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3 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer
Authors: Ziyad S. Haidar
Abstract:
Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation
Procedia PDF Downloads 912 An Artificial Intelligence Framework to Forecast Air Quality
Authors: Richard Ren
Abstract:
Air pollution is a serious danger to international well-being and economies - it will kill an estimated 7 million people every year, costing world economies $2.6 trillion by 2060 due to sick days, healthcare costs, and reduced productivity. In the United States alone, 60,000 premature deaths are caused by poor air quality. For this reason, there is a crucial need to develop effective methods to forecast air quality, which can mitigate air pollution’s detrimental public health effects and associated costs by helping people plan ahead and avoid exposure. The goal of this study is to propose an artificial intelligence framework for predicting future air quality based on timing variables (i.e. season, weekday/weekend), future weather forecasts, as well as past pollutant and air quality measurements. The proposed framework utilizes multiple machine learning algorithms (logistic regression, random forest, neural network) with different specifications and averages the results of the three top-performing models to eliminate inaccuracies, weaknesses, and biases from any one individual model. Over time, the proposed framework uses new data to self-adjust model parameters and increase prediction accuracy. To demonstrate its applicability, a prototype of this framework was created to forecast air quality in Los Angeles, California using datasets from the RP4 weather data repository and EPA pollutant measurement data. The results showed good agreement between the framework’s predictions and real-life observations, with an overall 92% model accuracy. The combined model is able to predict more accurately than any of the individual models, and it is able to reliably forecast season-based variations in air quality levels. Top air quality predictor variables were identified through the measurement of mean decrease in accuracy. This study proposed and demonstrated the efficacy of a comprehensive air quality prediction framework leveraging multiple machine learning algorithms to overcome individual algorithm shortcomings. Future enhancements should focus on expanding and testing a greater variety of modeling techniques within the proposed framework, testing the framework in different locations, and developing a platform to automatically publish future predictions in the form of a web or mobile application. Accurate predictions from this artificial intelligence framework can in turn be used to save and improve lives by allowing individuals to protect their health and allowing governments to implement effective pollution control measures.Air pollution is a serious danger to international wellbeing and economies - it will kill an estimated 7 million people every year, costing world economies $2.6 trillion by 2060 due to sick days, healthcare costs, and reduced productivity. In the United States alone, 60,000 premature deaths are caused by poor air quality. For this reason, there is a crucial need to develop effective methods to forecast air quality, which can mitigate air pollution’s detrimental public health effects and associated costs by helping people plan ahead and avoid exposure. The goal of this study is to propose an artificial intelligence framework for predicting future air quality based on timing variables (i.e. season, weekday/weekend), future weather forecasts, as well as past pollutant and air quality measurements. The proposed framework utilizes multiple machine learning algorithms (logistic regression, random forest, neural network) with different specifications and averages the results of the three top-performing models to eliminate inaccuracies, weaknesses, and biases from any one individual model. Over time, the proposed framework uses new data to self-adjust model parameters and increase prediction accuracy. To demonstrate its applicability, a prototype of this framework was created to forecast air quality in Los Angeles, California using datasets from the RP4 weather data repository and EPA pollutant measurement data. The results showed good agreement between the framework’s predictions and real-life observations, with an overall 92% model accuracy. The combined model is able to predict more accurately than any of the individual models, and it is able to reliably forecast season-based variations in air quality levels. Top air quality predictor variables were identified through the measurement of mean decrease in accuracy. This study proposed and demonstrated the efficacy of a comprehensive air quality prediction framework leveraging multiple machine learning algorithms to overcome individual algorithm shortcomings. Future enhancements should focus on expanding and testing a greater variety of modeling techniques within the proposed framework, testing the framework in different locations, and developing a platform to automatically publish future predictions in the form of a web or mobile application. Accurate predictions from this artificial intelligence framework can in turn be used to save and improve lives by allowing individuals to protect their health and allowing governments to implement effective pollution control measures.Air pollution is a serious danger to international wellbeing and economies - it will kill an estimated 7 million people every year, costing world economies $2.6 trillion by 2060 due to sick days, healthcare costs, and reduced productivity. In the United States alone, 60,000 premature deaths are caused by poor air quality. For this reason, there is a crucial need to develop effective methods to forecast air quality, which can mitigate air pollution’s detrimental public health effects and associated costs by helping people plan ahead and avoid exposure. The goal of this study is to propose an artificial intelligence framework for predicting future air quality based on timing variables (i.e. season, weekday/weekend), future weather forecasts, as well as past pollutant and air quality measurements. The proposed framework utilizes multiple machine learning algorithms (logistic regression, random forest, neural network) with different specifications and averages the results of the three top-performing models to eliminate inaccuracies, weaknesses, and biases from any one individual model. Over time, the proposed framework uses new data to self-adjust model parameters and increase prediction accuracy. To demonstrate its applicability, a prototype of this framework was created to forecast air quality in Los Angeles, California using datasets from the RP4 weather data repository and EPA pollutant measurement data. The results showed good agreement between the framework’s predictions and real-life observations, with an overall 92% model accuracy. The combined model is able to predict more accurately than any of the individual models, and it is able to reliably forecast season-based variations in air quality levels. Top air quality predictor variables were identified through the measurement of mean decrease in accuracy. This study proposed and demonstrated the efficacy of a comprehensive air quality prediction framework leveraging multiple machine learning algorithms to overcome individual algorithm shortcomings. Future enhancements should focus on expanding and testing a greater variety of modeling techniques within the proposed framework, testing the framework in different locations, and developing a platform to automatically publish future predictions in the form of a web or mobile application. Accurate predictions from this artificial intelligence framework can in turn be used to save and improve lives by allowing individuals to protect their health and allowing governments to implement effective pollution control measures.Keywords: air quality prediction, air pollution, artificial intelligence, machine learning algorithms
Procedia PDF Downloads 1311 Impacts of Transformational Leadership: Petronas Stations in Sabah, Malaysia
Authors: Lizinis Cassendra Frederick Dony, Jirom Jeremy Frederick Dony, Cyril Supain Christopher
Abstract:
The purpose of this paper is to improve the devotion to leadership through HR practices implementation at the PETRONAS stations. This emphasize the importance of personal grooming and Customer Care hospitality training for their front line working individuals and teams’ at PETRONAS stations in Sabah. Based on Thomas Edison, International Leadership Journal, theory, research, education and development practice and application to all organizational phenomena may affect or be affected by leadership. FINDINGS – PETRONAS in short called Petroliam Nasional Berhad is a Malaysian oil and gas company that was founded on August 17, 1974. Wholly owned by the Government of Malaysia, the corporation is vested with the entire oil and gas resources in Malaysia and is entrusted with the responsibility of developing and adding value to these resources. Fortune ranks PETRONAS as the 68th largest company in the world in 2012. It also ranks PETRONAS as the 12th most profitable company in the world and the most profitable in Asia. As of the end of March 2005, the PETRONAS Group comprised 103 wholly owned subsidiaries, 19 partly owned outfits and 57 associated companies. The group is engaged in a wide spectrum of petroleum activities, including upstream exploration and production of oil and gas to downstream oil refining, marketing and distribution of petroleum products, trading, gas processing and liquefaction, gas transmission pipeline network operations, marketing of liquefied natural gas; petrochemical manufacturing and marketing; shipping; automotive engineering and property investment. PETRONAS has growing their marketing channel in a competitive market. They have combined their resources to pursue common goals. PETRONAS provides opportunity to carry out Industrial Training Job Placement to the University students in Malaysia for 6-8 months. The effects of the Industrial Training have exposed them to the real working environment experience acting representing on behalf of General Manager for almost one year. Thus, the management education and reward incentives schemes have aspire the working teams transformed to gain their good leadership. Furthermore, knowledge and experiences are very important in the human capital development transformation. SPSS extends the accurate analysis PETRONAS achievement through 280 questionnaires and 81 questionnaires through excel calculation distributed to interview face to face with the customers, PETRONAS dealers and front desk staffs stations in the 17 stations in Kota Kinabalu, Sabah. Hence, this research study will improve its service quality innovation and business sustainability performance optimization. ORIGINALITY / VALUE – The impact of Transformational Leadership practices have influenced the working team’s behaviour as a Brand Ambassadors of PETRONAS. Finally, the findings correlation indicated that PETRONAS stations needs more HR resources practices to deploy more customer care retention resources in mitigating the business challenges in oil and gas industry. Therefore, as the business established at stiff competition globally (Cooper, 2006; Marques and Simon, 2006), it is crucial for the team management should be capable to minimize noises risk, financial risk and mitigating any other risks as a whole at the optimum level. CONCLUSION- As to conclude this research found that both transformational and transactional contingent reward leadership4 were positively correlated with ratings of platoon potency and ratings of leadership for the platoon leader and sergeant were moderately inter correlated. Due to this identification, we recommended that PETRONAS management should offers quality team management in PETRONAS stations in a broader variety of leadership training specialization in the operation efficiency at the front desk Customer Care hospitality. By having the reliability and validity of job experiences, it leverages diversity teamwork and cross collaboration. Other than leveraging factor, PETRONAS also will strengthen the interpersonal front liners effectiveness and enhance quality of interaction through effective communication. Finally, through numerous CSR correlation studies regression PETRONAS performance on Corporate Social Performance and several control variables.1 CSR model activities can be mis-specified if it is not controllable under R & D which evident in various feedbacks collected from the local communities and younger generation is inclined to higher financial expectation from PETRONAS. But, however, it created a huge impact on the nation building as part of its social adaptability overreaching their business stakeholders’ satisfaction in Sabah.Keywords: human resources practices implementation (hrpi), source of competitive advantage in people’s development (socaipd), corporate social responsibility (csr), service quality at front desk stations (sqafd), impacts of petronas leadership (iopl)
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