Search results for: clinical trial optimization

Authors: Fatmah Almathkour

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Managing and controlling the construction supply chain (CSC) are very important components of effective construction project execution. The goals of managing the CSC are to reduce uncertainty and optimize the performance of a construction project by improving efficiency and reducing project costs. The heart of much SC activity is addressing risk, and the CSC is no different. The delivery and consumption of construction materials is highly variable due to the complexity of construction operations, rapidly changing demand for certain components, lead time variability from suppliers, transportation time variability, and disruptions at the job site. Current notions of managing and controlling CSC, involve focusing on one project at a time with a push-based material ordering system based on the initial construction schedule and, then, holding a tremendous amount of inventory. A two-stage methodology was proposed to coordinate the feed-forward control of advanced order placement with a supplier to a feedback local control in the form of adding the ability to transship materials between projects to improve efficiency and reduce costs. It focused on the single supplier integrated production and transshipment problem with multiple products. The methodology is used as a design tool for the CSC because it includes an external storage site not associated with one of the projects. The idea is to add this feature to a highly constrained environment to explore its effectiveness in buffering the impact of variability and maintaining project schedule at low cost. The methodology uses deterministic optimization models with objectives that minimizing the total cost of the CSC. To illustrate how this methodology can be used in practice and the types of information that can be gleaned, it is tested on a number of cases based on the real example of multiple construction projects in Kuwait.

Keywords: construction supply chain, inventory control supply chain, transshipment

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Authors: Vera Marcantonio, Marcello De Falco, Mauro Capocelli, Álvaro Amado-Fierro, Teresa A. Centeno, Enrico Bocci

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Concerns about energy security, energy prices, and climate change led scientific research towards sustainable solutions to fossil fuel as renewable energy sources coupled with hydrogen as an energy vector and carbon capture and conversion technologies. Among the technologies investigated in the last decades, biomass gasification acquired great interest owing to the possibility of obtaining low-cost and CO₂ negative emission hydrogen production from a large variety of everywhere available organic wastes. Upstream and downstream treatment were then studied in order to maximize hydrogen yield, reduce the content of organic and inorganic contaminants under the admissible levels for the technologies which are coupled with, capture, and convert carbon dioxide. However, studies which analyse a whole process made of all those technologies are still missing. In order to fill this lack, the present paper investigated the coexistence of hydrothermal carbonization (HTC), sorption enhance gasification (SEG), hot gas cleaning (HGC), and CO₂ conversion by dielectric barrier discharge (DBD) plasma reactor for H₂ production from biomass waste by means of Aspen Plus software. The proposed model aimed to identify and optimise the performance of the plant by varying operating parameters (such as temperature, CaO/biomass ratio, separation efficiency, etc.). The carbon footprint of the global plant is 2.3 kg CO₂/kg H₂, lower than the latest limit value imposed by the European Commission to consider hydrogen as “clean”, that was set to 3 kg CO₂/kg H₂. The hydrogen yield referred to the whole plant is 250 gH₂/kgBIOMASS.

Keywords: biomass gasification, hydrogen, aspen plus, sorption enhance gasification

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Authors: Nevila Bardhi, Joanna Magda, Kolapo Alex-Oni, Slavenka Sedlar, Paromita Hore

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The New York City Department of Health and Mental Hygiene (NYC DOHMH) receives blood lead test results for NYC residents and conducts lead poisoning case investigations for individuals with elevated blood lead levels exposed to lead occupationally and non-occupationally. To (1) improve participant engagement, (2) aid the identification of potential lead sources, and (3) better tailor recommendations to reduce lead exposure, Motivational Interviewing (MI) techniques were incorporated during risk assessment interviews of non-pregnant adults by DOHMH’s Adult Lead Poisoning Prevention (ALP) Program. MI is an evidence-based counselling method used in clinical settings that have been effective in promoting behavior change by resolving ambivalence and enhancing motivation in treating both physiological and psychological health conditions. The incorporation of MI techniques in the ALP risk assessment interview was effective in improving the identification of lead sources for non-pregnant adult cases, thus, allowing for the opportunity to better tailor lead poisoning prevention recommendations. The embedding of MI cues in the ALP risk assessment interview also significantly increased engagement in the interview process, resulting in approximately 50 more interviews conducted per year and a decrease in interview refusals during case investigations. Additionally, the pre-MI interview completion rate was 57%, while the post-MI Interview completion rate was 68%. We recommend MI techniques to be used by other lead poisoning prevention programs during lead poisoning investigations in similar diverse populations.

Keywords: lead poisoning prevention, motivational interviewing, behavior change, lead poisoning risk factors, self-efficacy

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Authors: Pamela E. Mukaire

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Anemia and chronic energy deficiency are significant manifestations of poor nutritional health. Anaemia and nutritional status screening are practical ways for assessing the prevalence of iron deficiency anemia in the food insecure populations with large groups of childbearing women and children. The objective of the study was to assess anemia prevalence and other clinical manifestations of malnutrition among pairs of mothers and young children in rural Uganda. This community cross-sectional study used consecutive sampling to select 214 mothers and 214 children for the study. Data was generated using structured questionnaire, anthropometric measurements and on site analysis for anemia. Bivariable and multivariable analyses were used to assess the effect of different factors on anaemia. Of the 214 mothers, 54.2% were 25-34 years of age, 76.7% unmarried, 63% low income, and 55% had more than four children. Of the 214 children, 57% were female, 50% between 1 to 3 years of age and 35% under one year, and. Overall, 38% of the households had more 4 children under the age of 12. The prevalence of anemia was 48% for mothers and 72% for children; 20.6% of mothers had moderate to severe chronic energy deficiency, 39% had moderately-severe anaemia (10 to 7.1 g/dL). Among children, 53% had moderately-severe anaemia, and 18.2% had severe anaemia. Parity X2 =20, p < .037, number of children under 12 years living in a household X2 =10, p < .015, and child’s gender X2 =6.5, p < .038, had a significant relationship with maternal anaemia. There was a significant relationship between household income X2 =10, p < .005, marital status X2 =9, p < .011, owing a piece of land X2 =18, p < .000, owing home X2 =7, p < .036, and anaemia in children. The prevalence of anemia was high in both mothers and children. Income, marital status, owing a piece of land, owing home, number of children under age 12 in a household were associated with anaemia. Hence, efforts should be made for early diagnosis and management of anaemia deficiencies with special emphasis on those households with large number of children under age 12.

Keywords: anemia, maternal-child, nutrition, rural population

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Authors: P. H. Tee, S. M. Zamri, K. M. Kasim, S. K. Tiew

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This study evaluates the management of osteoporosis in a tertiary care government hospital in Malaysia. As the number of admitted patients having osteoporotic fractures is on the rise, osteoporotic medications are an increasing financial burden to government hospitals because they account for half of the orthopedic budget and expenditure. Comprehensive knowledge among practitioners is important to detect early and avoid this preventable disease and its serious complications. The purpose of this study is to evaluate the awareness, knowledge, and practices in managing osteoporosis among practitioners in Hospital Tengku Ampuan Rahimah (HTAR), Klang. A questionnaire from an overseas study in managing osteoporosis among primary care physicians is adapted to Malaysia’s Clinical Practice Guideline of Osteoporosis 2012 (revised 2015) and international guidelines were distributed to all orthopedic practitioners in HTAR Klang (including surgeons, orthopedic medical officers), endocrinologists, rheumatologists and geriatricians. The participants were evaluated on their expertise in the diagnosis, prevention, treatment decision and medications for osteoporosis. Collected data were analyzed for all descriptive and statistical analyses as appropriate. All 45 participants responded to the questionnaire. Participants scored highest on expertise in prevention, followed by diagnosis, treatment decision and lastly, medication. Most practitioners stated that own-initiated continuing professional education from articles and books was the most effective way to update their knowledge, followed by attendance in conferences on osteoporosis. This study confirms the importance of comprehensive training and education regarding osteoporosis among tertiary care physicians and surgeons, predominantly in pharmacotherapy, to deliver wholesome care for osteoporotic patients.

Keywords: awareness, knowledge, osteoporosis, practices

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Authors: F. Lazzeri, I. Reiter

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Energy production optimization has been traditionally very important for utilities in order to improve resource consumption. However, load forecasting is a challenging task, as there are a large number of relevant variables that must be considered, and several strategies have been used to deal with this complex problem. This is especially true also in microgrids where many elements have to adjust their performance depending on the future generation and consumption conditions. The goal of this paper is to present a solution for short-term load forecasting in microgrids, based on three machine learning experiments developed in R and web services built and deployed with different components of Cortana Intelligence Suite: Azure Machine Learning, a fully managed cloud service that enables to easily build, deploy, and share predictive analytics solutions; SQL database, a Microsoft database service for app developers; and PowerBI, a suite of business analytics tools to analyze data and share insights. Our results show that Boosted Decision Tree and Fast Forest Quantile regression methods can be very useful to predict hourly short-term consumption in microgrids; moreover, we found that for these types of forecasting models, weather data (temperature, wind, humidity and dew point) can play a crucial role in improving the accuracy of the forecasting solution. Data cleaning and feature engineering methods performed in R and different types of machine learning algorithms (Boosted Decision Tree, Fast Forest Quantile and ARIMA) will be presented, and results and performance metrics discussed.

Keywords: time-series, features engineering methods for forecasting, energy demand forecasting, Azure Machine Learning

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Authors: Zheng Ruoyuan

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With the rapid development of economic globalization and increasingly fierce international competition, multinational companies have carried out investment strategy shifts and innovations, and actively promoted localization strategies. Localization strategies have become the main trend in the development of multinational companies. Large-scale entry of multinational companies China has a history of more than 20 years. With the sustained and steady growth of China's economy and the optimization of the investment environment, multinational companies' investment in China has expanded rapidly, which has also had an important impact on the Chinese economy: promoting employment, foreign exchange reserves, and improving the system. etc., has brought a lot of high-tech and advanced management experience; but it has also brought challenges and survival pressure to China's local enterprises. In recent years, multinational companies have gradually regarded China as an important part of their global strategies and began to invest in China. Actively promote localization strategies, including production, marketing, scientific research and development, etc. Many multinational companies have achieved good results in localized operations in China. Not only have their benefits continued to improve, but they have also established a good corporate image and brand in China. image, which has greatly improved their competitiveness in the international market. However, there are also some multinational companies that have difficulties in localized operations in China. This article will closely follow the background of economic globalization and comprehensively use the theory of multinational companies and strategic management theory and business management theory, using data and facts as the entry point, combined with typical cases of representative significance for analysis, to conduct a systematic study of the localized operations of multinational companies in China. At the same time, for each specific link of the operation of multinational companies, we provide multinational enterprises with some inspirations and references.

Keywords: localization, business management, multinational, marketing

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Authors: Boukhatem Mohamed Nadjib, Ferhat Mohamed Amine

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Essential Oils (EO) produced by medicinal plants have been traditionally used for respiratory tract infections and are used nowadays as ethical medicines for colds. The aim of this study was to test the efficacy of the Algerian EGEO against some respiratory tract pathogens by disc diffusion and vapour diffusion methods at different concentrations. The chemical composition of the EGEO was analysed by Gas Chromatography-Mass Spectrometry. Fresh leaves of E. globulus on steam distillation yielded 0.96% (v/w) of essential oil whereas the analysis resulted in the identification of a total of 11 constituents, 1.8 cineole (85.8%), α-pinene (7.2%) and β-myrcene (1.5%) being the main components. By disc diffusion method, EGEO showed potent antimicrobial activity against Gram-positive more than Gram-negative bacteria. The Diameter of Inhibition Zone (DIZ) varied from 69 mm to 75 mm for Staphylococcus aureus and Bacillus subtilis (Gram +) and from 13 to 42 mm for Enterobacter sp and Escherichia coli (Gram-), respectively. However, the results obtained by both agar diffusion and vapour diffusion methods were different. Significantly higher antibacterial activity was observed in the vapour phase at lower concentrations. A. baumanii and Klebsiella pneumoniae were the most susceptible strains to the oil vapour with DIZ varied from 38 to 42 mm. Therefore, smaller doses of EO in the vapour phase can be inhibitory to pathogenic bacteria. Else, the DIZ increased with increase in the concentration of the oil. There is growing evidence that EGEO in the vapour phase are effective antibacterial systems and appears worthy to be considered for practical uses in the treatment or prevention of patients with respiratory tract infections or as air decontaminants in the hospital. The present study indicates that EGEO has considerable antimicrobial activity, deserving further investigation for clinical applications.

Keywords: eucalyptus globulus, essential oils, respiratory tract pathogens, antimicrobial activity, vapour phase

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Authors: Nagui A. Abdel-Khalek, Khaled A. Selim, Ahmed Hamdy

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Kaolin is naturally occurring ore predominantly containing kaolinite mineral in addition to some gangue minerals. Typical impurities present in kaolin ore are quartz, iron oxides, titanoferrous minerals, mica, feldspar, organic matter, etc. The main coloring impurity, particularly in the ultrafine size range, is titanoferrous minerals. Kaolin is used in many industrial applications such as sanitary ware, table ware, ceramic, paint, and paper industries, each of which should be of certain specifications. For most industrial applications, kaolin should be processed to obtain refined clay so as to match with standard specifications. For example, kaolin used in paper and paint industries need to be of high brightness and low yellowness. Egyptian kaolin is not subjected to any beneficiation process and the Egyptian companies apply selective mining followed by, in some localities, crushing and size reduction only. Such low quality kaolin can be used in refractory and pottery production but not in white ware and paper industries. This paper aims to study the amenability of beneficiation of an Egyptian kaolin ore of El-Teih locality, Sinai, to be suitable for different industrial applications. Attrition scrubbing and classification followed by magnetic separation are applied to remove the associated impurities. Attrition scrubbing and classification are used to separate the coarse silica and feldspars. Wet high intensity magnetic separation was applied to remove colored contaminants such as iron oxide and titanium oxide. Different variables affecting of magnetic separation process such as solid percent, magnetic field, matrix loading capacity, and retention time are studied. The results indicated that substantial decrease in iron oxide (from 1.69% to 0.61% ) and TiO2 (from 3.1% to 0.83%) contents as well as improving iso-brightness (from 63.76% to 75.21% and whiteness (from 79.85% to 86.72%) of the product can be achieved.

Keywords: Kaolin, titanoferrous minerals, beneficiation, magnetic separation, attrition scrubbing, classification

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Authors: Donatella Giuliani

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In this research, we propose an unsupervised grayscale image segmentation method based on a combination of the Firefly Algorithm and the Gaussian Mixture Model. Firstly, the Firefly Algorithm has been applied in a histogram-based research of cluster means. The Firefly Algorithm is a stochastic global optimization technique, centered on the flashing characteristics of fireflies. In this context it has been performed to determine the number of clusters and the related cluster means in a histogram-based segmentation approach. Successively these means are used in the initialization step for the parameter estimation of a Gaussian Mixture Model. The parametric probability density function of a Gaussian Mixture Model is represented as a weighted sum of Gaussian component densities, whose parameters are evaluated applying the iterative Expectation-Maximization technique. The coefficients of the linear super-position of Gaussians can be thought as prior probabilities of each component. Applying the Bayes rule, the posterior probabilities of the grayscale intensities have been evaluated, therefore their maxima are used to assign each pixel to the clusters, according to their gray-level values. The proposed approach appears fairly solid and reliable when applied even to complex grayscale images. The validation has been performed by using different standard measures, more precisely: the Root Mean Square Error (RMSE), the Structural Content (SC), the Normalized Correlation Coefficient (NK) and the Davies-Bouldin (DB) index. The achieved results have strongly confirmed the robustness of this gray scale segmentation method based on a metaheuristic algorithm. Another noteworthy advantage of this methodology is due to the use of maxima of responsibilities for the pixel assignment that implies a consistent reduction of the computational costs.

Keywords: clustering images, firefly algorithm, Gaussian mixture model, meta heuristic algorithm, image segmentation

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Authors: X. Han, S. Duan, C. Liu, C. Zhou, W. Zhu, L. Kong

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The ionic imprinting technique refers to the three-dimensional rigid structure with the fixed pore sizes, which was formed by the binding interactions of ions and functional monomers and used ions as the template, it has a high level of recognition to the ionic template. The preparation of monolithic column by the in-situ polymerization need to put the compound of template, functional monomers, cross-linking agent and initiating agent into the solution, dissolve it and inject to the column tube, and then the compound will have a polymerization reaction at a certain temperature, after the synthetic reaction, we washed out the unread template and solution. The monolithic columns are easy to prepare, low consumption and cost-effective with fast mass transfer, besides, they have many chemical functions. But the monolithic columns have some problems in the practical application, such as low-efficiency, quantitative analysis cannot be performed accurately because of the peak shape is wide and has tailing phenomena; the choice of polymerization systems is limited and the lack of theoretical foundations. Thus the optimization of components and preparation methods is an important research direction. During the preparation of ionic imprinted monolithic columns, pore-forming agent can make the polymer generate the porous structure, which can influence the physical properties of polymer, what’ s more, it can directly decide the stability and selectivity of polymerization reaction. The compounds generated in the pre-polymerization reaction could directly decide the identification and screening capabilities of imprinted polymer; thus the choice of pore-forming agent is quite critical in the preparation of imprinted monolithic columns. This article mainly focuses on the research that when using different pore-forming agents, the impact of zinc ion imprinted monolithic column on the enrichment performance of zinc ion.

Keywords: high performance liquid chromatography (HPLC), ionic imprinting, monolithic column, pore-forming agent

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Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

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Diabetes mellitus type 2 (DM2) prevalence, is increasing on the world, in Brazil is considered a public health problem. Treatment focuses on glycemic control depending primarily of lifestyle changes - not drug treatment (NDT), may involve drug therapy (DT) and requires continuous health monitoring. In Brazil this monitoring is performed by the Unified Health System (SUS) through Primary Health Care (PHC), which stimulate people with DM2 empowerment for care management. SUS was approved in 1988 and the PHC operationalization was strengthened with the creation of the Family Health Strategy (FHS) in 1994. Our aim was to analyze the people with DM2 participation in front of the care management health monitoring in the FHS. Qualitative research was carried out through non-participant observation of attendance of 25 people with DM2 in the FHS and interviewed at home. Ethical guidelines were followed. It was found that people with DM2 only follow professionals’ recommendations that make sense according to their own conceptions of health/disease; most of them emphasize the importance of (DT) with little emphasis on the NDT, was found great difficulty in the NDT and lack of knowledge about the disease and care. As regards monitoring the FHS, were observed therapeutic practices based on the bio medical model, although the APS search for another care perspective; NDT is not systematically accompanied by the health team and takes place a few educational activities on the DM2 in the FHS, with low user adoption. The work of the FHS is done by multidisciplinary teams, but we see the need for greater participation of nurses in clinical-care follow-up of this population and may also act in adapting to the NDT. Finally we emphasize the need for professional practices that consider the difficulties to care management by people with DM2, especially because of the NDT. It is noticed that the measures recommended by the FHS professionals are not always developed by people with DM2. We must seek the empowerment of people with DM2 to manage the form of care associated with the FHS team, seeking to reduce the incidence of complications and higher quality of life.

Keywords: diabetes mellitus, primary health care, nursing, management of care

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Fedili Benamar, Beloulou Mohamed Lamine, Ouahes Hassane, Ghattas Samir

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Background and aims: While in Western countries, unilateral spinal anesthesia has been widely practiced for a long time, it remains little known in the local anesthesia community, and has not been the object of many studies. However, it is a simple, practical and effective technique. Our objective was to evaluate this practice in emergency anesthesia management in frail patients and to compare it with conventional spinal anesthesia. Methods: This is a prospective, observational, comparative study between hypobaric unilateral and conventional spinal anaesthesia for hip fracture surgery carried out in the operating room of the university military hospital of Staoueli. The work was spread over of 12-month period from 2019 to 2020. The parameters analyzed were hemodynamic variations, vasopressor use, block efficiency, postoperative adverse events, and postoperative morphine consumption. Results: -75 cases (mean age 72±14 years) -Group1= 41 patients (54.6%) divided into (ASA1=14.6% ASA2=60.98% ASA3=24.39%) single shoot spinal anaesthesia -Group2= 34 patients (45.3%) divided into (ASA1=2.9%, ASA2=26.4% ASA3=61.7%, ASA4=8.8%) unilateral hypobaric spinal anesthesia. -Hemodynamic variations were more severe in group 1 (51% hypotension) compared to 30% in group 2 RR=1.69 and odds ratio=2.4 -these variations were more marked in the ASA3 subgroup (group 1=70% hypotension versus group 2=30%) with an RR=2.33 and an odds ratio=5.44 -39% of group 1 required vasoactive drugs (15mg +/- 11) versus 32% of group 2 (8mg+/- 6.49) - no difference in the use of morphine in post-op. Conclusions: Within the limits of the population studied, this work demonstrates the clinical value of unilateral spinal anesthesia in ortho-trauma surgery in the frail patient.

Keywords: spinal anaesthesia, vasopressor, morphine, hypobaric unilateral spinal anesthesia, ropivacaine, hip surgery, eldery, hemodynamic

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Authors: Hande Yesil, Seda Aycan Altan, M. Vehbi Bal, Alper Uyar, O. Cumhur Sipahi

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Purpose: Fixed partial dentures (FPDs) must fulfill functional requirements such as phonetics, chewing efficiency and esthetics especially in the anterior region. A convex type tissue surface is usually recommended for pontics of FPDs. That pontic design also provides suitable oral hygiene and ease of cleaning. However, high esthetic requirements and correct emergence profile are not always achievable because of the convex shape of adjacent soft tissues. Therefore, the ovate type pontic which fulfills the high esthetic demands of the patients may be a good alternative to the modified ridge lap pontic design. Clinical Report: A female patient referred with the complaint of anterior upper edentulousness. In the oral examination it was determined that teeth 11, 12, 21, 22 were deficient. A thick and convex gingival tissue that may cause aesthetic problems was also observed.. Periodontal augmentation surgery was performed to ensure proper papillary configuration and gingival contour. An interim removable partial denture (IRPD) which applied pressure to operated gingival tissues was fabricated postoperatively. The IRPD was used for 4 weeks and after completion of tissue sculpting, the permanent FPD with an ovate pontic was fabricated and cemented. After a follow-up period of 6 months, not any esthetical and hygienic problem was detected and the patient was satisfied with her prosthesis. Conclusion: It was concluded that shaping of gingival contours with IRPD and use of a FPD with ovate pontic fulfills all esthetic and hygienic requirements.

Keywords: interim appliance, ovate pontic, tissue sculpturing, fixed partial denture

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Authors: Nesreddine Djafar Henni, Akram Khelaifia, Salah Guettala, Rachid Chebili

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Reinforced concrete shear walls and vertical plate-like elements play a pivotal role in efficiently managing a building's response to seismic forces. This study investigates how the performance of reinforced concrete buildings equipped with shear walls featuring different shear wall-to-frame stiffness ratios aligns with the requirements stipulated in the Algerian seismic code RPA99v2003, particularly in high-seismicity regions. Seven distinct 3D finite element models are developed and evaluated through nonlinear static analysis. Engineering Demand Parameters (EDPs) such as lateral displacement, inter-story drift ratio, shear force, and bending moment along the building height are analyzed. The findings reveal two predominant categories of induced responses: force-based and displacement-based EDPs. Furthermore, as the shear wall-to-frame ratio increases, there is a concurrent increase in force-based EDPs and a decrease in displacement-based ones. Examining the distribution of shear walls from both force and displacement perspectives, model G with the highest stiffness ratio, concentrating stiffness at the building's center, intensifies induced forces. This configuration necessitates additional reinforcements, leading to a conservative design approach. Conversely, model C, with the lowest stiffness ratio, distributes stiffness towards the periphery, resulting in minimized induced shear forces and bending moments, representing an optimal scenario with maximal performance and minimal strength requirements.

Keywords: dual RC buildings, RC shear walls, modeling, static nonlinear pushover analysis, optimization, seismic performance

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Authors: Dimitra V. Peristeri, Hussameldin M. Nour, Amiya Ahsan, Sameh Abogabal, Krishna K. Singh, Muhammad Shafique Sajid

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Introduction: The use of optimal skin antiseptic agents for the prevention of surgical site infection (SSI) is of critical importance, especially during abdominal surgical procedures. Alcohol-based chlorhexidine gluconate (CHG) and aqueous-based povidone-iodine (PVI) are the two most common skin antiseptics used nowadays. The objective of this article is to evaluate the effectiveness of alcohol-based CHG versus aqueous-based PVI used for skin preparation before abdominal surgery to reduce SSIs. Methods: Standard medical databases such as MEDLINE, Embase, Pubmed, and Cochrane Library were searched to find randomised, controlled trials (RCTs) comparing alcohol-based CHG skin preparation versus aqueous-based PVI in patients undergoing abdominal surgery. The combined outcomes of SSIs were calculated using an odds ratio (OR) with 95% confidence intervals (95% CI). All data were analysed using Review Manager (RevMan) Software 5.4, and the meta-analysis was performed with a random effect model analysis. Results: A total of 11 studies, all RCTs, were included (n= 12072 participants), recruiting adult patients undergoing abdominal surgery. In the random effect model analysis, the use of alcohol-based CHG in patients undergoing abdominal surgery was associated with a reduced risk of SSI compared to aqueous-based PVI (OR: 0.84; 95% CI [0.74, 0.96], z= 2.61, p= 0.009). Conclusion: Alcohol-based CHG may be more effective for preventing the risk of SSI compared to aqueous-based PVI agents in abdominal surgery. The conclusion of this meta-analysis may add a guiding value to reinforce current clinical practice guidelines.

Keywords: skin preparation, surgical site infection, chlorhexidine, skin antiseptics

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Authors: Wadsana Sarakarn, Pimonpan Charoensri, Baliya Chaiyara

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Objectives: To study the outcomes of the developed nursing model to prevent early postpartum hemorrhage (PPH). Materials and Methods: The analytical study was conducted in Sunpasitthiprasong Hospital during October 1st, 2015, until May 31st, 2017. After review the prevalence, risk factors, and outcomes of postpartum hemorrhage of the parturient who gave birth in Sunpasitthiprasong Hospital, the nursing model was developed under research regulation of Kemmis&McTaggart using 4 steps of operating procedures: 1) analyzing problem situation and gathering 2) creating the plan 3) noticing and performing 4) reflecting the result of the operation. The nursing model consisted of the screening tools for risk factors associated with PPH, the clinical nursing practice guideline (CNPG), and the collecting bag for measuring postpartum blood loss. Primary outcome was early postpartum hemorrhage. Secondary outcomes were postpartum hysterectomy, maternal mortality, personnel’s practice, knowledge, and satisfaction of the nursing model. The data were analyzed by using content analysis for qualitative data and descriptive statistics for quantitative data. Results: Before using the nursing model, the prevalence of early postpartum hemorrhage was under estimated (2.97%). There were 5 cases of postpartum hysterectomy and 2 cases of maternal death due to postpartum hemorrhage. During the study period, there was 22.7% prevalence of postpartum hemorrhage among 220 pregnant women who were vaginally delivered at Sunpasitthiprasong Hospital. No maternal death or postpartum hysterectomy was reported after using the nursing model. Among 16 registered nurses at the delivery room who evaluated using of the nursing model, they reported the high level of practice, knowledge, and satisfaction Conclusion: The nursing model for the prevention of early PPH is effective to decrease early PPH and other serious complications.

Keywords: the development of a nursing model, prevention of postpartum hemorrhage, pregnant women, postpartum hemorrhage

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Authors: William L. Whitehouse, Louisa H. Y. Lo, Andrew B. Kinghorn, Simon C. C. Shiu, Julian. A. Tanner

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C-reactive protein (CRP) is an acute-phase reactant and sensitive indicator for sepsis and other life-threatening pathologies, including systemic inflammatory response syndrome (SIRS). Currently, clinical turn-around times for established CRP detection methods take between 30 minutes to hours or even days from centralized laboratories. Here, we report the development of an electrochemical biosensor using redox probe-tagged DNA aptamers functionalized onto cheap, commercially available screen-printed electrodes. Binding-induced conformational switching of the CRP-targeting aptamer induces a specific and selective signal-ON event, which enables single-step and reagentless detection of CRP in as little as 1 minute. The aptasensor dynamic range spans 5-1000nM (R=0.97) or 5-500nM (R=0.99) in 50% diluted human serum, with a LOD of 3nM, corresponding to 2-orders of magnitude sensitivity under the clinically relevant cut-off for CRP. The sensor is stable for up to one week and can be reused numerous times, as judged from repeated real-time dosing and dose-response assays. By decoupling binding events from the signal induction mechanism, structure-switching electrochemical aptamer-based sensors (SS-EABs) provide considerable advantages over their adsorption-based counterparts. Our work expands on the retinue of such sensors reported in the literature and is the first instance of an SS-EAB for reagentless CRP detection. We hope this study can inspire further investigations into the suitability of SS-EABs for diagnostics, which will aid translational R&D toward fully realized devices aimed at point-of-care applications or for use more broadly by the public.

Keywords: structure-switching, C-reactive protein, electrochemical, biosensor, aptasensor.

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Authors: Pompilia Buzatu, Hazim Qiblawey, Albert Odai, Jana Jamaleddin, Mustafa Nasser, Simon J. Judd

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Membrane bioreactor (MBR) technology is challenged by the tendency for the membrane permeability to decrease due to ‘clogging’. Clogging includes ‘sludging’, the filling of the membrane channels with sludge solids, and ‘ragging’, the aggregation of short filaments to form long rag-like particles. Both sludging and ragging demand manual intervention to clear out the solids, which is time-consuming, labour-intensive and potentially damaging to the membranes. These factors impact on costs more significantly than membrane surface fouling which, unlike clogging, is largely mitigated by the chemical clean. However, practical evaluation of MBR clogging has thus far been limited. This paper presents the results of recent work attempting to quantify sludging and clogging based on simple bench-scale tests. Results from a novel ragging simulation trial indicated that rags can be formed within 24-36 hours from dispersed < 5 mm-long filaments at concentrations of 5-10 mg/L under gently agitated conditions. Rag formation occurred for both a cotton wool standard and samples taken from an operating municipal MBR, with between 15% and 75% of the added fibrous material forming a single rag. The extent of rag formation depended both on the material type or origin – lint from laundering operations forming zero rags – and the filament length. Sludging rates were quantified using a bespoke parallel-channel test cell representing the membrane channels of an immersed flat sheet MBR. Sludge samples were provided from two local MBRs, one treating municipal and the other industrial effluent. Bulk sludge properties measured comprised mixed liquor suspended solids (MLSS) concentration, capillary suction time (CST), particle size, soluble COD (sCOD) and rheology (apparent viscosity μₐ vs shear rate γ). The fouling and sludging propensity of the sludge was determined using the test cell, ‘fouling’ being quantified as the pressure incline rate against flux via the flux step test (for which clogging was absent) and sludging by photographing the channel and processing the image to determine the ratio of the clogged to unclogged regions. A substantial difference in rheological and fouling behaviour was evident between the two sludge sources, the industrial sludge having a higher viscosity but less shear-thinning than the municipal. Fouling, as manifested by the pressure increase Δp/Δt, as a function of flux from classic flux-step experiments (where no clogging was evident), was more rapid for the industrial sludge. Across all samples of both sludge origins the expected trend of increased fouling propensity with increased CST and sCOD was demonstrated, whereas no correlation was observed between clogging rate and these parameters. The relative contribution of fouling and clogging was appraised by adjusting the clogging propensity via increasing the MLSS both with and without a commensurate increase in the COD. Results indicated that whereas for the municipal sludge the fouling propensity was affected by the increased sCOD, there was no associated increased in the sludging propensity (or cake formation). The clogging rate actually decreased on increasing the MLSS. Against this, for the industrial sludge the clogging rate dramatically increased with solids concentration despite a decrease in the soluble COD. From this was surmised that sludging did not relate to fouling.

Keywords: clogging, membrane bioreactors, ragging, sludge

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Authors: Shah Abid

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Leishmaniasis is a collection of zoonotic infections that affect the viscera, skin, and mucous membrane and are spread by several species of female sandflies in the subfamily phlebotominae. The study's goal was to assess the prevalence of Cutaneous Leishmaniasis in District Kurram using descriptive and cross-sectional methods. From December 2022 to May 2023, the study was carried out at Tehsil Head Quarter (THQ) Hospital, Sadda, District Kurram in the Dermatology Department. The disease was identified using a laboratory method based on clinical manifestations of leishmaniasis. A clean slide's surface was applied to the scraped-off portion of the lesions and rubbed over the blood to make a smear on the slide. The slides were methanol-fixed, stained with traditional Giemsa, and meticulously examined at high magnification to search for LD bodies. The necessary information, such as residence area, lesion kind and location, age, sex, and the total number of lesions, was meticulously acquired. During the time of the investigation, 393 instances of cutaneous leishmaniasis were observed. 1 year to 70 years old was the age range (mean age: 35.45). The age group that was most severely impacted, 16 years and older, had 23 (11.67%) children with this condition. Male to female ratio was 9.7:10. Most of the cases (n=52, 26.29%), were reported in the month of May. Majority of the patients 102 (51.77%) had lesion on face. 42 (16.73) patients had multiple lesions on their body. Face was the most common site followed by lower limbs 93 (37.05). Weekly intralesional injections of sodium stibogluconate (glucantime) were administered to all patients. Without any noticeable adverse effects, all patients had positive responses to the treatment. The condition affects adults more commonly than children, according to analysis of the combined results, and it is more common in women than in men.

Keywords: District Kurram, cutaneous leishmaniasis, zoonosis, glucantime

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Authors: Janos Juhasz, Sandor Pongor, Balazs Ligeti

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Next-generation sequencing, especially whole genome shotgun sequencing, is becoming a common approach to gain insight into the microbiomes in a culture-independent way, even in clinical practice. It does not only give us information about the species composition of an environmental sample but opens the possibility to detect antimicrobial resistance and novel, or currently unknown, pathogens. Accurately and reliably detecting the microbial strains is a challenging task. Here we present a sensitive approach for detecting pathogens in metagenomics samples with special regard to detecting novel variants of known pathogens. We have developed a pipeline that uses fast, short read aligner programs (i.e., Bowtie2/BWA) and comprehensive nucleotide databases. Taxonomic binning is based on the lowest common ancestor (LCA) principle; each read is assigned to a taxon, covering the most significantly hit taxa. This approach helps in balancing between sensitivity and running time. The program was tested both on experimental and synthetic data. The results implicate that our method performs as good as the state-of-the-art BLAST-based ones, furthermore, in some cases, it even proves to be better, while running two orders magnitude faster. It is sensitive and capable of identifying taxa being present only in small abundance. Moreover, it needs two orders of magnitude less reads to complete the identification than MetaPhLan2 does. We analyzed an experimental anthrax dataset (B. anthracis strain BA104). The majority of the reads (96.50%) was classified as Bacillus anthracis, a small portion, 1.2%, was classified as other species from the Bacillus genus. We demonstrate that the evaluation of high-throughput sequencing data is feasible in a reasonable time with good classification accuracy.

Keywords: metagenomics, taxonomy binning, pathogens, microbiome, B. anthracis

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Authors: A. Rostampouryasouri, A. Maghoul, S. Tahersima

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The rapid growth of urbanization and the subsequent increase in population in cities have resulted in the destruction of the environment to cater to the needs of citizens. The industrialization of urban life has led to the production of pollutants, which has significantly contributed to the rise of air pollution. Infrastructure can have both positive and negative effects on air pollution. The effects of infrastructure on air pollution are complex and depend on various factors such as the type of infrastructure, location, and context. This study examines the effects of infrastructure on air pollution, drawing on a range of empirical evidence from Iran and China. Our paper focus for analyzing the data is on the following concepts: 1. Urban design and planning principles and practices 2. Infrastructure efficiency and optimization strategies 3. Public transportation systems and their environmental impact 4. GHG emissions reduction strategies in urban areas 5. Case studies and best practices in sustainable urban development This paper employs a mixed methodology approach with a focus on developmental and applicative purposes. The mixed methods approach combines both quantitative and qualitative research methods to provide a more comprehensive understanding of the research topic. A group of 20 architectural specialists and experts who are proficient in the field of research, design, and implementation of green architecture projects were interviewed in a systematic and purposeful manner. The research method was based on content analysis using MAXQDA2020 software. The findings suggest that policymakers and urban planners should consider the potential impacts of infrastructure on air pollution and take measures to mitigate negative effects while maximizing positive ones. This includes adopting a nature-based approach to urban planning and infrastructure development, investing in information infrastructure, and promoting modern logistic transport infrastructure.

Keywords: GHG emissions, infrastructure efficiency, urban development, urban design

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Authors: Ana Belon Hercilla

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The study is developed in “Reactivos Jeans” company, in the city of Arequipa, whose main business is the laundry of garments at an industrial level. In 2012 the company initiated actions to provide a dry cleaning service of alpaca fiber garments, recognizing that this item is in a growth phase in Peru. Additionally this company took the initiative to use a new greenwashing technology which has not yet been developed in the country. To accomplish this, a redesign of both the process and the plant layout was required. For redesigning the plant, the methodology used was the Systemic Layout Planning, allowing this study divided into four stages. First stage is the information gathering and evaluation of the initial situation of the company, for which a description of the areas, facilities and initial equipment, distribution of the plant, the production process and flows of major operations was made. Second stage is the development of engineering techniques that allow the logging and analysis procedures, such as: Flow Diagram, Route Diagram, DOP (process flowchart), DAP (analysis diagram). Then the planning of the general distribution is carried out. At this stage, proximity factors of the areas are established, the Diagram Paths (TRA) is developed, and the Relational Diagram Activities (DRA). In order to obtain the General Grouping Diagram (DGC), further information is complemented by a time study and Guerchet method is used to calculate the space requirements for each area. Finally, the plant layout redesigning is presented and the implementation of the improvement is made, making it possible to obtain a model much more efficient than the initial design. The results indicate that the implementation of the new machinery, the adequacy of the plant facilities and equipment relocation resulted in a reduction of the production cycle time by 75.67%, routes were reduced by 68.88%, the number of activities during the process were reduced by 40%, waits and storage were removed 100%.

Keywords: redesign, time optimization, industrial laundry, greenwashing

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Authors: Salma Loukman, Reda Benmrid, Najat Bouchmaa, Hicham Hboub, Rachid El Fatimy, Rachid Benhida

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In this study, it use integrated transcriptomic datasets from the GEO repository with the purpose of investigating immune dysregulation in COVID-19. Thus, in this context, we decided to be focused on NK cells and CD14+ monocytes gene expression, considering datasets GSE165461 and GSE198256, respectively. Other datasets with PBMCs, lung, olfactory, and sensory epithelium and lymph were used to provide robust validation for our results. This approach gave an integrated view of the immune responses in COVID-19, pointing out a set of potential biomarkers and therapeutic targets with special regard to standards of physiological conditions. IFI27, MKI67, CENPF, MBP, HBA2, TMEM158, THBD, HBA1, LHFPL2, SLA, and AC104564.3 were identified as key genes from our analysis that have critical biological processes related to inflammation, immune regulation, oxidative stress, and metabolic processes. Consequently, such processes are important in understanding the heterogeneous clinical manifestations of COVID-19—from acute to long-term effects now known as 'long COVID'. Subsequent validation with additional datasets consolidated these genes as robust biomarkers with an important role in the diagnosis of COVID-19 and the prediction of its severity. Moreover, their enrichment in key pathophysiological pathways presented them as potential targets for therapeutic intervention.The results provide insight into the molecular dynamics of COVID-19 caused by cells such as NK cells and other monocytes. Thus, this study constitutes a solid basis for targeted diagnostic and therapeutic development and makes relevant contributions to ongoing research efforts toward better management and mitigation of the pandemic.

Keywords: SARS-COV-2, RNA-seq, biomarkers, severity, long COVID-19, bio analysis

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Authors: N. Haj Salem, M. Belhadj, S. Ben Jomâa, S. Saadi, R. Dhouieb, A. Chadly

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Introduction: Sudden death in young is seen as a dramatic phenomenon requiring knowledge of its impact and determining their causes. Aim: We aim to study the epidemiological characteristics of sudden death in young, and to discuss the mechanism and the importance of autopsy in these situations. Material and methods: We performed a retrospective cohort study using autopsy data from the department of forensic medicine at the University Hospital of Fattouma Bourguiba, Monastir-Tunisia. A review of all autopsies performed during 23 years was done. In each case, clinical information and circumstances of death were obtained. We have included all sudden death in persons aged between 1 year and 35 years for the male and from one year to 45 years for female. We collected 312 cases of sudden death during the studied period. The collected data were processed using SPSS 20. The significance level was set at 0.05. Results: Thirty-two cases of cardiac ischemic sudden death have been collected. Myocardial infarction was the second cause of sudden death in young patients. There was a male predominance. The most affected subjects were aged between 25-45 years. The death occurred more frequently at rest. Coronary artery disease has been discovered in twenty-four cases (75%). A severe coronary artery disease was observed in two children with medical history of familial hypercholesterolemia. The myocardial infarction occurred in healthy coronary arteries in eight cases. An anomalous course of coronary arteries, in particular, myocardial bridging, was found in eight cases (25%). Toxicological screening was negative in all cases. Second cause of death was hypertrophic cardiomyopathy. Neurological and respiratory causes of death were implicated respectively in 10% and 15%. Conclusion: Identifying epidemiological characteristics of sudden death in this population is important for guiding approaches to prevention that must be based on dietary hygienic measures and the control of cardiovascular risk factors.

Keywords: autopsy, cardiac death, sudden death, young

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Authors: Abdulla Rahil, Rupert Gammon, Neil Brown

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The rapid growth of renewable energy sources and their integration into the grid have been motivated by the depletion of fossil fuels and environmental issues. Unfortunately, the grid is unable to cope with the predicted growth of renewable energy which would lead to its instability. To solve this problem, energy storage devices could be used. Electrolytic hydrogen production from an electrolyser is considered a promising option since it is a clean energy source (zero emissions). Choosing flexible operation of an electrolyser (producing hydrogen during the off-peak electricity period and stopping at other times) could bring about many benefits like reducing the cost of hydrogen and helping to balance the electric systems. This paper investigates the price of hydrogen during flexible operation compared with continuous operation, while serving the customer (hydrogen filling station) without interruption. The optimization algorithm is applied to investigate the hydrogen station in both cases (flexible and continuous operation). Three different scenarios are tested to see whether the off-peak electricity price could enhance the reduction of the hydrogen cost. These scenarios are: Standard tariff (1 tier system) during the day (assumed 12 p/kWh) while still satisfying the demand for hydrogen; using off-peak electricity at a lower price (assumed 5 p/kWh) and shutting down the electrolyser at other times; using lower price electricity at off-peak times and high price electricity at other times. This study looks at Derna city, which is located on the coast of the Mediterranean Sea (32° 46′ 0 N, 22° 38′ 0 E) with a high potential for wind resource. Hourly wind speed data which were collected over 24½ years from 1990 to 2014 were in addition to data on hourly radiation and hourly electricity demand collected over a one-year period, together with the petrol station data.

Keywords: hydrogen filling station off-peak electricity, renewable energy, off-peak electricity, electrolytic hydrogen

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Authors: Man Ying Kang, Joshua Kin Man Nan

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The prolonged pandemic has posed alarming public health challenges to various parts of the world, and face-to-face mental health treatment is largely discounted for the control of virus transmission, online psychological services and self-help mental health kits have become essential. Online self-help mindfulness-based interventions have proved their effects on fostering mental health for different populations over the globe. This paper was to test the effectiveness of an online short-term audio-based mindfulness (SAM) program in enhancing wellbeing, dispositional mindfulness, and reducing stress and negative affect in community settings in China, and to explore possible mechanisms of how dispositional mindfulness, stress, and negative affect influenced the intervention effects on wellbeing. Community-dwelling adults were recruited via online social networking sites (e.g., QQ, WeChat, and Weibo). Participants (n=100) were randomized into the mindfulness group (n=50) and a waitlist control group (n=50). In the mindfulness group, participants were advised to spend 10–20 minutes listening to the audio content, including mindful-form practices (e.g., eating, sitting, walking, or breathing). Then practice daily mindfulness exercises for 3 weeks (a total of 21 sessions), whereas those in the control group received the same intervention after data collection in the mindfulness group. Participants in the mindfulness group needed to fill in the World Health Organization Five Well-Being Index (WHO), Positive and Negative Affect Schedule (PANAS), Perceived Stress Scale (PSS), and Freiburg Mindfulness Inventory (FMI) four times: at baseline (T0) and at 1 (T1), 2 (T2), and 3 (T3) weeks while those in the waitlist control group only needed to fill in the same scales at pre- and post-interventions. Repeated-measure analysis of variance, paired sample t-test, and independent sample t-test was used to analyze the variable outcomes of the two groups. The parallel process latent growth curve modeling analysis was used to explore the longitudinal moderated mediation effects. The dependent variable was WHO slope from T0 to T3, the independent variable was Group (1=SAM, 2=Control), the mediator was FMI slope from T0 to T3, and the moderator was T0NA and T0PSS separately. The different levels of moderator effects on WHO slope was explored, including low T0NA or T0PSS (Mean-SD), medium T0NA or T0PSS (Mean), and high T0NA or T0PSS (Mean+SD). The results found that SAM significantly improved and predicted higher levels of WHO slope and FMI slope, as well as significantly reduced NA and PSS. FMI slope positively predict WHO slope. FMI slope partially mediated the relationship between SAM and WHO slope. Baseline NA and PSS as the moderators were found to be significant between SAM and WHO slope and between SAM and FMI slope, respectively. The conclusion was that SAM was effective in promoting levels of mental wellbeing, positive affect, and dispositional mindfulness as well as reducing negative affect and stress in community settings in China. SAM improved wellbeing faster through the faster enhancement of dispositional mindfulness. Participants with medium-to-high negative affect and stress buffered the therapy effects of SAM on wellbeing improvement speed.

Keywords: mindfulness, negative affect, stress, wellbeing, randomized control trial

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

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