whose members, to a large extent, belong to various religious lines of the Russian and Protestant Church. It was found that the majority of immigrants had experienced some discrimination in matters of hiring, employment, recognition of educational qualifications from home countries, and simply felt a sort of dislike from society in various everyday situations. Many noted complete absences or very limited state assistance in terms of employment, training, education, and housing. For instance, the Australian Government Department of Human Services not only does not stimulate job search but, on the contrary, encourages to refuse short-term works and employment. On the other hand, offered free courses on adaptation, and the English language proved to be ineffective and unpopular amongst immigrants. Many interviewees have reported overstated requirements for English proficiency and local work experience, whereas it was not critical for the given task or job. Based on the result of long-term monitoring, the researcher also had the courage to assert the negative and decelerating roles of immigrants’ communities, particularly religious communities, on processes of integration and assimilation. The findings suggest that governments should either change current immigration policies in the direction of their toughening or to take more proactive and responsible role in dealing with immigrant-related issues; for instance, increasing assistance and support to all immigrants and probably, paying more attention to and taking stake in managing and organizing lives of immigrants’ communities rather, simply leaving it all to chance.

Keywords: Australia, immigration, integration, perceptions

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Hao Huang

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INTRODUCTION: The Association of American Colleges and Universities (AACU) recommends the development of ‘high-impact practices,’ in an effort to increase rates of student retention and student engagement at undergraduate institutions. To achieve these goals, the Scripps College Humanities Institute and HI Fellows Seminar not only featured distinguished academics presenting their scholarship about current immigration policy and its consequences in the USA and around the world but integrated socially significant community leaders and creative activists/artivists in public talks, student workshops and collaborative art events. Students participated in experiential learning that involved guest personal presentations and discussions, oral history interviews that applied standard oral history methodologies, detailed cultural documentation, collaborative artistic interventions, and weekly posts in Internet Digital Learning Environment Sakai collaborative course forums and regular responses to other students’ comments. Our teaching pedagogies addressed the four learning styles outlined in Kolb’s Learning Style Inventory. PROJECT DESCRIPTION: Over the academic year 2017-18, the Scripps College Humanities Institute and HI Fellows Seminar presented a Fall 2017 topic, ‘The World at Our Doorsteps: Immigration and Deportation in Los Angeles’. Our purpose was to address how current federal government anti-immigration measures have affected many students of color, some of whom are immigrants, many of whom are related to and are friends with people who are impacted by the attitudes as well as the practices of the U.S. Citizenship and Immigration Services. In Spring 2018, we followed with the topic, ‘Exclusive Nationalisms: Global Migration and Immigration’. This addresses the rise of white supremacists who have ascended to position of power worldwide, in America, Europe, Russia, and xenophobic nationalisms in China, Myanmar and the Philippines. Recent scholarship has suggested the existence of categories of refugees beyond the political or social, who fit into the more inclusive category of migrants. ASSESSMENT METHODOLOGIES: Assessment methodologies not only included qualitative student interviews and quantitative student evaluations in standard rubric format, but also Outcome Assessments, Formative Evaluations, and Outside Guest Teacher feedback. These indicated that the most effective educational practices involved collaborative inquiry in undergraduate research, community-based learning, and capstone projects. Assessments of E-portfolios, written and oral coursework, and final creative projects with associated 10-12 page analytic paper revealed that students developed their understanding of how government and social organizations work; they developed communication skills that enhanced working with others from different backgrounds; they developed their ability to thoughtfully evaluate their course performance by adopting reflective practices; they gained analytic and interpretive skills that encouraged self-confidence and self- initiative not only academically, but also with regards to independent projects. CONCLUSION: Most importantly, the Scripps Humanities Institute experiential learning project spurred on real-world actions by our students, such as a public symposium on how to cope with bigots, a student tutoring program for immigrant staff children, student negotiations with the administration to establish meaningful, sustainable diversity and inclusion programs on-campus. Activism is not only to be taught to and for our students– it has to be enacted by our students.

Keywords: immigration, migration, human rights, learning assessment

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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: Olga Kononova, Sergey Lyapin

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Global information society requirements are transparency and reliability of data, as well as ability to manage information resources independently; particularly to search, to analyze, to evaluate information, thereby obtaining new expertise. Moreover, it is satisfying the society information needs that increases the efficiency of the enterprise management and public administration. The study of structurally organized thematic and semantic contexts of different types, automatically extracted from unstructured data, is one of the important tasks for the application of information technologies in education, science, culture, governance and business. The objectives of this study are the contextual knowledge typologization, selection or creation of effective tools for extracting and analyzing contextual knowledge. Explication of various kinds and forms of the contextual knowledge involves the development and use full-text search information systems. For the implementation purposes, the authors use an e-library 'Humanitariana' services such as the contextual search, different types of queries (paragraph-oriented query, frequency-ranked query), automatic extraction of knowledge from the scientific texts. The multifunctional e-library «Humanitariana» is realized in the Internet-architecture in WWS-configuration (Web-browser / Web-server / SQL-server). Advantage of use 'Humanitariana' is in the possibility of combining the resources of several organizations. Scholars and research groups may work in a local network mode and in distributed IT environments with ability to appeal to resources of any participating organizations servers. Paper discusses some specific cases of the contextual knowledge explication with the use of the e-library services and focuses on possibilities of new types of the contextual knowledge. Experimental research base are science texts about 'e-government' and 'computer games'. An analysis of the subject-themed texts trends allowed to propose the content analysis methodology, that combines a full-text search with automatic construction of 'terminogramma' and expert analysis of the selected contexts. 'Terminogramma' is made out as a table that contains a column with a frequency-ranked list of words (nouns), as well as columns with an indication of the absolute frequency (number) and the relative frequency of occurrence of the word (in %% ppm). The analysis of 'e-government' materials showed, that the state takes a dominant position in the processes of the electronic interaction between the authorities and society in modern Russia. The media credited the main role in these processes to the government, which provided public services through specialized portals. Factor analysis revealed two factors statistically describing the used terms: human interaction (the user) and the state (government, processes organizer); interaction management (public officer, processes performer) and technology (infrastructure). Isolation of these factors will lead to changes in the model of electronic interaction between government and society. In this study, the dominant social problems and the prevalence of different categories of subjects of computer gaming in science papers from 2005 to 2015 were identified. Therefore, there is an evident identification of several types of contextual knowledge: micro context; macro context; dynamic context; thematic collection of queries (interactive contextual knowledge expanding a composition of e-library information resources); multimodal context (functional integration of iconographic and full-text resources through hybrid quasi-semantic algorithm of search). Further studies can be pursued both in terms of expanding the resource base on which they are held, and in terms of the development of appropriate tools.

Keywords: contextual knowledge, contextual search, e-library services, frequency-ranked query, paragraph-oriented query, technologies of the contextual knowledge extraction

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Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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Authors: Adriana De Serio, Donato Forenza

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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

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Authors: Lolwa Alansari, Hanen Mrabet, Kholoud Khaled, Abdelhamid Azhaghdani, Sufia Athar, Aska Kaima, Zaineb Mhamdia, Zubaria Altaf, Almunzer Zakaria, Tamara Alshadafat

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Introduction: The Obstetrics and Gynecology Emergency Department at Alwakra Hospital has faced significant challenges, which have been further worsened by the impact of the COVID-19 pandemic. These challenges involve issues such as overcrowding, extended wait times, and a notable surge in demand for emergency care services. Moreover, prolonged waiting times have emerged as a primary factor contributing to situations where patients leave without receiving attention, known as left without being seen (LWBS), and unexpectedly abscond. Addressing the issue of insufficient patient mobility in the obstetrics and gynecology emergency department has brought about substantial improvements in patient care, healthcare administration, and overall departmental efficiency. These changes have not only alleviated overcrowding but have also elevated the quality of emergency care, resulting in higher patient satisfaction, better outcomes, and operational rewards. Methodology: The COVID-19 pandemic has served as a catalyst for substantial transformations in the obstetrics and gynecology emergency, aligning seamlessly with the strategic direction of Hamad Medical Corporation (HMC). The fundamental aim of this initiative is to revolutionize the operational efficiency of the OB-GYN ED. To accomplish this mission, a range of transformations has been initiated, focusing on essential areas such as digitizing systems, optimizing resource allocation, enhancing budget efficiency, and reducing overall costs. The project utilized the Plan-Do-Study-Act (PDSA) model, involving a diverse team collecting baseline data and introducing throughput improvements. Post-implementation data and feedback were analysed, leading to the integration of effective interventions into standard procedures. These interventions included optimized space utilization, real-time communication, bedside registration, technology integration, pre-triage screening, enhanced communication and patient education, consultant presence, and a culture of continuous improvement. These strategies significantly reduced waiting times, enhancing both patient care and operational efficiency. Results: Results demonstrated a substantial reduction in overall average waiting time, dropping from 35 to approximately 14 minutes by August 2023. The wait times for priority 1 cases have been reduced from 22 to 0 minutes, and for priority 2 cases, the wait times have been reduced from 32 to approximately 13.6 minutes. The proportion of patients spending less than 8 hours in the OB ED observation beds rose from 74% in January 2022 to over 98% in 2023. Notably, there was a remarkable decrease in LWBS and absconded patient rates from 2020 to 2023. Conclusion: The project initiated a profound change in the department's operational environment. Efficiency became deeply embedded in the unit's culture, promoting teamwork among staff that went beyond the project's original focus and had a positive influence on operations in other departments. This effectiveness not only made processes more efficient but also resulted in significant cost reductions for the hospital. These cost savings were achieved by reducing wait times, which in turn led to fewer prolonged patient stays and reduced the need for additional treatments. These continuous improvement initiatives have now become an integral part of the Obstetrics and Gynecology Division's standard operating procedures, ensuring that the positive changes brought about by the project persist and evolve over time.

Keywords: overcrowding, waiting time, person centered care, quality initiatives

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Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

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Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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