Search results for: high performance working systems

Authors: Suang K. Lau, Ismail Goolam, Rafid Al-Asady

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Background: The majority of patients with hepatocellular carcinoma (HCC) are not suitable for curative treatment, in the form of surgical resection or transplantation, due to tumour extent and underlying liver dysfunction. In these non-resectable cases, a variety of non-surgical therapies are available, including microwave ablation (MWA), which has shown increasing popularity due to its low morbidity, low reported complication rate, and the ability to perform multiple ablations simultaneously. Objective: The aim of this study was to evaluate the validity of MWA as a viable treatment option in the management of HCC and hepatic metastatic disease, by assessing its efficacy and complication rate at a tertiary hospital situated in Westmead (Australia). Methods: A retrospective observational study was performed evaluating patients that underwent MWA between 1/1/2017–31/12/2018 at Westmead Hospital, NSW, Australia. Outcome measures, including residual disease, recurrence rates, as well as major and minor complication rates, were retrospectively analysed over a 12-months period following MWA treatment. Excluded patients included those whose lesions were treated on the basis of residual or recurrent disease from previous treatment, which occurred prior to the study window (11 patients) and those who were lost to follow up (2 patients). Results: Following treatment of 106 new hepatic lesions, the complete response rate (CR) was 86% (91/106) at 12 months follow up. 10 patients had the residual disease at post-treatment follow up imaging, corresponding to an incomplete response (ICR) rate of 9.4% (10/106). The local recurrence rate (LRR) was 4.6% (5/106) with follow-up period up to 12 months. The minor complication rate was 9.4% (10/106) including asymptomatic pneumothorax (n=2), asymptomatic pleural effusions (n=2), right lower lobe pneumonia (n=3), pain requiring admission (n=1), hypotension (n=1), cellulitis (n=1) and intraparenchymal hematoma (n=1). There was 1 major complication reported, with pleuro-peritoneal fistula causing recurrent large pleural effusion necessitating repeated thoracocentesis (n=1). There was no statistically significant association between tumour size, location or ablation factors, and risk of recurrence or residual disease. A subset analysis identified 6 segment VIII lesions, which were treated via a trans-pleural approach. This cohort demonstrated an overall complication rate of 33% (2/6), including 1 minor complication of asymptomatic pneumothorax and 1 major complication of pleuro-peritoneal fistula. Conclusions: Microwave ablation therapy is an effective and safe treatment option in cases of non-resectable hepatocellular carcinoma and liver metastases, with good local tumour control and low complication rates. A trans-pleural approach for high segment VIII lesions is associated with a higher complication rate and warrants greater caution.

Keywords: hepatocellular carcinoma, liver metastases, microwave ablation, trans-pleural approach

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Authors: Victor Pena Ribeiro, Caroline Arruda, Jennyfer Andrea Aldana Mejia, Jairo Kenupp Bastos

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Leishmaniasis is a serious health problem around the world. The treatment of infected individuals with pentavalent antimonial drugs is the main therapeutic strategy. However, they present high toxicity and persistence side effects. Therefore, the discovery of new and safe natural-derived therapeutic agents against leishmaniasis is important. Propolis is a resin of viscous consistency produced by Apis mellifera bees from parts of plants. The main types of Brazilian propolis are green, red, yellow and brown. Thus, the aim of this work was to investigate the chemical composition and leishmanicidal properties of a brown propolis (BP). For this purpose, the hydroalcoholic crude extract of BP was obtained and was fractionated by liquid-liquid chromatography. The chemical profile of the extract and its fractions were obtained by HPLC-UV-DAD. The fractions were submitted to preparative HPLC chromatography for isolation of the major compounds of each fraction. They were analyzed by NMR for structural determination. The volatile compounds were obtained by hydrodistillation and identified by GC/MS. Promastigote forms of Leishmania amazonensis were cultivated in M199 medium and then 2×106 parasites.mL-1 were incubated in 96-well microtiter plates with the samples. The BP was dissolved in dimethyl sulfoxide (DMSO) and diluted into the medium, to give final concentrations of 1.56, 3.12, 6.25, 12.5, 25 and 50 µg.mL⁻¹. The plates were incubated at 25ºC for 24 h, and the lysis percentage was determined by using a Neubauer chamber. The bioassays were performed in triplicate, using a medium with 0.5% DMSO as a negative control and amphotericin B as a positive control. The leishimnicidal effect against promastigote forms was also evaluated at the same concentrations. Cytotoxicity experiments also were performed in 96-well plates against normal (CHO-k1) and tumor cell lines (AGP01 and HeLa) using XTT colorimetric method. Phenolic compounds, flavonoids, and terpenoids were identified in brown propolis. The major compounds were identified as follows: p-coumaric acid (24.6%) for a methanolic fraction, Artepelin-C (29.2%) for ethyl acetate fraction and the compounds of hexane fraction are in the process of structural elucidation. The major volatile compounds identified were β-caryophyllene (10.9%), germacrene D (9.7%), nerolidol (10.8%) and spathulenol (8.5%). The propolis did not show cytotoxicity against normal cell lines (CHO) with IC₅₀ > 100 μg.mL⁻¹, whereas the IC₅₀ < 10 μg.mL⁻¹ showed a potential against the AGP01 cell line, propolis did not demonstrate cytotoxicity against HeLa cell lines IC₅₀ > 100 μg.mL⁻¹. In the determination of the leishmanicidal activity, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations of the crude extract caused the lysis of 76% and 45% of promastigote forms of L. amazonensis, respectively. To the amastigote form, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations caused the mortality of 89% and 75% of L. amazonensis, respectively. The IC₅₀ was 2.8 μg.mL⁻¹ to amastigote form and 3.9 μg.mL⁻¹ to promastigote form, showing a promising activity against Leishmania amazonensis.

Keywords: amastigote, brown propolis, cytotoxicity, promastigote

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Authors: Audrey Ngambia, Ondrej Masek, Valentina Erastova

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Biochar is an amorphous carbon-rich material generated from the pyrolysis of biomass with multifarious properties and functionality. Biochar has shown proven applications in the treatment of flue gas and organic and inorganic pollutants in soil and water/wastewater as a result of its multiple surface functional groups and porous structures. These properties have also shown potential in energy storage and carbon capture. The availability of diverse sources of biomass to produce biochar has increased interest in it as a sustainable and environmentally friendly material. The properties and porous structures of biochar vary depending on the type of biomass and high heat treatment temperature (HHT). Biochars produced at HHT between 400°C – 800°C generally have lower H/C and O/C ratios, higher porosities, larger pore sizes and higher surface areas with temperature. While all is known experimentally, there is little knowledge on the porous role structure and functional groups play on processes occurring at the atomistic scale, which are extremely important for the optimization of biochar for application, especially in the adsorption of gases. Atomistic simulations methods have shown the potential to generate such amorphous materials; however, most of the models available are composed of only carbon atoms or graphitic sheets, which are very dense or with simple slit pores, all of which ignore the important role of heteroatoms such as O, N, S and pore morphologies. Hence, developing realistic models that integrate these parameters are important to understand their role in governing adsorption mechanisms that will aid in guiding the design and optimization of biochar materials for target applications. In this work, molecular dynamics simulations in the isobaric ensemble are used to generate realistic biochar models taking into account experimentally determined H/C, O/C, N/C, aromaticity, micropore size range, micropore volumes and true densities of biochars. A pore generation approach was developed using virtual atoms, which is a Lennard-Jones sphere of varying van der Waals radius and softness. Its interaction via a soft-core potential with the biochar matrix allows the creation of pores with rough surfaces while varying the van der Waals radius parameters gives control to the pore-size distribution. We focused on microporosity, creating average pore sizes of 0.5 - 2 nm in diameter and pore volumes in the range of 0.05 – 1 cm3/g, which corresponds to experimental gas adsorption micropore sizes of amorphous porous biochars. Realistic biochar models with surface functionalities, micropore size distribution and pore morphologies were developed, and they could aid in the study of adsorption processes in confined micropores.

Keywords: biochar, heteroatoms, micropore size, molecular dynamics simulations, surface functional groups, virtual atoms

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Authors: Charmaine B. Distor

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Collaboration has long been recognized in different fields, but there’s been little research on operationalizing it especially on a multi-sectoral setting as per the author’s best knowledge. Also, communication is one of the factors that is usually overlooked when studying it. Specifically, this study aimed to describe the organizational profile and tasks of collaborators in the visitor management program of Make It Makiling (MIM). It also identified the factors that motivated collaborators to collaborate in MIM while determining the communication dimensions in the collaborative process. It also determined the communication channels used by collaborators in MIM while identifying the outcomes of collaboration in MIM. This study also found out if a relationship exists between collaborators’ motivations for collaboration and their perceived outcomes of collaboration, and collaborators' communication dimensions and their perceived outcomes of collaboration. Lastly, it also provided recommendations to improve the communication in MIM. Data were gathered using a self-administered survey that was patterned after Mattessich and Monsey’s (1992) collaboration experience questionnaire. Interviews and secondary sources mainly provided by the Makiling Center for Mountain Ecosystems (MCME) were also used. From the seven MIM collaborating organizations that were selected through purposive sampling, 86 respondents were chosen. Then, data were analyzed through frequency counts, percentages, measures of central tendencies, and Pearson’s and Spearman rho correlations. Collaborators’ length of collaboration ranged from seven to twenty years. Furthermore, six out of seven of the collaborators were involved in the task of 'emergency, rescue, and communication'. For the other aspect of the antecedents, the history of previous collaboration efforts ranked as the highest rated motivation for collaboration. In line with this, the top communication dimension is the governance while perceived effectiveness garnered the highest overall average among the perceived outcomes of collaboration. Results also showed that the collaborators highly rely on formal communication channels. Meetings and memos were the most commonly used communication channels throughout all tasks under the four phases of MIM. Additionally, although collaborators have a high view towards their co-collaborators, they still rely on MCME to act as their manager in coordinating with one another indirectly. Based on the correlation analysis, antecedent (motivations)-outcome relationship generally had positive relationships. However, for the process (communication dimensions)-outcome relationship, both positive and negative relationships were observed. In conclusion, this study exhibited the same trend with existing literature which also used the same framework. For the antecedent-outcome relationship, it can be deduced that MCME, as the main organizer of MIM, can focus on these variables to achieve their desired outcomes because of the positive relationships. For the process-outcome relationship, MCME should also take note that there were negative relationships where an increase in the said communication dimension may result in a decrease in the desired outcome. Recommendations for further study include a methodology that contains: complete enumeration or any parametric sampling, a researcher-administered survey, and direct observations. These might require additional funding, but all may yield to richer data.

Keywords: antecedent-outcome relationship, carrying capacity, organizational communication, process-outcome relationship

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Authors: Alua Masalimova, Dameli Sulubecova, Talgat Isaev, Raushan Magzumova

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The usual relation to nurses of heads of medical organizations in Kazakhstan is to use them only for per performing medical manipulations, but new economic conditions require the introduction of nursing innovations. There is an increasing need for managers of hospital departments and regions of ambulatory clinics to ensure comfortable conditions for doctors, nurses, aides, as well as monitoring marketing technology (the needs and satisfaction of staff work, the patient satisfaction of the department). It is going to the past the nursing activities as physician assistant performing his prescriptions passively. We are suggesting a model for the developing the head nurse as the manager on the example of Blood Service. We have studied in the scientific-production center of blood transfusion head nurses by the standard method of interviewing for involvement in coordinating the flow of information, promoting the competitiveness of the department. Results: the average age of the respondents 43,1 ± 9,8, female - 100%; manager in the Organization – 9,3 ± 10,3 years. Received positive responses to the knowledge of the nearest offices in providing similar medical service - 14,2%. The cost of similar medical services in other competitive organizations did not know 100%, did a study of employee satisfaction Division labour-85,7% answered negatively, the satisfaction donors work staff studied in 50.0% of cases involved in attracting paid Services Division showed a 28.5% of the respondent. Participation in management decisions medical organization: strategic planning - 14,2%, forming analysis report for the year – 14,2%, recruitment-30.0%, equipment-14.2%. Participation in the social and technical designing workplaces Division staff showed 85,0% of senior nurses. Participate in the cohesion of the staff of the Division method of the team used the 10.0% of respondents. Further, we have studied the behavioral competencies for senior sisters: customer focus – 20,0% of respondents have attended, the ability to work in a team – 40,0%. Personal qualities senior nurses were apparent: sociability – 80,0%, the ability to manage information – 40,0%, to make their own decisions - 14,2%, 28,5% creativity, the desire to improve their professionalism – 50,0%. Thus, the modern market conditions dictate this organization, which works for the rights of economic management; include the competence of the post of the senior nurse knowledge and skills of Marketing Management Department. Skills to analyses the information collected and use of management offers superior medical leadership organization. The medical organization in the recruitment of the senior nurse offices take into account personal qualities: flexibility, fluency of thinking, communication skills and ability to work in a team. As well as leadership qualities, ambition, high emotional and social intelligence, that will bring out the medical unit on competitiveness within the country and abroad.

Keywords: blood service, head nurse, manager, skills

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Rosemary Saunders, Courtney Glass, Karla Seaman, Karen Gullick, Julie Andrew, Anne Wilkinson, Ashwini Davray

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Current literature demonstrates that most Australians receive end-of-life care in a hospital setting, despite most hoping to die within their own home. The necessity for high quality end-of-life care has been emphasised by the Australian Commission on Safety and Quality in Health Care and the National Safety and Quality in Health Services Standards depict the requirement for comprehensive care at the end of life (Action 5.20), reinforcing the obligation for continual organisational assessment to determine if these standards are suitably achieved. Limited research exploring clinical staff perspectives of end-of-life care delivery has been conducted within an Australian private health context. This study aimed to investigate clinical staff member perceptions of end-of-life care delivery at a private hospital in Western Australia. The study comprised of a multi-faceted mixed-methods methodology, part of a larger study. Data was obtained from clinical staff utilising surveys and focus groups. A total of 133 questionnaires were completed by clinical staff, including registered nurses (61.4%), enrolled nurses (22.7%), allied health professionals (9.9%), non-palliative care consultants (3.8%) and junior doctors (2.2%). A total of 14.7% of respondents were palliative care ward staff members. Additionally, seven staff focus groups were conducted with physicians (n=3), nurses (n=26) and allied health professionals including social workers (n=1), dietitians (n=2), physiotherapists (n=5) and speech pathologists (n=3). Key findings from the surveys highlighted that the majority of staff agreed it was part of their role to talk to doctors about the care of patients who they thought may be dying, and recognised the importance of communication, appropriate training and support for clinical staff to provide quality end-of-life care. Thematic analysis of the qualitative data generated three key themes: creating the setting which highlighted the importance of adequate resourcing and conducive physical environments for end-of-life care and to support staff and families; planning and care delivery which emphasised the necessity for collaboration between staff, families and patients to develop care plans and treatment directives; and collaborating in end-of-life care, with effective communication and teamwork leading to achievable care delivery expectations. These findings contribute to health professionals better understanding of end-of-life care provision and the importance of collaborating with patients and families in care delivery. It is crucial that health care providers implement strategies to overcome gaps in care, so quality end-of-life care is provided. Findings from this study have been translated into practice, with the development and implementation of resources, training opportunities, support networks and guidelines for the delivery of quality end-of-life care.

Keywords: clinical staff, end-of-life care, mixed-methods, private hospital.

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Authors: Rochelle Daley, Eric Garraway, Catherine Murphy

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Crime is a major problem in Jamaica as well as the high number of unsolved violent crimes. The introduction of forensic entomology in criminal investigations has the potential to decrease the number of unsolved violent crimes through the estimation of PMI (post-mortem interval) or time since death. Though it has great potential, forensic entomology requires data from insects specific to a geographical location to be credibly applied in legal investigations. It is a relatively new area of study in the Caribbean, with multiple pioneer research opportunities. Of critical importance in forensic entomology is the ability to identify the species of interest. Larvae are commonly collected at crime scenes and a means of rapid identification is crucial. Moreover, a low-cost method is critical in countries with limited budget available for crime fighting. Sarcophagids are one of the most important colonisers of a carcass however, they are difficult to distinguish using morphology due to their similarities, however, there is a lack of research on the larvae of this family. This research contributes to that, having identified the larvae of three species from the family Sarcophagidae: Peckia nicasia, Peckia chrysostoma and Blaesoxipha plinthopyga; important agents in flesh decomposition. Adults of Sarcophidae are also difficult to differentiate, often requiring study of the genitalia; the use of larvae in species identification is important in such cases. Adult Sarcophagids were attracted using bottle traps baited with pig liver. These adults larviposited and the larvae were collected and colonises (generation 2 and 3) reared at room temperature for morphological work (n=50). The posterior ends of the larvae from segments 9 or 10 were removed and mounted posterior end upwards to allow study using a light microscope at magnification X200 (posterior cavity and intersegmental spine bands) and X640 (anterior and posterior spiracle). The remaining sections of the larvae were cleared in 10 % KOH and the cephalopharyngeal skeleton dissected out and measured at different points. The cephalopharyngeal skeletons show observable differences in the shapes and sizes of the mouth hooks as well as the length of the ventral cornua. The most notable difference between species is in the general shape of the anal segments and the shape of the posterior spiracles. Intersegmental spine bands of these larvae become less pigmented and visible as the larvae change instars. Spine bands along with anterior spiracle are not recommended as features for species distinction. Larvae can potentially be used to distinguish Sarcophagids to the level of species, with observable differences in the anal segments and the cephalopharyngeal skeletons. However, this method of identification should be tested by comparing these morphological features with other Jamaican Sarcophagids to further support this conclusion.

Keywords: 3rd instar larval morphology, forensic entomology, Jamaica, Sarcophagidae

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Authors: Muhammad Naveed Tahir, Wang Yingkuan, Huang Wenjiang, Raheel Osman

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Numerous models used in prediction and decision-making process but most of them are linear in natural environment, and linear models reach their limitations with non-linearity in data. Therefore accurate estimation is difficult. Artificial Neural Networks (ANN) found extensive acceptance to address the modeling of the complex real world for the non-linear environment. ANN’s have more general and flexible functional forms than traditional statistical methods can effectively deal with. The link between information technology and agriculture will become more firm in the near future. Monitoring crop biophysical properties non-destructively can provide a rapid and accurate understanding of its response to various environmental influences. Crop chlorophyll content is an important indicator of crop health and therefore the estimation of crop yield. In recent years, remote sensing has been accepted as a robust tool for site-specific management by detecting crop parameters at both local and large scales. The present research combined the ANN model with satellite-derived chlorophyll indices from LANDSAT 8 imagery for predicting real-time wheat chlorophyll estimation. The cloud-free scenes of LANDSAT 8 were acquired (Feb-March 2016-17) at the same time when ground-truthing campaign was performed for chlorophyll estimation by using SPAD-502. Different vegetation indices were derived from LANDSAT 8 imagery using ERADAS Imagine (v.2014) software for chlorophyll determination. The vegetation indices were including Normalized Difference Vegetation Index (NDVI), Green Normalized Difference Vegetation Index (GNDVI), Chlorophyll Absorbed Ratio Index (CARI), Modified Chlorophyll Absorbed Ratio Index (MCARI) and Transformed Chlorophyll Absorbed Ratio index (TCARI). For ANN modeling, MATLAB and SPSS (ANN) tools were used. Multilayer Perceptron (MLP) in MATLAB provided very satisfactory results. For training purpose of MLP 61.7% of the data, for validation purpose 28.3% of data and rest 10% of data were used to evaluate and validate the ANN model results. For error evaluation, sum of squares error and relative error were used. ANN model summery showed that sum of squares error of 10.786, the average overall relative error was .099. The MCARI and NDVI were revealed to be more sensitive indices for assessing wheat chlorophyll content with the highest coefficient of determination R²=0.93 and 0.90 respectively. The results suggested that use of high spatial resolution satellite imagery for the retrieval of crop chlorophyll content by using ANN model provides accurate, reliable assessment of crop health status at a larger scale which can help in managing crop nutrition requirement in real time.

Keywords: ANN, chlorophyll content, chlorophyll indices, satellite images, wheat

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Authors: Premalatha B. S., Shenoy A. M.

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Background: Rehabilitation of swallowing is as vital as speech in surgically treated head and neck cancer patients to maintain nutritional support, enhance wound healing and improve quality of life. Aspiration following supraglottic laryngectomy is very common, and rehabilitation of the same is crucial which requires involvement of speech therapist in close contact with head and neck surgeon. Objectives: To examine the functions of swallowing outcomes after intensive therapy in supraglottic laryngectomy. Materials: Thirty-nine supra glottic laryngectomees were participated in the study. Of them, 36 subjects were males and 3 were females, in the age range of 32-68 years. Eighteen subjects had undergone standard supra glottis laryngectomy (Group1) for supraglottic lesions where as 21 of them for extended supraglottic laryngectomy (Group 2) for base tongue and lateral pharyngeal wall lesion. Prior to surgery visit by speech pathologist was mandatory to assess the sutability for surgery and rehabilitation. Dysphagia rehabilitation started after decannulation of tracheostoma by focusing on orientation about anatomy, physiological variation before and after surgery, which was tailor made for each individual based on their type and extent of surgery. Supraglottic diet - Soft solid with supraglottic swallow method was advocated to prevent aspiration. The success of intervention was documented as number of sessions taken to swallow different food consistency and also percentage of subjects who achieved satisfactory swallow in terms of number of weeks in both the groups. Results: Statistical data was computed in two ways in both the groups 1) to calculate percentage (%) of subjects who swallowed satisfactorily in the time frame of less than 3 weeks to more than 6 weeks, 2) number of sessions taken to swallow without aspiration as far as food consistency was concerned. The study indicated that in group 1 subjects of standard supraglottic laryngectomy, 61% (n=11) of them were successfully rehabilitated but their swallowing normalcy was delayed by an average 29th post operative day (3-6 weeks). Thirty three percentages (33%) (n=6) of the subjects could swallow satisfactorily without aspiration even before 3 weeks and only 5 % (n=1) of the needed more than 6 weeks to achieve normal swallowing ability. Group 2 subjects of extended SGL only 47 %( n=10) of them could achieved satisfactory swallow by 3-6 weeks and 24% (n=5) of them of them achieved normal swallowing ability before 3 weeks. Around 4% (n=1) needed more than 6 weeks and as high as 24 % (n=5) of them continued to be supplemented with naso gastric feeding even after 8-10 months post operative as they exhibited severe aspiration. As far as type of food consistencies were concerned group 1 subject could able to swallow all types without aspiration much earlier than group 2 subjects. Group 1 needed only 8 swallowing therapy sessions for thickened soft solid and 15 sessions for liquids whereas group 2 required 14 sessions for soft solid and 17 sessions for liquids to achieve swallowing normalcy without aspiration. Conclusion: The study highlights the importance of dysphagia intervention in supraglottic laryngectomees by speech pathologist.

Keywords: dysphagia management, supraglotic diet, supraglottic laryngectomy, supraglottic swallow

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Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

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Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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Authors: Djamila Chabane, Asma Rouane, Karim Arab

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Depending of the chemical substances responsible for the pharmacological effects, a future therapeutic drug might be produced by extraction from whole plants or by callus initiated from some parts. The optimized callus culture protocols now offer the possibility to use cell culture techniques for vegetative propagation and open minds for further studies on secondary metabolites and drug establishment. In Algerian traditional medicine, Pulicaria incisa (Asteraceae) is used in the treatment of daily troubles (stomachache, headhache., cold, sore throat and rheumatic arthralgia). Field findings revealed that many healers use some fresh parts (leaves, flowers) of this plant to treat skin wounds. This study aims to evaluate the healing efficiency of artisanal cream prepared from sticky mucilage isolated from calluses on dermal wounds of animal models. Callus cultures were initiated from reproductive explants (young inflorescences) excised from adult plants and transferred to a MS basal medium supplemented with growth regulators and maintained under dark for for months. Many calluses types were obtained with various color and aspect (friable, compact). Several subcultures of calli were performed to enhance the mucilage accumulation. After extraction, the mucilage extracts were tested on animal models as follows. The wound healing potential was studied by causing dermal wounds (1 cm diameter) at the dorsolumbar part of Rattus norvegicus; different samples of the cream were applied after hair removal on three rats each, including two controls (one treated by Vaseline and one without any treatment), two experimental groups (experimental group 1, treated with a reference ointment "Madecassol® and experimental group 2 treated by callus mucilage cream for a period of seventeen days. The evolution of the healing activity was estimated by calculating the percentage reduction of the area wounds treated by all compounds tested compared to the controls by using AutoCAD software. The percentage of healing effect of the cream prepared from callus mucilage was (99.79%) compared to that of Madecassol® (99.76%). For the treatment time, the significant healing activity was observed after 17 days compared to that of the reference pharmaceutical products without any wound infection. The healing effect of Madecassol® is more effective because it stimulates and regulates the production of collagen, a fibrous matrix essential for wound healing. Mucilage extracts also showed a high capacity to heal the skin without any infection. According to this pharmacological activity, we suggest to use calluses produced by in vitro culture to producing new compounds for the skin care and treatment.

Keywords: calluses, Pulicaria incisa, mucilage, Wounds

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Authors: Mikel W. Cole, Stephanie M. Madison, Adam Henze

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Since 2004, the U.S. immigrant detention system has imprisoned more than five million people. President John F. Kennedy famously dubbed this country a “Nation of Immigrants.” Like many of the nation’s imagined ideals, the historical record finds its practices have never lived up to the tenets championed as defining qualities.The United Nations High Commission on Refugees argues the educational needs of people in carceral spaces, especially those in immigrant detention centers, are urgent and supported by human rights guarantees. However, there is a genuine dearth of literacy research in immigrant detention centers, compounded by a general lack of access to these spaces. Denying access to literacy education in detention centers is one way the history of xenophobic immigration policy persists. In this conceptual exploration, first-hand accounts from detained individuals, their families, and the organizations that work with them have been shared with the authors. In this paper, the authors draw on experiences, reflections, and observations from serving as volunteers to develop a conceptual framework for the ways in which literacy practices are enacted in detention centers. Literacy is an essential tool for accessing those detained in immigrant detention centers and a critical tool for those being detained to access legal and other services. One of the most striking things about the detention center is how to behave; gaining access for a visit is neither intuitive nor straightforward. The men experiencing detention are also at a disadvantage. The lack of access to their own documents is a profound barrier to men navigating the complex immigration process. Literacy is much more than a skill for gathering knowledge or accessing carceral spaces; literacy is fundamentally a source of personal empowerment. Frequently men find a way to reclaim their sense of dignity through work on their own terms by exchanging their literacy services for products or credits at the commissary. They write cards and letters for fellow detainees, read mail, and manage the exchange of information between the men and their families. In return, the men who have jobs trade items from the commissary or transfer money to the accounts of the men doing the reading, writing, and drawing. Literacy serves as a form of resistance by providing an outlet for productive work. At its core, literacy is the exchange of ideas between an author and a reader and is a primary source of human connection for individuals in carceral spaces. Father’s Day and Christmas are particularly difficult at detention centers. Men weep when speaking about their children and the overwhelming hopelessness they feel by being separated from them. Yet card-writing campaigns have provided these men with words of encouragement as thousands of hand-written cards make their way to the detention center. There are undoubtedly more literacies being practiced in the immigrant detention center where we work and at other detention centers across the country, and these categories are early conceptions with which we are still wrestling.

Keywords: detention centers, education, immigration, literacy

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Authors: Chuanqiao Zheng, Wei Zeng, Haozhen Lin

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As of March 2020, the number of Chinese netizens has reached 904 million. The proportion of Internet users accessing the Internet through mobile phones is as high as 99.3%. Under the background of 'Internet +', tourists have a stronger sense of independence in the choice of tourism destinations and tourism products. Tourists are more inclined to learn about the relevant information on tourism destinations and other tourists' evaluations of tourist products through the Internet. The search engine, as an integrated platform that contains a wealth of information, is highly valuable to the analysis of the characteristics of the Internet attention given to various tourism destinations, through big data mining and analysis. This article uses the Baidu Index as the data source, which is one of the products of Baidu Search. The Baidu Index is based on big data, which collects and shares the search results of a large number of Internet users on the Baidu search engine. The big data used in this article includes search index, demand map, population profile, etc. The main research methods used are: (1) based on the search index, analyzing the Internet attention given to the tourism in five cities in Northeast Sichuan at different times, so as to obtain the overall trend and individual characteristics of tourism development in the region; (2) based on the demand map and the population profile, analyzing the demographic characteristics and market positioning of the tourist groups in these cities to understand the characteristics and needs of the target groups; (3) correlating the Internet attention data with the permanent population of each province in China in the corresponding to construct the Boston matrix of the Internet attention rate of the Northeast Sichuan tourism, obtain the tourism target markets, and then propose development strategies for different markets. The study has found that: a) the Internet attention given to the tourism in the region can be categorized into tourist off-season and peak season; the Internet attention given to tourism in different cities is quite different. b) tourists look for information including tour guide information, ticket information, traffic information, weather information, and information on the competing tourism cities; with regard to the population profile, the main group of potential tourists searching for the keywords of tourism in the five prefecture-level cities in Northeast Sichuan are youth. The male to female ratio is about 6 to 4, with males being predominant. c) through the construction of the Boston matrix, it is concluded that the star market for tourism in the Northeast Sichuan Economic Zone includes Sichuan and Shaanxi; the cash cows market includes Hainan and Ningxia; the question market includes Jiangsu and Shanghai; the dog market includes Hubei and Jiangxi. The study concludes with the following planning strategies and recommendations: i) creating a diversified business format that integrates cultural and tourism; ii) creating a brand image of niche tourism; iii) focusing on the development of tourism products; iv) innovating composite three-dimensional marketing channels.

Keywords: Baidu Index, big data, internet attention, tourism

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Authors: Nur Rafeeda Daut

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The significance of this paper is to provide an insight on the role of social movement in building stronger ethnic relations in Malaysia. In particular, it focuses on how the BERSIH movement have been able to bring together the different ethnic groups in Malaysia to resist the present political administration that is seen to manipulate the electoral process and oppress the basic freedom of expression of Malaysians. Attention is given on how and why this group emerged and its mobilisation strategies. Malaysia which is a multi-ethnic and multi-religious society gained its independence from the British in 1957. Like many other new nations, it faces the challenges of nation building and governance. From economic issues to racial and religious tension, Malaysia is experiencing high level of corruption and income disparity among the different ethnic groups. The political parties in Malaysia are also divided along ethnic lines. BERSIH which is translated as ‘clean’ is a movement which seeks to reform the current electoral system in Malaysia to ensure equality, justice, free and fair elections. It was originally formed in 2007 as a joint committee that comprised leaders from political parties, civil society groups and NGOs. In April 2010, the coalition developed as an entirely civil society movement unaffiliated to any political party. BERSIH claimed that the electoral roll in Malaysia has been marred by fraud and other irregularities. In 2015, the BERSIH movement organised its biggest rally in Malaysia which also includes 38 other rallies held internationally. Supporters of BERSIH that participated in the demonstration were comprised of all the different ethnic groups in Malaysia. In this paper, two social movement theories are used: resource mobilization theory and political opportunity structure to explain the emergence and mobilization of the BERSIH movement in Malaysia. Based on these two theories, corruption which is believed to have contributed to the income disparity among Malaysians has generated the development of this movement. The rise of re-islamisation values propagated by certain groups in Malaysia and the shift in political leadership has also created political opportunities for this movement to emerge. In line with the political opportunity structure theory, the BERSIH movement will continue to create more opportunities for the empowerment of civil society and the unity of ethnic relations in Malaysia. Comparison is made on the degree of ethnic unity in the country before and after BERSIH was formed. This would include analysing the level of re-islamisation values and also the level of corruption in relation to economic income under the premiership of the former Prime Minister Mahathir and the present Prime Minister Najib Razak. The country has never seen such uprisings like BERSIH where ethnic groups which over the years have been divided by ethnic based political parties and economic disparity joined together with a common goal for equality and fair elections. As such, the BERSIH movement is a unique case where it illustrates the change of political landscape, ethnic relations and civil society in Malaysia.

Keywords: ethnic relations, Malaysia, political opportunity structure, resource mobilization theory and social movement

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Authors: William Gallagher, Harriet Bothwell, Lowri Evans, Kevin Jones

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Background: Worldwide, a third of adult deaths are caused by cardiovascular disease, a high proportion occurring in the developing world. Contributing to these poor outcomes are suboptimal assessments, treatments and monitoring of the acutely unwell patient. Successful training in trauma and neonates is recognised in the developing world but there is little literature supporting adult resuscitation. As far as the authors are aware no literature has been published on resuscitation training in Uganda since 2000 when a resuscitation training officer ran sessions in neonatal and paediatric resuscitation. The aim of this project was to offer training in Basic Life Support ( BLS) to staff and healthcare students based at Villa Maria Hospital in the Kalungu District, Central Uganda. This project was undertaken as a student selected component (SSC) offered by Swindon Academy, based at the Great Western Hospital, to medical students in their fourth year of the undergraduate programme. Methods: Semi-structured, informal interviews and focus groups were conducted with different clinicians in the hospital. These interviews were designed to focus on the level of training and understanding of BLS. A training session was devised which focused on BLS (excluding the use of an automatic external defribrillator) involving pre and post-training questionnaires and clinical assessments. Three training sessions were run for different cohorts: a pilot session for 5 Ugandan medical students, a second session for a group of 8 nursing and midwifery students and finally, a third was devised for physicians. The data collected was analysed in excel. Paired T-Tests determined statistical significance between pre and post-test scores and confidence before and after the sessions. Average clinical skill assessment scores were converted to percentages based on the area of BLS being assessed. Results: 27 participants were included in the analysis. 14 received ‘small group training’ whilst 13 received’ large group training’ 88% of all participants had received some form of resuscitation training. Of these, 46% had received theory training, 27% practical training and only 15% received both. 12% had received no training. On average, all participants demonstrated a significant increase of 5.3 in self-assessed confidence (p <0.05). On average, all participants thought the session was very useful. Analysis of qualitative date from clinician interviews in ongoing but identified themes identified include rescue breaths being considered the most important aspect resuscitation and doubts of a ‘good’ outcome from resuscitation. Conclusions: The results of this small study reflect the need for regular formal training in BLS in low resource settings. The active engagement and positive opinions concerning the utility of the training are promising as well as the evidence of improvement in knowledge.

Keywords: basic life support, education, resuscitation, sub-Saharan Africa, training, Uganda

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Authors: Katarina Revocati Mteule

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The background of this research arises from global demands for fair business opportunities. As one of responses to these demands, nations embarked on reforms in commercial laws. In 1990s Tanzania resorted to economic transformation through liberalization to attract more investments included reform in commercial laws enforcement. This research scrutinizes the effectiveness of reforms in Tanzania in comparison with Canada and Singapore and the role of technology. The methodology to be used is doctrinal legal research mixed with international comparative legal research. It involves comparative analysis of library, online, and internet resources as well as Case Laws and Statutory Laws. Tanzania, Canada and Singapore are sampled comparators basing on their distinct level of economic development. The criteria of analysis includes the nature of reforms, type of technology, technological infrastructure and human resource technical competence in each country. As the world progresses towards reforms in commercial laws, improvements in law, policy, and regulatory frameworks are paramount. Specifically, commercial laws are essential in contract enforcement and dispute resolution and how it copes with modern technologies is a concern. Harnessing the best technology is necessary to cope with the modernity in world businesses. In line with this, Tanzania is improving its business environment, including law enforcement mechanisms that are supportive to investments. Reforms such as specialized commercial law enforcement coupled with alternative dispute resolutions such as arbitration, mediation, and reconciliation are emphasized. Court technology as one of the reform tools given high priority. This research evaluates the progress and the effectiveness of the reforms in Commercial Laws towards friendly business environment in Tanzania in comparison with Canada and Singapore. The experience of Tanzania is compared with Canada and Singapore to see what to improve for each country to enhance quick and fair enforcement of commercial law. The research proposes necessary global standards of procedures and in national laws to offer a business-friendly environment and the use of appropriate technology. Solutions are proposed in tackling the challenges of delays in enforcing Commercial Laws such as case management, funding, legal and procedural hindrances, laxity among staff, and abuse of Court process among litigants, all in line with modern technology. It is the finding of the research that proper use of technology has managed to reduce case backlogs and time taken to resolve a commercial dispute, to increase court integrity by minimizing human contacts in commercial law enforcement which may lead to solicitation of favors and saving of parties’ time due to online service. Among the three countries, each one is facing a distinct challenge due to the level of poverty and remoteness from online service. How solutions are found in one country is a lesson to another. To conclude, this paper is suggesting solutions for improving the commercial law enforcement mechanisms in line with modern technology. The call for technological transformation is essential for the enforcement of commercial laws.

Keywords: commercial law, enforcement, technology

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Authors: Shivakumar M, Leslie Edward S Lewis, Shashikala Devadiga, Sonia Khurana

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Introduction: Methylxanthines are used for the treatment of AOP, to facilitate extubation and as a prophylactic agent to prevent apnea. Though the popularity of Caffeine has risen, it is expensive in a resource constrained developing countries like India. Objective: To evaluate the cost-effectiveness of Caffeine compared with Aminophylline treatment for AOP with respect to additional ventilatory resource utilized in different birth weight categorization. Design, Settings and Participants – Single centered, retrospective economic evaluation was done. Participants included preterm newborns with < 34 completed weeks of gestation age that were recruited under an Indian Council of Medical Research funded randomized clinical trial. Per protocol data was included from Neonatal Intensive Care Unit, Kasturba Hospital, Manipal, India between April 2012 and December 2014. Exposure: Preterm neonates were randomly allocated to either Caffeine or Aminophylline as per the trial protocol. Outcomes and Measures – We assessed surfactant requirement, duration of Invasive and Non-Invasive Ventilation, Total Methylxanthine cost and additional cost for respiratory support bared by the payers per day during hospital stay. For the purpose of this study Newborns were stratified as Category A – < 1000g, Category B – 1001 to 1500g and Category C – 1501 to 2500g. Results: Total 146 (Caffeine -72 and Aminophylline – 74) babies with Mean ± SD gestation age of 29.63 ± 1.89 weeks were assessed. 32.19% constitute of Category A, 55.48% were B and 12.33% were C. The difference in median duration of additional NIV and IMV support was statistically insignificant. However 60% of neonates who received Caffeine required additional surfactant therapy (p=0.02). The total median (IQR) cost of Caffeine was significantly high with Rs.10535 (Q3-6317.50, Q1-15992.50) where against Aminophylline cost was Rs.352 (Q3-236, Q1-709) (p < 0.001). The additional costs spent on respiratory support per day in neonates on either Methylxanthines were found to be statistically insignificant in the entire weight based category of our study. Whereas in Category B, the median O2 charges per day were found to have more in Caffeine treated newborns (p=0.05) with border line significance. In category A, providing one day NIV or IMV support significantly increases the unit log cost of Caffeine by 13.6% (CI – 95% ranging from 4 to 24; p=0.005) over log cost of Aminophylline. Conclusion: Cost of Caffeine is expensive than Aminophylline. It was found to be equally efficacious in reducing the number duration of NIV or IMV support. However adjusted with the NIV and IMV days of support, neonates fall in category A and category B who were on Caffeine pays excess amount of respiratory charges per day over aminophylline. In perspective of resource poor settings Aminophylline is cost saving and economically approachable.

Keywords: methylxanthines include caffeine and aminophylline, AOP (apnea of prematurity), IMV (invasive mechanical ventilation), NIV (non invasive ventilation), category a – <1000g, category b – 1001 to 1500g and category c – 1501 to 2500g

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Authors: Md. S. Sabuz

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Bangladesh, a South Asian developing country, has achieved a remarkable breakthrough in health indicators during the last four decades despite immense income inequality. This phenomenon results in the mystical exclusion of marginalized people from obtaining health care facilities. However, the persistence of exclusion of the disadvantaged remains troubling. Exclusion occurs from occupational inferiority, pay and wage differences, educational backwardness, gender disparity to urban-rural complexity and eliminate the unprivileged from seeking and availing the health services. Evidence from Bangladesh shows that many sick people prefer to die at home without securing medical services because in previous times they were not treated well, not because the medical facilities were inadequate or antediluvian but the socio-economic class allows them to receive obdurate treatment. Furthermore, government and policymakers have given enormous emphasis on infrastructural development and achieving health indicators instead of ensuring quality services and inclusiveness of people from all spheres. Therefore, it is high time to address the issues concerning this and highlight the impact of economic status on health status in a sociological perspective. The objective of this study is to consider ways of assessing and exploring the impact of economic status for instance: occupational status, pay and wage variable, on health status in the context of Bangladesh. The hypotheses are that there are a significant number of factors affecting economic status which are impactful for health status eventually, but acute income inequality is a prominent factor. Illiteracy, gender disparity, remoteness, incredibility on services, superior costs, superstition etc. are the dominant indicators behind the economic factors influencing the health status. The chosen methodologies are a qualitative and quantitative approaches to accomplish the research objectives. Secondary sources of data will be used to conduct the study. Surveys will be conducted on the people who have ever been through the health care facilities and people from the different socio-economic and cultural backgrounds. Focus group discussions will be conducted to acquire the data from different cultural and regional citizens. The findings show that 48% of people who are from disadvantaged communities have been deprived of proper health care facilities. The general reasons behind this are the higher cost of medicines and other equipment. A significant number of people are unaware of the appropriate facilities. It was found that the socio-economic variables are the main influential factors that work as the driving force for both economic dimension and health status. Above all regional variables and gender, dimensions have an enormous effect on determining the health status of an individual or community. Amidst many positive achievements for example decrease in the child mortality rate, an increase in the immunization programs of the child etc., the inclusiveness of all classes of people in health care facilities has been overshadowed in Bangladesh. However, this phenomenon along with the socio-economic and cultural phenomena significantly demolishes the quality and inclusiveness of the health status of people.

Keywords: cultural context of health, economic status, gender and health, rural health care

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Authors: Linyi Fan, C.J. Schumaker

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Background: Biomedical efforts to treat Alzheimer’s disease (AD) have typically produced mixed to poor results, while more lifestyle-focused treatments such as exercise may fare better than existing biomedical treatments. A few promising studies have indicated that activities of daily life (ADL) may be a useful way of predicting AD. However, the existing cross-sectional studies fail to show how functional-related issues such as ADL in early years predict AD and how social factors influence health either in addition to or in interaction with individual risk factors. This study would helpbetterscreening and early treatments for the elderly population and healthcare practice. The findings have significance academically and practically in terms of creating positive social change. Methodology: The purpose of this quantitative historical, correlational study was to examine the relationship between early years’ ADL and the development of AD in later years. The studyincluded 4,526participantsderived fromRAND HRS dataset. The Health and Retirement Study (HRS) is a longitudinal household survey data set that is available forresearchof retirement and health among the elderly in the United States. The sample was selected by the completion of survey questionnaire about AD and dementia. The variablethat indicates whether the participant has been diagnosed with AD was the dependent variable. The ADL indices and changes in ADL were the independent variables. A four-step multilevel regression model approach was utilized to address the research questions. Results: Amongst 4,526 patients who completed the AD and dementia questionnaire, 144 (3.1%) were diagnosed with AD. Of the 4,526 participants, 3,465 (76.6%) have high school and upper education degrees,4,074 (90.0%) were above poverty threshold. The model evaluatedthe effect of ADL and change in ADL on onset of AD in late years while allowing the intercept of the model to vary by level of education. The results suggested that the only significant predictor of the onset of AD was changes in early years’ ADL (b = 20.253, z = 2.761, p < .05). However, the result of the sensitivity analysis (b = 7.562, z = 1.900, p =.058), which included more control variables and increased the observation period of ADL, are not supported this finding. The model also estimated whether the variances of random effect vary by Level-2 variables. The results suggested that the variances associated with random slopes were approximately zero, suggesting that the relationship between early years’ ADL were not influenced bysociodemographic factors. Conclusion: The finding indicated that an increase in changes in ADL leads to an increase in the probability of onset AD in the future. However, this finding is not support in a broad observation period model. The study also failed to reject the hypothesis that the sociodemographic factors explained significant amounts of variance in random effect. Recommendations were then made for future research and practice based on these limitations and the significance of the findings.

Keywords: alzheimer’s disease, epidemiology, moderation, multilevel modeling

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Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Tuji Jemal Ahmed, Abdi Mohammed, Geremew Geidare Kailo

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Food security, foodborne illness, and food safety are critical issues that affect the East Harerghe region of Oromia, Ethiopia. Despite the region's potential for agriculture, food insecurity remains a significant problem, with many households experiencing chronic hunger and malnutrition. The region also experiences high rates of foodborne illnesses, including cholera, typhoid, and diarrhea, which are caused by poor hygiene and sanitation practices. Additionally, food safety is a significant challenge, particularly in rural areas, where there is a lack of infrastructure, inadequate food storage facilities, and limited access to information about food safety. There are several factors that contribute to the current situation in the East Harerghe region; firstly, the region is susceptible to natural disasters, for instance, drought, which affects crop yields and livestock production. Secondly, the region also experiences poor infrastructure, which affects the storage and transportation of food, particularly in rural areas. Thirdly, there is a lack of awareness and knowledge on good hygiene and sanitation practices, specifically during food handling, processing, and storage. Fourthly, unitability due to conflict and other forms of land degradation exacerbates food insecurity and malnutrition. Finally, limited access to financial resources and markets commonly affects smallholder farmers by their ability to produce and sell food. To address the current situation in that area, several potential solutions can be implemented; investment in infrastructure is necessary, especially in rural areas, to improve the storage and transportation of food. Education and awareness programs on good hygiene and sanitation practices should target local communities, smallholder farmers, and food vendors. Financial resources and markets should be made more accessible to smallholder farmers, particularly through the provision of credit and improved access to markets. Addressing the underlying causes of conflict and promoting peaceful coexistence can help to reduce displacement and loss of livelihoods. Finally, the enforcement of food safety regulations and the implementation of standards for food processing and storage facilities are necessary to ensure food safety. In conclusion, addressing the challenges of food security, foodborne illness, and food safety in the East Harerghe region requires a coordinated effort from various stakeholders, including the government, non-governmental organizations, and local communities. By implementing the solutions outlined above, the region can improve its food security, prevent foodborne illnesses, and keep food safe for its population. Eventually, building the resilience of communities to shocks such as droughts, floods, and conflict is necessary to ensure long-term food security in the region.

Keywords: foodborne illness, food handling, food safety, food security

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Authors: Rajkumar Ghosh

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Fluoride contamination is a growing concern in various regions across the globe, including North 24 Parganas in West Bengal, India. The presence of excessive fluoride in the environment can have detrimental effects on crops, soil quality, and water resources. This note aims to shed light on the implications of fluoride contamination and its impact on the agricultural sector in North 24 Parganas. The agricultural lands in North 24 Parganas have been significantly affected by fluoride contamination, leading to adverse consequences for crop production. Excessive fluoride uptake by plants can hinder their growth, reduce crop yields, and impact the quality of agricultural produce. Certain crops, such as paddy, vegetables, and fruits, are more susceptible to fluoride toxicity, resulting in stunted growth, leaf discoloration, and reduced nutritional value. Fluoride-contaminated water, often used for irrigation, contributes to the accumulation of fluoride in the soil. Over time, this can lead to soil degradation and reduced fertility. High fluoride levels can alter soil pH, disrupt the availability of essential nutrients, and impair microbial activity critical for nutrient cycling. Consequently, the overall health and productivity of the soil are compromised, making it increasingly challenging for farmers to sustain agricultural practices. Fluoride contamination in North 24 Parganas extends beyond the soil and affects water resources as well. The excess fluoride seeps into groundwater, making it unsafe for consumption. Long-term consumption of fluoride-contaminated water can lead to various health issues, including dental and skeletal fluorosis. These health concerns pose significant risks to the local population, especially those reliant on contaminated water sources for their daily needs. Addressing fluoride contamination requires concerted efforts from various stakeholders, including government authorities, researchers, and farmers. Implementing appropriate water treatment technologies, such as defluoridation units, can help reduce fluoride levels in drinking water sources. Additionally, promoting alternative irrigation methods and crop diversification strategies can aid in mitigating the impact of fluoride on agricultural productivity. Furthermore, creating awareness among farmers about the adverse effects of fluoride contamination and providing access to alternative water sources are crucial steps toward safeguarding the health of the community and sustaining agricultural activities in the region. Fluoride contamination poses significant challenges to crop production, soil health, and water resources in North 24 Parganas, West Bengal. It is imperative to prioritize efforts to address this issue effectively and implement appropriate measures to mitigate fluoride contamination. By adopting sustainable practices and promoting awareness, the community can work towards restoring the agricultural productivity, soil quality and ensuring access to safe drinking water in the region.

Keywords: fluoride contamination, drinking water, toxicity, soil health

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Authors: Nuray Ocakli

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19th century was the era of changes and transformations for the Ottoman Empire. The first sultan of this century, Mahmud II (1808-1839), was the architect of Ottoman modernization and fundamental changes. The most radical of these was abolishing the Janissary corps and the traditional Ottoman military band, Mehteran. Mahmud II introduced modernized military corps as well as western style royal and military music. Mahmut II invited the Italian composer Giuseppe Donizetti to establish a modern military band for the new army and to compose the Sultan’s royal anthem. In 1828, Donizetti composed the first western-style Ottoman anthem, Mahmudiyye anthem. During the 19th and early 20th century, four other western style Ottoman anthems (Aziziyye, Mecidiyye, Hamidiyye, and Resadiyye) were composed but the last anthem adopted in the reign of Mehmet VI (r. 1918-1922) was again Mahmudiyye anthem. This paper aims to analyze the Mahmudiyye anthem composed as royal anthem in 1828 but adopted as national anthem in 1918. Research questions of this paper are as follows: What were the characteristics of the Mahmudiyye anthem making it the best choice of the last sultan for the last national anthem? Are there specific reasons of the last sultan to adopt Mahmudiyye anthem or not to adopt any of the other four anthems? The musical characteristics of the anthem are analyzed based on the Cerulo’s empirical research. Cerulo examined the musical structures of 124 western style anthems from 150 countries in the 1580-1976 period. Cerulo’s research categorizes musical codes of the anthems as basic and embellished related with the level of sociopolitical control. Musical analysis of the anthem indicates that the basic musical code of the anthem implies a high level of socio-political control during the reign of both Mahmut II and Mehmet VI. Historical analysis of each sultans’ reign shows that both sultans were autocratic. Mahmut II designed authoritarian government policies to suppress possible reactions against his reforms. On the other hand, authoritarian policies of Mehmet VI are related with the domestic and international political conditions following the World War I. Historical analysis of the research questions show that compared to the other western style Ottoman anthems, Mahmudiyye anthem remained the only neutral anthem symbolizing modernization and westernization of the empire. Other anthems were all the symbols of failed ideologies such as Ottomanism, pan-Islamism, and pan-Turkism. In the early 20th century, there were a few common things remained among the diverse communities of the Ottoman Empire: The land they shared as homeland and the idea of modernization to save the homeland. For this reason, the last sultan Mehmet VI adopted Mahmudiyye anthem as the memory of a unified empire under the rule of a powerful and modernist sultan. The last sultan’s reign lasted just for four years, and the Ottoman Empire disintegrated in 1922, but his adaptation of the Mahmudiyye anthem indicates his unifying policies, his attitudes to save the empire and the caliphate.

Keywords: Mahmudiyye anthem, musical code, national anthem, Ottoman Empire, royal anthem

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Authors: Zia Ul Haq, Saleem Muhammad, Naeem Ullah, Abbas Shah, Abdullah Shah

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Pakistan being the developing country is facing double burden of communicable and non-communicable disease. The aspect of secondary prevention of ischemic heart disease in developing countries is the dire need for public health specialists, clinicians and policy makers. There is some evidence that psychotherapeutic measures, including psychotherapy, recreation, exercise and stress management training have positive impact on secondary prevention of cardiovascular diseases but there are some contradictory findings as well. Cardiac rehabilitation program (CRP) has not yet fully implemented in Pakistan. Psychological, physical and specific health-related quality of life (HRQoL) outcomes needs assessment with respect to its practicality, effectiveness, and success. Objectives: To determine the effect of cardiac rehabilitation program (CRP) on the health-related quality of life (HRQoL) measures of post MI patients compared to the usual care. Hypothesis: Post MI patients who receive the interventions (CRP) will have better HRQoL as compared to those who receive the usual cares. Methods: The randomized control trial was conducted at a Cardiac Rehabilitation Unit of Lady Reading Hospital (LRH), Peshawar. LRH is the biggest hospital of the Province Khyber Pakhtunkhwa (KP). A total 206 participants who had recent first myocardial infarction were inducted in the study. Participants were randomly allocated into two group i.e. usual care group (UCG) and cardiac rehabilitation group (CRG) by permuted-block randomization (PBR) method. CRP was conducted in CRG in two phases. Three HRQoL outcomes i.e. general health questionnaire (GHQ), self-rated health (SRH) and MacNew quality of life after myocardial infarction (MacNew QLMI) were assessed at baseline and follow-up visits among both groups. Data were entered and analyzed by appropriate statistical test in STATA version 12. Results: A total of 195 participants were assessed at the follow-up period due to lost-to-follow-up. The mean age of the participants was 53.66 + 8.3 years. Males were dominant in both groups i.e. 150 (76.92%). Regarding educational status, majority of the participants were illiterate in both groups i.e. 128 (65.64%). Surprisingly, there were 139 (71.28%) who were non-smoker on the whole. The comorbid status was positive in 120 (61.54%) among all the patients. The SRH at follow-up among UCG and CRG was 4.06 (95% CI: 3.93, 4.19) and 2.36 (95% CI: 2.2, 2.52) respectively (p<0.001). GHQ at the follow-up of UCG and CRG was 20.91 (95% CI: 18.83, 21.97) and 7.43 (95% CI: 6.59, 8.27) respectively (p<0.001). The MacNew QLMI at follow-up of UCG and CRG was 3.82 (95% CI: 3.7, 3.94) and 5.62 (95% CI: 5.5, 5.74) respectively (p<0.001). All the HRQoL measures showed strongly significant improvement in the CRG at follow-up period. Conclusion: HRQOL improved in post MI patients after comprehensive CRP. Education of the patients and their supervision is needed when they are involved in their rehabilitation activities. It is concluded that establishing CRP in cardiac units, recruiting post-discharged MI patients and offering them CRP does not impose high costs and can result in significant improvement in HRQoL measures. Trial registration no: ACTRN12617000832370

Keywords: cardiovascular diseases, cardiac rehabilitation, health-related quality of life, HRQoL, myocardial infarction, quality of life, QoL, rehabilitation, randomized control trial

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Authors: Rajwanlop Kumpoopong, Sukit Yindeesuk, Pornchai Silarom

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On May 5, 2014, an earthquake of magnitude 6.3 Richter hit the Northern part of Thailand. The epicenter was in Phan District, Chiang Rai Province. This earthquake or the so-called 2014-Chiang Rai Earthquake is the strongest ground shaking that Thailand has ever been experienced in her modern history. The 2014-Chiang Rai Earthquake confirms the geological evidence, which has previously been ignored by most engineers, that earthquakes of considerable magnitudes 6 to 7 Richter can occurr within the country. This promptly stimulates authorized agencies to pay more attention at the safety of their assets and promotes the comprehensive review of seismic resistance design of their building structures. The focus of this paper is to summarize the damages of highway bridges as a result of the 2014-Chiang Rai ground shaking, the remedy actions, and the research needs. The 2014-Chiang Rai Earthquake caused considerable damages to nearby structures such as houses, schools, and temples. The ground shaking, however, caused damage to only one highway bridge, Mae Laos Bridge, located several kilometers away from the epicenter. The damage of Mae Laos Bridge was in the form of concrete spalling caused by pounding of cap beam on the deck structure. The damage occurred only at the end or abutment span. The damage caused by pounding is not a surprise, but the pounding by only one bridge requires further investigation and discussion. Mae Laos Bridge is a river crossing bridge with relatively large approach structure. In as much, the approach structure is confined by strong retaining walls. This results in a rigid-like approach structure which vibrates at the acceleration approximately equal to the ground acceleration during the earthquake and exerts a huge force to the abutment causing the pounding of cap beam on the deck structure. Other bridges nearby have relatively small approach structures, and therefore have no capability to generate pounding. The effect of mass of the approach structure on pounding of cap beam on the deck structure is also evident by the damage of one pedestrian bridge in front of Thanthong Wittaya School located 50 meters from Mae Laos Bridge. The width of the approach stair of this bridge is wider than the typical one to accommodate the stream of students during pre- and post-school times. This results in a relatively large mass of the approach stair which in turn exerts a huge force to the pier causing pounding of cap beam on the deck structure during ground shaking. No sign of pounding was observed for a typical pedestrian bridge located at another end of Mae Laos Bridge. Although pounding of cap beam on the deck structure of the above mentioned bridges does not cause serious damage to bridge structure, this incident promotes the comprehensive review of seismic resistance design of highway bridges in Thailand. Given a proper mass and confinement of the approach structure, the pounding of cap beam on the deck structure can be easily excited even at the low to moderate ground shaking. In as much, if the ground shaking becomes stronger, the pounding is certainly more powerful. This may cause the deck structure to be unseated and fall off in the case of unrestrained bridge. For the bridge with restrainer between cap beam and the deck structure, the restrainer may prevent the deck structure from falling off. However, preventing free movement of the pier by the restrainer may damage the pier itself. Most highway bridges in Thailand have dowel bars embedded connecting cap beam and the deck structure. The purpose of the existence of dowel bars is, however, not intended for any seismic resistance. Their ability to prevent the deck structure from unseating and their effect on the potential damage of the pier should be evaluated. In response to this expected situation, Thailand Department of Highways (DOH) has set up a team to revise the standard practices for the seismic resistance design of highway bridges in Thailand. In addition, DOH has also funded the research project 'Seismic Resistance Evaluation of Pre- and Post-Design Modifications of DOH’s Bridges' with the scope of full-scale tests of single span bridges under reversed cyclic static loadings for both longitudinal and transverse directions and computer simulations to evaluate the seismic performance of the existing bridges and the design modification bridges. The research is expected to start in October, 2015.

Keywords: earthquake, highway bridge, Thailand, damage, pounding, seismic resistance

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Authors: Qian Chen, Lin Xu, Ping Ju, Zhuoran Li, Yiping Yu, Yuqing Jin

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The operation of power grid is becoming more and more complex and difficult due to its rapid development towards high voltage, long distance, and large capacity. For instance, many large-scale wind farms have connected to power grid, where their fluctuation and randomness is very likely to affect the stability and safety of the grid. Fortunately, many new-type equipments based on power electronics have been applied to power grid, such as UPFC (Unified Power Flow Controller), TCSC (Thyristor Controlled Series Compensation), STATCOM (Static Synchronous Compensator) and so on, which can help to deal with the problem above. Compared with traditional equipment such as generator, new-type controllable devices, represented by the FACTS (Flexible AC Transmission System), have more accurate control ability and respond faster. But they are too expensive to use widely. Therefore, on the basis of the comparison and analysis of the controlling characteristics between traditional control equipment and new-type controllable equipment in both time and space scale, a coordinated optimizing control method within mutil-time-space frame is proposed in this paper to bring both kinds of advantages into play, which can better both control ability and economical efficiency. Firstly, the coordination of different space sizes of grid is studied focused on the fluctuation caused by large-scale wind farms connected to power grid. With generator, FSC (Fixed Series Compensation) and TCSC, the coordination method on two-layer regional power grid vs. its sub grid is studied in detail. The coordination control model is built, the corresponding scheme is promoted, and the conclusion is verified by simulation. By analysis, interface power flow can be controlled by generator and the specific line power flow between two-layer regions can be adjusted by FSC and TCSC. The smaller the interface power flow adjusted by generator, the bigger the control margin of TCSC, instead, the total consumption of generator is much higher. Secondly, the coordination of different time sizes is studied to further the amount of the total consumption of generator and the control margin of TCSC, where the minimum control cost can be acquired. The coordination method on two-layer ultra short-term correction vs. AGC (Automatic Generation Control) is studied with generator, FSC and TCSC. The optimal control model is founded, genetic algorithm is selected to solve the problem, and the conclusion is verified by simulation. Finally, the aforementioned method within multi-time-space scale is analyzed with practical cases, and simulated on PSASP (Power System Analysis Software Package) platform. The correctness and effectiveness are verified by the simulation result. Moreover, this coordinated optimizing control method can contribute to the decrease of control cost and will provide reference to the following studies in this field.

Keywords: FACTS, multi-space-time frame, optimal control, TCSC

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Authors: Ion Robu, Claudiu Mazilu, Radu Deju

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Natural aggregates (gravel and crushed) are essential non-renewable resources which are used for infrastructure works and civil engineering. In European Union member states from Southeast Europe, it is estimated that the construction industry will grow by 4.2% thereafter complicating aggregate supply management. In addition, a significant additional problem that can be associated to the aggregates industry is wasting potential resources through waste dumping of inert waste, especially waste from construction and demolition activities. In 2012, in Romania, less than 10% of construction and demolition waste (including concrete) are valorized, while the European Union requires that by 2020 this proportion should be at least 70% (Directive 2008/98/EC on waste, transposed into Romanian legislation by Law 211/2011). Depending on the efficiency of waste processing and the quality of recycled aggregate concrete (RCA) obtained, poor quality aggregate can be used as foundation material for roads and at the high quality for new concrete on construction. To obtain good quality concrete using recycled aggregate is necessary to meet the minimum requirements defined by the rules for the manufacture of concrete with natural aggregate. Properties of recycled aggregate (density, granulosity, granule shape, water absorption, weight loss to Los Angeles test, attached mortar content etc.) are the basis for concrete quality; also establishing appropriate proportions between components and the concrete production methods are extremely important for its quality. This paper presents a study on the use of recycled aggregates, from a concrete of specified class, to acquire new cement concrete with different percentages of recycled aggregates. To achieve recycled aggregates several batches of concrete class C16/20, C25/30 and C35/45 were made, the compositions calculation being made according NE012/2007 CP012/2007. Tests for producing recycled aggregate was carried out using concrete samples of the established three classes after 28 days of storage under the above conditions. Cubes with 150mm side were crushed in a first stage with a jaw crusher Liebherr type set at 50 mm nominally. The resulting material was separated by sieving on granulometric sorts and 10-50 sort was used for preliminary tests of crushing in the second stage with a jaw crusher BB 200 Retsch model, respectively a hammer crusher Buffalo Shuttle WA-12-H model. It was highlighted the influence of the type of crusher used to obtain recycled aggregates on granulometry and granule shape and the influence of the attached mortar on the density, water absorption, behavior to the Los Angeles test etc. The proportion of attached mortar was determined and correlated with provenance concrete class of the recycled aggregates and their granulometric sort. The aim to characterize the recycled aggregates is their valorification in new concrete used in construction. In this regard have been made a series of concrete in which the recycled aggregate content was varied from 0 to 100%. The new concrete were characterized by point of view of the change in the density and compressive strength with the proportion of recycled aggregates. It has been shown that an increase in recycled aggregate content not necessarily mean a reduction in compressive strength, quality of the aggregate having a decisive role.

Keywords: recycled concrete aggregate, characteristics, recycled aggregate concrete, properties

Procedia PDF Downloads 188

Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

Procedia PDF Downloads 387