Search results for: retail food risk factor study

Authors: Yasuyuki Takahashi, Hayato Ishimura, Masao Miyagawa, Teruhito Mochizuki

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Quantitative measurement of myocardium perfusion is possible with single photon emission computed tomography (SPECT) using a semiconductor detector. However, accumulation of ^99mTc-tetrofosmin in the liver may make it difficult to assess that accurately in the inferior myocardium. Our idea is to reduce the high accumulation in the liver by using dynamic SPECT imaging and a technique called time subtraction. We evaluated the performance of a new SPECT system with a cadmium-zinc-telluride solid-state semi- conductor detector (Discovery NM 530c; GE Healthcare). Our system acquired list-mode raw data over 10 minutes for a typical patient. From the data, ten SPECT images were reconstructed, one for every minute of acquired data. Reconstruction with the semiconductor detector was based on an implementation of a 3-D iterative Bayesian reconstruction algorithm. We studied 20 patients with coronary artery disease (mean age 75.4 ± 12.1 years; range 42-86; 16 males and 4 females). In each subject, 259 MBq of ^99mTc-tetrofosmin was injected intravenously. We performed both a phantom and a clinical study using dynamic SPECT. An approximation to a liver-only image is obtained by reconstructing an image from the early projections during which time the liver accumulation dominates (0.5~2.5 minutes SPECT image-5~10 minutes SPECT image). The extracted liver-only image is then subtracted from a later SPECT image that shows both the liver and the myocardial uptake (5~10 minutes SPECT image-liver-only image). The time subtraction of liver was possible in both a phantom and the clinical study. The visualization of the inferior myocardium was improved. In past reports, higher accumulation in the myocardium due to the overlap of the liver is un-diagnosable. Using our time subtraction method, the image quality of the ^99mTc-tetorofosmin myocardial SPECT image is considerably improved.

Keywords: 99mTc-tetrofosmin, dynamic SPECT, time subtraction, semiconductor detector

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Authors: Binod Shrestha, Sandrine Hoppe, Thierry Ghislain, Phillipe Marchal, Nicolas Brosse, Anthony Dufour

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The thermochemical conversion of lignin has received an increasing interest in the frame of different biorefinery concepts for the production of chemicals or energy. It is needed to better understand the physical and chemical conversion of lignin for feeder and reactor designs. In-situ rheology reveals the viscoelastic behaviour of lignin upon thermal conversion. The softening, re-solidification (char formation), swelling and shrinking behaviours are quantified during pyrolysis in real-time [1]. The in-situ rheology of an alkali lignin (Protobind 1000) was conducted in high torque controlled strain rheometer from 35°C to 400°C with a heating rate of 5°C.min-1. The swelling, through glass phase transition overlapped with depolymerization, and solidification (crosslinking and “char” formation) are two main phenomena observed during lignin pyrolysis. The onset of temperatures for softening and solidification for this lignin has been found to be 141°C and 248°C respectively. An ex-situ characterization of lignin/char residues obtained at different temperatures after quenching in the rheometer gives a clear understanding of the pathway of lignin degradation. The lignin residues were sampled from the mid-point temperatures of the softening range and solidification range to study the chemical transformations undergoing. Elemental analysis, FTIR and solid state NMR were conducted after quenching the solid residues (lignin/char). The quenched solid was also extracted by suitable solvent and followed by acetylation and GPC-UV analysis. The combination of 13C NMR and GPC-UV reveals the depolymerization followed by crosslinking of lignin/char. NMR and FTIR provide the evolution of functional moieties upon temperature. Physical and chemical mechanisms occurring during lignin pyrolysis are accounted in this study. Thanks to all these complementary methods.

Keywords: pyrolysis, bio-chemicals, valorization, mechanism, softening, solidification, cross linking, rheology, spectroscopic methods

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Authors: Ana L. Martins, Luis Orfão

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Healthcare systems have been subject to various research efforts aiming at process improvement under a lean approach. Another perspective, agility, has also been used, though in a lower scale, in order to analyse the ability of different hospital services to adapt to demand uncertainties. Both perspectives have a common denominator, the improvement of effectiveness and efficiency of the services in a healthcare setting context. Mixing the two approached allows, on one hand, to streamline the processes, and on the other hand the required flexibility to deal with demand uncertainty in terms of both volume and variety. The present research aims to analyse the impacts of the combination of both perspectives in the effectiveness and efficiency of an hospital service. The adopted methodology is based on a case study approach applied to the process of the ambulatory surgery service of Hospital de Lamego. Data was collected from direct observations, formal interviews and informal conversations. The analyzed process was selected according to three criteria: relevance of the process to the hospital, presence of human resources, and presence of waste. The customer of the process was identified as well as his perception of value. The process was mapped using flow chart, on a process modeling perspective, as well as through the use of Value Stream Mapping (VSM) and Process Activity Mapping. The Spaghetti Diagram was also used to assess flow intensity. The use of the lean tools enabled the identification of three main types of waste: movement, resource inefficiencies and process inefficiencies. From the use of the lean tools improvement suggestions were produced. The results point out that leagility cannot be applied to the process, but the application of lean and agility in specific areas of the process would bring benefits in both efficiency and effectiveness, and contribute to value creation if improvements are introduced in hospital’s human resources and facilities management.

Keywords: case study, healthcare systems, leagility, lean management

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Authors: Minhui Chiu

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According to relevant studies, clinical nurses have high work pressure and relatively high job adaptation needs. The nurses who work in oncology wards have more adaptation needs when they face repeating hospitalization patients. The aims of this study were to investigate the job stress adaptation and related factors of nurses in oncology wards and to understand the predictors of job stress adaptation needs. Convenience sampling was used in this study. The nurses in the oncology specialist ward of a regional teaching hospital in southern Taiwan were selected as the research objects. A cross-sectional survey was conducted using a structured questionnaire, random sampling, and the questionnaires were filled out by the participating nurses. A total of 68 people were tested, and 65 valid questionnaires (95.6%). One basic data questionnaire and nurses’ job stress adaptation needs questionnaire were used. The data was archived with Microsoft Excel, and statistical analysis was performed with JMP12.0. The results showed that the average age was 28.8 (±6.7) years old, most of them were women, 62 (95.38%), and the average clinical experience in the hospital was 5.7 years (±5.9), and 62 (95.38%) were university graduates. 39 people (60.0%) had no work experience. 39 people (60.0%) liked nursing work very much, and 23 people (35.3%) just “liked”. 47 (72.3%) people were supported to be oncology nurses by their families. The nurses' job stress adaptation needs were 119.75 points (±17.24). The t-test and variance analysis of the impact of nurses' job pressure adaptation needs were carried out. The results showed that the score of college graduates was 121.10 (±16.39), which was significantly higher than that of master graduates 96.67 (±22.81), and the degree of liking for nursing work also reached a Significant difference. These two variables are important predictors of job adaptation needs, and the R Square is 24.15%. Conclusion: Increasing the love of clinical nurses in nursing and encouraging university graduation to have positive effects on job pressure adaptation needs and can be used as a reference for the management of human resources hospitals for oncology nurses.

Keywords: oncology nurse, job stress, job stress adaptation needs, manpower

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Authors: Fabiana Franceschi, Martha Cobo, Manuel Figueredo

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Bogotá, the capital of Colombia, is its largest city and one of the most polluted in Latin America due to the fast economic growth over the last ten years. Bogotá has been affected by high pollution events which led to the high concentration of PM10 and NO2, exceeding the local 24-hour legal limits (100 and 150 g/m3 each). The most important pollutants in the city are PM10 and PM2.5 (which are associated with respiratory and cardiovascular problems) and it is known that their concentrations in the atmosphere depend on the local meteorological factors. Therefore, it is necessary to establish a relationship between the meteorological variables and the concentrations of the atmospheric pollutants such as PM10, PM2.5, CO, SO2, NO2 and O3. This study aims to determine the interrelations between meteorological variables and air pollutants in Bogotá, using data mining techniques. Data from 13 monitoring stations were collected from the Bogotá Air Quality Monitoring Network within the period 2010-2015. The Principal Component Analysis (PCA) algorithm was applied to obtain primary relations between all the parameters, and afterwards, the K-means clustering technique was implemented to corroborate those relations found previously and to find patterns in the data. PCA was also used on a per shift basis (morning, afternoon, night and early morning) to validate possible variation of the previous trends and a per year basis to verify that the identified trends have remained throughout the study time. Results demonstrated that wind speed, wind direction, temperature, and NO2 are the most influencing factors on PM10 concentrations. Furthermore, it was confirmed that high humidity episodes increased PM2,5 levels. It was also found that there are direct proportional relationships between O3 levels and wind speed and radiation, while there is an inverse relationship between O3 levels and humidity. Concentrations of SO2 increases with the presence of PM10 and decreases with the wind speed and wind direction. They proved as well that there is a decreasing trend of pollutant concentrations over the last five years. Also, in rainy periods (March-June and September-December) some trends regarding precipitations were stronger. Results obtained with K-means demonstrated that it was possible to find patterns on the data, and they also showed similar conditions and data distribution among Carvajal, Tunal and Puente Aranda stations, and also between Parque Simon Bolivar and las Ferias. It was verified that the aforementioned trends prevailed during the study period by applying the same technique per year. It was concluded that PCA algorithm is useful to establish preliminary relationships among variables, and K-means clustering to find patterns in the data and understanding its distribution. The discovery of patterns in the data allows using these clusters as an input to an Artificial Neural Network prediction model.

Keywords: air pollution, air quality modelling, data mining, particulate matter

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Authors: Tsai Yu-hsin, Chung Yi-Hsin

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The employment of an HSR system, resulting in elevation in the inter-city/-region accessibility, is likely to promote spatial interaction between places in the HSR and extended territory. The inter-city/-region travel via HSR could be, among others, affected by the land use, transportation, and location of the HSR station at both trip origin and destination ends. However, relatively few insights have been shed on these impacts and spatial patterns of the HSR travel. The research purposes, as phase one of a series of HSR related research, of this study are threefold: to analyze the general spatial patterns of HSR trips, such as the spatial distribution of trip origins and destinations; to analyze if specific land use, transportation characteristics, and trip characteristics affect HSR trips in terms of the use of HSR, the distribution of trip origins and destinations, and; to analyze the socio-economic characteristics of HSR travelers. With the Taiwan HSR starting operation in 2007, this study emphasizes on the intermediate-term impact of HSR, which is made possible with the population and housing census and industry and commercial census data and a station area intercept survey conducted in the summer 2014. The analysis will be conducted at the city, inter-city, and inter-region spatial levels, as necessary and required. The analysis tools include descriptive statistics and multivariate analysis with the assistance of SPSS, HLM and ArcGIS. The findings, on the one hand, can provide policy implications for associated land use, transportation plan and the site selection of HSR station. On the other hand, on the travel the findings are expected to provide insights that can help explain how land use and real estate values could be affected by HSR in following phases of this series of research.

Keywords: high speed rail, land use, travel, spatial pattern

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Authors: Yakin Ekin, Onur Akbulut

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This study aims not only to create a summarized background for the effective and efficient use of the potential of Izmir by providing the strategic planning works and institutional and sectoral strategy documents with different purposes realized by all relevant institutions and organizations in Izmir and Aegean Region to steer towards the same priorities and aims, but also focuses on a criticism and comparison viewpoint about tourism sector in Izmir.

Keywords: regional plan, Izmir, tourism, sectoral strategy

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Authors: Amira A. A. Abdallah, Amir A. Beltagi

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Background: Core stability training has recently attracted attention for improving muscle balance and optimizing performance in healthy and unhealthy individuals. Purpose: This study investigated the effect of beginner’s core stability exercises on trunk flexors’/extensors’ peak torque ratio and trunk flexors’ and extensors’ peak torques. Methods: Thirty five healthy individuals participated in the study. They were randomly assigned to two groups; experimental “group I, n=20” and control “group II, n=15”. Their mean age, weight and height were 20.7±2.4 vs. 20.3±0.61 years, 66.5±12.1 vs. 68.57±12.2 kg and 166.7±7.8 vs. 164.28 ±7.59 cm. for group I vs. group II. Data were collected using the Biodex Isokinetic system. The participants were tested twice; before and after a 6-week period during which group I performed a core stability training program. Results: The 2x2 Mixed Design ANOVA revealed that there were no significant differences (p>0.025) in the trunk flexors’/extensors’ peak torque ratio between the pre-test and post-test conditions for either group. Moreover, there were no significant differences (p>0.025) in the trunk flexion/extension ratios between both groups at either condition. However, the 2x2 Mixed Design MANOVA revealed significant increases (p<0.025) in the trunk flexors’ and extensors’ peak torques in the post-test condition compared with the pre-test in group I with no significant differences (p>0.025) in group II. Moreover, there was a significant increase (p<0.025) in the trunk flexors’ peak torque only in group I compared with group II in the post-test condition with no significant differences in the other conditions. Interpretation/Conclusion: The improvement in muscle performance indicated by the increase in the trunk flexors’ and extensors’ peak torques in the experimental group recommends including core stability training in the exercise programs that aim to improve muscle performance.

Keywords: core stability, isokinetic, trunk muscles, muscle balance

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Rami Qaoud, Alkama Djamal

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When we ask about the impact of rising architectural façade in improving the terms physical urban ambiance inside the free space for urban fabric. Considered as bringing back life and culture values and civilization to these cities. And This will be the theme of this search. Where we have conducted the study about the relationship that connects the empty and full of in the urban fabric in terms of the density construction and the architectural elevation of its façade to street view. In this framework, we adopted in the methodology of this research the technical field experience. And according to three types of Street engineering(H≥2W, H=W, H≤0.5W). Where we conducted a field to raise the values of the physical ambiance according to three main axes of ambiance. The first axe 1 - Thermal ambiance. Where the temperature values were collected, relative humidity, wind speed, temperature of surfaces (the outer wall-ground). The second axe 2- Visual ambiance. Where we took the values of natural lighting levels during the daytime. The third axe 3- Acoustic ambiance . Where we take sound values during the entire day. That experience, which lasted for three consecutive days, and through six stations of measuring, where it has been one measuring station for each type of the street engineering and in two different way street. Through the obtained results and with the comparison of those values. We noticed the difference between this values and the three type of street engineering. Where the difference the calorific values of air equal 4 ° C , in terms of the visual ambiance the difference in the direct lighting natural periods amounted six hours between the three types of street engineering. As well in terms of sound ambience, registered a difference in values of up 15 (db) between the three types. This difference in values indicates The impact of rising architectural façade in improving the physical urban ambiance within the free field - street- for urban fabric.

Keywords: street, physical urban ambience, rising architectural façade, urban fabric

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Authors: Vephkhvia Grigalashvili

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The defense of Georgia is every citizen’s duty. The present article reviews the principles and standards of gender policy in the Georgian national defense sector. In addition, it looks at mechanisms for ensuring gender equality, going through the relevant Georgian legislation. Furthermore, this work aims to conduct a comparative analysis of defense models of Georgia, Finland, and the Baltic States in order to identify core institutional challenges. The study produced the following findings:(a) The national defense planning is based on the Total Defense approach, which implies a wide involvement of the country`s population in state defense. (b) This political act does not specify gender equality aspects of the Total Defense strategy; (c) According to the Constitution of Georgia, irrespective of gender factors, every citizen of Georgia is legally obliged to participate in state security activities. However, the state has an authority (power of choice) to decide which gender group (male or/and female citizen) must fulfill above mentioned their constitutional commitment. For instance, completion of compulsory military and reserve military services is a male citizen’s duty, whereas professional military service is equally accessible to both genders. The study concludes that effective implementation of the Total Defense concept largely depends on how Georgia uses its capabilities and human resources. Based on the statistical fact that more than 50% of the country’s population are women, Georgia has to elaborate on relevant institutional mechanisms for implementation of gender equality in the national defense organization. In this regard, it would be advisable: (i) to give the legal opportunity to women to serve in compulsory military service, and (ii) to develop labor reserve service as a part of the anti-crisis management system of Georgia.

Keywords: gender in defense organisation, gender mechanisms, gender in defense policy, gender policy

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Authors: Eunice Chiamaka Allen-Ngbale

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Prior to bill of lading (BOL), merchants travelled along with their goods; then recorded the goods in the ship’s mates’ register; and finally started selling the goods while in transit by way of BOL, indicative that BOL is negotiable. Common law doctrine of privity of contract did not allow the transfer of right to sue to a non-party to the contract. This created hardship to cargo owners, which made many jurisdictions enact laws in this regard. Bill of Lading Act 1855 (BLA) was enacted in the United Kingdom, which applied as statute of general application under section 375 Merchant Shipping Act 1990 (MSA) in Nigeria; and conferred contractual rights of the suit on consignees and endorsees, but on the passing of ownership upon or by reason of such consignment or endorsement on the shipment of the goods simultaneously. The repeal of section 375 MSA by section 439 MSA 2007 created a lacuna, and the doctrine of privity of contract is the extant law in Nigeria. The aim of this study is to evaluate laws governing the transfer of the contractual right of suit to a third party under the bill of lading in Nigeria. The specific objectives of this study are to ascertain: (i) whether the extant law of common law doctrine of privity of the contract covers the transfer of the right of suit to the third party under the bill of lading in Nigeria; (ii) impediment(s) of the common law to transfer such right in Nigeria in the absence of any legislation; (iii) the level of applicability of the doctrine of privity of contract as it relates to transfer of the contractual right of suit to third party under the bill of lading in Nigeria; and (iv) whether to proffer possible suggestion on how to fill the lacuna left by the repeal of Merchant Shipping Act 1990. This work adopted a doctrinal approach with reliance on primary and secondary source materials. It finds that the common law doctrine of privity of contract in Nigeria is retrogressive. This work recommends for amendment of the relevant statute to cure this defect/lacuna like other commonwealth nations for best international practices.

Keywords: contract of carriage by sea, doctrine of privity of contract, lawful holder of bill of lading, third party right of suit

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Authors: Cemil Kutlutürk

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Hindu culture and religious doctrines such as caste, reincarnation, yoga, nirvana have always proved a popular theme for the film industry. The analyzing of these motifs in the movies with a scientific approach enables to individuals either to comprehend the messages and deep meanings of films or to understand others’ religious beliefs systems and daily lives in a properly way. The primary aim of this study is to handle the subtle influence of Hindu doctrines on cinema industry by focusing on James Cameron’s film, Avatar and its relationship with Hindu concept of avatara by referring to original Hindu sacred texts where this doctrine is basically clarified. The Sanskrit word avatara means to come down or to descend. Although an avatara is commonly considered as an appearance of any deity on earth, the term refers the Vishnu’s descending on earth. When the movie avatar and avatara doctrine are compared, various similarities have noteworthy revealed. Firstly in the movie, Jake is chosen by Eywa to protect Pandora from evils. Similarly in the movie, avatar is born when there is a rise of jealousy and unrighteousness. The same concept is found in avatara doctrine. According to this belief whenever righteousness (dharma) wanes and unrighteousness (adharma) increases God incarnates himself as an avatara. In Hindu tradition, the ten avataras of Vishnu are the most popular. This standard list of ten avataras includes the Fish, the Tortoise, the Boar, the Man-Lion (Narasimha), the Dwarf, Parasurama, Rama, Krishna, the Buddha and Kalki. In the movie the avatar has tail, eyes, nose, ear which is similar to Narasimha (half man-half lion) avatara. On the other hand use of bow and arrow by Navis in the film, evokes us Rama avatara whose basic gun is same. Navis fly on a dragon like bird called Ikra and ride a horse-like quadruped animal. The vehicle for transformation of the avatar in the movie is also resemblance with the idea of Garuda, the great mythical bird, which is used by Vishnu in Hindu mythology. In addition, the last avatara, Kalki, will be seen on a white horse according to Puranas. The basic difference is that for Hinduism avatara means descent of a God, yet in the movie, a human being named Jake Sully, is manifested as humanoid of another planet, this is called as avatar. While in the movie the avatar manifests himself in another planet, Pandora, in Hinduism avataras descent on this world. On the other hand, in Hindu scriptures, there are many avataras and they are categorized according to their functions and attributes. These sides of avatara doctrine cannot be also seen clearly in the film. Even though there are some differences between each other, the main hypothesis of this study is that the general character of the movie is similar to avatara doctrine. In the movie instead of emphasizing on a specific avatara, qualities of different Vishnu avataras have been properly used.

Keywords: film industry, Hinduism, incarnation, James Cameron, movie avatar

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Authors: Athicha Cherdpunt, Patompong Satapornpong

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The medical cannabis is made up of components also known as cannabinoids, which consists of two ingredients which are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Interestingly, the Cannabinoid can be used for many treatments such as chemotherapy, including nausea and vomiting, cachexia, anorexia nervosa, spinal cord injury and disease, epilepsy, pain, and many others. However, the adverse drug reactions (ADRs) of THC can cause sedation, anxiety, dizziness, appetite stimulation and impairments in driving and cognitive function. Furthermore, genetic polymorphisms of CYP2C9, CYP2C19 and CYP3A4 influenced the THC metabolism and might be a cause of ADRs. Particularly, CYP2C19*17 allele increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (UM). The aim of this study, is to investigate the frequency of CYP2C19*17 alleles in Thai patients who have been treated with medical cannabis. We prospectively enrolled 60 Thai patients who were treated with medical cannabis and clinical data from College of Pharmacy, Rangsit University. DNA of each patient was isolated from EDTA blood, using the Genomic DNA Mini Kit. CYP2C19*17 genotyping was conducted using the real time-PCR ViiA7 (ABI, Foster City, CA, USA). 30 patients with medical cannabis-induced ADRs group, 20 (67%) were female, and 10 (33%) were male, with an age range of 30-69 years. On the other hand, 30 patients without medical cannabis-induced ADRs (control group) consist of 17 (57%) female and 13 (43%) male. The most ADRs for medical cannabis treatment in the case group were dry mouth and dry throat (77%), tachycardia (70%), nausea (30%) and arrhythmia(10%). Accordingly, the case group carried CYP2C19*1/*1 (normal metabolizer) approximately 93%, while 7% patients carrying CYP2C19*1/*17 (ultra rapid metabolizers) exhibited in this group. Meanwhile, we found 90% of CYP2C19*1/*1 and 10% of CYP2C19*1/*17 in control group. In this study, we identified the frequency of CYP2C19*17 allele in Thai population which will support the pharmacogenetics biomarkers for screening and avoid ADRs of medical cannabis treatment.

Keywords: CYP2C19, allele frequency, ultra rapid metabolizer, medical cannabis

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Authors: Isaac Kofi Mensah

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The manual system of voting has been the most widely used system of electing representatives around the globe, particularly in Africa. Due to the known numerous problems and challenges associated with the manual system of voting, many countries are migrating to the electronic voting system as a suitable and credible means of electing representatives over the manual paper-based system. This research paper therefore investigated the factors influencing adoption and use of an electronic voting system in Ghana. A total of 400 Questionnaire Instruments (QI) were administered to potential respondents in Ghana, of which 387 responded representing a response rate of 96.75%. The Technology Acceptance Model was used as the theoretical framework for the study. The research model was tested using a simple linear regression analysis with SPSS. A little of over 71.1% of the respondents recommended the Electoral Commission (EC) of Ghana to adopt an electronic voting system in the conduct of public elections in Ghana. The results indicated that all the six predictors such as perceived usefulness (PU), perceived ease of use (PEOU), perceived free and fair elections (PFFF), perceived credible elections (PCE), perceived system integrity (PSI) and citizens trust in the election management body (CTEM) were all positively significant in predicting the readiness of citizens to adopt and use an electronic voting system in Ghana. However, jointly, the hypotheses tested revealed that apart from Perceived Free and Fair Elections and Perceived Credible and Transparent Elections, all the other factors such as PU, Perceived System Integrity and Security and Citizen Trust in the Election Management Body were found to be significant predictors of the Willingness of Ghanaians to use an electronic voting system. All the six factors considered in this study jointly account for about 53.1% of the reasons determining the readiness to adopt and use an electronic voting system in Ghana. The implications of this research finding on elections in Ghana are discussed.

Keywords: credible elections, Election Management Body (EMB), electronic voting, Ghana, Technology Acceptance Model (TAM)

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Authors: Gurbanova Lamiya

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The Republic of Azerbaijan is considered a region with limited water resources, as up to 70% of surface water is formed outside the country's borders, and most of its territory is an arid (dry) climate zone. It is located at the lower limit of transboundary flows, which is the weakest source of natural water resources in the South Caucasus. It is essential to correctly assess the quality of natural, collector-drainage and groundwater of the area and their suitability for irrigation in order to properly carry out land reclamation measures, provide the normal water-salt regime, and prevent repeated salinization. Through the 141-km-long main Mil-Mugan collector, groundwater, household waste, and floodwaters generated during floods and landslides are poured into the Caspian Sea. The hydrochemical composition of the samples taken from the Sabir irrigation canal passing through the center of the Kura-Araz plain, the Main Mil-Mugan Collector, and the groundwater of the region, which we chose as our research object, were studied and the obtained results were compared by periods. A model is proposed that allows for a complete visualization of the primary materials collected for the study area. The practical use of the established digital model provides all possibilities. The practical use of the established digital model provides all possibilities. An extensive database was created with the ArcGis 10.8 package, using publicly available LandSat satellite images as primary data in addition to ground surveys to build the model. The principles of the construction of the geographic information system of modern GIS technology were developed, the boundary and initial condition of the research area were evaluated, and forecasts and recommendations were given.

Keywords: irrigation channel, groundwater, collector, meliorative measures

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Authors: Othman Maklouf, Ahmed Adwaib

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This paper introduces a comparative study between the main GPS/INS coupling schemes, this will include the loosely coupled and tightly coupled configurations, several types of situations and operational conditions, in which the data fusion process is done using Kalman filtering. This will include the importance of sensors calibration as well as the alignment of the strap down inertial navigation system. The limitations of the inertial navigation systems are investigated.

Keywords: GPS, INS, Kalman filter, sensor calibration, navigation system

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Authors: Ali Raouli, Amin Chegenizadeh, Hamid Nikraz

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The Perth metropolitan area and its surrounding regions have been expanding rapidly in recent decades and it is expected that this growth will continue in the years to come. With this rapid growth and the resulting increase in population, consideration should be given to strategic planning and modelling for the future expansion of Perth. The accurate estimation of projected traffic volumes has always been a major concern for the transport modelers and planners. Development of a reliable strategic transport model depends significantly on the inputs data into the model and the calibrated parameters of the model to reflect the existing situation. Trip distribution is the second step in four-step modelling (FSM) which is complex due to its behavioral nature. Gravity model is the most common method for trip distribution. The spatial separation between the Origin and Destination (OD) zones will be reflected in gravity model by applying deterrence functions which provide an opportunity to include people’s behavior in choosing their destinations based on distance, time and cost of their journeys. Deterrence functions play an important role for distribution of the trips within a study area and would simulate the trip distances and therefore should be calibrated for any particular strategic transport model to correctly reflect the trip behavior within the modelling area. This paper aims to review the most common deterrence functions and propose a calibrated deterrence function for work trips within the Perth Metropolitan Area based on the information obtained from the latest available Household data and Perth and Region Travel Survey (PARTS) data. As part of this study, a four-step transport model using EMME software has been developed for Perth Metropolitan Area to assist with the analysis and findings.

Keywords: deterrence function, four-step modelling, origin destination, transport model

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Authors: Rebin Mzhda Mohammed, Hoshmand Ali Hama Agha

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Excess skin, often consequential to substantial weight loss or the aging process, introduces physical discomfort, obstructs daily activities, and undermines an individual's self-esteem. As these challenges become increasingly prevalent, the need to explore viable solutions grows in significance. Extra skin removal surgery, colloquially known as body contouring surgery, has emerged as a compelling intervention to ameliorate the physical and psychological burdens of excess skin. This study undertakes a comprehensive review to illuminate the intricacies of extra skin removal surgery, encompassing its diverse procedures, associated risks, benefits, and psychological implications on patients. The methodological approach adopted involves a systematic and exhaustive review of pertinent scholarly literature sourced from reputable databases, including PubMed, Google Scholar, and specialized cosmetic surgery journals. Articles are meticulously curated based on their relevance, credibility, and recency. Subsequently, data from these sources are synthesized and categorized, facilitating a comprehensive understanding of the subject matter. Qualitative analysis serves to unravel the nuanced psychological effects, while quantitative data, where available, are harnessed to underpin the study's conclusions. In terms of major findings, the research underscores the manifold advantages of extra skin removal surgery. Patients experience a notable improvement in physical comfort, amplified mobility, enhanced self-confidence, and a newfound ability to don clothing comfortably. Nonetheless, the benefits are juxtaposed with potential risks, encompassing infection, scarring, hematoma, delayed healing, and the challenge of achieving symmetry. A salient discovery is the profound psychological impact of the surgery, as patients consistently report elevated body image satisfaction, heightened self-esteem, and a substantial enhancement in overall quality of life. In summation, this research accentuates the pivotal role of extra skin removal surgery in ameliorating the intricate interplay of physical and psychological difficulties posed by excess skin. By elucidating the diverse procedures, associated risks, and psychological outcomes, the study contributes to a comprehensive and informed comprehension of the surgery's multifaceted effects. Therefore, individuals contemplating this transformative surgical option are equipped with comprehensive insights, ultimately fostering informed decision-making, guided by the expertise of medical professionals.

Keywords: extra skin removal surgery, body contouring, abdominoplasty, brachioplasty, thigh lift, body lift, benefits, risks, psychological effects

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Authors: Harsha B. R., Anil Kumar K. S.

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Climate and soils are the two most dynamic entities among the factors affecting growth and grapes productivity. Studying of prevailing climate over the years in a region provides sufficient information related to management practices to be carried out in vineyards. Evaluating the suitability of vineyard soils under different climatic conditions serves as the yardstick to analyse the performance of grapevines. This study was formulated to study the climate and evaluate the site-suitability of soils in vineyards of southern Karnataka, which has registered its superiority in the quality production of wine. Ten soil profiles were excavated for suitability evaluation of soils, and six taluks were studied for climatic analysis. In almost all the regions studied, recharge starts at the end of the May or June months, peaking in either September or October months. Soil Starts drying from mid of December months in the taluks studied. Bangalore North (Rajanukunte) soils were highly suited for grapes cultivation with no or slight limitations. Bangalore North (GKVK Farm) was moderately suited with slight to moderate limitations of slope and available nitrogen content. Moderate suitability was observed in the rest of the profiles studied in Eastern dry zone soils with the slight to moderate limitations of either organic carbon or available nitrogen or both in the Eastern dry zone. Magadi (Southern dry zone) soils were moderately suitable with slight to moderate limitations of graveliness, available nitrogen, organic carbon, and exchangeable sodium percentage. Sustainable performance of vineyards in terms of yield can be achieved in these taluks by managing the constraints existing in soils.

Keywords: climatic analysis, dry zone, water recharge, growing period, suitability, sustainability

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Authors: Louise Ödlund, Danica Djuric Ilic

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Sustainable development includes many challenges related to energy use, such as (1) developing flexibility on the demand side of the electricity systems due to an increased share of intermittent electricity sources (e.g., wind and solar power), (2) overcoming economic challenges related to an increased share of renewable energy in the transport sector, (3) increasing efficiency of the biomass use, (4) increasing utilization of industrial excess heat (e.g., approximately two thirds of the energy currently used in EU is lost in the form of excess and waste heat). The European Commission has been recognized DH technology as of essential importance to reach sustainability. Flexibility in the fuel mix, and possibilities of industrial waste heat utilization, combined heat, and power (CHP) production and energy recovery through waste incineration, are only some of the benefits which characterize DH technology. The aim of this study is to provide an overview of the possible business strategies which would enable DH to have an important role in future sustainable energy systems. The methodology used in this study is a systematic literature review. The study includes a systematic approach where DH is seen as a part of an integrated system that consists of transport , industrial-, and electricity sectors as well. The DH technology can play a decisive role in overcoming the sustainability challenges related to our energy use. The introduction of biofuels in the transport sector can be facilitated by integrating biofuel and DH production in local DH systems. This would enable the development of local biofuel supply chains and reduce biofuel production costs. In this way, DH can also promote the development of biofuel production technologies that are not yet developed. Converting energy for running the industrial processes from fossil fuels and electricity to DH (above all biomass and waste-based DH) and delivering excess heat from industrial processes to the local DH systems would make the industry less dependent on fossil fuels and fossil fuel-based electricity, as well as the increasing energy efficiency of the industrial sector and reduce production costs. The electricity sector would also benefit from these measures. Reducing the electricity use in the industry sector while at the same time increasing the CHP production in the local DH systems would (1) replace fossil-based electricity production with electricity in biomass- or waste-fueled CHP plants and reduce the capacity requirements from the national electricity grid (i.e., it would reduce the pressure on the bottlenecks in the grid). Furthermore, by operating their central controlled heat pumps and CHP plants depending on the intermittent electricity production variation, the DH companies may enable an increased share of intermittent electricity production in the national electricity grid.

Keywords: energy system, district heating, sustainable business strategies, sustainable development

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Authors: Bhenjamin Jordan L. Ona

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Weather modification is an act of altering weather systems that catches interest on scientific studies. Cloud seeding is a common form of weather alteration. On the same principle, tropical cyclone mitigation experiment follows the methods of cloud seeding with intensity to account for. This study will present the effects of aerosol to tropical cyclone cloud microphysics and intensity. The framework of Weather Research and Forecasting (WRF) model incorporated with Thompson aerosol-aware scheme is the prime host to support the aerosol-cloud microphysics calculations of cloud condensation nuclei (CCN) ingested into the tropical cyclones before making landfall over the Philippine coast. The coupled microphysical and radiative effects of aerosols will be analyzed using numerical data conditions of Tropical Storm Ketsana (2009), Tropical Storm Washi (2011), and Typhoon Haiyan (2013) associated with varying CCN number concentrations per simulation per typhoon: clean maritime, polluted, and very polluted having 300 cm-3, 1000 cm-3, and 2000 cm-3 aerosol number initial concentrations, respectively. Aerosol species like sulphates, sea salts, black carbon, and organic carbon will be used as cloud nuclei and mineral dust as ice nuclei (IN). To make the study as realistic as possible, investigation during the biomass burning due to forest fire in Indonesia starting October 2015 as Typhoons Mujigae/Kabayan and Koppu/Lando had been seeded with aerosol emissions mainly comprises with black carbon and organic carbon, will be considered. Emission data that will be used is from NASA's Moderate Resolution Imaging Spectroradiometer (MODIS). The physical mechanism/s of intensification or deintensification of tropical cyclones will be determined after the seeding experiment analyses.

Keywords: aerosol, CCN, IN, tropical cylone

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Authors: Samineh Barmaki, Ville Jokinen, Esko Kankuri

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We report a microfluidic chip that can be used to modify the gaseous microenvironment of a cell-culture in ambient atmospheric conditions. The aim of the study is to show the cellular response to nitric oxide (NO) under hypoxic (oxygen < 5%) condition. Simultaneously targeting to hypoxic and nitric oxide will provide an opportunity for NO‑based therapeutics. Studies on cellular responses to lowered oxygen concentration or to gaseous mediators are usually carried out under a specific macro environment, such as hypoxia chambers, or with specific NO donor molecules that may have additional toxic effects. In our study, the chip consists of a microfluidic layer and a cell culture well, separated by a thin gas permeable polydimethylsiloxane (PDMS) membrane. The main design goal is to separate the gas oxygen scavenger and NO donor solutions, which are often toxic, from the cell media. Two different types of gas exchangers, titled 'pool' and 'meander' were tested. We find that the pool design allows us to reach a higher level of oxygen depletion than meander (24.32 ± 19.82 %vs -3.21 ± 8.81). Our microchip design can make the cells culture more simple and makes it easy to adapt existing cell culture protocols. Our first application is utilizing the chip to create hypoxic conditions on targeted areas of cell culture. In this study, oxygen scavenger sodium sulfite generates hypoxia and its effect on human embryonic kidney cells (HEK-293). The PDMS membrane was coated with fibronectin before initiating cell cultures, and the cells were grown for 48h on the chips before initiating the gas control experiments. The hypoxia experiments were performed by pumping of O₂-depleted H₂O into the microfluidic channel with a flow-rate of 0.5 ml/h. Image-iT® reagent as an oxygen level responser was mixed with HEK-293 cells. The fluorescent signal appears on cells stained with Image-iT® hypoxia reagent (after 6h of pumping oxygen-depleted H₂O through the microfluidic channel in pool area). The exposure to different levels of O₂ can be controlled by varying the thickness of the PDMS membrane. Recently, we improved the design of the microfluidic chip, which can control the microenvironment of two different gases at the same time. The hypoxic response was also improved from the new design of microchip. The cells were grown on the thin PDMS membrane for 30 hours, and with a flowrate of 0.1 ml/h; the oxygen scavenger was pumped into the microfluidic channel. We also show that by pumping sodium nitroprusside (SNP) as a nitric oxide donor activated under light and can generate nitric oxide on top of PDMS membrane. We are aiming to show cellular microenvironment response of HEK-293 cells to both nitric oxide (by pumping SNP) and hypoxia (by pumping oxygen scavenger solution) in separated channels in one microfluidic chip.

Keywords: hypoxia, nitric oxide, microenvironment, microfluidic chip, sodium nitroprusside, SNP

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Authors: Emad A. S. Abu-Ayyash

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Cohesive devices, the linguistic tools that are usually employed to hold the different parts of the text together, have been the focus of a significant number of discourse analysis studies. These linguistic tools have grabbed the attention of researchers since the inception of the first and most comprehensive model of cohesion in 1976. However, it was noticed that some cohesive devices (e.g., endophoric reference, conjunctions, ellipsis, substitution, and lexical ties) – being thought of as more popular than others (e.g., exophoric reference) – were over-researched. The present paper explores the usage of two cohesive devices that have been evidently almost absent from discourse analysis studies. These cohesive devices are exophoric and homophoric references, the linguistic items that can be interpreted in terms of the physical and cultural contexts of discourse. The significance of the current paper, therefore, stems from the fact that it attempts to fill a gap in the research conducted so far on cohesive devices. This study provides an explanation of the concepts of the cohesive devices that have been employed in a plethora of research on cohesion and elucidates the relevant context-related concepts. The paper also identifies the gap in cohesive devices research. Exophora and homophora, the least visited cohesive devices in previous studies, were qualitatively and quantitatively explored in six opinion articles, four produced by eight postgraduate English as a Foreign Language (EFL) students in a university in the United Arab Emirates and two by professional NS writers in the Independent and the Guardian. The six pieces were about the United Kingdom Independent Party (UKIP) leader’s call to ban the burqa in the UK and were analysed vis-a-vis the employment and function of homophora and exophora. The study found that both EFL students and native speakers employed exophora and homophora considerably in their writing to serve a variety of functions, including building assumptions, supporting main ideas, and involving the readers among others.

Keywords: cohesive devices, context, culture, exophoric reference, homophoric reference

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Authors: Akpobome Harrison

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Community radio serves as a potent vehicle for amplifying local voices and driving community progress worldwide. It facilitates grassroots communication, empowers residents, and significantly contributes to social, cultural, and economic development. This study investigates the pivotal roles of community radio in elevating local voices and advancing development within Emuoha, Obio-Akpor, and Ikwerre Local Government Areas in Rivers State. Employing a quantitative methodology, the research involved random sampling of respondents via questionnaires. The findings underscore the transformative power of community radio in promoting local voices and fostering development, particularly within Rivers State. Moreover, community radio platforms empower marginalized populations, providing them with a voice and an opportunity to actively participate in the media landscape, share their stories, and express their concerns. This empowerment holds the potential to enhance civic engagement and communal harmony. Community radio stations often prioritize local news, events, and subjects that may not receive adequate coverage in mainstream media, thus facilitating the dissemination of vital community information, including local news, weather updates, and emergency alerts. In light of these observations, this paper advocates for the encouragement of community radio by both the state government and private media entities to facilitate seamless information dissemination. Additionally, the paper highlights the significant role played by the use of Pidgin English as a communication tool, particularly in providing understanding and a voice to marginalized individuals in rural communities.

Keywords: community radio, local voices, marginalized populations, information dissemination, pidgin english, grassroots communication

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Authors: L. Donelle, S. Regan, R. Booth, M. Kerr, J. McMurray, D. Fitzsimmons

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Palliative home health care provision within the Canadian context is challenged by: (i) a shortage of registered nurses (RN) and RNs with palliative care expertise, (ii) an aging population, (iii) reliance on unpaid family caregivers to sustain home care services with limited support to conduct this ‘care work’, (iv) a model of healthcare that assumes client self-care, and (v) competing economic priorities. In response, an interprofessional team of service provider organizations, a software/technology provider, and health care providers developed and implemented a technology-enabled model of home care, the eShift model of palliative home care (eShift). The eShift model combines communication and documentation technology with non-traditional utilization of health human resources to meet patient needs for palliative care in the home. The purpose of this study was to investigate the structure, processes, and outcomes of the eShift model of care. Methodology: Guided by Donebedian’s evaluation framework for health care, this qualitative-descriptive study investigated the structure, processes, and outcomes care of the eShift model of palliative home care. Interviews and focus groups were conducted with health care providers (n= 45), decision-makers (n=13), technology providers (n=3) and family care givers (n=8). Interviews were recorded, transcribed, and a deductive analysis of transcripts was conducted. Study Findings (1) Structure: The eShift model consists of a remotely-situated RN using technology to direct care provision virtually to patients in their home. The remote RN is connected virtually to a health technician (an unregulated care provider) in the patient’s home using real-time communication. The health technician uses a smartphone modified with the eShift application and communicates with the RN who uses a computer with the eShift application/dashboard. Documentation and communication about patient observations and care activities occur in the eShift portal. The RN is typically accountable for four to six health technicians and patients over an 8-hour shift. The technology provider was identified as an important member of the healthcare team. Other members of the team include family members, care coordinators, nurse practitioners, physicians, and allied health. (2) Processes: Conventionally, patient needs are the focus of care; however within eShift, the patient and the family caregiver were the focus of care. Enhanced medication administration was seen as one of the most important processes, and family caregivers reported high satisfaction with the care provided. There was perceived enhanced teamwork among health care providers. (3) Outcomes: Patients were able to die at home. The eShift model enabled consistency and continuity of care, and effective management of patient symptoms and caregiver respite. Conclusion: More than a technology solution, the eShift model of care was viewed as transforming home care practice and an innovative way to resolve the shortage of palliative care nurses within home care.

Keywords: palliative home care, health information technology, patient-centred care, interprofessional health care team

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Authors: Faris Tarlochan, Siva Mahesh Tangutooru

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Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.

Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses

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Authors: Ravid Yinon

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Introduction: Pelvic trauma causes high mortality, particularly among the elderly population. Pelvic injury ranges from low-energy incidents such as falls to high-energy trauma like motor vehicle accidents. The mortality rate among high-energy trauma patients is higher, as can be expected. The elderly population is more vulnerable to pelvic trauma even at low energy mechanisms due to the fragility and diminished physiological reserve of these patients. The aim of this study is to examine whether there is a higher long-term mortality in pelvic injuries in the elderly from the low-energy mechanism than those injured in high energy. Methods: A retrospective cohort study was conducted in a level 1 trauma center with injured patients aged 65 years and over with pelvic trauma. The patients were divided into two groups of low and high-energy mechanisms of injury. Multivariate analysis was conducted to characterize the differences between the groups. Results: There were 585 consecutive injured patients over the age of 65 with a documented pelvic injury who were treated at the primary trauma center between 2008-2020. The injured in the high energy group were younger (mean HE- 75.18, LE-80.73), with fewer comorbidities (mean 0.78 comorbidities at HE and 1.28 at LE), more men (52.6% at HE and 27.4% at LE), were consumed more treatments facilities such as angioembolization, ICU admission, emergency surgeries and blood products transfusion and higher mortality rate at admission (HE- 19/133, 14.28%, LE- 10/452, 2.21%) compared to the low energy group. However, in a long-term follow-up of one year after the injury, mortality in the low-energy group was significantly higher (HE- 14/114, 12.28%, LE- 155/442, 35.06%). Discussion: Although it can be expected that in the mechanism of high energy, the mortality rate in the long term would be higher, it was found that mortality at the low energy patient was higher. Apparently, low-energy pelvic injury in geriatric patients is a measure of frailty in these patients, causes injury to more frail and morbid patients, and is a predictor of mortality in this population in the long term. Conclusion: The long-term follow-up of injured elderly with pelvic trauma should be more intense, and the healthcare provider should put more emphasis on the rehabilitation of these special patient populations in an attempt to prevent long-term mortality.

Keywords: pelvic trauma, elderly trauma, high energy trauma, low energy trauma

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Authors: Svetlana Guryeva, Inna Kornienko, Elena Petersen

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At present, translational medicine is a rapidly developing branch of biomedicine. The main idea of translational medicine is a practical application of fundamental research. One of the possible applications for translational medicine is researching therapies that improve human age-related organism condition. To fill the gap between experiments and clinical practice, it is necessary to create the standardized system for the investigation of different effects on cellular aging models. In this study, primary human fibroblasts derived from patients of different ages were used as a cellular aging model. The senescence-associated β-galactosidase activity, lipofuscin, γ-H2AX, the reactive oxygen species level, and cell death markers (annexin V/propidium iodide) were used as biomarkers of the cell functional state. The effects of damaging exposures (oxidative stress and heat shock), potential positive factors (metformin and acetaminophen), and their combinations were investigated using the described biomarkers. Oxidative stress and heat shock caused the increase in the levels of all biomarkers, and only the cells from young patients partly coped with stress 3 days after the exposures. Metformin improved the state of pretreatment cells from young and old patients. The acetaminophen did not show significant changes in the biomarker levels compare to the action of metformin. This study proved the opportunity to develop a standardized screening system based on biomarkers of the cell functional state to identify potential positive or negative effects of some physical and chemical exposures. Moreover, such a system can be useful for the aims of regenerative medicine to determine the effect of cell pretreatment before transplantation.

Keywords: biomarkers, primary fibroblasts, regenerative medicine, senescence, test system, translational medicine

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Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

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Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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