Search results for: horizontal control points

Authors: Tianyu Wang, Nikita Karandikar

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The uncertainty around cost, safety, and feasibility of the decarbonized shipping fuels has made it increasingly complex for the shipping companies to set pricing strategies and forecast their freight revenues going forward. The increase in the green fuel surcharges will ultimately influence the automobile’s consumer prices. The auto shipping demand (ton-miles) has been gradually shifting from long-haul to short-sea trade over the past years following the relocation of the original equipment manufacturer (OEM) manufacturing to regions such as South America and Southeast Asia. The objective of this paper is twofold: 1) to investigate the car-carriers freight revenue development over the years when the trade pattern is gradually shifting towards short-sea exports 2) to empirically identify the quantitative impact of such trade pattern shifting to mainly freight rate, but also vessel size, fleet size as well as Green House Gas (GHG) emission in Roll on-Roll Off (Ro-Ro) shipping. In this paper, a model of analyzing and forecasting ton-miles and freight revenues for the trade routes of AS-NA (Asia to North America), EU-NA (Europe to North America), and SA-NA (South America to North America) is established by deploying Automatic Identification System (AIS) data and the financial results of a selected car carrier company. More specifically, Wallenius Wilhelmsen Logistics (WALWIL), the Norwegian Ro-Ro carrier listed on Oslo Stock Exchange, is selected as the case study company in this paper. AIS-based ton-mile datasets of WALWIL vessels that are sailing into North America region from three different origins (Asia, Europe, and South America), together with WALWIL’s quarterly freight revenues as reported in trade segments, will be investigated and compared for the past five years (2018-2022). Furthermore, ordinary‐least‐square (OLS) regression is utilized to construct the ton-mile demand and freight revenue forecasting. The determinants of trade pattern shifting, such as import tariffs following the China-US trade war and fuel prices following the 0.1% Emission Control Areas (ECA) zone requirement after IMO2020 will be set as key variable inputs to the machine learning model. The model will be tested on another newly listed Norwegian Car Carrier, Hoegh Autoliner, to forecast its 2022 financial results and to validate the accuracy based on its actual results. GHG emissions on the three routes will be compared and discussed based on a constant emission per mile assumption and voyage distances. Our findings will provide important insights about 1) the trade-off evaluation between revenue reduction and energy saving with the new ton-mile pattern and 2) how the trade flow shifting would influence the future need for the vessel and fleet size.

Keywords: AIS, automobile exports, maritime big data, trade flows

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Authors: Alexandra Sargent, Sarah Ferris, Ioannis Theofanous

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The Abbott RealTime High Risk HPV test (RealTime HPV) is one of five assays clinically validated and approved by the English NHS Cervical Screening Programme (CSP) for HPV triage of low grade dyskaryosis and test-of-cure of treated Cervical Intraepithelial Neoplasia. The assay is a highly automated multiplex real-time PCR test for detecting 14 high risk (hr) HPV types, with simultaneous differentiation of HPV 16 and HPV 18 versus non-HPV 16/18 hrHPV. An endogenous internal control ensures sample cellularity, controls extraction efficiency and PCR inhibition. The original cervical specimen collected in SurePath (SP) liquid-based cytology (LBC) medium (BD Diagnostics) and the SP post-gradient cell pellets (SPG) after cytological processing are both CE marked for testing with the RealTime HPV test. During the 2011 NHSCSP validation of new tests only the original aliquot of SP LBC medium was investigated. Residual sample volume left after cytology slide preparation is low and may not always have sufficient volume for repeat HPV testing or for testing of other biomarkers that may be implemented in testing algorithms in the future. The SPG samples, however, have sufficient volumes to carry out additional testing and necessary laboratory validation procedures. This study investigates the correlation of RealTime HPV results of cervical specimens collected in SP LBC medium from women with low grade cytological abnormalities observed with matched pairs of original SP LBC medium and SP post-gradient cell pellets (SPG) after cytology processing. Matched pairs of SP and SPG samples from 750 women with borderline (N = 392) and mild (N = 351) cytology were available for this study. Both specimen types were processed and parallel tested for the presence of hrHPV with RealTime HPV according to the manufacturer´s instructions. HrHPV detection rates and concordance between test results from matched SP and SPGCP pairs were calculated. A total of 743 matched pairs with valid test results on both sample types were available for analysis. An overall-agreement of hrHPV test results of 97.5% (k: 0.95) was found with matched SP/SPG pairs and slightly lower concordance (96.9%; k: 0.94) was observed on 392 pairs from women with borderline cytology compared to 351 pairs from women with mild cytology (98.0%; k: 0.95). Partial typing results were highly concordant in matched SP/SPG pairs for HPV 16 (99.1%), HPV 18 (99.7%) and non-HPV16/18 hrHPV (97.0%), respectively. 19 matched pairs were found with discrepant results: 9 from women with borderline cytology and 4 from women with mild cytology were negative on SPG and positive on SP; 3 from women with borderline cytology and 3 from women with mild cytology were negative on SP and positive on SPG. Excellent correlation of hrHPV DNA test results was found between matched pairs of SP original fluid and post-gradient cell pellets from women with low grade cytological abnormalities tested with the Abbott RealTime High-Risk HPV assay, demonstrating robust performance of the test with both specimen types and reassuring the utility of the assay for cytology triage with both specimen types.

Keywords: Abbott realtime test, HPV, SurePath liquid based cytology, surepath post-gradient cell pellet

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Authors: Kamal Agrawal, Ved Prakash Nayak, Akshay Patil

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Raipur is known as a city of water bodies. The city had around 200 man-made and natural lakes of varying sizes. These structures were constructed to collect rainwater and control flooding in the city. Due to the transition from community participation to state government, as well as rapid urbanisation, Raipur now has only about 80 lakes left. Rapid and unplanned growth has resulted in pollution, encroachment, and eutrophication of the city's lakes. The state government keeps these lakes in good condition by cleaning them and proposing lakefront developments. However, maintaining individual lakes is insufficient because urban lakes are not distinct entities. It is a system comprised of the lake, shore, catchment, and other components. While Urban lake system (ULS) is a combination of multiple such lake systems interacting in a complex urban setting. Thus, the project aims to propose a co-evolution model for urban lake systems (ULS) and rapid urbanization in Raipur. The goals are to comprehend the ULS and to identify elements and dimensions of urbanization that influence the ULS. Evaluate the impact of rapid urbanization on the ULS & vice versa in the study area. Determine how to maximize the positive impact while minimizing the negative impact identified in the study area. Propose short-, medium-, and long-term planning interventions to support the ULS's co-evolution with rapid urbanization. A complexity approach is used to investigate the ULS. It is a technique for understanding large, complex systems. A complex system is one with many interconnected and interdependent elements and dimensions. Thus, elements of ULS and rapid urbanization are identified through a literature study to evaluate statements of their impacts (Beneficial/ Adverse) on one another. Rapid urbanization has been identified as having elements such as demography, urban legislation, informal settlement, urban infrastructure, and tourism. Similarly, the catchment area of the lake, the lake's water quality, the water spread area, and lakefront developments are all being impacted by rapid urbanisation. These nine elements serve as parameters for the subsequent analysis. Elements are limited to physical parameters only. The city has designated a study area based on the definition provided by the National Plan for the Conservation of Aquatic Ecosystems. Three lakes are discovered within a one-kilometer radius, establishing a tiny urban lake system. Because the condition of a lake is directly related to the condition of its catchment area, the catchment area of these three lakes is delineated as the study area. Data is collected to identify impact statements, and the interdependence diagram generated between the parameters yields results in terms of interlinking between each parameter and their impact on the system as a whole. The planning interventions proposed for the ULS and rapid urbanisation co-evolution model include spatial proposals as well as policy recommendations for the short, medium, and long term. This study's next step will be to determine how to implement the proposed interventions based on the availability of resources, funds, and governance patterns.

Keywords: urban lake system, co-evolution, rapid urbanization, complex system

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Authors: Trina Isabel D. Santiago, Juan Raphael M. Perez, Maria Angelica O. Soriano, Teresita B. Suing, Jumee F. Tayaban

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To achieve universal healthcare for everyone, the World Health Organization has emphasized the importance of National Medicines Policies for increased accessibility and utilization of high-quality and affordable medications. In the Philippines, significant challenges have been identified surrounding the sustainability of essential medicines, resulting in limited access such as high cost and dominance and market dominance and monopoly of multinational companies (MNCs) in the Philippine pharmaceutical industry. These identified challenges have been addressed by several initiatives, such as the Philippine National Drug Policy and Generics Act of 1988 (Republic Act 6675), to attempt to reduce drug prices. Despite these efforts, the concerns with drug accessibility and affordability continue to persist; hence, Republic Act 9502 was enacted. This paper attempts to review RA 9502 in the pursuit of making medicines more affordable for Filipinos, analyze and critique the problems and challenges associated with the law, and provide recommendations to address identified problems and challenges. A literature search and review, as well as an analysis of the law, has been done to evaluate the policy. RA 9502 recognizes the importance of market competition in drug price reduction and quality medicine accessibility. Contentious issues prior to enactment of the law include 1) parallel importation, pointing out that the drug price will depend on the global market price, 2) contrasting approaches in the drafting of the law as the House version focused on medicine price control while the Senate version prioritized market competition, and 3) MNCs opposing the amendments with concerns on discrimination, constitutional violations, and noncompliance with international treaty obligations. There are also criticisms and challenges with the implementation of the law in terms of content or modeling, interpretation and implementation, and other external factors or hindrances. The law has been criticized for its narrow scope as it only covers specific essential medicines with no cooperation with the national health insurance program. Moreover, the law has sections taking advantage of the TRIPS flexibilities, which disallow smaller countries to reap the benefits of flexibilities. The sanctions and penalties have an insignificant role in implementation as they only ask for a small portion of the income of MNCs. Proposed recommendations for policy improvement include aligning existing legislation through strengthened price regulation and expanded law coverage, strengthening penalties to promote law adherence, and promoting research and development to encourage and support local initiatives. Through these comprehensive recommendations, the issues surrounding the policy can be addressed, and the goal of enhancing the affordability and accessibility of medicines in the country can be achieved.

Keywords: drug accessibility, drug affordability, price regulation, Republic Act 9502

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Authors: Razieh Karimi Aghcheh, Christian Kubicek, Joseph Strauss, Gerhard Braus

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Filamentous fungi are of considerable economic and social significance for human health, nutrition and in white biotechnology. These organisms are dominant producers of a range of primary metabolites such as citric acid, microbial lipids (biodiesel) and higher unsaturated fatty acids (HUFAs). In particular, they produce also important but structurally complex secondary metabolites with enormous therapeutic applications in pharmaceutical industry, for example: cephalosporin, penicillin, taxol, zeranol and ergot alkaloids. Several fungal secondary metabolites, which are significantly relevant to human health do not only include antibiotics, but also e.g. lovastatin, a well-known antihypercholesterolemic agent produced by Aspergillus. terreus, or aflatoxin, a carcinogen produced by A. flavus. In addition to their roles for human health and agriculture, some fungi are industrially and commercially important: Species of the ascomycete genus Hypocrea spp. (teleomorph of Trichoderma) have been demonstrated as efficient producer of highly active cellulolytic enzymes. This trait makes them effective in disrupting and depolymerization of lignocellulosic materials and thus applicable tools in number of biotechnological areas as diverse as clothes-washing detergent, animal feed, and pulp and fuel productions. Fungal LaeA/LAE1 (Loss of aflR Expression A) homologs their gene products act at the interphase between secondary metabolisms, cellulase production and development. Lack of the corresponding genes results in significant physiological changes including loss of secondary metabolite and lignocellulose degrading enzymes production. At the molecular level, the encoded proteins are presumably methyltransferases or demethylases which act directly or indirectly at heterochromatin and interact with velvet domain proteins. Velvet proteins bind to DNA and affect expression of secondary metabolites (SMs) genes and cellulases. The dynamic interplay between LaeA/LAE1, velvet proteins and additional interaction partners is the key for an understanding of the coordination of metabolic and morphological functions of fungi and is required for a biotechnological control of the formation of desired bioactive products. Aspergilli and Trichoderma represent different biotechnologically significant species with significant differences in the LaeA/LAE1-Velvet protein machinery and their target proteins. We, therefore, performed a comparative study of the interaction partners of this machinery and the dynamics of the various protein-protein interactions using our robust proteomic and mass spectrometry techniques. This enhances our knowledge about the fungal coordination of secondary metabolism, cellulase production and development and thereby will certainly improve recombinant fungal strain construction for the production of industrial secondary metabolite or lignocellulose hydrolytic enzymes.

Keywords: cellulases, LaeA/1, proteomics, secondary metabolites

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Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour

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Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.

Keywords: quality of life, lung cancer, metastasis, symptoms burden

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Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

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When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

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Authors: Mauro Cristeche

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This paper approaches the intervention of the American State in the social arena and the modeling of the rights system from the Argentinian experience, by observing the characteristics of its federal budgetary system, the evolution of social public spending and welfare programs in recent years, labor and poverty statistics, and the changes on the labor market structure. The analysis seeks to combine different methodologies and sources: in-depth interviews with specialists, analysis of theoretical and mass-media material, and statistical sources. Among the results, it could be mentioned that the tendency to state interventionism (what has been called ‘nationalization of social life’) is quite evident in the United States, and manifests itself in multiple forms. The bibliography consulted, and the experts interviewed pointed out this increase of the state presence in historical terms (beyond short-term setbacks) in terms of increase of public spending, fiscal pressure, public employment, protective and control mechanisms, the extension of welfare policies to the poor sectors, etc. In fact, despite the significant differences between both countries, the United States and Argentina have common patterns of behavior in terms of the aforementioned phenomena. On the other hand, dissimilarities are also important. Some of them are determined by each country's own political history. The influence of political parties on the economic model seems more decisive in the United States than in Argentina, where the tendency to state interventionism is more stable. The centrality of health spending is evident in America, while in Argentina that discussion is more concentrated in the social security system and public education. The biggest problem of the labor market in the United States is the disqualification as a consequence of the technological development while in Argentina it is a result of its weakness. Another big difference is the huge American public spending on Defense. Then, the more federal character of the American State is also a factor of differential analysis against a centralized Argentine state. American public employment (around 10%) is comparatively quite lower than the Argentinian (around 18%). The social statistics show differences, but inequality and poverty have been growing as a trend in the last decades in both countries. According to public rates, poverty represents 14% in The United States and 33% in Argentina. American public spending is important (welfare spending and total public spending represent around 12% and 34% of GDP, respectively), but a bit lower than Latin-American or European average). In both cases, the tendency to underemployment and disqualification unemployment does not assume a serious gravity. Probably one of the most important aspects of the analysis is that private initiative and public intervention are much more intertwined in the United States, which makes state intervention more ‘fuzzy’, while in Argentina the difference is clearer. Finally, the power of its accumulation of capital and, more specifically, of the industrial and services sectors in the United States, which continues to be the engine of the economy, express great differences with Argentina, supported by its agro-industrial power and its public sector.

Keywords: state intervention, welfare policies, labor market, system of rights, United States of America

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Authors: Ali Kassem, Ehab Fawzy, Mahmoud Sef el-eslam, Fatma Salah- Eldeen, El zahraa Mohamed

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Introduction: The combination of interferon (INF) and ribavirin is the preferred treatment for chronic hepatitis C viral (HCV) infection. However, nonresponse to this therapy remains common and is associated with several factors such as HCV genotype and HCV viral load in addition to host factors such as sex, HLA type and cytokine polymorphisms. Aim of the work: The aim of this study was to determine predictors of response to (INF) therapy in chronic HCV infected patients treated with INF alpha and ribavirin combination therapy. Patients and Methods: The present study included 110 patients (62 males, 48 females) with chronic HCV infection. Their ages ranged from 20-59 years. Inclusion criteria were organized according to the protocol of the Egyptian National Committee for control of viral hepatitis. Patients included in this study were recruited to receive INF ribavirin combination therapy; 54 patients received pegylated NF α-2a (180 μg) and weight based ribavirin therapy (1000 mg if < 75 kg, 1200 mg if > 75 kg) for 48 weeks and 53 patients received pegylated INF α-2b (1.5 ug/kg/week) and weight based ribavirin therapy (800 mg if < 65 kg, 1000 mg if 65-75 kg and 1200 mg if > 75kg). One hundred and seven liver biopsies were included in the study and submitted to histopathological examination. Hematoxylin and eosin (H&E) stained sections were done to assess both the grade and the stage of chronic viral hepatitis, in addition to the degree of steatosis. Modified hepatic activity index (HAI) grading, modified Ishak staging and Metavir grading and staging systems were used. Laboratory follow up including: HCV PCR at the 12th week to assess the early virologic response (EVR) and at the 24th week were done. At the end of the course: HCV PCR was done at the end of the course and tested 6 months later to document end virologic response (ETR) and sustained virologic response (SVR) respectively. Results One hundred seven patients; 62 males (57.9 %) and 45 females (42.1%) completed the course and included in this study. The age of patients ranged from 20-59 years with a mean of 40.39±10.03 years. Six months after the end of treatment patients were categorized into two groups: Group (1): patients who achieved sustained virological response (SVR). Group (2): patients who didn't achieve sustained virological response (non SVR) including non-responders, breakthrough and relapsers. In our study, 58 (54.2%) patients showed SVR, 18 (16.8%) patients were non-responders, 15 (14%) patients showed break-through and 16 (15 %) patients were relapsers. Univariate binary regression analysis of the possible risk factors of non SVR showed that the significant factors were higher age, higher fasting insulin level, higher Metavir stage and higher grade of hepatic steatosis. Multivariate binary regression analysis showed that the only independent risk factor for non SVR was high fasting insulin level. Conclusion: Younger age, lower Metavir stage, lower steatosis grade and lower fasting insulin level are good predictors of SVR and could be used in predicting the treatment response of pegylated interferon/ribavirin therapy.

Keywords: chronic HCV infection, interferon ribavirin combination therapy, predictors to antiviral therapy, treatment response

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Authors: Yixin Zhu, Lishengsa Yue, Jian Sun, Lanyue Tang

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Modeling driving distraction in microscopic traffic simulation is crucial for enhancing simulation accuracy. Current driving distraction models are mainly derived from physical motion constraints under distracted states, in which distraction-related error terms are added to existing microscopic driver models. However, the model accuracy is not very satisfying, due to a lack of modeling the cognitive mechanism underlying the distraction. This study models driving distraction based on the Queueing Network Human Processor model (QN-MHP). This study utilizes the queuing structure of the model to perform task invocation and switching for distracted operation and control of the vehicle under driver distraction. Based on the assumption of the QN-MHP model about the cognitive sub-network, server F is a structural bottleneck. The latter information must wait for the previous information to leave server F before it can be processed in server F. Therefore, the waiting time for task switching needs to be calculated. Since the QN-MHP model has different information processing paths for auditory information and visual information, this study divides driving distraction into two types: auditory distraction and visual distraction. For visual distraction, both the visual distraction task and the driving task need to go through the visual perception sub-network, and the stimuli of the two are asynchronous, which is called stimulus on asynchrony (SOA), so when calculating the waiting time for switching tasks, it is necessary to consider it. In the case of auditory distraction, the auditory distraction task and the driving task do not need to compete for the server resources of the perceptual sub-network, and their stimuli can be synchronized without considering the time difference in receiving the stimuli. According to the Theory of Planned Behavior for drivers (TPB), this study uses risk entropy as the decision criterion for driver task switching. A logistic regression model is used with risk entropy as the independent variable to determine whether the driver performs a distraction task, to explain the relationship between perceived risk and distraction. Furthermore, to model a driver’s perception characteristics, a neurophysiological model of visual distraction tasks is incorporated into the QN-MHP, and executes the classical Intelligent Driver Model. The proposed driving distraction model integrates the psychological cognitive process of a driver with the physical motion characteristics, resulting in both high accuracy and interpretability. This paper uses 773 segments of distracted car-following in Shanghai Naturalistic Driving Study data (SH-NDS) to classify the patterns of distracted behavior on different road facilities and obtains three types of distraction patterns: numbness, delay, and aggressiveness. The model was calibrated and verified by simulation. The results indicate that the model can effectively simulate the distracted car-following behavior of different patterns on various roadway facilities, and its performance is better than the traditional IDM model with distraction-related error terms. The proposed model overcomes the limitations of physical-constraints-based models in replicating dangerous driving behaviors, and internal characteristics of an individual. Moreover, the model is demonstrated to effectively generate more dangerous distracted driving scenarios, which can be used to construct high-value automated driving test scenarios.

Keywords: computational cognitive model, driving distraction, microscopic traffic simulation, psychological-physical constraints

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Authors: Fatih Kılıç, Burak Birol, Necmettin Maraşlı

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The directional solidification process is generally used for homogeneous compound production, single crystal growth, and refining (zone refining), etc. processes. The most important two parameters that control eutectic structures are temperature gradient and grain growth rate which are called as solidification parameters The solidification behavior and microstructure characteristics is an interesting topic due to their effects on the properties and performance of the alloys containing eutectic compositions. The solidification behavior of multicomponent and multiphase systems is an important parameter for determining various properties of these materials. The researches have been conducted mostly on the solidification of pure materials or alloys containing two phases. However, there are very few studies on the literature about multiphase reactions and microstructure formation of multicomponent alloys during solidification. Because of this situation, it is important to study the microstructure formation and the thermodynamical, thermophysical and microstructural properties of these alloys. The production process is difficult due to easy oxidation of magnesium and therefore, there is not a comprehensive study concerning alloys containing high Mg (> 30 wt.% Mg). With the increasing amount of Mg inside Al alloys, the specific weight decreases, and the strength shows a slight increase, while due to formation of β-Al8Mg5 phase, ductility lowers. For this reason, production, examination and development of high Mg containing alloys will initiate the production of new advanced engineering materials. The original value of this research can be described as obtaining high Mg containing (> 30% Mg) Al based multicomponent alloys by melting under vacuum; controlled directional solidification with various growth rates at a constant temperature gradient; and establishing relationship between solidification rate and microstructural, mechanical, electrical and thermal properties. Therefore, within the scope of this research, some > 30% Mg containing ternary or quaternary Al alloy compositions were determined, and it was planned to investigate the effects of directional solidification rate on the mechanical, electrical and thermal properties of these alloys. Within the scope of the research, the influence of the growth rate on microstructure parameters, microhardness, tensile strength, electrical conductivity and thermal conductivity of directionally solidified high Mg containing Al-32,2Mg-0,37Si; Al-30Mg-12Zn; Al-32Mg-1,7Ni; Al-32,2Mg-0,37Fe; Al-32Mg-1,7Ni-0,4Si; Al-33,3Mg-0,35Si-0,11Fe (wt.%) alloys with wide range of growth rate (50-2500 µm/s) and fixed temperature gradient, will be investigated. The work can be planned as; (a) directional solidification of Al-Mg based Al-Mg-Si, Al-Mg-Zn, Al-Mg-Ni, Al-Mg-Fe, Al-Mg-Ni-Si, Al-Mg-Si-Fe within wide range of growth rates (50-2500 µm/s) at a constant temperature gradient by Bridgman type solidification system, (b) analysis of microstructure parameters of directionally solidified alloys by using an optical light microscopy and Scanning Electron Microscopy (SEM), (c) measurement of microhardness and tensile strength of directionally solidified alloys, (d) measurement of electrical conductivity by four point probe technique at room temperature (e) measurement of thermal conductivity by linear heat flow method at room temperature.

Keywords: directional solidification, electrical conductivity, high Mg containing multicomponent Al alloys, microhardness, microstructure, tensile strength, thermal conductivity

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Authors: Rumbidzai Sipiwe Zimvumi

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The study aimed to identify the top management team attributes for ambidexterity in small and medium-sized enterprises by utilizing the upper echelons theory. The conventional opinion holds that an organization's ability to pursue both exploitative and explorative innovation methods at the same time is reflected in its ambidexterity. Top-level managers are critical to this matrix because they forecast and explain strategic choices that guarantee success by improving organizational performance. Since the focus of the study was on the unique characteristics of TMTs that can facilitate ambidexterity, the primary goal was to comprehend how TMTs in SMEs can better manage ambidexterity. The study used document analysis to collect information on ambidexterity and TMT traits. Finding, choosing, assessing, and synthesizing data from peer-reviewed publications allowed for the review and evaluation of papers. The fact that SMEs will perform better if they can achieve a balance between exploration and exploitation cannot be overstated. Unfortunately, exploitation is the main priority for most SMEs. The results showed that some of the noteworthy TMT traits that support ambidexterity in SMEs are age diversity, shared responsibility, leadership impact, psychological safety, and self-confidence. It has been shown that most SMEs confront significant obstacles in recruiting people, including formalizing their management and assembling executive teams with seniority. Small and medium-sized enterprises (SMEs) are often held by families or people who neglect to keep their personal lives apart from the firm, which eliminates the opportunity for management and staff to take the initiative. This helps to explain why exploitative strategies, which preserve present success, are used rather than explorative strategies, which open new economic opportunities and dimensions. It is evident that psychological safety deteriorates, and creativity is hindered in the process. The study makes the case that TMTs who are motivated to become ambidextrous can exist. According to the report, small- and medium-sized business owners should value the opinions of all parties involved and provide their managers and regular staff the freedom to think creatively and in a safe environment. TMTs who experience psychological safety are more likely to be inventive, creative, and productive. A team's collective perception that it is acceptable to take chances, voice opinions and concerns, ask questions, and own up to mistakes without fear of unfavorable outcomes is known as team psychological safety. Thus, traits like age diversity, leadership influence, learning agility, psychological safety, and self-assurance are critical to the success of SMEs. As a solution to ensuring ambidexterity is attained, the study suggests a clear separation of ownership and control, the adoption of technology to stimulate creativity, team spirit and excitement, shared accountability, and good management of diversity. Among the suggestions for the SME's success are resource allocation and important collaborations.

Keywords: navigating, ambidexterity, top management team, small and medium enterprises

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Authors: Celine Shi Ying Lee, Jong Jian Lee

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Background: Infectious keratitis is one of the leading causes of blindness worldwide. Prompt treatment with effective medication will control the infection early, preventing corneal scarring and visual loss. fluoroquinolones ophthalmic medication is used because of its broad-spectrum properties, potency, good intraocular penetration, and low toxicity. The study aims to evaluate the treatment outcome of corneal ulcers using Levofloxacin 1.5% ophthalmic solution (LVFX) with adjuvant oral ciprofloxacin when indicated and apply this treatment strategy in primary health care as first-line treatment. Methods: Patients with infective corneal ulcer treated in an eye center were recruited. Inclusion criteria includes Corneal infection consistent with bacterial keratitis, single or multiple small corneal ulcers. Treatment regime: LVFX hourly for the first 2 days, 2 hourly from the 3rd day, and 3 hourly on the 5th day of review. Adjuvant oral ciprofloxacin 500mg BD was administered for 5 days if there were multiple corneal ulcers or when the location of the cornea ulcer was central or paracentral. Results: 47 subjects were recruited. There were 16 (34%) males and 31 (66%) females. 40 subjects (85%) were contact lens (CL) related to corneal ulcer, and 7 subjects (15%) were non-contact lens related. 42 subjects (89%) presented with one ulcer, of which 20 of them (48%) needed adjuvant therapy. 5 subjects presented with 2 or 3 ulcers, of which 3 needed adjuvant therapy. A total of 23 subjects (49%) was given adjuvant therapy (oral ciprofloxacin 500mg BD for 5 days).21 of them (91%) were CL related. All subjects recovered fully, and the average duration of treatment was 3.7 days, with 49% of the subjects resolved on the 3rd day, 38% on the 5thday of and 13% on the 7thday. All subjects showed symptoms of relief of pain, light-sensitivity, and redness on the 3rd day with full visual recovery post-treatment. No adverse drug reactions were recorded. Conclusion: Our treatment regime demonstrated good clinical outcome as first-line treatment for corneal ulcers. A corneal ulcer is a common eye condition in Singapore, mainly due to CL wear. Pseudomonas aeruginosa is the most frequent and potentially sight-threatening pathogen involved in CL related corneal ulcer. Coagulase-negative Staphylococci, Staphylococcus aureus, and Streptococcus Pneumoniae were seen in non-CL users. All these bacteria exhibit good sensitivity rates to ciprofloxacin and levofloxacin. It is therefore logical in our study to use LVFX Eyedrops and adjuvant ciprofloxacin oral antibiotics when indicated as first line treatment for most corneal ulcers. Our study of patients, both CL related and non-CL related, have shown good clinical response and full recovery using the above treatment strategy. There was also a full restoration of visual acuity in all the patients. Eye-trained primary Healthcare practitioners can consider adopting this treatment strategy as first line treatment in patients with corneal ulcers. This is relevant during the COVID pandemic, where hospitals are overwhelmed with patients and in regions with limited access to specialist eye care. This strategy would enable early treatment with better clinical outcome.

Keywords: corneal ulcer, levofloxacin hydrate, treatment strategy, ciprofloxacin

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Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

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Authors: Rodrigo Calili, Anna Carolina Sermarini, João Henrique Azevedo, Vanessa Cardoso de Albuquerque, Felipe Gonçalves, Gilberto Jannuzzi

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The diffusion of Distributed Energy Resources (DER) has caused structural changes in the relationship between consumers and electrical systems. The Photovoltaic Distributed Generation (PVDG), in particular, is an essential strategy for achieving the 2030 Agenda goals, especially SDG 7 and SDG 13. However, it is observed that most projects involving this technology in Brazil are restricted to the wealthiest classes of society, not yet reaching the low-income population, aligned with theories of energy justice. Considering the research for energy equality, one of the policies adopted by governments is the social electricity tariff (SET), which provides discounts on energy tariffs/bills. However, just granting this benefit may not be effective, and it is possible to merge it with DER technologies, such as the PVDG. Thus, this work aims to evaluate the economic viability of the policy to replace the social electricity tariff (the current policy aimed at the low-income population in Brazil) by PVDG projects. To this end, a proprietary methodology was developed that included: mapping the stakeholders, identifying critical variables, simulating policy options, and carrying out an analysis in the Brazilian context. The simulation answered two key questions: in which municipalities low-income consumers would have lower bills with PVDG compared to SET; which consumers in a given city would have increased subsidies, which are now provided for solar energy in Brazil and for the social tariff. An economic model was created for verifying the feasibility of the proposed policy in each municipality in the country, considering geographic issues (tariff of a particular distribution utility, radiation from a specific location, etc.). To validate these results, four sensitivity analyzes were performed: variation of the simultaneity factor between generation and consumption, variation of the tariff readjustment rate, zeroing CAPEX, and exemption from state tax. The behind-the-meter modality of generation proved to be more promising than the construction of a shared plant. However, although the behind-the-meter modality presents better results than the shared plant, there is a greater complexity in adopting this modality due to issues related to the infrastructure of the most vulnerable communities (e.g., precarious electrical networks, need to reinforce roofs). Considering the shared power plant modality, many opportunities are still envisaged since the risk of investing in such a policy can be mitigated. Furthermore, this modality can be an alternative due to the mitigation of the risk of default, as it allows greater control of users and facilitates the process of operation and maintenance. Finally, it was also found, that in some regions of Brazil, the continuity of the SET presents more economic benefits than its replacement by PVDG. However, the proposed policy offers many opportunities. For future works, the model may include other parameters, such as cost with low-income populations’ engagement, and business risk. In addition, other renewable sources of distributed generation can be studied for this purpose.

Keywords: low income, subsidy policy, distributed energy resources, energy justice

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Authors: Sadi Ali, Yaser Kishawi

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As part of Palestine, Gaza Strip (365 km2 and 1.8 million habitants) is considered a semi-arid zone relies solely on the Coastal Aquifer. The coastal aquifer is only source of water with only 5-10% suitable for human use. This barely cover the domestic and agricultural needs of Gaza Strip. Palestinian Water Authority Strategy is to find non-conventional water resource from treated wastewater to irrigate 1500 hectares and serves over 100,000 inhabitants. A new WWTP project is to replace the old-overloaded Biet Lahia WWTP. The project consists of three parts; phase A (pressure line & 9 infiltration basins - IBs), phase B (a new WWTP) and phase C (Recovery and Reuse Scheme – RRS – to capture the spreading plume). Currently, phase A is functioning since Apr 2009. Since Apr 2009, a monitoring plan is conducted to monitor the infiltration rate (I.R.) of the 9 basins. Nearly 23 million m3 of partially treated wastewater were infiltrated up to Jun 2014. It is important to maintain an acceptable rate to allow the basins to handle the coming quantities (currently 10,000 m3 are pumped an infiltrated daily). The methodology applied was to review and analysis the collected data including the I.R.s, the WW quality and the drying-wetting schedule of the basins. One of the main findings is the relation between the Total Suspended Solids (TSS) at BLWWTP and the I.R. at the basins. Since April 2009, the basins scored an average I.R. of about 2.5 m/day. Since then the records showed a decreasing pattern of the average rate until it reached the lower value of 0.42 m/day in Jun 2013. This was accompanied with an increase of TSS (mg/L) concentration at the source reaching above 200 mg/L. The reducing of TSS concentration directly improved the I.R. (by cleaning the WW source ponds at Biet Lahia WWTP site). This was reflected in an improvement in I.R. in last 6 months from 0.42 m/day to 0.66 m/day then to nearly 1.0 m/day as the average of the last 3 months of 2013. The wetting-drying scheme of the basins was observed (3 days wetting and 7 days drying) besides the rainfall rates. Despite the difficulty to apply this scheme accurately a control of flow to each basin was applied to improve the I.R. The drying-wetting system affected the I.R. of individual basins, thus affected the overall system rate which was recorded and assessed. Also the ploughing activities at the infiltration basins as well were recommended at certain times to retain a certain infiltration level. This breaks the confined clogging layer which prevents the infiltration. It is recommended to maintain proper quality of WW infiltrated to ensure an acceptable performance of IBs. The continual maintenance of settling ponds at BLWWTP, continual ploughing of basins and applying soil treatment techniques at the IBs will improve the I.R.s. When the new WWTP functions a high standard effluent quality (TSS 20mg, BOD 20 mg/l and TN 15 mg/l) will be infiltrated, thus will enhance I.R.s of IBs due to lower organic load.

Keywords: SAT, wastewater quality, soil remediation, North Gaza

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Authors: Jelvin Tom Sebastian, Vinod Yeldho Baby

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In space, electronic devices are constantly attacked with radiation, which causes certain parts to fail or behave in unpredictable ways. To advance the thermal controllability for microsatellites, we need a new approach and thermal control system that is smaller than that on conventional satellites and that demand no electric power. Heat exchange inside the microsatellites is not that easy as conventional satellites due to the smaller size. With slight mass gain and no electric power, accommodating heat using phase change materials (PCMs) is a strong candidate for solving micro satellites' thermal difficulty. In other words, PCMs can absorb or produce heat in the form of latent heat, changing their phase and minimalizing the temperature fluctuation around the phase change point. The main restriction for these systems is thermal conductivity weakness of common PCMs. As PCM is having low thermal conductivity, it increases the melting and solidification time, which is not suitable for specific application like electronic cooling. In order to increase the thermal conductivity nanoparticles are introduced. Adding the nanoparticles in base PCM increases the thermal conductivity. Increase in weight concentration increases the thermal conductivity. This paper numerically investigates the thermal energy storage panel with nanoparticle enhanced phase change material. Silver nanostructure have increased the thermal properties of the base PCM, eicosane. Different weight concentration (1, 2, 3.5, 5, 6.5, 8, 10%) of silver enhanced phase change material was considered. Both steady state and transient analysis was performed to compare the characteristics of nanoparticle enhanced phase material at different heat loads. Results showed that in steady state, the temperature near the front panel reduced and temperature on NePCM panel increased as the weight concentration increased. With the increase in thermal conductivity more heat was absorbed into the NePCM panel. In transient analysis, it was found that the effect of nanoparticle concentration on maximum temperature of the system was reduced as the melting point of the material reduced with increase in weight concentration. But for the heat load of maximum 20W, the model with NePCM did not attain the melting point temperature. Therefore it showed that the model with NePCM is capable of holding more heat load. In order to study the heat load capacity double the load is given, maximum of 40W was given as first half of the cycle and the other is given constant OW. Higher temperature was obtained comparing the other heat load. The panel maintained a constant temperature for a long duration according to the NePCM melting point. In both the analysis, the uniformity of temperature of the TESP was shown. Using Ag-NePCM it allows maintaining a constant peak temperature near the melting point. Therefore, by altering the weight concentration of the Ag-NePCM it is possible to create an optimum operating temperature required for the effective working of the electronics components.

Keywords: carbon-fiber-reinforced polymer, micro/nano-satellite, nanoparticle phase change material, thermal energy storage

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Authors: Eszter Repasi, Akos Koller

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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

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Authors: Ayesha Mushtaq

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Asthma is a pulmonary disease in which blockade of the airway takes place due to inflammation as a response to certain allergens. Breathing troubles, cough, and dyspnea are one of the few symptoms. Several studies have indicated a significant effect on asthma due to changes in dietary routines. Certain food items, such as oily foods and other materials, are known to cause an increase in the symptoms of asthma. Low dietary intake of fruits and vegetables may be important in relation to asthma prevalence. The objective of this study is to assess and compare the nutritional status of asthmatic and non-asthmatic patients. The significance of this study lies in the factor that it will help nutritionists to arrange a feasible dietary routine for asthmatic patients. This research was conducted at the Pulmonology Department of the Pakistan Institute of Medical Science Islamabad. About thirty hundred thirty-four million people are affected by asthma worldwide. Pakistan is on the verge of being an uplifted urban population and asthma cases are increasingly high these days. Several studies suggest an increase in the Asthmatic patient population due to improper diet. This is a cross-sectional study aimed at assessing the nutritious standing of Asthmatic and non-asthmatic patients. This research took place at the Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. The research included asthmatic and non-asthmatic patients coming to the pulmonology department clinic at the Pakistan Institute of Medical Sciences (PIMS). These patients were aged between 20-60 years. A questionnaire was developed for these patients to estimate their dietary plans in these patients. The methodology included four sections. The first section was the Socio-Demographic profile, which included age, gender, monthly income and occupation. The next section was anthropometric measurements which included the weight, height and body mass index (BMI) of an individual. The next section, section three, was about the biochemical attributes, such as for biochemical profiling, pulmonary function testing (PFT) was performed. In the next section, Dietary habits were assessed by a food frequency questionnaire (FFQ) through food habits and consumption pattern was assessed. The next section life style data, in which the person's level of physical activity, sleep and smoking habits were assessed. The next section was statistical analysis. All the data obtained from the study were statistically analyzed and assessed. Most of the asthma Patients were females, with weight more than normal or even obese. Body Mass Index (BMI) was higher in asthma Patients than those in non-Asthmatic ones. When the nutritional Values were assessed, we came to know that these patients were low on certain nutrients and their diet included more junk and oily food than healthy vegetables and fruits. Beverages intake was also included in the same assessment. It is evident from this study that nutritional status has a contributory effect on asthma. So, patients on the verge of developing asthma or those who have developed asthma should focus on their diet, maintain good eating habits and take healthy diets, including fruits and vegetables rather than oily foods. Proper sleep may also contribute to the control of asthma.

Keywords: BMI, nutrition, PAL, diet

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Authors: Tristan R. Fraser, Christopher D. Steadman, Christopher J. Boos

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Myopericarditis is an inflammation syndrome characterised by clinical diagnostic criteria for pericarditis, such as chest pain, combined with evidence of myocardial involvement, such as elevation of biomarkers of myocardial damage, e.g., troponins. It can rarely be a complication of therapeutics used for dysregulated immune-mediated diseases such as inflammatory bowel disease (IBD), for example, mesalazine. The infrequency of mesalazine-induced myopericarditis adds to the challenge in its recognition. Rapid diagnosis and the early introduction of treatment are crucial. This case report follows a 24-year-old professional footballer with a past medical history of ulcerative colitis, recently started on mesalazine for disease control. Three weeks after mesalazine was initiated, he was admitted with fever, shortness of breath, and chest pain worse whilst supine and on deep inspiration, as well as elevated venous blood cardiac troponin T level (cTnT, 288ng/L; normal: <13ng/L). Myocarditis was confirmed on initial inpatient cardiac MRI, revealing the presence of florid myocarditis with preserved left ventricular systolic function and an ejection fraction of 67%. This was a longitudinal case study following the progress of a single individual with myopericarditis over four acute hospital admissions over nine weeks, with admissions ranging from two to five days. Parameters examined included clinical signs and symptoms, serum troponin, transthoracic echocardiogram, and cardiac MRI. Serial measurements of cardiac function, including cardiac MRI and transthoracic echocardiogram, showed progressive deterioration of cardiac function whilst mesalazine was continued. Prior to cessation of mesalazine, transthoracic echocardiography revealed a small global pericardial effusion of < 1cm and worsening left ventricular systolic function with an ejection fraction of 45%. After recognition of mesalazine as a potential cause and consequent cessation of the drug, symptoms resolved, with cardiac MRI performed as an outpatient showing resolution of myocardial oedema. The patient plans to make a return to competitive sport. Patients suffering from myopericarditis are advised to refrain from competitive sport for at least six months in order to reduce the risk of cardiac remodelling and sudden cardiac death. Additional considerations must be taken in individuals for whom competitive sport is an essential component of their livelihood, such as professional athletes. Myopericarditis is an uncommon, however potentially serious medical condition with a wide variety of aetiologies, including viral, autoimmune, and drug-related causes. Management is mainly supportive and relies on prompt recognition and removal of the aetiological process. Mesalazine-induced myopericarditis is a rare condition; as such increasing awareness of mesalazine as a precipitant of myopericarditis is vital for optimising the management of these patients.

Keywords: myopericarditis, mesalazine, inflammatory bowel disease, professional athlete

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Authors: Sakinah Idris, Gabrine Jagersma, Bjorn Jaime Van Pelt, Kirstin Greaves-Lord

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Background: The PEERS (Program for the Education and Enrichment of Relational Skills) intervention can be considered a well-established, evidence-based intervention in the USA. However, testing the efficacy of cultural adaptations of PEERS is still ongoing. More and more, the involvement of all stakeholders in the development and evaluation of interventions is acknowledged as crucial for the longer term implementation of interventions across settings. Therefore, in the current project, teens with ASD (Autism Spectrum Disorder), their neurotypical peers, parents, teachers, as well as clinicians were involved in the development and evaluation of the Dutch version of PEERS. Objectives: The current presentation covers (1) the formative phase and (2) the preliminary adaptation test phase of the cultural adaptation of evidence-based interventions. In the formative phase, we aim to describe the process of adaptation of the PEERS program to the Dutch culture and care system. In the preliminary adaptation phase, we will present results from the preliminary adaptation test among 32 adolescents with ASD. Methods: In phase 1, a group discussion on common vocabulary was conducted among 70 teenagers (and their teachers) from special and regular education aged 12-18 years old. This inventory concerned 14 key constructs from PEERS, e.g., areas of interests, locations for making friends, common peer groups and crowds inside and outside of school, activities with friends, commonly used ways for electronic communication, ways for handling disagreements, and common teasing comebacks. Also, 15 clinicians were involved in the translation and cultural adaptation process. The translation and cultural adaptation process were guided by the research team, and who included input and feedback from all stakeholders through an iterative feedback incorporation procedure. In phase 2, The parent-reported Social Responsiveness Scale (SRS), the Test of Adolescent Social Skills Knowledge (TASSK), and the Quality of Socialization Questionnaire (QSQ) were assessed pre- and post-intervention to evaluate potential treatment outcome. Results: The most striking cultural adaptation - reflecting the standpoints of all stakeholders - concerned the strategies for handling rumors and gossip, which were suggested to be taught using a similar approach as the teasing comebacks, more in line with ‘down-to-earth’ Dutch standards. The preliminary testing of this adapted version indicated that the adolescents with ASD significantly improved their social knowledge (TASSK; t₃₁ = -10.9, p < .01), social experience (QSQ-Parent; t₃₁ = -4.2, p < .01 and QSQ-Adolescent; t₃₂ = -3.8, p < .01), and in parent-reported social responsiveness (SRS; t₃₃ = 3.9, p < .01). In addition, subjective evaluations of teens with ASD, their parents and clinicians were positive. Conclusions: In order to further scrutinize the effectiveness of the Dutch version of the PEERS intervention, we recommended performing a larger scale randomized control trial (RCT) design, for which we provide several methodological considerations.

Keywords: cultural adaptation, PEERS, preliminary testing, translation

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Bei Shan Lin, Chun Mei Lu, Ya Ping Chen, Li Chen Lu

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This study explores the ethical issues concerning the use of physical restraint in geriatric care. Physical restraint use in a medical care setting is seen as a controversial form of treatment that has occurred over decades. There is no doubt that people nowadays are living longer than previous generations. The ageing process is inevitable. Common disease such as impaired comprehension, memory loss, and trouble expressing one’s self contribute to the difficulty that these older patients have in adapting to medical institution. For these reasons, physical restraint is often used in reducing the risk of falling, managing wandering behaviour, preventing agitation, and promoting patient compliance in geriatric care. It can mean that physical restraints are considered as a common practice that is used in the care of older patients. It is most commonly used for three specific purposes, including procedural restraint, restraint to prevent falls, and behavioural restraints. Although there have been well documented instances of morbidity and mortality recognised as being potential risks associated with physical restraint use, it continues to be permitted and used in healthcare, often in the name of safety. However, there is insufficient evidence supporting the effectiveness of physical restraint use reducing injuries from falls and controlling challenging behaviour in geriatric care settings. There is barely any empirical evidence of either a scientific basis or clinical trials have evaluated the improvement in patient safety following physical restraint. In difficult clinical situations, guidelines and practical suggestions for Healthcare professionals to comply requirements can help those making appropriate decisions and to facilitate better judgement regarding physical restraint use. The following recommendations are given for physical restraint use in long-term care settings: an interdisciplinary team approach to assess, evaluate, and treat underlying diseases to determine if treatment can ease issues precipitating physical restraint use; a clearly stated purpose of treatment plan should be made after weighing up the risk of physical restraint use against the risk of without physical restraint use; a care plan for physical restraint has to include individualised treatment planning, informed consent, identification and remedial action to avoid negative consequences, regular assessment and modification, reduction and removal of risks; patients and their families must have the opportunity to consider and give voluntary informed consent prior to physical restraint utilisation; patients, family members, and Healthcare professionals should be educated on use and adverse consequences of physical restraints in order to make raise awareness of potential risks and to take appropriate steps to prevent unnecessary harm; after physical restraint removal, Healthcare professionals should discuss with patients and family members about their experience, feelings, and any anxieties regarding the treatment. Physical restraint should always be considered a last resort as deprive patient’s freedom, control, and individuality. Healthcare professionals should emphasise on providing individualized care, interdisciplinary decision-making process, and creative and collaborative alternatives to promote older patient’s rights, dignity and overall well-being as much as possible.

Keywords: ethics healthcare, geriatric care, healthcare, physical restraint

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Authors: Joao Almeida, Ana Azevedo, Myriam Kanoun-Boule, Maria Ines Santos, Antonio Tadeu

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The effects of the increasing expansion of cities and climate changes have encouraged European countries and regions to adopt nature-based solutions with ability to mitigate environmental issues and improve life in cities. Among these strategies, green roofs and urban gardens have been considered ingenious solutions, since they have the desirable potential to improve air quality, prevent floods, reduce the heat island effect and restore biodiversity in cities. However, an additional consumption of fresh water and mineral nutrients is necessary to sustain larger green urban areas. This communication discusses the main technical features of a new system to manage urine recovery at the building level and its application in green roofs. The depletion of critical nutrients like phosphorus constitutes an emergency. In turn, their elimination through urine is one of the principal causes for their loss. Thus, urine recovery in buildings may offer numerous advantages, constituting a valuable fertilizer abundantly available in cities and reducing the load on wastewater treatment plants. Although several urine-diverting toilets have been developed for this purpose and some experiments using urine directly in agriculture have already been carried out in Europe, several challenges have emerged with this practice concerning collection, sanitization, storage and application of urine in buildings. To our best knowledge, current buildings are not designed to receive these systems and integrated solutions with ability to self-manage the whole process of urine recovery, including separation, maturation and storage phases, are not known. Additionally, if from a hygiene point of view human urine may be considered a relatively safe fertilizer, the risk of disease transmission needs to be carefully analysed. A reduction in microorganisms can be achieved by storing the urine in closed tanks. However, several factors may affect this process, which may result in a higher survival rate for some pathogens. In this work, urine effluent was collected under real conditions, stored in closed containers and kept in climatic chambers under variable conditions simulating cold, temperate and tropical climates. These samples were subjected to a first physicochemical and microbiological control, which was repeated over time. The results obtained so far suggest that maturation conditions were reached for all the three temperatures and that a storage period of less than three months is required to achieve a strong depletion of microorganisms. The authors are grateful for the Project WashOne (POCI-01-0247-FEDER-017461) funded by the Operational Program for Competitiveness and Internationalization (POCI) of Portugal 2020, with the support of the European Regional Development Fund (FEDER).

Keywords: sustainable green roofs and urban gardens, urban nutrient cycle, urine-based fertilizers, urine recovery in buildings

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Authors: Sharad Kumar Kulshreshtha

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India is a great land of cultural and traditional diversity. Its spectrums create a unique ambiance in all over the country. Specially, fairs and festivals are ancient phenomena in Indian culture. In India, there are thousands of such religious, spiritual, cultural fairs organized on auspicious occasions. These fairs reflect the effective and efficient role of social governance and responsibility of Indian society. In this context a mega event known as ‘Kumbha Mela’ literally mean ‘Kumbha Fair’ which is organize after every twelve years at (Prayaag) Allahabad an ancient city of India, now is in the state of Uttar Pradesh. Kumbh Mela is one of the largest human congregations on the Earth. The Kumbha Mela that is held here is considered to be the largest and holiest city among the four cities where Kubha fair organize. According to the Hindu religious scripture a dip for possessing the holy confluence, known as Triveni Sangam, which is a meeting point of the three sacred rivers of India i.e., –Ganges, Yamuna and Saraswati (mythical). During the Kumbha fair the River Ganges is believed to turn to nectar, bringing great blessing to everyone who bathes in it. Other activities include religious discussions, devotional singings and mass feedings pilgrims and poor. The venue for Kumbh Mela (fair) depends on the position Sun, Moon, and Jupiter which holds in that period in different zodiac signs. More than 120 Millions (12 Crore) people visited in the Kumbha Fair-2013 in Allahabad. A temporary tented city was set up for the pilgrims over an area of 2 hectares of the land along the river of Ganges. As many as 5 power substations, temporary police stations, hospitals, bus terminals, stalls were set up for providing various facilities to the visitors and thousands of volunteers participated for assistance of this event. All efforts made by fair administration to provide facility to visitors, such security and sanitation, medical care and frequent water and power supply. The efficient and timely arrangement at the Kumbha Mela attracted the attention of many government and institutions. The Harvard University of USA conducted research to find out how it was made possible. This paper will focuses on effective and efficient planning and preparation of Kumbha Fair which includes facilitation process, role of various coordinating agencies. risk management crisis management strategies Prevention, Preparedness, Response, and Recovery (PPRR Approach), emergency response plan (ERP), safety and security issues, various environmental aspects along with health hazards and hygiene crowd management, evacuation, monitoring, control and evaluation.

Keywords: event planning and facility arrangement, risk management, crowd management, India

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Authors: Emma Castiglioni, Nigel Scrutton, Derren Heyes, Alistair Fielding

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By using light as trigger, it is possible to study many biological processes, such as the activity of genes, proteins, and other molecules, with precise spatiotemporal control. Caged compounds, where biologically active molecules are generated from an inert precursor upon laser photolysis, offer the potential to initiate such biological reactions with high temporal resolution. As light acts as the trigger for cleaving the protecting group, the ‘caging’ technique provides a number of advantages as it can be intracellular, rapid and controlled in a quantitative manner. We are developing caging strategies to study the catalytic cycle of a number of enzyme systems, such as nitric oxide synthase and ethanolamine ammonia lyase. These include the use of caged substrates, caged electrons and the possibility of caging the enzyme itself. In addition, we are developing a novel freeze-quench instrument to study these reactions, which combines rapid mixing and flashing capabilities. Reaction intermediates will be trapped at low temperatures and will be analysed by using electron paramagnetic resonance (EPR) spectroscopy to identify the involvement of any radical species during catalysis. EPR techniques typically require relatively long measurement times and very often, low temperatures to fully characterise these short-lived species. Therefore, common rapid mixing techniques, such as stopped-flow or quench-flow are not directly suitable. However, the combination of rapid freeze-quench (RFQ) followed by EPR analysis provides the ideal approach to kinetically trap and spectroscopically characterise these transient radical species. In a typical RFQ experiment, two reagent solutions are delivered to the mixer via two syringes driven by a pneumatic actuator or stepper motor. The new mixed solution is then sprayed into a cryogenic liquid or surface, and the frozen sample is then collected and packed into an EPR tube for analysis. The earliest RFQ instrument consisted of a hydraulic ram unit as a drive unit with direct spraying of the sample into a cryogenic liquid (nitrogen, isopentane or petroleum). Improvements to the RFQ technique have arisen from the design of new mixers in order to reduce both the volume and the mixing time. In addition, the cryogenic isopentane bath has been coupled to a filtering system or replaced by spraying the solution onto a surface that is frozen via thermal conductivity with a cryogenic liquid. In our work, we are developing a novel RFQ instrument which combines the freeze-quench technology with flashing capabilities to enable the studies of both thermally-activated and light-activated biological reactions. This instrument also uses a new rotating plate design based on magnetic couplings and removes the need for mechanical motorised rotation, which can otherwise be problematic at cryogenic temperatures.

Keywords: caged compounds, freeze-quench apparatus, photolysis, radicals

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Authors: Katharina Lapin, Debashis Sanyal

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Worldwide urban areas are growing. Urbanization has a great impact on social and economic development and ecosystem services. This global trend of urbanization also has significant impact on habitat and biodiversity. The impact of urbanization on the biodiversity of cities in Europe and North America is well studied, while there is a lack of data from cities in currently fast growing urban areas. Indian cities are expanding. The scientific community and the governmental authorities are facing the ongoing urbanization process as an opportunity for the environment. This case study supports the evaluation of urban biodiversity of the city Raipur in the North-West of India. The aim of this study is to assess the overview of the environmental and ecological implications of urbanization. The collected data and analysis was used to discuss the challenges for the sustainable city development. Vascular plants were chosen as an appropriate indicator for the assessment of local biodiversity changes. On the one hand, the vegetation cover is sensible to anthropogenic influence, and in the other hand, the local species composition is comparable to changes at the regional and national scale, using the plant index of India. Further information of abiotic situation can be gathered with the determination of indicator species. In order to calculate the influence of urbanization on the native plant diversity, the Shannon diversity index H´ was chosen. The Pielou`s pooled quadrate method was used for estimating diversity when a random sample is not expected. It was used to calculate the Pilou´s index of evenness. The estimated species coverage was used for calculating the H´ and J. Pearson correlation was performed to test the relationship between urbanization pattern and plant diversity. Further, a SWOT analysis was used in for analyzing internal and external factors impinging on a decision making process. The city of Raipur (21.25°N 81.63°E) has a population of 1,010,087 inhabitants living in an urban area of 226km², in the district of the Indian state of Chhattisgarh. Within the last decade, the urban area of Raipur increased. The results show that various novel ecosystems exist in the urban area of Raipur. The high amount of native flora is mainly to find at the shore of urban lakes and along the river Karun. These areas of high Biodiversity Index are to protect as urban biodiversity hot spots. The governmental authorities are well informed about the environmental challenges for the sustainable development of the city. Together with the scientific community of the Technical University of Raipur many engineering solutions are discussed for implementation of the future. The case study helped to point out the importance environmental measures that support the ecosystem services of green infrastructure. The fast process of urbanization is difficult to control. Uncontrolled creation of urban housing leads to difficulties in unsustainable use of natural resources. This is the major threat for the urban biodiversity.

Keywords: India, novel ecosystems, plant diversity, urban ecology

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Authors: Syue-Wen Lin

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Objective: This article explores the nursing experience of an 84-year-old male lung cancer patient who underwent a thoracoscopic right lower lobectomy and treatment. The patient has multiple medical histories, including hypertension and diabetes. The nursing process involved cancer treatment, postoperative pain management, as well as wound care and healing. Methods: The nursing period is from February 10 to February 17, 2024. During the nursing process, pain management strategies are implemented, including morphine drugs and non-drug methods, and music therapy, essential oil massage, and extended reception time are used to make patients feel physically and mentally comfortable so as to reduce postoperative pain and encourage active participation in rehabilitation. Strict sterile wound dressing procedures and advanced wound care techniques are used to promote wound healing and prevent infection. Due to septic shock, dialysis is used to relieve worsening symptoms. Taking into account the patient's cancer status, the nursing team provides comprehensive cancer care based on the patient's physical and psychological needs. Given the complexity of the patient's condition, including advanced cancer, palliative care is also incorporated throughout the care process to relieve discomfort and provide psychological support. Results: Through comprehensive health assessment, the nursing team fully understood the patient's condition and developed a personalized care plan based on the patient's condition. The interprofessional critical care team provides respiratory therapy and lung expansion exercises to reduce muscle loss while addressing the patient's psychological status, pain management, and vital sign stabilization needs, resulting in a comprehensive approach to care. Lung expansion exercises and the use of a high-frequency chest wall oscillation vest successfully improved sputum drainage and facilitated weaning from mechanical ventilation. In addition, helping patients stabilize their vital signs and the integration of cancer care, pain management, wound care and palliative care helps the patient be fully supported throughout the recovery process, ultimately improving his quality of life. Conclusion: Lung cancer and septic shock present significant challenges to patients, and the nursing team not only provides critical care but also addresses the unique needs of patients through comprehensive infection control, cancer care, pain management, wound care, and palliative care interventions. These measures effectively improve patients' quality of life, promote recovery, and provide compassionate palliative care for terminally ill patients. Nursing staff work closely with family members to develop a comprehensive care plan to ensure that patients receive high-quality medical care as well as psychological support and a comfortable recovery environment.

Keywords: septic shock, lung cancer, palliative care, nursing experience

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Authors: Dylan Santos De Pinho, Nabil Ouerhani

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Energy consumption of machine-tools is becoming critical for machine-tool builders and end-users because of economic, ecological and legislation-related reasons. Many machine-tool builders are seeking for solutions that allow the reduction of energy consumption of machine-tools while preserving the same productivity rate and the same quality of machined parts. In this paper, we present the first results of a project conducted jointly by academic and industrial partners to reduce the energy consumption of a Swiss-Type lathe. We employ genetic algorithms to find optimal machining parameters – the set of parameters that lead to the best trade-off between energy consumption, part quality and tool lifetime. Three main machining process parameters are considered in our optimization technique, namely depth of cut, spindle rotation speed and material feed rate. These machining process parameters have been identified as the most influential ones in the configuration of the Swiss-type machining process. A state-of-the-art multi-objective genetic algorithm has been used. The algorithm combines three fitness functions, which are objective functions that permit to evaluate a set of parameters against the three objectives: energy consumption, quality of the machined parts, and tool lifetime. In this paper, we focus on the investigation of the fitness function related to energy consumption. Four different energy consumption related fitness functions have been investigated and compared. The first fitness function refers to the Kienzle cutting force model. The second fitness function uses the Material Removal Rate (RMM) as an indicator of energy consumption. The two other fitness functions are non-deterministic, learning-based functions. One fitness function uses a simple Neural Network to learn the relation between the process parameters and the energy consumption from experimental data. Another fitness function uses Lasso regression to determine the same relation. The goal is, then, to find out which fitness functions predict best the energy consumption of a Swiss-Type machining process for the given set of machining process parameters. Once determined, these functions may be used for optimization purposes – determine the optimal machining process parameters leading to minimum energy consumption. The performance of the four fitness functions has been evaluated. The Tornos DT13 Swiss-Type Lathe has been used to carry out the experiments. A mechanical part including various Swiss-Type machining operations has been selected for the experiments. The evaluation process starts with generating a set of CNC (Computer Numerical Control) programs for machining the part at hand. Each CNC program considers a different set of machining process parameters. During the machining process, the power consumption of the spindle is measured. All collected data are assigned to the appropriate CNC program and thus to the set of machining process parameters. The evaluation approach consists in calculating the correlation between the normalized measured power consumption and the normalized power consumption prediction for each of the four fitness functions. The evaluation shows that the Lasso and Neural Network fitness functions have the highest correlation coefficient with 97%. The fitness function “Material Removal Rate” (MRR) has a correlation coefficient of 90%, whereas the Kienzle-based fitness function has a correlation coefficient of 80%.

Keywords: adaptive machining, genetic algorithms, smart manufacturing, parameters optimization

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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